BCMA monoclonal antibody-drug conjugate

Patent metadata

Field	Value
Publication number	US-10988546-B2
Application number	US-201816050944-A
Country	US
Kind code	B2
Filing date	Jul 31, 2018
Priority date	Aug 1, 2017
Publication date	Apr 27, 2021
Grant date	Apr 27, 2021

Abstract

The disclosure is directed to an antibody-drug conjugate (ADC) comprising a monoclonal antibody, or an antigen-binding fragment thereof, directed against B-cell maturation antigen (BCMA) conjugated to a cytotoxin. The disclosure also provides compositions comprising the antibody-drug conjugate and methods of killing multiple myeloma cells (including multiple myeloma stems cells) that express BCMA by contacting multiple myeloma cells with the ADC.

First claim

The invention claimed is:

1. An antibody-drug conjugate (ADC) comprising a monoclonal antibody or an antigen-binding fragment thereof, conjugated to a cytotoxin, wherein the monoclonal antibody or antigen-binding fragment thereof is capable of binding to human B-cell maturation antigen (BCMA) and comprises (a) a heavy chain variable region comprising a complementarity determining region 1 (HCDR1) amino acid sequence of SEQ ID NO: 1, an HCDR2 amino acid sequence of SEQ ID NO: 2, and an HCDR3 amino acid sequence of SEQ ID NO: 3 and (b) a light chain variable region comprising a complementarity determining region 1 (LCDR1) amino acid sequence of SEQ ID NO: 4, an LCDR2 amino acid sequence of SEQ ID NO: 5, and an LCDR3 amino acid sequence of SEQ ID NO: 6.

2. The antibody-drug conjugate of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7.

3. The antibody-drug conjugate of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 8.

4. The antibody-drug conjugate of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 8.

5. The antibody-drug conjugate of claim 1 , wherein the cytotoxin is an anti-microtubule agent, a pyrrolobenzodiazepine (PBD), an RNA polymerase II inhibitor, or a DNA alkylating agent.

6. The antibody-drug conjugate of claim 5 , wherein the cytotoxin is an anti-microtubule agent selected from the group consisting of a maytansinoid, an auristatin, and a tubulysin.

7. The antibody-drug conjugate of claim 5 , wherein the cytotoxin is a pyrrolobenzodiazepine (PBD).

8. The antibody-drug conjugate of claim 7 , wherein the pyrrolobenzodiapezine (PBD) is SG3249 having the following formula:

9. A composition comprising the antibody-drug conjugate of claim 1 and a pharmaceutically-acceptable carrier.

10. A monoclonal antibody or an antigen-binding fragment thereof, wherein the monoclonal antibody or antigen-binding fragment thereof is capable of binding to human B-cell maturation antigen (BCMA) and comprises (a) a heavy chain variable region comprising a complementarity determining region 1 (HCDR1) amino acid sequence of SEQ ID NO: 1, an HCDR2 amino acid sequence of SEQ ID NO: 2, and an HCDR3 amino acid sequence of SEQ ID NO: 3 and (b) a light chain variable region comprising a complementarity determining region 1 (LCDR1) amino acid sequence of SEQ ID NO: 4, an LCDR2 amino acid sequence of SEQ ID NO: 5, and an LCDR3 amino acid sequence of SEQ ID NO: 6.

11. The monoclonal antibody or antigen-binding fragment thereof of claim 10 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7.

12. The monoclonal antibody or antigen-binding fragment thereof of claim 10 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 8.

13. The monoclonal antibody or antigen-binding fragment thereof of claim 10 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 8.

14. A composition comprising the monoclonal antibody or antigen-binding fragment thereof of claim 10 and a pharmaceutically-acceptable carrier.

Assignees

• Medimmune Llc

Inventors

• Kinneer Krista
• Varkey Reena
• Xiao Xiaodong
• Hurt Elaine M
• Tice David

Classifications

• A61K47/6803 Primary

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• C07K16/3061 Primary

  Blood cells · CPC title

• A61K47/68035

  the drug being a pyrrolobenzodiazepine · CPC title

• A61K47/68031

  the drug being an auristatin · CPC title

• A61K31/202 Primary

  having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557) · CPC title