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(12) United States Patent (10) Patent No.: US 9,073,982 B2 Demore Et Al

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(12) United States Patent (10) Patent No.: US 9,073,982 B2 Demore Et Al US009073982B2 (12) United States Patent (10) Patent No.: US 9,073,982 B2 DeMore et al. (45) Date of Patent: *Jul. 7, 2015 (54) TARGETS FOR REGULATION OF (56) References Cited ANGIOGENESIS U.S. PATENT DOCUMENTS (71) Applicant: The University of North Carolina at 5,885,808 A 3/1999 Spooner et al. Chapel Hill, Chapel Hill, NC (US) 6,017,949 A 1/2000 D'Amato et al. 7,026,445 B2 4/2006 LaVallie et al. 7,304,071 B2 12/2007 Cochran et al. (72) Inventors: Nancy Klauber DeMore, Durham, NC 7,348,335 B2 3/2008 Bethliel et al. (US); Cam Patterson, Chapel Hill, NC 7,348,418 B2 3/2008 Singh et al. (US); Rajendra Bhati. Durham, NC 7.465,449 B2 12/2008 Violette et al. 8,734,789 B2* 5/2014 DeMore et al. ............ 424,130.1 (US); Bradley G. Bone, Apex, NC (US) 2001 OO18186 A1 8, 2001 Hirth 2002fOOO6966 A1 1/2002 Arbiser (73) Assignee: The University of North Carolina at 2002fOO19382 A1 2/2002 Snyder et al. 2002fOO86341 A1 7/2002 Nguyen Chapel Hill, Chapel Hill, NC (US) 2004/OOO9541 A1 1/2004 Singh et al. 2004/OO77544 A1 4/2004 Varner 2005/025O163 A1 11/2005 Lorens et al. (*) Notice: Subject to any disclaimer, the term of this 2006,0166251 A1 7/2006 Archambault patent is extended or adjusted under 35 2006/0269921 A1 11/2006 Segara et al. U.S.C. 154(b) by 0 days. 2007/0054271 A1 3/2007 Polyak et al. 2007/0O87365 A1 4/2007 Van Criekinge et al. This patent is Subject to a terminal dis 2007/0105.133 A1 5/2007 Clarke et al. claimer. 2007, 0161018 A1 7/2007 Inazawa et al. 2007. O184439 A1 8, 2007 Guilford et al. 2007/0243214 A1 10/2007 Schiemann et al. (21) Appl. No.: 14/222,926 2007/0258952 A1 1 1/2007 Tong et al. (22) Filed: Mar 24, 2014 FOREIGN PATENT DOCUMENTS EP 1733739 A1 12/2006 (65) Prior Publication Data WO WO O2/24957 A1 3, 2002 US 2014/0294848A1 Oct. 2, 2014 OTHER PUBLICATIONS Adam et al., "Arylamine N-acetyltransferase-1 is highly expressed in breast cancers and conveys enhanced growth and resistance to Related U.S. Application Data etoposide in vitro.” Mol. Cancer. Res. 1:826-835 (2003). Allinen et al., “Molecular characterization of the tumor (63) Continuation of application No. 12/945,298, filed on microenvironment in breast cancer.” Cancer Cell 6:17-32 (2004). Nov. 12, 2010, now Pat. No. 8,734,789, and a Becker et al., “The carcinogenic potential of tacrolimus ointment continuation-in-part of application No. beyond imunne Suppression: a hypothesis creating case report.” PCT/US2009/003047, filed on May 15, 2009. BMC Cancer 6:7 (2006). Bhati et al., “A Novel Technique for Laser Capture Microdissection (60) Provisional application No. 61/316,068, filed on Mar. of Tumor Endothelium for mRNA Analysis.” American Association 22, 2010, provisional application No. 61/053,397, for Cancer Research Special Conference on Angiogenesis and Drug Delivery to Tumors: Bench to Bedside and Back, Waltham, MA, Nov. filed on May 15, 2008. 9-13, 2005. Bhati et al., “Discovery of Novel Tumor Endothelial Markers in Breast Cancer', Presentation and Abstract, Society of Surgical (51) Int. Cl. Oncology (SSO) 60' Annual Cancer Symposium, Mar. 16, 2007, A 6LX39/395 (2006.01) Washington, D.C. CI2P 2/08 (2006.01) Bhati et al., “Molecular Characterization of Human Breast Cancer C07K 16/00 (2006.01) Endothelium.” Surgical Grand Rounds, UNC Lineberger Compre A6 IK38/00 (2006.01) hensive Cancer Center, Feb. 28, 2007. C07K 6/8 (2006.01) A6 IK38/3 (2006.01) (Continued) C07K 6/28 (2006.01) Primary Examiner — Christine J Saoud C07K 6/40 (2006.01) Assistant Examiner — Jegatheesan Seharaseyon CI2N IS/II3 (2010.01) (74) Attorney, Agent, or Firm — Myers Bigel Sibley & GOIN33/574 (2006.01) Sajovec, P.A. (52) U.S. Cl. CPC ................. C07K 16/18 (2013.01); A61K 38/13 (57) ABSTRACT (2013.01); C07K 16/28 (2013.01); C07K 16/40 The present invention relates to the identification of poly (2013.01); C07K 231.6/96 (2013.01); C07K nucleotides and polypeptides having increased expression in 2317/34 (2013.01); C12N 15/113 (2013.01); tumor blood vessels. The invention further relates to the use of CI2N 2310/14 (2013.01); G0IN33/57415 the identified polynucleotides and polypeptides, and inhibi (2013.01); G0IN 2800/00 (2013.01) tors of the polynucleotides and polypeptides, in the regulation (58) Field of Classification Search of angiogenesis and the diagnosis and treatment of angiogen None esis-related diseases Such as cancer. See application file for complete search history. 9 Claims, 24 Drawing Sheets US 9,073,982 B2 Page 2 (56) References Cited Kunnumakkara et al., "Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction OTHER PUBLICATIONS with multiple cell signaling proteins.” Cancer Lett. 269:199-225 Bhati et al., “Molecular Characterization of Human Breast Tumor (2008). Vascular Cells.” Am. J. Pathol. 172: 1381-1390 (2008) epub Apr. 10, Kussie et al., J., Immunol., 152: 146-152, 1994. 2008. Lee et al., “Secreted frizzled-related protein 2 (SFRP2) is highly Buckanovich et al., “Tumor vascular proteins as biomarkers in expressed in canine mammary gland tumors but not in normal mam ovarian cancer.” J. Clin. Oncol. 25:852-861 (2007). mary glands.” Breast Cancer Res. Treat. 84:139-149 (2004). Cance et al., “Protein kinases in human breast cancer. Breast Cancer Lescher et al. (1998), Development Dynamics, vol. 213, pp. 440-451. Res. Treat. 35:105-114 (1995). Loeffler et al., “Targeting tumor-associated fibroblasts improves can Cao et al., “gro-beta, a -C-X-C—chemokine, is an angiogenesis cer chemotherapy by increasing intratumoral drug uptake.” J. Clin. inhibitor that Suppresses the growth of Lewis lung carcinoma in mice.” J. Exp. Med. 182:2069-2077 (1995). Invest. 116:1955-1962 (2006). Cao et al., “Only low levels of exogenous N-acetyltransferase activ Madden et al., “Vascular gene expression in nonneoplastic and malig ity, can be achieved in transgenic mice. Pharmacogenomics J. 5:255 nant brain.” Am. J. Pathol. 165:601-608 (2004). 261 (2005). Medyouf et al., “Targeting calcineurin activation as a therapeutic Chen et al., “Curcumin inhibited the arylamines N-acetyltransferase strategy for t-cell acute lymphoblastic leukemia,” Nat. Med. 13:736 activity, gene expression and DNA adduct formation in human lung 741 (2007). cancer cells (A549).” Toxicol. In Vitro 17:323-333 (2003). Ngoetal. (1994), The Protein Folding Problemand Tertiary Structure Chen et al., EMBO.J., 14:2784-2794, 1995. Prediction, pp. 491-495. Colman, Research in Immunology, 145:33-36, 1994. Parker et al., “Alterations in vascular gene expression in invasive Deb et al., “SFRP2 regulates cardiomyogenic differentiation by breast carcinoma.” Cancer Res.64:7857-7866 (2004). inhibiting a positive transcriptional autofeedback loop of Wnt3a.” Ragunathan et al., “Identification of the Xenobiotic-Metabolizing Stem Cells 26:35-44 (2008). Enzyme Arylamine N-Acetyltransferase 1 as a New Target of Dufourcq et al., “FrzA, a secreted frizzled related protein, induced Cisplatin in Breast Cancer Cells: Molecular and Cellular Mecha angiogenic response.” Circulation 106:3097-3103 (2002). nisms of Inhibition.” Mol. Pharmacol. 73:1761-1768 (2008). E-mail from Katherine Moore, Ph.D. dated Jul. 21, 2013, confirming Rudikoff et al., Proc. Natl Acad Sci USA, 79: 1979-1983, 1982. the date of receipt of the 4' annual report for grant W81XWH-04-1- Shafqat et al., “Hep27, a member of the short-chain dehydrogenase/ 0434 to Nancy Klauber-DeMore, M.D. reductase family, is an NADPH-dependent dicarbonyl reductase EP09747001.7 European Extended Search Report (EESR) mailed expressed in vascular endothelial tissue.” Cell Mol. Life Sci. Apr. 18, 2012. 63:1205-1213 (2006). Goodman et al., “Seprase, a membrane-bound protease, alieviates the Srisuma et al., “Identification of genes promoting angiogenesis in serum growth requirement of human breast cancer cells. Clin. Exp. mouse lung by transcriptional profiling.” Am. J. Resp. Cell Mol. Biol. Metastasis 20:459-470 (2003). 29: 172-179 (2003). Huang et al., “Seprase promotes rapid tumor growth and increased St Croix et al., “Genes expressed in human tumor endothelium.” microvessel density in a mouse model of human breast cancer.” Science 289:1197-1202 (2000). Cancer Res. 64:2712-2716 (2004). Wakefield et al., "Arylamine N-acetyltransferase 2 expression in the International Application No. PCT/US2009/003047 International developing heart.” J. Histochem. Cytochem, 53:583-592 (2005). Search Report & Written Opinion (ISR/WO) mailed Nov. 17, 2010. Wawrzak et al., “Wnt3a binds to several sRRPs in the nanomolar International Application No. PCT/US2011/29301 International range.” Biochem. Biophys. Res. Commun. 357: 1119-1123 (2007). Search Report & Written Opinion (ISR/WO) mailed Jul. 26, 2011 Wells et al. (1990), Biochemistry, vol. 29, No. 37, pp. 8509-8517. International Preliminary Reporton Patentability (IPRP) for Interna Yarosh et al., "Calcineurin inhibitors decrease DNA repair and tional Application No. PCT/US2009/003047, mailed Nov. 25, 2010. apoptosis in human keratinocytes following ultraviolet B irradia Kawamoto et al., “DNA methylation and histone modifications cause tion.” J. Invest. Dermatol. 125:1020-1025 (2005). silencing of Wnt antagonist gene in human renal cell carcinoma cell Yeh et al., “The Inhibition of N-Acetyltransferase Activity and Gene lines.” Int. J. Cancer 123:535-542 (2008). Expression in Human Bladder Cancer Cells (T24) by Shikonin.” In Klauber-DeMore, “Characterization of gene expression in human vivo 18:21-32 (2004). breast tumor epithelium.” Annual Summary report for grant Mirotsou et al. “Secreted frizzled related protein 2 (Sfrp2) is the key W81XWH-04-1-0434, pp. 1-15 (May 1, 2008).
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