DOCSLIB.ORG

WO 2016/077720 Al 19 May 2016 (19.05.2016) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2016/077720 Al 19 May 2016 (19.05.2016) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/077720 Al 19 May 2016 (19.05.2016) P O P C T (51) International Patent Classification: Shigui; C/o Protein One, LLC, 15601 Crabbs Branch Way, C12N 15/00 (2006.01) C07K 16/46 (2006.01) Rockville, MD 20855 (US). A61K 39/395 (2006.01) C12N 1/19 (2006.01) (74) Agent: HALLORAN, Patrick, J.; 3 141 Muirfield Road, C07K 16/28 (2006.01) C12P 21/08 (2006.01) Center Valley, PA 18034 (US). C07K 16/30 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/US20 15/060622 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) International Filing Date: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 13 November 2015 (13.1 1.2015) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/079,635 14 November 2014 (14. 11.2014) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: PROTEIN ONE, LLC [US/US]; 15601 (84) Designated States (unless otherwise indicated, for every Crabbs Branch Way, Rockville, MD 20855 (US). kind of regional protection available): ARIPO (BW, GH, (72) Inventors: YANG, Xiang; C/o Protein One, LLC, 15601 GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, Crabbs Branch Way, Rockville, MD 20855 (US). ZHU, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, [Continued on nextpage] (54) Title: BINDING AGENTS AND USES THEREOF FIGURE 1 BiTE T-cel HLA AGE l l Cancer cell Killed Cancer Cells © v o [Continued on nextpage] o TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, Published: DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, — with international search report (Art. 21(3)) LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (57) Abstract: The technology relates to monoclonal antibodies useful in detecting and / or treating cancer. In some embodiments, binding agents with specificity for at least one tumor antigen and T cell receptors (e.g., human CD3) are provided. In some em bodiments, methods for treating cancer using such binding agents are provided. BINDING AGENTS AND USES THEREOF [001] RELATED APPLICATIONS [002] This application claims priority to U.S. Ser. No. 62/079,635 filed November 14, 2014. [003] FIELD OF THE DISCLOSURE [004] The technology relates to monoclonal antibodies useful in the identification of cancer cells, as well as the diagnosis and treatment of cancer. [005] BACKGROUND INFORMATION [006] Patients with metastatic melanoma have a poor prognosis because the survival rate is only 5%. Although IL-2 can mediate complete regressions in 5-10% of patients, complete regressions are rare when using the anti-CTLA4 antibody ipilimumab or PLX4032, an inhibitor of mutated BRAF gene products. The adoptive transfer of human tumor infiltrating lymphocytes (TIL) selected for specific tumor reactivity led to objective clinical responses in 50-70% of patients with metastatic melanoma, including complete regressions in approximately 10-40% of patients who were pre-treated with lympho- depleting regimens. Therapies that can be more readily applied to a wider patient population, such as the use of non-selected TIL, are also currently being evaluated. However, the clinical efficacy of TIL generated from histologies other than melanoma has not been demonstrated. [007] Attempts to develop more broadly applicable cancer therapies have focused on genetic modifications that confer autologous peripheral blood mononuclear cells (PBMC) with the ability to recognize antigens specifically expressed on tumor cells. The first clinical cancer trial to evaluate the efficacy of T cells whose target specificity has been re-directed towards tumor cells was carried out using cells that were genetically modified to express a TCR directed against an HLA-A*0201 restricted epitope of the MART-1 antigen. This molecule is a member of the melanocyte differentiation antigen (MDA) family of antigens that are expressed on 80-90% of melanoma but not other cancer types, and are limited in their expression in normal tissues to melanocytes. In this trial, complete regressions were observed in two out of 17 melanoma patients who received autologous PBMC that were retrovirally transduced with a MART-1-reactive TCR. In a subsequent trial, treatment of patients with autologous PBMC that were transduced either with a second MART-1 reactive TCR or a TCR directed against an HLA-A*0201- restricted epitope of the MDA gp100 lead to objective clinical response rates of 30% and 19%, respectively. The significant skin, eye and ear toxicities observed in this trial, which presumably resulted from responses to the normal melanocytes resident in these tissues, may have been a consequence of the relatively high avidities of these TCRs. [008] A recent report detailed the results of a clinical trial carried out with T cells that were transduced with a TCR that recognized NY-ESO-1, a protein encoded by a member of the cancer/germline family of genes. These genes are expressed in approximately one third of a variety of tumor types that include metastatic melanomas, lung, breast, prostate, bladder, and head and neck cancers, as well as 80% of synovial cell sarcoma, but are limited in their expression in normal adult tissues to the testis. Objective clinical responses were observed in five out of 11 melanoma patients and four out of six synovial cell sarcoma patients treated with a high-avidity TCR directed against an HLA-A*0201 -restricted NY-ESO-1 epitope, supporting the efficacy of adoptive immunotherapy for treatment of patients other than those with melanoma. [009] Binding agents such as antibodies have proven useful in the diagnosis and treatment of diseases such as cancer. Bi-specific antibodies, molecules in which one antibody has been genetically linked to another antibody, have also been used to target T cells to cell surface antigens that are over-expressed on tumors or that are expressed in a highly tissue-specific manner on the tumor cell surface. In contrast to TCR mediated T cell therapy, bi-specific antibodies do not need to be personalized. [0010] There is a need in the field for improved reagents and methods for treating cancer. Such improved reagents and methods are provided by this disclosure. [001 1] SUMMARY OF THE DISCLOSURE [0012] The technology relates to monoclonal antibodies useful in the identification of cancer cells, as well as the diagnosis and treatment of cancer. In one embodiment, mAbs with specificity for tumor antigens are provided. In one embodiment, bi-specific antibodies are provided. In some embodiments, methods for using such binding agents to detecting cancerous cells are provided. In some embodiments, methods for treating cancer using such binding agents are provided. In another embodiment, kits for detecting cancerous cells are provided. [0013] BRIEF DESCRIPTION OF THE DRAWINGS [0014] Figure 1. Exemplary (BiTE) bi-specific antibody system. [0015] Figure 2. Gel filtration FPLC profiles of HLA A 1 reconstitution from recombinant heavy chain and p2-microglobulin with and without peptides (a) MAGE A3: EVDPIGHLY, (b) no peptide. [0016] Figure 3. ELISA with w6/32 showed the right conformation of the refolding proteins. [0017] Figure 4. Staining of tetramer with TCR transfected T cells and positive staining. [0018] Figure 5. ELISA of scFv binding to the antigen complexes. [0019] Figure 6. scFv 8E4 staining 1300A1 cells. [0020] Figure 7. Western blot hybridization of 8EC3 and CD19X3 generated from yeast. [0021] Figure 8. Production of IFNy following linking Cancer Cells with 8EC3. [0022] DETAILED DESCRIPTION [0023] This disclosure relates to binding agents that bind one or more tumor antigens on the surface of cells in vitro and / or in vivo. The binding agents may also bind isolated tumor antigen polypeptides and / or fragments and / or derivatives thereof, typically in vitro. Also provided are methods for using such binding agents to diagnose, treat, prevent and / or ameliorate one or more diseases associated with the existence of cells expressing tumor antigens. For instance, the binding agents may be antibodies (e.g., monoclonal antibodies) that may react with and / or bind to the epitopes of tumor antigens. An exemplary use for the binding agents described herein is the selective targeting and elimination of cells expressing the tumor antigen(s) to which the binding agents bind. In some embodiments, the binding agents may be multi-specific, such as bi-specific, meaning that a single binding agent comprises at least two regions having specificity for different epitopes. The different epitopes may be found on tumor antigens or a tumor antigen and another antigen such as a cell surface receptor. An exemplary cell surface receptor is the T cell receptor (TCR), also known as CD3. Other embodiments, uses and the like are described below. A general illustration of an embodiment of this system is illustrated in Fig. 1. As shown therein, in some embodiments, a bi-specific binding agent having specificity for both TCR (CD3) and tumor antigen (a bi-specific T cell engager or "BiTE") serves to associate a T cell with a tumor cell resulting in killing of the tumor cell by the cell.
Load more

Recommended publications
  • Fig. 1C Combination Therapy of Tumor Targeted ICOS Agonists with T-Cell Bispecific Molecules
    ( (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07K 16/30 (2006.01) A61P 35/00 (2006.01) kind of national protection av ailable) . AE, AG, AL, AM, C07K 16/28 (2006.01) A 6IK 39/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, C07K 16/40 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (21) International Application Number: HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, PCT/EP20 18/086046 KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 20 December 2018 (20. 12.2018) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available) . ARIPO (BW, GH, 17209444.3 2 1 December 2017 (21. 12.2017) EP GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (71) Applicant (for all designated States except US): F. HOFF- TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, MANN-LA ROCHE AG [CH/CH]; Grenzacherstrasse EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 124, 4070 Basel (CH).
    [Show full text]
  • International Patent Classification: KR, KW, KZ, LA, LC, LK, LR, LS, LU
    ( 2 (51) International Patent Classification: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, A61K 39/42 (2006.01) C07K 16/10 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, C07K 16/08 (2006.01) KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/US20 19/033 995 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (22) International Filing Date: TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 24 May 2019 (24.05.2019) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available) . ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (26) Publication Language: English UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 62/676,045 24 May 2018 (24.05.2018) US EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (71) Applicant: LANKENAU INSTITUTE FOR MEDICAL TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, RESEARCH [US/US]; 100 Lancaster Avenue, Wyn- KM, ML, MR, NE, SN, TD, TG).
    [Show full text]
  • Affinity Chromatography (AC)
    Affinity Chromatography (AC) 1 Affinity Chromatography (AC) • Principles of AC • Main stages in Chromatography • How to prepare Affinity gel - Ligand Immobilization - Spacer arms – Coupling methods – Coupling tips • Types of AC • Elution Conditions • Binding equilibrium, competitive elution, kinetics • Industrial Examples: Protein A/G for Therapeutic proteins • Future Considerations 2 What is affinity chromatography? Affinity chromatography is a technique of liquid chromatography which separates molecules through biospecific interactions. The molecule to be purified is specifically and reversibly adsorbed to a specific ligand The ligand is immobilized to an insoluble support (“matrix”): resin, “chip”, Elisa plate, membrane, Western, IP (immuneprecipitation), etc Introduction of a “spacer arm” between the ligand and the matrix to improve binding Elution of the bound target molecule a) non specific or b) specific elution method 3 What is it used for? Monoclonal and polyclonal antibodies Fusion proteins Enzymes DNA-binding proteins . ANY protein where we have a binding partner!! 4 Designing and preparing an affinity gel Choosing the matrix Designing the ligand - Spacer arms Coupling methods 5 Ligand Immobilization Ligand + Activating agent + Matrix Activated Immobilised matrix ligand 6 Designing the ligand Essential ligand properties: interacts selectively and reversibly with the target Carries groups which can couple it to the matrix without losing its binding activity Available in a pure form 7 Steric considerations & spacer arms Small ligand (<1,000) Risk of steric interference with binding between matrix and target molecule Often need spacer arm but watch out for Spacer arm adsorption to the spacer! 8 Design of spacer arms Alkyl chain Real risk of unspecific interactions between H H spacer and target molecule O O Hydrophilic chain Risk of unspecific interactions greatly O H reduced No coupling reaction will use 100% of the available binding sites.
    [Show full text]
  • EURL ECVAM Recommendation on Non-Animal-Derived Antibodies
    EURL ECVAM Recommendation on Non-Animal-Derived Antibodies EUR 30185 EN Joint Research Centre This publication is a Science for Policy report by the Joint Research Centre (JRC), the European Commission’s science and knowledge service. It aims to provide evidence-based scientific support to the European policymaking process. The scientific output expressed does not imply a policy position of the European Commission. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use that might be made of this publication. For information on the methodology and quality underlying the data used in this publication for which the source is neither Eurostat nor other Commission services, users should contact the referenced source. EURL ECVAM Recommendations The aim of a EURL ECVAM Recommendation is to provide the views of the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) on the scientific validity of alternative test methods, to advise on possible applications and implications, and to suggest follow-up activities to promote alternative methods and address knowledge gaps. During the development of its Recommendation, EURL ECVAM typically mandates the EURL ECVAM Scientific Advisory Committee (ESAC) to carry out an independent scientific peer review which is communicated as an ESAC Opinion and Working Group report. In addition, EURL ECVAM consults with other Commission services, EURL ECVAM’s advisory body for Preliminary Assessment of Regulatory Relevance (PARERE), the EURL ECVAM Stakeholder Forum (ESTAF) and with partner organisations of the International Collaboration on Alternative Test Methods (ICATM). Contact information European Commission, Joint Research Centre (JRC), Chemical Safety and Alternative Methods Unit (F3) Address: via E.
    [Show full text]
  • Generation of Novel Intracellular Binding Reagents Based on the Human Γb-Crystallin Scaffold
    Generation of novel intracellular binding reagents based on the human γB-crystallin scaffold Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) vorgelegt der Naturwissenschaftlichen Fakultät I-Biowissenschaften der Martin-Luther-Universität Halle-Wittenberg Institut für Biochemie und Biotechnologie von Ewa Mirecka geboren am 17. Dezember 1976 in Gdynia, Polen Table of contents Table of contents 1. INTRODUCTION.........................................................................................................1 1.1 Monoclonal antibodies as a biomolecular scaffold..........................................................1 1.2 Binding molecules derived from non-immunoglobulin scaffolds.....................................3 1.2.1 Alternative protein scaffolds – general considerations............................................................ 3 1.2.2 Application of alternative binding molecules ........................................................................... 6 1.3 Affilin – novel binding molecules based on the human γB-crystallin scaffold................... 6 1.3.1 Human γB-crystallin as a molecular scaffold........................................................................... 6 1.3.2 Generation of a human γB-crystallin library and selection of first-generation Affilin molecules ................................................................................................................................ 8 1.4 Selection of binding proteins by phage display ...................................................................
    [Show full text]
  • Selection of an Artificial Binding Protein Against the Ectodomain of PTH1R
    Selection of an artificial binding protein against the ectodomain of PTH1R Dissertation Zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) vorgelegt bei der Naturwissenschaftlichen Fakultät I Biowissenschaften der Martin-Luther-Universität Halle-Wittenberg von Qi Zhang geboren am 21.09.1983 in Shaanxi, China Gutachter /in 1. PD. Dr. Hauke Lilie 2. Prof. Dr. Jochen Balbach 3. Prof. Dr. Annette G. Beck-Sickinger Verteidigungsdatum: 14.03.2013 Zusammenfassung In den vergangenen Jahrzehnten fanden mehr als 30 Immunglobuline (IgGs) und deren Derivate Anwendung in der klinischen Praxis. Trotz des großen Erfolgs solcher Antikörper-basierter Medikamente traten auch einige Limitationen auf. Gerüstproteine stellen eine Alternative zu herkömmlichen Antikörpern dar. Sie weisen meist eine hohe thermodynamische Stabilität auf und bestehen aus einer einzelnen Polypeptidkette ohne Disulfidbrücken. Universelle Bindestellen können wie beim humanen Fibronectin III und bei Anticalinen in flexiblen Loop-Regionen erzeugt werden oder auf rigiden Sekundärstrukturelementen, wie im Fall der Affibodies, DARPine und Affiline. In der vorliegenden Arbeit wurde eine Protein-Bibliothek auf Basis des humanen γB-Kristallins, unter Randomisierung von 8 oberflächenexponierten Aminosäuren auf einem β-Faltblatt der N-terminalen Domäne des Proteins, hergestellt. Ein kürzlich entwickeltes Screening-System, das T7-basierte Phagen-Display, wurde zur Durchmusterung der Bibliothek auf potentielle Binder angewandt. Dabei erfolgt die Assemblierung der Protein-präsentierenden Phagenpartikel ohne einen Transportschritt über die Zellmembran hinweg bereits im Cytoplasma von E. coli. G-Protein gekoppelte Rezeptoren (GPCRs) bilden nur schwerlich für Strukturuntersuchungen geeignete, geordnete Kristallstrukturen aus. Kleine, gut lösliche Bindeproteine könnten sie in einer bestimmten Konformation fixieren und so den Anteil an hydrophilen Resten auf der Proteinoberfläche erhöhen.
    [Show full text]
  • Understanding Ubiquitin Recognition and Generating Affinity Reagents
    Ubiquitin Engineering: Understanding Ubiquitin Recognition and Generating Affinity Reagents by Isabel Leung A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Molecular Genetics University of Toronto © Copyright by Isabel Leung 2017 Abstract Ubiquitin Engineering: Understanding Ubiquitin Recognition and Generating Affinity Reagents Isabel Leung Doctor of Philosophy Department of Molecular Genetics University of Toronto 2016 Protein-protein interactions are necessary for virtually all biological processes. There have been tremendous efforts to document the diversity of molecular recognition, and to understand how molecular recognition occurs. The understanding of molecular interaction has also served as the foundation for designing novel protein interactions for use in therapeutics, diagnostics and basic sciences. An attractive system for studying protein-protein interactions is the ubiquitin (Ub) system. Ub is a protein modifier that is combinatorially ligated onto substrate proteins to influence substrate turnover and function. Ub uses a common surface to interact with more than 1000 proteins and plays pivotal roles in cell physiology. Despite the substantial structural information on Ub mediated interactions, there is no clear understanding of how individual Ub residues contribute to Ub’s broad scope of interactions. To address this question, I used affinity enhanced Ub variants (Ubvs) as proxies of native Ub in saturation scanning. Using saturation scanning, I studied the interactions between Ubvs and two Ub specific proteases (USP), USP2 and USP21, and elucidated a common functional epitope that is critical for USP recognition. The functional epitope recognizes USP residues that are conserved among the human USP family, suggesting it may make functional contributions in many other USP interactions.
    [Show full text]
  • WO 2018/218207 Al 29 November 2018 (29.11.2018) W !P O PCT
    (t) include a VL chain of SEQ ID NO: 24 and a VH chain of SEQ ID NO: 25; (u) include a VL chain of SEQ ID NO: 84 and a VH chain of SEQ ID NO: 83; (v) include a VL chain of SEQ ID NO: 154 and a VH chain of SEQ ID NO: 155; (w) include CDRs including SEQ ID NO: 85; SEQ ID NO: 86; SEQ ID NO: 87; SEQ ID NO: 88; SEQ ID NO: 89; and SEQ ID NO: 90; (x) include CDRs including SEQ ID NO: 130; SEQ ID NO: 13 1; SEQ ID NO: 132; SEQ ID NO: 133; SEQ ID NO: 134; and SEQ ID NO: 135; (y) include CDRs including SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 , and SEQ ID NO: 111; (z) include CDRs including SEQ ID NO: 112 , SEQ ID NO: 113 , SEQ ID NO: 114 , SEQ ID NO: 115 , SEQ ID NO: 116 , and SEQ ID NO: 117 ; (aa) include CDRs including SEQ ID NO: 118 , SEQ ID NO: 119 , SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, and SEQ ID NO: 123; (bb) include CDRs including SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129; (cc) include CDRs including SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, and SEQ ID NO: 14 1; (dd) include CDRs including SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, and SEQ ID NO: 147 (ee) include CDRs including SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, and SEQ ID NO: 99; (ff) include CDRs including SEQ ID NO: 100, SEQ ID NO: 10 1, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 105; (gg) include CDRs including SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 15 1, SEQ ID NO: 152, and SEQ ID NO: 153; (hh) includes a humanized sequence of an antibody disclosed herein; and/or (ii) binds to endogenous human CD33 with a KD of less than 10 nM.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0112915 A1 Bardroff Et Al
    US 201401 12915A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0112915 A1 Bardroff et al. (43) Pub. Date: Apr. 24, 2014 (54) IL-18 BINDING MOLECULES Publication Classification (71) Applicants: Michael Otto Bardroff, Loerrach (DE); (51) Int. Cl. Barbara Brannetti, Basel (CH); Emma C07K 6/24 (2006.01) Michelle Campbell, Surrey (GB); Beate GOIN33/68 (2006.01) Diefenbach-Streiber, Windach (DE): (52) U.S. Cl. Adina Eberth, Munich (DE); Christian CPC .......... C07K 16/244 (2013.01); G0IN33/6854 Carsten Silvester Kunz, Muenchen (2013.01) (DE); Sylwia Marshall, Epsom (GB); USPC ... 424/133.1; 424/139.1; 435/7.92; 435/69.6; Jean-Michel Rene Rondeau, Rixheim 435/331; 435/320.1; 530/387.3; 530/387.9; (FR); Jean-Marc Alfred Schlaeppi, 536/2353 Allschwil (CH); Gino Anselmus Van Heeke, Upper Beeding (GB) (57) ABSTRACT (72) Inventors: Michael Otto Bardroff, Loerrach (DE); Barbara Brannetti, Basel (CH); Emma Michelle Campbell, Surrey (GB); Beate IL-18 participates in both innate and acquired immunity. The Diefenbach-Streiber, Windach (DE): bioactivity of IL-18 is negatively regulated by the IL-18 bind Adina Eberth, Munich (DE); Christian ing protein (IL18BP), a naturally occurring and highly spe Carsten Silvester Kunz, Muenchen cific inhibitor. This soluble proteinforms a complex with free (DE); Sylwia Marshall, Epsom (GB); IL-18 preventing its interaction with the IL-18 receptor, thus Jean-Michel Rene Rondeau, Rixheim neutralizing and inhibiting its biological activity. The present (FR); Jean-Marc Alfred Schlaeppi, invention discloses binding molecules, in particular antibod Allschwil (CH); Gino Anselmus Van ies or fragments thereof, which bind IL-18 and do not bind Heeke, Upper Beeding (GB) IL-18 bound to IL-18BP (IL-18/IL-18BP complex).
    [Show full text]
  • Download Book
    Methods in Molecular Biology 1701 Michael Hust Theam Soon Lim Editors Phage Display Methods and Protocols M ETHODS IN M OLECULAR B IOLOGY Series Editor John M. Walker School of Life and Medical Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB, UK For further volumes: http://www.springer.com/series/7651 Phage Display Methods and Protocols Edited by Michael Hust Technische Universit€at Braunschweig, Braunschweig, Germany Theam Soon Lim Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang, Malaysia Editors Michael Hust Theam Soon Lim Technische Universit€at Braunschweig Institute for Research in Molecular Medicine Braunschweig, Germany Universiti Sains Malaysia Minden, Penang, Malaysia ISSN 1064-3745 ISSN 1940-6029 (electronic) Methods in Molecular Biology ISBN 978-1-4939-7446-7 ISBN 978-1-4939-7447-4 (eBook) DOI 10.1007/978-1-4939-7447-4 Library of Congress Control Number: 2017956713 © Springer Science+Business Media LLC 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication.
    [Show full text]
  • Suderman Et Al. 2017
    Protein Expression and Purification 134 (2017) 114e124 Contents lists available at ScienceDirect Protein Expression and Purification journal homepage: www.elsevier.com/locate/yprep Development of polyol-responsive antibody mimetics for single-step protein purification * Richard J. Suderman a, , Daren A. Rice a, Shane D. Gibson a, Eric J. Strick a, David M. Chao a, b a Nectagen, Inc., 2002 W. 39th Ave, Kansas City, KS 66103, USA b Stowers Institute for Medical Research, BioMed Valley Discoveries, Inc., USA article info abstract Article history: The purification of functional proteins is a critical pre-requisite for many experimental assays. Immu- Received 24 March 2017 noaffinity chromatography, one of the fastest and most efficient purification procedures available, is often Received in revised form limited by elution conditions that disrupt structure and destroy enzymatic activity. To address this 13 April 2017 limitation, we developed polyol-responsive antibody mimetics, termed nanoCLAMPs, based on a 16 kDa Accepted 15 April 2017 carbohydrate binding module domain from Clostridium perfringens hyaluronidase. nanoCLAMPs bind Available online 17 April 2017 targets with nanomolar affinity and high selectivity yet release their targets when exposed to a neutral polyol-containing buffer, a composition others have shown to preserve quaternary structure and enzy- Keywords: Affinity purification matic activity. We screened a phage display library for nanoCLAMPs recognizing several target proteins, fi fi Antibody mimetics produced af nity resins with the resulting nanoCLAMPs, and successfully puri ed functional target nanoCLAMPs proteins by single-step affinity chromatography and polyol elution. To our knowledge, nanoCLAMPs Immunoaffinity constitute the first antibody mimetics demonstrated to be polyol-responsive.
    [Show full text]
  • Beyond Antibodies Protein Engineering & Design
    Register Today to Hear New Data on Over 40 Antibody Alternative and Protein Engineering Projects IBC's 4th Annual Protein Beyond Engineering Antibodies & Design Novel Scaffolds, Clinical Progress Enabling Technologies and Creative and Manufacturing the Engineering to Improve Drug-Like Next Generation of Therapeutics Properties of Proteins September 21-23, 2009 • Town and Country Hotel • San Diego, CA Accelerate your own projects by applying Improve the functionality and biophysical lessons you will learn from multiple scaffolds properties of your molecules by applying progressing to the clinic: novel approaches to engineering: • Clinical and preclinical results of non-antibody • Engineering proteins for mulitfunctionality and antibody-like scaffolds • Improving half-life/PK, protein stability and delivery • FDA perspective on regulation of next generation antibodies and antibody alternatives • “Designer” protein engineering and computational modeling • Modified antibody formats: Bi-specifics and multi-specifics • Engineering and designing peptides, chemokines, enzymes and other scaffolds • Novel and emerging scaffolds • Conjugation approaches and new frontiers in • Downstream considerations to inform your protein engineering discovery and design efforts Keynote Presentation Featured Presentations Recombinant Immunotoxins: An FDA Perspective Building on Success in Hairy Cell Leukemia Marjorie Shapiro, Ph.D., CDER/FDA Ira Pastan, M.D., Chief, Laboratory of Molecular Biology, National Cancer Institute, NIH Two-in-One Antibody Germaine Fuh, Ph.D., Genentech Silver Scientific The Antibody Society Event Sponsor: Sponsor: Partner Register Early & Save www.IBCLifeSciences.com/Beyond Engineering the Next Generation of Protein Therapeutics This one-of-a-kind meeting features over 40 exclusive case studies giving you insights into novel strategies for accelerating antibody- like and non-antibody scaffolds to the clinic and emerging protein engineering and design strategies to improve properties of current platforms.
    [Show full text]