Humanized and affinity matured antibodies to FcRH5 and methods of use

Patent metadata

Field	Value
Publication number	US-12030947-B2
Application number	US-202117514824-A
Country	US
Kind code	B2
Filing date	Oct 29, 2021
Priority date	Jun 16, 2015
Publication date	Jul 9, 2024
Grant date	Jul 9, 2024

Abstract

The present invention relates to anti-FcRH5 antibodies, including anti-FcRH5 antibodies comprising an FcRH5 binding domain and a CD3 binding domain (e.g., FcRH5 T cell-dependent bispecific (TDB) antibodies), and methods of using the same.

First claim

What is claimed is:

1. A method of treating or delaying the progression of an FcRH5-positive cancer in a subject in need thereof, the method comprising administering to the subject a bispecific antibody comprising a first binding domain that binds Fc Receptor-like 5 (FcRH5) and a second binding domain that binds cluster of differentiation 3 (CD3), wherein the first binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1;
(b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 8;
(c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9;
(d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12;
(e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 16; and
(f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 23.

2. The method of claim 1 , wherein the second binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 115;
(b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 116;
(c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 117;
(d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 118;
(e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 119; and
(f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 120.

3. A method of treating or delaying the progression of an FcRH5-positive cancer in a subject in need thereof, the method comprising administering to the subject a bispecific antibody comprising a first binding domain that binds FcRH5 and a second binding domain that binds CD3, wherein the first binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1;
(b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 8;
(c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9;
(d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12;
(e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 16; and
(f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 23 and the second binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 115;
(b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 116;
(c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 117;
(d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 118;
(e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 119; and
(f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 120.

4. A method of treating or delaying the progression of an FcRH5-positive cancer in a subject in need thereof, the method comprising administering to the subject a bispecific antibody comprising a first binding domain that binds Fc Receptor-like 5 (FcRH5) and a second binding domain that binds cluster of differentiation 3 (CD3), wherein (a) the first binding domain comprises a heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 104 and a light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 105 and (b) the second binding domain comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 133 and a VL domain comprising the amino acid sequence of SEQ ID NO: 134.

5. The method of claim 1 , wherein the FcRH5-positive cancer is a B cell cancer.

6. The method of claim 5 , wherein the B cell cancer is selected from the group consisting of multiple myeloma (MM), chronic lymphoid leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL).

7. The method of claim 6 , wherein the B cell cancer is MM.

8. The method of claim 1 , further comprising administering to the subject a PD-1 axis binding antagonist and/or an additional therapeutic agent.

9. The method of claim 8 , wherein the PD-1 axis binding antagonist or additional therapeutic agent is administered prior to or subsequent to the administration of the anti-FcRH5 antibody.

10. The method of claim 9 , wherein the PD-1 axis binding antagonist or additional therapeutic agent is administered concurrently with the anti-FcRH5 antibody.

11. The method of claim 8 , wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-L1 binding antagonist, a PD-1 binding antagonist, and a PD-L2 binding antagonist.

12. The method of claim 11 , wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.

13. The method of claim 12 , wherein the PD-L1 binding antagonist is selected from the group consisting of MPDL3280A (atezolizumab), MDX-1105, MED14736 (durvalumab), and MSB0010718C (avelumab).

14. The method of claim 13 , wherein the PD-L1 binding antagonist is MPDL3280A (atezolizumab).

15. The method of claim 11 , wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.

16. The method of claim 15 , wherein the PD-1 binding antagonist is selected from the group consisting of MDX 1106 (nivolumab), MK-3475 (pembrolizumab), MEDI-0680 (AMP-514), PDR001, REGN2810, and BGB-108.

17. The method of claim 11 , wherein the PD-1 axis binding antagonist is a PD-L2 binding antagonist.

18. The method of claim 17 , wherein the PD-L2 binding antagonist is an antibody or an immunoadhesin.

19. The method of claim 1 , further comprising administering to the subject a steroid, an immunomodulator (IMiD), a proteosome inhibitor (PI), or a combination thereof.

20. The method of claim 19 , wherein the steroid is a glucocorticoid.

21. The method of claim 20 , wherein the glucocorticoid is dexamethasone.

22. The method of claim 19 , wherein the IMiD is lenalidomide.

23. The method of claim 19 , wherein the PI is bortezomib.

24. The method of claim 1 , wherein the method comprises administering the anti-FcRH5 antibody intravenously, subcutaneously, or intraperitoneally.

25. The method of claim 24 , wherein the method comprises administering the anti-FcRH5 antibody intravenously.

26. The method of claim 24 , wherein the method comprises administering the anti-FcRH5 antibody subcutaneously.

27. The method of claim 3 , wherein the FcRH5-positive cancer is a B cell cancer.

28. The method of claim 27 , wherein the B cell cancer is selected from the group consisting of MM, CLL, MCL, DLBCL, and FL.

29. The method of claim 28 , wherein the B cell cancer is MM.

30. The method of claim 3 , further comprising administering to the subject a PD-1 axis binding antagonist and/or an additional therapeutic agent.

31. The method of claim 30 , wherein the PD-1 axis binding antagonist or additional therapeutic agent is administered prior to or subsequent to the administration of the anti-FcRH5 antibody.

32. The method of claim 31 , wherein the PD-1 axis binding antagonist or additional therapeutic agent is administered concurrently with the anti-FcRH5 antibody.

33. The method of claim 30 , wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-L1 binding antagonist, a PD-1 binding antagonist, and a PD-L2 binding antagonist.

34. The method of claim 33 , wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.

35. The method of claim 34 , wherein the PD-L1 binding antagonist is selected from the

Assignees

• Genentech Inc

Inventors

• Hotzel Isidro
• Junttila Teemu T
• Li Ji
• Scheer Justin
• Dicara Danielle
• Ellerman Diego
• Spiess Christoph
• Carter Paul J

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K39/39566

  against immunoglobulins, e.g. anti-idiotypic antibodies · CPC title