Anti-CD137 antibodies and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11242385-B2
Application number	US-201815951950-A
Country	US
Kind code	B2
Filing date	Apr 12, 2018
Priority date	Apr 13, 2017
Publication date	Feb 8, 2022
Grant date	Feb 8, 2022

Abstract

The instant disclosure provides antibodies that specifically bind to CD137 (e.g., human CD137) and increases CD137 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

First claim

What is claimed:

1. A polynucleotide encoding a VH, a VL, or a VH and a VL of an antibody that comprises: a VH comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence of SEQ ID NO: 7; and/or a VL comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence of SEQ ID NO: 8.

2. The polynucleotide of claim 1 , wherein the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences of SEQ ID NOs: 1, 2, 3, 4, 5, and 6, respectively.

3. The polynucleotide of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 7, and the VL comprises the amino acid sequence of SEQ ID NO: 8.

4. The polynucleotide of claim 1 , wherein the antibody comprises a heavy chain constant region selected from the group consisting of IgG 1 , IgG 2 , IgG 3 , IgG 4 , IgA 1 , and IgA 2 , optionally wherein:
(a) the heavy chain constant region is human IgG 1 constant region comprising an N297A mutation;
(b) the heavy chain constant region is human IgG 1 constant region comprising S267E and L328F mutations;
(c) the heavy chain constant region is human IgG 2 constant region comprising a N297A mutation; or
(d) the heavy chain constant region is human IgG 4 constant region comprising an S228P mutation.

5. The polynucleotide of claim 4 , wherein the heavy chain constant region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 15-20.

6. The polynucleotide of claim 1 , wherein the antibody comprises a light chain constant region selected from the group consisting of a human kappa light chain constant region and a human lambda light chain constant region.

7. The polynucleotide of claim 6 , wherein the light chain constant region comprises the amino acid sequence of SEQ ID NO: 22.

8. The polynucleotide of claim 1 , wherein the antibody comprises a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 9-14 and 49-54, and a light chain comprising the amino acid sequence of SEQ ID NO: 21.

9. The polynucleotide of claim 8 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9, and a light chain comprising the amino acid sequence of SEQ ID NO: 21.

10. A vector comprising the polynucleotide of claim 1 .

11. A vector comprising the polynucleotide of claim 3 .

12. A vector comprising the polynucleotide of claim 9 .

13. A recombinant host cell comprising:
(a) a polynucleotide encoding a VH and a VL of an antibody; or
(b) a first polynucleotide encoding a VH of an antibody and second polynucleotide encoding a VL of the antibody,
wherein the antibody comprises: a VH comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence of SEQ ID NO: 7; and a VL comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence of SEQ ID NO: 8.

14. The recombinant host cell of claim 13 , wherein the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences of SEQ ID NOs: 1, 2, 3, 4, 5, and 6, respectively.

15. The recombinant host cell of claim 13 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 7, and the VL comprises the amino acid sequence of SEQ ID NO: 8.

16. The recombinant host cell of claim 13 , wherein the antibody comprises a heavy chain constant region selected from the group consisting of IgG 1 ,IgG 2 , IgG 3 , IgG 4 , IgA 1 , and IgA 2 , optionally wherein:
(a) the heavy chain constant region is human IgG 1 constant region comprising an N297A mutation;
(b) the heavy chain constant region is human IgG 1 constant region comprising S267E and L328F mutations;
(c) the heavy chain constant region is human IgG 2 constant region comprising a N297A mutation; or
(d) the heavy chain constant region is human IgG 4 constant region comprising an S228P mutation.

17. The recombinant host cell of claim 16 , wherein the heavy chain constant region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 15-20.

18. The recombinant host cell of claim 13 , wherein the antibody comprises a light chain constant region selected from the group consisting of a human kappa light chain constant region and a human lambda light chain constant region.

19. The recombinant host cell of claim 18 , wherein the light chain constant region comprises the amino acid sequence of SEQ ID NO: 22.

20. The recombinant host cell of claim 13 , wherein the antibody comprises a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 9-14 and 49-54, and a light chain comprising the amino acid sequence of SEQ ID NO: 21.

21. The recombinant host cell of claim 20 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9, and a light chain comprising the amino acid sequence of SEQ ID NO: 21.

22. A method of producing an antibody that specifically binds to human CD137, the method comprising culturing the host cell of claim 13 under suitable conditions so that the polynucleotide is expressed and the antibody is produced.

23. A method of producing an antibody that specifically binds to human CD137, the method comprising culturing the host cell of claim 15 under suitable conditions so that the polynucleotide is expressed and the antibody is produced.

24. A method of producing an antibody that specifically binds to human CD137, the method comprising culturing the host cell of claim 21 under suitable conditions so that the polynucleotide is expressed and the antibody is produced.

Assignees

• Agenus Inc

Inventors

• Xiao Yanping
• Wilson Nicholas Stuart
• Morin Benjamin Maxime
• Findeis Mark Arthur
• Mundt Cornelia Anne
• Van Dijk Marc
• Chand Dhan Sidhartha
• Savitsky David Adam
• Underwood Dennis John
• Ignatovich Olga

Classifications

• C12N5/0636

  T lymphocytes · CPC title

• C12N5/0635

  B lymphocytes · CPC title

• C12N15/79

  Vectors or expression systems specially adapted for eukaryotic hosts · CPC title

• C12N15/63

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

• C12N15/64

  General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host · CPC title