Anti-BCMA antibodies and uses thereof

• US 10,072,088 B2
• Filed: 08/16/2016
• Issued: 09/11/2018
• Est. Priority Date: 08/17/2015
• Status: Active Grant

• Current Assignee: Janssen Biotech, Inc. (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Pillarisetti, Kodandaram, Baldwin, Eric Thomas, Powers, Gordon D., Cardoso, Rosa Maria Fernandes, Attar, Ricardo, Gaudet, Francois
• Primary Examiner(s): STOICA, ELLY GERALD
• Application Number:
  US15/237,889
• Publication Number:
  US 20170051068A1
• Time in Patent Office: 756 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 16/3061 Blood cells
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Provided herein are antibodies that immunospecifically bind to BCMA. Also described are related polynucleotides capable of encoding the provided BCMA-specific antibodies or antigen-binding fragments, cells expressing the provided antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled antibodies or antigen-binding fragments. In addition, methods of using the provided antibodies are described. For example, the provided antibodies may be used to diagnose, treat, or monitor BCMA-expressing cancer progression, regression, or stability; to determine whether or not a patient should be treated for cancer; or to determine whether or not a subject is afflicted with BCMA-expressing cancer and thus may be amenable to treatment with a BCMA-specific anti-cancer therapeutic, such as the multispecific antibodies against BCMA and CD3 described herein.

Claims

1. A recombinant antibody, or an antigen-binding fragment thereof, that binds immunospecifically to BCMA, wherein the antibody has a heavy chain and a light chain, said heavy chain and light chain comprising:

a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO;

4, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO;

5, and a heavy chain CDR3 having the amino acid sequence of SEQ ID NO;

6, a light chain CDR1 having the amino acid sequence of SEQ ID NO;

24, a light chain CDR2 having the amino acid sequence of SEQ ID NO;

25, and a light chain CDR3 having the amino acid sequence of SEQ ID NO;

26.

2. The antibody or antigen-binding fragment of claim 1, wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:

27, and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO;

28.

3. The antibody or antigen-binding fragment of any one of claims 1 and 2, wherein the antibody or antigen-binding fragment thereof binds to the extracellular domain of human BCMA.

4. The antibody or antigen-binding fragment of any one of claims 1 and 2, wherein the antibody or antigen-binding fragment is a human antibody or antigen-binding fragment.

5. The antigen binding fragment of any one of claims 1 and 2, wherein the antigen binding fragment is a Fab fragment, a Fab2 fragment, or a single chain antibody.

6. The antibody or antigen-binding fragment of any one of claims 1 and 2, wherein the antibody or antigen-binding fragment thereof inhibits the interaction of BCMA and APRIL.

7. The antibody or antigen-binding fragment of claim 6, wherein the antibody or antigen-binding fragment exhibits an IC₅₀ for the interaction of BCMA and APRIL of about 5.9 nM as measured by ELISA.

8. The antibody or antigen-binding fragment of any one of claims 1 and 2, wherein the antibody or antigen-binding fragment thereof is an IgG.

9. The antibody or antigen-binding fragment of any one of claims 1 and 2, is an IgG4 isotype.

10. The antibody of claim 9 wherein the IgG4 has a S228P substitution, a L234A substitution and a L235A substitution in its Fc region.

11. The antibody or antigen-binding fragment of any one of claims 1 and 2, wherein the antibody or antigen-binding fragment thereof immunospecifically binds human BCMA and cross reacts to cynomolgus monkey BCMA.

12. The antibody or antigen-binding fragment of any one of claims 1 and 2, wherein the antibody or antigen-binding fragment thereof binds BCMA on the surface of human myeloma cells.

13. The antibody or antigen-binding fragment of any one of claims 1 and 2, wherein the antibody or antigen-binding fragment thereof binds BCMA on the surface of human multiple myeloma cells.

14. A recombinant cell expressing the antibody or antigen-binding fragment of any one of claims 1 and 2.

15. The cell of claim 14 wherein the cell is a hybridoma.

16. The cell of claim 14 wherein the antibody is recombinantly produced.