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(12) United States Patent (10) Patent No.: US 9,593,164 B2 Chiu Et Al

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(12) United States Patent (10) Patent No.: US 9,593,164 B2 Chiu Et Al USOO95931 64B2 (12) United States Patent (10) Patent No.: US 9,593,164 B2 Chiu et al. (45) Date of Patent: Mar. 14, 2017 (54) BISPECIFIC EGFR/C-MET ANTIBODIES 5,403.484 A 4/1995 Ladner et al. 5,427,908 A 6/1995 Dower et al. 5,558,864 A 9/1996 Bendig et al. (71) Applicant: Janssen Biotech, Inc., Horsham, PA 5,571,698 A 11/1996 Ladner et al. (US) 5,580,717 A 12/1996 Dower et al. 5,885,793 A 3, 1999 Griffiths et al. (72) Inventors: Mark Chiu, Spring House, PA (US); 5,891,996 A 4, 1999 Mateo de Acosta del Rio et al. Sheri Moores, Spring House, PA (US); 5,969,108 A 10/1999 McCafferty et al. 6,172,197 B1 1/2001 McCafferty et al. Joost Neijssen, Ultrecht (NL); Paul 6,521.404 B1 2/2003 Griffiths et al. Parren, Ultrecht (NL); Janine 6,544,731 B1 4/2003 Griffiths et al. Schuurman, Ultrecht (NL) 6,555,313 B1 4/2003 Griffiths et al. 6,582,915 B1 6/2003 Griffiths et al. 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(Continued) C07K 6/28 (2006.01) A 6LX 39/395 (2006.01) OTHER PUBLICATIONS A 6LX 3/57 (2006.01) Adjei, et al., “Early Clinical Development of ARQ 197, a Selective, A6 IK 45/06 (2006.01) Non-ATP-Competitive Inhibitor Targeting MET Tyrosine Kinase A6 IK 3L/4545 (2006.01) for the Treatment of Advanced Cancers,” the Oncologist, 16: A6 IK 3/437 (2006.01) 788-799 (2011). A 6LX 3/5.377 (2006.01) Amado, et al., “Wild-Type KRAS Is Required for Panitumumab A6 IK 33/24 (2006.01) Efficacy in Patients With Metastatic Colorectal Cancer,” Journal of A61 K 39/00 (2006.01) Clinical Oncology, 26(10): 1626-1634 (2008). (52) U.S. Cl. Baselga, et al., “Critical Update and Emerging Trends in Epidermal CPC ........ C07K 16/2863 (2013.01); A61K 31/437 Growth Factor Receptor Targeting in Cancer,” Journal of Clinical Oncology, 23(11): 2445-2459 (2005). (2013.01); A61K 31/4545 (2013.01); A61 K Batley, et al., “Inhibition of FGF-1 Receptor Tyrosine Kinase 31/517 (2013.01); A61 K3I/5377 (2013.01); Activity by PD 161570, a New Protein-Tyrosine Kinase Inhibitor.” A61K 33/24 (2013.01); A61K 39/395 Life Sciences, 62(2): 143-150 (1998). (2013.01); A61K 39/3955 (2013.01); A61 K Bean, et al., “MET amplification occurs with or without T790M 45/06 (2013.01); A61 K 2039/505 (2013.01); mutations in EGFR mutant lung tumors with acquired resistance to C07K 23.17/31 (2013.01); C07K 2317/73 gefitinib or erlotinib,” Proceedings of the National Academy of (2013.01); C07K 2317/76 (2013.01); C07K Science, 104(52): 20932-20937 (2007). 23 18/20 (2013.01) (Continued) (58) Field of Classification Search None Primary Examiner — Ruixiang Li See application file for complete search history. (74) Attorney, Agent, or Firm — Kirk Baumeister (56) References Cited (57) ABSTRACT U.S. PATENT DOCUMENTS Bispecific EGFR/c-Met antibodies and methods of making and using the molecules. 5,212.290 A 5/1993 Vogelstein et al. 5,223,409 A 6, 1993 Ladner et al. 2 Claims, 18 Drawing Sheets US 9,593.164 B2 Page 2 (56) References Cited Ichimura, et al., “Expression of c-met/HGF Receptor in Human Non-Small Cell Lung Carcinomas in vitro and in vivo and Its FOREIGN PATENT DOCUMENTS Prognostic Significance.” Japan Journal of Cancer Research, 87: 1063-1069 (1996). WO WO 2008/O77546 A1 T 2008 Jänne, et al., “Effect of Epidermal Growth Factor Receptor Tyrosine WO WO 2008, 127710 A2 10, 2008 Kinase Domain Mutations on the Outcome of Patients with Non WO WO 2009/03O239 A1 3, 2009 Small Cell Lung Cancer Treated with Epidermal Growth Factor WO WO 2009/085462 A1 T 2009 Receptor Tyrosine Kinase Inhibitors.” Clinical Cancer Research, WO WO 2009, 111691 A2 9, 2009 12(14 Suppl): 4416s-4420s (2006). 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