Vista antagonist and methods of use

Patent metadata

Field	Value
Publication number	US-11752189-B2
Application number	US-201916669552-A
Country	US
Kind code	B2
Filing date	Oct 31, 2019
Priority date	Jun 22, 2012
Publication date	Sep 12, 2023
Grant date	Sep 12, 2023

Abstract

The present invention is directed to a peptide, multimer, conjugate, analog, derivative or mimetic thereof that inhibits the activity of VISTA. The invention further contemplates therapeutic use of the VISTA antagonist peptide, multimer, conjugate, derivative or mimetic thereof, including treating or preventing cancer, bacterial infections, viral infections, parasitic infections and fungal infections, as well as research uses of the antagonist.

First claim

What is claimed is:

1. A method for blocking, inhibiting or neutralizing VISTA-mediated T cell suppression, comprising administering to a subject in need thereof an effective amount of a VISTA antagonist comprising a peptide which is identical to the amino acid sequence of SEQ ID NO:1 (Ser-Ser-Ala-Cys-Asp-Trp-Ile-Lys-Arg-Ser-Cys-His), or a multimer, or a conjugate thereof.

2. A method for stimulating an immune response in a subject, comprising administering to the subject in need thereof an effective amount of a VISTA antagonist comprising a peptide which is identical to the amino acid sequence of SEQ ID NO:1 (Ser-Ser-Ala-Cys-Asp-Trp-Ile-Lys-Arg-Ser-Cys-His), or a multimer, or a conjugate thereof.

3. A method for enhancing anti-cancer or anti-tumor immunity, comprising administering to a subject in need thereof an effective amount of a VISTA antagonist comprising a peptide which is identical to the amino acid sequence of SEQ ID NO:1 (Ser-Ser-Ala-Cys-Asp-Trp-Ile-Lys-Arg-Ser-Cys-His), or a multimer, or a conjugate thereof.

4. The method of claim 1 , which includes the administration of another therapeutic agent wherein the other therapeutic agent is an anti-cancer agent, an anti-viral or other anti-infectious agent, a cytokine or an immune agonist.

5. The method of claim 4 , wherein the immune agonist or anti-cancer agent is selected from CTLA-4-1g, anti-PD-1, PD-L1 or PD-L2 fusion proteins, and EGFR antagonists.

6. The method of claim 1 , wherein the VISTA antagonist is attached to an albumin or an immunoglobulin polypeptide or a fragment thereof and/or the VISTA antagonist is attached to a polyethylene glycol and/or is acetylated.

7. The method of claim 6 , wherein said immunoglobulin polypeptide comprises a human IgG1, IgG2, IgG3 or IgG4 constant region or fragment thereof.

8. The method of claim 7 , wherein said immunoglobulin polypeptide comprises a human IgG1 constant region or fragment thereof.

9. The method of claim 1 , wherein the VISTA antagonist is attached to a moiety that targets said peptide to a target site.

10. The method of claim 2 , wherein the VISTA antagonist is attached to a moiety that targets said peptide to a target site.

11. The method of claim 3 , wherein the VISTA antagonist is attached to a moiety that targets said peptide to a target site.

12. The method of claim 9 , wherein said moiety comprises an antibody or ligand that binds to an antigen, or receptor expressed by a target cell or an infectious agent.

13. The method of claim 10 , wherein said moiety comprises an antibody or ligand that binds to an antigen, or receptor expressed by a target cell or an infectious agent.

14. The method of claim 11 , wherein said moiety comprises an antibody or ligand that binds to an antigen, or receptor expressed by a target cell or an infectious agent.

15. The method of claim 1 , wherein said VISTA antagonist is expressed by a recombinant cell.

16. The method of claim 2 , wherein said VISTA antagonist is expressed by a recombinant cell.

17. The method of claim 3 , wherein said VISTA antagonist is expressed by a recombinant cell.

Assignees

• Dartmouth College
• King S College London

Inventors

• Noelle Randolph J
• Ceeraz Sabrina
• Lemercier Isabelle
• Nowak Elizabeth
• Lines Janet
• Wang Li
• Spaller Mark

Classifications

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K38/10 Primary

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title