IP Library › Granted Patent US 12,281,176
Granted Patent B2
US 12,281,176 · App. 17/336,152 · Granted Apr 22, 2025

Binding molecules for BCMA and CD3

Inventors: Peter Kufer (Munich, DE); Tobias Raum (Munich, DE); Patrick Hoffmann (Munich, DE); Roman Kischel (Munich, DE); Ralf Lutterbuese (Munich, DE); Doris Rau (Munich, DE); Paul Adam (Munich, DE); Eric Borges (Munich, DE); Barbara Hebeis (Munich, DE); Susanne Hipp (Munich, DE)
Assignees: Amgen Inc.; Amgen Research (Munich) GmbH
C07K16/468A61K39/0005C07K14/70578C07K16/2809C07K16/2875C07K16/2878A61K2039/505A61K2039/575C07K2317/31C07K2317/33C07K2317/34C07K2317/56C07K2317/565C07K2317/622C07K2317/73C07K2317/92C07K2317/94C07K2319/00C07K2319/21C07K2319/30C07K2319/31C07K2319/43
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Quick Facts
Patent No.
US 12,281,176
App. No.
17/336,152
Granted
Apr 22, 2025
Kind
B2
Abstract

The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

Claims (10)

1. An antibody comprising:

a binding domain that binds to human CD3; and

further a polypeptide comprising the amino acid sequence of SEQ ID NO: 737 with 0, 1, 2, 3, 4, 5, or 6 amino acid substitutions and 0, 1, or 2 amino acid insertions or deletions to SEQ ID NOs: 731, 732 and/or 733 contained within SEQ ID NO: 737, and

0, 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions and 0, 1, 2, 3 or 4 amino acid insertions or deletions to the remainder of SEQ ID NO: 737.

2. The antibody of claim 1 , wherein the antibody is human or humanized.

3. The antibody of claim 1 , further comprising an IgG framework.

4. The antibody of claim 1 , further comprising an Fc constant domain.

5. The antibody of claim 1 , wherein every amino acid substitution is a naturally occurring amino acid.

6. The antibody of claim 1 , wherein the binding domain that binds to human CD3 is linked to the polypeptide via at least one disulfide bond.

7. The antibody of claim 1 , wherein the antibody is human or humanized, and further comprises an Fc constant domain.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 25, 2024
From: BOEHRINGER INGELHEIM INTERNATIONAL GMBH
To: AMGEN INC.
Reel/Frame 069394/0779 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 25, 2024
From: KUFER, PETER; RAUM, TOBIAS; HOFFMANN, PATRICK; KISCHEL, ROMAN; LUTTERBUESE, RALF; RAU, DORIS; ADAM, PAUL; BORGES, ERIC; HEBEIS, BARBARA; HIPP, SUSANNE
To: AMGEN RESEARCH (MUNICH) GMBH; BOEHRINGER INGELHEIM INTERNATIONAL GMBH
Reel/Frame 069394/0875 →
Continuity (10)
Continuation 17011849 · Sep 3, 2020
Continuation 14358511
Provisional Application 61651486 · May 24, 2012
Provisional Application 61651474 · May 24, 2012
Provisional Application 61560183 · Nov 15, 2011
Provisional Application 61560162 · Nov 15, 2011
Provisional Application 61560149 · Nov 15, 2011
Provisional Application 61560144 · Nov 15, 2011
Provisional Application 61560178 · Nov 15, 2011
Related Publication 20220356268A1 · Nov 10, 2022
References Cited (400)
US 3691016A · Patel et al. · 1972 [cited by applicant]
US 3773919A · Boswell et al. · 1973 [cited by applicant]
US 3969287A · Jaworek et al. · 1976 [cited by applicant]
US 4179337A · Davis et al. · 1979 [cited by applicant]
US 4195128A · Hildebrand et al. · 1980 [cited by applicant]
US 4229537A · Hodgins et al. · 1980 [cited by applicant]
US 4247642A · Hirohara et al. · 1981 [cited by applicant]
US 4263428A · Apple et al. · 1981 [cited by applicant]
US 4281061A · Zuk et al. · 1981 [cited by applicant]
US 4301144A · Iwashita et al. · 1981 [cited by applicant]
US 4330440A · Ayers et al. · 1982 [cited by applicant]
US 4439196A · Higuchi · 1984 [cited by applicant]
US 4447224A · DeCant, Jr. et al. · 1984 [cited by applicant]
US 4447233A · Mayfield · 1984 [cited by applicant]
US 4475916A · Himmelstein · 1984 [cited by applicant]
US 4485045A · Regen · 1984 [cited by applicant]
US 4486194A · Ferrara · 1984 [cited by applicant]
US 4487603A · Harris · 1984 [cited by applicant]
US 4496689A · Mitra · 1985 [cited by applicant]
US 4544545A · Ryan et al. · 1985 [cited by applicant]
US 4596556A · Morrow et al. · 1986 [cited by applicant]
US 4615885A · Nakagame et al. · 1986 [cited by applicant]
US 4619794A · Hauser · 1986 [cited by applicant]
US 4640835A · Shimizu et al. · 1987 [cited by applicant]
US 4670417A · Iwasaki et al. · 1987 [cited by applicant]
US 4694778A · Learn et al. · 1987 [cited by applicant]
US 4751180A · Cousens et al. · 1988 [cited by applicant]
US 4767628A · Hutchinson · 1988 [cited by applicant]
US 4790824A · Morrow et al. · 1988 [cited by applicant]
US 4791192A · Nakagawa et al. · 1988 [cited by applicant]
US 4816397A · Boss et al. · 1989 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 4879231A · Stroman et al. · 1989 [cited by applicant]
US 4935233A · Bell et al. · 1990 [cited by applicant]
US 4941880A · Burns · 1990 [cited by applicant]
US 4946778A · Ladner et al. · 1990 [cited by applicant]
US 5013556A · Woodle et al. · 1991 [cited by applicant]
US 5064413A · McKinnon et al. · 1991 [cited by applicant]
US 5223409A · Ladner et al. · 1993 [cited by applicant]
US 5225539A · Winter · 1993 [cited by applicant]
US 5260203A · Ladner et al. · 1993 [cited by applicant]
US 5292658A · Cormier et al. · 1994 [cited by applicant]
US 5312335A · McKinnon et al. · 1994 [cited by applicant]
US 5383851A · McKinnon et al. · 1995 [cited by applicant]
US 5399163A · Peterson et al. · 1995 [cited by applicant]
US 5418155A · Cormier et al. · 1995 [cited by applicant]
US 5470582A · Supersaxo et al. · 1995 [cited by applicant]
US 5476786A · Huston · 1995 [cited by applicant]
US 5476996A · Wilson et al. · 1995 [cited by applicant]
US 5545806A · Lonberg et al. · 1996 [cited by applicant]
US 5545807A · Surani et al. · 1996 [cited by applicant]
US 5565332A · Hoogenboom et al. · 1996 [cited by applicant]
US 5569825A · Lonberg et al. · 1996 [cited by applicant]
US 5585089A · Queen et al. · 1996 [cited by applicant]
US 5591669A · Krimpenfort et al. · 1997 [cited by applicant]
US 5612205A · Kay et al. · 1997 [cited by applicant]
US 5625126A · Lonberg et al. · 1997 [cited by applicant]
US 5633425A · Lonberg et al. · 1997 [cited by applicant]
US 5643763A · Dunn et al. · 1997 [cited by applicant]
US 5648260A · Winter et al. · 1997 [cited by applicant]
US 5661016A · Lonberg et al. · 1997 [cited by applicant]
US 5683888A · Campbell · 1997 [cited by applicant]
US 5693761A · Queen et al. · 1997 [cited by applicant]
US 5693762A · Queen et al. · 1997 [cited by applicant]
US 5698767A · Wilson et al. · 1997 [cited by applicant]
US 5721367A · Kay et al. · 1998 [cited by applicant]
US 5731168A · Carter et al. · 1998 [cited by applicant]
US 5741668A · Ward et al. · 1998 [cited by applicant]
US 5770429A · Lonberg et al. · 1998 [cited by applicant]
US 5777079A · Tsien et al. · 1998 [cited by applicant]
US 5789215A · Berns et al. · 1998 [cited by applicant]
US 5789650A · Lonberg et al. · 1998 [cited by applicant]
US 5804387A · Cormack et al. · 1998 [cited by applicant]
US 5814318A · Lonberg et al. · 1998 [cited by applicant]
US 5821337A · Carter et al. · 1998 [cited by applicant]
US 5859205A · Adair et al. · 1999 [cited by applicant]
US 5874299A · Lonberg et al. · 1999 [cited by applicant]
US 5874304A · Zolotukhin et al. · 1999 [cited by applicant]
US 5876995A · Bryan · 1999 [cited by applicant]
US 5877397A · Lonberg et al. · 1999 [cited by applicant]
US 5925558A · Tsien et al. · 1999 [cited by applicant]
US 5939598A · Kucherlapati et al. · 1999 [cited by applicant]
US 5958765A · Brams et al. · 1999 [cited by applicant]
US 5976796A · Szalay et al. · 1999 [cited by applicant]
US 5977322A · Marks et al. · 1999 [cited by applicant]
US 5981175A · Loring et al. · 1999 [cited by applicant]
US 6023010A · Krimpenfort et al. · 2000 [cited by applicant]
US 6037453A · Jardieu et al. · 2000 [cited by applicant]
US 6075181A · Kucherlapati et al. · 2000 [cited by applicant]
US 6114598A · Kucherlapati et al. · 2000 [cited by applicant]
US 6146826A · Chalfie et al. · 2000 [cited by applicant]
US 6150584A · Kucherlapati et al. · 2000 [cited by applicant]
US 6162963A · Kucherlapati et al. · 2000 [cited by applicant]
US 6214388B1 · Benz et al. · 2001 [cited by applicant]
US 6255458B1 · Lonberg et al. · 2001 [cited by applicant]
US 6300064B1 · Knappik et al. · 2001 [cited by applicant]
US 6407213B1 · Carter et al. · 2002 [cited by applicant]
US 6458547B1 · Bryan et al. · 2002 [cited by applicant]
US 6673986B1 · Kucherlapati et al. · 2004 [cited by applicant]
US 6774106B2 · Theill et al. · 2004 [cited by applicant]
US 6833268B1 · Green et al. · 2004 [cited by applicant]
US 7112324B1 · Dorken et al. · 2006 [cited by applicant]
US 7125689B2 · Carr et al. · 2006 [cited by applicant]
US 7435871B2 · Green et al. · 2008 [cited by applicant]
US 7625472B2 · Kufer et al. · 2009 [cited by applicant]
US 7728114B2 · Mach et al. · 2010 [cited by applicant]
US 8076459B2 · Hofmeister et al. · 2011 [cited by applicant]
US 8105603B2 · Kelley et al. · 2012 [cited by applicant]
US 8236308B2 · Kischel et al. · 2012 [cited by applicant]
US 8784821B1 · Kufer et al. · 2014 [cited by applicant]
US 8790645B2 · Kufer et al. · 2014 [cited by applicant]
US 9034324B2 · Kalled et al. · 2015 [cited by applicant]
US 9150664B2 · Kufer · 2015 [cited by examiner]
US 9260522B2 · Kufer et al. · 2016 [cited by applicant]
US 9340621B2 · Kufer · 2016 [cited by examiner]
US 9410994B2 · Heo et al. · 2016 [cited by applicant]
US 9598500B2 · Kufer · 2017 [cited by examiner]
US 9725506B2 · Dillon et al. · 2017 [cited by applicant]
US 9850320B2 · Bernett et al. · 2017 [cited by applicant]
US 9856327B2 · Bernett et al. · 2018 [cited by applicant]
US 10059766B2 · Xiao et al. · 2018 [cited by applicant]
US 10294300B2 · Raum et al. · 2019 [cited by applicant]
US 10301391B2 · Raum · 2019 [cited by examiner]
US 10519241B2 · Raum et al. · 2019 [cited by applicant]
US 10683351B2 · Raum et al. · 2020 [cited by applicant]
US 10752694B2 · Kufer · 2020 [cited by examiner]
US 10766969B2 · Kufer · 2020 [cited by examiner]
US 10781264B2 · Raum et al. · 2020 [cited by applicant]
US 10851170B2 · Raum et al. · 2020 [cited by applicant]
US 10981998B2 · Kufer et al. · 2021 [cited by applicant]
US 11352433B2 · Raum · 2022 [cited by examiner]
US 11434302B2 · Raum et al. · 2022 [cited by applicant]
US 11447567B2 · Raum et al. · 2022 [cited by applicant]
US 11472886B2 · Kufer et al. · 2022 [cited by applicant]
US 11591396B2 · Raum et al. · 2023 [cited by applicant]
US 20020173629A1 · Jakobovits et al. · 2002 [cited by applicant]
US 20030070185A1 · Jakobovits et al. · 2003 [cited by applicant]
US 20030078385A1 · Arathoon et al. · 2003 [cited by applicant]
US 20030091561A1 · van de Winkel et al. · 2003 [cited by applicant]
US 20040052783A1 · Weiner et al. · 2004 [cited by applicant]
US 20050076395A1 · Kucherlapati et al. · 2005 [cited by applicant]
US 20050249723A1 · Lazar et al. · 2005 [cited by applicant]
US 20050265993A1 · Mach et al. · 2005 [cited by applicant]
US 20060193852A1 · Dorken et al. · 2006 [cited by applicant]
US 20070212733A1 · Martin · 2007 [cited by applicant]
US 20070264687A1 · Chou et al. · 2007 [cited by applicant]
US 20080260738A1 · Moore et al. · 2008 [cited by applicant]
US 20080299129A1 · Lewis et al. · 2008 [cited by applicant]
US 20080311078A1 · Gokarn et al. · 2008 [cited by applicant]
US 20090252683A1 · Kischel et al. · 2009 [cited by applicant]
US 20090252729A1 · Farrington et al. · 2009 [cited by applicant]
US 20090304696A1 · Lawson et al. · 2009 [cited by applicant]
US 20090325196A1 · Dillon et al. · 2009 [cited by applicant]
US 20100150918A1 · Kufer et al. · 2010 [cited by applicant]
US 20100183615A1 · Kufer et al. · 2010 [cited by applicant]
US 20110123532A1 · Gurney et al. · 2011 [cited by applicant]
US 20110212094A1 · Ghayur et al. · 2011 [cited by applicant]
US 20110274685A1 · Keler et al. · 2011 [cited by applicant]
US 20110293579A1 · Nielsen et al. · 2011 [cited by applicant]
US 20110294619A1 · Kufer et al. · 2011 [cited by applicant]
US 20120034228A1 · Kufer et al. · 2012 [cited by applicant]
US 20120244162A1 · Kufer et al. · 2012 [cited by applicant]
US 20130078249A1 · Ast et al. · 2013 [cited by applicant]
US 20130078250A1 · Ast et al. · 2013 [cited by applicant]
US 20130129723A1 · Blankenship et al. · 2013 [cited by applicant]
US 20130273055A1 · Borges et al. · 2013 [cited by applicant]
US 20140112914A1 · Nezu et al. · 2014 [cited by applicant]
US 20140154253A1 · Ng et al. · 2014 [cited by applicant]
US 20140288275A1 · Moore et al. · 2014 [cited by applicant]
US 20140302035A1 · Harms et al. · 2014 [cited by applicant]
US 20140302037A1 · Borges et al. · 2014 [cited by applicant]
US 20140308285A1 · Yan et al. · 2014 [cited by applicant]
US 20150376287A1 · Vu et al. · 2015 [cited by applicant]
US 20160122436A1 · Kufer et al. · 2016 [cited by applicant]
US 20160152707A1 · Kufer et al. · 2016 [cited by applicant]
US 20160257748A1 · Michaels et al. · 2016 [cited by applicant]
US 20170029502A1 · Raum et al. · 2017 [cited by applicant]
US 20170037149A1 · Raum et al. · 2017 [cited by applicant]
US 20170165373A1 · Armitage et al. · 2017 [cited by applicant]
US 20170218078A1 · Raum et al. · 2017 [cited by applicant]
US 20170349668A1 · Rattel et al. · 2017 [cited by applicant]
US 20180142021A1 · Weiss et al. · 2018 [cited by applicant]
US 20190151448A1 · Abel et al. · 2019 [cited by applicant]
US 20190169310A1 · Kufer et al. · 2019 [cited by applicant]
US 20190263920A1 · Vu et al. · 2019 [cited by applicant]
US 20200048357A1 · Raum · 2020 [cited by examiner]
US 20200095319A1 · Kufer et al. · 2020 [cited by applicant]
US 20220064336A1 · Kufer · 2022 [cited by examiner]
US 20220251243A1 · Kufer et al. · 2022 [cited by applicant]
US 20220356268A1 · Kufer et al. · 2022 [cited by applicant]
US 20230357444A1 · Kufer et al. · 2023 [cited by applicant]
EP 0133988A2 · 1985 [cited by applicant]
EP 0171496A2 · 1986 [cited by applicant]
EP 0173494A2 · 1986 [cited by applicant]
EP 0239400A2 · 1987 [cited by applicant]
EP 0244234A2 · 1987 [cited by applicant]
EP 0402226A1 · 1990 [cited by applicant]
EP 0773288A2 · 1997 [cited by applicant]
EP 0843961A1 · 1998 [cited by applicant]
EP 1223964B1 · 2007 [cited by applicant]
EP 1806143A2 · 2007 [cited by applicant]
EP 2520590A2 · 2012 [cited by applicant]
EP 2762497A1 · 2014 [cited by applicant]
EP 2780375B1 · 2019 [cited by applicant]
GB 2177096A · 1987 [cited by applicant]
WO WO1987005330A1 · 1987 [cited by applicant]
WO WO1991006319A1 · 1991 [cited by applicant]
WO WO1992015673A1 · 1992 [cited by applicant]
WO WO1992022645A1 · 1992 [cited by applicant]
WO WO1992022647A1 · 1992 [cited by applicant]
WO WO1992022670A1 · 1992 [cited by applicant]
WO WO1996034096A1 · 1996 [cited by applicant]
WO WO199901556A2 · 1999 [cited by applicant]
WO WO199966951A2 · 1999 [cited by applicant]
WO WO2000006605A2 · 2000 [cited by applicant]
WO WO2000034317A2 · 2000 [cited by applicant]
WO WO2000040716A2 · 2000 [cited by applicant]
WO WO2000041474A2 · 2000 [cited by applicant]
WO WO2001012812A2 · 2001 [cited by applicant]
WO WO2001024811A1 · 2001 [cited by applicant]
WO WO2001087977A2 · 2001 [cited by applicant]
WO WO2002053596A2 · 2002 [cited by applicant]
WO WO2002066516A2 · 2002 [cited by applicant]
WO WO2003040170A2 · 2003 [cited by applicant]
WO WO2003047336A2 · 2003 [cited by applicant]
WO WO2003087131A2 · 2003 [cited by applicant]
WO WO2004106381A1 · 2004 [cited by applicant]
WO WO2004106383A1 · 2004 [cited by applicant]
WO WO2005040220A1 · 2005 [cited by applicant]
WO WO2005056606A2 · 2005 [cited by applicant]
WO WO2005061547A2 · 2005 [cited by applicant]
WO WO2005075511A1 · 2005 [cited by applicant]
WO WO2005118635A2 · 2005 [cited by applicant]
WO WO2006031370A2 · 2006 [cited by applicant]
WO WO2006138181A2 · 2006 [cited by applicant]
WO WO2007009064A2 · 2007 [cited by applicant]
WO WO2007033230A1 · 2007 [cited by applicant]
WO WO2007042261A2 · 2007 [cited by applicant]
WO WO2007097812A2 · 2007 [cited by applicant]
WO WO2007146968A2 · 2007 [cited by applicant]
WO WO2008119565A2 · 2008 [cited by applicant]
WO WO2008119566A2 · 2008 [cited by applicant]
WO WO2008119567A2 · 2008 [cited by applicant]
WO WO2009132058A2 · 2009 [cited by applicant]
WO WO2010037835A2 · 2010 [cited by applicant]
WO WO2010037836A2 · 2010 [cited by applicant]
WO WO2010037837A2 · 2010 [cited by applicant]
WO WO2010037838A2 · 2010 [cited by applicant]
WO WO2010060486A1 · 2010 [cited by applicant]
WO WO2010104949A2 · 2010 [cited by applicant]
WO WO2012066058A1 · 2012 [cited by applicant]
WO WO2012163805A1 · 2012 [cited by applicant]
WO WO2013072406A1 · 2013 [cited by applicant]
WO WO2013072415A1 · 2013 [cited by applicant]
WO WO2014047231A1 · 2014 [cited by applicant]
WO WO2014089335A2 · 2014 [cited by applicant]
WO WO2012088461A2 · 2014 [cited by applicant]
WO WO2014122143A1 · 2014 [cited by applicant]
WO WO2014138449A1 · 2014 [cited by applicant]
WO WO2017134134A1 · 2017 [cited by applicant]
Rudikoff et al., PNAS 79: 1979-1983 (Year: 1982). [cited by examiner]
Ito et al., FEBS Letters 309(1): 85-88 (Year: 1992). [cited by examiner]
Wu et al., J Mol Biol 294: 151-162 (Year: 1999). [cited by examiner]
Lloyd et al., Protein Engineering, Design & Selection 22:159-168 (Year: 2009). [cited by examiner]
Edwards et al., J Mol Biol. 334(1): 103-118 (Year: 2003). [cited by examiner]
Piche-Nicholas et al., MABS 10(1): 81-94 (Year: 2018). [cited by examiner]
Baeuerle et al., “Bispecific T-Cell Engaging Antibodies for Cancer Therapy”, Cancer Res, 2009, vol. 69, No. 12, pp. 4941-4944. [cited by applicant]
Bargou et al., “Tumor Regression in Cancer Patients by Very Low Doses of a T Ceil-Engaging Antibody”, Science, 2008, vol. 321, pp. 974-976. [cited by applicant]
Bellucci et al., “Complete response to donor lymphocyte infusion in multiple myeloma is associated with antibody responses to highly expressed antigens”, Blood, 2004, vol. 103, No. 2, pp. 656-663. [cited by applicant]
Bellucci et al., “Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor”, Blood, 2005, vol. 105, No. 10, pp. 3945-3950. [cited by applicant]
Bio-Techne, “Human BCMA-TNFRSF17 antibody—technical sheet” bio-techne (R&D Systems), MAB193, Aug. 15, 2016, 1 page. [cited by applicant]
Bodmer et al., “The molecular architecture of the TNF superfamily”, Trends in Biochemical Sciences, 2002, vol. 27, No. 1, pp. 19-26. [cited by applicant]
Bossen et al., “BAFF, APRIL and their receptors: Structure, function and signaling”, Seminars in Immunology, vol. 18, pp. 263-275. [cited by applicant]
Casset et al., “A Peptide Mimetic of an Anti-CD4 Monoclonal Antibody by Rational Design,” Biochemical and Biophysical Research Communications, 2003, vol. 307, pp. 198-205. [cited by applicant]
Chames et al., “Bispecific antibodies for cancer therapy—The light at the end of the tunnel?” rnAbs, 2009, vol. 1, No. 6, pp. 539-547. [cited by applicant]
Chames et al., “Bispecific antibodies for cancer therapy”, Curr Opin Drug Disc Devel., 2009, vol. 12, No. 2, pp. 276-283. [cited by applicant]
Chen et al., “Selection and Analysis of an Optimized Anti-VEGF Antibody: Crystal Structure of an Affinity Matured Fab in Complex with Antigen,” J. Mol. Biol., 1999, vol. 293, pp. 865-881. [cited by applicant]
Choi et al., “Bispecific antibodies engage T cells for antitumor immunotherapy”, Expert Opin Bio Ther., 2011, vol. 11, pp. 843-853. [cited by applicant]
Clayton et al., “CD311 and CD3' are alternatively spliced products of a common genetic locus and are 17 transcriptionally and/ or post-transcriptionally regulated during T-cell development”, PNAS, 1991, vol. 88, pp. 520… [cited by applicant]
Colman, “Effects of amino acid sequence changes on antibody-antigen interactions,” Research in Immunology, vol. 145, pp. 33-36, 1994. [cited by applicant]
De Pascalis et al., “Grafting of ‘Abbreviated’ Complementarity Determining Regions Containing|Specificity Determining Residues Essential for Ligand Contact to Engineer a Less Immunogenic Humanized Monoclonal Antibody,” … [cited by applicant]
Dillon et al., “An April to remember: novel TNF ligands as therapeutic targets”, Nature Reviews, 2006, vol. 5, pp. 235-246. [cited by applicant]
Enzo—Santa Cruz Biotechnology, Inc., “BCMA (Vicky-1): sc-57037—Product Data Sheet”, Dec. 20, 2019, 4 pages. [cited by applicant]
Fitzgerald et al., “Gene structure”, The Cytokine FactsBook, 2001, 5 pages. [cited by applicant]
Frank, A., [cited by applicant]
GenBank accession No. NM _000733, [cited by applicant]
GenBank— [cited by applicant]
Guy et al., “Organization of proximal signal initiation at the TCR: CD3 complex”, Immunol Review, 2009, vol. 232, Issue 1, pp. 7-21. [cited by applicant]
Hager-Braun et al., “Determination of protein-derived epitopes by mass spectrometry”, Expert Rev Proteomics, 2005, vol. 2, pp. 745-756. [cited by applicant]
Hipp et al., “A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo”, Leukemia, 2017, vol. 31, Issue 8, pp. 1743-1751. [cited by applicant]
Hönemann et al., “A novel recombinant bispecific single-chain antibody, bscWue-1 x CD3, induces T-cell-mediated cytotoxicity towards human multiple myeloma cells”, Leukemia, 2004, vol. 18, Issue 3, pp. 636-644. [cited by applicant]
Huang et al., “Mapping binding epitopes of monoclonal antibodies targeting major histocompatibility complex class I c 1ain-reiated A (MICA) with hydrogen/deuterium exchange and electron-transfer dissociation mass spectr… [cited by applicant]
Hymowitz, S.G., et al., “Structures of April-Receptor Complexes”, J Biol Chem., 2005, vol. 280, pp. 7218-7227. [cited by applicant]
Ito, W. et al., “The His-probe method: effects of histidine residues introduced into the complementary- determining regions of antibodies on antigen-antibody interactions at different pH values”, FEBS, Aug. 1992, vol. 3… [cited by applicant]
Kellner et al., “Effector Cell Recruitment by Bispecific Antibodies”, in [cited by applicant]
Kjer-Nielsen, L. et al., “Crystal structure of the human T cell receptor CD3ay heterodimer complexed to the therapeutic mAb OKT3”, PNAS, May 2004, vol. 101, Issue 20, pp. 7675-7680. [cited by applicant]
Koarada et al., “Autoantibody-producing RP105(-) B cells, from patients with systemic lupus erythematosus, showed more preferential expression of BCMA compared with BAFF-R than normal subjects”, Rheumatology, 2010, vol.… [cited by applicant]
Kontermann R.E., “Recombinant bispecific antibodies for cancer therapy”, Acta Pharmacologica Sinica, 2005, vol. 26, Issue 1, pp. 1-9. [cited by applicant]
Kontermann R.E., “Bispecific Antibodies: Developments and Current Perspectives”, in [cited by applicant]
Kontermann R.E., “Bispecific Antibodies: Developments and Current Perspectives”, in [cited by applicant]
Kufer, “A revival of bispecific antibodies”, Trends in Biotechnology, 2004, vol. 22, Issue 5, pp. 238-244. [cited by applicant]
Kuhns et al., “Deconstructing the Form and Function of the TCR/CD3 Complex” Immunity, 2006, vol. 24, pp. 133-139. [cited by applicant]
Lamminmaki et al., “Crystal Structure of a Recombinant Anti-estradiol Fab Fragment in Complex with 17ß-Estradiol,” The Journal of Biological Chemistry, vol. 276 (39), Sep. 28, 2001, pp. 36687-36694. [cited by applicant]
Leiba et al., “Activation of B-cell Maturation Antigen (BCMA)on Human Multiple Myeloma Cells by Proliferation-Inducing Ligand (APRIL) Promotes Myeloma Cell Function in the Bone Marrow Microenvironment”, Blood, 2007, vol… [cited by applicant]
Li et al., “Mapping the Energetic Epitope of an Antibody/Interleukin-23 Interaction with Hydrogen/Deuterium Exchange, Fast photochemical Oxidation of Proteins Mass Spectrometry, and Alanine Shave Mutagenesis”, Analyt Ch… [cited by applicant]
Liu, Y., et al., “Ligand-receptor binding revealed by the TNF family member TALL-1.”, Nature, 2003, vol. 423, Issue 6935, pp. 49-56. [cited by applicant]
Löfblom et al., “Alternative Scaffolds as Bispecific Antibody Mimetics”, in [cited by applicant]
Maccallum et al., “Antibody-antigen Interactions: Contact Analysis and Binding Site Topography,” J Mol Biol., 1996, vol. 262, pp. 732-745. [cited by applicant]
Müller et al., “Recombinant bispecific antibodies for cellular cancer immunotherapy”, Curr Opin Mol Thera., 2006, vol. 9, pp. 319-326. [cited by applicant]
Müller et al., “Recombinant Bispecific Antibodies for Cancer Therapy”, in [cited by applicant]
NCBI Reference Sequence NP 001183 (Apr. 26, 2014). [cited by applicant]
Neisig et al., “Assembly of the T-cell antigen receptor. Participation of the CD3 omega chain”, J Immunol., 1993, vol. 151, pp. 870-879. [cited by applicant]
Novak et al., “Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival”, Blood, 2004, vol. 103, pp. 689-694. [cited by applicant]
Padlan et al., “Structure of an Antibody-Antigen Complex: Crystal Structure of the HyHEL 10 Fab-Lysozyme Complex,” Proc. Natl. Acad. Sci., vol. 86, Aug. 1989, pp. 5938-5942. [cited by applicant]
Panowski et al., “Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma”, Molecular Cancer Therapeutics, 2019, vol. 18, No. 11, pp. 2008-202… [cited by applicant]
Patel et al., “Engineering an April-specific B cell maturation antigen”, J Biol Chem., 2004, vol. 279, Issue 16, pp. 16727-16735. [cited by applicant]
Pelekanou et al., “Expression of TNF-superfamily members BAFF and April in breast cancer . . . ” BMC Cancer, 2008, vol. 8, No. 76, pp. 1-9. [cited by applicant]
Puchades et al., “Epitope mapping of diverse influenza Hemagglutinin drug candidates using HDX-MS”, Sci Rep., 2019, vol. 9, Issue 1, 4735 in 10 pages. [cited by applicant]
Ramadoss, et al., “An Anti-B Cell Maturation Antigen Bispecific Antibody for Multiple Myeloma,” J Am Chem Soc., 2015, vol. 137, pp. 5288-5291. [cited by applicant]
Rennert et al., “A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor|family member April, inhibits tumor cell growth.” J Exp Med., 2000, vol. 192, Issue 11, pp. 1677-1683. [cited by applicant]
Rudikoff et al. “Single Amino Acid Substitution Altering Antigen Binding Specificity”, Proc. Natl. Acad. Sci., 1982, vol. 79, pp. 1979-1983. [cited by applicant]
Ryan, M.C., et al., “Antibody targeting of B-cell maturation antigen on malignant plasma cells”, Mol Cancer Ther, 2007, vol. 6, Issue 11, pp. 3009-3018. [cited by applicant]
Sequence alignment of BCMA extracellular domain; human, rhesus macaque, 1 page. [cited by applicant]
Sequence alignment of CD3 epsilon N-term aal-27; human, crab eating macaque, rhesus macaque, 1 page. [cited by applicant]
Sequence alignment of CD3 epsilon; crab-eating macaque, rhesus macaque, 1 page. [cited by applicant]
Terpos et al., “TRACP-5b: A Novel Marker for Monitoring Bisphosphonates Treatment in Multiple Myeloma”, Myeloma Biology II, 2002, Abstract #3204, p. 811a. [cited by applicant]
Thakur et al., “Cancer therapy with bispecific antibodies: Clinical experience.” Curr Opin Mol Ther., 2010, vol. 12, No. 3, pp. 340-349. [cited by applicant]
Vidal-Laliena et al., “Characterization of antibodies submitted to the B cell section of the 8th Human Leukocyte Differentiation . . . ”, Cellular Immunol., 2005, vol. 236, Issue 1-2, pp. 6-16. [cited by applicant]
Vajdos et al., “Comprehensive Functional Maps of the Antigen Binding Site of an Anti ErbB2 Antibody Obtained with Shotgun Scanning Mutagenesis,” J. Mol. Biol., 2002, vol. 320, pp. 415-428. [cited by applicant]
Wallweber et al., “The crystal structure of a proliferation—inducing ligand, April.”, J Mol Biol., 2004, vol. 343, Issue 2, pp. 283-290. [cited by applicant]
Walters et al., “Minimizing back exchange in the hydrogen exchange—mass spectrometry experiment.” J Am Soc Mass Spectrom., 2012, vol. 23, No. 12, pp. 2132-2139. [cited by applicant]
Wu et al., “Humanization of a Murine Monoclonal Antibody by Simultaneous Optimization of Framework and CDR Residues,” J. Mol. Biol., 1999, vol. 294, pp. 151-162. [cited by applicant]
Yu, L., et al., “Interaction between Bevacizumab and Murine VEGF-A: A Reassessment”, Investigative Ophthalmology & Visual Science, 2008, vol. 49, pp. 522-527. [cited by applicant]
Zhang et al., “Epitope mapping of a 95 kDa antigen in complex with antibody by solution—phase amide backbone hydrogen/deuterium exchange . . . ” Analytical Chemistry, 2011, vol. 83, Issue 18, pp. 7129-7136. [cited by applicant]
Zhang et al., “Epitope Mapping by HDX-MS Elucidates the Surface Coverage of Antigens Associated with High Blocking . . . ” Anal Chem., 2018, vol. 90, Issue 19, 11315-11323. [cited by applicant]
Zhang et al., “Epitope and Paratope Mapping of PD-1/Nivolumab by Mass Spectrometry-based Hydrogen/Deuterium Exchange, Cross-linking, and Molecular Docking”, Anal Chem., May 2020 online, vol. 92, Issue 13, pp. 9086-9094. [cited by applicant]
Declaration of Dr. Rui Zhu, Jun. 9, 2020, 34 pages. [cited by applicant]
Declaration Nathan D. Trinklein, Ph.D., Jun. 8, 2020, 22 pages. [cited by applicant]
Declaration of Kevin C. Lindquist, Jun. 9, 2020, 11 pages. [cited by applicant]
International Search Report and Written Opinion and International Search Report for International Application No. PCT/EP2012/072699; mailed on Mar. 27, 2013 in 14 pages. (WO 2013/072406). [cited by applicant]
Angeletti R., “Design of useful peptide antigens”, J Biomol Tech., 1999, vol. 10, Issue 1, pp. 2-10. [cited by applicant]
Carter et al., “Humanization of an anti-p185 [cited by applicant]
Chen et al., “Enhancement and Destruction of Antibody Function by Somatic Mutation: Unequal Occurrence is Controlled by V Gene Combinatorial Associations”, The EMBO Journal, vol. 14, No. 12, 1995, pp. 2784-2794. [cited by applicant]
Chien et al., “Significant structural and functional change of an antigen-binding site by a distant amino acid substitution: Proposal of a structural mechanism”, Proc. Natl. Acad. Sci. USA, Jul. 1989, vol. 86, pp. 5532-… [cited by applicant]
Cochran et al., “Domain-level antibody epitope mapping through yeast surface display of epidermal growth factor receptor fragments”, Journal of Immunological Methods, 2004, vol. 287, pp. 147-158. [cited by applicant]
Criado et al., “Variability of invariant mouse CD3epsilon chains detected by anti-CD3 antibodies ”, Eur J Immunol., 2000, vol. 30, Issue 5, pp. 1469-1479. [cited by applicant]
Da Costa et al., “Immune recruitment by bispecific antibodies for the treatment of Hodgkin disease”, Cancer Chemo Pharmacol., Springer Verlag, Berlin, 2000, vol. 46, No. Suppl, pp. S35-S36. [cited by applicant]
Dufner et al., “Harnessing phage and ribosome display for antibody optimisation”, Trends in Biotechnology, 2006, vol. 24, Issue 11, pp. 523-529. [cited by applicant]
Edwards et al., “The Remarkable Flexibility of the Human Antibody Repertoire; Isolation of Over One Thousand Different Antibodies to a Single Protein, BLyS”, J. Mol. Biol. vol. 334, No. 1, 2003, pp. 103-118. [cited by applicant]
Enzo Life Sciences, Inc. “BCMA (human) monoclonal antibody (Vicky-1)”, Product Data Sheet ALX-804-151, rev. Dec. 23, 2016 in 2 pages. [cited by applicant]
Gall, J. et al., “T cells armed with anti-CD3 x anti-CD20 bispecific antibody enhance killing of CD20+ malignant B cells and bypass complement-mediated rituximab resistance in vitro”, Exper Hematol., Apr. 2005, vol. 33,… [cited by applicant]
Gallart et al., “Anti-Sia-lb (anti-Gd) cold agglutinins bind the domain NeuNAc alpha2-3Gal in sialyl Lewis(x), sialyl Lewis(a), and related carbohydrates on nucleated cells and in soluble cancer-associated mucins”, Bloo… [cited by applicant]
Golay et al., “Mechanism of action of therapeutic monoclonalantibodies:Promises and pitfalls of invitroandinvivo assays”, Archives of Biochemistry and Biophysics, vol. 526, 2012, pp. 146-153. [cited by applicant]
Harlow et al., [cited by applicant]
Hay et al., “Cinical development success rates for investigational drugs”, Nature Biotechnology, vol. 32, Issue 1, Jan. 2014, pp. 40-51. [cited by applicant]
Hayashi et al., “A highly effective and stable bispecific diabody for cancer immunotherapy: cure of xenografted tumors by bispecific diabody and T-LAK cells”, Cancer Immunology, Immunotherapy: CII, Jun. 2004, vol. 53, N… [cited by applicant]
Kumar et al., “Preclinical models for pediatric solid tumor drug discovery: current trends, challenges and the scopes for improvement”, Expert Opinion Drug Discovery, 2012, vol. 7, No. 11, pp. 1093-1106. [cited by applicant]
Kussie et al., “A Single Engineered Amino Acid Substitution Changes Antibody Fine Specificity”, J Immunol., 1994, vol. 152, pp. 146-152. [cited by applicant]
Levine M.N., “Trastuzumab cardiac side effects: only time will tell”, J Clin Oncol. 2005, vol. 23, Issue 31, pp. 7775-7776. [cited by applicant]
Lloyd, C. et al. Modelling the Human Immune Response: Performance of a 1011 Human Antibody|Repertoire Against a Broad Panel of Therapeutically Relevant Antigens, Protein Engineering, Design & Selection, 2009, vol. 22, I… [cited by applicant]
Reusch, U. et al., “Effect of tetravalent bispecific CD19xCD3 recombinant antibody construct and CD28 costimulation on lysis of malignant B cells from patients with chronic lymphocytic leukemia by autologous T cells”, I… [cited by applicant]
Shalaby et al., “Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene”, J Exp Med., 1992, vol. 175, Issue 1, pp. 217-225. [cited by applicant]
Uniprot “Tumor necrosis factor receptor superfamily member 17”, Q02223-TNR17, Jul. 27, 2011, 8 pages. [cited by applicant]
Winkler et al., “Changing the Antigen Binding Specificity by Single Point Mutations of an Anti-p24 (HIV-1) Antibody”, The Journal of Immunology, 2000, vol. 165:4505-4514. [cited by applicant]
Yoshino et al., “Upgrading of flow cytometric analysis for absolute counts, cytokines and other antigenic molecules of cynomolgus monkeys ( [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/EP2012/072730; mailed on Mar. 27, 2013 in 14 pages. (WO 2013/072415). [cited by applicant]
International Search Report and Written Opinion and for International Application No. PCT/EP2011/070301; mailed on Jan. 6, 2012 in 11 pages. (WO 2012/066058). [cited by applicant]
Ansell et al., “Phase I/II Study of an Anti-CD30 Monoclonal Antibody (MDX-060) in Hodgkin's Lymphoma and Anaplastic Large-Cell Lymphoma”, J Clin Oncol., 2007, vol. 25, Issue 19, pp. 2764-2769, Opposition Exhibit D109. [cited by applicant]
Amgen—In-house data showing the KD of E1/E4-BCMA/CD3 Bispecific Antibodies and E3-BCMA/CD3 Bispecific Antibodies, 1 page, Feb. 1, 2021, Opposition Exhibit D101. [cited by applicant]
Bluemel et al., “Epitope Distance to the Target Cell Membrane and Antigen Size Determine the Potency of T Cell-mediated Lysis by BiTE Antibodies Specific for a Large Melanoma Surface Antigen”, Cancer Immunol Immunother.… [cited by applicant]
Declaration—Dr. Robert Saller, Amgen Research Executive Director, Jan. 2, 2010, 1 page, Opposition Exhibit D102. [cited by applicant]
Declaration—Dr. Kara Olson, Regeneron Senior Staff Scientist, 5 pages, May 14, 2021, Opposition Exhibit D107. [cited by applicant]
Caldas et al., “Humanization of the anti-CD18 antibody 6.7: an unexpected effect of a framework residue in binding to antigen”, Mol Immunol., 2003, vol. 39, pp. 941-952. [cited by applicant]
European Medicines Agency, The [EMA], “Herceptin: EPAR—Scientific Discussion”, EMA Oct. 21, 2005, pp. 1-42. [cited by applicant]
Even-Desrumeaux et al., “State of the Art in Tumor Antigen and Biomarker Discovery”, Cancers 2011, vol. 3, pp. 2554-2596, Opposition Exhibit D116. [cited by applicant]
Frank S.A., “Specificity and Cross-Reactivity” in [cited by applicant]
Genbank—Accession No. AB052772.1, “ [cited by applicant]
Genentech, Inc., Package Insert for Herceptin® (Trastuzumab), Sep. 26, 2003, pp. 1-14. [cited by applicant]
Gruss et al., “Structural and Biological Features of the TNF Receptor and TNF Ligand Superfamilies: Interactive Signals in the Pathobiology of Hodgkin's Disease”, Anals Oncol. 1996, vol. 7, (Suppl.4), pp. S19-S26, Oppos… [cited by applicant]
Hansen et al., “Treatment of CD30-positive Diseases, Such as Hodgkin's Lymphoma, by Administration of a Combination of Sheddase Inhibitor and Anti-CD30 Immunotherapeutic Agents”, Exp Opin Ther Patents, 2008, vol. 18, Is… [cited by applicant]
Janeway et al. [Eds.], Figure 6.8, “The T-cell receptor complex is made up of antigen-recognition proteins and invariant signaling proteins”, in Immunobiology: The Immune System in Health and Disease, 5 [cited by applicant]
Jubala et al., “CD20 Expression in Normal Canine B Cells and in Canine non-Hodgkin Lymphoma”, Vet Pathol., 2005, vol. 42, 468-476. [cited by applicant]
Kapoor et al., “Anti-CD20 Monoclonal Antibody Therapy in Multiple Myeloma”, Br J Haematol. 2008, vol. 141, Issue 2, pp. 135-148, Opposition Exhibit D103. [cited by applicant]
Levine S.J., “Mechanisms of Soluble Cytokine Receptor”, J Immunol., 2004, vol. 173, pp. 5343-5348, Opposition Exhibit D95. [cited by applicant]
Matthey et al., “Metalloproteinase Inhibition Augments Antitumor Efficacy of the Anti-DC30 Immunotoxin Ki-3(scFv)-ETA' Against Human Lymphomas In Vivo”, Int J Cancer, 2004, vol. 111, pp. 568-574, Opposition Exhibit D113. [cited by applicant]
Moreaux et al., “April and TACI interact with syndecan-1 on the surface of multiple myeloma cells to form an essential survival loop”, European J Haematol., 2009, vol. 83, Issue 2, pp. 119-129, Opposition Exhibit D34. [cited by applicant]
Muller et al., “The Minimum Anticipated Biological Effect Level (MABEL) for Selection of First Human Dose in Clinical Trials with Monoclonal Antibodies”, Curr Opin Biotech. 2009, vol. 20, pp. 722-729, Opposition Exhibit… [cited by applicant]
Reichert et al., “Development Trends for Monoclonal Antibody Cancer Therapeutics”, Nat Reviews Drug Disc., May 2007, vol. 6, pp. 349-356, Opposition Exhibit D96. [cited by applicant]
Sanchez et al., “Serum B-cell Maturation Antigen is Elevated in Multiple Myeloma and Correlates with Disease Status and Survival”, Br J Haematol. 2012, vol. 158, Issue 6, pp. 727-728, Opposition Exhibit D97. [cited by applicant]
Tarte et al., “BAFF Is a Survival Factor for Multiple Myeloma Cells”, Myeloma Biology II, Abstract #3203/623-III, p. 811a, 2002, Opposition Exhibit D39. [cited by applicant]
Topp et al., “Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma”, J Clin Oncol. 2020, vol. 38, pp. 775-783, Opposition Exhibit D98. [cited by applicant]
Verkleij et al., “T-cell Redirecting Bispecific Antibodies Targeting BCMA for the Treatment of Multiple Myeloma”, Oncotarget, 2020, vol. 11, Issue 45, pp. 4076-4081, Opposition Exhibit D118. [cited by applicant]
Vonderheide et al., “Clinical Activity and Immune Modulation in Cancer Patients Treated with CP-870,893, a Novel CD40 Agonist Monoclonal Antibody”, J Clin Oncol. 2007, vol. 25, Issue 7, pp. 876-883, Opposition Exhibit D… [cited by applicant]
Who, International Nonproprietary Names for Pharmaceutical Substances (Proposed INN)—List 123 ‘Pacanalotamab’, WHO Drug Information, 2020, vol. 34, Issue 2, in 5 pages, Opposition Exhibit D100. [cited by applicant]
Zhang et al., “Epitope and Paratope Mapping of PD-1/Nivolumab by Mass Spectrometry-based Hydrogen/Deuterium Exchange, Cross-linking, and Molecular Docking”, Anal Chem. May 22, 2020, vol. 92, Issue 13, 9086-9094, Opposit… [cited by applicant]
EP Notice of Opposition by AbbVie Inc. [O1] filed Mar. 6, 2020 against EP 2780375, granted Sep. 11, 2019, 9 pages. [cited by applicant]
EP Opposition Brief by AbbVie Inc. [O1] filed Jun. 11, 2020 in opposition to EP 2780375, 109 pages. [cited by applicant]
EP Communication Re Supplementary Submissions by AbbVie Inc. [O1] and Regeneron Pharmaceuticals, Inc. [05] filed May 18 & 19, 2021 in opposition to EP 2780375, 110 pages. [cited by applicant]
EP Notice of Opposition by Janssen Biotech, Inc. [O2] filed Apr. 14, 2020 against EP 2780375, granted Sep. 11, 2019, 7 pages. [cited by applicant]
EP Opposition Brief by Janssen Biotech, Inc. [O2] filed Apr. 14, 2020 in opposition to EP 2780375, 74 pages. [cited by applicant]