Anti-CTLA-4 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-12024570-B2
Application number	US-202017070129-A
Country	US
Kind code	B2
Filing date	Oct 14, 2020
Priority date	Jul 27, 2017
Publication date	Jul 2, 2024
Grant date	Jul 2, 2024

Abstract

The present invention provides antibodies that bind to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that specifically bind to CTLA-4. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing CTLA-4 activity, thus providing a means of activating T-cells and/or for treating a disease or disorder such as cancer or viral infection.

First claim

What is claimed is:

1. A pair of polynucleotide molecules encoding a heavy chain variable region (HCVR) and a light chain variable region (LCVR), respectively, of an antibody or antigen-binding fragment thereof that binds specifically to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), wherein the HCVR comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 196, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 198, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 200, and the LCVR comprises three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3), wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 204, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 206, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 208.

2. The pair of polynucleotide molecules of claim 1 , wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 194.

3. The pair of polynucleotide molecules of claim 1 , wherein the polynucleotide comprises an HCDR1 nucleic acid sequence set forth in SEQ ID NO: 195, an HCDR2 nucleic acid sequence set forth in SEQ ID NO: 197, and an HCDR3 nucleic acid sequence set forth in SEQ ID NO: 199.

4. The pair of polynucleotide molecules of claim 1 , wherein the polynucleotide comprises the nucleic acid sequence of SEQ ID NO: 193.

5. The pair of polynucleotide molecules of claim 1 , further encoding an immunoglobulin heavy chain constant region of the antibody.

6. The pair of polynucleotide molecules of claim 5 , wherein the immunoglobulin heavy chain constant region is a human IgG1 constant region.

7. The pair of polynucleotide molecules of claim 6 , wherein the polynucleotide encodes a heavy chain of the antibody comprising the amino acid sequence of SEQ ID NO: 509.

8. A recombinant expression vector comprising the pair of polynucleotide molecules of claim 1 .

9. An isolated host cell comprising the vector of claim 8 .

10. The pair of polynucleotide molecules of claim 1 , wherein the LCVR comprises the amino acid sequence of SEQ ID NO: 202.

11. The pair of polynucleotide molecules of claim 1 , wherein the polynucleotide comprises an LCDR1 nucleic acid sequence set forth in SEQ ID NO: 203, an LCDR2 nucleic acid sequence set forth in SEQ ID NO: 205, and an LCDR3 nucleic acid sequence set forth in SEQ ID NO: 207.

12. The pair of polynucleotide molecules of claim 1 , wherein the polynucleotide comprises the nucleic acid sequence of SEQ ID NO: 201.

13. The pair of polynucleotide molecules of claim 1 , further encoding an immunoglobulin light chain constant region of the antibody.

14. The pair of polynucleotide molecules of claim 13 , wherein the immunoglobulin light chain constant region is a human kappa constant region.

15. The pair of polynucleotide molecules of claim 14 , wherein the polynucleotide encodes a light chain of the antibody comprising the amino acid sequence of SEQ ID NO: 510.

16. A pair of recombinant expression vectors comprising the pair of polynucleotide molecules, respectively, of claim 1 .

17. An isolated host cell comprising the pair of vectors of claim 16 .

18. An isolated host cell comprising a first polynucleotide encoding a heavy chain variable region (HCVR) of an antibody or antigen-binding fragment thereof that binds specifically to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), wherein the HCVR comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 196, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 198, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 200, and a second polynucleotide encoding a light chain variable region (LCVR) of an antibody or antigen-binding fragment thereof that binds specifically to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), wherein the LCVR comprises three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3), wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 204, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 206, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 208.

19. The isolated host cell of claim 18 , wherein the first polynucleotide encodes a heavy chain of the antibody comprising the amino acid sequence of SEQ ID NO: 509, and the second polynucleotide encodes a light chain of the antibody comprising the amino acid sequence of SEQ ID NO: 510.

20. A method of producing an anti-CTLA-4 antibody or antigen-binding fragment thereof by culturing the isolated host cell of claim 18 under conditions permitting production of the antibody or antigen-binding fragment, and recovering the antibody or antigen-binding fragment so produced.

21. The method of claim 20 , wherein the isolated host cell is a CHO cell.

Assignees

• Regeneron Pharma

Inventors

• Hermann Aynur
• Ioffe Ella
• Burova Elena
• Thurston Gavin
• Olson William

Classifications

• C07K2317/76

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

• C07K16/2887

  against CD20 · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title