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( 12 ) United States Patent US010195209B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 195 ,209 B2 Gish et al. (45 ) Date of Patent: * Feb . 5 , 2019 (54 ) ANTI- HULRRC15 ANTIBODY DRUG 4 ,634 ,665 A 1 / 1987 Axel 4 ,716 , 111 A 12 / 1987 Osband CONJUGATES AND METHODS FOR THEIR 4 ,737 , 456 A 4 / 1988 Weng USE 4 , 816 ,397 A 3 / 1989 Boss 4 , 816 ,457 A 3 / 1989 Baldwin (71 ) Applicants :AbbVie Inc. , North Chicago , IL (US ) ; 4 , 968 ,615 A 11 / 1990 Koszinowski AbbVie Biotherapeutics Inc. , 5 , 168 , 062 A 12 / 1992 Stinski 5 , 179 ,017 A 1 / 1993 Axel Redwood City , CA (US ) 5 , 225 , 539 A 7 / 1993 Winter 5 , 413 , 923 A 5 / 1995 Kucherlapati ( 72 ) Inventors : Kurt C . Gish , Piedmont, CA (US ) ; 5 ,530 , 101 A 6 /1996 Queen Jonathan A . Hickson , Lake Villa , IL 5 , 545 , 806 A 8 / 1996 Lonberg (US ) ; Susan Elizabeth Morgan - Lappe , 5 , 565 ,332 A 10 / 1996 Hoogenboom Riverwoods, IL (US ) ; James W . 5 , 569 , 825 A 10 / 1996 Lonberg 5 ,585 ,089 A 12 / 1996 Queen Purcell, San Francisco , CA (US ) 5 ,625 , 126 A 4 / 1997 Lonberg 5 ,633 , 425 A 5 / 1997 Lonberg ( 73 ) Assignees: AbbVie Inc. , North Chicago , IL (US ) ; 5 ,658 , 570 A 8 / 1997 Newman AbbVie Biotherapeutics Inc . , 5 ,661 ,016 A 8 / 1997 Lonberg Redwood City , CA (US ) 5 ,681 , 722 A 10 / 1997 Newman 5 ,693 , 761 A 12 / 1997 Queen 5 ,693 , 762 A 12 / 1997 Queen ( * ) Notice : Subject to any disclaimer, the term of this 5 ,693 , 780 A 12 / 1997 Newman patent is extended or adjusted under 35 5 , 807 ,715 A 9 / 1998 Morrison U . S . C . 154 (b ) by 25 days. 5 ,814 , 318 A 9 / 1998 Lonberg 5 , 885 , 793 A 3 / 1999 Griffiths This patent is subject to a terminal dis 5 , 916 ,771 A 6 / 1999 Hori claimer . 5 , 939 , 598 A 8 / 1999 Kucherlapati 6 , 180 , 370 B1 1 /2001 Queen 7 ,217 , 797 B2 5 / 2007 Hinton (21 ) Appl. No. : 15 / 363, 786 7 , 223 , 837 B2 5 / 2007 De Groot 7 , 399 , 469 B2 7 / 2008 Zhang (22 ) Filed : Nov . 29, 2016 7 , 521 , 541 B2 4 / 2009 Eigenbrot 7 .855 ,275 B2 12 /2010 Eigenbrot (65 ) Prior Publication Data 7 , 989 ,434 B2 8 /2011 Feng US 2017 /0151344 A1 Jun . 1 , 2017 (Continued ) Related U . S . Application Data FOREIGN PATENT DOCUMENTS (60 ) Provisional application No . 62 /417 ,489 , filed on Nov. EP 0239400 A2 9 / 1987 4 , 2016 , provisional application No . 62 / 261, 114 , filed EP 0519596 Al 12 / 1992 on Nov . 30 , 2015 . (Continued ) (51 ) Int. Cl. OTHER PUBLICATIONS A61K 38 /07 ( 2006 . 01 ) Paul, Fundamental Immunology , 3rd Edition , 1993 , pp . 292 -295 . * A61K 31/ 5517 ( 2006 . 01 ) Rudikoff et al. , Proc . Natl. Acad . Sci . USA , 1982 , 79 ( 6 ) : 1979 COZK 16 /30 ( 2006 . 01 ) 1983 . * A61K 39 / 395 ( 2006 . 01 ) Colman , Research in Immunology , 1994 , 145 : 33 - 36 . * A61K 47 / 06 ( 2006 .01 ) Bendig , Methods: A Companion to Methods in Enzymology , 1995 ; CO7K 16 / 28 ( 2006 .01 ) 8 : 83 - 93 . * A61K 47 /68 (2017 .01 ) Khantasup et al . , Monoclonal Antibodies in Immunodiagnosis and (52 ) U . S . CI. Immunotherapy , 2015 , 34 ( 6 ) : 404 -417 . * CPC . .. A61K 31/ 5517 ( 2013 .01 ) ; A61K 38 /07 Alley et al. , 2008 " Contribution of Linker Stability to the Activities ( 2013 .01 ) ; A61K 47 /6803 ( 2017 .08 ) ; A61K of Anticancer Immunoconjugates , ” Bioconjugate Chem 19 ( 3 ) :795 47 /6849 (2017 .08 ) ; A61K 47 /6851 ( 2017 .08 ) ; 765 . A61K 47 /6889 ( 2017 .08 ) ; C07K 16 / 28 (Continued ) (2013 . 01 ) ; CO7K 16 /30 (2013 .01 ) ; CO7K 2317/ 24 ( 2013 .01 ) ; CO7K 2317 / 77 ( 2013 .01 ) ; Primary Examiner — Hong Sang CO7K 2317 /92 (2013 .01 ) ( 74 ) Attorney , Agent, or Firm — Dechert LLP (58 ) Field of Classification Search None (57 ) ABSTRACT See application file for complete search history . The present disclosure provides antibodies , antibody bind ( 56 ) References Cited ing fragments , and antibody drug conjugates that bind human LRRC15 , their methods ofmaking , and their uses to U . S . PATENT DOCUMENTS treat patients having cancer . 4 ,299 ,216 A 11/ 1981 Bernard et al. 4 ,444 , 887 A 4 / 1984 Hoffmann 32 Claims, 36 Drawing Sheets 4 ,510 , 245 A 4 / 1985 Cousens Specification includes a Sequence Listing . US 10 ,195 ,209 B2 Page 2 (56 ) References Cited Diamond et al ., 1974 " Interpretation of nonelectrolyte partition coefficients between dimyristoyi lecithin and water ,” J Membr Biol U . S . PATENT DOCUMENTS 17 ( 1 ) : 121 - 154 . Dornina et al ., 2003 “ Development of potent monoclonal antibody 8 , 455 ,622 B2 6 / 2013 McDonagh auristatin conjugates for cancer therapy ," Nat Biotechnol 21 ( 7 ) :778 8 , 535 ,678 B2 9 / 2013 Law 8 , 568 , 728 B2 10 / 2013 Jeffrey 784 . 9 , 089 ,615 B2 7 / 2015 Stull Dornina et al ., 2006 “ Enhanced Activity ofMonomethylauristatin F 9 , 242 ,013 B2 1 / 2016 Howard through Monoclonal Antibody Delivery : Effects of Linker Technol 2005 / 0271615 Al 12 / 2005 Shabat ogy on Efficacy and Toxicity , " Bioconjugate Chem 17 ( 1 ) : 114 - 124 . 2006 / 0116422 A16 / 2006 De Groot Dornina et al ., 2008 “ Novel Peptide Linkers for Highly Potent 2007 / 0280931 Al 12 / 2007 Chen Antibody - Auristatin Conjugate, ” Bioconjugate Chem 19 ( 10 ) : 1960 2013 /0309256 AL 11 / 2013 Lyon 1963 . Droujinine et al ., 2013 " To grab the stroma by the horns: From FOREIGN PATENT DOCUMENTS biology to cancer therapy with mesenchymal stem cells, ” Oncotarget 4 ( 5 ) :651 -664 . EP 0592106 Al 4 / 1994 Dubowchik et al ., 1998 " Cathepsin B - sensitive dipeptide prodrugs WO WO 1989 / 12624 A2 12 / 1989 1 . A model study of structural requirements for efficient release of WO WO 1991/ 09967 Al 7 / 1991 doxorabicin ,” Bioorg Med Chem Lett 8 ( 23 ) :3341 - 3346 . WO WO 1991 / 10741 Al 7 / 1991 Eisenhauer et al ., 2009 “ New response evaluation criteria in solid WO WO 1992 / 01047 A1 1 / 1992 tumours : Revised RECIST guideline (version 1 . 1 ) ,” European Jour WO WO 1996 / 33735 Al 10 / 1996 nal of Cancer 45 :228 -247 . WO WO 1996 / 34096 A1 10 / 1996 Elenbaas et al. , 2001 " Human breast cancer cells generated by WO WO 1997 / 34631 Al 9 / 1997 WO WO 1998 / 16654 Al 4 / 1998 oncogenic transformation of primary mammary epithelial cells ," WO WO 1998 / 24893 A2 6 / 1998 Genes Dev 15 :50 -65 . WO WO 1998 / 46645 A2 10 / 1998 Francisco et al. , 2003 " CAC10 - vcMMAE , an anti -CD30 WO WO 1998 / 50433 A2 11 / 1998 monomethyl auristatin E conjugate with potent and selective anti WO WO 2002 /060919 A2 8 / 2002 tumor activity, ” Blood 102 ( 4 ) : 1458 - 1465 . WO WO 2004 /010957 A2 2 / 2004 Gerber et al. , 2009 “ Antibody drug -cojugates targeting the tumor WO WO 2005 / 123780 A2 12 / 2005 vasculature , " mAbs 1 ( 3 ) :247 - 253 . WO WO 2007 / 089149 A2 8 / 2007 Goldmacher et al . , 2013 “ Linker Technology and Impact of Linker WO WO 2009 /073445 A2 6 / 2009 Design on ADC Properties, ” Antibody - Drug Conjugates and WO WO 2010 / 068795 A2 6 / 2010 Immunotoxins , Part of the series Cancer Drug Discovery and WO WO 2010 / 138719 Al 12 / 2010 Development Chapter 7 pp . 117 - 135 . WO WO 2011/ 120053 Al 9 / 2011 WO WO 2013 / 085925 A1 6 / 2013 Griffon - Etienne et al ., 1999 “ Taxane -induced Apoptosis Decom WO WO 2013 /096901 A1 6 / 2013 presses Blood Vessels and Lowers Interstitial Fluid Pressure in Solid WO WO 2014 / 008375 A1 1 / 2014 Tumors : Clinical Implications, ” Cancer Res 59 ( 15 ) :3776 - 3782 . WO WO 2014 / 093379 A1 6 / 2014 Gupta et al. , 2009 “ Identification of selective inhibitors of cancer WO WO 2014 /093394 A1 6 / 2014 stem cells by high - throughput screening ,” Cell 138 ( 4 ) :645 -659 . wo WO 2014 / 093640 A1 6 / 2014 Hamblett et al . , 2004 “ Effects of Drug Loading on the Antitumor Activity of Monoclonal Antibody Drug Conjugate , " Clin Cancer Res 20 : 7063 - 7070 . OTHER PUBLICATIONS Helft et al. , 2004 “ A Phase I Study of Cantuzumab Mertansine Administered as a Single Intravenous Infusion Once Weekly in Axup et al. , 2012 “ Synthesis of site - specific antibody -drug conju Patients with Advanced Solid Tumors, ” Clin Cancer Res 10 ( 13 ): 4363 gates using unnatural amino acids, " Proc Natl Acad Sci USA 4368 . 109 (40 ) : 16101 - 16106 . Helma et al. , 2015 “ Nanobodies and recombinant binders in cell Bornstein , 2015 “ Antibody Drug Conjugates: Preclinical Consid biology , ” J Cell Biol 209 ( 5 ) :633 -644 . erations, ” AAPS J 17 ( 3 ) : 525 -534 . Hollander et al. , 2008 “ Selection of Reaction Additives Used in the Boswell et al. , 2012 “ Differential Effects of Predosing on Tumor and Preparation of Monomeric Antibody -Calicheamicin Conjugates ," Tissue Uptake of an 111 In -Labeled Anti - TENB2 Antibody - Drug Bioconjugate Chem 19 ( 1 ) : 358 - 361. Conjugate , " J Nucl Med 53 ( 9 ) : 1454 - 1461 . Ippolito et al. , 2016 “ Metabolic shift toward oxidative phosphorylation Boswell et al ., 2013 “ An integrated approach to identify normal in docetaxel resistant prostate cancer cells, ” Oncotarget 7 (38 ): 61890 tissue expression of targets for antibody -drug conjugates : case study 61904 . of TENB2 , ” Br J Pharmacol 168 : 415 -457 . Kalluri , 2016 “ The biology and function of fibroblasts in cancer, " Burke et al. , 2009 “ Design , Synthesis, and Biological Evaluation of Nat Rev Cancer 16 ( 9 ) : 582 - 598 . Antibody - Drug Conjugates Comprised of Potent Camptothecin Karnoub et al. , 2007 “Mesenchymal stem cells within tumour Analogues, ” Bioconjugate Chem 20 ( 6 ) : 1242 - 1250 . stroma promote breast cancer metastasis ,” Nature 449 :557 -563 . Camps et al ., 1990 " Fibroblast- mediated acceleration of human Kellogg et al. , 2011 “ Disufide - Linked Antibody -Maytansinoid Con epithelial tumor growth in vivo ,” Proc Natl Acad Sci USA 87 ( 1 ) :75 jugates: Optimization of In Vivo Activity by Varying the Steric 79 . Hindrance at Carbon Atoms Adjacent to the Disfulfide Linkage, " Chari, 2008 “ Targeted Cancer Therapy : Conferring Specificity to Bioconjugate Chem 22( 4 ) :717 -727 .
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