US 2010.0062444A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0062444 A1 Ring et al. (43) Pub. Date: Mar. 11, 2010

(54) TLE3 ASA MARKER FORCHEMOTHERAPY (22) Filed: Oct. 13, 2009 Related U.S. Application Data (75) Inventors: Brian Z. Ring, Foster City, CA (US); Douglas T. Ross, (63) Continuation of application No. 12/277,920, filed on Burlingame, CA (US); Robert S. Nov. 25, 2008. Seitz, Hampton Cove, AL (US); (60) Provisional application No. 60/991.487, filed on Nov. Rodney A. Beck, Harvest, AL (US) 30, 2007. Publication Classification Correspondence Address: CHOATE, HALL & STEWART LLP (51) Int. Cl. TWO INTERNATIONAL PLACE CI2O I/68 (2006.01) BOSTON, MA 02110 (US) (52) U.S. Cl...... 435/6 (57) ABSTRACT (73) Assignee: APPLIED GENOMICS, INC., Methods of using TLE3 as a marker for predicting the likeli Huntsville, AL (US) hood that a patient's cancer will respond to chemotherapy. Methods of using TLE3 as a marker for selecting a chemo (21) Appl. No.: 12/578,255 therapy for a cancer. Patent Application Publication Mar. 11, 2010 Sheet 1 of 18 US 2010/0062444 A1

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TLE3 ASA MARKER FOR CHEMOTHERAPY 0005 Expression of TLE3 can be detected using any known method. Thus, while the inventive methods have been CROSS REFERENCE TO RELATED exemplified by detecting TLE3 polypeptides using antibod APPLICATION ies, in certain embodiments TLE3 polynucleotides may be 0001. This application is a continuation of U.S. patent detected using one or more primers as is well known in the art. application Ser. No. 12/277,920, filed Nov. 25, 2008, which 0006. In general, TLE3 can be used in conjunction with claims priority to U.S. Provisional Patent Application Ser. other markers or clinical factors (e.g., stage, tumor size, node No. 60/991.487, filed Nov.30, 2007, both of which are hereby characteristics, age, etc.) to further improve the predictive incorporated herein by reference in their entireties. power of the inventive methods. BRIEF DESCRIPTION OF THE APPENDIX SEQUENCE LISTING 0007. This patent application refers to material compris 0002. In accordance with 37 C.F.R. S.1.52(e)(5), a ing a table and data presented as Appendix A immediately Sequence Listing in the form of a text file (entitled “Sequence after the section entitled “Exemplification” and immediately Listing..txt, created on Oct. 13, 2009, and 90 kilobytes) is before the section entitled “Other Embodiments.” Specifi incorporated herein by reference in its entirety. cally, Appendix A is a table that lists a variety of markers that could be used in a panel in conjunction with the TLE3 marker BACKGROUND OF THE INVENTION in an inventive method. The table includes the antibody ID, 0003. A major challenge of cancer treatment is the selec parent gene name, EntreZ Gene ID, known aliases for the tion of chemotherapies that maximize efficacy and minimize parent gene, peptides that may be used in preparing antibod toxicity for a given patient. Assays for cell Surface markers, ies and exemplary antibody titers for staining Using the par e.g., using immunohistochemistry (IHC), have provided ent gene name, Entrez, Gene ID and/or known aliases for the means for dividing certain cancers into Subclasses. For parent gene, a skilled person can readily obtain the nucleotide example, one factor considered in prognosis and treatment (and corresponding amino acid) sequences for each and every decisions for breast cancer is the presence or absence of the one of the parent genes that are listed in Appendix A from a estrogen receptor (ER). ER-positive breast cancers typically public database (e.g., GenBank, Swiss-Prot or any future respond much more readily to hormonal therapies such as derivative of these). The nucleotide and corresponding amino tamoxifen, which acts as an anti-estrogen in breast tissue, acid sequences for each and every one of the parent genes that than ER-negative cancers. Though useful, these analyses only are listed in Appendix A are hereby incorporated by reference in part predict the clinical behavior of breast cancers. There is from these public databases. Antibodies with IDs that begin phenotypic diversity present in cancers that current diagnos with S5 or S6 may be obtained from commercial sources as tic tools fail to detect. As a consequence, there is still much indicated. controversy over how to stratify patients amongst potential treatments in order to optimize outcome (e.g., for breast can BRIEF DESCRIPTION OF THE DRAWING cer see "NIH Consensus Development Conference State ment: Adjuvant Therapy for Breast Cancer, Nov. 1-3, 2000', 0008 FIG. 1 compares IHC images of TLE3-negative J. Nat. Cancer Inst. Monographs, 30:5-15, 2001 and Di Leo (S0643-) and TLE3-positive (S0643+) samples from breast et al., Int. J. Clin. Oncol. 7:245-253, 2002). In particular, there cancer patients. is currently no tool for predictingapatient's likely response to 0009 FIG. 2 shows Kaplan-Meier recurrence curves that treatment with paclitaxel, a chemotherapeutic with particu were generated using all patients in the Huntsville Hospital (HH) breast cancer cohort after classification based on stain larly adverse side-effects. There clearly exists a need for ing with an antibody raised against the TLE3 marker. Recur improved methods and reagents for classifying cancers and rence data from TLE3-positive and TLE3-negative patients thereby selecting therapeutic regimens that maximize effi were used to generate the top and bottom curves, respectively. cacy and minimize toxicity for a given patient. As shown in the Figure, antibody binding to the TLE3 marker correlates with improved prognosis across this breast cancer SUMMARY OF THE INVENTION cohort (HR=0.573, p<0.004). 0004 We have identified a correlation between the expres 0010 FIG. 3 shows Kaplan-Meier recurrence curves that sion of TLE3 (transducin-like enhancer of split 3, Entrez were generated using all patients in the Roswell Park Cancer Gene ID 7090) and a cancer's response to chemotherapy. This Institute (RPI) breast cancer cohort after classification based correlation has been demonstrated using TLE3 antibodies on staining with an antibody raised against the TLE3 marker. and samples from breast cancer cohorts which include both The selected patients in the RP cohort were all triple negative treated and untreated patients with known outcome. The for the ER (estrogen receptor, Entrez GeneID 2099), PR inventors have also observed that binding of TLE3 antibodies (progesterone receptor, Entrez, GeneID 5241) and HER-2 in samples from treated ovarian cancer patients correlates markers (v-erb-b2 erythroblastic leukemia viral oncogene with improved prognosis. In one aspect, the present invention homolog 2. Entrez, GeneID 2064). Recurrence data from therefore provides methods of using TLE3 as a marker for TLE3-positive and TLE3-negative patients were used to gen predicting the likelihood that a patient's cancer will respond erate the top and bottom curves, respectively. As shown in the to chemotherapy. In another aspect, the present invention Figure, antibody binding to the TLE3 marker correlates with provides methods of using TLE3 as a marker for deciding improved prognosis across this breast cancer cohort (HR=0. whether to administer chemotherapy to a cancer patient. In 24, p<0.011). yet another aspect, the present invention provides methods of 0011 FIG. 4 shows Kaplan-Meier recurrence curves that using TLE3 as a marker for selecting a chemotherapy for a were generated using patients in the HH breast cancer cohort cancer patient. of FIG. 1 that did not receive chemotherapy. Recurrence data US 2010/0062444 A1 Mar. 11, 2010 from TLE3-positive and TLE3-negative patients in this sub of FIG. 6 that received CA chemotherapy only (i.e., without a set were used to generate the top and bottom curves, respec taxane). Recurrence data from TLE3-positive and TLE3 tively. As shown in the Figure, antibody binding to the TLE3 negative patients in this Subset were used to generate the top marker loses its correlation with prognosis in breast cancer and bottom curves, respectively. As shown in the Figure, there patients that did not receive chemotherapy (HR=0.788, p=0. is no correlation between antibody binding to the TLE3 49). marker and prognosis in this subset of treated patients (HR=0. 0012 FIG. 5 shows Kaplan-Meier recurrence curves that 759, p=0.81). were generated using patients in the HH breast cancer cohort 0019 FIG. 12 shows Kaplan-Meier recurrence curves that of FIG. 1 that did receive chemotherapy. Recurrence data were generated using patients in the RP breast cancer cohort from TLE3-positive and TLE3-negative patients in this sub of FIG. 6 that received CA in combination with a taxane. set were used to generate the top and bottom curves, respec Recurrence data from TLE3-positive and TLE3-negative tively. As shown in the Figure, the correlation between anti patients in this Subset were used to generate the top and body binding to the TLE3 marker and prognosis was restored bottom curves, respectively. As shown in the Figure, antibody in patients that did receive chemotherapy (HR=0.539, p<0. binding to the TLE3 marker correlates with improved prog 013). nosis across this subset of treated patients (HR=0.142, p=0. 0013 FIG. 6 shows Kaplan-Meier recurrence curves that 011). were generated using patients in the RP breast cancer cohort 0020 FIG. 13 shows Kaplan-Meier recurrence curves that of FIG. 2 that did receive chemotherapy. Recurrence data were generated using patients in the RP breast cancer cohort from TLE3-positive and TLE3-negative patients in this sub of FIG. 6 that received a taxane or CMF. Some of the patients set were used to generate the top and bottom curves, respec receiving a taxane also received CA. Recurrence data from tively. As shown in the Figure, antibody binding to the TLE3 TLE3-positive and TLE3-negative patients in this subset marker correlates with improved prognosis across this Subset were used to generate the top and bottom curves, respectively. of breast cancer patients (HR=0.194, p=0.010). These results As shown in the Figure, antibody binding to the TLE3 marker parallel those obtained in FIG. 5 with the HH cohort. correlates with improved prognosis across this Subset of 0014 FIG. 7 shows Kaplan-Meier recurrence curves that treated patients (HR=0.137, p=0.011). were generated using patients in the HH breast cancer cohort 0021 FIG. 14 shows Kaplan-Meier recurrence curves that of FIG. 5 that received CMF (cyclophosphamide, methotrex were generated using patients in the RP breast cancer cohort ate and 5-fluorouracil) chemotherapy. Recurrence data from of FIG. 6 that received neoadjuvant chemotherapy. Recur TLE3-positive and TLE3-negative patients in this subset rence data from TLE3-positive and TLE3-negative patients in were used to generate the top and bottom curves, respectively. this Subset were used to generate the top and bottom curves, As shown in the Figure, antibody binding to the TLE3 marker respectively. The sample size was small (N=12); however, as correlates with improved prognosis across this Subset of shown in the Figure, antibody binding to the TLE3 marker treated patients (HR=0.398, p<0.019). showed significant correlation with improved prognosis 0015 FIG. 8 shows Kaplan-Meier recurrence curves that across this Subset of treated patients when measured using the were generated using patients in the HH breast cancer cohort Fisher Exact Test (p=0.005). of FIG. 5 that received CA (cyclophosphamide and adriamy (0022 FIGS. 15-17 show Kaplan-Meier recurrence curves cin) or CAF (cyclophosphamide, adriamycin and 5-fluorou that were generated using patients in the RP breast cancer racil) chemotherapy (with or without a taxane). Recurrence cohort of FIG. 6 that received chemotherapy. Recurrence data data from TLE3-positive and TLE3-negative patients in this from TLE3-positive and TLE3-negative patients with stage Subset were used to generate the top and bottom curves, 11+(FIG. 15), stage IIb+ (FIG. 16) and stage III+ (FIG. 17) respectively. As shown in the Figure, the correlation between cancers were used to generate the top and bottom curves, antibody binding to the TLE3 marker and prognosis loses respectively. In each case, antibody binding to the TLE3 significance in this subset of treated patients (HR=0.666, marker correlated with improved prognosis across these Sub p=0.22). sets of treated patients. The sample size was Small in the 0016 FIG. 9 shows Kaplan-Meier recurrence curves that subset of FIG. 17 (N=19); however significance was obtained were generated using patients in the HH breast cancer cohort when measured using the Fisher Exact Test (p=0.020). of FIG. 8 that received CA or CAF chemotherapy only (i.e., 0023 FIG. 18 shows Kaplan-Meier recurrence curves that without a taxane). Recurrence data from TLE3-positive and were generated using patients in the University of Alabama at TLE3-negative patients in this Subset were used to generate Birmingham (UAB) ovarian cancer cohort. All patients the top and bottom curves, respectively. As shown in the received paclitaxel. Most patients also received platinum che Figure, there is no correlation between antibody binding to motherapy (carboplatin or cisplatin). Recurrence data from the TLE3 marker and prognosis in this subset of treated TLE3-positive and TLE3-negative patients in this subset patients (HR=1.03, p=0.95). were used to generate the top and bottom curves, respectively. 0017 FIG. 10 shows Kaplan-Meier recurrence curves that As shown in the Figure, antibody binding to the TLE3 marker were generated using patients in the HH breast cancer cohort correlated with prognosis in these treated patients (HR-0.64, of FIG. 8 that received CA or CAF in combination with a p<0.049). taxane. Recurrence data from TLE3-positive and TLE3-nega tive patients in this Subset were used to generate the top and DEFINITIONS bottom curves, respectively. As shown in the Figure, the cor 0024 Binds When an interaction partner “binds a relation between antibody binding to the TLE3 marker and marker they are linked by direct non-covalent interactions. prognosis was restored in this Subset of treated patients 0025 Cancer markers—“Cancer markers' or “markers’ (HR=0.114, p=0.038). are molecular entities that are detectable in cancer samples. 0018 FIG. 11 shows Kaplan-Meier recurrence curves that Generally, markers may be polypeptides (e.g., TLE3 protein) were generated using patients in the RP breast cancer cohort or polynucleotides (e.g., TLE3 mRNA) that are indicative of US 2010/0062444 A1 Mar. 11, 2010 the expression of a gene (e.g., TLE3 gene) and present within ner will likely be an acceptable reagent for diagnostic pur the cancer Sample, e.g., within the cytoplasm or membranes poses even if it lacks specificity. of cancerous cells and/or secreted from Such cells. 0030 Primer A “primer' is an oligonucleotide entity 0026 Cancer sample—As used herein, the term “cancer that physically hybridizes with a polynucleotide marker. In sample' or “sample' is taken broadly to include cell or tissue general, a primer is said to “hybridize specifically” with a marker if it hybridizes at a detectable level with the marker samples removed from a cancer patient (e.g., from a tumor, and does not hybridize detectably with unrelated molecular from the bloodstream, etc.), cells derived from a tumor that entities (e.g., other markers) under similar conditions. Spe may be located elsewhere in the body (e.g., cells in the blood cific hybridization between a marker and a primer will typi stream or at a site of metastasis), or any material derived from cally be dependent upon the presence of a particular nucle Such a sample. Derived material may include, for example, otide sequence of the target marker which is complementary nucleic acids or proteins extracted from the sample, cell prog to the nucleotide sequence of the primer. In general, it is to be eny, etc. In one embodiment, a cancer sample may be a tumor understood that specificity need not be absolute. The degree sample. of specificity of a primer will depend on the context in which 0027 Correlation “Correlation” refers to the degree to it is being used. In general, a primer exhibits specificity for a which one variable can be predicted from another variable, particular marker if it favors hybridization with that partner e.g., the degree to which a cancer's response to therapy can be above hybridization with other potential partners, e.g., other predicted from the expression of a marker in a cancer sample. markers. One of ordinary skill in the art will be able to select A variety of Statistical methods may be used to measure primers having a sufficient degree of specificity to perform correlation between two variables, e.g., without limitation the appropriately in any given application. It is also to be under student t-test, the Fisher exact test, the Pearson correlation stood that specificity may be evaluated in the context of coefficient, the Spearman correlation coefficient, the Chi additional factors such as the affinity of the primer for the squared test, etc. Results are traditionally given as a measured target marker versus the affinity of the primer for other poten correlation coefficient with a p-value that provides a measure tial partners, e.g., other markers. If a primer exhibits a high of the likelihood that the correlation arose by chance. A affinity for a target marker and low affinity for non-target correlation with a p-value that is less than 0.05 is generally molecules, the primer will likely be an acceptable reagent for considered to be statistically significant. Preferred correla diagnostic purposes even if it lacks specificity. tions have p-values that are less than 0.01, especially less than 0031 Response The “response' of a cancer to therapy O.OO1. may represent any detectable change, for example at the molecular, cellular, organellar, or organismal level. For 0028. Hybridized When a primer and a marker are instance, tumor size, patient life expectancy, recurrence, or physically “hybridized with one anotheras described herein, the length of time the patient Survives, etc., are all responses. they are non-covalently linked by base pair interactions. Responses can be measured in any of a variety of ways, 0029 Interaction partner—An “interaction partner is an including for example non-invasive measuring of tumor size entity that binds a polypeptide marker. For example and with (e.g., CT Scan, image-enhanced visualization, etc.), invasive out limitation, an interaction partner may be an antibody or a measuring of tumor size (e.g., residual tumor resection, etc.), fragment thereof that binds a marker. In general, an interac Surrogate marker measurement (e.g., serum PSA, etc.), clini tion partner is said to “bind specifically with a marker if it cal course variance (e.g., measurement of patient quality of binds at a detectable level with the marker and does not bind life, time to relapse, Survival time, etc.). detectably with unrelated molecular entities (e.g., other 0032 Small molecule—A “small molecule' is a non markers) under similar conditions. Specific association polymeric molecule. A Small molecule can be synthesized in between a marker and an interaction partner will typically be a laboratory (e.g., by combinatorial synthesis) or found in dependent upon the presence of a particular structural feature nature (e.g., a natural product). A Small molecule is typically of the target marker Such as an antigenic determinant or characterized in that it contains several carbon-carbon bonds epitope recognized by the interaction partner. In general, it is and has a molecular weight of less than about 1500 Da. to be understood that specificity need not be absolute. For although this characterization is not intended to be limiting example, it is well known in the art that antibodies frequently for the purposes of the present invention. cross-react with other epitopes in addition to the target epitope. Such cross-reactivity may be acceptable depending DETAILED DESCRIPTION OF CERTAIN upon the application for which the interaction partner is to be PREFERRED EMBODIMENTS OF THE used. Thus the degree of specificity of an interaction partner INVENTION will depend on the context in which it is being used. In general, an interaction partner exhibits specificity for a par 0033. As noted above, we have identified a correlation ticular marker if it favors binding with that partner above between the expression of TLE3 (transducin-like enhancer of binding with other potential partners, e.g., other markers. One split 3, Entrez, Gene ID 7090) in a cancer sample and a of ordinary skill in the art will be able to select interaction cancer's response to chemotherapy. As described in the partners having a sufficient degree of specificity to perform Examples, this correlation has been demonstrated using appropriately in any given application (e.g., for detection of a TLE3 antibodies and samples from two breast cancer cohorts target marker, for therapeutic purposes, etc.). It is also to be which include both treated and untreated patients with known understood that specificity may be evaluated in the context of outcome. We have also shown that this predictive model is additional factors such as the affinity of the interaction partner consistent when applied to samples from a cohort of treated for the target marker versus the affinity of the interaction ovarian cancer patients. We have also demonstrated the utility partner for other potential partners, e.g., other markers. If an of TLE3 for predicting response to specific types of chemo interaction partner exhibits a high affinity for a target marker therapies including treatments which involve the administra and low affinity for non-target molecules, the interaction part tion of cell cycle specific chemotherapeutics, e.g., methotr US 2010/0062444 A1 Mar. 11, 2010

exate and taxanes. Since these chemotherapeutics have thereof). For example, as described below one may use a known utility across different cancer types, these results Sug TLE3 antibody as an interaction partner and detect TLE3 gest that the inventive methods will also be useful in predict expression by contacting the cancer sample with the TLE3 ing their efficacy across different cancer types. antibody. In Such embodiments, the inventive methods may involve providing a cancer sample from a cancer patient, Predicting Response to Chemotherapy and Selecting Chemo contacting the cancer sample with an antibody directed to therapy TLE3, and predicting the likelihood that the patient's cancer 0034. In one aspect, the present invention provides meth will respond to chemotherapy based upon binding of the ods of using TLE3 as a marker for predicting the likelihood antibody to the cancer sample. In one embodiment, the step of that a patient's cancer will respond to chemotherapy. In gen predicting may comprise predicting that the patient’s cancer eral, these methods involve providing a cancer sample from a is likely to respond to chemotherapy based upon binding of cancer patient, determining whether TLE3 is expressed in the the antibody to the cancer sample. In another embodiment, cancer sample, and predicting the likelihood that the patient's the step of predicting may comprise predicting that the cancer will respond to chemotherapy based upon a result of patient's cancer is unlikely to respond to chemotherapy based the step of determining. In one embodiment, the step of pre upon lack of binding of the antibody to the cancer sample. dicting comprises predicting that the patient's cancer is likely 0039. In another embodiment, TLE3 polynucleotides may to respond to chemotherapy based upon the presence ofTLE3 be detected using one or more primers that hybridize with a expression in the cancer sample. In one embodiment, the step TLE3 polynucleotide (e.g., a TLE3 mRNA, cDNA or RNA). of predicting comprises predicting that the patient's cancer is In such embodiments, the inventive methods may involve unlikely to respond to chemotherapy based upon the absence providing a cancer Sample from a cancer patient, contacting of TLE3 expression in the cancer sample. the cancer sample with one or more primers that hybridize 0035. In certain embodiments, a negative control sample with TLE3, and predicting the likelihood that the patient’s is provided and the step of determining comprises detecting a cancer will respond to chemotherapy based upon hybridiza level of TLE3 expression in the cancer sample and the nega tion of the one or more primers to the cancer sample. In one tive control sample and comparing the level of expression of embodiment, the step of predicting may comprise predicting TLE3 in the cancer sample and the negative control sample. that the patient's cancer is likely to respond to chemotherapy In general, the negative control sample can be any sample that based upon hybridization of the one or more primers to the does not reproducibly express TLE3. In one embodiment, the cancer Sample. In another embodiment, the step of predicting negative control sample can be a sample that does not repro may comprise predicting that the patient's cancer is unlikely ducibly bind TLE3 antibodies. In one embodiment, the nega to respond to chemotherapy based upon lack of hybridization tive control sample can be a sample that does not reproducibly of the one or more primers to the cancer Sample. produce a detectable level of TLE3 mRNA. In one embodi 0040. In another aspect, the present invention provides ment, the negative control sample can be from a patient with methods for deciding whether to administer chemotherapy to a TLE3-negative cancer. In one embodiment, the negative the cancer patient based upon the likelihood that the patient’s control sample can be from a patient without cancer. In cer cancer will respond to chemotherapy. In one embodiment, the tain embodiments the negative control sample may originate step of deciding comprises deciding to administer chemo from the same tissue type as the cancer in question (e.g., therapy to the cancer patient based upon the presence ofTLE3 breast tissue when considering breast cancer). In other expression in the cancer sample. In one embodiment, the step embodiments, the negative control sample may originate of deciding comprises deciding not to administer chemo from a different tissue type or even a different organism, or a therapy to the cancer patient based upon the absence of TLE3 cell line. expression in the cancer sample. 0036 Additionally or alternatively, in certain embodi 0041. In yet another aspect, the present invention provides ments, a positive control sample is provided and the step of methods for selecting a chemotherapy for a cancer patient. In determining comprises detecting a level of TLE3 expression general, these methods comprise providing a cancer sample in the cancer sample and the positive control sample and from a cancer patient, determining whether TLE3 is comparing the level of expression of TLE3 in the cancer expressed in the cancer sample, and selecting a chemotherapy sample and the positive control sample. In general, the posi for the cancer patient based upon the results of the step of tive control sample can be any sample that reproducibly determining. In one embodiment, the step of selecting com expresses TLE3. In one embodiment, the negative control prises selecting a chemotherapy based upon the presence of sample can be a sample that reproducibly bind TLE3 antibod TLE3 expression in the cancer sample. ies. In one embodiment, the negative control sample can be a 0042. As described in the Examples, we have demon sample that reproducibly produces a detectable level of TLE3 strated that TLE3 expression correlates with response to che mRNA. In one embodiment, the positive control sample can motherapy with methotrexate (see FIG. 7) and taxanes (see be from a patient with a TLE3-positive cancer. In certain FIGS. 10, 12 and 13). Methotrexate and taxanes are thought embodiments the positive control sample may originate from to be cell cycle specific chemotherapeutics (e.g., see Good the same tissue type as the cancer in question (e.g., breast man & Gilman's The Pharmacological Basis of Therapeutics, tissue when considering breast cancer). In other embodi IX. Chemotherapy of Neoplastic Diseases Chapter 51. Anti ments, the positive control sample may originate from a dif neoplastic Agents, 11th Edition, Laurence L. Brunton, editor ferent tissue type or even a different organism, or cell line. in-chief, John S. Lazo and Keith L. Parker, Associate Editors). 0037 Expression of TLE3 can be determined using any Cell cycle specific chemotherapeutics exhibit their mecha known method. nism of action within a specific phase of the cell cycle in 0038. In one embodiment, TLE3 polypeptides may be contrast to non-cell cycle specific chemotherapeutics that detected using an interaction partner that binds a TLE3 work equally with all phases including the resting phase (GO). polypeptide (e.g., TLE3 protein or an antigenic fragment Other plant alkaloids besides the taxanes have also been clas US 2010/0062444 A1 Mar. 11, 2010

sified in the literature as cell cycle specific chemotherapeutics deciding whether to administer, methotrexate in combination as have other antimetabolites besides methotrexate. In con with one or more additional chemotherapeutics. For example, trast, many alkylating agents such as cisplatin and cyclopho methotrexate is commonly administered to cancer patients as samide have been classified as non-cell cycle specific chemo a combination called CMF which also includes cyclophos therapeutics. Our results suggest that the predictive power of phamide and 5-fluorouracil. TLE3 may extend to other cell cycle specific chemotherapeu 0046 Taxanes are diterpenes produced by the plants of the tics besides methotrexate and taxanes. genus Taxus. Taxanes can be obtained from natural sources or 0043. In some embodiments, the inventive methods may produced synthetically. Taxanes include paclitaxel therefore be used to select, or decide whether to administer, a (TAXOLTM) and docetaxel (TAXOTERETM). Taxanes work cell cycle specific chemotherapeutic. In one embodiment, the by interfering with normal microtubule growth during cell inventive methods may be used to select, or decide whether to division. In certain embodiments, the inventive methods com administer, an antimetabolite. In one embodiment, the inven prise a step of selecting, or deciding whether to administer, a tive methods may be used to select, or decide whether to taxane (e.g., paclitaxel or docetaxel) in combination with one administer, a plant alkaloid. In one embodiment, the inventive or more additional chemotherapeutics. For example, taxanes methods may be used to select, or decide whether to admin are commonly administered to cancer patients incombination ister, methotrexate. In another embodiment, the inventive with cyclophosphamide and adriamycin (doxorubicin) and methods may be used to select, or decide whether to admin optionally 5-fluorouracil (i.e., with CA or CAF). ister, a taxane. In one embodiment the taxane is paclitaxel. In 0047 Paclitaxel has been approved for the treatment of one embodiment the taxane is docetaxel. breast cancer, Kaposi's sarcoma, lung cancer and ovarian 0044. In each case it will be appreciated that these chemo cancer (Paclitaxel in BC Cancer Agency Cancer Drug therapeutics may be administered alone or in combination Manual, 2007 and Mekhail and Markman, Expert Opin. with other chemotherapeutics as is known in the art and Pharmacother. 3:755-66, 2002). Paclitaxel has also been discussed below. It will also be appreciated that the present shown to be useful in treating cervical cancer (pp. 1124-34 in invention encompasses methods in which the selected che AHFS 2005 Drug Information. Bethesda, Md.: American motherapeutic is a methotrexate or taxane derivative, i.e., a Society of Health-System Pharmacists, 2005), endometrial compound with a structure which is derived from methotrex cancer (Paclitaxel in BC Cancer Agency Cancer Drug ate or a taxane. Derivatives will typically share most of the Manual, 2007), bladder cancer (Paclitaxel in UpToDate, structure of the parent compound but may include different 2007), head and neck cancer (Paclitaxel in UpToDate, 2007), Substituents, heteroatoms, ring fusions, levels of saturation, leukemia (Paclitaxel in UpToDate, 2007) and malignant isomerism, stereoisomerism, etc. at one or more positions melanoma (Paclitaxel in UpToDate, 2007). Side effects of within the parent compound. Without limitation, the follow paclitaxel include hyperSensitivity reactions such as flushing ing U.S. patents describe the preparation of exemplary meth of the face, skin rash, or shortness of breath. Patients often otrexate derivatives that could be employed according to an receive medication to prevent hypersensitivity reactions inventive method: U.S. Pat. Nos. 6,559,149 and 4,374,987. before they take paclitaxel. Paclitaxel can also cause tempo Without limitation, the following U.S. patents describe the rary damage to the bone marrow. Bone marrow damage can preparation of exemplary taxane derivatives that could be cause a person to be more Susceptible to infection, anemia, employed according to an inventive method: U.S. Pat. Nos. and bruise or bleed easily. Other side effects may include joint 7,074,945; 7,063,977; 6,906,101; 6,649,778; 6,596,880; or muscle pain in the arms or legs; diarrhea, nausea and 6,552,205; 6,531,611; 6,482,963; 6,482,850; 6,462,208: Vomiting; numbness, burning, or tingling in the hands or feet; 6,455,575; 6,441,026; 6,433, 180; 6,392,063; 6,369,244; and loss of hair. 6,339,164; 6,291,690; 6,268,381; 6,239,167; 6,218,553; 0048 Docetaxel has been approved for the treatment of 6,214,863; 6,201,140; 6,191,290; 6,187,916; 6,162,920; breast cancer (Aapro, Seminars in Oncology 25(5 Suppl 12): 6,147,234; 6,136,808: 6,114,550; 6,107,332: 6,051,600; 7-11, 1998: Nabholtz et al., Journal of Clinical Oncology 6,025,385; 6,011,056; 5,955,489; 5,939,567; 5,912,263; 17(5):1413-24, 1999; Sostrom et al., European Journal of 5,908,835; 5,869,680; 5,861,515; 5,821,263; 5,763,477; Cancer 35 (8): 1194-201, 1999; and Burstein et al., Journal of 5,750,561; 5,728,687; 5,726,346; 5,726,318; 5,721,268; Clinical Oncology 18(6):1212-9, 2000), non-small cell lung 5,719,177; 5,714,513; 5,714,512; 5,703,117; 5,698,582: cancer (Fossella et al., Journal of Clinical Oncology 18(12): 5,686,623: 5,677,462; 5,646,176; 5,637,723; 5,621, 121: 2354-62, 2000 and Hainsworth et al., Cancer 89(2):328-33, 5,616,739; 5,606,083: 5,580,899; 5,476,954; 5,403,858: 2000) and ovarian cancer (Kaye et al., European Journal of 5,380,916: 5,254,703; and 5,250,722. The entire contents of Cancer 33(13):2167-70, 1997). Docetaxel has also been each of the aforementioned patents and any other reference shown to be useful in treating esothelioma (Vorobiof et al., which is cited herein is hereby incorporated by reference. Proc Am Soc Clin Oncol 19:578a, 2000), prostate cancer 0045 Methotrexate acts by inhibiting the metabolism of (Picus et al., Seminars in Oncology 26(5 Suppl 17): 14-8. folic acid and has has been approved for the treatment of 1999 and Petrylak et al., Journal of Clinical Oncology 17(3): bladder cancer, breast cancer, gastric cancer, choriocarci 958-67, 1999), urothelial transitional cell cancer (Dimopou noma, head and neck cancer, leptomeningeal cancer, leuke los et al., Annals of Oncology 10(11): 1385-8, 1999 and Pecta mia (acute meningeal, acute lymphoblastic, acute lympho sides et al., European Journal of Cancer 36(1):74–9, 2000), cytic), lymphoma (Burkitt's, childhood, non-Hodgkin's), head and neck cancer (Docetaxel in USPDI, 2000 and Cou mycosis fungoides, primary unknown cancer and lymphatic teau et al., British Journal of Cancer81(3):457-62, 1999) and sarcoma (Methotrexate in BC Cancer Agency Cancer Drug Small cell lung cancer (Smyth et al., European Journal of Manual, 2007). Methotrexate has also been shown to be use Cancer 30A(8): 1058-60, 1994). ful for treating esophageal cancer, lung cancer and testicular 0049. Our observation that improved response to chemo cancer (Methotrexate in UpToDate, 2007). In certain embodi therapy is observed for both breast and ovarian cancer ments, the inventive methods comprise a step of selecting, or patients that are TLE3-positive suggests that the inventive US 2010/0062444 A1 Mar. 11, 2010

methods may be useful across different cancer types. Our ments, FV fragments, or SFV fragments, etc.; see, for example, observation that TLE3 expression is associated with Inbar et al., Proc. Nat. Acad. Sci. USA 69:2659, 1972; Hoch improved response to treatment with methotrexate and tax man et al., Biochem. 15:2706, 1976; and Ehrlich et al., Bio anes further Suggest that the inventive methods may be appli chem. 19:4091, 1980; Huston et al., Proc. Nat. Acad. Sci. USA cable across cancers that respond to these chemotherapeutics. 85:5879, 1998: U.S. Pat. Nos. 5,091,513 and 5,132,405 to As discussed above, this includes without limitation breast Huston et al.; and U.S. Pat. No. 4,946,778 to Ladner et al., cancer, ovarian cancer, lung cancer, bladder cancer, gastric each of which is incorporated herein by reference). In certain cancer, head and neck cancer, and leukemia. embodiments, interaction partners may be selected from 0050. In one embodiment, the inventive methods may be libraries of mutant antibodies (or fragments thereof). For used with a cancer patient that has breast cancer. In one example, collections of antibodies that each include different embodiment, the inventive methods may be used with a can point mutations may be screened for their association with a cer patient that has ovarian cancer. In one embodiment, the marker of interest. Yet further, chimeric antibodies may be inventive methods may be used with a cancer patient that has used as interaction partners, e.g., “humanized' or "veneered lung cancer. In one embodiment, the inventive methods may antibodies as described in greater detail below. be used with a cancer patient that has bladder cancer. In one 0057 When antibodies are used as interaction partners, embodiment, the inventive methods may be used with a can these may be prepared by any of a variety of techniques cer patient that has gastric cancer. In one embodiment, the known to those of ordinary skill in the art (e.g., see Harlow inventive methods may be used with a cancer patient that has and Lane, Antibodies. A Laboratory Manual, Cold Spring head and neck cancer. In one embodiment, the inventive Harbor Laboratory, 1988, see also the Examples). For methods may be used with a cancer patient that has leukemia. example, antibodies can be produced by cell culture tech 0051. As demonstrated in the Examples, in one embodi niques, including the generation of monoclonal antibodies, or ment, the correlation between TLE3 expression and response via transfection of antibody genes into suitable bacterial or to chemotherapy was observed with breast cancer patients mammalian cell hosts, in order to allow for the production of that are triple negative for the ER (estrogen receptor, Entrez recombinant antibodies. In one technique, an “immunogen GeneID 2099), PR (progesterone receptor, Entrez, GeneID comprising an antigenic portion of a marker of interest (or the 5241) and HER-2 markers (v-erb-b2 erythroblastic leukemia marker itself) is initially injected into any of a wide variety of viral oncogene homolog 2. Entrez, GeneID 2064). In certain mammals (e.g., mice, rats, rabbits, sheep or goats). In this embodiments, the inventive methods may therefore be used step, a marker (or an antigenic portion thereof) may serve as with breast cancer patients that belong to this class. the immunogen without modification. Alternatively, particu 0052. As demonstrated in the Examples, the correlation larly for relatively short markers, a Superior immune response between TLE3 expression and response to chemotherapy was may be elicited if the marker isjoined to a carrier protein, Such found to also exist when treatment was administered in a as bovine serum albumin or keyhole limpet hemocyanin neoadjuvant setting. Thus, in certain embodiments, the inven (KLH). The immunogen is injected into the animal host, tive methods may be used with patients receiving chemo preferably according to a predetermined schedule incorporat therapy in a neoadjuvant setting. In other embodiments, the ing one or more booster immunizations and the animals are chemotherapy may be administered in an adjuvant setting. bled periodically. Polyclonal antibodies specific for the 0053 As demonstrated in the Examples, the correlation marker may then be purified from such antisera by, for between TLE3 expression and response to chemotherapy was example, affinity chromatography using the marker (or an also found to be independent of stage. Thus, in certain antigenic portion thereof) coupled to a suitable solid Support. embodiments, the inventive methods may be used with An exemplary method is described in the Examples. patients with a stage 11+(i.e., stage 11 or greater) cancer. In 0.058 If desired for diagnostic or therapeutic purposes, certain embodiments, the inventive methods may be used monoclonal antibodies specific for TLE3 may be prepared, with patients with a stage IIb-- or a stage III+ cancer. for example, using the technique of Kohler and Milstein, Eur: J. Immunol. 6:511, 1976 and improvements thereto. Briefly, Detecting TLE3 Expression these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specific 0054 As mentioned above, expression of TLE3 can be ity (i.e., reactivity with the marker of interest). Such cell lines determined using any known method. In one embodiment, may be produced, for example, from spleen cells obtained TLE3 expression may be determined by detecting TLE3 from an animal immunized as described above. The spleen polypeptide markers using interaction partners (e.g., antibod cells are then immortalized by, for example, fusion with a ies). In another embodiment, TLE3 expression may be deter myeloma cell fusion partner, preferably one that is Syngeneic mined by detecting TLE3 polynucleotide markers using with the immunized animal. A variety of fusion techniques primers. may be employed. For example, the spleen cells and myeloma cells may be combined with a nonionic detergent for a few Detecting TLE3 Polypeptide Markers minutes and then plated at low density on a selective medium 0055 TLE3 polypeptide markers may be detected using that supports the growth of hybrid cells, but not myeloma any interaction partner that binds a TLE3 polypeptide marker cells. A preferred selection technique uses HAT (hypoxan (which could be a TLE3 protein or an antigenic fragment thine, aminopterin, thymidine) selection. After a sufficient thereof). Thus, any entity that binds detectably to the TLE3 time, usually about 1 to 2 weeks, colonies of hybrids are marker may be utilized as an interaction partnerinaccordance observed. Single colonies are selected and their culture super with the present invention, so long as it binds the marker with natants tested for binding activity against the marker. Hybri an appropriate combination of affinity and specificity. domas having high reactivity and specificity are preferred. 0056 Particularly preferred interaction partners are anti 0059 Monoclonal antibodies may be isolated from the bodies, or fragments (e.g., F(ab) fragments, F(ab')2 frag Supernatants of growing hybridoma colonies. In addition, US 2010/0062444 A1 Mar. 11, 2010 various techniques may be employed to enhance the yield, 0061 Any available strategy or system may be utilized to such as injection of the hybridoma cell line into the peritoneal detect association between an interaction partner and the cavity of a suitable vertebrate host, such as a mouse. Mono TLE3 marker. In certain embodiments, association can be clonal antibodies may then be harvested from the ascites fluid detected by adding a detectable label to the interaction part or the blood. Contaminants may be removed from the anti ner. In other embodiments, association can be detected by bodies by conventional techniques. Such as chromatography, using a labeled secondary interaction partner that binds spe gel filtration, precipitation and extraction. TLE3 may be used cifically with the primary interaction partner, e.g., as is well in the purification process in, for example, an affinity chro known in the art of antigen/antibody detection. The detect matography step. able label may be directly detectable or indirectly detectable, e.g., through combined action with one or more additional 0060. It is to be understood that the present invention is not members of a signal producing system. Examples of directly limited to using antibodies or antibody fragments as interac detectable labels include radioactive, paramagnetic, fluores tion partners. In particular, the present invention also encom cent, light scattering, absorptive and colorimetric labels. passes the use of synthetic interaction partners that mimic the Examples of indirectly detectable include chemiluminescent functions of antibodies. Several approaches to designing and/ labels, e.g., enzymes that are capable of converting a substrate or identifying antibody mimics have been proposed and dem to a chromogenic product such as alkaline phosphatase, onstrated (e.g., see the reviews by Hsieh-Wilson et al., Acc. horseradish peroxidase and the like. Chem. Res. 29:164, 2000 and Peczuh and Hamilton, Chem. Rev. 100:2479, 2000). For example, small molecules that bind 0062 Once a labeled interaction partner has bound the protein Surfaces in a fashion similar to that of natural proteins TLE3 marker, the complex may be visualized or detected in a have been identified by screening synthetic libraries of small variety of ways, with the particular manner of detection being molecules or natural product isolates (e.g., see Gallop et al., J. chosen based on the particular detectable label, where repre Med. Chem. 37:1233, 1994; Gordon et al., J. Med. Chem. sentative detection means include, e.g., Scintillation counting, 37:1385, 1994; DeWitt et al., Proc. Natl. Acad. Sci. U.S.A. autoradiography, measurement of paramagnetism, fluores 90:6909, 1993; Bunin et al., Proc. Natl. Acad. Sci. U.S.A. cence measurement, light absorption measurement, measure 91:4708, 1994; Virgilio and Ellman, J. Am. Chem. Soc. 116: ment of light scattering and the like. 11580, 1994; Wang et al., J. Med. Chem. 38:2995, 1995; and 0063. In general, association between an interaction part Kick and Ellman, J. Med. Chem. 38:1427, 1995). Similarly, ner and the TLE3 marker may be assayed by contacting the combinatorial approaches have been Successfully applied to interaction partner with a cancer sample that includes the screen libraries of peptides and proteins for their ability to marker. Depending upon the nature of the sample, appropri bind a range of proteins (e.g., see Cullet al., Proc. Natl. Acad. ate methods include, but are not limited to, immunohis Sci. U.S.A. 89:1865, 1992; Mattheakis et al., Proc. Natl. Acad. tochemistry (IHC), radioimmunoassay, ELISA, immunoblot Sci. U.S.A. 91:9022, 1994; Scott and Smith, Science 249:386, ting and fluorescence activates cell sorting (FACS). In the 1990; Devlin et al., Science 249:404, 1990; Corey et al., Gene case where the protein is to be detected in a tissue sample, 128:129, 1993: Bray et al., Tetrahedron Lett. 31:5811, 1990; e.g., a biopsy sample, IHC is a particularly appropriate detec Fodor et al., Science 251:767, 1991; Houghten et al., Nature tion method. Techniques for obtaining tissue and cell samples 354:84, 1991; Lam et al., Nature 354:82, 1991; Blake and and performing IHC and FACS are well known in the art. Litzi-Davis, Bioconjugate Chem. 3:510, 1992: Needels et al., 0064. Where large numbers of samples are to be handled Proc. Natl. Acad. Sci. U.S.A. 90:10700, 1993; and Ohlmeyer (e.g., when simultaneously analyzing several samples from et al., Proc. Natl. Acad. Sci. U.S.A. 90:10922, 1993). Similar the same patient or samples from different patients), it may be approaches have also been used to study carbohydrate-pro desirable to utilize arrayed and/or automated formats. In cer tein interactions (e.g., see Oldenburg et al., Proc. Natl. Acad. tain embodiments, tissue arrays as described in the Examples Sci. U.S.A. 89:5393, 1992) and polynucleotide-protein inter may be used. Tissue arrays may be constructed according to a actions (e.g., see Ellington and Szostak, Nature 346:818, variety of techniques. According to one procedure, a com 1990 and Tuerk and Gold, Science 249:505, 1990). These mercially-available mechanical device (e.g., the manual tis approaches have also been extended to study interactions sue arrayer MTA1 from Beecher Instruments of Sun Prairie, between proteins and unnatural biopolymers such as oligo Wis.) is used to remove an 0.6-micron-diameter, full thick carbamates, oligoureas, oligosulfones, etc. (e.g., see Zucker ness “core' from a paraffin block (the donor block) prepared mannet al., J. Am. Chem. Soc. 114: 10646, 1992; Simon et al., from each patient, and to insert the core into a separate par Proc. Natl. Acad. Sci. U.S.A. 89:9367, 1992: Zuckermann et affin block (the recipient block) in a designated location on a al., J. Med. Chem. 37:2678, 1994: Burgess et al., Angew. grid. In preferred embodiments, cores from as many as about Chem. Int. Ed. Engl. 34:907, 1995; and Cho et al., Science 400 patients (or multiple cores from the same patient) can be 261: 1303, 1993). Yet further, alternative protein scaffolds that inserted into a single recipient block; preferably, core-to-core are loosely based around the basic fold of antibody molecules spacing is approximately 1 mm. The resulting tissue array have been suggested and may be used in the preparation of may be processed into thin sections for staining with interac inventive interaction partners (e.g., see Ku and Schultz Proc. tion partners according to standard methods applicable to Natl. Acad. Sci. U.S.A. 92:6552, 1995). Antibody mimics paraffin embedded material. comprising a scaffold of a small molecule Such as 3-aminom 0065. Whatever the format, and whatever the detection ethylbenzoic acid and a Substituent consisting of a single strategy, identification of a discriminating titer can simplify peptide loop have also been constructed. The peptide loop binding studies to assess the desirability of using an interac performs the binding function in these mimics (e.g., see tion partner. In such studies, the interaction partner is con Smythe et al., J. Am. Chem. Soc. 116:2725, 1994). A synthetic tacted with a plurality of different samples that preferably antibody mimic comprising multiple peptide loops built have at least one common trait (e.g., tissue of origin), and around a calixarene unit has also been described (e.g., see often have multiple common traits (e.g., tissue of origin, U.S. Pat. No. 5,770.380 to Hamilton et al.). stage, microscopic characteristics, etc.). In some cases, it will US 2010/0062444 A1 Mar. 11, 2010

be desirable to select a group of samples with at least one labeled secondary primer that hybridizes specifically with the common trait and at least one different trait, so that a titer is primary primer (e.g., a region of the primary primer that does determined that distinguishes the different trait. In other not hybridize with the TLE3 marker). In yet other embodi cases, it will be desirable to select a group of samples with no ments it may be advantageous to amplify the TLE3 marker detectable different traits, so that a titer is determined that within the cancer sample by PCR using a set of primers distinguishes among previously indistinguishable samples. designed to amplify a region of the TLE3 gene. The resulting Those of ordinary skill in the art will understand, however, product can then be detected, e.g., using a labeled secondary that the present invention often will allow both of these goals primer that hybridizes with the amplified product. Those to be accomplished even in studies of sample collections with skilled in the art will appreciate variations on these embodi varying degrees of similarity and difference. mentS. 0066. As discussed above and in the Examples, the inven 0070 Considerations for primer design are well known in tors have applied these techniques to samples from breast and the art and are described, for example, in Newton, et al. (eds.) ovarian cancer patients. The invention also encompasses the PCR: Essential data Series, John Wiley & Sons: PCR Primer: recognition that markers that are secreted from the cells in A Laboratory Manual, Cold Spring Harbor Laboratory Press, which they are produced may be present in serum, enabling Cold Spring Harbor, N.Y., 1995; White, et al. (eds.) PCR their detection through a blood test rather than requiring a Protocols. Current methods and Applications, Methods in biopsy specimen. An interaction partner that binds to Such Molecular Biology, The Humana Press, Totowa, N.J., 1993. markers represents a particularly preferred embodiment of In addition, a variety of computer programs known in the art the invention. may be used to select appropriate primers. 0067. In general, the results of such an assay can be pre 0071. In general, a detectable label may be directly detect sented in any of a variety of formats. The results can be able or indirectly detectable, e.g., through combined action presented in a qualitative fashion. For example, the test report with one or more additional members of a signal producing may indicate only whether or not the TLE3 marker was system. Examples of directly detectable labels include radio detected, perhaps also with an indication of the limits of active, paramagnetic, fluorescent, light scattering, absorptive detection. Additionally the test report may indicate the sub and colorimetric labels. Examples of indirectly detectable cellular location of binding, e.g., nuclear Versus cytoplasmic include chemiluminescent labels, e.g., enzymes that are and/or the relative levels of binding in these different subcel capable of converting a Substrate to a chromogenic product lular locations. The results may be presented in a semi-quan Such as alkaline phosphatase, horseradish peroxidase and the titative fashion. For example, various ranges may be defined like. and the ranges may be assigned a score (e.g., 0 to 5) that (0072. Once a labeled primer has hybridized with the TLE3 provides a certain degree of quantitative information. Such a marker, the complex may be visualized or detected in a vari score may reflect various factors, e.g., the number of cells in ety of ways, with the particular manner of detection being which the marker is detected, the intensity of the signal chosen based on the particular detectable label, where repre (which may indicate the level of expression of the marker), sentative detection means include, e.g., Scintillation counting, etc. The results may be presented in a quantitative fashion, autoradiography, measurement of paramagnetism, fluores e.g., as a percentage of cells in which the marker is detected, cence measurement, light absorption measurement, measure as a concentration, etc. As will be appreciated by one of ment of light scattering and the like. ordinary skill in the art, the type of output provided by a test 0073. In general, hybridization between a primer and the will vary depending upon the technical limitations of the test TLE3 marker may be assayed by contacting the primer with and the biological significance associated with detection of a cancer sample that includes the marker. Depending upon the the marker. For example, in certain circumstances a purely nature of the cancer sample, appropriate methods include, but qualitative output (e.g., whether or not the marker is detected are not limited to, microarray analysis, in situ hybridization, at a certain detection level) provides significant information. Northern blot, and various nucleic acid amplification tech In other cases a more quantitative output (e.g., a ratio of the niques such as PCR, RT-PCR, quantitative PCR, the ligase level of expression of the marker in two samples) is necessary. chain reaction, etc. Detecting TLE3 Polynucleotide Markers Identification of Novel Therapies 0068 Although in many cases detection of polypeptide 0074 The predictive power of TLE3 is useful according to markers using interaction partners such as antibodies may the present invention not only to classify cancers with respect represent the most convenient means of determining whether to their likely responsiveness to known therapies, but also to TLE3 is expressed in a particular sample, the inventive meth identify potential new therapies or therapeutic agents that ods also encompass the use of primers for the detection of could be useful in the treatment of cancer. polynucleotide markers. A variety of methods for detecting 0075 Indeed, TLE3 represents an attractive candidate for the presence of a particular polynucleotide marker are known identification of new therapeutic agents (e.g., via screens to in the art and may be used in the inventive methods. In detect compounds or entities that bind or hybridize to the general, these methods rely on hybridization between one or marker, preferably with at least a specified affinity and/or more primers and the polynucleotide marker. specificity, and/or via Screens to detect compounds or entities 0069. Any available strategy or system may be utilized to that modulate (i.e., increase or decrease) expression, local detect hybridization between primers and the TLE3 poly ization, modification, or activity of the marker. Thus, in one nucleotides (which could be a TLE3 mRNA, a cDNA pro embodiment the present invention provides methods com duced by RT-PCR from mRNA, RNA produced from such prising steps of contacting a test compound with a cell cDNA, etc.). In certain embodiments, hybridization can be expressing the TLE3 marker (e.g., individual engineered cells detected by simply adding a detectable label to the primer. In or in the context of a tissue, etc.); and determining whether the other embodiments, hybridization can be detected by using a test compound modulates the expression, localization, modi US 2010/0062444 A1 Mar. 11, 2010

fication, or activity of the TLE3 marker. In many instances, pairs include protein/co-factor and enzyme? substrate pairs. interaction partners or primers (e.g., antisense or RNAi prim Besides the commonly used biotin/avidin pair, these include ers) themselves may prove to be useful therapeutics. without limitation, biotin/streptavidin, digoxigeninfanti 0076. Thus the present invention provides interaction part digoxigenin, FK506/FK506-binding protein (FKBP), rapa ners and primers that are themselves useful therapeutic mycin/FKBP, cyclophilin/cyclosporin and glutathione/glu agents. For example, binding by an antibody raised against tathione transferase pairs. Other suitable ligand/receptor TLE3 to cancerous cells might inhibit growth of those cells. pairs would be recognized by those skilled in the art, e.g., Alternatively or additionally, interaction partners defined or monoclonal antibodies paired with a epitope tag such as, prepared according to the present invention could be used to without limitation, glutathione-S-transferase (GST), c-myc, deliver a therapeutic agent to a cancer cell. In particular, FLAG(R) and maltose binding protein (MBP) and further interaction partners (e.g., an antibody raised against TLE3) those described in Kessler pp. 105-152 of Advances in may be coupled to one or more therapeutic agents. Suitable Mutagenesis' Ed. by Kessler, Springer-Verlag, 1990; “Affin agents in this regard include radionuclides and drugs. Pre ity Chromatography. Methods and Protocols (Methods in ferred radionuclides include Y, I, I, I, Re, Molecular Biology) Ed. by Pascal Baillon, Humana Press, '''At and ''Bi. Preferred drugs include chlorambucil, ifos 2000; and “Immobilized Affinity Ligand Techniques” by Her phamide, meclorethamine, cyclophosphamide, carboplatin, manson et al., Academic Press, 1992. cisplatin, procarbazine, decarbazine, carmustine, cytarabine, 0079. Where a therapeutic agent is more potent when free hydroxyurea, mercaptopurine, methotrexate, paclitaxel, doc from the interaction partner, it may be desirable to use a linker etaxel, thioguanine, 5-fluorouracil, actinomycin D, bleomy group which is cleavable during or upon internalization into a cin, daunorubicin, doxorubicin, etoposide, vinblastine, Vinc cell. A number of different cleavable linker groups have been ristine, L-asparginase, adrenocorticosteroids, canciclovir described. The mechanisms for the intracellular release of an triphosphate, adenine arabinonucleoside triphosphate, agent from these linker groups include cleavage by reduction 5-aziridinyl-4-hydroxylamino-2-nitrobenzamide, acrolein, of a disulfide bond (e.g., U.S. Pat. No. 4,489,710 to Spitler), phosphoramide mustard, 6-methylpurine, etoposide, benzoic by irradiation of a photolabile bond (e.g., U.S. Pat. No. 4,625, acid mustard, cyanide and nitrogen mustard. 014 to Senter et al.), by hydrolysis of derivatized amino acid 0077 According to such embodiments, the therapeutic side chains (e.g., U.S. Pat. No. 4,638.045 to Kohn et al.), by agent may be coupled with an interaction partner by director serum complement-mediated hydrolysis (e.g., U.S. Pat. No. indirect covalent or non-covalent interactions. A direct inter 4,671,958 to Rodwell et al.) and by acid-catalyzed hydrolysis action between a therapeutic agent and an interaction partner (e.g., U.S. Pat. No. 4,569,789 to Blattler et al.). is possible when each possesses a Substituent capable of 0080. In certain embodiments, it may be desirable to reacting with the other. For example, a nucleophilic group, couple more than one therapeutic agent to an interaction Such as an amino or sulfhydryl group, on one may be capable partner. In one embodiment, multiple molecules of an agent of reacting with a carbonyl-containing group. Such as an are coupled to one interaction partner molecule. In another anhydride oran acid halide, or with an alkyl group containing embodiment, more than one type of therapeutic agent may be a good leaving group (e.g., a halide) on the other. Indirect coupled to one interaction partner molecule. Regardless of interactions might involve a linker group that is itself non the particular embodiment, preparations with more than one covalently bound to both the therapeutic agent and the inter agent may be prepared in a variety of ways. For example, action partner. A linker group can function as a spacer to more than one agent may be coupled directly to an interaction distance an interaction partner from an agent in order to avoid partner molecule, or linkers that provide multiple sites for interference with association capabilities. A linker group can attachment can be used. also serve to increase the chemical reactivity of a substituent I0081 Alternatively, a carrier can be used. A carrier may on an agent or an interaction partner and thus increase the bear the agents in a variety of ways, including covalent bond coupling efficiency. An increase in chemical reactivity may ing either directly or via a linker group. Suitable carriers also facilitate the use of agents, or functional groups on include proteins such as albumins (e.g., U.S. Pat. No. 4,507, agents, which otherwise would not be possible. 234 to Kato et al.), peptides, and polysaccharides such as 0078. It will be evident to those skilled in the art that a aminodextran (e.g., U.S. Pat. No. 4,699.784 to Shih et al.). A variety of bifunctional or polyfunctional reagents, both carrier may also bear an agent by non-covalent bonding or by homo- and hetero-functional (such as those described in the encapsulation, such as within a liposome vesicle (e.g., U.S. catalog of the Pierce Chemical Co., Rockford, Ill.), may be Pat. Nos. 4,429,008 to Martinet al. and 4,873,088 to Mayhew employed as the linker group. Coupling may be effected, for et al.). Carriers specific for radionuclide agents include radio example, through amino groups, carboxyl groups, Sulfydryl halogenated Small molecules and chelating compounds. For groups or oxidized carbohydrate residues. There are numer example, U.S. Pat. No. 4,735,792 to Srivastava discloses rep ous references describing Such methodology, e.g., U.S. Pat. resentative radiohalogenated Small molecules and their syn No. 4,671,958, to Rodwell et al. It will further be appreciated thesis. A radionuclide chelate may be formed from chelating that a therapeutic agent and an interaction partner may be compounds that include those containing nitrogen and Sulfur coupled via non-covalent interactions, e.g., ligand/receptor atoms as the donor atoms for binding the metal, or metal type interactions. Any ligand/receptor pair with a sufficient oxide, radionuclide. For example, U.S. Pat. No. 4,673,562 to stability and specificity to operate in the context of the inven Davison et al. discloses representative chelating compounds tion may be employed to couple a therapeutic agent and an and their synthesis. interaction partner. To give but an example, a therapeutic I0082. When interaction partners are themselves therapeu agent may be covalently linked with biotin and an interaction tics, it will be understood that, in many cases, any interaction partner with avidin. The strong non-covalent binding of biotin partner that binds the same marker may be so used. to avidin would then allow for coupling of the therapeutic I0083. In one preferred embodiment of the invention, the agent and the interaction partner. Typical ligand/receptor therapeutic agents (whetherinteraction partners or otherwise) US 2010/0062444 A1 Mar. 11, 2010

are antibodies, e.g., an antibody against the TLE3 marker. As invention bind to markers (e.g., TLE3) that serve as targets for is well known in the art, when using an antibody or fragment therapeutic agents. Also, inventive interaction partners may thereoffortherapeutic purposes it may prove advantageous to be used to deliver a therapeutic agent to a cancer cell. For use a “humanized' or “veneered version of an antibody of example, interaction partners provided inaccordance with the interest to reduce any potential immunogenic reaction. In present invention may be coupled to one or more therapeutic general, “humanized' or “veneered antibody molecules and agents. fragments thereof minimize unwanted immunological I0088. The invention includes pharmaceutical composi responses toward antihuman antibody molecules which can tions comprising these inventive therapeutic agents. In gen limit the duration and effectiveness of therapeutic applica eral, a pharmaceutical composition will include a therapeutic tions of those moieties in human recipients. agent in addition to one or more inactive agents such as a 0084. A number of “humanized' antibody molecules sterile, biocompatible carrier including, but not limited to, comprising an antigen binding portion derived from a non sterile water, saline, buffered saline, or dextrose solution. The human immunoglobulin have been described in the art, pharmaceutical compositions may be administered either including chimeric antibodies having rodent variable regions alone or in combination with other therapeutic agents includ and their associated complementarity-determining regions ing other chemotherapeutic agents, hormones, vaccines and/ (CDRs) fused to human constant domains (e.g., see Winter et or radiation therapy. By “in combination with, here and al., Nature 349:293, 1991; Lobuglio et al., Proc. Nat. Acad. elsewhere in the specification, it is not intended to imply that Sci. USA 86:4220, 1989: Shaw et al., J. Immunol. 138:4534, the agents must be administered at the same time or formu 1987; and Brown et al., Cancer Res. 47:3577, 1987), rodent lated for delivery together, although these methods of deliv CDRS grafted into a human Supporting framework region ery are within the scope of the invention. In general, each (FR) prior to fusion with an appropriate human antibody agent will be administered at a dose and on a time schedule constant domain (e.g., see Riechmann et al., Nature 332:323, determined for that agent. Additionally, the invention encom 1988; Verhoeyen et al., Science 239:1534, 1988; and Jones et passes the delivery of the inventive pharmaceutical composi al. Nature 321:522, 1986) and rodent CDRS supported by tions in combination with agents that may improve their recombinantly veneered rodent FRS (e.g., see European bioavailability, reduce or modify their metabolism, inhibit Patent Publication No. 519,596, published Dec. 23, 1992). It their excretion, or modify their distribution within the body. is to be understood that the invention also encompasses “fully Although the pharmaceutical compositions of the present human antibodies produced using the XenoMouseTM tech invention can be used for treatment of any subject (e.g., any nology (AbCienix Corp., Fremont, Calif.) according to the animal) in need thereof, they are most preferably used in the techniques described in U.S. Pat. No. 6,075,181. treatment of humans. I0085. Yet further, so-called “veneered antibodies may be I0089. The pharmaceutical compositions of this invention used that include “veneered FRs'. The process of veneering can be administered to humans and other animals by a variety involves selectively replacing FR residues from, e.g., a of routes including oral, intravenous, intramuscular, intra murine heavy or light chain variable region, with human FR arterial, Subcutaneous, intraventricular, transdermal, rectal, residues in order to provide a Xenogeneic molecule compris intravaginal, intraperitoneal, topical (as by powders, oint ing an antigen binding portion which retains Substantially all ments, or drops), bucal, or as an oral or nasal spray or aerosol. of the native FR protein folding structure. Veneering tech In general the most appropriate route of administration will niques are based on the understanding that the antigen bind depend upon a variety of factors including the nature of the ing characteristics of an antigen binding portion are deter agent (e.g., its stability in the environment of the gastrointes mined primarily by the structure and relative disposition of tinal tract), the condition of the patient (e.g., whether the the heavy and light chain CDR sets within the antigen-asso patient is able to tolerate oral administration), etc. At present ciation Surface (e.g., see Davies et al., Ann. Rev. Biochem. the intravenous route is most commonly used to deliverthera 59:439, 1990). Thus, antigen association specificity can be peutic antibodies. However, the invention encompasses the preserved in a humanized antibody only wherein the CDR delivery of the inventive pharmaceutical composition by any structures, their interaction with each other and their interac appropriate route taking into consideration likely advances in tion with the rest of the variable region domains are carefully the sciences of drug delivery. maintained. By using veneering techniques, exterior (e.g., solvent-accessible) FR residues which are readily encoun 0090 General considerations in the formulation and tered by the immune system are selectively replaced with manufacture of pharmaceutical agents may be found, for human residues to provide a hybrid molecule that comprises example, in Remington's Pharmaceutical Sciences, 19" ed., either a weakly immunogenic, or substantially non-immuno Mack Publishing Co., Easton, Pa., 1995. genic veneered surface. I0086 Preferably, interaction partners suitable for use as EXEMPLIFICATION therapeutics (ortherapeutic agent carriers) exhibit high speci ficity for the target marker (e.g., TLE3) and low background Example 1 binding to other markers. In certain embodiments, mono clonal antibodies are preferred for therapeutic purposes. Raising Antibodies 0091. This example describes a method that was Pharmaceutical Compositions employed to generate the TLE3 antibodies used in these 0087 As mentioned above, the present invention provides Examples. Similar methods may be used to generate an anti new therapies and methods for identifying these. In certain body that binds to any marker of interest (e.g., to proteins that embodiments, an interaction partner or primer may be a use are or are derived from other markers listed in Appendix A). ful therapeutic agent. Alternatively or additionally, interac In some cases, antibodies may be obtained from commercial tion partners defined or prepared according to the present Sources (e.g., Chemicon, Dako, Oncogene Research Prod US 2010/0062444 A1 Mar. 11, 2010 11 ucts, NeoMarkers, etc.) or other publicly available sources 0.126 N-Fmoc protected amino acids attached to Wang (e.g., Imperial Cancer Research Technology, etc.). Resin from Calbiochem. See 97-98 Catalog pp. 161 164. Materials and Solutions (O127 NMP (Cat. No. CAS872-50-4, Burdick and Jack son, Muskegon, Mich.) 0092 Anisole (Cat. No. A4405, Sigma, St. Louis, Mo.) 0.128 Peptide (Synthesized by Research Genetics. 0093 2,2'-azino-di-(3-ethyl-benzthiazoline-sulfonic Details given below) acid) (ABTS) (Cat. No. A6499, Molecular Probes, 0129. Piperidine (Cat. No. 80640, Fluka, available Eugene, Oreg.) through Sigma) 0094) Activated maleimide Keyhole Limpet Hemocya 0130 Sodium Bicarbonate (Cat. No. BP328-1, Fisher) nin (Cat. No. 77106, Pierce, Rockford, Ill.) 0131 Sodium Borate (Cat. No. B9876, Sigma) (0095 Keyhole Limpet Hemocyanin (Cat. No. 77600, (0132) Sodium Carbonate (Cat. No. BP357-1, Fisher) Pierce, Rockford, Ill.) 0.133 Sodium Chloride (Cat. No. BP358-10, Fisher) (0096 Phosphoric Acid (HPO) (Cat. No. P6560, 0134 Sodium Hydroxide (Cat. No. SS 255-1, Fisher) Sigma) 0135 Streptavidin (Cat. No. 1520, Boehringer Man 0097 Glacial Acetic Acid (Cat No. BP1185-500, nheim) Fisher) 0136. Thioanisole (Cat. No. T-2765, Sigma) 0.098 EDC (EDAC) (Cat No. 341006, Calbiochem) 0.137 Trifluoroacetic acid (Cat. No. TX 1275-3, EM (0099 25% Glutaraldehyde (Cat No. G-5882, Sigma) Sciences) 0100 Glycine (Cat No. G-8898, Sigma) 0138 Tween-20 (Cat. No. BP 337-500, Fisher) 0101 Biotin (Cat. No. B2643, Sigma) 0139 Wetbox (Rectangular Servin SaverTM Part No. 0102 Boric acid (Cat. No. B0252, Sigma) 3862, Rubbermaid, Wooster, Ohio) (0103 Sepharose 4B (Cat. No. 17-0120-01, LKB/Phar 0140 BBS Borate Buffered Saline with EDTA dis macia, Uppsala, Sweden) solved in distilled water (pH 8.2 to 8.4 with HCl or 0104 Bovine Serum Albumin (LP) (Cat. No. 100 350, NaOH), 25 mMSodium borate (Borax), 100 mM Boric Boehringer Mannheim, Indianapolis, Ind.) Acid, 75 mM NaCl and 5 mM EDTA. 0105 Cyanogen bromide (Cat. No. C6388, Sigma) 0.141 0.1 NHCl in saline as follows: concentrated HCl 0106 Dialysis tubing Spectra/Por Membrane MWCO: (8.3 ml/0.917 liter distilled water) and 0.154M NaCl 6-8,000 (Cat. No. 132665, Spectrum Industries, Laguna 0142 Glycine (pH 2.0 and pH3.0) dissolved in distilled Hills, Calif.) water and adjusted to the desired pH, 0.1 M glycine and 0107 Dimethyl formamide (DMF) (Cat. No. 22705-6, 0.154 MNaCl. Aldrich, Milwaukee, Wis.) 0.143 5x Borate 1x Sodium Chloride dissolved in dis 0108 DIC (Cat. No. BP 592-500, Fisher) tilled water, 0.11 M NaCl, 60 mM Sodium Borate and 0109 Ethanedithiol (Cat. No. 39, 802-0, Aldrich) 250 mM Boric Acid. 0110 Ether (Cat. No. TX 1275-3, EM Sciences) 0144. Substrate Buffer in distilled water adjusted to pH 0111 Ethylenediaminetetraacetatic acid (EDTA) (Cat. 4.0 with sodium hydroxide, 50 to 100 mM Citric Acid. No. BP 120-1, Fisher, Springfield, N.J.) (0145 AA solution: HOBt is dissolved in NMP (8.8 0112 1-ethyl-3-(3' dimethylaminopropyl)-carbodiim grams HOBt to 1 liter NMP). Fmoc-N-a-amino at a ide, HCL (EDC) (Cat. no. 341-006, Calbiochem, San concentration at 0.53 M. Diego, Calif.) 0146 DIC solution: 1 part DIC to 3 parts NMP. 0113 Freund's Adjuvant, complete (Cat. No. M-0638 0147 Deprotecting solution: 1 part Piperidine to 3 parts 50B, Lee Laboratories, Grayson, Ga.) DMF. 0114 Freund's Adjuvant, incomplete (Cat. No. 0.148 Reagent R: 2 parts anisole, 3 parts ethanedithiol, M-0639-50B, Lee Laboratories) 5 parts thioanisole and 90 parts trifluoroacetic acid. 0115 Fritted chromatography columns (Column part No. 12131011: Frit Part No. 12131029, Varian Sample Equipment Preparation Products, Harbor City, Calif.) 0116 Gelatin from Bovine Skin (Cat. No. G9382, 0149 MRX Plate Reader (Dynatech, Chantilly, Va.) Sigma) 0.150 Hamilton Eclipse (Hamilton Instruments, Reno, Nev.) 0117 Goat anti-rabbit IgG, biotinylated (Cat. No. A 0151. Beckman TJ-6 Centrifuge (Model No. TJ-6, 0418, Sigma) Beckman Instruments, Fullerton, Calif.) 0118 HOBt (Cat. No. 01-62-0008, Calbiochem) 0152 Chart Recorder (Recorder 1 Part No. 18-1001-40, 0119 Horseradish peroxidase (HRP) (Cat. No. 814 Pharmacia LKB Biotechnology) 393, Boehringer Mannheim) 0153 UV Monitor (Uvicord SII Part No. 18-1004-50, I0120 HRP-Streptavidin (Cat. No. S5512, Sigma) Pharmacia LKB Biotechnology) I0121 Hydrochloric Acid (Cat. No. 71445-500, Fisher) 0154) Amicon Stirred Cell Concentrator (Model 8400, I0122) Hydrogen Peroxide 30% w/w (Cat. No. H1009, Amicon, Beverly, Mass.) Sigma) O155 30 kD MW cut-off filter (Cat. No.YM-30 Mem (0123 Methanol (Cat. No. A412-20, Fisher) branes Cat. No. 13742, Amicon) (0.124 Microtiter plates, 96 well (Cat. No. 2595, Corn 0156 Multi-channel Automated Pipettor (Cat. No. ing-Costar, Pleasanton, Calif.) 4880, Corning Costar, Cambridge, Mass.) 0.125 N-Fmoc protected amino acids from Calbio (O157 pH Meter Corning 240 (Corning Science Prod chem. See 97-98 Catalog pp. 1-45. ucts, Corning Glassworks, Corning, N.Y.) US 2010/0062444 A1 Mar. 11, 2010 12

0158 ACT396 peptide synthesizer (Advanced sizer dictated) and 250 ml of DIC solution were added ChemTech, Louisville, Ky.) to the reaction vessel. The reaction vessel was incu 0159 Vacuum dryer (Box from Labconco, Kansas City, bated for thirty minutes and washed once. The cou Mo. and Pump from Alcatel, Laurel, Md.). pling step was repeated once. 0160 Lyophilizer (Unitop 600S 1 in tandem with Freez (0168 2d Wash Cycle emobile 12, both from Virtis, Gardiner, N.Y.) (0169 Step 3 Final Deprotection: Steps 2a and 2b were performed one last time. Peptide Selection 0170 Resins were deswelled in methanol (rinsed twice in 0161 Peptide or peptides against which antibodies would 5 ml methanol, incubated 5 minutes in 5 ml methanol, rinsed be raised were selected from within the protein sequence of in 5 ml methanol) and then vacuum dried. interest using a program that uses the Hopp/Woods method 0171 Peptide was removed from the resin by incubating 2 (described in Hopp and Woods, Mol. Immunol. 20:483, 1983 hours in reagent R and then precipitated into ether. Peptide and Hopp and Woods, Proc. Nat. Acad. Sci. U.S.A. 78:3824, was washed in ether and then vacuum dried. Peptide was 1981). The program uses a scanning window that identifies resolubilized in diHO, frozen and lyophilized overnight. peptide sequences of 15-20 amino acids containing several Conjugation of Peptide with Keyhole Limpet Hemocyanin putative antigenic epitopes as predicted by low solvent acces 0172 Peptide (6 mg) was conjugated with Keyhole Lim sibility. This is in contrast to most implementations of the pet Hemocyanin (KLH). If the selected peptide includes at Hopp/Woods method, which identify single short (-6 amino least one cysteine, three aliquots (2 mg) can be dissolved in acids) presumptive antigenic epitopes. Occasionally the pre PBS (2 ml) and coupled to KLH via glutaraldehyde, EDC or dicted solvent accessibility was further assessed by PHD maleimide activated KLH (2 mg) in 2 ml of PBS for a total prediction of loop structures (described in Rost and Sander, volume of 4 ml. When the peptide lacks cysteine (as in the Proteins 20:216, 1994). Preferred peptide sequences display TLE3 peptide), two aliquots (3 mg) can be coupled via glut minimal similarity with additional known human proteins. araldehyde and EDC methods. Similarity was determined by performing BLASTP align 0173 Maleimide coupling can be accomplished by mix ments, using a wordsize of 2 (described in Altschul et al., J. ing 2 mg of peptide with 2 mg of maleimide-activated KLH Mol. Biol. 215:403, 1990). All alignments given an EXPECT dissolved in PBS (4 ml) and incubating 4 hr. value less than 1000 were examined and alignments with 0.174 EDC coupling can be accomplished by mixing 2 mg similarities of greater than 60% or more than four residues in of peptide, 2 mgunmodified KLH, and 20 mg of EDC in 4 ml an exact contiguous non-gapped alignment forced those pep PBS (lowered to pH5 by the addition of phosphoric acid), and tides to be rejected. When it was desired to target regions of incubating for 4 hours. The reaction is then stopped by the proteins exposed outside the cell membrane, extracellular slow addition of 1.33 ml acetic acid (pH 4.2). When using regions of the protein of interest were determined from the EDC to couple 3 mg of peptide, the amounts listed above are literature or as defined by predicted transmembrane domains increased by a factor of 1.5. using a hidden Markov model (described in Krogh et al., J. 0.175. Glutaraldehyde coupling occurs when 2 mg of pep Mol. Biol. 305:567, 2001). When the peptide sequence was in tide are mixed with 2 mg of KLH in 0.9 ml of PBS. 0.9 ml of an extracellular domain, peptides were rejected if they con 0.2% glutaraldehyde in PBS is added and mixed for one hour. tained N-linked glycosylation sites. As shown in Appendix A, 0.46 ml of 1 M glycine in PBS is added and mixed for one for the preparation of TLE3 antibodies a single peptide was hour. When using glutaraldehyde to couple 3 mg of peptide, used having the amino acid sequence KNHHELDHRERES the above amounts are increased by a factor of 1.5. SAN (SEQ ID NO. 383). Appendix A provides one to three 0176 The conjugated aliquots were subsequently peptide sequences that can be used in preparing antibodies repooled, mixed for two hours, dialyzed in 1 liter PBS and against other markers. lyophilized.

Peptide Synthesis Immunization of Rabbits 0162 The sequence of the desired peptide was provided to the peptide synthesizer. The C-terminal residue was deter (0177. Two New Zealand White Rabbits were injected with mined and the appropriate Wang Resin was attached to the 250 ug (total) KLH conjugated peptide in an equal Volume of reaction vessel. The peptide or peptides were synthesized complete Freund's adjuvant and saline in a total volume of 1 C-terminus to N-terminus by adding one amino acid at a time ml. 100 ug KLH conjugated peptide in an equal Volume of using a synthesis cycle. Which amino acid is added was incomplete Freund's Adjuvant and saline were then injected controlled by the peptide synthesizer, which looks to the into three to four subcutaneous dorsal sites for a total volume sequence of the peptide that was entered into its database. The of 1 ml two, six, eight and twelve weeks after the first immu synthesis steps were performed as follows: nization. The immunization schedule was as follows: (0163 Step 1 Resin Swelling: Added 2 ml DMF, incu bated 30 minutes, drained DMF. 0164. Step 2 Synthesis cycle (repeated over the length Day 0 Pre-immune bleed, primary immunization Day 15 1st boost of the peptide) Day 27 1st bleed 0.165 2a Deprotection: 1 ml deprotecting solution Day 44 2nd boost was added to the reaction vessel and incubated for 20 Day 57 2nd bleed and 3rd boost minutes. Day 69 3rd bleed Day 84 4th boost (0166 2b Wash Cycle Day 98 4th bleed 0.167 2c Coupling: 750 ml of amino acid solution (changed as the sequence listed in the peptide synthe US 2010/0062444 A1 Mar. 11, 2010

Collection of Rabbit Serum BBS. The column was washed with enough volume for the optical density at 280 nm to reach baseline. (0178. The rabbits were bled (30 to 50 ml) from the auricu lar artery. The blood was allowed to clot at room temperature Affinity Purification of Antibodies for 15 minutes and the serum was separated from the clot 0182. The peptide affinity column was attached to a UV using an IEC DPR-6000 centrifuge at 5000 g. Cell-free serum monitor and chart recorder. The titered rabbit antiserum was was decanted gently into a clean test tube and stored at -20° thawed and pooled. The serum was diluted with one volume C. for affinity purification. of BBS and allowed to flow through the columns at 10 ml per minute. The non-peptide immunoglobulins and other proteins Determination of Antibody Titer were washed from the column with excess BBS until the optical density at 280 nm reached baseline. The columns were 0179 All solutions with the exception of wash solution disconnected and the affinity purified column was eluted were added by the Hamilton Eclipse, a liquid handling dis using a stepwise pH gradient from pH 7.0 to 1.0. The elution penser. The antibody titer was determined in the rabbits using was monitored at 280 nm and fractions containing antibody an ELISA assay with peptide on the solid phase. Flexible high (pH3.0 to 1.0) were collected directly into excess 0.5MBBS. binding ELISA plates were passively coated with peptide Excess buffer (0.5 MBBS) in the collection tubes served to diluted in BBS (100 ul, 1 g/well) and the plate was incubated neutralize the antibodies collected in the acidic fractions of at 4°C. in a wetbox overnight (air-tight container with moist the pH gradient. ened cotton balls). The plates were emptied and then washed 0183 The entire procedure was repeated with “depleted three times with BBS containing 0.1% Tween-20 (BBS-TW) serum to ensure maximal recovery of antibodies. The eluted by repeated filling and emptying using a semi-automated material was concentrated using a stirred cell apparatus and a plate washer. The plates were blocked by completely filling membrane with a molecular weight cutoff of 30 kD. The each well with BBS-TW containing 1% BSA and 0.1% gela concentration of the final preparation was determined using tin (BBS-TW-BG) and incubating for 2 hours at room tem an optical density reading at 280 nm. The concentration was perature. The plates were emptied and sera of both pre- and determined using the following formula: mg/ml=ODs/1.4. post-immune serum were added to wells. The first well con 0184. It will be appreciated that in certain embodiments, tained sera at 1:50 in BBS. The sera were then serially titrated additional steps may be used to purify antibodies of the inven eleven more times across the plate at a ratio of 1:1 for a final tion. In particular, it may prove advantageous to repurify (twelfth) dilution of 1:204.800. The plates were incubated antibodies, e.g., against one of the peptides that was used in overnight at 4°C. The plates were emptied and washed three generating the antibodies. It is to be understood that the times as described. present invention encompasses antibodies that have been pre 0180 Biotinylated goatanti-rabbit IgG (100 ul) was added pared with Such additional purification or repurification steps. to each microtiter plate test well and incubated for four hours It will also be appreciated that the purification process may at room temperature. The plates were emptied and washed affect the binding between samples and the inventive antibod three times. Horseradish peroxidase-conjugated Streptavidin 1CS (100 ul diluted 1:10,000 in BBS-TW-BG) was added to each well and incubated for two hours at room temperature. The Example 2 plates were emptied and washed three times. The ABTS was Preparing and Staining Tissue Arrays prepared fresh from stock by combining 10 ml of citrate buffer (0.1 M at pH 4.0), 0.2 ml of the stock solution (15 0185. This example describes a method that was mg/ml in water) and 10 ul of 30% hydrogen peroxide. The employed to prepare the tissue arrays that were used in the ABTS solution (100 ul) was added to each well and incubated Examples. This example also describes how the antibody at room temperature. The plates were read at 414 nm, 20 staining was performed. minutes following the addition of substrate. 0186 Tissue arrays were prepared by inserting full-thick ness cores from a large number of paraffin blocks (donor Preparation of Peptide Affinity Purification Column: blocks) that contain fragments of tissue derived from many different patients and/or different tissues or fragments of tis 0181. The affinity column was prepared by conjugating 5 Sues from a single patient, into a virgin paraffin block (recipi mg of peptide to 10 ml of cyanogen bromide-activated ent block) in a grid patternat designated locations in a grid. A Sepharose 4B and 5 mg of peptide to hydrazine-Sepharose standard slide of the paraffin embedded tissue (donor block) 4B. Briefly, 100 ul of DMF was added to peptide (5 mg) and was then made which contained a thin section of the specimen the mixture was vortexed until the contents were completely amenable to H & E staining A trained pathologist, or the wetted. Water was then added (900 ul) and the contents were equivalent versed in evaluating tumor and normal tissue, des vortexed until the peptide dissolved. Half of the dissolved ignated the region of interest for sampling on the tissue array peptide (500 ul) was added to separate tubes containing 10 ml (e.g., a tumor area as opposed to stroma). A commercially of cyanogen-bromide activated Sepharose 4B in 0.1 ml of available tissue arrayer from Beecher Instruments was then borate buffered saline at pH 8.4 (BBS) and 10 ml of hydra used to remove a core from the donor block which was then Zine-Sepharose 4B in 0.1 M carbonate buffer adjusted to pH inserted into the recipient block at a designated location. The 4.5 using excess EDC in citrate buffer pH 6.0. The conjuga process was repeated until all donor blocks had been inserted tion reactions were allowed to proceed overnight at room into the recipient block. The recipient block was then thin temperature. The conjugated Sepharose was pooled and sectioned to yield 50-300 slides containing cores from all loaded onto fitted columns, washed with 10 ml of BBS, cases inserted into the block. blocked with 10 ml of 1 M glycine and washed with 10 ml 0.1 0187. The selected antibodies were then used to perform M glycine adjusted to pH 2.5 with HCl and re-neutralized in immunohistochemical staining using the DAKO Envision+, US 2010/0062444 A1 Mar. 11, 2010

Peroxidase IHC kit (DAKO Corp., Carpenteria, Calif.) with the HH cohort that were treated with CA (cyclophosphamide DAB Substrate according to the manufacturer's instructions. and adriamycin, HR=1.000) or CAF (cyclophosphamide, FIG. 1 shows exemplary IHC staining images of samples that adriamycin and 5-fluorouracil, HR=1.000) we were able to are TLE3-negative (S0643-) and TLE3-positive (S0643+). establish that the predictive correlation in FIG. 7 is between TLE3 binding and treatment with methotrexate (see also FIG. Example 3 9 which combines the CA and CAF treated subsets, HR=1. 030). TLE3 Expression Correlates with Response to Che 0.192 FIG. 8 shows Kaplan-Meier recurrence curves that motherapy in Cancer Patients were generated using patients in the HH breast cancer cohort 0188 Tumor samples from two different breast cancer of FIG. 5 that received CA or CAF chemotherapy (with or cohorts—Huntsville Hospital (HH) and Roswell Park Cancer without a taxane). As shown in the Figure, the correlation Institute (RP)—were stained with the TLE3 antibody of between antibody binding to the TLE3 marker and prognosis Example 1. Treatment and recurrence data were available for loses significance in this subset of treated patients (HR=0. all patients in both cohorts. FIG. 2 shows Kaplan-Meier 666, p=0.22). When the curves were generated using patients recurrence curves that were generated using all patients in the that received CA or CAF chemotherapy only (i.e., without a HH cohort after classification based on staining with the taxane) the significance was further reduced (see FIG. 9. TLE3 antibody. Recurrence data from TLE3-positive and HR=1.030, p=0.95). However, the correlation was restored in TLE3-negative patients were used to generate the top and patients that received CA or CAF in combination with a bottom curves, respectively. As shown in the Figure, antibody taxane (see FIG. 10, HR=0.114, p=0.038). These results dem binding to the TLE3 marker correlates with improved prog onstrate a correlation between TLE3 binding and treatment nosis across this breast cancer cohort (HR-0.573, p=0.004). with a taxane. FIG.3 shows Kaplan-Meier recurrence curves that were gen 0193 FIG. 11 shows Kaplan-Meier recurrence curves that erated in a similar fashion using all patients in the RP cohort. were generated using patients in the RP breast cancer cohort As with the HH cohort, antibody binding to the TLE3 marker of FIG. 6 that received CA chemotherapy only (i.e., without a was found to correlate with improved prognosis (HR=0.239, taxane). Recurrence data from TLE3-positive and TLE3 p=0.011). negative patients in this Subset were used to generate the top (0189 In order to determine whether TLE3 expression is and bottom curves, respectively. As shown in the Figure, there correlated with response to chemotherapy, separate Kaplan is no correlation between antibody binding to the TLE3 Meier recurrence curves were generated using HH cohort marker and prognosis in this subset of treated patients (HR=0. patients that did or did not receive chemotherapy (FIGS. 4 and 759, p=0.81). The correlation was restored when the curves 5, respectively). As shown in FIG. 4, antibody binding to the were generated using patients that received CA chemo TLE3 marker lost its correlation with prognosis in patients therapy in combination with a taxane (see FIG. 12, HR=0. that did not receive chemotherapy (HR=0.788, p=0.490). 153, p=0.018). These results support the results of FIGS. 8 However, as shown in FIG. 5, the correlation was restored in and 9 that were obtained using samples from the HH cohort. patients that did receive chemotherapy (HR-0.539, p=0.013). 0194 FIG. 13 shows Kaplan-Meier recurrence curves that These results demonstrate that TLE3 expression is correlated were generated using patients in the RP breast cancer cohort with improved response to chemotherapy (i.e., TLE3-positive of FIG. 6 that received a taxane or CMF. Some of the patients cancers are more likely to respond to chemotherapy than receiving a taxane also received CA. Recurrence data from TLE-3 negative cancers). Kaplan-Meier recurrence curves TLE3-positive and TLE3-negative patients in this subset that were generated using patients in the RP breast cancer were used to generate the top and bottom curves, respectively. cohort that received chemotherapy are consistent with this As shown in the Figure, antibody binding to the TLE3 marker prediction model (see FIG. 6, HR=0.194, p=0.010). Kaplan correlates with improved prognosis across this Subset of Meier recurrence curves that were generated using patients in treated patients (HR=0.137, p=0.011). the UAB ovarian cancer cohort that received chemotherapy 0.195 FIG. 14 shows Kaplan-Meier recurrence curves that are also consistent with this prediction model (see FIG. 18. were generated using patients in the RP breast cancer cohort HR=0.64, p=0.049). of FIG. 6 that received neoadjuvant chemotherapy. Recur rence data from TLE3-positive and TLE3-negative patients in Example 4 this Subset were used to generate the top and bottom curves, Specific Chemotherapeutic Correlations respectively. The sample size was small (N=12); however, as shown in the Figure, antibody binding to the TLE3 marker (0190. Since different patients in the HH and RP cohorts showed significant correlation with improved prognosis received different types of chemotherapy we were also able to across this Subset of treated patients when measured using the determine whether TLE3 expression correlates with response Fisher Exact Test (p=0.005). In addition, of the 12 patients to specific types of chemotherapy. receiving neoadjuvant chemotherapy, two received CA (both 0191 FIG. 7 shows Kaplan-Meier recurrence curves that showed recurrence) while ten received CA with a taxane were generated using patients in the HH breast cancer cohort (seven showed recurrence, three did not). Notably, the three of FIG. 5 that received CMF (cyclophosphamide, methotrex patients that did not show any recurrence were the only ate and 5-fluorouracil) chemotherapy. Recurrence data from patients with TLE3-positive samples. These results are sig TLE3-positive and TLE3-negative patients in this subset nificant since they show that the correlation between TLE3 were used to generate the top and bottom curves, respectively. binding and response to chemotherapy applies irrespective of As shown in FIG. 7, antibody binding to the TLE3 marker whether treatment is administered in an adjuvant or neoadju correlates with improved prognosis across this Subset of vant setting. treated patients (HR=0.398, p=0.019). Based on the results (0196. FIGS. 15-17 show Kaplan-Meier recurrence curves below which demonstrated a loss of correlation for patients in that were generated using patients in the RP breast cancer US 2010/0062444 A1 Mar. 11, 2010 15 cohort of FIG. 6 that received chemotherapy. Recurrence data results are summarized in Table 1 below. As shown in the from TLE3-positive and TLE3-negative patients with stage Table, prediction using TLE3 remained significant in all 11+(FIG. 15), stage IIb+ (FIG. 16) and stage III+ (FIG. 17) bivariate analyses demonstrating its independence of other cancers were used to generate the top and bottom curves, clinical factors. respectively. In each case, antibody binding to the TLE3 marker correlated with improved prognosis across these Sub TABLE 1 sets of treated patients. The sample size was Small in the subset of FIG. 17 (N=19); however significance was obtained Bivariate Analysis when measured using the Fisher Exact Test (p=0.020). These HR for for results are of clinical importance since they demonstrate that Factor 1 Factor 2 N TLE3 E. HR P the predictive power of the TLE3 marker is independent of TLE3 81 0.239 O.O110 Stage and remains significant even in patients with the worst TLE3 Age 81 0.223 O.OO82 0.967 0.1200 prognosis (e.g., stage III+ patients). TLE3 Tumor Size 78 O.219 O.OO77 1.292 O.OOO2 TLE3 Nodes Met Ca 79 0.2S2 OO150 1.066 O.OO86 TLE3 Necrosis 72 0.232 O.O1OO 1903 0.2600 Example 5 TLE3 Vasc. Lymph Inv.2 74 0.205 O.OO71 O.412 O.O790 TLE3 Stage 80 O.284 O.O280 2.063 O.O130 Bivariate Analysis TLE3 coins Tax 7O 0.168 O.OO61 2.749 O.O980 10197) In order to confirm that the predictive power of "Nodes found with metastatic cancer. TLE3 is independent of other clinical factors (e.g., age, tumor ‘Vascular lymphatic invasion. size, nodes status, necrosis, etc.) we performed bivariate sta- Taxane containing regimens. tistical analysis using results from the RP breast cohort. The

Appendix A

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SOO11 vav 3 oncogene 10451 WAV3; WAV3 ONCOGENE, ONCOGENE TEESINDEDIY EKRTNGLR DYISKSKED 1 : 9 O VAV3; vav 3 oncogene KGLPDLIDE RTPKOVD WKLK (3) 1: 3 OO (1) (2)

SOO17 WAP four-disul- 104O6 WFDC2; WAP5; d.J461P17. 6; major EKTGVCPELQ PNDKEGSC RDOCOVDT 1:25 fide core domain epididymis-specific protein ADQNCTOE POVNIN (5) QCPGOMK 1 : 5 OO 2 E4; epididymal secretory pro - (4) (6) tein E4; WAP four-disulfide core domain 2; WAP domain containing protein HE4-W4; epididymis-specific, whey acidic protein type, four disulfide core WAP four disulfide

SOO18 secretoglobin, 4250 UGB2; MGB1; SCGB2A2; mamma- SKTINPOVSK DDNATTNAI NOTDETLSN 1:3 OO family 2A, globin 1; secretoglobin, TEYKELLOE DELKEC (8) VEVFMO 1 : 1 OOO member 2 family 2A, member 2 (7) (9)

SOO2O PPAR binding 5469 RB18A TRIP2, PPARGBP: PBP SSDDGIRPLP DGKSKDKP NKTKKKKSS 1 : 1 OO protein CRSP1, PPARBP, CRSP2OO; EYSTEKHKK PKRKKADTE RLPPEK DRIP 23 O. PPAR-BINDING PROTEIN (10) (11) (12) PPARG binding protein; PPAR binding protein; CRSP, 200-KD SUBUNIT: PEROXISOME PROLIFERA TOR-ACTIWATED RECEPTOR-BINDING PROTEIN THYROID HORMONE RE CEPTOR INTERACTOR 2; RECOGN

SOO21 hypothetical 222256 FLJ23834; hypothetical protein KNKEPLTKKG KLTCTDLDS EVDYENPS 1:2 OO protein FLJ23834 FLJ23834 ETKTAERD SPRSFRYS NLAAGNKYT 1:2500 (13) (14) (15)

SOO22 cytochrome P450 199974 CYP4Z1; cytochrome P450 421; KTLQVFNPLR QHFAIIECKV RKFLAPDHS 1 : 50 421 cytochrome P450, family 4, FSRENSEKIH AVALT (17) RPPOPVRO 1 : 5 OO sub-family Z, polypeptide 1 (16) (18)

SOO24 RAS-like 85004 RERG; RAS-like, estrogen- MAKSAEWKLA WLPLKNILDE YELCREWRR. 1:9 OO estrogen-regul- regulated, growth-inhibitor IFGRAGVGK IKKPKN (2O) RRMVOGKT 1:27 OO lated, growth- (19) (21) inhibitor US 2010/0062444 A1 Mar. 11, 2010 16

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SOO32 fatty acid bind 21.70 MDGI; O-FABP; FABP3; FABP11; TKPTTIEKNG KNTEISFKL HLOKWDGO 1: 225 ing protein 3, H-FABP, FATTY ACID-BINDING DILTLKTH GWEFDE ETTLVRE muscle and heart PROTEIN, SKELETAL MUSCLE; (22) (23) (24) (mammary-derived Fatty acid-binding protein growth 3, muscle; fatty acid inhibitor) binding protein 11; FATTY ACID-BINDING PROTEIN MUSCLE AND HEART; fatty acid binding protein 3, muscle and heart (mammary- de

SOO36 gamma-aminobuty 2568 GABRP; GAMMA-AMINOBUTYRIC ACID DGNDWEFTW LQQMAAKD KRKISFASIE 1:25 O ric acid (GABA) RECEPTOR PI; GABA-A RECEPTOR LRGNDSVRG RGTTKEVEE ISSDNWDYS 1 : 5OO A receptor, pi PI POLYPEPTIDE; gamma-aminobu - LEH (25) WS (26) D (27) tyric acid (GABA) A receptor, pi

SOO37 annexin A8 244 ANX8; ANXA8; annexin VIII; OROOIAKSFK REIMKAYEE EEYEKIANK annexin A8 AQFGKDLTE DYGSSLEED SIEDSIKSE (28) IQ (29) (30)

SOO39 CDNA FLJ25076 1341.11 similar to 311 OOO6E14Rik pro- EGGSLVPAA RKAGKSKK. KTHEKYGW 1 : 50 - fis, clone tein; CDNA FLJ 25076 fis, clone RQOHCTOVR SFSRKEAE WTPPVSDG 1: 3 OOOO CBLO 6117 CBLO 6117 SRR (31) (32) (33)

SOO4 O ATP-binding cas 5243 P-gp; PGY1; CLCS; ABCB1; MDLEGDRNG NLEDLMSNI RGSQAQDR 1:2OO sette sub ABC2O, CD243; GP17O; MDR1; GAKKKN (34) TNRSDINDT KLSTKEA. 1: 4 OO family B doxorubicin resistance; col- G (35) (36) (MDR/TAP), chicin sensitivity; P-GLYCO member 1 PROTEIN 1; multidrug resis tance 1; P glycoprotein 1; ATP-binding cassette sub family B member 1; ATP BINDING CASSETTE SUBFAMILY B, MEMBER 1 ATP-bin

SOO41 ATP-binding cas 5.244 MDR3; PGY3; PFIC-3; ABCB4; MDLEAAKNG NFSFPWNFS KNSOMCOK 1: 60 sette sub ABC21; MDR2/3 ; P-GLYCOPROTEIN TAWRPTSAE LSLLNPGK SLDWETDG 1: 3 OO family B 3 ; MULTIDRUG RESISTANCE 3 ; P- (37) (38) (39) (MDR/TAP), glycoprotein-3/multiple drug member 4 resistance-3 ; P glycoprotein 3/multiple drug resistance 3; ATP-binding cassette, sub family B (MDR/TAP), member 4; ATP-binding cassette, sub

SOO42 ATP-binding cas 43.63 ABCC1; MRP1; GS-X; ABC29; MALRGFCSA KNWKKECA DSIERRPWK 1: 4 O sette sub multidrug resistance protein; DGSD (40) KTRKOPVK DGGGTNS 1 : 5OO family C MULTIDRUG RESISTANCE-ASSOCI- (41) (42) (CFTRAMRP), ATED PROTEIN 1; multiple drug member 1 resistance-associated protein; multiple drug resistance pro tein 1 ATP-BINDING CASSETTE, SUBFAMILY C MEMBER 1 ATP binding cassette, sub-fami

SOO43 ATP-binding cas 1244 MRP2; cMRP CMOAT; ABCC2; MLEKFCNSTF SILCGTFOF ENNESSNN 1 : 50 - sette sub ABC3 O; DJS; MULTIDRUG RESIS- WNSSFLDSP OTLIRT (44) PSSIAS 1: 333 family C TANCE-ASSOCIATED PROTEIN 2; E (43) (45) (CFTRAMRP), canalicular multispecific or member 2 ganic anion transporter; MUL TISPECIFIC ORGANIC ANION TRANSPORTER, CANALICULAR ATP BINDING CASSETTE SUBFAMILY C, MEMBER. 2; ATP-binding cassette, US 2010/0062444 A1 Mar. 11, 2010 17

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SOO44 ATP-binding cas- 10257 MOAT-B; MRP4 MOATB, ABCC4; QEWKPNPLO DEISQRNRO VODFTAFW 1: 2O sette sub EST17 O2O5 ; MULTIDRUG RESIS- DANICSR LPSDGKK DKASETPTL 1:100 family C TANCE-ASSOCIATED PROTEIN 4; (4 6) (47) Q (48) (CFTRAMRP), MULTISPECIFIC ORGANIC ANION member 4 TRANSPORTER B, ATP-binding cassette, sub-family C, member 4 ATP-BINDING CASSETTE SUB FAMILY C MEMBER 4 ATP-bind ing cassette, sub-family C (CFT

SOO45 ATP-binding cas- 871.4 MOAT-D; ABC31; MLP2; ABCC3; MDALCGSGE RKOEKOTA DPOSVERK 1:2OOO sette sub E5T9 O757, cMOAT2; MULTIDRUG LGSKFWDSN RHKASAA TISPG family C RESISTANCE-ASSOCIATED PROTEIN (49) (5O) (51) (CFTRAMRP), 3; canicular multi specific or - member 3 ganic anion transporter; CAN ALICULAR MULTISPECIFIC ORGANIC ANION TRANSPORTER 2 ATP BINDING CASSETTE SUBFAMILY C, MEMBER 3; ATP-binding cas

SOO46 ATP-binding cas- 10057 MOAT- C, ABCC5; MRP5; MKDIDIGKEYI RDREDSKF SKHESSDW 1 : 1.OO sette sub EST2771.45 ABC33, SMRP; IPSPGYRS RRTRPLEC NCRRLER 1: 450 family C pABC11; MOATC; MULTIDRUG RE- (52) QD (53) (54) (CFTRAMRP), SISTANCE-ASSOCIATED PROTEIN 5 ; member 5 canalicular multispecific or ganic anion transporter C; ATP-binding cassette, Sub family C, member 5; ATP BINDING CASSETTE SUBFAMILY C, MEMBER 5; ATP-bi

SOO47 ATP-binding cas- 368 MRP6; ARA; E5T349056; ABCC6; MAAPAEPCA DPGWWDSS HTLWAENAM 1 : 50 sette sub MOATE; PXE; MLP1; ABC34; GQGWWNOTE SSGSAAGK NAEK (57) family C ANTHRACYCLINE RESISTANCE- PE (55) D (56) (CFTRAMRP), ASSOCIATED PROTEIN MULTIDRUG member 6 RESISTANCE-ASSOCIATED PROTEIN 6; ATP-binding cassette, sub family C, member 6; ATP BINDING CASSETTE SUBFAMILY C, MEMBER 6; ATP-binding cassette,

SOO48 ATP-binding cas- 8647 BSEP; ABCB11; PFIC-2; SPGP; MSDSVILRSIKTNSSLNON QEWLSKIOH 1: 6OO sette sub PGY4; PFIC2, ABC16, SISTER OF KFGEEND MTNGTR GHTIIS family B P-GLYCOPROTEIN; bile salt ex- (58) (59) (60) (MDR/TAP), port pump; progressive famil member 11 ial intrahepatic cholestasis 2; ABC member 16, MDR/TAP sub family; ATP-BINDING CASSETTE, SUBFAMILY B MEMBER 11 ATP binding cassette, sub-fam

SOO49 ATP-binding cas- 23456 MTABC2, E5T2O237; MABC2 GADDPSSWT NAWASPEFP KPNGIYRKL 1 : 1.O- sette sub M-ABC2; ABCB10; MITOCHONDRIAL AEEIOR (61) PRFNT (62) MNKOSFISA 1:25 family B ABC PROTEIN 2 ATP-BINDING (63) (MDR/TAP), CASSETTE SUBFAMILY B MEMBER member 10 10; ATP-binding cassette, sub family B, member 10; ATP binding cassette, sub-family B (MDR/TAP), member 10

SOO50 transporter 1, 6890 RING4; ABC17; D6S114E; ABCB2; MASSRCPAP QGGSGNPV EFWGDGIYN ATP-binding cas TAP1 APT1, PEPTIDE TRANS RGCR (64) RR (65) NTMGHWHS sette sub PORTER PSF1, TRANSPORTER, ABC, (66) family B MHC, 1 ; ABC transporter, MHC (MDR/TAP) 1; antigen peptide transporter 1; peptide supply factor 1; ABC TRANSPORTER, MHC, 1 ATP BINDING CASSETTE SUBFAMILY B, MEMBER. 2; TRANSPORTER US 2010/0062444 A1 Mar. 11, 2010 18

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SOO52 ATP-binding cas 6833 SUR1; MRP8, PHHI, ABC36; MPLAFCGSE DHLGKEND EIREEOCAP 1: 25 sette sub ABCC8; HRINS; sulfonylurea NHSAAYR WFOPKTOFL, HEPTPOG 1: 15 O family C receptor (hyperinsulinemia); (67) G (68) (69) (CFTRAMRP), SULFONYLUREA RECEPTOR BETA member 8 CELL HIGH-AFFINITY; ATP binding cassette, sub-family C member 8; ATP-BINDING CASSETTE SUBFAMILY C MEMBER 8; ATP-binding cassette, sub family C

SOO53 ATP-binding cas ABCC9; ABC37; sulfonylurea re- MSLSFCGNNI QRVNETON DEIGDDSW 1: 25 sette sub ceptor 2A; ATP-BINDING CAS (7O) GTNNTTGIS RTGESSLPF 1: SO family C SETTE SUBFAMILY C MEMBER 9; E (71) E (72) (CFTRAMRP), ATP-binding cassette, sub member 9 family C (CFTR/MRP), member 9; ATP-binding cassette, sub family C, member 9 isoform SUR2B; ATP-binding cassette, sub-family C, member 9 isoform

SOO55 integral mem 9.445 E25B; ABRI; E3-16; FBD; BRI2; MVKWTFNSAL OTIEENIKIF HDKETYKLQ : 450 - brane protein 2B BRICD2B, ITM2B, BRI GENE; AOKEAKKDE EEEEVE (74) RRETIKGIO : SOO BRICHOS domain containing 2B; (73) KRE (75) integral membrane protein 2B

SOO57 ankyrin 3, node 288 ankyrin-G; ANK3; ankyrin-3, MAHAASQLK HKKETESD EGFKWKTKK : 750 of Ranvier node of Ranvier; ankyrin 3 KNRDLEINAE ODDEIEKTD EIRHWEKKS (ankyrin G) isoform 1; ankyrin 3 isoform (76) RRO (77) HS (78) 2; ankyrin 3, node of Ranvier (ankyrin G)

SOO58 hypothetical FLJ21918; hypothetical protein ERALAAAQR TAGMKDLLS DPPRTWLOA protein FLJ21918 FLJ21918 CHKKWMKER WFOAYO PKEWWCL (79) (80) (81)

SOO59 tripartite 23.650 ATDC; TRIM29; tripartite mo MEAADASRS ELHLKPHLE EGEGLIGOS : 50 - motif- containing tif- containing 29; ataxia NGSSPEARD GAAFRDHQ LGNFKDDLL : 3 OOO 29 telangiectasia group D (82) (83) N (84) associated protein; tripartite motif protein TRIM29 isoform alpha; tripartite motif pro tein TRIM29 isoform beta

SOO59P tripartite 23.650 ATDC; TRIM29; tripartite mo ELHLKPHLEG NAA NAA : 3 O 2 motif- containing tif- containing 29; ataxia AAFRDHQ : 90 29 telangiectasia group D (85) associated protein; tripar tite motif protein TRIM29 iso form alpha; tripartite motif protein TRIM29 isoform beta

SOO63 iroquois homeo - 79191 IRX3; iroquois homeobox GSEERGAGR KIWSLAETA. KKLLKTAFO 1: box protein 3 protein 3 GSSGGREE TSPDNPRR PWPRRPON : 12 OO (86) S (87) HL.D (88)

SOO68 RAS-like, RERG; RAS-like, estrogen RRSSTTHVK N/A NAA : 5OO estrogen-regul regulated, growth-inhibitor OAINKMLTKIS : 4 OOOO lated, growth (89) inhibitor

SOO7 O G protein 26996 GPCR150; GPR160; putative G MRRKNTCON INETILYFPFS KVOIPAYIE 1: coupled receptor protein-coupled receptor; G FMEYFCISLA SHSSYTVRS MNIPLVILCO 1: 160 protein-coupled receptor 16 O (90) KK (91) (92) US 2010/0062444 A1 Mar. 11, 2010 19

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SOO72 S100 calcium 6279 CP-10; L1Ag; CAL PROTECTIN; MLTELEKALN RDDLKKLLE KMGWAAHK 1: 65 OO binding protein 6 OB8AG; S100A8; MIF; CAGA; SIIDWYHK TECPOYIRK KSHEESHKE 1 : 1.OOOO A8 (calgranulin NIF; MRP8; MA387; CFAG; CGLA (93) KGAD (94) (95) A) S100A8/S100A9 COMPLEX; cystic fibrosis antigen; S1 OO calcium-binding protein A8; S100 calcium binding protein A8 (calgranulin A)

SOO73 forkhead box A1 31.69 HNF3A, MGC33105 TCF3A. FOXA1; PESRKDPSG HGLAPHES EQOHKLDF 1 : 1.OO forkhead box A1; HEPATOCYTE ASNPSADS QLHLKGD KAYEQALOY 1:27 OO NUCLEAR FACTOR 3-ALPHA; (96) (97) S (98) hepatocyte nuclear factor 3, alpha

SOO73P forkhead box A1 31.69 HNF3A, MGC33105 TCF3A. FOXA1; HGLAPHESQ NAA 2 forkhead box A1; HEPATOCYTE (99) 1: 450 NUCLEAR FACTOR 3-ALPHA; hepatocyte nuclear factor 3, alpha

SOO74 trefoil factor 3 7033 TFF3; trefoil factor 3 (intes EEYWGLSAN RWDCGYPH WPWCFKPL : 25 OO (intestinal) tinal); trefoil factor 3. OCAVPAKDR WTPKECN OEAECTF : 3 OOOO HITF, human intestinal trefoil (100) (101) (102) factor

SOO74P trefoil factor 3 7033 TFF3; trefoil factor 3 (intes NAA NAA : 4 OO 3 (intestinal) tinal); trefoil factor 3, EAECTF : 810 HITF, human intestinal trefoil (103) factor

SOO76x keratin 17 3872 PC2, PCHC1; KRT17; K17; KKEPVTTROV ODGKVISSR SSSIKGSSG : 2OO CYTOKERATIN 17; keratin 17 RTIVEE EOVHOTTR LGGGSS (104) (105) (106)

SOO78 kynureninase (L- 8942 3.7.1.3; XANTHURENICACIDURIA; DEEDKLRHFR KPREGEETL EERGCOLTI : 18O kynurenine KYNU, HYDROXYKYNURENINURIA; ECFYIPKIOD RIEDILEWIE TFSVPNKDV : 2OO hydrolase) KYNURENINASE DEFICIENCY, (107) KE (108) FOE (109) XANTHURENIC ACIDURIA; kynureninase (L-kynurenine hydrolase)

SOO79 solute carrier 258OO SLC39A6; LIV-1 protein, estro DHNHAASGK EEPAMEMK ORYSREELK family 39 (zinc gen regulated; solute carrier NKRKALCPD RGPLFSHLS DAGWATL transporter), family 39 (zinc transporter), HD (110) SONI (111) (112) member 6 member 6; solute carrier fami ly 39 (metal ion transporter), member 6

SOO81 N-acetyltrans AAC1; 2.3.1.5; NAT1; arylamine MDIEAYLERI QMWOPLELI FNISLORKL ferase 1 (aryla N-acetyltransferase-1; ACETYL GYKKSRNKL SGKDQPQV WPKHGDRF 1:24 O mine N-acetyl CoA: ARYLAMINE N DLE (113) PCWFR FTI (115) transferase) ACETYLTRANSFERASE, ARYLAMINE (114) N-ACETYLTRANSFERASE 1: N acetyltransferase 1 (arylamine N-acetyltransferase); aryla mide acetylase 1 (N-acetyl transferase 1)

SOO86 X-box binding 7494 XBP2; TREB5: XBP1; X-box RORLTHLSPE EKTHGLWWE OPPFL COW 1 : 18O protein 1 binding protein-1; X BOX EKALRRKLKN NOELRORL GRHOPSWK 1: 4 OO BINDING PROTEIN 1. X BOX R (116) GMD (117) PLMN (118) BINDING PROTEIN 2; X-box binding protein 1

SOO88 claudin 10 9071 CPETRL3; OSP-L; CLDN10; clau NKITTEEFDPL FSISDNNKT EDFKTTNPS 1: 333 din 10; claudin 10 isoform a ; FVEOK (119) PRYTYNGAT KOFDKNAY 1 : 1.OOO claudin 10 isoform b (120) W (121) US 2010/0062444 A1 Mar. 11, 2010 20

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SOO90 sparc / osteonec 9806 KIAAO275; testican-2; SPOCK2; EGDAKGLKE EWCFCFWR EEEGEAGE 1 : 1.OO tin, cw cv and TESTICAN 2; SPARCA OSTEONECTIN GETPGNFME EKPPCLAEL ADDGGYIW 1: 8OO kazal-like do CWCW AND KAZAL - LIKE DOMAINS DE (122) ER (123) (124) mains proteo PROTEOGLYCAN 2; sparc / osteo glycan nectin, cWCV and kazal-like (testican) 2 domains proteoglycan (testican) 2

SOO91 lipocal in 2 3934 UTEROCALIN; NGAL; LCN2; DKDPOKMYA KKCDYWIRT ENFIRESKY 1:100 (oncogene 24p3) NEUTROPHIL GELATINASE TIYE (125) FWPGCO LGLPEN ASSOCIATED LIPOCALIN ONCOGEN (126) (127) IC LIPOCALIN 24P3; lipocalin 2 (oncogene 24p3)

SOO92 paired box gene 7849 PAX8; paired box gene 8; DDSDODSCR ROHYPEAY NTPLGRNLS 1:30 - 8 paired box gene 8 isoform LSIDSQ ASPSHTK. THOTYPVVA 1:100 PAX8C; paired box gene 8 iso (128) (129) D (130) form PAX8D; paired box gene 8 isoform PAX8E; paired box gene 8 isoform PAX8A; paired box gene 8 isoform PAX8B; PAIRED DOMAIN GENE 8 PAX8/PPARG FUSION GENE

SOO93 mesothelin 10232 CAK1; SMR; MSLN; mesothelin; RLWSCPGPLD KMSPEDIRK SPEELSSWP 1 : 5OO MEGAKARYOCYTE-POTENTIATING QDQQE WNWTSLETL PSSIWAWRP FACTOR; SOLUBLE MPF/MESO (131) K (132) QD (133) THELIN-RELATED PROTEIN; meso thelin isoform 2 precursor; mesothelin isoform 1 precur sor ; megakaryocyte potentiat ing factor precursor; ANTIGEN RECOGNIZED BY MONOCLONAL ANTIBODY

SOO94 kallikrein 6 5653 Bssp; PRSS18; KLK6; Klk7; EEONKLWHG ELIOPLPLER GKTADGDF 1: 15 O (neurosin, zyme) SP59; PRSS9; MGC9355; protease GPCDKTSH DCSANT PDTIOC 1: 3 OO M; kallikrein 6 preproprotein; (134) (135) (136) protease, serine, 18; pro tease, serine, 9; kallikrein 6 (neurosin, zyme)

SOO95 Rap guanine nu 10411 bcme10; MGC21.410; REOWPERRR KVNSAGDAI QQLKVIDNQ 1:250 cleotide ex 933 O17 OPOSRik EPAC, RAPGEF3; CHRLENGCG GLOPDAR RELSRLSRE 1: 1.OOO change factor cAMP-GEFI, RAP guanine NA (137) (139) LE (140) (GEF) 3 nucleotide-exchange factor 3; EXCHANGE PROTEIN ACTIVATED BY cAMP; RAP guanine-nucleotide exchange factor (GEF) 3; cAMP REGULATED GUANINE NUCLEOTIDE EXCHANGE FACTOR I, RAP GUANINE NUCLE

SOO96 ATPase, H+ 525 V ma2; VPP3, ATP6V1B1; RTA1B, REHMOAVTR KKSKAVLDY DEFYSREG 1 : 1.OO transporting, 3. 6.3.14; WATB; ATP6B1; W NYITHPR HDDN (142) RLODLAPDT 1: 8OO lysosomal 56/58 ATPase B1 subunit; H+-ATPase (141) AL (143) kDa, W1 subunit beta 1 subunit; H (+)-trans B, isoform 1 porting two-sector ATPase, 58 (Renal tubular kD subunit; vacuolar proton acidosis with pump, subunit 3; endomembrane deafness) proton pump 58 kDa subunit; ATPase, H+ transporting, lysos

SO097 frizzled homolog 8325 FZ-8; hEZ8; FZD8; frizzled 8; KOODGPTKT ELRVLSKAN RRGGEGGE 1 : 1.OO 8 (Drosophila) frizzled homolog 8 HKLEKLMIR AIWPGLSGG ENPSAAKG 1 : 5OO (Drosophila); FRIZZLED, (144) E (145) HLMG (146) DROSOPHILA HOMOLOG OF 8

SOO 99 histone 1, H2ba 255 626 HIST1H2BA; histone 1, H2ba MPEWSSKGA GFKKAWWKT KEGKKRKR 1: 333 TISKK (147) OK (148) TRKE (149) 1:5OO US 2010/0062444 A1 Mar. 11, 2010 21

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO11 O hypothetical 8425.9 MGC2714; hypothetical protein RYAFDFARDK SVFYOYLEQ EDGAWPWL 1 : 5OO protein MGC2714 MGC2714 DORSLDID SKYRWMNK LDEFVEWO 1:25 OO (15O) DQ (151) KVROTS (152)

SO117 reproduction 8 7993 D8S 2298E; REP8; reproduction SFKSPQVYLK RKKQQEAQ EDIGITWDTW 1:2OO 8; Reproduction/chromosome 8 EEEEKNEKR GEKASRYIE LILEEKEOT 1: 375 (153) (154) N (155)

SO119 slit homolog 1 6585 SLIT3; MEGF4; SLIL1; Slit-1; KAFRGATDLK DERCEEGO DGTSFAEEW 19 OO (Drosophila) SLIT1; slit homolog 1 NLRLDKNO EEGGCLPR EKPTKCGC (Drosophila); SLIT, (156) PO (157) ALCA (158) DROSOPHILA HOMOLOG OF 1, MULTIPLE EPIDERMAL GROWTH FACTOR-LIKE DOMAINS 4

SO122 leucyl-tRNA 233.95 6.1.1. 4; MGC 26121; KIAAOO28; QRIKEQASKI HAKTKEKLE KSPOPOLLS 1: 15 O synthetase 2, LEURS; LARS2; leucine trans- SEADKSKPKF WTWEKMSK NKEKAEARK mitochondrial lase; leucine-tRNA ligase; (159) SKHN (16O) (161) LEUCYL-tRNA SYNTHETASE, MITO CHONDRIAL; leucyl-tRNA synthe tase 2, mitochondrial; leucyl tRNA synthetase 2, mitochon drial precursor

SO123 homeo box D4 3233 HOX4B; HOXD4; HHO. C13; HOX- MLFEOGOOA KDOKAKGIL HSSOGRLP 1 : 1.OO 5.1; HOMEOBOX D4; HOMEOBOX 4B, LELPECT HSPASQSP EAPKLTHL 1 : 5OO HOMEOBOX X; homeo box D4; (162) ERS (163) (164) homeobox protein Hox-D4; Hox- 4.2, mouse, homolog of homeo box X

SO124 sphingosine-1- 8879 KIAA1252; SPL; SGPL1; KRGARRGGW KIWRVPLTK QFLKDIRES 1: 990 phosphate lyase sphingosine-1-phosphate lyase KRKMPSTDL MMEVDVR WTOIMKNPK 1: 15 OO 1. 1. (165) (166) A (167)

SO126 HBXAg transacti 55789 XTP1; HBxAg transactivated SKOGVWILDD WOTFSRCIL LKKPFOPFO 1: 450 vated protein 1 protein 1 KSKELPHW CSKDEWDLD RTRSFRM 1: 16 OO (168) EL (169) (17O)

SO132 SRY (Sex deter 6.662 SRA1, CMD1, CMPD1; SOX9, SRY- MNLLDPFMK NTFPKGEPD KNGOAEAE 1 : 1.OO - mining region BOX 9; transcription factor MTDEOEKGL LKKESEEDK EATEOTHIS 1 : 5 OO Y) -box 9 (campo SOX9, SRY -RELATED HMG-BOX GENES (171) (172) PN (173) melic dysplasia 9; SEX REVERSAL AUTOSOMAL, 1; autosomal sex SRY (sex- determining region reversal) Y) -box 9 protein; SRY (sex determining region Y) -box 9 (campomelic dysplasia, auto somal sex-reversal); SRY (

SO137 cadherin, EGF 1952 Flamingo1; CELSR2; EGFL2; OASSLRLEPG ELKGFAERL RSGKSOPS 1 : 18 OO LAG seven-pass KIAAO279, MEGF3; CDHF10; EGF- RANDGDWH QRNESGLD YIPFLLREE 1: SOOO G-type receptor like-domain, multiple 2; epi- (174) SGR (175 (176) 2 (flamingo dermal growth factor-like 2; homolog, multiple epidermal growth Drosophila) factor-like domains 3; cad her in EGF LAG seven-pass G type receptor 2; cadherin, EGF LAG seven-pass G-type receptor 2

SO139 gamma-glutamyl 8836 3.4.19.9; GGH; gamma-glutamyl RRSDYAKVA KNFTMNEKL EFFWNEARK 1:25 OO hydrolase hydrolase precursor; gamma- KIFYNLSIOSF KKFFNVLTT NNHHFKSE 1: 3 OOOO (conjugase, glutamyl hydrolase (conjugase, DD (177) N (178) SEE (179) folylpolygamma folylpolygammaglutamyl glutamyl hydrolase) hydrolase) US 2010/0062444 A1 Mar. 11, 2010 22

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO14 O bullous pemphi 667 BP240; FLJ13425; FLJ32235; KNTOAAEALW OENOPENS KOMEKDLA 1:25 O goid antigen 1, FLJ21489; FLJ3 O627; CATX-15; KLYETKLCE KTLATOLNQ FOKOVAEK 1:2OOOO 23 OA240 kDa KIAAO728; BPAG1; dystonin; (180) (181) QLK (182) hemides mosomal plaque protein; bullous pemphigoid antigen 1, 230/240 kDa; bullous pemphi goid antigen 1 (230/240 kD) ; bullous pemphigoid antigen 1 isoform 1.e.A precursor; bullo

SO143 fatty acid 21.94 2.3.1. 85; OA-519; FASN; EFVEOLRKEG DRHPOALE REVROLTLR 1:5 OOO synthase MGC14367, MGC15706; fatty acid VFAKEVR AAQAELQQ KLOELSSKA 1: 3 OOOO synthase (183) HD (184) DE (185)

SO143P fatty acid 21.94 2.3.1. 85; OA-519; FASN; REVROLTLRK N/A NAA 1:2OO 3 synthase MGC14367; MGC15706; fatty acid LQELSSKADE 1: 630 synthase (186)

SO144 matrix metallo 4323 MMP-X1; 3. 4. 24. - ; MMP14; AYIREGHEKO DEASLEPGY RGSFMGSD 1 : 5OO proteinase 14 MTMMP1; MT1-MMP; membrane- ADIMIFFAE PKHIKELGR EVFTYFYK 1:2OOOO (membrane type-1 matrix metalloprotein- (187) (188) (189) inserted) ase; matrix metalloproteinase 14 preproprotein; MATRIX METAL LOPROTEINASE 14 MEM BRANE-TYPE; matrix metal loproteinase 14 (membrane inserted) ; membrane-type matrix metalloprotein

SO147 cystatin A 1475 STF1; CSTA; STFA; cystatin AS; MIPGGLSEAK NETYGKLEA DLVLTGYOV 1: 100 (Stefin A) cystatin A (Stef in A) PATPEIOEIV VOYKTO DKNKDDELT 1: SOOO (190) (191) GF (192)

SO149 transient recep 55503 TRPV6; ECAC2; CAT1, CATL; RQEHCMSEH OGHKWGES RACGKRWS 1: 4 OO tor potential CALCIUM TRANSPORTER 1; CALCIUM FKNRPACLGA PSOGTOAG EGDRNGSG 1:2OOOO cation channel, TRANSPORTER-LIKE PROTEIN; R (193 ) AGK (194) GGKWG subfamily V, EPITHELIAL CALCIUM CHANNEL 2 (195) member 6 transient receptor potential cation channel, subfamily V, member 6

SO156 fatty acid 2173. B-FABP, FABP7, FABPB, MRG; MVEAFCATW QVGNVTKP KWWIRTLSTF 1: 1.OO binding protein mammary-derived growth inhibi - KLTNSQN TVIISOE KNTE (198) 1:2OOOO 7 brain tor-related; FATTY ACID- (196) (197) BINDING PROTEIN 7; FATTY ACID BINDING PROTEIN, BRAIN; fatty acid binding protein 7, brain

SO158 cadherin 3, type 1 OO1 CDHP; HJMD; PCAD; CDH3; pla- RAVFREAEVT OEPALFSTD OKYEAHVP 1: 15 O 1, P-cadherin cental cadherin; CADHERIN LEAGGAEOE NDDFTWRN ENAWGHE 1:2OOO (placental) PLACENTAL; cadherin 3, P- (199) (2OO (201) cadherin (placental) ; calcium dependent adhesion protein, placental; cadherin 3, type 1 preproprotein; cadherin 3, type 1, P-cadherin (placental)

SO165 chemokine (C-X-C 291.9 MGSA-a; NAP-3; CXCL1; SCYB1; KKIIEKMLNSD NAA NAA 1 : 1.OO motif) ligand 1 GROa; GRO1, FORMERLY; GRO PRO - KSN (2O2) 1 : 5OO (melanoma growth TEIN, ALPHA; GRO1 ONCOGENE, stimulating ac FORMERLY MELANOMA GROWTH tivity, alpha) STIMULATORY ACTIVITY ALPHA; GRO1 oncogene (melanoma growth-stimulating activity) ; CHEMOKINE, CXC MOTIF LIGAND 1; GRO1 oncogene (melanoma grow

SO171 baculoviral IAP null BIRC5; baculoviral IAP repeat - GKPGNONSK QAEAPLVPL NCFLTERKA 1: 225 OO repeat- contain containing 5 ( survivin) NEPPKKRER SRONK QPDE (2O5) 1:3 OOOO ing 5 (survivin) ER (2O3) (2O4) US 2010/0062444 A1 Mar. 11, 2010 23

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO193 pro collagen 5352 PLOD2; LYSYL HYDROXYLASE 2; EFDTWDLSAW NKEWYHEK KQVDLENV 1:2OOOO lysine, 2-oxo LYSINE HYDROXYLASE 2 DVHPN (2O6) DIKVFFDKA WLDFIRE glutarate 5 PROCOLLAGEN-LYSINE, 2- K (2O7 (208) dioxygenase OXOGLUTARATE 5-DIOXYGENASE 2; (lysine hydroxy pro collagen-lysine, 2-oxoglu lase) 2 tarate 5-dioxygenase (lysine hydroxylase) 2; procollagen lysine, 2-oxoglutarate 5 dioxygenase (lysine hydroxy lase) 2 isoform

PTK7 protein 5754 PTK7, CCK4; protein-tyrosine LKKPODSQLE KAKRLQKQ KDRPSFSEI 1 : 5OO tyrosine kinase kinase PTK7; colon carcinoma EGKPGYLD PEGEEPEM ASALGDSTW 1: 8OO 7 kinase- 4; PTK7 protein tyro- (209) E (210 DSKP (211) sine kinase 7; PTK7 protein tyrosine kinase 7 isoform e precursor; PTK7 protein tyro sine kinase 7 isoform a pre cursor; PTK7 protein tyrosine kinase 7 isoform d precursor;

SO211 cytochrome P450, 1549 CYPIIA7; P450-IIA4; 1.14.14.1; KRGIEERIOE DRVIGKNRO NPOHFLDD 1 : 5OO family 2, sub CPA7; CYP2A7; CPAD; CYTOCHROME ESGFLIE PKFEDRTK KGOFKKSD 1:25 OO family A, poly P450, SUBFAMILY IIA POLYPEP- (212) (213) (214) peptide 7 TIDE 7; cytochrome P450, sub family IIA (phenobarbital inducible), polypeptide 7; cytochrome P450, family 2, subfamily A, polypeptide 7; cytochrome P450, family 2, su

SO218 solute carrier 222962 SLC29A4; solute carrier family RHCILGEWLP KQRELAGN RNAHGSCL family 29 29 (nucleoside transporters), ILIMAVFN TMTVSYMS HASTANGSI (nucleoside member 4 (215) (216) LAGL (217) transporters), member 4

SO221 solute carrier 915.3 HCNT2, SLC28A2; His T17153; ELMEKEWEPE KARSFCKTH KNKRLSGM 1 : 5OO family 28 SPNT1 CONCENTRATIVE NUCLEO- GSKRTD ARLFKK EEWIEGEK 1 : 12 OO (sodium- coupled SIDE TRANSPORTER 2; SODIUM- (218) (219) (220) nucleoside DEPENDENT PURINE NUCLEOSIDE transporter), TRANSPORTER 1; solute carrier member 2 family 28 (sodium- coupled nucleoside transporter), member 2

SO223 angiopoietin 51129 HFARP, FIAF, ANGPTL4; PGAR; EGSTDLPLAP KVAQQQRH DHKHLDHE like 4 angiopoietin-like 4; FASTING- ESRVDPE LEKOHLR WAKPARRK 1 : 1.OOOO INDUCED ADIPOSE FACTOR; PPARG (221) (222) RLPE (223) ANGIOPOIETIN-RELATED PROTEIN; HEPATIC FIBRINOGENIANGIOPOIE TIN-RELATED PROTEIN

SO235 carcinoembryonic 104.8 CEACAM5; CD66e; carcinoembryo - KLTIESTPFNV KSDLVNEEA KPWEDKDAW 1 : 5OO antigen-related nic antigen-related cell adhe- AEGKEC TGOFRVYP AFTCEPEAO 1: 45 OO cell adhesion Sion molecule 5 (224) ELPK (225) (226) molecule 5

SO237 podocalyxin-like podocalyxin-like; Gp200; PCLP; DEKLISLICRA. KDKWDELK DSWIWPLDN 1 : 1.OOO PODXL; PODOCALYXIN-LIKE WKATFNPAOD EAGVSDMK LTKDDLDEE 1:2OOO PROTEIN; podocalyxin-like K (227) LGD (228) EDTHL (229) precursor

SO238 Xenotropic and 92.13 X3, XPR1; X RECEPTOR; SYG1 EAWWTNELED RRYRDTKR KARDTKWLI 1 : 1.OO polytropic re YEAST, HOMOLOG OF; xenotropic GDRQKAMKR AFPHLWNAG EDTDDEANT 1 : 5OO tro virus and polytropic retrovirus LR (23 O) K. (231) (232) receptor receptor US 2010/0062444 A1 Mar. 11, 2010 24

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO241 glycyl-tRNA 26.17 GlyRS; GARS, CMT2D; 6.1.1. 14; RKRWLEAKEL RHGVSHKW EARYPLFEG 1 : 5OO synthetase SMAD1; GLYCYL-tRNA SYNTHETASE; ALOPKDDIVD DDSSGSIGR OETGKKETI 1:75 OO glycine tRNA ligase; Charcot (233) RYAR (234) EE (235) Marie-Tooth neuropathy, neuronal type, D

SO244 dachshund homo 16O2 DACH1; FLJ101.38; dachshund DLAGHDMGH EKOVOLEKT EADRSGGR 1 : 1.OO log 1 homolog (Drosophila) ; ESKRMHIEKD ELKMDFLRE TDAERTIOD 1: 3 OOO (Drosophila) DACHSHUND, DROSOPHILA E (236) RE (237) GR (238) HOMOLOG OF; dachshund homolog 1 (Drosophila); dachshund homolog 1 isoform a; dachshund homolog 1 isoform b; dachshund homolog 1 isoform c

SO251 transcription 298.41 TFCP2L2; LBP-32; MGR; GRHL1; EALYPORRS DYYKVPRE DKYDWPHD 1:54 OO factor CP2-like mammalian grainyhead; LBP pro YTSEDEAWK RRSSTAKPE KIGKIFKKCK 2 tein 32; transcription CP2 (239) WE (240) K (241) like 2; leader-binding protein 32 isoform 2; leader-binding protein 32 isoform 1

SO253 lysosomal as 5.535.3 LAPTM4B; lysosomal associated DPDOYNFSS EYIROLPPN DTTWLLPPY : 5OO sociated protein protein transmembrane 4 beta SELGGDFEF FPYRDD DDATWINGA : 2OOO transmembrane MDD (242) (243) AKE (244) 4 beta

SO255 cyclin E2 9134 CYCE2; CCNE2; cyclin E2; G1/S- RREEWTKKH KESRYWHD DFFDRFMLT : 1.OOO specific cyclin E2; cyclin E2 OYEIR (245) KHFEWLHSD OKDINK : 2OOO isoform 2; cyclin E2 isoform LE (246) (247) 3; cyclin E2 isoform 1

SO26 O nica strin 233.85 KIAAO253; nica strin; NCSTN; ESKHFTRDLM ETDRLPRCW ESRWKDIRA : 24 OO APH2, ANTERIOR PHARYNX DEFEC EKLKGRTSR RSTARLAR RIFLIASKEL : 54 OO TIVE 2, C. ELEGANS, HOMOLOG OF (248) (249) E (25O)

SO265 FXYD domain 5349 MAT-8; MAT8; PLML, FXYD3; KWTLGLLWFL SEWRSSGE KCKCKFGO : 4 OO containing ion phospholemman-like protein; AGFPWLDAND QAGR (252) KSGHHPGE : 12 OO transport regul MAMMARY TUMOR, 8-KD; FXYD do LED (251) (253) lator 3 main-containing ion transport regulator 3; FXYD domain con taining ion transport regula tor 3; FXYD domain containing ion transport regulator 3 iso form 2 precursor; FXYD domai

SO267 immunoglobulin 3321 EWI-3; V8; IGSF3; immunoglobin KWAKESDSWF EREKTVTGE KRAEDTAG 1:2OO superfamily, superfamily, member 3; immuno WLKIYHLROE FIDKESKRP OTALTVMRP 1:250 member 3 globulin superfamily, member 3 D (254) K (255) D (256)

SO27 O signal trans 10254 STAM2B, STAM2; DKFZp564 Co47; KWARKWRALY ETEWAAWDK EIKKSEPEP 1 : 1.OOO ducing adaptor Hbp; STAM2A; SIGNAL-TRANSDUC DFEAWEDNE LNWIDDDWE WYIDEDKMD 1:9 OOO molecule (SH3 ING ADAPTOR MOLECULE 2; signal (257) (258) R (259) domain and ITAM transducing adaptor molecule motif) 2 2; STAM-like protein contain ing SH3 and ITAM domains 2; signal transducing adaptor molecule (SH3 domain and ITAM motif) 2

SO273 dickkopf homolog 22943 DKK1; DKK-1; SK; dickkopf -1 DEECGTDEY RGEIEETITE 1: 4 OO 1 (Xenopus like; dickkopf (Xenopus CASPTRGGD SFGNDHSTL 1 : 5OO laevis) laevis) homolog 1; dickkopf (260) D (261) homolog 1 (Xenopus laevis); DICKKOPF, XENOPUS, HOMOLOG OF 1.

SO28O solute carrier 65010 SLC26A6; solute carrier family MDLRRRDYH DTDIYRDWA EFYSDALKO 1 : 18 OO family 26, 26, member 6 MERPLLNOE EYSEAKE RCGWDVDF 1:24 OO member 6 HLEE (262) (263) LISOKKK (264) US 2010/0062444 A1 Mar. 11, 2010 25

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO286 WNT inhibitory 11197 WIF1; WIF-1; WNT inhibitory DAHOARVLIG ERRICECPD KRYEASLIH 1:90 factor 1 factor 1; Wnt inhibitory FEEDILIWSE GFHGPHCE ALRPAGAQL factor-1 precursor (265) K. (266) R (267)

SO288 preferentially 23 532 MAPE, PRAME; OPA-INTERACTING KRKWDGLSTE KEGACDELF DIKMILKMW 1 : 12 OO expressed anti PROTEIN 4; Opa-interacting AEOPFIPVE SYLIEKWKR QLDSIEDLE gen in melanoma protein OIP4; preferentially (268) KK (269) (27 O) expressed antigen in melanoma; melanoma antigen preferential ly expressed in tumors

SO295 prostaglandin E 9536 PGES; TP531.12; MGST1L1; RLRKKAFANP RSDPDWER RWAHTWAYL 1 : 1.OO synthase PP1294, PP102; PTGES; EDALR (271) CLRAHRND GKLRAPIR 1:24 OO MGC10317; PIG12; MGST1-L1; (272) (273) MGST-IV; MGST1-like 1; p53 INDUCED GENE 12; prostaglandin E synthase; p53-induced apop tosis protein 12; prostaglan din E synthase isoform 2; prostaglandin E synthase isoform 1 ; micros

SO296 solute carrier 814 O SLC7A5; MPE16; D16S469E, CD98; KRRALAAPAA EAREKMLAA MIWLRHRKP 1: 3 OO family 7 LAT1; 4 F2 light chain; Mem- EEKEEAR KSADGSAP ELERPIK 1 : 5OOO (cationic amino brane protein E16; L-TYPE (274) AGE (275) (276) acid transpor AMINO ACID TRANSPORTER 1; ter, y' system), Solute carrier family 7, mem member 5 ber 5; solute carrier family 7 (cationic amino acid trans porter, y' system), member 5

SO296P solute carrier 814 O SLC7A5; MPE16; D165469E, CD98; KRRALAAPAA NAA NAA 1: 225 1. family 7 LAT1; 4 F2 light chain; Mem- EEKEEAR 1: 3150 (cationic amino brane protein E16; L-TYPE (277) acid transpor AMINO ACID TRANSPORTER 1; ter, y' system), Solute carrier family 7, member 5 member 5; solute carrier family 7 (cationic amino acid transporter, y' system), member 5

SO297 w-malf 7975 FLJ322O5 NFE2U MAFK, NFE2, KPNKALKWKK KRVTOKEEL RLELDALRS 1: 333 musculoaponeuro 18-KD SUBUNIT; nuclear factor EAGE (278) ERQRVELO KYE (28 O) 1: 8OO tic fibrosarcoma erythroid-2, ubiquitous (p.18); OEVEK (279 oncogene homolog NUCLEAR FACTOR ERYTHROID 2. K (avian) UBIQUITOUS SUBUNIT, v-maf mus culoaponeurotic fibrosarcoma oncogene homolog K (avian) ; v-maf avian musculoaponeurotic fibrosarcoma oncogen

signal peptide, sffs SCUBE2; signal peptide, CUB KMHTDGRSC KKGFKLLTD KRTEKRLRK 1:35 OO CUB domain domain EGF-like 2 LEREDTWLEV EKSCODVD AIRTLRKAW 1:54 OO EGF-like 2 TE (281) E (282) HRE (283)

gamma-amino 2564 GABRE GABA-A RECEPTOR EPSI- RVEGPOTES EETKSTETE KWENFKLEI 1: 3 OO butyric acid LON POLYPEPTIDE; GAMMA- KNEASSRD TGSRWGKLP NEKNSWKL 1 : 5OO (GABA) A recep AMINOBUTYRIC ACID RECEPTOR, (284) E (285) FOFD (286) tor, epsilon EPSILON; gamma-aminobutyric acid (GABA) A receptor, epsi lon; gamma-aminobutyric acid (GABA) A receptor, epsilon isoform 2 ; gamma-aminobutyric acid (GABA) A receptor, epsilon is US 2010/0062444 A1 Mar. 11, 2010 26

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO305 S100 calcium 6281 CAL1L; GP11; p.10; 42C; DKGYLTKEDL KDPLAVDKI N/A 1: 8332 binding protein S100A10; ANX2LG; CLP11; Ca1; RVLMEKE MKDLDOCR 1:24996 A10 (annexin II CALPACTIN I, p11. SUBUNIT; AN- (287) DGK (288) ligand, calpac NEXIN II, LIGHT CHAIN; CAL tin I, light PACTIN I, LIGHT CHAIN; S1 OO polypeptide calcium-binding protein A10 (p11) ) (annexin II ligand, calpact in I, light polypeptide (p11)) ; S100 calcium binding protein A1O

SO311 v-myb myeloblas 4605 MYBL2, MGC156OO MYB-RELATED MSRRTRCED EEDLKEWLR RRSPIKKWR 1: 750 tosis viral on GENE BMYB; MYB-related protein LDELHYODTD SEAGIELIIE KSLALDIWD 1 : 5OOO cogene homolog B; v-myb myeloblastosis viral SD (289 DDIR (29O) ED (291) (avian) - like 2 oncogene homolog (avian) - like 2; V-MYB AVIAN MYELOBLASTOSIS WIRAL ONCOGENE HOMOLOG-LIKE 2

SO312 nucleoside 486 O NP; 2.4.2.1; nucleoside phos - EDYKNTAEW DERFGDRF KWIMDYESL 1: 1.OOO phosphorylase phorylase; PURINE- LLSHTKHR PAMSDAYD EKANHEE 1:36 OO NUCLEOSIDE: ORTHOPHOSPHATE (292) RTMROR (294) RIBOSYLTRANSFERASE; purine (293) nucleoside phosphorylase; PNP NUCLEOSIDE PHOSPHORYLASE DEFICIENCY ATAXIA WITH DE FICIENT CELLULAR IMMUNITY

SO314 chaperonin con 22948 KIAAOO98; CCT5; chaperonin DQDRKSRLM KGWIWDKDF RMILKIDDIR 1: 6OOO taining TCP1, containing TCP1, subunit 5 GLEALKSHIM SHPOMPKK KPGESEE 1: 3 OOOO subunit 5 (epsilon) AAK (295) VED (296) (297) (epsilon)

SO315 non-metastatic 483 O GAAD; NME1; NDPKA; 2.7. 4. 6; RLOPEFKPKO KFMOASED DSWESAEKE 1: 9 OOO cells 1, protein NM23-H1; AWD NM23H1B; GZMA- LEGTMANCE LLKEHYWDL IGLWFHPEE 1: 18 OOO (NM23A) ex ACTIVATED DNase; NUCLEOSIDE R (298) KDR (299) LVD (3 OO pressed in DIPHOSPHATE KINASE-A; AWD DROSOPHILA HOMOLOG OF; METASTASIS INHIBITION FACTOR NM23; nucleoside-diphosphate kinase 1 isoform b : NONMETA STATIC PROTEIN 23, HOMOLOG 1; nucleo

SO316 squalene 6713 SQLE; 1.14.99.7; squalene KSPPESENKE RDGRKWTWI DHLKEPFLE 1: 1.OOO epoxidase epoxidase; squalene QLEARRRR ERDLKEPDR ATDNSHLR 1 : 1.OOOO monooxygenase (301) (3 O2) (303)

SO319 pregnancy 29948 OKL38; pregnancy-induced DLEVKDWMO EYHKVHOM RHOLLCFKE 1:9 OO induced growth growth inhibitor; PREGNANCY- KKRRGLRNS MREOSILSP DCQAVFOD inhibitor INDUCED GROWTH INHIBITOR OKL38 R. (3O4) SPYEGYR LEGWEK (3 O5) (306)

SO326 mal T-cell 114569 MAL2; mall T-cell differentia - GPDILRTYSG CSLGLALRR NA 1 : 12 O differentiation tion protein 2 AFWCLE WRP (3O8) 1 : 12 OO protein 2 (3 O7)

SO33 O aldo-keto re 1645 1.1.1.213; 2-ALPHA-HSD; RYLTLDIFAG NAA NAA 1:25 OO ductase family 1.3.1.20; 20-ALPHA-HSD; PPNYPFSDEY 1:75 OOO 1, member C 1/2 MGC8954; H-37; HAKRC, MBAB; (309) (dihydrodiol C9; DDH1; AKR1C1; trans-1 2 dehydrogenase 1 ; dihydrobenzene-1,2-diol dehy 2O-alpha (3- drogenase; chlordecone reduc alpha) -hydroxy tase homolog; aldo-keto reduc steroid dehydro tase C; 20 alpha-hydroxyster genase) oid dehydrogenase; hepatic dihydrodiol

SO33 O aldo-keto re 1645 1.1.1.213; 2-ALPHA-HSD; RYLTLDIFAG NAA NAA 1: 6OO X1 ductase family 1.3.1.20; 20-ALPHA-HSD; PPNYPFSDEY 1, member C 1/2 MGC8954; H-37; HAKRC, MBAB; (310) (dihydrodiol C9; DDH1; AKR1C1; trans-1 2 US 2010/0062444 A1 Mar. 11, 2010 27

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER dehydrogenase 1 ; dihydrobenzene-1,2-diol de 2O-alpha (3- hydrogenase; chlordecone re alpha) -hydroxy ductase homolog; aldo-keto steroid dehydro reductase C; 2 O alpha-hydroxy genase) steroid dehydrogenase; hepatic dihydrodiol

SO331 aldo-keto re 8644 HA1753; 1.1.1. 188; DD3; HYENSDSFAS N/A 1: 3 OO ductase family hIuPGFS; HSD17B5; 1.3.1.20; HPNYPYSDE 1:999 1, member C3 (3- 1.1.1.213; AKR1C3; KIAAO119; Y (311) alpha hydroxy HAKRB; HAKRe; trans-1,2-dihy steroid dehydro drobenzene-1,2-diol dehydro genase, type II) genase; chlordecone reductase homolog; dihydrodiol dehydro genase 3; prostaglandin F syn thase; ALDO-KETO REDUCTASE B; 3

SO331 aldo-keto re 8644 HA1753; 1.1.1. 188; DD3; HYENSDSFAS N/A 1: 15 O X1 ductase family hIuPGFS; HSD17B5; 1.3.1.20; HPNYPYSDE 1: 3 OO 1, member C3 (3- 1.1.1.213; AKR1C3; KIAAO119; Y (312) alpha hydroxy HAKRB; HAKRe; trans-1,2-dihy steroid dehydro drobenzene-1,2-diol dehydro genase, type II) genase; chlordecone reductase homolog; dihydrodiol dehydro genase 3; prostaglandin F syn thase; ALDO-KETO REDUCTASE B; 3

SO332 aldo-keto re 1645 1.1.1.213; 2-ALPHA-HSD; RYWWMDELM NAA 1: 3 OO ductase family 1.3.1.20; 2O-ALPHA-HSD; DHPDYPFSD 1: 4 OO 1, member C4 MGC8954; H-37; HAKRC, MBAB; EY (313) (dihydrodiol C9; DDH1; AKR1C1; trans-1 2 dehydrogenase 1 ; dihydrobenzene-1,2-diol dehy 2O-alpha (3- drogenase; chlordecone reduc alpha) -hydroxy tase homolog; aldo-keto reduc steroid tase C; 20 alpha-hydroxyster dehydrogenase) oid dehydrogenase; hepatic dihydrodiol

SO332 aldo-keto re 1645 1.1.1.213; 2-ALPHA-HSD; RYWWMDELM NAA 1: 75 X1 ductase family 1.3.1.20; 2O-ALPHA-HSD; DHPDYPFSD 1:150 1, member C4 MGC8954; H-37; HAKRC, MBAB; EY (314) C9; (dihydrodiol DDH1; AKR1C1; trans-1 2-di dehydrogenase 1 ; hydrobenzene-1,2-diol dehydro 2O-alpha (3- genase; chlordecone reductase alpha) -hydroxy homolog; aldo-keto reductase steroid C; 20 alpha-hydroxysteroid de dehydrogenase) hydrogenase; hepatic dihydrodiol

SO336 chromosome 2 O 1. 40809 C2Oorf139; chromosome 20 open DPAKVQSLV RETIPAKLW 1: 16 OO open reading reading frame 139 DTIREDPD QSTLSDLR 1:24 OO frame 139 (315) (316)

SO342 solute carrier 1. SLC2A12; solute carrier family SDTTEELTVIK N/A 1: 4 OO family 2 (facil 2 (facilitated glucose trans- SSLKDE 1: 1250 itated glucose porter), member 12 (317) transporter), member 12

SO343 solute carrier 1. SLC2A12; solute carrier family HSRSSLMPLR N/A family 2 (facil 2 (facilitated glucose trans- NDVDKR 1: 125 itated glucose porter), member 12 (318) transporter), member 12

SO357 HTPAP protein 84513 HTPAP; HTPAP protein YRNPYWEAE NAA 1 : 1.OO YFPTKPMFWI 1: 3 OO A (319) US 2010/0062444 A1 Mar. 11, 2010 28

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO364 KIAAO 746 protein 23231 KIAAO746; KIAAO746 protein KKFPRFRNRE NAA NAA : 2OO LEATRRORM : 3 OO D (32O)

SO367 peroxisomal 12297 O PTE2B; peroxisomal acyl-CoA SGNTAINYKH NAA : 2OO acyl-CoA thioesterase 2B SSIP (321) : 6OO thioesterase 2B

SO374 chloride intra 534 OS CLIC5; chloride intracellular DANTCGEDK NAA : 5OOO cellular channel channel 5 GSRRKFLDG : 9 OOO 5 DE (322)

keratinocyte 2 OO 634 KRTCAP3; keratinocyte associ QLEEMTELES NAA : 2OOO associated ated protein 3 PKCKROENE : 9 OOO protein 3 Q (323)

SO384 FERM, RhoGEF 1016 O p63RhoGEF, CDEP, FARP1; QADGAASAP NAA : 1.OO (ARHGEF) and chondrocyte-derived ezrin-like TEEEEEWWKD pleckstrin do protein; FERM, RhoGEF, and R (324.) main protein 1 pleckstrin domain protein 1; (chondrocyte FERM, ARHGEF, AND PLECKSTRIN derived) DOMAIN- CONTAINING PROTEIN 1. FERM, RhoGEF (ARHGEF) and pleckstrin domain protein 1 (chondrocyte-derived)

SO388 trichorhino 7227 GC79, TRPS1, TRPS1. GENE; SGDSLETKED NAA 1: 6OO phalangeal trichorhinophalangeal syndrome OKMSPKATE syndrome I I; zinc finger transcription E (325) factor TRPS1

SO396 cytochrome, 1576 1. 14.14.1; HLP; CYP3A3; RKSWKRMIKE NAA 1: 15 P450, family 3, CYP3A4, P450 C3 NF-25 CP33; SRLEDTOKH subfamily A, CP34; P450-III, STEROID-INDUC RV (326) polypeptide 4 IBLE; nifedipine oxidase; glu cocorticoid-inducible P450; CYTOCHROME P45 OPCN1; P450, FAMILY III; P450-III, steroid inducible; cytochrome P450, subfamily IIIA, polypeptide 4;

SO398 FAT tumor sup 21.95 CDHF7; FAT; cadherin ME5; FAT KIRLPEREKP NAA 1: 45 pressor homolog tumor suppressor precursor; DRERNARRE 1:2OO 1 (Drosophila) cadherin-related tumor sup P (327) pressor homolog precursor ; cadherin family member 7 pre cursor; homolog of Drosophila Fat protein precursor; FAT tumor suppressor homolog 1 (Drosophila); FAT TUMOR SUPPRESS

SO4. O1 granulin 2896 ACROGRANIN PROEPITHELIN; RGTKCLRRE NAA 1: 6OO PROGRANULIN; PEPI. PCDGF; APRWDAPLR 1: 3 OOO granulin; GRN; EPITHELIN DP (328) PRECURSOR

SO4. O4 N-myc downstream 10397 HMSNL; TARG1 CMT4D, RTP; GTRSRSHTS NAA 1 : 1.OO regulated gene 1 PROXY1; NDRG1; GC4; NMSL; EGTRSRSHT 1:9 OO TDD5; RIT42; NDR1; differenti SE (329) ation-related gene 1 protein; nickel-specific induction protein Cap43; protein regul lated by oxygen-1; NMYC DOWN STREAM-REGULATED GENE 1: re ducing agents and tunicamycin respon US 2010/0062444 A1 Mar. 11, 2010 29

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO411 fatty acid bind 2171 PAFABP, EPABP, E-FABP, FABP5; EETTADGRKT N/A NAA 1 : 18 OO ing protein 5 PA-FABP, FATTY ACID-BINDING QTVCNFTD (psoriasis PROTEIN, EPIDERMAL, FATTY (330) associated) ACID-BINDING PROTEIN 5 ; FATTY ACID-BINDING PROTEIN PSORIA SIS-ASSOCIATED; fatty acid binding protein 5 (psoriasis associated)

SO413 cyclin-dependent 1028 WBS; p57 (KIP2), BWCR; CDKN1C; AKRKRSAPE NAA NAA 1:27 OO kinase inhibitor BWS; Beckwith-Wiedemann syn KSSGDWP 1C (p57, Kip2) drome; cyclin-dependent kinase (331) inhibitor 1C (p57, Kip2)

SO414 alpha-methyl 236OO AMACR; 5.1.99. 4; ALPHA-METHYL RWDRPGSRY NAA NAA 1:100 acyl-CoA ACYL-CoA RACEMASE; AMACR DE DWSRLGRGK accease FICIENCY AMACR ALPHA-METHYL RS (332) ACYL-CoA RACEMASE DEFICIENCY, alpha-methylacyl-CoA racemase isoform 1 ; alpha-methylacyl CoA racemase isoform 2

SO415 gamma-amino 2562 MGC9051; GABRB3; GABA-A ETVDKLLKGY NAA NAA 1: 6OO butyric acid RECEPTOR BETA-3 POLYPEPTIDE; DIRLRPD 1 : 18 OO (GABA) A recep GAMMA-AMINOBUTYRIC ACID (333) tor, beta 3 RECEPTOR, BETA-3 ; gamma aminobutyric acid (GABA) A receptor, beta 3 ; gamma-amino butyric acid (GABA) A recep tor, beta 3 isoform 2 precur sor; gamma-aminobutyric acid (GABA) A rece

SO417 HSV-1 stimula 22879 HSRG1; KIAAO872; HSV-1 stim APGGAEDLE NAA NAA 1:9 OOO tion-related ulation-related 1; HSV-1 stim DTOFPSEEAR gene 1 ulation-related gene 1 E (334)

SO425 tumor necrosis 27242 TNFRSF21; DR6; BM-O18, TNFR RKSSRTLKKG N/A NAA 1:9 OOO factor receptor related death receptor 6; PRODPSAIVE superfamily, tumor necrosis factor receptor (335) member 21 superfamily, member 21; tumor necrosis factor receptor superfamily, member 21 precursor

SO429 Jumonji domain 221 O37 JMJD1C; TRIP8; jumonji domain GSESGDSDE NAA NAA 1 : 12 OO containing 1C containing 1C; THYROID HORMONE SESKSEORTK RECEPTOR INTERACTOR 8 R (336)

SO432 chromosome 9 null C9orf140; chromosome 9 open EADSGDARR NAA 1:90 open reading reading frame 14 O LPRARGERR 1: 3 OO frame 14 O RH (337)

SO44 O cell division 994 3.1.3.48; CDC25B; cell divi RLERPODRD NAA 1: 350 cycle 25B sion cycle 25B; cell division TPVONKRRR 1:36 OO cycle 25B isoform 4 ; cell di S (338) vision cycle 25B isoform 5; cell division cycle 25B iso form 1 ; cell division cycle 25B isoform 2; cell division cycle 25B isoform 3

SO445 laminin, beta 1 3912 LAMB1; LAMININ BETA-1, CUTIS DRWEDWMME NAA NAA 1: 6OO LAXA-MARFANOID SYNDROME; RESOFKEKO 1 : 18 OO laminin, beta 1; laminin, beta E (339) 1 precursor; LAMB1 NEONATAL CUTIS LAXA WITH MARFANOID PHENOTYPE US 2010/0062444 A1 Mar. 11, 2010 30

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO447 papillary renal 5546 TPRC, MGC17178, MGC4723, PRCC, DEAFKRLQG N/A NAA 1: 4 OOO cell carcinoma proline-rich protein PRCC; KRNRGREE 1: 6OOO (translocation RCCP1 PRCC/TFE3 FUSION GENE; (340) associated) papillary renal cell carcinoma (translocation-associated) ; RENAL CELL CARCINOMA PAPIL LARY, 1 GENE; papillary renal cell carcinoma translocation associated gene product

SO455 tumor necrosis 8743 APO2L; TL2; Apo-2L; TNFSF10; RFOEEIKENT NAA 1:9 OO factor (ligand) Apo -2 ligand; APO2 LIGAND; KNDKO (341) superfamily, TNF-RELATED APOPTOSIS-INDUCING member 10 LIGAND; TNF-related apoptosis inducing ligand TRAIL; tumor necrosis factor (ligand) superfamily, member 10; TUMOR NECROSIS FACTOR LIGAND SUPER FAMILY MEMBER 10

SO459 tiltin 7273 connectin; TMD; tiltin; CMD1G; KRDKEGWRW NAA 1:27 OO CMPD4; TTN, FLJ32O4. O. CMH9, TKCNKKTLTD 1: 81. OO included; tiltin isoform N2-A; (342) titlin isoform N2-B; tiltin iso form novex-1; tiltin isoform novex-2; tiltin isoform novex 3; cardiomyopathy, dilated 1G (autosomal dominant); TTN CARDIOMYOPATHY, FAMILIAL

SO469 DNA fragmenta 1676 DFF45; DFF1; DFFA, ICAD; DFF- KEGSLLSKOE NAA 1: 6OO tion factor, 45 45; INHIBITOR OF CASPASE- ESKAAFGEE kDa, alpha poly ACTIVATED DNase; DNA FRAGMEN- (343) peptide TATION FACTOR, 45-KD ALPHA SUBUNIT; DNA fragmentation factor, 45 kDa, alpha poly peptide; DNA fragmentation factor, 45 kD, alpha subunit; DNA fragmentation factor, 45 kD, alp

SO494 caspase 2, 835 ICH-1L/1S; CASP2; ICH1; CASP ESDAGKEKLP NAA 1:2OOO apoptosis 2; ICH-1 protease; caspase 2 KMRLPTRSD related cysteine isoform 3 ; caspase 2 isoform (344) protease (neural 4; NEDD2 apoptosis regulatory precursor cell gene; caspase 2 isoform 2 pre expressed, de cursor; caspase 2 isoform 1 velopmentally preproprotein; NEURAL PRECUR down-regulated SOR CELL, EXPRESSED, DEVELOP 2 MENTALLY DOWNREGULATED 2;

SOSO1 G1 to S phase 2935 GSPT1; eRF3a; ETF3A; GST1, ERDKGKTWE NAA 1: 15 OOO transition 1 YEAST HOMOLOG OF PEPTIDE WGRAYFETEK CHAIN RELEASE FACTOR 3A; G1 (345) TO S-PHASE TRANSITION 1: G1 to S phase transition 1

SOSO2 GCN5 general 2648 hCGCN5; GCN5L2; GCN5 (general EKFRVEKDKL N/A 1:9 OOO control of control of amino-acid synthe- WPEKR amino-acid sis, yeast, homolog) -like 2; (346) synthesis 5 GCN5 general control of amino like 2 (yeast) acid synthesis 5-like 2 (yeast) ; General control of amino acid synthesis, yeast, homolog-like 2

SOSO3 geminin, DNA 51053 GMNN; geminin, DNA replication EVAEKRRKAL N/A 1: 333 replication inhibitor YEALKENEK inhibitor (347) US 2010/0062444 A1 Mar. 11, 2010

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SOSOf ADP-ribosylation 64225 ARL6IP2; ADP-ribosylation ENYEDDDLV N/A NAA : 8OOO factor-like 6 factor-like 6 interacting NSDEWMKKP : 9 OOO interacting protein 2 (348) protein 2

SO511 DNA replication 51659 Pfs2; DNA replication complex PKADEIRTLV N/A : 2OOO complex GINS GINS protein PSF2 KDMWDTR protein PSF2 (349)

SO524 ankyrin repeat 55608 ANKRD10; ankyrin repeat domain RKRCLEDSE NAA : 45 OO domain 10 10 DFGWKKARTE (35O)

SO527 potassium null KCTD2; potassium channel EPKSFLCRLC N/A : 9 OO channel tetra tetramerisation domain COEDPELDS : 15 OO merisation do containing 2 (351) main containing 2

SO528 rab connectin-3 23312 RC3; KIAAO856; rabconnectin-3 EEYDRESKS N/A 1: 350 SDDWDYRGS 1 : 12 OO (352)

SO538 acidic (leucine 81611 ANP32E.; acidic (leucine-rich) CVNGEIEGLN NAA 1 : 12 OO rich) nuclear nuclear phosphoprotein 32 DTEKELEF phosphoprotein family, member E (353) 32 family, member E

SO544 chromosome 9 84904 C9orf 100; chromosome 9 open EORARWERK N/A 1: 4 O open reading r eading frame 100 RACTARE 1:24 O frame 1 OO (354)

SO545 Hpall tiny 27 O37 D22 S1733E; HTF9C; Hpall tiny ERKOLECEO NAA 1:9 OO fragments locus fragments locus 9C; Hpall tiny VLQKLAKE 1:54 OO 9C fragments locus 9C isoform2; (355) Hpall tiny fragments locus 9C isoform 1

SO546 cell division 157313 CDCA2; cell division cycle RNSETKVRR NAA 1 : 12 OO cycle associated associated 2 STRLQKDLEN 2 (356)

SO553 mitotic phos 1294 O1 MP44; NUP35; LOC1294 O1; SDYOVISDRO NAA 1: 3 OOO phoprotein 44 NUCLEOPORIN, 35-KD; mitotic TPKKDE 1:54 OO phosphoprotein 44 (357)

SO557 SMC4 structural SMC4L1; CAPC; hdAP-C; chromo DIEGKLPQTE NAA 1:2OO maintenance of some-associated polypeptide C; QELKE (358) chromosomes 4 SMC4 (structural maintenance like 1 (yeast) of chromosomes 4 yeast) - like 1; SMC4 structural maintenance of chromosomes 4-like 1 (yeast) ; structural mainten ance of chromosomes (SMC) family member, chromosome-ass

SO564 phosphatidyl 97.91 KIAAOO24; PSSA; PTDSS1; DDVNYKMHF NAA 1 : 1.OOO serine synthase phosphatidylserine synthase 1 RMINEOOVE 1: 8OOO 1. D (359)

SO565 polo-like kinase 5347 2.7.1. - ; PLK1; STPK13; polo ENPLPERPRE NAA 1 : 1.O- 1 (Drosophila) like kinase (Drosophila); polo KEEPWWR 1:100 (Drosophia) - like kinase; (360) SERINE/THREONINE PROTEIN KINASE 13; polo - like kinase 1 (Drosophila)

SO567 Pirin 8544 Pirin; PIR REOSEGVGA NAA 1:24 O RWRRSIGRPE (361) US 2010/0062444 A1 Mar. 11, 2010 32

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO578 ATP-binding 21 ABCA3; ABC3; LBM18 O; ABC-C; PRAWAGKEE NAA NAA 1: 15 OO cassette sub EST111653; ABC transporter 3; EDSDPEKALR family A (ABC1), ATP-binding cassette 3; ATP (362) member 3 BINDING CASSETTE TRANSPORTER 3; ATP-BINDING CASSETTE SUB FAMILY A MEMBER 3; ATP-bind ing cassette, sub-family A member 3; ATP-binding cas sette, subfamily A (ABC1), memo

SO579 ATP-binding 10347 ABCX; ABCA7; ABCA-SSN; autoan EKADTDMEG NAA 1: 3 OO cassette sub tigen SS-N; macrophage ABC SWDTROEK 1: 4 OO family A (ABC1), transporter; SJOGREN SYNDROME (363) member 7 ANTIGEN SS-N; ATP-BINDING CASSETTE SUBFAMILY A MEMBER 7; ATP-binding cassette, sub family A (ABC1), member 7; ATP-binding cassette, sub family A, member 7 isoform a ; A.

SO581 ATP-binding 22 ABCB7; Atm1p; ASAT; ABC7; RVONHDNPK NAA 1: 4 OOO cassette sub E5T14 O535; ABC TRANSPORTER 7; WEAKKENISK 1 : 1.OOOO family B ATP-binding cassette 7; ATP (364) (MDR/TAP), BINDING CASSETTE TRANSPORTER member 7 7; Anemia, sideroblastic, with spinocerebellar ataxia; ATP BINDING CASSETTE SUBFAMILY B, MEMBER 7; ATP-binding cas sette, sub-family B, member

SO585 ATP-binding 9416 O MRP9; ABCC12; MULTIDRUG RSPPAKGAT NAA 1 : 5OO cassette sub RESISTANCE-ASSOCIATED PROTEIN GPEEOSDSL family C 9; ATP-BINDING CASSETTE, K (365) (CFTRAMRP), SUBFAMILY C MEMBER 12 ATP member 12 binding cassette, sub-family C (CFTRAMRP), member 12

SO586 ATP-binding 9.429 ABC15 MXR1; ABCP, EST157481; REEDFKATEII NAA NA 1: 333 cassette sub MRX; ABCG2, BCRP1, BMDP; EPSKQDKP 1: 4 OO family G MITOXANTRONE-RESISTANCE (366) (WHITE) , member PROTEIN; mitoxantrone resis 2 tance protein; placent a speci fic MDR protein; ATP-BINDING CASSETTE TRANSPORTER, PLACENTA-SPECIFIC; breast can cer resistance protein; ATP BINDING CASS

SO593 solute carrier 28234 OATP1B3; SLC21A8; OATP8; DKTCMKWST 1 : 5OO organic anion SLCO1B3; ORGANIC ANION TRANS NSCGAQ 1:24 OO transporter PORTER 8; solute carrier or - (367) family, member ganic anion transporter fam 1B3 ily, member 1B3; SOLUTE CAR RIER FAMILY 21 MEMBER 8 (OR GANIC ANION TRANSPORTER) ; solute carrier family 21 (organic anion transporter), member 8

SO597 solute carrier 9356 ROAT1, MGC4526 O HOAT1, PAHT; DANLSKNGG NAA 1: 3 OOO family 22 (or SLC22A6; PAH TRANSPORTER, LEWWL (368) ganic anion para-aminohippurate transpor transporter), ter; renal organic anion member 6 transporter 1; solute carrier family 22 member 6 isoform b; solute carrier family 22 mem ber 6 isoform c; solute car rier family 22 member 6 isoform US 2010/0062444 A1 Mar. 11, 2010 33

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

solute carrier UGT2, UGTL. UGAT; SLC35A2; EPFLPKLLTK N/A NAA 1:24 OO family 35 (UDP UGT1; UDP-galactose translo- (369) galactose cator; UDP-GALACTOSE TRANS transporter), PORTER, ISOFORM 2, UGALT UDP member A2 GALACTOSE TRANSPORTER, ISOFORM 1; solute carrier family 35 (UDP-galactose transporter), member A2; solute carrier family 35 (UDP-galactose transpo

SO607 cell division 994 3.1.3.48; CDC25B; cell divi - RKSEAGSGA NAA 1 : 18 OO cycle 25B sion cycle 25B; cell division ASSSGEDKE cycle 25B isoform 4 ; cell di- N (370) vision cycle 25B isoform 5; cell division cycle 25B iso form 1 ; cell division cycle 25B isoform 2; cell division cycle 25B isoform 3

SO609 Stearoyl-CoA 6319 SCD; acyl-CoA desaturase; DDIYDPTYKD N/A 1:2OOO desaturase Stearoyl-CoA desaturase KEGPSPKWE 1 : 5OOO (delta-9- (delta-9- desaturase); fatty (371) desaturase) acid desaturase

SO611 mitogen 63 OO SAPK3; p38gamma; SAPK-3; p38- QSDEAKNNM N/A 1:100 activated pro GAMMA; PRKM12; MAPK12; ERK3; KGLPELEKKD tein kinase 12 ERK6; EXTRACELLULAR SIGNAL - (372) REGULATED KINASE 6; mitogen activated protein kinase 3; stress-activated protein kinase 3 ; mitogen-activated protein kinase 12

SO612 nuclear factor 47.91 LYT-10, LYT1 O; NFKB2, ONCOGENESRPOGLTEAE NAA 1: 45 OO of kappa light LYT 1 O TRANSCRIPTION FACTOR QRELEQEAK polypeptide gene NFKB2; NFKB, p52/p1oo SUBUNIT; (373) enhancer in B LYMPHOCYTE TRANSLOCATION cells 2 CHROMOSOME 10: NUCLEAR FACTOR (p49/p100) KAPPA-B SUBUNIT 2; Nuclear factor of kappa light chain gene enhancer in B-cells 2; nuclear factor of kappa I

SO613 tumor necrosis 958 Bp5o; TNFRSF5, MGC9013; CDW4 O, RVOOKGTSE NAA 1:25 O factor receptor CD4 O antigen; CD4 OL receptor; TDTIC (374) 1:27 O superfamily, B CELL-ASSOCIATED MOLECULE member 5 CD40; CD40 type II isoform; B cell surface antigen CD40; nerve growth factor receptor related B-lymphocyte activa tion molecule; tumor necrosis factor receptor superfam

SO614 Epstein-Barr 10148 EBI3; IL27, EBI3 SUBUNIT, WRLSPLAERO NAA 1 : 12 OO virus induced EPSTEIN-BARR WIRUS-INDUCED LOWOWE 1: 3 OOO gene 3 GENE 3; INTERLEUKIN 27, EBI3 (375) SUBUNIT; Epstein-Barr virus induced gene 3; Epstein-Barr virus induced gene 3 precursor

SO 616 zinc finger 58.495 ZNF339; zinc finger protein RRSLGVSVR NAA 1:25 OO protein 339 339 SWDELPDEK R (376)

SO617 DAB2 interacting 15309 O DAB2IP; DAB2 interacting DEGLGPDPP NAA 1: 6OO protein protein HRDRLRSK (377) US 2010/0062444 A1 Mar. 11, 2010 34

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SO618 protein tyrosine MGC268OO; LIP1; PPFIA1; LIP 1; SGKRSSDGS NAA NAA 1:150 phosphatase, LAR-interacting protein 1; ISHEEDLAK receptor type, PTPRF interacting protein al (378) f polypeptide pha 1 isoform a; PTPRF inter (PTPRF) inter acting protein alpha 1 isoform acting protein b; protein tyrosine phospha (liprin), alpha tase, receptor type, f poly 1. peptide (PTPRF), interacting protein (liprin), alpha 1.

SO 631 RGM domain fam 56963 RGMA, REPULSIVE GUIDANCE SOERSDSPEI N/A 1: 6OO ily, member A MOLECULE; RGM domain family, CHYEKSFHK member A. (379)

SO 633 hypothetical 144347 LOC144347; hypothetical KVNPEPTHEI N/A 1 : 1.OO protein protein LOC144347 RCNSEWK 1:2OO LOC144347 (380)

SO 639 tetratricopep st 217 TTC 7; tetratricopeptide repeat RELREVLRTV N/A 1:2OOO tide repeat domain 7 ETKATON 1: 3 OOO domain 7 (381)

SO 64 O protein C (in 5 624 PROC; 3. 4. 21.69; PROC DEFICI RDTEDOEDO NAA 1 : 1.OOO activator of ENCY PROTEIN C THROMBOPHILIA WDPRLIDGK 1 : 18 OO coagulation fac HEREDITARY, DUE TO PC (382) tors Wa and DEFICIENCY PROTEIN C DEFICI VIIIa) ENCY, CONGENITAL THROMBOTIC DISEASE DUE TO; protein C (in activator of coagulation fac tors Wa and VIIIa)

SO 643 transducin-like His T18976; KIAA1547, ESG3; KNHHELDHR NAA 1:2OO enhancer of TLE3; transducin-like enhancer ERESSAN 1 : 144 O split 3 (E (sp1) protein 3; enhancer of split (383) homolog, groucho 3 ; transducin-like Drosophila) enhancer of split 3 (E (sp1) homolog, Drosophila)

SO 645 frizzled homolog 8324 FzE3; FZD7; frizzled 7; SDGRGRPAF NAA 1:9 OO 7 (Drosophila) frizzled homolog 7 PFSCPRO (Drosophila) ; Frizzled, (384) drosophila, homolog of , 7

SO 646 solute carrier MDU1; 4T2HC; SLC3A2; NACAE; GSKEDFDSLL NAA 1:36 OO family 3 (acti 4F2HC, 4F2 HEAVY CHAIN; CD98 QSAKK (385) 1:54 OO vators of di HEAVY CHAIN; CD98 MONOCLONAL basic and neu ANTIBODY 44D7; ANTIGEN DEFINED tral amino acid BY MONOCLONAL ANTIBODY 4F2, transport), mem HEAVY CHAIN; antigen identi ber 2 fied by monoclonal antibodies 4F2, TRA1.10, TROP4, and T43; SOLUTE CARRIER FAMILY 3

SO648 KIAAO 738 gene 97.47 KIAAO738; KIAAO738 gene EYRNOTNLPT N/A 1:2OO product product ENVDK (386)

SO651 phospholipase A2 22925 PLA2IR; PLA2-R; PLA2R1; OKEEKTWHE NAA 1:36 OO receptor 1, PLA2C1R; PHOSPHOLIPASE A2 RE ALRSCOADN 180 kDa CEPTOR, 18O-KD; phospholipase (387) A2 receptor 1, 180 kDa

SO654 KIAAO182 protein 231.99 KIAAO182; KIAAO182 protein EKAEEGPRK NAA 1: 4 OO REPAPLDK (388)

SO659 thymidine kinase 7084 TK2, THYMIDINE, KINASE, EONRDRILTP NAA 1: 3 OO 2, mitochondrial MITOCHONDRIAL; thymidine ENRK (389) kinase 2 mitochondrial US 2010/0062444 A1 Mar. 11, 2010 35

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) ITER

SO663 chromosome 14 64430 C14orf135; chromosome 14 open RDWYIGLWSD NAA NAA : 9 OO open reading reading frame 135 EKWK (3.9 O) frame 135

SO665 KIAA.1007 protein 23 O19 KIAA.1007; KIAA.1007 protein; DSYLKTRSPW NAA : 15 OO adrenal gland protein AD - OO5; TFLSDLR : 3 OOO KIAA.1007 protein isoform a ; (391) KIAA.1007 protein isoform b SO670 DKFZP566O1646 25.936 DC8; DKFZP566O1646 protein KCRGETWAK NAA : 9 OO protein EISEAMKS (392)

SO672 B-cell 605 BCL 7A; B-cell CLL/lymphoma-7; QRGSOIGRE NAA : 8OO CLL/lymphoma 7A B-cell CLL/lymphoma 7A PIGLSGD (393)

SO673 likely ortholog 2.8987 ART-4; NOB1P; adenocarcinoma KPPOETEKG NAA : SO of mouse nin antigen recognized by T HSACEPEN one binding lymphocytes 4; likely ortholog (394) protein of mouse nin one binding protein

SO676 guanine nucleo 2768 RMP; NNX3; GNA12, GUANINE ERRAGSGAR NAA 1 : 12 OO tide binding NUCLEOTIDE-BINDING PROTEIN, DAERE (395) 1:24 OO protein (G pro ALPHA-12; guanine nucleotide tein) alpha 12 binding protein (G protein) alpha 12

SO677 GrpE-like 1, HMGE GRPEL1, HUMAN SEOKADPPAT NAA : 5OO mitochondrial MITOCHONDRIAL GrpE PROTEIN; EKTLLE : 1.OOO (E. coli) GrpE-like 1, mitochondrial (396) (E. coli) ; Grp E, E. COLI, HOMOLOG OF 1

SO 684 hypothetical 916. Of FLJ34922; hypothetical protein EAEWSQGWO NAA : 81. OO protein FLJ34922 FLJ34922 GTLRIKKYLT (397)

SO 687 hypothetical 54942 FLJ20457; hypothetical protein EESKSITEGL NAA : 6OO protein FLJ20457 FLJ2O457 LTOKOYE : 1260 (398)

SO691 solute carrier 23657 CCBR1; SLC7A11; xCT; cystine/ ONFKDAFSG NAA : 1.OOO family 7, (ca glutamate transporter; SYSTEM RDSSITR : 1575 tionic amino Xc (-) TRANSPORTER-RELATED (399) acid transpor PROTEIN SOLUTE CARRIER FAMILY ter, y' system) 7, MEMBER 11; solute carrier member 11 family 7, (cationic amino acid transporter, y' system) member 11

SO692 glutamate 2729 GLCLC; GCLC; 6.3.2.2; GCS; EKIHLDDANE NAA 1 : 1.OO cysteine ligase, GAMMA - GLUTAMYLCYSTEINE SYNTHE SDHFEN 1: 4 OO catalytic TASE, CATALYTIC SUBUNIT; glu (4 OO) subunit tamate-cysteine ligase, cata lytic subunit

SO695 integrin, beta 4 3691 ITGB4; INTEGRIN BETA-4; TEDVDEFRNK N/A 1:27 OO integrin, beta 4 LOGER (4 O1 1: 4 OsO

SOf O2 solute carrier 814 O SLC7A5; MPE16; D165469E, CD98; KGDWSNLDP NAA 1: 2116 O family 7 (ca LAT1; 4 F2 light chain; Mem NFSFEGTKLD 1: 1782OO tionic amino brane protein E16; L-TYPE W (4 O2) acid transpor AMINO ACID TRANSPORTER 1; ter, y' system), Solute carrier family 7, e member 5 ber 5; solute carrier family 7 (cationic amino acid transpor ter, y' system), member 5 US 2010/0062444 A1 Mar. 11, 2010 36

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

SOf OS breast cancer 25855 DKFZp564AO63; BRMS1; breast KARAAVSPQ NAA NAA 1 : 1.OOO metastasis Sup cancer metastasis - suppressor KRKSDGP 1:2OOO pressor 1 1; breast cancer metastasis (403) suppressor 1

SOf O6 KiSS-1 3814 MGC39258; KISS1; KiSS-1 RQIPAPOGAV NAA NAA 1 : 18O metastasis metastasis-suppressor; KISS 1 LVQREKD suppressor METASTIN; malignant melanoma (4O4) metastasis-suppressor; KISS1 METASTASIS SUPPRESSOR

SOf O8 cofactor re 9439 DKFZp434HO117; CRSP133; SUR2; SVKEQVEKIIC N/A NAA 1: 2430 quired for Sp1 DRIP130; CRSP3; mediator; NLKPALK transcriptional transcriptional co-activator (138) activation, sub CRSP13 O, CRSP 13 O-KD SUBUNIT, unit 3, 130 kDa CRSP 13 O-kD subunit; 133 kDa transcriptional co-activator; 130 kDa transcriptional co activator; vitamin D3 receptor interacting protein; c

SSOO2 keratin 14 3861 CK; KRT14; K14; EBS4; EBS3; Antibody obtained from Chemicon 1 : 50 (epidermolysis cytokeratin 14; CK 14; KERA bullosa simplex, TIN TYPE I CYTOSKELETAL 14; Dowling-Meara, keratin 14 (epidermolysis Koebner) bullosa simplex, Dowling Meara, Koebner)

SSOO3 keratin 17 3872 PCHC1, PC, PC2; 39.1; KRT17; Antibody obtained from Dako 1 : 1.O- K17, CYTOKERATIN 17; VERSION 1:25 1, CK 17, KERATIN TYPE I CYTOSKELETAL 17

SSOO4 keratin 18 3875 K18; CYK18; KRT18; CYTOKERATIN Antibody obtained from Dako 1:2OO 18; CK 18; KERATIN TYPE I 1: 4 OO CYTOSKELETAL 18

SSOOS keratin 18 3875 K18; CYK18; KRT18; CYTOKERATIN Antibody obtained from Becton 1 : 50 - 18; CK 18; KERATIN TYPE I Dickinson 1:100 CYTOSKELETAL 18

tumor-associated 4. Of2 TROP1; LY74; Ep- CAM; GA733-2; Antibody obtained from Oncogene 1: 4 O calcium signal EGP4O; MK-1; CO17-1A; EPCAM; Research Products (Calbiochem) transducer 1 M4S1; KSA; TACSTD1; EGP; MK-1 antigen; EPITHELIAL CELLULAR ADHESION MOLECULE; GASTRO INTESTINAL TUMIOR-ASSOCIATED ANTIGEN 2, 35-KD GLYCOPROTEIN; tumor-associated calcium signal transducer 1 precurso

estrogen recep 21OO ER-BETA, ESR-BETA; ESR2; Erb; Antibody obtained from Oncogene 1:25 OO tor 2 (ER beta) ESRB, NR3A2, ESTROGEN RECEP- Research Products (Calbiochem) TOR, BETA; estrogen receptor 2 (ER beta)

S5038 mucin 1, 4582 PEMT; MUC1; episialin; EMA; Antibody obtained from Imperial 1 : 1 transmembrane PUM., H23AG; CD227; PEM Cancer Research Technology (ICRT) CARCINOMA-ASSOCIATED MUCIN; H23 antigen; TUMOR-ASSOCIATED MUCIN; DF3 antigen; peanut reactive urinary mucin; mucin 1, transmembrane; poly morphic epithelial mucin; MUCIN 1, URINARY MUCIN, TUMIOR-ASSOCIATE US 2010/0062444 A1 Mar 11, 2010

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

S5044 transferrin re 7037 P90; TR, TFRC; TFR, CD71; T9; Antibody obtained from NeoMarkers ceptor TRFR, ANTIGEN CD71; TRANSFER (pg O, CD71) RIN RECEPTOR PROTEIN; trans ferrin receptor (pe O, CD71 SSO45 w-ero-lo2 HER-2; ERBB2; NGL; P185ERBB2; Antibody obtained from NeoMarkers 1: 6OO erythroblastic HER2; C-ERBB-2; NEU; MLN 19; leukemia viral EC 2.7.1. 112, TKR1 HERSTATIN; oncogene homolog NEU PROTO-ONCOGENE, ONCOGENE 2, neuro / ERBB2; RECEPTOR PROTEIN glioblastoma TYROSINE KINASE ERBB-2 derived oncogene PRECURSOR ONCOGENE NGL, homolog (avian) NEUROBLASTOMA- OR GLIOBLASTOMA-DERIVED; TYROSINE KINASE-TYPE CELL

SSO47 major vault 99.61 MVP; LRP, WAULT1: LUNG Antibody obtained from NeoMarkers 1: 3 OO protein RESISTANCE-RELATED PROTEIN MAJOR WAULT PROTEIN, RAT HOMOLOG OF

S5064 tumor protein 8626 LMS, TP73L, KET; SHFM4; p 73H; Antibody obtained from Dako p73-like EEC3; TP63; p51; TUMOR PRO TEIN pé3; TUMOR PROTEIN p73 - LIKE; p53 -RELATED PROTEIN p63; tumor protein 63 kDa. With strong homology to p53

S5065 estrogen re 2099 ER; NR3A1; ESR1; Era; ESR; ER- Antibody obtained from Dako ceptor 1 ALPHA; ESRA; ESTRADIOL RECEP TOR; ESTROGEN RECEPTOR ALPHA; estrogen receptor 1 (alpha)

S5066 w-ero-lo2 HER-2; ERBB2; NGL; P185ERBB2; Antibody obtained from Dako 1: 3 OO erythroblastic HER2; C-ERBB-2; NEU; MLN 19; leukemia viral EC 2.7.1. 112, TKR1 HERSTATIN; oncogene homolog NEU PROTO-ONCOGENE, ONCOGENE 2, neuro / ERBB2; RECEPTOR PROTEIN glioblastoma TYROSINE KINASE ERBB-2 derived oncogene PRECURSOR ONCOGENE NGL, homolog (avian) NEUROBLASTOMA- OR GLIOBLASTOMA-DERIVED; TYROSINE KINASE-TYPE CELL

S5067 cathepsin D 1509 CTSD, MGC2311, CPSD, EC Antibody obtained from Dako (lysosomal 3. 4.23. 5; cathepsin D prepro aspartyl protein; Cathepsin D precur protease) sor; cathepsin D (lysosomal aspartyl protease) ;

S5069 CA 125 Antibody obtained from Dako

SSOf O CA 15-3 Antibody obtained from Dako

S5071 CA 19-9 Antibody obtained from Dako

S5072 v-myc myelo c-Myc, MYC; ONCOGENE MYC; Myc Antibody obtained from Dako cytomatosis proto-oncogene protein; viral oncogene PROTOONCOGENE HOMOLOGOUS TO homolog (avian) MYELOCYTOMATOSIS VIRUS; v-myc myelocytomatosis viral onco gene homolog (avian) ; v-myc avian myelocytomatosis viral oncogene homolog; Avian myelo cytomatosis viral (v-myc) onco

S5073 cadherin. 1, type 999 CDH1; Cadherin-1; Arc-1; ECAD; Antibody obtained from Dako 1 : 1.OO 1, E-cadherin CDHE; Uvomorulin; LCAM; 1:150 (epithelial) Epithelial-cadherin precursor; cell-CAM 12O/8 O; CADHERIN, EPITHELIAL; calcium-dependent US 2010/0062444 A1 Mar. 11, 2010 38

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER adhesion protein, epithelial; cadherin. 1, E-cadherin (epithelial) ; cadherin. 1, type 1 preproprotein; cadherin. 1, S5074 glutathione S- 295 O GSTP1, DFN7; GSTP1-1; GST3; Antibody obtained from Dako 1 : 50 transferase pi GSTPP; GST class-pi; glutathione transferase; EC 2.5.1.18; glutathione S-trans ferase pi; GST, CLASS PI; deafness, X-linked 7; GLUTA THIONE S-TRANSFERASE 3; GLUTATHIONE S-TRANSFERASE, PI; FAEES3 GLUTATHIONE S TRANSFERASE PI PSEUD

S5075 tumor protein 7157 p53; TP53; TRP53; PHOSPHOPRO- Antibody obtained from Dako 1 : 50 p53 (Li-Fraumeni TEIN P53, TRANSFORMATION syndrome) RELATED PROTEIN 53; TUMOR SUPPRESSOR P53, CELLULAR TUMOR ANTIGEN P53; tumor protein p53 (Li-Fraumeni syndrome)

S5076 progesterone 5241 NR3 C3; PR; PGR, PROGESTERONE Antibody obtained from Dako 1 : 50 receptor RESISTANCE; PSEUDOCORPUS LUTEUM INSUFFICIENCY PROGESTERONE RECEPTOR

S5077 trefoil factor 1 7031 Antibody obtained from Dako 1 : 50 - (breast cancer, 1:100 estrogen inducible se quence expressed in)

S5079 enolase 2, 2026 NSE; ENO2; 2-phospho-D- Antibody obtained from Dako 1: 4 OO (gamma, glycerate hydro-lyase; ENO neuronal) LASE GAMMA; neurone-specific enolase; ENOLASE, NEURON SPECIFIC; 2-phospho-D- glycerate hydrolyase; EC 4.2.1. 11; Neural enolase; enolase-2, gamma, neuronal; neuron specific gamma enolase; enolase 2 (gamma,

S508 O B-cell CLL/ 596 BCL2; FOLLICULAR LYMPHOMA; Antibody obtained from Dako 1 : 50 lymphoma 2 APOPTOSIS REGULATOR BCL-2; B-cell CLL/lymphoma 2; B-cell ymphoma protein 2 alpha; B cell lymphoma protein 2 beta; ONCOGENE B- CELL LEUKEMIA 2 LEUKEMIA, CHRONIC LYMPHATIC, TYPE 2

S5081 retinoblastoma 1. 5925 p105-Rb; PP110; Retinoblas- Antibody obtained from Dako 1: 2O (including toma-1; RB; RB1; RETINOBLAS osteosarcoma) TOMA-ASSOCIATED PROTEIN; RB OSTEOSARCOMA, RETINOBLASTOMA RELATED; retinoblastoma 1 (including osteosarcoma) S5082 synaptophysin 6855 SYP; Synaptophysin; Major Antibody obtained from Dako 1 : 50 synaptic vesicle protein P38

S5083 BCL2-associated 581 BAX; BCL2-associated X pro- Antibody obtained from Dako 1 : 5OO X protein tein; APOPTOSIS REGULATOR BAX, MEMBRANE, ISOFORM ALPHA US 2010/0062444 A1 Mar. 11, 2010 39

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

S5086 estrogen recep 21OO ER-BETA, ESR-BETA, ESR2; Erb, Antibody obtained from Abcam 1:2OO tor 2 (ER beta) ESRB, NR3A2, ESTROGEN RECEP TOR, BETA; estrogen receptor 2 (ER beta)

S5087 mucin 1, 4582 PEMT; MUC1; episialin; EMA; Antibody obtained from Zymed 1:2OO transmembrane PUM., H23AG; CD227; PEM 1: 16 OO CARCINOMA-ASSOCIATED MUCIN; H23 antigen; TUMOR-ASSOCIATED MUCIN; DF3 antigen; peanut reactive urinary mucin; mucin 1, transmembrane; polymorphic epithelial mucin; MUCIN 1, URINARY MUCIN, TUMOR ASSOCIATE

estrogen recep 2099 ER; NR3A1; ESR1; Era; ESR; ER Antibody obtained from US Labs 1 : 1 tor 1. ALPHA; ESRA; ESTRADIOL RECEP TOR; ESTROGEN RECEPTOR ALPHA; estrogen receptor 1 (alpha)

progesterone 5241 NR3 C3, PR, PGR, PROGESTERONE Antibody obtained from US Labs 1 : 1 receptor RESISTANCE; PSEUDOCORPUS LUTEUM INSUFFICIENCY PROGESTERONE RECEPTOR

w-ero-lo2 HER-2; ERBB2; NGL; P185ERBB2; Antibody obtained from US Labs 1 : 1 erythroblastic C-ERBB-2; NEU; MLN 19, leukemia viral EC 2.7.1. 112, TKR1 HERSTATIN; oncogene homolog NEU PROTO-ONCOGENE, ONCOGENE 2, neuro / ERBB2; RECEPTOR PROTEIN glioblastoma TYROSINE KINASE ERBB-2 derived oncogene PRECURSOR ONCOGENE NGL, homolog (avian) NEUROBLASTOMA- OR GLIOBLASTOMA-DERIVED; TYROSINE KINASE-TYPE CELL

B-cell CLL/ 596 BCL2; FOLLICULAR LYMPHOMA; Antibody obtained from US Labs 1 : 1 lymphoma 2 APOPTOSIS REGULATOR BCL-2; B-cell CLL/lymphoma 2; B-cell lymphoma protein 2 alpha; B cell lymphoma protein 2 beta; ONCOGENE B- CELL LEUKEMIA 2 LEUKEMIA, CHRONIC LYMPHATIC, TYPE 2

S6005 keratin 5 3852 KRT5; EBS2; Keratin-5; K5; Antibody obtained from US Labs (epidermolysis CYTOKERATIN 5 ; CK 5; 58 KDA bullosa simplex, CYTOKERATIN KERATIN TYPE II Dowling-Meara/ CYTOSKELETAL 5; keratin 5 Kobner /Weber (epidermolysis bullosa sim Cockayne types) plex, Dowling-Meara/Kobner/ Weber-Cockayne types)

tumor protein 71.57 TRP53 ; PHOSPHOPRO Antibody obtained from US Labs p53 (Li-Fraumeni TEIN P53, TRANSFORMATION syndrome) RELATED PROTEIN 53; TUMOR SUPPRESSOR P53, CELLULAR TUMOR ANTIGEN P53; tumor protein p53 (Li-Fraumeni syndrome)

S6007 KI67 Antibody obtained from US Labs

S6008 epidermal growth 1956 S7; EGFR; 2.7.1.1.12; ERBB ; ON Antibody obtained from US Labs factor receptor COGENE ERBB; ERBB1 SPECIES (erythroblastic ANTIGEN 7: V-ERB-B AVIAN leukemia viral ERYTHROBLASTIC LEUKEMIA WIRAL (v-erb-b) onco ONCOGENE HOMOLOG; epidermal gene homolog, growth factor receptor (avian avian) erythroblastic leukemia viral (v-erb-b) oncogene homolog) US 2010/0062444 A1 Mar. 11, 2010 40

AppendiX A- continued

ENTREZ. PEPTIDE 1 PEPTIDE 2 PEPTIDE 3 GENE (SEQ ID (SEQ ID (SEQ ID AGI ID GENE NAME ID ALIASES NO.) NO.) NO.) TITER

S6011 enolase 2, 2026 NSE; ENO2; 2-phospho-D- Antibody obtained from US Labs 1 : 1 (gamma, glycerate hydro-lyase; ENO neuronal) LASE GAMMA; neurone-specific enolase; ENOLASE, NEURN SPECIFIC; 2-phospho-D- glycerate hydrolyase; EC 4.2.1. 11; Neural enolase; enolase-2, gamma, neuronal; neuron specific gamma enolase; enolase 2 (gamma, S6012 thyroid 7080 benign chorea; chorea, heredi - Antibody obtained from US Labs 1 : 1 transcription tary benign; NK-2 (Drosophila) factor 1 homolog A (thyroid nuclear factor); Thyroid transcription factor 1 (NK-2, Drosophila, homolog of, A) ; BCH; BHC; TEBP, TTF1, NKX2A, TTF-1; NKX2.1

S6O13 w- ero-lo2 2O64 HER-2; ERBB2; NGL; P185ERBB2; Antibody obtained from US Labs 1 : 1 erythroblastic HER2; C-ERBB-2; NEU; MLN 19; leukemia viral EC 2.7.1. 112, TKR1 HERSTATIN; oncogene homolog NEU PROTO-ONCOGENE, ONCOGENE 2, neuro / ERBB2; RECEPTOR PROTEIN glioblastoma TYROSINE KINASE ERBB-2 derived oncogene PRECURSOR ONCOGENE NGL, homolog (avian) NEUROBLASTOMA- OR GLIOBLASTOMA-DERIVED; TYROSINE KINASE-TYPE CELL

Other Embodiments specification or practice of the invention disclosed herein. It is intended that the specification and examples be considered as 0198 Other embodiments of the invention will be appar- exemplary only, with the true scope of the invention being ent to those skilled in the art from a consideration of the indicated by the following claims.

SEQUENCE LISTING

<16 Os NUMBER OF SEO ID NOS: 4 O4

SEO ID NO 1 LENGTH: 2O TYPE PRT ORGANISM: Homo sapiens

< 4 OOs SEQUENCE: 1 Thr Glu Glu Ser Ile Asn Asp Glu Asp Ile Tyr Lys Gly Lieu Pro Asp 1. 5 1O 15 Lieu. Ile Asp Glu

SEO ID NO 2 LENGTH: 15 TYPE PRT ORGANISM: Homo sapiens

< 4 OOs SEQUENCE: 2 Glu Lys Arg Thir Asn Gly Lieu. Arg Arg Thr Pro Lys Glin Val Asp 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 41

- Continued

<210s, SEQ ID NO 3 &211s LENGTH: 13 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 3 Asp Tyr Ile Ser Lys Ser Lys Glu Asp Wall Lys Lieu Lys 1. 5 1O

<210s, SEQ ID NO 4 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 4 Glu Lys Thr Gly Val Cys Pro Glu Lieu. Glin Ala Asp Glin Asn. Cys Thr 1. 5 1O 15

Glin Glu

<210s, SEQ ID NO 5 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 5 Pro ASn Asp Lys Glu Gly Ser Cys Pro Glin Val ASn Ile ASn 1. 5 1O

<210s, SEQ ID NO 6 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 6 Arg Asp Glin Cys Glin Val Asp Thr Glin Cys Pro Gly Gln Met Lys 1. 5 1O 15

<210s, SEQ ID NO 7 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 7 Ser Lys Thr Ile Asn Pro Glin Val Ser Lys Thr Glu Tyr Lys Glu Lieu. 1. 5 1O 15

Lieu. Glin Glu

<210s, SEQ ID NO 8 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 8 Asp Asp Asn Ala Thir Thr Asn Ala Ile Asp Glu Lieu Lys Glu. Cys 1. 5 1O 15

<210s, SEQ ID NO 9 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens US 2010/0062444 A1 Mar. 11, 2010 42

- Continued <4 OOs, SEQUENCE: 9 Asn Glin Thr Asp Glu Thir Lieu Ser Asn Val Glu Val Phe Met Glin 1. 5 1O 15

<210s, SEQ ID NO 10 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 10 Ser Ser Asp Asp Gly Ile Arg Pro Lieu Pro Glu Tyr Ser Thr Glu Lys 1. 5 1O 15 His Llys Llys

<210s, SEQ ID NO 11 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 11 Asp Gly Lys Ser Lys Asp Llys Pro Pro Lys Arg Llys Lys Ala Asp Thr 1. 5 1O 15

Glu

<210 SEQ ID NO 12 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 12 Asn Llys Thir Lys Llys Llys Llys Ser Ser Arg Lieu Pro Pro Glu Lys 1. 5 1O 15

<210s, SEQ ID NO 13 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 13 Lys Asn Lys Glu Pro Lieu. Thir Lys Lys Gly Glu Thir Lys Thir Ala Glu 1. 5 1O 15 Arg Asp

<210s, SEQ ID NO 14 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 14 Llys Lieu. Thir Cys Thr Asp Lieu. Asp Ser Ser Pro Arg Ser Phe Arg Tyr 1. 5 1O 15

Ser

<210s, SEQ ID NO 15 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 15 US 2010/0062444 A1 Mar. 11, 2010 43

- Continued Glu Val Asp Tyr Glu Asn Pro Ser Asn Lieu Ala Ala Gly Asn Llys Tyr 1. 5 1O 15

Thir

<210s, SEQ ID NO 16 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 16 Llys Thr Lieu. Glin Val Phe Asn Pro Lieu. Arg Phe Ser Arg Glu Asn. Ser 1. 5 1O 15 Glu Lys Ile His 2O

<210s, SEQ ID NO 17 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 17 Glin His Phe Ala Ile Ile Glu. Cys Llys Val Ala Val Ala Lieu. Thr 1. 5 1O 15

<210s, SEQ ID NO 18 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 18 Arg Llys Phe Lieu Ala Pro Asp His Ser Arg Pro Pro Gln Pro Val Arg 1. 5 1O 15

Glin

<210s, SEQ ID NO 19 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 19 Met Ala Lys Ala Glu Val Llys Lieu Ala Ile Phe Gly Arg Ala Gly Val 1. 5 1O 15 Gly Lys

<210s, SEQ ID NO 2 O &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 2O Val Lieu Pro Lieu Lys Asn. Ile Lieu. Asp Glu Ile Llys Llys Pro Lys Asn 1. 5 1O 15

<210s, SEQ ID NO 21 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 21 Tyr Glu Lieu. Cys Arg Glu Val Arg Arg Arg Arg Met Val Glin Gly Lys US 2010/0062444 A1 Mar. 11, 2010 44

- Continued

1. 5 1O 15

Thir

<210s, SEQ ID NO 22 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 22 Thr Llys Pro Thr Thr Ile Ile Glu Lys Asn Gly Asp Ile Lieu. Thir Lieu. 1. 5 1O 15 Lys Thr His

<210s, SEQ ID NO 23 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 23 Lys Asn Thr Glu Ile Ser Phe Llys Lieu. Gly Val Glu Phe Asp Glu 1. 5 1O 15

<210s, SEQ ID NO 24 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 24 His Lieu Gln Lys Trp Asp Gly Glin Glu Thir Thr Lieu Val Arg Glu 1. 5 1O 15

<210s, SEQ ID NO 25 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 25 Asp Gly Asn Asp Val Glu Phe Thir Trp Lieu. Arg Gly Asn Asp Ser Val 1. 5 1O 15 Arg Gly Lieu. Glu. His 2O

<210s, SEQ ID NO 26 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 26 Lieu. Glin Gln Met Ala Ala Lys Asp Arg Gly. Thir Thr Lys Glu Val Glu 1. 5 1O 15

Glu Wal Ser

<210s, SEQ ID NO 27 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 27 Lys Arg Lys Ile Ser Phe Ala Ser Ile Glu Ile Ser Ser Asp Asn. Wall 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 45

- Continued

Asp Tyr Ser Asp 2O

<210s, SEQ ID NO 28 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 28 Glin Arg Glin Glin Ile Ala Lys Ser Phe Lys Ala Glin Phe Gly Lys Asp 1. 5 1O 15

Lieu. Thir Glu

<210s, SEQ ID NO 29 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 29 Arg Glu Ile Met Lys Ala Tyr Glu Glu Asp Tyr Gly Ser Ser Lieu. Glu 1. 5 1O 15 Glu Asp Ile Glin 2O

<210 SEQ ID NO 3 O &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 30 Glu Glu Tyr Glu Lys Ile Ala Asn Llys Ser Ile Glu Asp Ser Ile Llys 1. 5 1O 15

Ser Glu

<210s, SEQ ID NO 31 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 31 Glu Gly Gly Ser Lieu Val Pro Ala Ala Arg Glin Gln His Cys Thr Glin 1. 5 1O 15 Val Arg Ser Arg Arg 2O

<210s, SEQ ID NO 32 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 32 Arg Lys Ala Gly Llys Ser Llys Llys Ser Ser Arg Lys Glu Ala Glu 1. 5 1O 15

<210s, SEQ ID NO 33 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 33 US 2010/0062444 A1 Mar. 11, 2010 46

- Continued

Lys Thr His Glu Lys Tyr Gly Trp Val Thr Pro Pro Val Ser Asp Gly 1. 5 1O 15

<210s, SEQ ID NO 34 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 34 Met Asp Lieu. Glu Gly Asp Arg Asn Gly Gly Ala Lys Llys Lys Asn 1. 5 1O 15

<210s, SEQ ID NO 35 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 35 Asn Lieu. Glu Asp Lieu Met Ser Asn. Ile Thr Asn Arg Ser Asp Ile Asn 1. 5 1O 15 Asp Thr Gly

<210s, SEQ ID NO 36 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 36 Arg Gly Ser Glin Ala Glin Asp Arg Llys Lieu. Ser Thr Lys Glu Ala 1. 5 1O 15

<210s, SEQ ID NO 37 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 37 Met Asp Lieu. Glu Ala Ala Lys Asn Gly. Thir Ala Trp Arg Pro Thir Ser 1. 5 1O 15

Ala Glu

<210s, SEQ ID NO 38 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 38 Asn Phe Ser Phe Pro Val Asn Phe Ser Leu Ser Lieu Lleu. Asn Pro Gly 1. 5 1O 15 Lys

<210s, SEQ ID NO 39 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 39 Lys Asn. Ser Gln Met Cys Gln Lys Ser Lieu. Asp Val Glu Thir Asp Gly 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 47

- Continued

<210s, SEQ ID NO 4 O &211s LENGTH: 13 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 4 O Met Ala Lieu. Arg Gly Phe Cys Ser Ala Asp Gly Ser Asp 1. 5 1O

<210s, SEQ ID NO 41 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 41 Lys Asn Trp Llys Lys Glu. Cys Ala Lys Thr Arg Lys Glin Pro Val Lys 1. 5 1O 15

<210s, SEQ ID NO 42 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 42 Asp Ser Ile Glu Arg Arg Pro Wall Lys Asp Gly Gly Gly Thr Asn. Ser 1. 5 1O 15

<210s, SEQ ID NO 43 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 43 Met Leu Glu Lys Phe Cys Asn Ser Thr Phe Trp Asn Ser Ser Phe Leu 1. 5 1O 15 Asp Ser Pro Glu 2O

<210s, SEQ ID NO 44 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 44 Ser Ile Lieu. Cys Gly Thr Phe Glin Phe Glin Thr Lieu. Ile Arg Thr 1. 5 1O 15

<210s, SEQ ID NO 45 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 45

Glu Asn. Asn. Glu Ser Ser Asn. Asn. Pro Ser Ser Ile Ala Ser 1. 5 1O

<210s, SEQ ID NO 46 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 46 US 2010/0062444 A1 Mar. 11, 2010 48

- Continued

Glin Glu Val Llys Pro Asn Pro Lieu. Glin Asp Ala Asn. Ile Cys Ser Arg 1. 5 1O 15

<210s, SEQ ID NO 47 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 47 Asp Glu Ile Ser Glin Arg Asn Arg Glin Lieu Pro Ser Asp Gly Lys Llys 1. 5 1O 15

<210s, SEQ ID NO 48 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 48 Val Glin Asp Phe Thr Ala Phe Trp Asp Lys Ala Ser Glu Thr Pro Thr 1. 5 1O 15

Lieu. Glin

<210s, SEQ ID NO 49 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 49 Met Asp Ala Lieu. Cys Gly Ser Gly Glu Lieu. Gly Ser Llys Phe Trp Asp 1. 5 1O 15

Ser Asn

<210s, SEQ ID NO 50 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 50 Arg Lys Glin Glu Lys Glin Thr Ala Arg His Lys Ala Ser Ala Ala 1. 5 1O 15

<210s, SEQ ID NO 51 &211s LENGTH: 13 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 51 Asp Pro Glin Ser Val Glu Arg Llys Thr Ile Ser Pro Gly 1. 5 1O

<210s, SEQ ID NO 52 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 52 Met Lys Asp Ile Asp Ile Gly Lys Glu Tyr Ile Ile Pro Ser Pro Gly 1. 5 1O 15 Tyr Arg Ser US 2010/0062444 A1 Mar. 11, 2010 49

- Continued

<210s, SEQ ID NO 53 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 53 Arg Asp Arg Glu Asp Ser Llys Phe Arg Arg Thr Arg Pro Lieu. Glu. Cys 1. 5 1O 15 Glin Asp

<210s, SEQ ID NO 54 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 54 Ser Lys His Glu Ser Ser Asp Wall Asn. Cys Arg Arg Lieu. Glu Arg 1. 5 1O 15

<210s, SEQ ID NO 55 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 55 Met Ala Ala Pro Ala Glu Pro Cys Ala Gly Glin Gly Val Trp Asin Gln 1. 5 1O 15

Thir Glu Pro Glu 2O

<210s, SEQ ID NO 56 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 56 Asp Pro Gly Val Val Asp Ser Ser Ser Ser Gly Ser Ala Ala Gly Lys 1. 5 1O 15

Ser

<210s, SEQ ID NO 57 &211s LENGTH: 13 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 57 His Thr Lieu Val Ala Glu Asn Ala Met Asn Ala Glu Lys 1. 5 1O

<210s, SEQ ID NO 58 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 58 Met Ser Asp Ser Val Ile Lieu. Arg Ser Ile Llys Llys Phe Gly Glu Glu 1. 5 1O 15

Asn Asp US 2010/0062444 A1 Mar. 11, 2010 50

- Continued <210s, SEQ ID NO 59 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 59 Thr Asn Ser Ser Lieu. Asn Glin Asn Met Thr Asn Gly Thr Arg 1. 5 1O

<210s, SEQ ID NO 60 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 60 Gln Glu Val Lieu Ser Lys Ile Gln His Gly His Thr Ile Ile Ser 1. 5 1O 15

<210s, SEQ ID NO 61 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 61 Gly Ala Asp Asp Pro Ser Ser Val Thir Ala Glu Glu Ile Glin Arg 1. 5 1O 15

<210s, SEQ ID NO 62 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 62 Asn Ala Val Ala Ser Pro Glu Phe Pro Pro Arg Phe Asn Thr 1. 5 1O

<210s, SEQ ID NO 63 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 63 Llys Pro Asn Gly Ile Tyr Arg Llys Lieu Met Asn Lys Glin Ser Phe Ile 1. 5 1O 15

Ser Ala

<210s, SEQ ID NO 64 &211s LENGTH: 13 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 64 Met Ala Ser Ser Arg Cys Pro Ala Pro Arg Gly Cys Arg 1. 5 1O

<210s, SEQ ID NO 65 &211s LENGTH: 10 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 65 Glin Gly Gly Ser Gly ASn Pro Val Arg Arg US 2010/0062444 A1 Mar. 11, 2010 51

- Continued

<210s, SEQ ID NO 66 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 66 Glu Phe Val Gly Asp Gly Ile Tyr Asn Asn Thr Met Gly His Val His 1. 5 1O 15

Ser

<210s, SEQ ID NO 67 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 67 Met Pro Lieu Ala Phe Cys Gly Ser Glu Asn His Ser Ala Ala Tyr Arg 1. 5 1O 15

<210s, SEQ ID NO 68 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens < 4 OO > SEQUENCE: 68 Asp His Lieu. Gly Lys Glu Asn Asp Val Phe Glin Pro Llys Thr Glin Phe 1. 5 1O 15 Lieu. Gly

<210s, SEQ ID NO 69 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 69 Glu Ile Arg Glu Glu Glin Cys Ala Pro His Glu Pro Thr Pro Glin Gly 1. 5 1O 15

<210s, SEQ ID NO 70 &211s LENGTH: 12 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 7 O Met Ser Leu Ser Phe Cys Gly Asn Asn Ile Ser Ser 1. 5 1O

<210s, SEQ ID NO 71 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 71 Glin Arg Val Asn Glu Thr Glin Asn Gly Thr Asn Asn Thr Thr Gly Ile 1. 5 1O 15

Ser Glu

<210s, SEQ ID NO 72 US 2010/0062444 A1 Mar. 11, 2010 52

- Continued

&211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 72 Asp Glu Ile Gly Asp Asp Ser Trp Arg Thr Gly Glu Ser Ser Lieu Pro 1. 5 1O 15

Phe Glu Ser

<210s, SEQ ID NO 73 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 73 Met Val Llys Val Thr Phe Asn. Ser Ala Lieu Ala Glin Lys Glu Ala Lys 1. 5 1O 15 Lys Asp Glu Pro Llys 2O

<210s, SEQ ID NO 74 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 74 Glin Thir Ile Glu Glu Asn. Ile Lys Ile Phe Glu Glu Glu Glu Val Glu 1. 5 1O 15

<210s, SEQ ID NO 75 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 75 His Asp Llys Glu Thir Tyr Llys Lieu. Glin Arg Arg Glu Thir Ile Lys Gly 1. 5 1O 15 Ile Glin Lys Arg Glu 2O

<210s, SEQ ID NO 76 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 76 Met Ala His Ala Ala Ser Glin Lieu Lys Lys Asn Arg Asp Lieu. Glu Ile 1. 5 1O 15

Asn Ala Glu Glu 2O

<210s, SEQ ID NO 77 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 77 His Llys Lys Glu Thr Glu Ser Asp Glin Asp Asp Glu Ile Glu Lys Thr 1. 5 1O 15 Asp Arg Arg Glin US 2010/0062444 A1 Mar. 11, 2010 53

- Continued

<210s, SEQ ID NO 78 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 78 Glu Gly Phe Llys Val Llys Thr Lys Lys Glu Ile Arg His Val Glu Lys 1. 5 1O 15 Lys Ser His Ser 2O

<210s, SEQ ID NO 79 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 79 Glu Arg Ala Lieu Ala Ala Ala Glin Arg Cys His Llys Llys Val Met Lys 1. 5 1O 15 Glu Arg

<210s, SEQ ID NO 8O &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 80 Thir Ala Gly Met Lys Asp Lieu. Lieu. Ser Val Phe Glin Ala Tyr Glin 1. 5 1O 15

<210s, SEQ ID NO 81 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 81 Asp Pro Pro Arg Thr Val Lieu. Glin Ala Pro Lys Glu Trp Val Cys Lieu 1. 5 1O 15

<210s, SEQ ID NO 82 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 82 Met Glu Ala Ala Asp Ala Ser Arg Ser Asn Gly Ser Ser Pro Glu Ala 1. 5 1O 15 Arg Asp Ala Arg 2O

<210s, SEQ ID NO 83 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 83 Glu Lieu. His Lieu Lys Pro His Lieu. Glu Gly Ala Ala Phe Arg Asp His 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 54

- Continued

Glin

<210s, SEQ ID NO 84 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 84 Glu Gly Glu Gly Lieu. Gly Glin Ser Lieu. Gly Asn. Phe Lys Asp Asp Lieu. 1. 5 1O 15

Lieu. Asn

<210s, SEQ ID NO 85 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 85 Glu Lieu. His Lieu Lys Pro His Lieu. Glu Gly Ala Ala Phe Arg Asp His 1. 5 1O 15

Glin

<210s, SEQ ID NO 86 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 86 Gly Ser Glu Glu Arg Gly Ala Gly Arg Gly Ser Ser Gly Gly Arg Glu 1. 5 1O 15

Glu

<210s, SEQ ID NO 87 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 87 Lys Ile Trp Ser Lieu Ala Glu Thir Ala Thir Ser Pro Asp Asin Pro Arg 1. 5 1O 15 Arg Ser

<210s, SEQ ID NO 88 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 88 Llys Llys Lieu. Lieu Lys Thr Ala Phe Glin Pro Val Pro Arg Arg Pro Glin 1. 5 1O 15 Asn His Lieu. Asp 2O

<210s, SEQ ID NO 89 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 89 US 2010/0062444 A1 Mar. 11, 2010 55

- Continued Arg Arg Ser Ser Thir Thr His Val Lys Glin Ala Ile Asn Llys Met Lieu 1. 5 1O 15 Thr Lys Ile Ser Ser 2O

<210s, SEQ ID NO 90 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 90 Met Arg Arg Lys Asn Thr Cys Glin Asn Phe Met Glu Tyr Phe Cys Ile 1. 5 1O 15

Ser Lieu Ala Phe 2O

<210s, SEQ ID NO 91 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 91 Asn Glu Thir Ile Leu Tyr Phe Pro Phe Ser Ser His Ser Ser Tyr Thr 1. 5 1O 15 Val Arg Ser Lys Llys 2O

<210s, SEQ ID NO 92 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 92 Llys Val Glin Ile Pro Ala Tyr Ile Glu Met Asn Ile Pro Leu Val Ile 1. 5 1O 15 Lieu. Cys Glin

<210s, SEQ ID NO 93 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 93 Met Lieu. Thr Glu Lieu. Glu Lys Ala Lieu. Asn. Ser Ile Ile Asp Val Tyr 1. 5 1O 15 His Lys

<210s, SEQ ID NO 94 &211s LENGTH: 22 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 94 Arg Asp Asp Lieu Lys Llys Lieu. Lieu. Glu Thr Glu. Cys Pro Glin Tyr Ile 1. 5 1O 15 Arg Llys Lys Gly Ala Asp 2O

<210s, SEQ ID NO 95 US 2010/0062444 A1 Mar. 11, 2010 56

- Continued

&211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 95 Llys Met Gly Val Ala Ala His Llys Llys Ser His Glu Glu Ser His Lys 1. 5 1O 15

Glu

<210s, SEQ ID NO 96 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 96 Pro Glu Ser Arg Lys Asp Pro Ser Gly Ala Ser Asn Pro Ser Ala Asp 1. 5 1O 15

Ser

<210s, SEQ ID NO 97 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 97 His Gly Lieu. Ala Pro His Glu Ser Gln Lieu. His Lieu Lys Gly Asp 1. 5 1O 15

<210s, SEQ ID NO 98 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 98 Glu Glin Gln His Llys Lieu. Asp Phe Lys Ala Tyr Glu Glin Ala Lieu. Glin 1. 5 1O 15

Tyr Ser

<210s, SEQ ID NO 99 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 99 His Gly Lieu Ala Pro His Glu Ser Glin Lieu. His Lieu Lys Gly Asp 1. 5 1O 15

<210s, SEQ ID NO 100 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 1.OO Glu Glu Tyr Val Gly Lieu. Ser Ala Asn Glin Cys Ala Val Pro Ala Lys 1. 5 1O 15 Asp Arg Val Asp 2O

<210s, SEQ ID NO 101 &211s LENGTH: 15 US 2010/0062444 A1 Mar. 11, 2010 57

- Continued

212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 101 Arg Val Asp Cys Gly Tyr Pro His Val Thr Pro Lys Glu. Cys Asn 1. 5 1O 15

<210s, SEQ ID NO 102 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 102 Val Pro Trp Cys Phe Llys Pro Leu Gln Glu Ala Glu. Cys Thr Phe 1. 5 1O 15

<210s, SEQ ID NO 103 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 103 Val Pro Trp Cys Phe Llys Pro Leu Gln Glu Ala Glu. Cys Thr Phe 1. 5 1O 15

<210s, SEQ ID NO 104 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 104 Lys Lys Glu Pro Val Thir Thr Arg Glin Val Arg Thr Ile Val Glu Glu 1. 5 1O 15

<210s, SEQ ID NO 105 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 105 Gln Asp Gly Llys Val Ile Ser Ser Arg Glu Glin Val His Glin Thr Thr 1. 5 1O 15 Arg

<210s, SEQ ID NO 106 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 106 Ser Ser Ser Ile Lys Gly Ser Ser Gly Lieu. Gly Gly Gly Ser Ser 1. 5 1O 15

<210s, SEQ ID NO 107 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 107 Asp Glu Glu Asp Llys Lieu. Arg His Phe Arg Glu. Cys Phe Tyr Ile Pro 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 58

- Continued Lys Ile Glin Asp 2O

<210s, SEQ ID NO 108 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 108 Llys Pro Arg Glu Gly Glu Glu Thir Lieu. Arg Ile Glu Asp Ile Lieu. Glu 1. 5 1O 15 Val Ile Glu Lys Glu 2O

<210s, SEQ ID NO 109 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 109 Glu Glu Arg Gly Cys Glin Lieu. Thir Ile Thr Phe Ser Val Pro Asn Lys 1. 5 1O 15 Asp Val Phe Glin Glu 2O

<210 SEQ ID NO 110 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 110 Asp His Asn His Ala Ala Ser Gly Lys Asn Lys Arg Lys Ala Lieu. Cys 1. 5 1O 15 Pro Asp His Asp 2O

<210s, SEQ ID NO 111 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 111 Glu Glu Pro Ala Met Glu Met Lys Arg Gly Pro Leu Phe Ser His Leu 1. 5 1O 15

Ser Ser Glin Asn. Ile 2O

<210s, SEQ ID NO 112 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 112 Glin Arg Tyr Ser Arg Glu Glu Lieu Lys Asp Ala Gly Val Ala Thr Lieu. 1. 5 1O 15

<210s, SEQ ID NO 113 &211s LENGTH: 22 212. TYPE: PRT <213> ORGANISM: Homo sapiens US 2010/0062444 A1 Mar. 11, 2010 59

- Continued <4 OOs, SEQUENCE: 113 Met Asp Ile Glu Ala Tyr Lieu. Glu Arg Ile Gly Tyr Llys Llys Ser Arg 1. 5 1O 15 Asn Llys Lieu. Asp Lieu. Glu 2O

<210s, SEQ ID NO 114 &211s LENGTH: 22 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 114 Gln Met Trp Gln Pro Leu Glu Lieu. Ile Ser Gly Lys Asp Glin Pro Glin 1. 5 1O 15 Val Pro Cys Val Phe Arg 2O

<210s, SEQ ID NO 115 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 115 Phe Asn. Ile Ser Lieu. Glin Arg Llys Lieu Val Pro Llys His Gly Asp Arg 1. 5 1O 15

Phe Phe Thir Ile 2O

<210s, SEQ ID NO 116 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 116 Arg Glin Arg Lieu. Thir His Lieu. Ser Pro Glu Glu Lys Ala Lieu. Arg Arg 1. 5 1O 15 Llys Lieu Lys Asn Arg 2O

<210s, SEQ ID NO 117 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 117 Glu Lys Thr His Gly Lieu Val Val Glu Asn. Glin Glu Lieu. Arg Glin Arg 1. 5 1O 15 Lieu. Gly Met Asp 2O

<210s, SEQ ID NO 118 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 118 Gln Pro Pro Phe Lieu. Cys Gln Trp Gly Arg His Gln Pro Ser Trp Llys 1. 5 1O 15

Pro Leu Met Asn US 2010/0062444 A1 Mar. 11, 2010 60

- Continued

<210s, SEQ ID NO 119 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 119 Asn Lys Ile Thr Thr Glu Phe Phe Asp Pro Leu Phe Val Glu Glin Lys 1. 5 1O 15

<210s, SEQ ID NO 120 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 120 Phe Ser Ile Ser Asp Asn Asn Llys Thr Pro Arg Tyr Thr Tyr Asn Gly 1. 5 1O 15

Ala Thr

<210s, SEQ ID NO 121 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens < 4 OO > SEQUENCE: 121 Glu Asp Phe Llys Thir Thr Asn. Pro Ser Lys Glin Phe Asp Lys Asn Ala 1. 5 1O 15 Tyr Val

<210s, SEQ ID NO 122 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 122 Glu Gly Asp Ala Lys Gly Lieu Lys Glu Gly Glu Thr Pro Gly Asn. Phe 1. 5 1O 15 Met Glu Asp Glu 2O

<210s, SEQ ID NO 123 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 123 Glu Trp Cys Phe Cys Phe Trp Arg Glu Lys Pro Pro Cys Lieu Ala Glu 1. 5 1O 15 Lieu. Glu Arg

<210s, SEQ ID NO 124 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 124 Glu Glu Glu Gly Glu Ala Gly Glu Ala Asp Asp Gly Gly Tyr Ile Trp 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 61

- Continued

<210s, SEQ ID NO 125 &211s LENGTH: 13 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 125 Asp Lys Asp Pro Gln Lys Met Tyr Ala Thir Ile Tyr Glu 1. 5 1O

<210s, SEQ ID NO 126 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 126 Lys Lys Cys Asp Tyr Trp Ile Arg Thr Phe Val Pro Gly Cys Glin 1. 5 1O 15

<210s, SEQ ID NO 127 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 127 Glu Asn. Phe Ile Arg Phe Ser Lys Tyr Lieu. Gly Lieu Pro Glu Asn 1. 5 1O 15

<210s, SEQ ID NO 128 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 128 Asp Asp Ser Asp Glin Asp Ser Cys Arg Lieu. Ser Ile Asp Ser Glin 1. 5 1O 15

<210s, SEQ ID NO 129 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 129 Arg Glin His Tyr Pro Glu Ala Tyr Ala Ser Pro Ser His Thr Lys 1. 5 1O 15

<210s, SEQ ID NO 130 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 130 Asn Thr Pro Leu Gly Arg Asn Lieu Ser Thr His Glin Thr Tyr Pro Val 1. 5 1O 15 Val Ala Asp

<210s, SEQ ID NO 131 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 131 US 2010/0062444 A1 Mar. 11, 2010 62

- Continued

Arg Lieu Val Ser Cys Pro Gly Pro Lieu. Asp Glin Asp Glin Glin Glu 1. 5 1O 15

<210s, SEQ ID NO 132 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 132 Llys Met Ser Pro Glu Asp Ile Arg Llys Trp Asn Val Thir Ser Lieu. Glu 1. 5 1O 15 Thir Lieu Lys

<210s, SEQ ID NO 133 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 133 Ser Pro Glu Glu Lieu. Ser Ser Val Pro Pro Ser Ser Ile Trp Ala Val 1. 5 1O 15 Arg Pro Glin Asp 2O

<210 SEQ ID NO 134 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 134 Glu Glu Glin Asn Llys Lieu Val His Gly Gly Pro Cys Asp Llys Thir Ser 1. 5 1O 15

His

<210s, SEQ ID NO 135 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 135 Glu Lieu. Ile Glin Pro Lieu Pro Lieu. Glu Arg Asp Cys Ser Ala Asn. Thir 1. 5 1O 15

<210s, SEQ ID NO 136 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 136 Gly Lys Thir Ala Asp Gly Asp Phe Pro Asp Thir Ile Glin Cys 1. 5 1O

<210s, SEQ ID NO 137 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 137 Arg Glu Gln Trp Pro Glu Arg Arg Arg Cys His Arg Lieu. Glu Asn Gly 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 63

- Continued

Cys Gly Asn Ala 2O

<210s, SEQ ID NO 138 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 138 Ser Val Lys Glu Glin Val Glu Lys Ile Ile Cys Asn Lieu Lys Pro Ala 1. 5 1O 15

Lieu Lys

<210s, SEQ ID NO 139 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 139 Llys Val Asn. Ser Ala Gly Asp Ala Ile Gly Lieu. Glin Pro Asp Ala Arg 1. 5 1O 15

<210s, SEQ ID NO 140 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 140 Glin Glin Lieu Lys Val Ile Asp Asn Glin Arg Glu Lieu. Ser Arg Lieu. Ser 1. 5 1O 15 Arg Glu Lieu. Glu 2O

<210s, SEQ ID NO 141 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 141 Arg Glu. His Met Glin Ala Val Thr Arg Asn Tyr Ile Thr His Pro Arg 1. 5 1O 15

<210s, SEQ ID NO 142 &211s LENGTH: 13 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 142 Llys Llys Ser Lys Ala Val Lieu. Asp Tyr His Asp Asp Asn 1. 5 1O

<210s, SEQ ID NO 143 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 143 Asp Glu Phe Tyr Ser Arg Glu Gly Arg Lieu. Glin Asp Lieu Ala Pro Asp 1. 5 1O 15

Thir Ala Lieu. US 2010/0062444 A1 Mar. 11, 2010 64

- Continued

<210s, SEQ ID NO 144 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 144 Lys Glin Glin Asp Gly Pro Thr Lys Thr His Llys Lieu. Glu Lys Lieu Met 1. 5 1O 15 Ile Arg

<210s, SEQ ID NO 145 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 145 Glu Lieu. Arg Val Lieu. Ser Lys Ala Asn Ala Ile Val Pro Gly Lieu. Ser 1. 5 1O 15 Gly Gly Glu

<210s, SEQ ID NO 146 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 146 Arg Arg Gly Gly Glu Gly Gly Glu Glu Asn Pro Ser Ala Ala Lys Gly 1. 5 1O 15 His Leu Met Gly 2O

<210s, SEQ ID NO 147 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 147 Met Pro Glu Val Ser Ser Lys Gly Ala Thr Ile Ser Lys Lys 1. 5 1O

<210s, SEQ ID NO 148 &211s LENGTH: 11 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 148 Gly Phe Llys Lys Ala Val Val Lys Thr Glin Lys 1. 5 1O

<210s, SEQ ID NO 149 &211s LENGTH: 12 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 149 Lys Glu Gly Lys Lys Arg Lys Arg Thr Arg Lys Glu 1. 5 1O

<210s, SEQ ID NO 150 US 2010/0062444 A1 Mar. 11, 2010 65

- Continued

&211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 150 Arg Tyr Ala Phe Asp Phe Ala Arg Asp Lys Asp Glin Arg Ser Lieu. Asp 1. 5 1O 15 Ile Asp

<210s, SEQ ID NO 151 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 151 Ser Val Phe Tyr Glin Tyr Lieu. Glu Glin Ser Lys Tyr Arg Val Met Asn 1. 5 1O 15 Lys Asp Glin

<210s, SEQ ID NO 152 &211s LENGTH: 22 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 152 Glu Asp Gly Ala Trp Pro Val Lieu. Lieu. Asp Glu Phe Val Glu Trp Gln 1. 5 1O 15 Llys Val Arg Glin Thir Ser 2O

<210s, SEQ ID NO 153 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 153 Ser Phe Llys Ser Pro Glin Val Tyr Lieu Lys Glu Glu Glu Glu Lys Asn 1. 5 1O 15 Glu Lys Arg

<210s, SEQ ID NO 154 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 154 Arg Llys Lys Glin Glin Glu Ala Glin Gly Glu Lys Ala Ser Arg Tyr Ile 1. 5 1O 15

Glu

<210s, SEQ ID NO 155 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 155 Glu Asp Ile Gly Ile Thr Val Asp Thr Val Lieu. Ile Lieu. Glu Glu Lys 1. 5 1O 15

Glu Glin. Thir Asn US 2010/0062444 A1 Mar. 11, 2010 66

- Continued

<210s, SEQ ID NO 156 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 156 Lys Ala Phe Arg Gly Ala Thr Asp Lieu Lys Asn Lieu. Arg Lieu. Asp Llys 1. 5 1O 15

ASn Glin

<210s, SEQ ID NO 157 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 157 Asp Phe Arg Cys Glu Glu Gly Glin Glu Glu Gly Gly Cys Lieu Pro Arg 1. 5 1O 15

Pro Glin

<210s, SEQ ID NO 158 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 158 Asp Gly. Thir Ser Phe Ala Glu Glu Val Glu Lys Pro Thr Lys Cys Gly 1. 5 1O 15 Cys Ala Lieu. Cys Ala 2O

<210s, SEQ ID NO 159 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 159 Glin Arg Ile Lys Glu Glin Ala Ser Lys Ile Ser Glu Ala Asp Llys Ser 1. 5 1O 15 Llys Pro Llys Phe 2O

<210s, SEQ ID NO 160 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 160 His Ala Lys Thir Lys Glu Lys Lieu. Glu Val Thir Trp Glu Lys Met Ser 1. 5 1O 15 Llys Ser Llys His Asn 2O

<210s, SEQ ID NO 161 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens US 2010/0062444 A1 Mar. 11, 2010 67

- Continued <4 OOs, SEQUENCE: 161 Llys Ser Pro Glin Pro Glin Lieu. Lieu. Ser Asn Lys Glu Lys Ala Glu Ala 1. 5 1O 15 Arg Llys

<210s, SEQ ID NO 162 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 162 Met Leu Phe Glu Gln Gly Glin Glin Ala Lieu. Glu Lieu Pro Glu. Cys Thr 1. 5 1O 15

<210s, SEQ ID NO 163 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 163 Lys Asp Gln Lys Ala Lys Gly Ile Lieu. His Ser Pro Ala Ser Glin Ser 1. 5 1O 15 Pro Glu Arg Ser 2O

<210s, SEQ ID NO 164 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 164 His Ser Ser Glin Gly Arg Lieu Pro Glu Ala Pro Llys Lieu. Thir His Lieu. 1. 5 1O 15

<210s, SEQ ID NO 165 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 165 Lys Arg Gly Ala Arg Arg Gly Gly Trp Lys Arg Llys Met Pro Ser Thr 1. 5 1O 15

Asp Lieu.

<210s, SEQ ID NO 166 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 166 Lys Ile Val Arg Val Pro Lieu. Thir Lys Met Met Glu Val Asp Val Arg 1. 5 1O 15

<210s, SEQ ID NO 167 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 167 Glin Phe Lieu Lys Asp Ile Arg Glu Ser Val Thr Glin Ile Met Lys Asn US 2010/0062444 A1 Mar. 11, 2010 68

- Continued

1. 5 1O 15 Pro Lys Ala

<210s, SEQ ID NO 168 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 168 Ser Lys Glin Gly Val Val Ile Lieu. Asp Asp Llys Ser Lys Glu Lieu Pro 1. 5 1O 15 His Trp

<210s, SEQ ID NO 169 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 169 Val Glin Thir Phe Ser Arg Cys Ile Lieu. Cys Ser Lys Asp Glu Val Asp 1. 5 1O 15 Lieu. Asp Glu Lieu. 2O

<210 SEQ ID NO 170 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 170 Lieu Lys Llys Pro Phe Gln Pro Phe Glin Arg Thr Arg Ser Phe Arg Met 1. 5 1O 15

<210s, SEQ ID NO 171 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 171 Met Asn Lieu. Lieu. Asp Pro Phe Met Lys Met Thr Asp Glu Glin Glu Lys 1. 5 1O 15 Gly Lieu. Ser

<210s, SEQ ID NO 172 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 172 Asn. Thir Phe Pro Llys Gly Glu Pro Asp Lieu Lys Lys Glu Ser Glu Glu 1. 5 1O 15 Asp Llys

<210s, SEQ ID NO 173 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 173 US 2010/0062444 A1 Mar. 11, 2010 69

- Continued Lys Asn Gly Glin Ala Glu Ala Glu Glu Ala Thr Glu Gln Thir His Ile 1. 5 1O 15

Ser Pro Asn

<210s, SEQ ID NO 174 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 174 Glin Ala Ser Ser Lieu. Arg Lieu. Glu Pro Gly Arg Ala Asn Asp Gly Asp 1. 5 1O 15 Trp. His

<210s, SEQ ID NO 175 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 175 Glu Lieu Lys Gly Phe Ala Glu Arg Lieu. Glin Arg Asn. Glu Ser Gly Lieu. 1. 5 1O 15 Asp Ser Gly Arg 2O

<210s, SEQ ID NO 176 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 176 Arg Ser Gly Lys Ser Glin Pro Ser Tyr Ile Pro Phe Leu Lieu. Arg Glu 1. 5 1O 15

Glu

<210s, SEQ ID NO 177 &211s LENGTH: 22 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 177 Arg Arg Ser Asp Tyr Ala Lys Val Ala Lys Ile Phe Tyr Asn Lieu. Ser 1. 5 1O 15 Ile Glin Ser Phe Asp Asp 2O

<210s, SEQ ID NO 178 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 178 Lys Asn. Phe Thir Met Asn. Glu Lys Lieu Lys Llys Phe Phe Asin Val Lieu. 1. 5 1O 15

Thir Thir ASn

<210s, SEQ ID NO 179 &211s LENGTH: 2O 212. TYPE: PRT US 2010/0062444 A1 Mar. 11, 2010 70

- Continued <213> ORGANISM: Homo sapiens <4 OO > SEQUENCE: 179 Glu Phe Phe Val Asn. Glu Ala Arg Lys Asn. Asn His His Phe Llys Ser 1. 5 1O 15

Glu Ser Glu Glu 2O

<210s, SEQ ID NO 18O &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 18O Lys Asn Thr Glin Ala Ala Glu Ala Lieu Val Lys Lieu. Tyr Glu Thir Lys 1. 5 1O 15 Lieu. Cys Glu

<210s, SEQ ID NO 181 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 181 Glin Glu Asn Glin Pro Glu Asn. Ser Lys Thir Lieu Ala Thr Glin Lieu. Asn 1. 5 1O 15

Glin

<210s, SEQ ID NO 182 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 182 Lys Glin Met Glu Lys Asp Lieu Ala Phe Glin Lys Glin Val Ala Glu Lys 1. 5 1O 15 Glin Lieu Lys

<210s, SEQ ID NO 183 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 183 Glu Phe Val Glu Glin Lieu. Arg Lys Glu Gly Val Phe Ala Lys Glu Val 1. 5 1O 15 Arg

<210s, SEQ ID NO 184 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 184 Asp Arg His Pro Glin Ala Lieu. Glu Ala Ala Glin Ala Glu Lieu. Glin Glin 1. 5 1O 15 His Asp US 2010/0062444 A1 Mar. 11, 2010 71

- Continued <210s, SEQ ID NO 185 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 185 Arg Glu Val Arg Glin Lieu. Thir Lieu. Arg Llys Lieu. Glin Glu Lieu. Ser Ser 1. 5 1O 15 Lys Ala Asp Glu 2O

<210s, SEQ ID NO 186 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 186 Arg Glu Val Arg Glin Lieu. Thir Lieu. Arg Llys Lieu. Glin Glu Lieu. Ser Ser 1. 5 1O 15 Lys Ala Asp Glu 2O

<210s, SEQ ID NO 187 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 187 Ala Tyr Ile Arg Glu Gly His Glu Lys Glin Ala Asp Ile Met Ile Phe 1. 5 1O 15

Phe Ala Glu

<210s, SEQ ID NO 188 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 188 Asp Glu Ala Ser Lieu. Glu Pro Gly Tyr Pro Llys His Ile Lys Glu Lieu 1. 5 1O 15 Gly Arg

<210s, SEQ ID NO 189 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 189 Arg Gly Ser Phe Met Gly Ser Asp Glu Val Phe Thr Tyr Phe Tyr Lys 1. 5 1O 15

<210s, SEQ ID NO 190 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 190 Met Ile Pro Gly Gly Lieu Ser Glu Ala Lys Pro Ala Thr Pro Glu Ile 1. 5 1O 15

Glin Glu Ilie Wall US 2010/0062444 A1 Mar. 11, 2010 72

- Continued

<210s, SEQ ID NO 191 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 191 Asn Glu Thir Tyr Gly Llys Lieu. Glu Ala Val Glin Tyr Llys Thr Glin 1. 5 1O 15

<210s, SEQ ID NO 192 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 192 Asp Lieu Val Lieu. Thr Gly Tyr Glin Val Asp Lys Asn Lys Asp Asp Glu 1. 5 1O 15 Lieu. Thr Gly Phe 2O

<210s, SEQ ID NO 193 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 193 Arg Glin Glu. His Cys Met Ser Glu. His Phe Lys Asn Arg Pro Ala Cys 1. 5 1O 15 Lieu. Gly Ala Arg 2O

<210s, SEQ ID NO 194 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 194 Gln Gly His Llys Trp Gly Glu Ser Pro Ser Glin Gly Thr Glin Ala Gly 1. 5 1O 15 Ala Gly Lys

<210s, SEQ ID NO 195 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 195 Arg Ala Cys Gly Lys Arg Val Ser Glu Gly Asp Arg Asn Gly Ser Gly 1. 5 1O 15 Gly Gly Lys Trp Gly 2O

<210s, SEQ ID NO 196 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 196 US 2010/0062444 A1 Mar. 11, 2010 73

- Continued Met Val Glu Ala Phe Cys Ala Thr Trp Llys Lieu. Thr Asn Ser Glin Asn 1. 5 1O 15

<210s, SEQ ID NO 197 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OO > SEQUENCE: 197 Glin Val Gly Asn Val Thr Lys Pro Thr Val Ile Ile Ser Glin Glu 1. 5 1O 15

<210s, SEQ ID NO 198 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 198 Llys Val Val Ile Arg Thr Lieu Ser Thr Phe Lys Asn Thr Glu 1. 5 1O

<210s, SEQ ID NO 199 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 199 Arg Ala Val Phe Arg Glu Ala Glu Val Thir Lieu. Glu Ala Gly Gly Ala 1. 5 1O 15

Glu Glin Glu

<210s, SEQ ID NO 2 OO &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 2OO Glin Glu Pro Ala Lieu. Phe Ser Thr Asp Asn Asp Asp Phe Thr Val Arg 1. 5 1O 15

Asn

<210s, SEQ ID NO 2 O1 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 2O1 Glin Llys Tyr Glu Ala His Val Pro Glu Asn Ala Val Gly His Glu 1. 5 1O 15

<210s, SEQ ID NO 202 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 2O2 Llys Lys Ile Ile Glu Lys Met Lieu. Asn. Ser Asp Llys Ser Asn 1. 5 1O

<210s, SEQ ID NO 203 &211s LENGTH: 2O US 2010/0062444 A1 Mar. 11, 2010 74

- Continued

212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 2O3 Gly Llys Pro Gly Asn Glin Asn. Ser Lys Asn. Glu Pro Pro Llys Lys Arg 1. 5 1O 15 Glu Arg Glu Arg 2O

<210s, SEQ ID NO 204 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 204 Glin Ala Glu Ala Pro Lieu Val Pro Lieu. Ser Arg Glin Asn Lys 1. 5 1O

<210s, SEQ ID NO 205 &211s LENGTH: 13 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 205 Asn. Cys Phe Lieu. Thr Glu Arg Lys Ala Glin Pro Asp Glu 1. 5 1O

<210s, SEQ ID NO 206 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 2O6 Glu Phe Asp Thr Val Asp Lieu. Ser Ala Val Asp Val His Pro Asn 1. 5 1O 15

<210s, SEQ ID NO 2 O7 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 2O7 Asn Lys Glu Val Tyr His Glu Lys Asp Ile Llys Val Phe Phe Asp Llys 1. 5 1O 15 Ala Lys

<210s, SEQ ID NO 208 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 208 Lys Glin Val Asp Lieu. Glu Asn Val Trp Lieu. Asp Phe Ile Arg Glu 1. 5 1O 15

<210s, SEQ ID NO 209 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 209 US 2010/0062444 A1 Mar. 11, 2010 75

- Continued Lieu Lys Llys Pro Glin Asp Ser Glin Lieu. Glu Glu Gly Llys Pro Gly Tyr 1. 5 1O 15 Lieu. Asp

<210s, SEQ ID NO 210 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 210 Lys Ala Lys Arg Lieu. Glin Lys Glin Pro Glu Gly Glu Glu Pro Glu Met 1. 5 1O 15

Glu

<210s, SEQ ID NO 211 &211s LENGTH: 22 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 211 Lys Asp Arg Pro Ser Phe Ser Glu Ile Ala Ser Ala Lieu. Gly Asp Ser 1. 5 1O 15 Thr Val Asp Ser Lys Pro 2O

<210s, SEQ ID NO 212 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 212 Lys Arg Gly Ile Glu Glu Arg Ile Glin Glu Glu Ser Gly Phe Lieu. Ile 1. 5 1O 15

Glu

<210s, SEQ ID NO 213 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 213 Asp Arg Val Ile Gly Lys Asn Arg Glin Pro Llys Phe Glu Asp Arg Thr 1. 5 1O 15 Lys

<210s, SEQ ID NO 214 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 214 Asn Pro Gln His Phe Lieu. Asp Asp Llys Gly Glin Phe Llys Llys Ser Asp 1. 5 1O 15

<210s, SEQ ID NO 215 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 215 US 2010/0062444 A1 Mar. 11, 2010 76

- Continued

Arg His Cys Ile Lieu. Gly Glu Trp Lieu Pro Ile Lieu. Ile Met Ala Val 1. 5 1O 15

Phe Asn

<210s, SEQ ID NO 216 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 216 Lys Glin Arg Glu Lieu Ala Gly Asn Thr Met Thr Val Ser Tyr Met Ser 1. 5 1O 15

<210s, SEQ ID NO 217 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 217 Arg Asn Ala His Gly Ser Cys Lieu. His Ala Ser Thr Ala Asn Gly Ser 1. 5 1O 15 Ile Lieu Ala Gly Lieu. 2O

<210 SEQ ID NO 218 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 218 Glu Lieu Met Glu Lys Glu Val Glu Pro Glu Gly Ser Lys Arg Thr Asp 1. 5 1O 15

<210s, SEQ ID NO 219 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 219 Lys Ala Arg Ser Phe Cys Llys Thr His Ala Arg Lieu. Phe Llys Llys 1. 5 1O 15

<210s, SEQ ID NO 220 &211s LENGTH: 16 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 220 Lys Asn Lys Arg Lieu. Ser Gly Met Glu Glu Trp Ile Glu Gly Glu Lys 1. 5 1O 15

<210s, SEQ ID NO 221 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 221 Glu Gly Ser Thr Asp Lieu Pro Lieu Ala Pro Glu Ser Arg Val Asp Pro 1. 5 1O 15

Glu US 2010/0062444 A1 Mar. 11, 2010 77

- Continued

<210s, SEQ ID NO 222 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 222 Llys Val Ala Glin Glin Glin Arg His Lieu. Glu Lys Glin His Lieu. Arg 1. 5 1O 15

<210s, SEQ ID NO 223 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 223 Asp His Llys His Lieu. Asp His Glu Val Ala Lys Pro Ala Arg Arg Llys 1. 5 1O 15 Arg Lieu Pro Glu 2O

<210s, SEQ ID NO 224 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens < 4 OO > SEQUENCE: 224 Lys Lieu. Thir Ile Glu Ser Thr Pro Phe Asin Val Ala Glu Gly Lys Glu 1. 5 1O 15 Cys

<210s, SEQ ID NO 225 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 225 Llys Ser Asp Lieu Val Asn. Glu Glu Ala Thr Gly Glin Phe Arg Val Tyr 1. 5 1O 15 Pro Glu Lieu Pro Llys 2O

<210s, SEQ ID NO 226 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 226 Llys Pro Val Glu Asp Lys Asp Ala Val Ala Phe Thr Cys Glu Pro Glu 1. 5 1O 15

Ala Glin

<210s, SEQ ID NO 227 &211s LENGTH: 22 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 227 Asp Glu Lys Lieu. Ile Ser Lieu. Ile Cys Arg Ala Wall Lys Ala Thr Phe 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 78

- Continued

Asn Pro Ala Glin Asp Llys 2O

<210s, SEQ ID NO 228 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 228 Lys Asp Llys Trp Asp Glu Lieu Lys Glu Ala Gly Val Ser Asp Met Lys 1. 5 1O 15 Lieu. Gly Asp

<210s, SEQ ID NO 229 &211s LENGTH: 23 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 229 Asp Ser Trp Ile Val Pro Lieu. Asp Asn Lieu. Thir Lys Asp Asp Lieu. Asp 1. 5 1O 15 Glu Glu Glu Asp Thr His Lieu. 2O

<210 SEQ ID NO 23 O &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 23 O Glu Ala Val Val Thr Asn. Glu Lieu. Glu Asp Gly Asp Arg Glin Lys Ala 1. 5 1O 15 Met Lys Arg Lieu. Arg 2O

<210s, SEQ ID NO 231 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 231 Arg Arg Tyr Arg Asp Thir Lys Arg Ala Phe Pro His Lieu Val Asn Ala 1. 5 1O 15 Gly Lys

<210s, SEQ ID NO 232 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 232 Lys Ala Arg Asp Thr Llys Val Lieu. Ile Glu Asp Thr Asp Asp Glu Ala 1. 5 1O 15

Asn. Thir

<210s, SEQ ID NO 233 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens US 2010/0062444 A1 Mar. 11, 2010 79

- Continued

<4 OOs, SEQUENCE: 233 Arg Lys Arg Val Lieu. Glu Ala Lys Glu Lieu Ala Lieu Gln Pro Lys Asp 1. 5 1O 15 Asp Ile Val Asp 2O

<210s, SEQ ID NO 234 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 234 Arg His Gly Val Ser His Llys Val Asp Asp Ser Ser Gly Ser Ile Gly 1. 5 1O 15 Arg Arg Tyr Ala Arg 2O

<210s, SEQ ID NO 235 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 235 Glu Ala Arg Tyr Pro Lieu. Phe Glu Gly Glin Glu Thr Gly Lys Lys Glu 1. 5 1O 15

Thir Ile Glu Glu 2O

<210s, SEQ ID NO 236 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 236 Asp Lieu Ala Gly His Asp Met Gly. His Glu Ser Lys Arg Met His Ile 1. 5 1O 15 Glu Lys Asp Glu 2O

<210s, SEQ ID NO 237 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 237 Glu Lys Glin Val Glin Lieu. Glu Lys Thr Glu Lieu Lys Met Asp Phe Lieu. 1. 5 1O 15 Arg Glu Arg Glu 2O

<210s, SEQ ID NO 238 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 238 Glu Ala Asp Arg Ser Gly Gly Arg Thr Asp Ala Glu Arg Thir Ile Glin 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 80

- Continued Asp Gly Arg

<210s, SEQ ID NO 239 &211s LENGTH: 18 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 239 Glu Ala Lieu. Tyr Pro Glin Arg Arg Ser Tyr Thr Ser Glu Asp Glu Ala 1. 5 1O 15 Trp Llys

<210s, SEQ ID NO 24 O &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 240 Asp Tyr Tyr Llys Val Pro Arg Glu Arg Arg Ser Ser Thr Ala Lys Pro 1. 5 1O 15

Glu Wall Glu

<210s, SEQ ID NO 241 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 241 Asp Llys Tyr Asp Val Pro His Asp Llys Ile Gly Lys Ile Phe Llys Llys 1. 5 1O 15 Cys Llys Llys

<210s, SEQ ID NO 242 &211s LENGTH: 21 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 242 Asp Pro Asp Glin Tyr Asn. Phe Ser Ser Ser Glu Lieu. Gly Gly Asp Phe 1. 5 1O 15 Glu Phe Met Asp Asp 2O

<210s, SEQ ID NO 243 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 243 Glu Tyr Ile Arg Glin Lieu Pro Pro Asn. Phe Pro Tyr Arg Asp Asp 1. 5 1O 15

<210s, SEQ ID NO 244 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 244 Asp Thir Thr Val Lieu. Lieu Pro Pro Tyr Asp Asp Ala Thr Val Asn Gly 1. 5 1O 15 US 2010/0062444 A1 Mar. 11, 2010 81

- Continued

Ala Ala Lys Glu 2O

<210s, SEQ ID NO 245 &211s LENGTH: 14 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 245 Arg Arg Glu Glu Val Thir Lys Llys His Glin Tyr Glu Ile Arg 1. 5 1O

<210s, SEQ ID NO 246 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 246 Lys Glu Ser Arg Tyr Val His Asp Llys His Phe Glu Val Lieu. His Ser 1. 5 1O 15 Asp Lieu. Glu

<210s, SEQ ID NO 247 &211s LENGTH: 15 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 247 Asp Phe Phe Asp Arg Phe Met Lieu. Thr Glin Lys Asp Ile Asn Lys 1. 5 1O 15

<210s, SEQ ID NO 248 &211s LENGTH: 19 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 248 Glu Ser Lys His Phe Thr Arg Asp Lieu Met Glu Lys Lieu Lys Gly Arg 1. 5 1O 15 Thir Ser Arg

<210s, SEQ ID NO 249 &211s LENGTH: 17 212. TYPE: PRT <213> ORGANISM: Homo sapiens

<4 OOs, SEQUENCE: 249 Glu Thir Asp Arg Lieu Pro Arg Cys Val Arg Ser Thr Ala Arg Lieu Ala 1. 5 1O 15 Arg

<210s, SEQ ID NO 250 &211s LENGTH: 2O 212. TYPE: PRT <213> ORGANISM: Homo sapiens <4 OOs, SEQUENCE: 250 Glu Ser Arg Trip Lys Asp Ile Arg Ala Arg Ile Phe Lieu. Ile Ala Ser 1. 5 1O 15