IP Library › Granted Patent US 12,668,638
Granted Patent B2
US 12,668,638 · App. 18/446,795 · Granted Jun 30, 2026

Antibodies that bind EGFR and cMET

Inventors: Cecilia Anna Wilhelmina Geuijen (Utrecht, NL); Robertus Cornelis Roovers (Utrecht, NL); Mark Throsby (Utrecht, NL); Cornelis Adriaan De Kruif (Utrecht, NL); Ton Logtenberg (Utrecht, NL)
Assignee: Merus B.V.
C07K16/2863A61P35/00C07K16/40A61K2039/505C07K2317/21C07K2317/31C07K2317/33C07K2317/35C07K2317/526C07K2317/565C07K2317/732C07K2317/76
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,668,638
App. No.
18/446,795
Filed
Aug 9, 2023
Granted
Jun 30, 2026
Kind
B2
Examiner
LI, RUIXIANG
Art Unit
1674
USPC
424/136.1
Abstract

The invention as disclosed herein relates to bispecific antibodies that comprises a first variable domain that can bind an extracellular part of epidermal growth factor receptor (EGFR) and a second variable domain that can bind an extracellular part of MET Proto-Oncogene, Receptor Tyrosine Kinase (cMET). The antibody may comprise a common light chain. It may be a human antibody. The antibody may be a full-length antibody. In some aspects, the bispecific antibody is an IgG1 format antibody having an anti-EGFR, anti-cMET stoichiometry of 1:1. In some aspects, the antibody has one variable domain that can bind EGFR and one variable domain that can bind cMET.

Claims (37)

1 . A method of treating a tumor in a subject, wherein the tumor is an EGFR positive tumor, a cMET positive tumor, or an EGFR and a cMET positive tumor, the method comprising administering to an individual in need thereof a bispecific antibody that comprises a first variable domain that can bind an extracellular part of human epidermal growth factor receptor (EGFR) and a second variable domain that can bind an extracellular part of human MET Proto-Oncogene, Receptor Tyrosine Kinase (cMET);

wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNANTNYAQKLQG (SEQ ID NO:155), and a CDR3 comprising the sequence DRHWHWWLDA (SEQ ID NO:139), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31); or

wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYSGNTNYAQKLQG (SEQ ID NO:140), and a CDR3 comprising the sequence DRHWHWWLDA (SEQ ID NO:139), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31); or

wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYSGNTNYAQKLQG (SEQ ID NO:140), and a CDR3 comprising the sequence DRHWHWWLDA (SEQ ID NO:139), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence SYSMN (SEQ ID NO: 28), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO: 157), and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30); or

wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNANTNYAQKLQG (SEQ ID NO:155), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO: 37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence SYSMN (SEQ ID NO: 28), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO: 157), and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30); or

wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNGNTNYAQKLQG (SEQ ID NO:113), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO: 37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31); or

wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNGNTNYAQKLQG (SEQ ID NO:113), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO: 37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence SYSMN (SEQ ID NO: 28), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO: 157), and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30); and

wherein the first and second variable domains further comprise a common light chain variable domain comprising a CDR1 sequence QSISSY (SEQ ID NO:38), a CDR2 sequence AAS, and a CDR3 sequence QQSYSTP (SEQ ID NO: 39).

2 . The method of claim 1 , wherein the tumor is a tumor of breast cancer, colon cancer, pancreatic cancer, gastric cancer, ovarian cancer, colorectal cancer, head and neck cancer, lung cancer, or bladder cancer.

3 . The method of claim 2 , wherein the cancer is lung cancer.

4 . The method of claim 1 , wherein the tumor is resistant to treatment with an EGFR tyrosine kinase inhibitor.

5 . The method of claim 4 , wherein the EGFR tyrosine kinase inhibitor is erlotinib, gefitinib, afatinib, or a combination of thereof.

6 . The method of claim 4 , wherein the EGFR tyrosine kinase inhibitor is erlotinib.

7 . The method of claim 1 , further comprising administering erlotinib to the individual in need thereof.

8 . The method of claim 7 , wherein the said bispecific antibody is administered simultaneously, sequentially or separately with said EGFR tyrosine kinase inhibitor.

9 . The method of claim 1 , wherein the heavy chain variable region of the second variable domain comprises the amino acid sequence of SEQ ID NO:13.

10 . The method of claim 1 , wherein the heavy chain variable region of the second variable domain comprises the amino acid sequence of SEQ ID NO: 23.

11 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNANTNYAQKLQG (SEQ ID NO:155), and a CDR3 comprising the sequence DRHWHWWLDA (SEQ ID NO:139), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31).

12 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNANTNYAQKLQG (SEQ ID NO:155), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO: 37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31).

13 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYSGNTNYAQKLQG (SEQ ID NO: 140), and a CDR3 comprising the sequence DRHWHWWLDA (SEQ ID NO: 139), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31).

14 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYSGNTNYAQKLQG (SEQ ID NO: 140), and a CDR3 comprising the sequence DRHWHWWLDA (SEQ ID NO: 139), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence SYSMN (SEQ ID NO: 28), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30).

15 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:79 and the second variable domain comprises the amino acid sequence of SEQ ID NO:13.

16 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:80 and the second variable domain comprises the amino acid sequence of SEQ ID NO:13.

17 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 78 and the second variable domain comprises the amino acid sequence of SEQ ID NO:13.

18 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYSGNTNYAQKLQG (SEQ ID NO:140), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO:37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence SYSMN (SEQ ID NO: 28), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO: 157), and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30).

19 . The method of claim 18 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNANTNYAQKLQG (SEQ ID NO:155), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO: 37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence SYSMN (SEQ ID NO: 28), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO: 157), and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30).

20 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNGNTNYAQKLQG (SEQ ID NO:113), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO: 37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31).

21 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNGNTNYAQKLQG (SEQ ID NO:113), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO: 37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence SYSMN (SEQ ID NO: 28), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO: 157), and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30).

22 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYSGNTNYAQKLQG (SEQ ID NO: 140), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO: 37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31).

23 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYSGNTNYAQKLQG (SEQ ID NO:140), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO:37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence SYSMN (SEQ ID NO: 28), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO: 157), and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30).

24 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region with a CDR1 sequence SYGIS (SEQ ID NO: 24), a CDR2 sequence WISAYNANTNYAQKLQG (SEQ ID NO:155), and a CDR3 comprising the sequence DRHWHWWLDAFDY (SEQ ID NO:37), and wherein the second variable domain comprises a heavy chain variable region with a CDR1 sequence TYSMN (SEQ ID NO: 152), a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO:157), and a CDR3 comprising the sequence ETYFYDRGGYPFDP (SEQ ID NO: 31).

25 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:79 and the second variable domain comprises the amino acid sequence of SEQ ID NO:23.

26 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:80 and the second variable domain comprises the amino acid sequence of SEQ ID NO:23.

27 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:78 and the second variable domain comprises the amino acid sequence of SEQ ID NO:23.

28 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:78.

29 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:79.

30 . The method of claim 1 , wherein the first variable domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:80.

Assignments (4)
CHANGE OF NAME Recorded May 27, 2026
From: MERUS N.V.
To: MERUS B.V.
Reel/Frame 075715/0280 →
NOTICE OF GRANT OF SECURITY INTEREST IN PATENTS Recorded Jan 30, 2026
From: MERUS B.V.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 074562/0322 →
SECURITY INTEREST Recorded Jan 29, 2026
From: MERUS B.V.
To: MORGAN STANLEY SENIOR FUNDING, INC.
Reel/Frame 074532/0434 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 10, 2025
From: GEUIJEN, CECILIA ANNA WILHELMINA; ROOVERS, ROBERTUS CORNELIS; THROSBY, MARK; DE KRUIF, CORNELIS ADRIAAN; LOGTENBERG, TON
To: MERUS N.V.
Reel/Frame 070803/0780 →
Priority Claims (1)
EP 17185572 · Aug 9, 2017 · regional
Continuity (2)
Division 16637464
Related Publication 20240174756A1 · May 30, 2024
References Cited (300)
US 4801687A · Ngo · 1989 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 5151504A · Croze · 1992 [cited by applicant]
US 5731168A · Carter et al. · 1998 [cited by applicant]
US 7642228B2 · Carter et al. · 2010 [cited by applicant]
US 7705103B2 · Sherman et al. · 2010 [cited by applicant]
US 8349574B2 · Bates et al. · 2013 [cited by applicant]
US 8592562B2 · Kannan et al. · 2013 [cited by applicant]
US 8628774B2 · Gurney et al. · 2014 [cited by applicant]
US 9220775B2 · Chowdhury et al. · 2015 [cited by applicant]
US 9248181B2 · De Kruif et al. · 2016 [cited by applicant]
US 9248182B2 · De Kruif et al. · 2016 [cited by applicant]
US 9358286B2 · De Kruif et al. · 2016 [cited by applicant]
US 9551208B2 · Ma et al. · 2017 [cited by applicant]
US 9758805B2 · De Kruif et al. · 2017 [cited by applicant]
US 9914777B2 · Bakker et al. · 2018 [cited by applicant]
US 9968676B2 · Adler et al. · 2018 [cited by applicant]
US 10208354B2 · Fernandez-Cuesta et al. · 2019 [cited by applicant]
US 10358492B2 · Bakker et al. · 2019 [cited by applicant]
US 10416162B2 · Huang et al. · 2019 [cited by applicant]
US 10844127B2 · Logtenberg et al. · 2020 [cited by applicant]
US 11773170B2 · Geuijen et al. · 2023 [cited by applicant]
US 20030078385A1 · Arathoon et al. · 2003 [cited by applicant]
US 20040071696A1 · Adams et al. · 2004 [cited by applicant]
US 20060212956A1 · Crocker et al. · 2006 [cited by applicant]
US 20090181022A1 · Nielsen et al. · 2009 [cited by applicant]
US 20090182127A1 · Kjaergaard et al. · 2009 [cited by applicant]
US 20090191559A1 · Huang et al. · 2009 [cited by applicant]
US 20100015133A1 · Igawa et al. · 2010 [cited by applicant]
US 20100183615A1 · Kufer et al. · 2010 [cited by applicant]
US 20100286374A1 · Kannan et al. · 2010 [cited by applicant]
US 20110077163A1 · Doranz · 2011 [cited by applicant]
US 20110195454A1 · Mcwhirter et al. · 2011 [cited by applicant]
US 20120107234A1 · Pedersen et al. · 2012 [cited by applicant]
US 20120107306A1 · Elis et al. · 2012 [cited by applicant]
US 20120270801A1 · Frejd et al. · 2012 [cited by applicant]
US 20120328623A1 · Takahashi · 2012 [cited by applicant]
US 20130071859A1 · Bates et al. · 2013 [cited by applicant]
US 20130084297A1 · Daly et al. · 2013 [cited by applicant]
US 20130095116A1 · Gurney et al. · 2013 [cited by applicant]
US 20130115208A1 · Ho et al. · 2013 [cited by applicant]
US 20130156779A1 · Clarke et al. · 2013 [cited by applicant]
US 20130185821A1 · Babb et al. · 2013 [cited by applicant]
US 20130251703A1 · Elis et al. · 2013 [cited by applicant]
US 20130259867A1 · Amler et al. · 2013 [cited by applicant]
US 20130336885A1 · Hongo et al. · 2013 [cited by applicant]
US 20130336981A1 · De Kruif et al. · 2013 [cited by applicant]
US 20130344093A1 · Daly et al. · 2013 [cited by applicant]
US 20140056898A1 · Zhang et al. · 2014 [cited by applicant]
US 20140072579A1 · De Kruif et al. · 2014 [cited by applicant]
US 20140120096A1 · Bakker et al. · 2014 [cited by applicant]
US 20140140999A1 · De Kruif et al. · 2014 [cited by applicant]
US 20140141019A1 · Kharrat et al. · 2014 [cited by applicant]
US 20140378664A1 · Suh et al. · 2014 [cited by applicant]
US 20150013996A1 · Davies et al. · 2015 [cited by applicant]
US 20150139996A1 · De Kruif et al. · 2015 [cited by applicant]
US 20150196637A1 · De Kruif et al. · 2015 [cited by applicant]
US 20150259423A1 · Kirshner et al. · 2015 [cited by applicant]
US 20160031984A1 · Reyes et al. · 2016 [cited by applicant]
US 20160229920A1 · Ward et al. · 2016 [cited by applicant]
US 20160367699A1 · Jackson et al. · 2016 [cited by applicant]
US 20170037145A1 · Geuijen et al. · 2017 [cited by applicant]
US 20170166653A1 · Garner et al. · 2017 [cited by applicant]
US 20200247892A1 · Geuijen et al. · 2020 [cited by applicant]
AU 2014212081A1 · 2015 [cited by applicant]
CN 103002916B · 2016 [cited by applicant]
EP 0120694A2 · 1984 [cited by applicant]
EP 0314161A1 · 1989 [cited by applicant]
EP 0481790A2 · 1992 [cited by applicant]
EP 0523949A1 · 1993 [cited by applicant]
EP 0870459A2 · 1998 [cited by applicant]
EP 2604625A1 · 2013 [cited by applicant]
JP H11500915A · 1999 [cited by applicant]
JP 2008531557A · 2008 [cited by applicant]
JP 2011508604A · 2011 [cited by applicant]
JP 2012509259A · 2012 [cited by applicant]
JP 2014508782A · 2014 [cited by applicant]
JP 2014511383A · 2014 [cited by applicant]
JP 2017507944A · 2017 [cited by applicant]
WO WO9627011A1 · 1996 [cited by applicant]
WO WO9850431A2 · 1998 [cited by applicant]
WO WO0063403A2 · 2000 [cited by applicant]
WO WO0120694A1 · 2001 [cited by applicant]
WO WO03004704A2 · 2003 [cited by applicant]
WO WO03107218A1 · 2003 [cited by applicant]
WO WO2004009618A2 · 2004 [cited by applicant]
WO WO2004061104A2 · 2004 [cited by applicant]
WO WO2005000894A2 · 2005 [cited by applicant]
WO WO2005118635A2 · 2005 [cited by applicant]
WO WO2006028936A2 · 2006 [cited by applicant]
WO WO2006044908A2 · 2006 [cited by applicant]
WO WO2006091209A2 · 2006 [cited by applicant]
WO WO2006106905A1 · 2006 [cited by applicant]
WO WO2007110205A2 · 2007 [cited by applicant]
WO WO2007147901A1 · 2007 [cited by applicant]
WO WO2008027236A2 · 2008 [cited by applicant]
WO WO2008100624A2 · 2008 [cited by applicant]
WO WO2008119353A1 · 2008 [cited by applicant]
WO WO2008140493A2 · 2008 [cited by applicant]
WO WO2009051974A1 · 2009 [cited by applicant]
WO WO2009080251A1 · 2009 [cited by applicant]
WO WO2009080252A1 · 2009 [cited by applicant]
WO WO2009080253A1 · 2009 [cited by applicant]
WO WO2009089004A1 · 2009 [cited by applicant]
WO WO2009098596A2 · 2009 [cited by applicant]
WO WO2009157771A2 · 2009 [cited by applicant]
WO WO2010022736A2 · 2010 [cited by applicant]
WO WO2010059315A1 · 2010 [cited by applicant]
WO WO2010084197A1 · 2010 [cited by applicant]
WO WO2010108127A1 · 2010 [cited by applicant]
WO WO2010129304A2 · 2010 [cited by applicant]
WO WO2010151792A1 · 2010 [cited by applicant]
WO WO2011022727A2 · 2011 [cited by applicant]
WO WO2011028952A1 · 2011 [cited by applicant]
WO WO2011028953A1 · 2011 [cited by applicant]
WO WO2011143545A1 · 2011 [cited by applicant]
WO WO2011151412A1 · 2011 [cited by applicant]
WO WO2012023053A2 · 2012 [cited by applicant]
WO WO2012058768A1 · 2012 [cited by applicant]
WO WO2012116317A2 · 2012 [cited by applicant]
WO WO2012125573A2 · 2012 [cited by applicant]
WO WO2012125864A2 · 2012 [cited by applicant]
WO WO2012131555A2 · 2012 [cited by applicant]
WO WO2012140274A9 · 2013 [cited by applicant]
WO WO2013048883A2 · 2013 [cited by applicant]
WO WO2013084151A2 · 2013 [cited by applicant]
WO WO2013107218A1 · 2013 [cited by applicant]
WO WO2013134686A1 · 2013 [cited by applicant]
WO WO2013149159A1 · 2013 [cited by applicant]
WO WO2013157953A1 · 2013 [cited by applicant]
WO WO2013157954A1 · 2013 [cited by applicant]
WO WO2014051433A1 · 2014 [cited by applicant]
WO WO2014060365A1 · 2014 [cited by applicant]
WO WO2014081954A1 · 2014 [cited by applicant]
WO WO2014159580A1 · 2014 [cited by applicant]
WO WO2014165855A1 · 2014 [cited by applicant]
WO WO2014182970A1 · 2014 [cited by applicant]
WO WO2015130172A1 · 2015 [cited by applicant]
WO WO2015130173A1 · 2015 [cited by applicant]
WO WO2016077734A2 · 2016 [cited by applicant]
WO WO2016090024A2 · 2016 [cited by applicant]
WO WO2017053856A1 · 2017 [cited by applicant]
WO WO2017069628A2 · 2017 [cited by applicant]
WO WO2018182422A1 · 2018 [cited by applicant]
Castoldi, R., et al., “A Novel Bispecific EGFR/Met Antibody Blocks Tumor-promoting Phenotypic Effects Induced by Resistance to EGFR Inhibition and Has Potent Antitumor Activity,” Oncogene 32(50):5593-5601, Nature Publis… [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/NL2018/050537, mailed on Jan. 30, 2019, European Patent Office, Rijswijk, Netherlands, 19 pages. [cited by applicant]
Labrijn, A.F., et al., “Efficient Generation of Stable Bispecific IgG1 by Controlled Fab-arm Exchange,” Proceedings of the National Academy of Sciences of the United States of America 110(13):5145-5150, United States (M… [cited by applicant]
Moores, S.L., et al., “A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors,” Cancer Research 76(13):3942-3953, United States (May 2016). [cited by applicant]
Mosmi, S., et al., “Role of MetMAb (OA-5D5) in c-MET Active Lung Malignancies,” Expert Opinion on Biological Therapy 11(12):1655-1662, Taylor & Francis, England (Dec. 2011). [cited by applicant]
Park, N.J., et al., “Measurement of Cetuximab and Panitumumab-Unbound Serum EGFR Extracellular Domain Using an Assay Based on Slow Off-Rate Modified Aptamer (SOMAmer) Reagents,” PloS One 8(8):e71703, Public Library of S… [cited by applicant]
Pan, D.S., et al., “Binding Characteristic of Fully Human Anti-EGFR Monoclonal Antibody to EGFR in Skin Tissues of Different Species of Animals,” Chinese Journal of New Drugs Co. Ltd 21(1):26-30, China (Jan. 2012). [cited by applicant]
Agus, D.B., et al., “Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth,” Cancer Cell 2(2): 127-137, Cell Press, United States (Aug. 2002). [cited by applicant]
Appella, E, and IT Weber, F Blasi, “Structure and Function of Epidermal Growth Factor-Like Regions In Proteins,” FEBS Letters 231(1):1-4, John Wiley & Sons Ltd, United Kingdom (Apr. 1988). [cited by applicant]
Ardeshirpour, Y., et al., “In vivo assessment of HER2 receptor density in HER2-positive tumors by near-infrared imaging, using repeated injections of the fluorescent probe,” Technology In Cancer Research & Treatment 13(… [cited by applicant]
Arteaga, C.L., et al., “Treatment of Her2-positive Breast Cancer: Current Status and Future Perspectives,” Nature Reviews Clinical Oncology 9(1):16-32, Nature Publishing Group, United Kingdom (Nov. 2011). [cited by applicant]
Bakker, A.B., et al., “C-type Lectin-like Molecule-1: a Novel Myeloid Cell Surface Marker Associated With Acute Myeloid Leukemia,” Cancer Research 64(22):8443-8450, American Association for Cancer Research, United State… [cited by applicant]
Balko, J.M., et al., The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. PNAS, 109(1): 221-226, U.S. National Academy of Science, United States (Jan. 2012). [cited by applicant]
Birchmeier, C., et al., “Met, Metastasis, Motility and More,” Nature Reviews Molecular Cell Biology 4(12):915-925, Nature Publishing Group, United Kingdom (Dec. 2003). [cited by applicant]
Buday, L. et al., “Epidermal growth factor regulates the exchange rate of guanine nucleotides on p21ras in fibroblasts,” Molecular and Cellular Biology 13(3):1903-1910, American Society for Microbiology, United States (… [cited by applicant]
Chames, P., and Baty, D., “Bispecific Antibodies for Cancer Therapy: The Light at the End of the Tunnel?” MAbs 1(6):539-547, Taylor & Francis, United States (Nov.-Dec. 2009). [cited by applicant]
Chandra, A., “The Role of ERBB3 Inhibitors as Cancer Therapeutics,” pp. 1-78, Boston University School of Medicine, United States (May 2015). [cited by applicant]
Chen, C.T., et al., “MET activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells,” Molecular Cancer Therapeutics 11(3):650-669, American Association for Cancer Research, Inc., Unite… [cited by applicant]
Chernomordik, V., et al., “Quantitative Analysis of HER2 Receptor Expression in Vivo By Near-Infrared Optical Imaging,” Molecular Imaging 9(4):192-200, SAGE Publications, United States (Aug. 2010). [cited by applicant]
Chien, N.C., et al., “Significant Structural and Functional Change of an Antigen-Binding Site by a Distant Amino Acid Substitution: Proposal of a Structural Mechanism,” Proceedings of the National Academy of Sciences US… [cited by applicant]
Conforti, F., et al., “Dissecting Breast Cancer Complexity: Specific Biological Features and Vulnerabilities of Triple Positive Breast Cancer Tumors,” Clinic of Oncology 2(1288):1-3, Remedy Publications LLC, United Stat… [cited by applicant]
Corona S.P., et al., “CDK4/6 Inhibitors in HER2-positive Breast Cancer,” Critical Reviews in Oncology/Hematology 118:208-214, Elsevier, Netherlands (2017). [cited by applicant]
Cui, H., et al., “Chemically Programmed Bispecific Antibodies That Recruit and Activate T Cells,” The Journal of Biological Chemistry 287(34):28206-28214, American Society for Biochemistry and Molecular Biology, United … [cited by applicant]
Curley, M.D., et al., “Seribantumab, An Anti-ERBB3 Antibody, Delays the Onset of Resistance and Restores Sensitivity to Letrozole in an Estrogen Receptor-Positive Breast Cancer Model,” Molecular Cancer Therapeutics 14(1… [cited by applicant]
De Kruif, J., et al., “Selection and Application of Human Single Chain Fv Antibody Fragments from a Semi-Synthetic Phage Antibody Display Library with Designed CDR3 Regions,” Journal of Molecular Biology 248(1):97-105, … [cited by applicant]
De Kruif, J., et al., “Generation of Stable Cell Clones Expressing Mixtures of Human Antibodies,” Biotechnology and Bioengineering 106(5):741-750, Wiley, United States (Aug. 2010). [cited by applicant]
Dreier, T., et al., “Extremely Potent, Rapid and Costimulation-Independent Cytotoxic T-Cell Response against Lymphoma Cells Catalyzed By a Single-Chain Bispecific Antibody,” International Journal of Cancer 100(6):690-69… [cited by applicant]
Fong, J.T., et al., “Alternative signaling pathways as potential therapeutic targets for overcoming EGFR and c-Met inhibitor resistance in non-small cell lung cancer,” PLoS One 8(11):e78398, Public Library of Science, U… [cited by applicant]
Fu, W., et al., “Insights into HER2 signaling from step-by-step optimization of anti-HER2 antibodies,” MAbs 6(4):978-990, Taylor & Francis, United Kingdom (Apr. 2014). [cited by applicant]
Gaborit, N., et al., “Emerging anti-cancer antibodies and combination therapies targeting HER3/ERBB3,” Human Vaccines and Immunotherapies, 12(3): 576-592, Taylor & Francis, United Kingdom (Nov. 2015). [cited by applicant]
Geuijen, C., et al., “Abstract LB-261: Mechanism of action of MCLA-128, a humanized bispecific IgG1 antibody targeting the HER2: HER3 heterodimer,” Cancer Research; 106th Annual Meeting of The American Association for C… [cited by applicant]
Geuijen, C.A.W., et al., “Unbiased Combinatorial Screening Identifies a Bispecific IgG1 that Potently Inhibits HER3 Signaling via HER2-Guided Ligand Blockade,” Cancer Cell 33(5):922-936, Elsevier, Netherlands (May 2018). [cited by applicant]
Gulli, L.F., et al., “Epidermal Growth Factor-induced Apoptosis in A431 Cells Can Be Reversed by Reducing the Tyrosine Kinase Activity,” Cell Growth & Differentiation 7(2):173-178, The Association, United States (Feb. 1… [cited by applicant]
Harms B., et al., “Understanding the Role of Cross-arm Binding Efficiency in the Activity of Monoclonal and Multispecific Therapeutic Antibodies”, Methods 65(1):95-104, Elsevier, Netherlands (Jan. 2014). [cited by applicant]
Hathaway, H.J., et al., “Detection of breast cancer cells using targeted magnetic nanoparticles and ultra-sensitive magnetic field sensors,” Breast Cancer Research 13(5):R108, BioMed Central, United Kingdom (Nov. 2011). [cited by applicant]
Hommel, U., et al., “Human Epidermal Growth Factor. High Resolution Solution Structure And Comparison With Human Transforming Growth Factor Alpha,” Journal of Molecular Biology 227(1):271-282, Elsevier, United Kingdom (… [cited by applicant]
Howarth, K.D., et al., “Nrg1 Fusions in Breast Cancer,” Breast Cancer Research 23(1):3, BioMed Central Ltd, United Kingdom (Jan. 2021). [cited by applicant]
Hu, T., and Li, C., “Convergence between Wnt-B-catenin and EGFR signaling in cancer,” Molecular Cancer 236: 1-7, BioMed Central, United States (Sep. 2010). [cited by applicant]
Huang W, et al., “Comparison of Central HER2 Testing With Quantitative Total HER2 Expression and HER2 Homodimer Measurements Using a Novel Proximity-Based Assay,” American Journal of Clinical Pathology 134(2):303-311, O… [cited by applicant]
Huhalov, A., et al., “MM-111, an ErbB2/ErbB3 Bispecific Antibody with Potent Activity in ErbB2-Overexpressing Cells, Positively Combines with Trastuzumab to Inhibit Growth of Breast Cancer Cells Driven by the ErbB2/ErbB… [cited by applicant]
International Search Report And Written Opinion for International Application No. PCT/NL2016/050726, European Patent Office, Netherlands, mailed Jun. 2, 2017, 20 pages. [cited by applicant]
Jackson, C., et al., “Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance,” International Journal of Cell Biology 2013: 973584, Hindawi, United Kingdom (Jul. 2013). [cited by applicant]
Jelovac, D., et al., “HER2-Directed Therapy for Metastatic Breast Cancer,” Oncology (Williston Park) 27(3):166-175, CMP Healthcare Media, United States (Mar. 2013). [cited by applicant]
Ji, H., et al., “Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors,” PNAS 103(20):7817-7822, United States National Academy of Sciences, United St… [cited by applicant]
Jin, H., et al., “Metmab, the One-Armed 5D5 Anti-C-Met Antibody, Inhibits Orthotopic Pancreatic Tumor Growth and Improves Survival,” Cancer Research 68(11):4360-4368, American Association for Cancer Research, United Sta… [cited by applicant]
Jorissen, R.N., et al., “Epidermal Growth Factor Receptor: Mechanisms of Activation and Signaling,” Experimental Cell Research 284(1):31-53, Academic Press, United States (Mar. 2003). [cited by applicant]
Jung, Y., et al., “VAMP2-NRG1 Fusion Gene is a Novel Oncogenic Driver of Non-Small-Cell Lung Adenocarcinoma,” J Thor Oncol 10(7): 1107-1111, International Association for the Study of Lung Cancer, United States (2015). [cited by applicant]
Junttila, T.T., et al., “Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941,” Cancer Cell, 15(5):429-440, Elsevier, Netherlands (2009). [cited by applicant]
Kang, J.C., et al., “Engineering Multivalent Antibodies to Target Heregulin-Induced HER3 Signaling in Breast Cancer Cells,” MAbs 6(2):340-353, Taylor & Francis, United Kingdom (Apr. 2014). [cited by applicant]
Kim, G.P., et al. “Targeting Colorectal Cancer with Human Anti-EGFR Monoclonocal Antibodies: Focus on Panitumumab,” Biologics 2(2):223-228, Dove Medical Press, New Zealand (Jun. 2008). [cited by applicant]
Kim, K.H., et al., “Progress of Antibody-Based Inhibitors of the Hgf-Cmet Axis in Cancer Therapy,” Experimental & Molecular Medicine 49(3):e307, Nature Publishing Group, United States (Mar. 2017). [cited by applicant]
Kodack, D.P., et al., “Combined Targeting of HER2 and VEGFR2 for Effective Treatment of HER2-amplified Breast Cancer Brain Metastases,” Proceedings of the National Academy of Sciences 109(45):E3119-E3127, National Acade… [cited by applicant]
Koide, A., et al., “The Fibronectin Type III Domain as a Scaffold for Novel Binding Proteins,” Journal of Molecular Biology 284(4):1141-1151, Academic Press, United States (Dec. 1998). [cited by applicant]
Kol, A., et al., “HER3, Serious Partner in Crime: Therapeutic Approaches and Potential Biomarkers for Effect of HER3-targeting,” Pharmacology & Therapeutics 143(1):1-11, Pergamon Press, United Kingdom (Jul. 2014). [cited by applicant]
Kontermann, R.E., “Dual Targeting Strategies with Bispecific Antibodies,” MAbs 4(2):182-197, Taylor and Francis, United States (Mar. 2012). [cited by applicant]
Landgraf, R., et al., “HER2 Therapy. HER2 (ERBB2): Functional Diversity from Structurally Conserved Building Blocks,” Breast Cancer Research 9(1):202, BioMed Central Ltd, United Kingdom (Jan. 2007). [cited by applicant]
Lanzavecchia, A. and Staerz, U.D., “Lysis of Nonnucleated Red Blood Cells by Cytotoxic T Lymphocytes,” European Journal of Immunology 17(7):1073-1074, Wiley-VCH, Germany (Jul. 1987). [cited by applicant]
Lazrek, Y., et al., “Anti-HER3 Domain 1 and 3 Antibodies Reduce Tumor Growth by Hindering HER2/HER3 Dimerization and AKT-Induced MDM2. XIAP, and Fox1 Phosphorylation,” NEOPLASIA 15(3):335-347, Neoplasia Press, United St… [cited by applicant]
Le Clorennec, C., et al., “Neuregulin 1 Allosterically Enhances the Antitumor Effects of the Noncompeting Anti-HER3 Antibody 9 F7-F11 by Increasing Its Binding to HER3,” Molecular Cancer Therapeutics, 16(7): 1312-1323, … [cited by applicant]
Lee, D., et al., “Development of antibody-based c-Met inhibitors for targeted cancer therapy,” Immunotargets and Therapy 9(4):34-44, Dove Medical Press, New Zealand (Feb. 2015). [cited by applicant]
Lee-Hoeflich, S.T., et al., “A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy,” Cancer Research, 68(14): 5878-5887, American Association for Cancer Research, United States (Jul.… [cited by applicant]
Lumachi F., et al., “Endocrine Therapy of Breast Cancer,” Current Medicinal Chemistry 18(4):513-522, Bentham Science Publishers, United Arab Emirates (2011). [cited by applicant]
Luo, H., et al., “Noninvasive Brain Cancer Imaging With a Bispecific Antibody Fragment, Generated via Click Chemistry,” Proceedings of the National Academy of Sciences of the United States of America 112(41):12806-12811… [cited by applicant]
Ma, P.C., et al., “C-Met: Structure, Functions and Potential for Therapeutic Inhibition,” Cancer and Metastasis Reviews 22:309-325, Kluwer Academic, Netherlands (Dec. 2003). [cited by applicant]
Malm, M., et al., “Engineering of a Bispecific Affibody Molecule Towards HER2 and HER3 by Addition of an Albumin-Binding Domain Allows for Affinity Purification and in Vivo Half-Life Extension,” Biotechnology Journal 9(… [cited by applicant]
Malm, M., et al., “Targeting HER3 using mono- and bispecific antibodies or alternative scaffolds,” mABS 8(7): 1195-1209, Taylor & Francis, United Kingdom (Oct. 2016). [cited by applicant]
Maulik, G., et al., Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition, Cytokine & Growth Factor Reviews 13(1):41-59, Elsevier Science, United Kingdom (Feb. 200… [cited by applicant]
Maussang-Detaille, D., et al., “The binding mode of the bispecific anti-HER2xHER3 antibody MCLA-128 is responsible for its potent inhibition of HRG-driven tumorigenesis,” Abstract 33, Research Poster Presentation Design… [cited by applicant]
May, C., et al., “Advances in Bispecific Biotherapeutics for the Treatment of Cancer,” Biochemical Pharmacology 84:1105-1112, Elsevier, Netherlands (Nov. 2012). [cited by applicant]
McDonagh, C.F., et al., “Antitumor Activity of a Novel Bispecific Antibody that Targets the ErbB2/ErbB3 Oncogenic Unit And Inhibits Heregulin-Induced Activation of ErbB3,” Molecular Cancer Therapeutics 11(3):582-593, Am… [cited by applicant]
Merchant, M.A., et al., “An efficient route to human bispecific IgG,” Nature Biotechnology, 16: 677-681, Nature Publishing Group, United States (Jul. 1998). [cited by applicant]
Merlino, G.T., et al., “Amplification and Enhanced Expression of the Epidermal Growth Factor Receptor Gene in A431 Human Carcinoma Cells,” Science 224(4647): 417-419, American Association for the Advancement of Science,… [cited by applicant]
Merus, “Merus selects clinical candidate for the treatment of acute myeloid leukemia (AML),” www.merus.nl, press release, 2 pages, dated Jan. 7, 2013. [cited by applicant]
Merus, “Merus presents preclinical data on its novel bispecific antibody MCLA-117 at EHA 2013,” www.merus.nl, press release, 3 pages, dated Jun. 17, 2013. [cited by applicant]
Momeny, M., et al., “Heregulin-HER3-HER2 signaling promotes matrix metalloproteinase-dependent blood-brain-barrier transendothelial migration of human breast cancer cell lines,” Oncotarget 6(6):3932-3946, Impact Journal… [cited by applicant]
Moore, P.A., et al., “Application of Dual Affinity Retargeting Molecules to Achieve Optimal Redirected T-cell killing of B-cell Lymphoma,” Blood 117(17):4542-4551, American Society of Hematology, United States (Apr. 201… [cited by applicant]
Morgillo, F., et al., “Mechanisms of resistance to EGFR targeted drugs: lung cancer,” ESMO Open Jan. 2016:e000060, 13 pages, Biomedical Journal, United States (May 2016). [cited by applicant]
Morrison, M.M., et al., “ErbB3 Downregulation Enhances Luminal Breast Tumor Response to Antiestrogens,” The Journal of Clinical Investigation 123(10):4329-4343, American Society for Clinical Investigation, United States… [cited by applicant]
Musolino, A., et al., “Immunoglobulin G Fragment C Receptor Polymorphisms and Clinical Efficacy of Trastuzumab-based Therapy in Patients With Her-2/neu-positive Metastatic Breast Cancer,” Journal of Clinical Oncology 26… [cited by applicant]
Nakade, J., et al., “Triple Inhibition of EGFR, MET, and VEGF Suppresses Regrowth of HGF-Triggered, Erlotinib-Resistant Lung Cancer Harboring an EGFR Mutation,” Journal of Thoracic Oncology 9(6):775-783, Elsevier, Unite… [cited by applicant]
Nieba, L., et al., “Disrupting the Hydrophobic Patches at the Antibody Variable/constant Domain Interface: Improved in Vivo Folding and Physical Characterization of an Engineered Scfv Fragment,” Protein Engineering 10(4… [cited by applicant]
Ocana, A., et al., “HER3 Overexpression and Survival in Solid Tumors: A Meta-Analysis,” J. Natl Cancer Inst., 105(4): 266-273, Oxford University Press, United Kingdom (Feb. 2013). [cited by applicant]
Omenn, G.S., et al., “A New Class of Protein Cancer Biomarker Candidates: Differentially-Expressed Splice Variants of ERBB2 (HER2/neu) and ERBB1 (EGFR) in Breast Cancer Cell Lines,” Journal of Proteomics 107:103-112, El… [cited by applicant]
Organ, S.L., et al., “An Overview of the C-Met Signaling Pathway,” Therapeutic Advances in Medical Oncology 3(1 Suppl):S7-S19, Sage, United Kingdom (Nov. 2011). [cited by applicant]
Osborne K.C., et al., “Mechanisms of Endocrine Resistance in Breast Cancer,” Annual review of medicine 62:233-247, Annual Reviews Inc., United States (Feb. 2011). [cited by applicant]
Panke, C., et al., “Quantification of Cell Surface Proteins with Bispecific Antibodies,” Protein Engineering Design and Selection 26(10):645-654, Oxford University Press, United Kingdom (Aug. 2013). [cited by applicant]
Pastore, S., et al., “Erk½ Regulates Epidermal Chemokine Expression and Skin Inflammation,” Journal of Immunology 174:5047-5056, American Association of Immunologists, United States (Apr. 2005). [cited by applicant]
Patel, D.K., “Clinical Use of Anti-epidermal Growth Factor Receptor Monoclonal Antibodies in Metastatic Colorectal Cancer,” Pharmacotherapy 28(11):31S-41S, Wiley, United States (Nov. 2008). [cited by applicant]
Paul, I., et al., “Current Understanding on EGFR and Wnt/Beta-Catenin Signaling in Glioma and Their Possible Crosstalk,” Genes & Cancer 4(11-12):427-446, SAGE, United States (Nov. 2013). [cited by applicant]
Pedersen, M.W., et al., “Targeting Three Distinct HER2 Domains with a Recombinant Antibody Mixture Overcomes Trastuzumab Resistance,” Molecular Cancer Therapeutics 14(3):669-680, American Association for Cancer Research… [cited by applicant]
Prigent, S., et al., “Identification of C-erbB-3 Binding Sites for Phosphatidylinositol 3′-kinase and SHC Using an EGF Receptor/c-erbB-3 Chimera,” The EMBO Journal 13(12):2831-2841, National Center for Biotechnology Inf… [cited by applicant]
Regina, A., et al., “ANG4043, a Novel Brain-Penetrant peptide-mAb Conjugate, Is Efficacious Against HER2-positive Intracranial Tumors in Mice,” Molecular Cancer Therapeutics 14(1):129-140, American Association for Cance… [cited by applicant]
Reusch, U., and Knackmuss, S., “Beyond mAbs with T and Abs,” Innovations in Pharmaceutical Technology, 4 pages, IPT Online, United Kingdom (2011). [cited by applicant]
Richards, D.A., et al., “A Phase 1 Study of Mm-111, a Bispecific HER2/HER3 Antibody Fusion Protein, Combined with Multiple Treatment Regimens in Patients with Advanced HER2-Positive Solid Tumors,” Journal of Clinical On… [cited by applicant]
Riemer, A.B., et al., “Matching of Trastuzumab (Herceptin) Epitope Mimics Onto the Surface of Her-2/neu—a New Method of Epitope Definition,” Molecular Immunology 42(9):1121-1124, Pergamon Press, United Kingdom (May 2005… [cited by applicant]
Robinson, M.K., et al., “Targeting ErbB2 and ErbB3 with a bispecific single-chain FV Enhances targeting selectivity and induces a therapeutic effect in Vitro”, British Journal of CA 99(9):1415-1425, Nature Publishing Gr… [cited by applicant]
Roskoski, R., “The ErbB/HER Family of Protein-Tyrosine Kinases and Cancer,” Pharmacological Research 79:34-74, Elsevier, Netherlands (Jan. 2014). [cited by applicant]
Sanchez-Valdivieso, E.A., et al., “y-Heregulin has No. biological significance in primary breast cancer,” British Journal of Cancer, 86(8): 1362-1366, Cancer Research UK, United Kingdom (Apr. 2002). [cited by applicant]
Schaefer, G., et al., “A Two-in-one Antibody Against Her3 and Egfr Has Superior Inhibitory Activity Compared With Monospecific Antibodies,” Cancer Cell 20(4):472-486, Cell Press, United States (Oct. 2011). [cited by applicant]
Schmitz, K., and Ferguson K.M., “Interaction of Antibodies With ErbB Receptor Extracellular Regions,” Experimental Cell Research 315(4):659-670, Academic Press, United States (Feb. 2009). [cited by applicant]
Schoeberl, B., et al., “An ErB3 Antibody, MM-121, Is Active in Cancers with Ligand-Dependent Activation,” Cancer Research, 70(6): 2485-2494, American Association for Cancer Research, United States (Mar. 2010). [cited by applicant]
Seidel, C., et al., “Role of hepatocyte growth factor and its receptor c-met in multiple myeloma,” Medical Oncology 15:145-153, Springer Nature, Switzerland (Sep. 1998). [cited by applicant]
Sergina, N.V., et al., “Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3,” Nature, 445(7126): 437-441, Springer, United Kingdom (Jan. 2007). [cited by applicant]
Seshagiri, S., et al., “Recurrent R-spondin Fusions in Colon Cancer,” Nature 488(7413):660-664, Nature Publishing Group, United Kingdom (Aug. 2012). [cited by applicant]
Shames, D.S., et al., “High Heregulin Expression Is Associated with Activated HER3 and May Define an Actionable Biomarker in Patients with Squamous Cell Carcinomas of the Head and Neck,” PLoS One 8(2):e56765, Public Lib… [cited by applicant]
Sheridan, C., “Amgen Swallows Micromet to BiTE Into All Market,” Nature Biotechnology 30(4):300-301, Nature America Publishing, United States (Apr. 2012). [cited by applicant]
Soltoff, S.P., et al., “ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor,” Molecular and Cellular Biology 14(6):3550-3558, American Society for Microbiology, United States (Jun… [cited by applicant]
Sorkin, A., “Internalization of the Epidermal Growth Factor Receptor: Role In Signaling,” Biochemical Society Transactions 29(Pt 4):480-484, Portland Press On The Behalf Of The Biochemical Society, United Kingdom (Aug. … [cited by applicant]
Staerz, U.D., and Bevan, M.J., “Hybrid Hybridoma Producing a Bispecific Monoclonal Antibody that can Focus Effector T-cell Activity,” Proceedings of the National Academy of Sciences USA 83(5):1453-1457, National Academy… [cited by applicant]
Stancovski, I., et al., “Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth,” Proceedings of the National Academy of Sciences USA 88(19):8691-8695, National Academ… [cited by applicant]
Strelkauskas, A., et al., “Human Monoclonal Antibody: 2. Simultaneous Expression of IgG and IgM with Similar Binding Specificities by a Human Hybrid Clone,” Hybridoma 6(5):479-488, Mary Ann Liebert, United States (Oct. … [cited by applicant]
Thery, J.C., et al., “Resistance to Human Epidermal Growth Factor Receptor Type 2-targeted Therapies,” European Journal of Cancer 50(5):892-901, Elsevier, Netherlands (Mar. 2014). [cited by applicant]
Troise, F., et al., “A novel ErbB2 epitope targeted by human antitumor immunoagents,” FEBS Journal 278:1156-1166, John Wiley & Sons, United States (Apr. 2011). [cited by applicant]
Uberall, I., et al.,“The status and role of ErbB receptors in human cancer,” Experimental and Molecular Pathology 84:79-89, Elsevier, Netherlands (Apr. 2008). [cited by applicant]
Vajdos, F.F., et al., “Comprehensive Functional Maps of The Antigen-binding Site of an Anti-Erbb2 Antibody Obtained with Shotgun Scanning Mutagenesis,” Journal of Molecular Biology 320(2):415-428, Academic Press, United… [cited by applicant]
Vecchione, L., et al., “EGFR-targeted therapy,” Experimental Cell Research 317(19): 2765-2771, Academic Press, United States (Nov. 2011). [cited by applicant]
Wadhwa, D., et al., “Trastuzumab Mediated Cardiotoxicity in the Setting of Adjuvant Chemotherapy for Breast Cancer: a Retrospective Study,” Breast Cancer Research and Treatment 117(2):357-364, Kluwer Academic, Netherlan… [cited by applicant]
Wehrman, T.S., et al., “A System for Quantifying Dynamic Protein Interactions Defines a Role for Herceptin in Modulating ErbB2 Interactions,” Proceedings of the National Academy of Sciences of the United States of Ameri… [cited by applicant]
Weidle, U. H., et al., “The intriguing options of multispecific antibody formats for treatment of cancer,” Cancer Genomics Proteomics 10(1):1-18, International Institute of Anticancer Research, Greece (Jan.-Feb. 2013). [cited by applicant]
Weinstein, E.J., et al., “The oncogene heregulin induces apoptosis in breast epithelial cells and tumors,” Oncogene 17(16):2107-2113, Nature Publishing Group, United Kingdom (Oct. 1998). [cited by applicant]
Wick, M.J., et al., “Establishment and Characterization of a HER2-positive, TDM1-Resistant PDX Breast Model,” Abstract C74 at AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics (Nov. 5-9,… [cited by applicant]
Wilson, T.R., et al., “Neuregulin-1-Mediated Autocrine Signaling Underlies Sensitivity to HER2 Kinase Inhibitors in a Subset of Human Cancer,” Cancer Cells, 20(2):158-172, Elsevier, Inc., Netherlands (Aug. 2011). [cited by applicant]
Wilson, T.R., et al., “Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors,” Nature, 487(7408):505-509, Springer, United Kingdom (Jul. 2012). [cited by applicant]
Winkler, K., et al., “Changing the Antigen Binding Specificity by Single Point Mutations of an Anti-p24 (HIV-1) Antibody,” The Journal of Immunology 165(8):4505-4514, The American Association of Immunologists, United St… [cited by applicant]
Wolff, A.C., et al., “Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update,” Jo… [cited by applicant]
Woning, S.V.D., et al., “Quantification of ErbB3 Receptor Density on Human Breast Cancer Cells, Using a Stable Radio-Labeled Mutant of Nrg1beta,” Biochemical and Biophysical Research Communications, 378(2):285-289, Else… [cited by applicant]
Xu, F., et al., “Antibody-Induced Growth Inhibition is Mediated Through Immunochemically and Functionally Distinct Epitopes on the Extracellular Domain of the c-erB-2 (HER-2/neu) Gene Product p185,” International Journa… [cited by applicant]
Yano, S. et al., “Hepatocyte Growth Factor Induces Gefitinib Resistance of Lung Adenocarcinoma With Epidermal Growth Factor Receptor-activating Mutations,” Cancer Research 68(22):9479-9487, American Association for Canc… [cited by applicant]
Yano, S., et al., “Molecular Mechanism of EGFR-TK1 Resistance,” Japanese Journal of Lung Cancer 49(6):939-943, The Japan Lung Cancer Society, Japan (Oct. 2009). [cited by applicant]
Yarden, Y. et al., “The EGFR family and its ligands in human cancer: signaling mechanisms and therapeutic opportunities,” European Journal of Cancer 37(Supp4):S3-S8, Research Gate GmbH, Netherlands (Sep. 2001). [cited by applicant]
Yarden, Y., et al., “The ERBB Network: At Last, Cancer Therapy Meets Systems Biology,” Nature Reviews Cancer 12(8):553-563, Nature Publishing Group, United Kingdom (Jul. 2012). [cited by applicant]
Yonesaka, K., et al., “Activation of ERBB2 Signaling Causes Resistance to the Egfr-Directed Therapeutic Antibody Cetuximab,” Science Translational Medicine 3(99):99ra86, American Association for the Advancement of Scien… [cited by applicant]
Zeidler, R., et al., “Simultaneous Activation of T Cells and Accessory Cells by a New Class of Intact Bispecific Antibody Results in Efficient Tumor Cell Killing,” Journal of Immunology 163(3):1246-1252, American Associ… [cited by applicant]
Zhang, H., et al., “ErbB receptors: from oncogenes to targeted cancer therapies,” J Clin Invest 117(8): 2051-2058, The American Society for Clinical Investigations, United States (Aug. 2007). [cited by applicant]
Zhang, Y.W., et al., “MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor-dependent fashion to suppress carcinoma growth,” Cancer Research 70(17… [cited by applicant]
Zhang, B., et al., “Abstract 655: Combination of Mm-111, an Erbb2/erbb3 Bispecific Antibody, With Endocrine Therapies as an Effective Strategy for Treatment of Er+/her2+ Breast Cancer,” Cancer Research 71(8):655-655, Am… [cited by applicant]
Zhao, X., et al., “Targeting C-type Lectin-like Molecule-1 for Antibody-mediated Immunotherapy in Acute Myeloid Leukemia,” Haematologica 95(1):71-78, Ferrata Storti Foundation, Italy (Jan. 2010). [cited by applicant]
Ahmed, M., et al., “Lack of in Vivo Antibody Dependent Cellular Cytotoxicity with Antibody Containing Gold Particles,” Bioconjugate Chem 26:812-816, American Chemical Society, United States (May 2015). [cited by applicant]
Almagro, J.C., et al., “Humanization of antibodies,” Front Biosci 13:1619-1633, IMR Press, Singapore (Jan. 2008). [cited by applicant]
Bardelli, A., et al., “Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer,” Cancer Discov 3(6):658-673, American Association for Cancer Research, United States (Jun. 2013). [cited by applicant]
Elliott, B.E., et al., “The role of hepatocyte growth factor (scatter factor) in epithelial-mesenchymal transition and cancer,” Can J Physiol Pharmacol 80(2):91-102, Canadian Science Publishing, Canada (Feb. 2002). [cited by applicant]
Ferguson, K.M., “Structure-based view of epidermal growth factor receptor regulation,” Annu Rev Biophys 37:353-373, Annual Reviews, United States (Jun. 2008). [cited by applicant]
Gale, N.W., et al., “Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras,” Nature 363:88-92, Nature Publishing Group, United Kingdom (May 1993). [cited by applicant]
Kubota, T., et al., “Engineered therapeutic antibodies with improved effector functions,” Cancer Sci 100(9):1566-1572, Wiley, United States (Sep. 2009). [cited by applicant]
Olayioye, M.A., et al., “The ErbB signaling network: receptor heterodimerization in development and cancer,” EMBO J 19(13):3159-3167, EMBO Press, United Kingdom (Jul. 2000). [cited by applicant]
Park, N.J., et al., “Measurement of Cetuximab and Panitumumab-Unbound Serum EGFR Extracellular Domain Using an Assay Based on Slow Off-Rate Modified Aptamer (SOMAmer) Reagents,” PLOS One 8(21):e71703, PLOS, United State… [cited by applicant]
Robertson, S.C., et al., “RTK mutations and human syndromes: when good receptors turn bad,” Trends Genet 16(6):265-271, Elsevier, Netherlands (Aug. 2000). [cited by applicant]
Siegfried, J.M., et al., “The clinical significance of hepatocyte growth factor for non-small cell lung cancer,” Ann Thoracic Surg 66(6):1915-1918, Elsevier, Netherlands (Dec. 1998). [cited by applicant]
Vecchione, L., et al., “EGFR-targeted therapy,” Experimental Cell Research 317(19):2765-2771, Elsevier, Netherlands (Nov. 2011). [cited by applicant]
Brown, M., et al., “Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR 2: a means of minimizing B cell wastage from somatic hypermutation?” J Immunol 156(9):3285-3291, American Association… [cited by applicant]
Liu, L., et al., “A novel MET-EGFR bispecific antibody LY3164530 shows advantage over combining MET and EGFR antibodies in tumor inhibition and overcome resistance,” Cancer Res 76(14 Suppl): Abstract 873, American Assoc… [cited by applicant]
Rudikoff, S., et al., “Single amino acid substitution altering antigen-binding specificity,” Proc Natl Acad Sci USA 79(6):1979-1983, National Academy of Science (Mar. 1982). [cited by applicant]
Buday, L., and Downward, J., “Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor,” Cell 73(3):611-620, Cell Press, United St… [cited by applicant]
Junttila, T.T., et al., “Superior in vivo efficacy of afucosylated trastuzumab in the treatment of HER2-amplified breast cancer,” Cancer Res 70(11):4481-4489, American Association for Cancer Research, United States (Jun… [cited by applicant]
Pilaro, A., Food and Drug Administration, “125084 Erbitux Pharmacology Review Part 2”, pp. 30-60 (2004). [cited by applicant]
Brinkmann, U. and Kontermann, R.E., “The making of bispecific antibodies,” MAbs 9(2):182-212, Landes Bioscience, United States (Feb./Mar. 2017). [cited by applicant]