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(12) United States Patent (10) Patent No.: US 8,945,572 B2 Chant Et Al

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(12) United States Patent (10) Patent No.: US 8,945,572 B2 Chant Et Al USOO8945572B2 (12) United States Patent (10) Patent No.: US 8,945,572 B2 Chant et al. (45) Date of Patent: Feb. 3, 2015 (54) METHODS AND COMPOSITIONS FOR THE FOREIGN PATENT DOCUMENTS DAGNOSIS AND TREATMENT OF CANCER WO WO 1999/44062 9, 1999 WO OOf 46343 8, 2000 (75) Inventors: John Chant, Millbrae, CA (US); WO O3,024987 A1 3, 2003 Anthony S. Guerrero, San Francisco, WO 2005/066211 A2 7/2005 CA (US); Peter Haverty, San Francisco, WO WO 2005,115363 12/2005 CA (US); Cynthia Honchell, San WO 2006/110581 A2 10, 2006 Francisco, CA (US); Kenneth Jung, San WO 2007 134210 A2 11/2007 Francisco, CA (US); Thomas Wu, San OTHER PUBLICATIONS Francisco, CA (US) Gura (Science, 1997, 278: 1041-1042).* (73) Assignee: Genentech, Inc., South San Francisco, Kaiser (Science, 2006, 313: 1370).* CA (US) Gura (Science, 1995, 270:575-577).* Tockman et al (Cancer Res., 1992, 52:271 1s-2718s).* (*) Notice: Subject to any disclaimer, the term of this Pritzker (Clinical Chemistry, 2002, 48: 1147-1150).* patent is extended or adjusted under 35 Bai et al. (Cancer Res., 2010, 70: 7630-9).* Otte et al. (European Journal of Clinical Investigation, 2000, 30, U.S.C. 154(b) by 902 days. 222-229).* Yoshino et al. (Oncology Reports 2005, 13: 247-252).* (21) Appl. No.: 12/300,156 Eswarakumar et al., “Cellular signaling by fibroblast growth factor receptors' Cytokine Growth Factor Rev. 16(2): 139-49 (Apr. 2005). (22) PCT Filed: May 11, 2007 Miki et al., “Determination of ligand-binding specificity by alterna tive splicing: two distinct growth factor receptors encoded by a single (86). PCT No.: PCT/US2007/068.737 gene” Proc Natl AcadSci U S A 89(1):246-50 (1992). Matsuikeet al., “Expression of fibroblast growth factor (FGF)-10 in S371 (c)(1), human colorectal adenocarcinoma cells' J Nippon Med Sch. (2), (4) Date: Mar. 17, 2009 68(5):397-404 (2001). Watanabe et al., “Overexpression of keratinocyte growth factor in (87) PCT Pub. No.: WO2007/134210 cancer cells and enterochromaffin cells in human colorectal cancer' Pathol Int. 50(5):363-72 (May 2000). PCT Pub. Date: Nov. 22, 2007 Al-Kuraya et al., “Prognostic relevance of gene amplifications and coamplifications in breast cancer Cancer Res.64(23):8534-40 (Dec. (65) Prior Publication Data 2004). US 2009/0311250 A1 Dec. 17, 2009 Post et al., “Keratinocyte growth factor and its receptor are involved in regulating early lung branching” Development 122(10):3107-15 (Oct. 1996). Katoh et al., "K-Sam gene encodes Secreted as well as transmembrane Related U.S. Application Data receptor tyrosine kinase” Proc Natl Acad Sci U S A. 89(7):2960-4 (Apr. 1992). (60) Provisional application No. 60/799,772, filed on May Takano et al. “Epidermal growth factor receptor gene mutations and 12, 2006. increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer J Clin Oncol. 23(28):6829-37 (51) Int. Cl. (Oct. 2005). A6 IK39/00 (2006.01) Moffa et al., “Transforming potential of alternatively spliced variants CI2O I/68 (2006.01) of fibroblast growth factor receptor 2 in human mammary epithelial (52) U.S. Cl. cells' Mol Cancer Res. 2(11):643-52 (Nov. 2004). Bernard-Pierrot et al., “Inhibition of human bladder tumour cell CPC ........ CI2O I/6886 (2013.01); C12O 2600/106 growth by fibroblast growth factor receptor 2b is independent of its (2013.01) kinase activity. Involvement of the carboxy-terminal region of the USPC .................. 424/181.1; 424/178.1; 424/133.1; receptor” Oncogene 23(57):920 1-11 (Dec. 2004). 435/6.14 (Continued) (58) Field of Classification Search USPC ........... 514/1.1; 435/6, 6.12, 6.14: 530/387.3: 424/130. 1, 133.1, 172.1, 178.1, 181.1 Primary Examiner — Mark Halvorson See application file for complete search history. Assistant Examiner — Yan Xiao (74) Attorney, Agent, or Firm — Jessica Richardson, Alissa (56) References Cited H. Faris; Arnold & Porter LLP U.S. PATENT DOCUMENTS (57) ABSTRACT 5,863,888 A 1/1999 Dionne 6,852,318 B1* 2/2005 Varner ....................... 424,130.1 2004/O137442 A1 7/2004 Slamon Methods and compositions are provided for the diagnosis and 2004/O138442 A1 7, 2004 Walke treatment of colorectal cancers associated with amplification 2004/0180002 A1* 9/2004 Young et al. ................. 424,149 or overexpression of the FGFR2 gene. 2004/01973.28 A1* 10/2004 Young et al. ... 424,141.1 2004/0258693 A1* 12/2004 Young et al. 424,155.1 2005/0244880 A1* 11/2005 Kallioniemi et al. ............. 435/6 2 Claims, 1 Drawing Sheet US 8,945,572 B2 Page 2 (56) References Cited Mohammadi et al., “Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors' Science OTHER PUBLICATIONS 276:955-60 (May 1997). Yamada et al., “Suppression of glioblastoma cell growth following Dionne et al., “Cloning and expression of two distinct high-affinity antisense oligonucleotide-mediated inhibition of fibroblast growth receptors cross-reacting with acidic and basic fibroblast growth fac factor receptor expression” Glia 28(1):66-76 (Oct. 1999). tors' EMBO J.9(9): 2685-92 (1990). Ornitz et al., “Receptor specificity of the fibroblast growth factor Bottaro et al., “A keratinocyte growth factor receptor-derived peptide family” Journal of Biological Chemistry 271(25): 15292-15297 (Jun. antagonist identifies part of the ligand binding site” J. Biol Chem. 21, 1996). 268(13):9180-3 (May 1993). Dell and Williams, “A novel form offibroblast growth factor receptor Edwards et al. “Gene amplifications associated with the development 2. Alternative splicing of the third immunoglobulin-like domain con of hormone-resistant prostate cancer. Clinical Cancer Research fers ligand binding specificity” Journal of Biological Chemistry 9:5271-5281, 2003. 267(29): 21225-21229 (Oct. 15, 1992). Plotnikov et al., “Crystal structures of two FGF-FGFR complexes Hattori et al. “Immunohistochemical detection of K-sam protein in reveal the determinants of ligand-receptor specificity” Cell stomach cancer', Clinical Cancer Research 2:1373-1381, 1996. 101(4):413-24 (May 2000). Kadota et al. “Identification of novel gene amplifications in breast Hattori et al., "K-sam, an amplified gene in stomach cancer, is a cancer and coexistence of gene amplification with an activating muta member of the heparin-binding growth factor receptor genes' Proc tion of PIK3CA, Cancer Research 69:7357-7365, 2009. Natl AcadSci U S A 87(15):5983-7 (1990). Tannheimeretal. “Characterization offibroblast growth factor recep Zhao et al., “Homozygous deletions and chromosome amplifications tor 2 overexpression in the human breast cancer cell line SUM in human lung carcinomas revealed by single nucleotide 52PE, Breast Cancer Research 2:311-320, 2000. polymorphism array analysis' Cancer Res. 65(13):5561-70 (Jul. 2005). * cited by examiner U.S. Patent Feb. 3, 2015 US 8,945,572 B2 (JequnuKdoo VNG)·yºf(JequunuÁd00 ·?? scasses zzzzz@@@zzzzzzzzzzzzzzzzzzz@% assassassaxaaxaasa SSSaaaaaaaaaaaaaaxxxxx US 8,945,572 B2 1. 2 METHODS AND COMPOSITIONS FOR THE (3 Suppl 1):43-48 (1997). However, patients that overex DAGNOSIS AND TREATMENT OF CANCER press erbB2 show greater response to treatment with taxanes. Id. This application is a US National Stage of PCT/US2007/ Overexpression of erbB2 has provided the basis for tar 068737, filed on May 11, 2007, which claims the benefit of 5 geted breast cancer therapies. A recombinant humanized anti U.S. Provisional Application 60/799,772, filed May 12, 2006. ErbB2 (anti-HER2) monoclonal antibody (HerceptinTM, The entire disclosures of the foregoing applications are incor Genentech, Inc.) has been Successfully used to treat patients porated by reference herein. with ErbB2-overexpressing metastatic breast cancer. (Baselga et al., J. Clin. Oncol., 14:737-744 (1996). REFERENCE TO ASEQUENCE LISTING 10 A continuing need exists for compositions and methods that target amplified genes and the products of those genes in The instant application contains a Sequence Listing which the diagnosis and treatment of cancer. has been submitted in ASCII format via EFS-Web and is A continuing need also exists for compositions and meth hereby incorporated by reference in its entirety. Said ASCII ods for the diagnosis and/or treatment of colorectal cancer. copy, created on Nov. 8, 2008, is named 15 Over 56,000 people died of colorectal cancer in the year 2000. P2364R1 sequence.txt and is 14328 bytes in size. See Holen and Kemeny (2002) “Colorectal Cancer: Epide miology and Treatment, in Encyclopedia of Cancer, Vol. 2 FIELD OF THE INVENTION (Elsevier Sciences, USA), pages 1-8. There are approxi mately 110,000 new cases of colon cancer diagnosed in the The present invention relates to methods and compositions United States each year, accounting for approximately 15% for the diagnosis and treatment of cancers associated with of all cancer cases. Id. There are approximately 45,000 new gene amplification. cases of rectal cancer diagnosed in the United States each year, accounting for approximately 30% of all colorectal BACKGROUND cancers. Id. 25 The invention described herein meets the above-described Cancer is characterized by an increase in the number of needs and provides other benefits. abnormal, or neoplastic, cells derived from a normal tissue that proliferate and, under certain circumstances, invade adja SUMMARY cent tissues and eventually metastasize via the blood or lym phatic system. Alteration of gene expression is intimately 30 In one aspect, methods and compositions are provided for related to uncontrolled cell growth and de-differentiation, the diagnosis and treatment of colorectal cancers associated which are common features of cancer. Certain cancers are with amplification and/or overexpression of the FGFR2 gene. characterized by overexpression of certain genes, e.g., onco In one aspect, a method of diagnosing the presence of a genes.
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