IP Library › Granted Patent US 12,246,066
Granted Patent B2
US 12,246,066 · App. 18/187,367 · Granted Mar 11, 2025

Anti-CTLA-4 antibodies and methods of use thereof

Inventors: Marc Van Dijk (Bosch En Duin, NL); Cornelia Anne Mundt (Lorrach, DE); Gerd Ritter (New York, NY); David Schaer (Mamaroneck, NY); Jedd David Wolchok (New York, NY); Taha Merghoub (Jersey City, NJ); Nicholas Stuart Wilson (San Carlos, CA); David Adam Savitsky (Boxford, MA); Mark Arthur Findeis (Lexington, MA); Dennis John Underwood (Lexington, MA); Jean-Marie Cuillerot (Somerville, MA); Igor Proscurshim (Carlisle, MA); Olga Shebanova (Somerville, MA)
Assignees: AGENUS INC.; Ludwig Institute for Cancer Research Ltd.; Memorial Sloan Kettering Cancer Center
A61K39/39558A61P11/00A61P35/04C07K16/2818A61K2039/505A61K2039/507A61K2039/572C07K2317/21C07K2317/52C07K2317/55C07K2317/732C07K2317/76Y02A50/30
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Quick Facts
Patent No.
US 12,246,066
App. No.
18/187,367
Granted
Mar 11, 2025
Kind
B2
Abstract

The instant disclosure provides antibodies that specifically bind to CTLA-4 (e.g., human CTLA-4) and antagonize CTLA-4 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.

Claims (35)

1. An isolated antibody that specifically binds to human CTLA-4, the antibody comprising:

a VH comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 20; and

a VL comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence set forth in SEQ ID NO: 9,

wherein the CDRH1, CDRH2, and CDRH3 sequences of the antibody are not SEQ ID NOs: 10, 11, and 13, respectively.

2. The isolated antibody of claim 1 , wherein: the VH comprises the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 2; and the VL comprises the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence set forth in SEQ ID NO: 9.

3. The isolated antibody of claim 1 , wherein: the VH comprises the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 4; and the VL comprises the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence set forth in SEQ ID NO: 9.

4. The isolated antibody of claim 1 , wherein: the VH comprises the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 6; and the VL comprises the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence set forth in SEQ ID NO: 9.

5. The isolated antibody of claim 1 , wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the antibody comprise the amino acid sequences set forth in SEQ ID NOs: 10, 18, 19, 15, 16, and 17, respectively.

6. The isolated antibody of claim 1 , wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the antibody comprise the amino acid sequences set forth in SEQ ID NOs: 10, 11, 14, 15, 16, and 17, respectively.

7. The isolated antibody of claim 1 , wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the antibody comprise the amino acid sequences set forth in SEQ ID NOs: 10, 12, 13, 15, 16, and 17, respectively.

8. The isolated antibody of claim 1 , wherein the antibody comprises:

a VH comprising an amino acid sequence which is at least 75% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-8 and 20; and/or

a VL comprising an amino acid sequence which is at least 75% identical to the amino acid sequence of SEQ ID NO: 9.

9. The isolated antibody of claim 1 , wherein the VH and the VL comprise the amino acid sequences set forth in SEQ ID NOs: 2 and 9; 3 and 9; 4 and 9; 5 and 9; 6 and 9; or 7 and 9, respectively.

10. The isolated antibody of claim 1 , wherein the antibody comprises a heavy chain constant region selected from the group consisting of human IgG 1 , IgG 2 , IgG 3 , IgG 4 , IgA 1 , and IgA 2 .

11. The isolated antibody of claim 1 , wherein:

the antibody comprises an IgG 1 heavy chain constant region, optionally wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 28;

the antibody comprises an IgG 1 heavy chain constant region comprising S239D/1332E mutations, numbered according to the EU numbering system, optionally wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 29;

the antibody comprises an IgG 1 heavy chain constant region comprising S239D/A330L/1332E mutations, numbered according to the EU numbering system, optionally wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 30; or

the antibody comprises an IgG 1 heavy chain constant region comprising L235V/F243L/R292P/Y300L/P396L mutations, numbered according to the EU numbering system, optionally wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 31.

12. The isolated antibody of claim 11 , wherein the IgG 1 heavy chain constant region is afucosylated IgG 1 .

13. The isolated antibody of claim 1 , wherein the antibody comprises a human IgG heavy chain constant region that is a variant of a wild type human IgG heavy chain constant region, wherein the variant human IgG heavy chain constant region binds to FcγRIIIA with a higher affinity than the wild type human IgG heavy chain constant region binds to FcγRIIIA, optionally wherein the variant human IgG heavy chain constant region is a variant human IgG 1 heavy chain constant region.

14. The isolated antibody of claim 1 , wherein the antibody comprises a light chain constant region selected from the group consisting of human Igk and Ig), optionally wherein the antibody comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO: 32.

15. The isolated antibody of claim 1 , wherein:

the antibody binds to the same epitope of human CTLA-4 as an antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 8 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 9; and/or

the antibody binds to an epitope located within a region of human CTLA-4 consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 34-39.

16. The isolated antibody of claim 1 conjugated to a cytotoxic agent, cytostatic agent, toxin, radionuclide, or detectable label.

17. An isolated antibody that specifically binds to human CTLA-4, the antibody comprising:

a heavy chain comprising the amino acid sequence of SEQ ID NO: 23, and a light chain comprising the amino acid sequence of SEQ ID NO: 27;

a heavy chain comprising the amino acid sequence of SEQ ID NO: 24, and a light chain comprising the amino acid sequence of SEQ ID NO: 27;

a heavy chain comprising the amino acid sequence of SEQ ID NO: 26, and a light chain comprising the amino acid sequence of SEQ ID NO: 27;

a heavy chain comprising the amino acid sequence of SEQ ID NO: 47, and a light chain comprising the amino acid sequence of SEQ ID NO: 27; or

a heavy chain comprising the amino acid sequence of SEQ ID NO: 48, and a light chain comprising the amino acid sequence of SEQ ID NO: 27.

18. A polypeptide comprising a VH comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 2, 4, 5, 6, 7, or 8.

19. A polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 23, 24, 25, 26, 47, or 48.

Assignments (6)
SECURITY INTEREST Recorded Mar 31, 2025
From: AGENUS, INC.
To: LIGAND PHARMACEUTICALS INCORPORATED
Reel/Frame 070680/0634 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2023
From: WILSON, NICHOLAS STUART; SAVITSKY, DAVID ADAM; FINDEIS, MARK ARTHUR; UNDERWOOD, DENNIS JOHN; CUILLEROT, JEAN-MARIE; PROSCURSHIM, IGOR; SHEBANOVA, OLGA
To: AGENUS INC.
Reel/Frame 063698/0191 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2023
From: VAN DIJK, MARC; MUNDT, CORNELIA ANNE
To: AGENUS SWITZERLAND INC.
Reel/Frame 063698/0227 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2023
From: AGENUS SWITZERLAND INC.
To: AGENUS INC.
Reel/Frame 063698/0248 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2023
From: SCHAER, DAVID; WOLCHOK, JEDD DAVID; MERGHOUB, TAHA
To: MEMORIAL SLOAN KETTERING CANCER CENTER
Reel/Frame 063698/0296 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2023
From: RITTER, GERD
To: LUDWIG INSTITUTE FOR CANCER RESEARCH LTD
Reel/Frame 063698/0308 →
Continuity (5)
Division 17121229 · Dec 14, 2020
Division 17030650 · Sep 24, 2020
Division 15834290 · Dec 7, 2017
Provisional Application 62431272 · Dec 7, 2016
Related Publication 20230330225A1 · Oct 19, 2023
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