IL10 agonists and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12187772-B2
Application number	US-202318308892-A
Country	US
Kind code	B2
Filing date	Apr 28, 2023
Priority date	May 12, 2020
Publication date	Jan 7, 2025
Grant date	Jan 7, 2025

Abstract

The present disclosure relates to IL10 agonists with improved anti-tumor therapeutic efficacy and uses thereof. Certain IL10 agonists disclosed herein comprise an IgG Fc domain, a linker moiety, and an IL10 moiety.

First claim

What is claimed is:

1. A method of treating cancer, the method comprising administering to a subject in need thereof:
(a) an IL10 agonist which comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOS: 34, 37, and 38 and lacks an antibody variable region; and
(b) an anti-PD1 antibody.

2. The method of claim 1 , wherein the IL10 agonist comprises CH2 and CH3 domains from an IgG1.

3. The method of claim 1 , wherein the IL10 agonist comprises CH2 and CH3 domains from an IgG4.

4. The method of claim 1 , wherein the IL10 agonist comprises the amino acid sequence of SEQ ID NO:31.

5. The method of claim 1 , wherein the IL10 agonist comprises a monomer or multimer of G n S wherein n is 1, 2 or 3.

6. The method of claim 1 , wherein the IL10 agonist comprises an amino acid sequence having at least 95% sequence identity to mature human IL10 (SEQ NO: 1).

7. The method of claim 6 , wherein the IL10 agonist comprises the amino acid sequence of mature human IL10 (SEQ NO: 1).

8. The method of claim 1 , wherein the IL10 agonist is a homodimer.

9. The method of claim 1 , wherein the IL10 agonist comprises two IgG Fc domains.

10. The method of claim 1 , wherein the IL10 agonist comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 34.

11. The method of claim 1 , wherein the IL10 agonist comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 37.

12. The method of claim 1 , wherein the IL10 agonist comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 38.

13. The method of claim 1 , wherein the IL10 agonist is the product of recombinant expression in a mammalian cell.

14. The method of claim 1 , wherein the IL10 agonist is in the form of a pharmaceutical composition comprising the IL10 agonist and an excipient.

15. The method of claim 14 , in which less than 30% of the IL10 agonist is present in the pharmaceutical composition in an aggregate form, as determined by size exclusion ultra performance liquid chromatography (SE-UPLC).

16. The method of claim 1 , wherein the anti-PD1 antibody is administered to the subject prior to administration of the IL10 agonist.

17. The method of claim 1 , wherein the anti-PD1 antibody is administered to the subject following administration of the IL10 agonist.

18. The method of claim 1 , wherein the anti-PD1 antibody is administered to the subject simultaneously with administration of the IL10 agonist.

19. The method of claim 1 , wherein the cancer is a solid tumor.

20. The method of claim 1 , wherein the solid tumor is colon cancer.

21. The method of claim 19 , wherein the solid tumor is melanoma.

22. The method of claim 19 , wherein the solid tumor is squamous cell carcinoma.

23. The method of claim 19 , wherein the solid tumor is lymphoma.

24. The method of claim 19 , wherein the solid tumor is a tumor of the pancreas.

25. The method of claim 19 , wherein the solid tumor is a tumor of the lung.

26. The method of claim 10 , wherein the IL10 agonist comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 34.

27. The method of claim 10 , wherein the IL10 agonist comprises the amino acid sequence of SEQ ID NO: 34.

28. The method of claim 11 , wherein the IL10 agonist comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 37.

29. The method of claim 11 , wherein the IL10 agonist comprises the amino acid sequence of SEQ ID NO: 37.

30. The method of claim 12 , wherein the IL10 agonist comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 38.

31. The method of claim 12 , wherein the IL10 agonist comprises the amino acid sequence of SEQ ID NO: 38.

Assignees

• Regeneron Pharma

Inventors

• Dai Jie
• Molina-Portela Maria Del Pilar
• Ioffe Ella
• Mohrs Markus

Classifications

• A61K47/68

  the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment · CPC title

• A61K47/6889

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title

• A61K38/2066

  IL-10 · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• C07K2317/53

  Hinge · CPC title