IP Library › Granted Patent US 12,290,565
Granted Patent B2
US 12,290,565 · App. 18/056,166 · Granted May 6, 2025

Methods of using anti-PSGL-1 antibodies in combination with JAK inhibitors to treat T-cell mediated inflammatory diseases or cancers

Inventors: Shih-Yao Lin (Taipei, TW); Feng-Lin Chiang (Taipei, TW); You-Chia Yeh (Taipei, TW)
Assignee: AltruBio Inc.
A61K39/3955A61K31/519A61P37/06C07K16/2896A61K2039/505A61K2039/545C07K2317/24C07K2317/92
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Quick Facts
Patent No.
US 12,290,565
App. No.
18/056,166
Granted
May 6, 2025
Kind
B2
Abstract

Provided herein are methods of treating or preventing a T-cell mediated inflammatory disease or cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds to human PSGL-1 in combination with a Janus kinase (JAK) inhibitor. In some embodiments, the T-cell mediated inflammatory disease is GVHD, e.g., acute GVHD or chronic GVHD.

Claims (23)

1. A method of treating a T-cell mediated inflammatory disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of an antibody that specifically binds to human PSGL-1 in combination with a Janus kinase (JAK) inhibitor; wherein the antibody that specifically binds to human PSGL-1 comprises a heavy chain comprising a heavy chain variable (VH) domain and a light chain comprising a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence SFGMH (SEQ ID NO:8), a CDR-H2 comprising the amino acid sequence YINGGSSTIFYANAVKG (SEQ ID NO:9), and a CDR-H3 comprising the amino acid sequence YASYGGGAMDY (SEQ ID NO:10), and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence RSSQSIVHNDGNTYFE (SEQ ID NO: 5), a CDR-L2 comprising the amino acid sequence KVSNRFS (SEQ ID NO:6), and a CDR-L3 comprising the amino acid sequence FQGSYVPLT (SEQ ID NO:7).

2. The method of claim 1 , wherein the JAK inhibitor inhibits JAK1 and/or JAK2.

3. The method of claim 1 , wherein the JAK inhibitor inhibits JAK1 and/or JAK3.

4. The method of claim 1 , wherein the JAK inhibitor is ruxolitinib or tofacitinib.

5. The method of claim 1 , wherein the antibody is a humanized antibody.

6. The method of claim 1 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO:4, and wherein the VL domain comprises the amino acid sequence of SEQ ID NO:3.

7. The method of claim 1 , wherein the antibody that specifically binds to human PSGL-1 comprises a heavy chain and a light chain, and wherein the heavy chain further comprises an antibody constant domain.

8. The method of claim 7 , wherein the constant domain is a human IgG4 constant domain.

9. The method of claim 8 , wherein the constant domain is a human IgG4 constant domain comprising an S228P amino acid substitution at position 228, wherein the numbering is according to EU numbering.

10. The method of claim 1 , wherein the antibody that specifically binds to human PSGL-1 comprises a heavy chain and a light chain, and wherein the light chain is a human kappa light chain.

11. The method of claim 1 , wherein the antibody that specifically binds to human PSGL-1 comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:2, and wherein the light chain comprises the amino acid sequence of SEQ ID NO:1.

12. The method of claim 1 , wherein the antibody that specifically binds to human PSGL-1 comprises the amino acid sequence of SEQ ID NO:23.

13. The method of claim 1 , wherein the T-cell mediated inflammatory disease is graft-versus-host disease (GVHD) or transplantation rejection.

14. The method of claim 13 , wherein the T-cell mediated inflammatory disease is acute GVHD, steroid-refractory acute GVHD (SR-aGVHD), treatment-refractory acute GVHD (TR-aGVHD), or chronic GVHD.

15. The method of claim 1 , wherein the T-cell mediated inflammatory disease is selected from the group consisting of: a skin disorder, multiple sclerosis, rheumatoid arthritis, juvenile arthritis, type I diabetes, lupus, inflammatory bowel disease, Crohn's disease, myasthenia gravis, immunoglobulin nephropathies, myocarditis, psoriasis, ankylosing spondylitis, arthritis, diabetes mellitus, systemic lupus erythematosus, dermatitis, Sjogren's Syndrome, ulcerative colitis, asthma, allergic asthma, scleroderma, autoimmune uveitis, Stevens-Johnson syndrome, vitiligo, alopecia areata, cytokine release syndrome, hidradenitis suppurativa, sarcoidosis, primary biliary cirrhosis, uveitis posterior, allergies, and autoimmune thyroid disorder.

16. The method of claim 1 , wherein human PSGL-1 comprises the amino acid sequence of SEQ ID NO:11 or SEQ ID NO:22.

17. The method of claim 1 , wherein the subject is a human.

18. The method of claim 1 , wherein the antibody is administered by intravenous infusion.

19. The method of claim 1 , wherein the antibody is a monoclonal antibody.

20. The method of claim 1 , wherein the JAK inhibitor is administered to the subject before, after, or simultaneous with administration of the antibody.

21. The method of claim 1 , wherein the JAK inhibitor is administered orally to the subject.

22. The method of claim 1 , wherein, prior to administration of the antibody and the JAK inhibitor, the subject has been treated with a corticosteroid.

23. The method of claim 1 , wherein administration of the antibody and the JAK inhibitor results in a reduction in one or more symptoms of the T-cell mediated inflammatory disease in the subject.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 5, 2023
From: LIN, SHIH-YAO; CHIANG, FENG-LIN; YEH, YOU-CHIA
To: ALTRUBIO INC.
Reel/Frame 062288/0789 →
Continuity (2)
Provisional Application 63280463 · Nov 17, 2021
Related Publication 20230149544A1 · May 18, 2023
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