IP Library › Granted Patent US 10,500,276
Granted Patent B2
US 10,500,276 · App. 16/270,317 · Granted Dec 10, 2019

Antibodies binding AXL

Inventors: Esther Breij (Utrecht, NL); David Satijn (Utrecht, NL); Edward Norbert Van Den Brink (Halfweg, NL); Dennis Verzijl (Amstelveen, NL); Rob N. De Jong (Utrecht, NL); Paul Parren (Utrecht, NL); Riemke Van Dijkhuizen Radersma (Zeist, NL)
Assignee: GENMAB A/S
A61K39/39558A61K47/6801A61K47/6855A61K47/6857A61K47/6869C07K16/2863C07K16/3061A61K2039/505A61K2121/00C07K2317/33C07K2317/34C07K2317/56C07K2317/732C07K2317/77C07K2317/92
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Quick Facts
Patent No.
US 10,500,276
App. No.
16/270,317
Granted
Dec 10, 2019
Kind
B2
Abstract

The present invention relates to anti-AXL antibodies, immunoconjugates, compositions and method of treatment of cancer with such anti-AXL antibodies, immunoconjugates, or compositions.

Claims (37)

1. An immunoconjugate comprising (a) an antibody which binds to AXL (SEQ ID NO: 130) and comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 36, 37, and 38, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 39, the amino acid sequence GAS, and SEQ ID NO: 40, respectively, (b) a mc-vc-PAB linker, and (c) a cytotoxic agent, which is MMAE.

2. The immunoconjugate of claim 1 , wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NOs: 1 and 2, respectively.

3. The immunoconjugate of claim 1 , wherein MMAE is linked to the antibody via the mc-vc-PAB linker, wherein the cytotoxic agent and the linker have the chemical structure;

wherein MAb is the antibody.

4. The immunoconjugate according to claim 1 , wherein the MMAE is conjugated to the antibody via a cysteine thiol or a lysine.

5. The immunoconjugate of claim 1 , wherein cytotoxic agent loading (p) is 1 to 8.

6. The immunoconjugate of claim 1 , wherein cytotoxic agent loading (p) is 10 to 30.

7. The immunoconjugate of claim 1 , wherein said antibody comprises a heavy chain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

8. The immunoconjugate of claim 1 , wherein the antibody is a full-length monoclonal antibody.

9. The immunoconjugate of claim 1 , wherein the antibody is a full-length monoclonal IgG1,κ antibody.

10. The immunoconjugate of claim 1 , wherein the antibody is a monovalent antibody.

11. The immunoconjugate of claim 1 , wherein the antibody is an antigen-binding fragment of an immunoglobulin molecule.

12. The immunoconjugate of claim 1 , wherein the antibody is a single-chain antibody.

13. The immunoconjugate of claim 1 , wherein the antibody is a human antibody.

14. A pharmaceutical composition comprising the immunoconjugate of claim 1 , and a pharmaceutical acceptable carrier.

15. A kit comprising the immunoconjugate of claim 1 .

16. The immunoconjugate of claim 6 , wherein cytotoxic agent loading (p) is 1 to 20.

17. The immunoconjugate of claim 6 , wherein cytotoxic agent loading (p) is 2 to 6.

18. The immunoconjugate of claim 6 , wherein cytotoxic agent loading (p) is 2 to 4.

19. An immunoconjugate comprising (a) an antibody which binds to AXL (SEQ ID NO: 130) and comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the VH region comprises the amino acid sequence of SEQ ID NO: 1 and the VL region comprises the amino acid sequence of SEQ ID NO: 2, (b) a mc-vc-PAB linker, and (c) a cytotoxic agent, which is MMAE.

20. The immunoconjugate of claim 19 , wherein the combination of the MMAE and the mc-vc-PAB linker has the chemical structure;

wherein MAb is the antibody.

21. The immunoconjugate according to claim 19 , wherein the MMAE is conjugated to the antibody via a cysteine thiol or a lysine.

22. The immunoconjugate of claim 19 , wherein cytotoxic agent loading (p) is 1 to 8.

23. The immunoconjugate of claim 19 , wherein cytotoxic agent loading (p) is 10 to 30.

24. The immunoconjugate of claim 19 , wherein said antibody comprises a heavy chain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

25. The immunoconjugate of claim 19 , wherein the antibody is a full-length monoclonal antibody.

26. The immunoconjugate of claim 19 , wherein the antibody is a full-length monoclonal IgG1,κ antibody.

27. The immunoconjugate of claim 19 , wherein the antibody is a monovalent antibody.

28. The immunoconjugate of claim 19 , wherein the antibody is a single-chain antibody.

29. The immunoconjugate of claim 19 , wherein the antibody is an antigen-binding fragment of an immunoglobulin molecule.

30. The immunoconjugate of claim 19 , wherein the antibody is a human antibody.

31. A pharmaceutical composition comprising the antibody of claim 19 , and a pharmaceutical acceptable carrier.

32. A kit comprising the immunoconjugate of claim 19 .

33. The immunoconjugate of claim 19 , wherein cytotoxic agent loading (p) is 1 to 20.

34. The immunoconjugate of claim 19 , wherein cytotoxic agent loading (p) is 2 to 6.

35. The immunoconjugate of claim 19 , wherein cytotoxic agent loading (p) is 2 to 4.

Assignments (3)
SECURITY INTEREST Recorded Dec 15, 2025
From: GENMAB A/S; GENMAB B.V.; GENMAB HOLDING B.V.
To: MORGAN STANLEY SENIOR FUNDING, INC.
Reel/Frame 073933/0597 →
NOTICE OF GRANT OF SECURITY INTEREST IN PATENTS Recorded Dec 15, 2025
From: GENMAB A/S; GENMAB B.V.; GENMAB HOLDING B.V.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 073949/0722 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 11, 2019
From: BREIJ, ESTHER; SATIJN, DAVID; VAN DEN BRINK, EDWARD; VERZIJL, DENNIS; DE JONG, ROB N.; PARREN, PAUL; VAN DIJKHUIZEN RADERSMA, RIEMKE
To: GENMAB A/S
Reel/Frame 048301/0831 →
Cited By (1)
US 12,589,150