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)

C07K16/2863 A61P35/00 C07K16/40 A61K2039/505 C07K2317/21 C07K2317/31 C07K2317/33 C07K2317/35 C07K2317/526 C07K2317/565 C07K2317/732 C07K2317/76

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Quick Facts

Patent No.: US 11,773,170
App. No.: 16/637,464
Granted: Oct 3, 2023
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

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 embodiments the bispecific antibody is an IgG1 format antibody having an anti-EGFR, anti-cMET stoichiometry of 1:1. In some embodiment the antibody has one variable domain that can bind EGFR and one variable domain that can bind cMET.

Claims (25)

1. 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);

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);

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);

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);

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);

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);

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 the 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 bispecific antibody of claim 1 , that is an IgG1 format antibody having an anti-EGFR, anti-cMET stoichiometry of 1:1.

3. The bispecific antibody of claim 1 , wherein the amino acids at positions 405 and 409 in one CH3 domain are the same as the amino acids at the corresponding positions in the other CH3 domain (EU-numbering).

4. The bispecific antibody of claim 1 , wherein the heavy chain variable region of the second variable domain comprises the amino acid sequence of one of the sequences of SEQ ID NO: 13 or 23.

5. The bispecific antibody of claim 1 , wherein the heavy chain variable region of the second variable domain comprises the amino acid sequence of one of the sequences of SEQ ID NO: 2; 7; 8; 10; 13 or 23.

6. The bispecific antibody 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).

7. The bispecific antibody 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).

8. The bispecific antibody 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).

9. The bispecific antibody 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).

10. The bispecific antibody 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 comprising the amino acid sequence of SEQ ID NO:13.

11. The bispecific antibody 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 comprising the amino acid sequence of SEQ ID NO:13.

12. The bispecific antibody 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 comprising the amino acid sequence of SEQ ID NO:13.

13. The bispecific antibody 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).

14. The bispecific antibody 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 SYSMN (SEQ ID NO: 28); a CDR2 sequence WINTYTGDPTYAQGFTG (SEQ ID NO: 157) and a CDR3 sequence ETYYYDRGGYPFDP (SEQ ID NO: 30).

15. The bispecific antibody 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).

16. The bispecific antibody 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).

Assignments (3)

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 Oct 1, 2020

From: GEUIJEN, CECILIA ANNA WILHELMINA; ROOVERS, ROBERTUS CORNELIS; THROSBY, MARK; DE KRUIF, CORNELIS ADRIAAN; LOGTENBERG, TON

To: MERUS N.V.