Combination therapies against cancer targeting CD38 and TGF-β

Patent metadata

Field	Value
Publication number	US-12590167-B2
Application number	US-201917259135-A
Country	US
Kind code	B2
Filing date	Jul 10, 2019
Priority date	Jul 10, 2018
Publication date	Mar 31, 2026
Grant date	Mar 31, 2026

Abstract

The present disclosure relates to combination cancer therapies targeting CD38 and TGF-β using antibodies specific for these targets. Also provided are compositions useful in the therapies.

First claim

What is claimed is:

1 . A method of treating a CD38-positive cancer in a human patient in need thereof, comprising administering to the patient
an anti-CD38 antibody that has heavy chain CDR1 (HCDR1), HCDR2, HCDR3, light chain CDR1 (LCDR1), LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 15-20, respectively, and an anti-TGF-β antibody or an antigen-binding fragment thereof that has HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 5-10, respectively, wherein the cancer is multiple myeloma that is refractory to treatment with Ab2, and the administering of the anti-CD38 antibody and the anti-TGF-β antibody or antigen-binding fragment slows cancer growth.

2 . The method of claim 1 , wherein the anti-CD38 antibody comprises a heavy chain variable domain (V H ) and a light chain variable domain (V L ) comprising the amino acid sequences of SEQ ID NOs: 13 and 14, respectively; and wherein the anti-TGF-β antibody comprises a V H and a V L comprising the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

3 . The method of claim 2 , wherein the anti-CD38 antibody has a heavy chain (HC) and a light chain (LC) comprising the amino acid sequences of SEQ ID NOs: 11 and 12, respectively; and wherein the anti-TGF-β antibody has an HC and an LC comprising the amino acid sequences of SEQ ID NOs: 1 and 2, respectively.

4 . A method of treating a CD38-positive cancer in a human patient in need thereof, comprising administering to the patient an anti-CD38 antibody and an anti-TGF-β antibody or an antigen-binding fragment thereof, wherein the anti-CD38 antibody:
a) has HCDR1-3 and LCDR1-3 comprising the amino acid sequences of SEQ ID NOs: 15-20, respectively;
b) has a heavy chain variable domain (V H ) and a light chain variable domain (V L ) comprising the amino acid sequences of SEQ ID NOs: 13 and 14, respectively; or
c) has a heavy chain (HC) and a light chain (LC) comprising the amino acid sequences of SEQ ID NOs: 11 and 12, respectively; and
wherein the anti-TGF-β antibody:
a) has HCDR1-3 and LCDR1-3 comprising the amino acid sequences of SEQ ID NOs: 5-10, respectively;
b) has a V H and a V L comprising the amino acid sequences of SEQ ID NOs: 3 and 4, respectively; or
c) has an HC and an LC comprising the amino acid sequences of SEQ ID NOs: 1 and 2, respectively,
wherein the cancer is multiple myeloma that is refractory to treatment with Ab2, and the administering of the anti-CD38 antibody and the anti-TGF-β antibody or antigen-binding fragment slows cancer growth.

5 . The method of claim 1 , wherein the anti-CD38 antibody comprises a human IgG 1 Fc region and the anti-TGF-β antibody comprises a human IgG 4 Fc region.

6 . A method of treating multiple myeloma in a human patient in need thereof, comprising administering to the patient an anti-CD38 antibody that comprises a heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 13 and a light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 14, and an anti-TGF-β antibody that comprises a V H amino acid sequence of SEQ ID NO: 3 and a V L amino acid sequence of SEQ ID NO: 4, wherein the cancer is multiple myeloma that is refractory to treatment with Ab2, and the administering of the anti-CD38 antibody and the anti-TGF-β antibody or antigen-binding fragment slows cancer growth.

7 . A method of treating multiple myeloma in a human patient in need thereof, comprising administering to the patient an anti-CD38 antibody that comprises a heavy chain (HC) amino acid sequence of SEQ ID NO: 11 and a light chain (LC) amino acid sequence of SEQ ID NO: 12, and an anti-TGF-β antibody that comprises an HC amino acid sequence of SEQ ID NO: 1 and an LC amino acid sequence of SEQ ID NO: 2, wherein the cancer is multiple myeloma that is refractory to treatment with Ab2, and the administering of the anti-CD38 antibody and the anti-TGF-β antibody or antigen-binding fragment slows cancer growth.

8 . The method of claim 1 , wherein the anti-CD38 antibody and the anti-TGF-β antibody or fragment are administered to the patient sequentially.

9 . The method of claim 1 , wherein the treatment results in less bone destruction than treatment with the anti-CD38 antibody alone.

10 . The method of claim 1 , wherein the treatment enhances bone healing.

11 . The method of claim 1 , wherein the treatment further comprises dexamethasone.

Assignees

• Sanofi Sa

Inventors

• Adrian Francisco
• Gregory Richard C
• Shapiro Gary
• Van De Velde Helgi

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/22

  against growth factors {; against growth regulators} · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• A61K31/12

  Ketones · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title