Il-15-based molecules and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2023233649-A1
Application number	US-202318175112-A
Country	US
Kind code	A1
Filing date	Feb 27, 2023
Priority date	Jun 30, 2014
Publication date	Jul 27, 2023
Grant date	—

Abstract

The invention features combination therapies using an IL-15-based superagonist complex and an antibody to effectively treat subjects with cancer and infectious diseases.

First claim

1 .- 30 . (canceled)

31 . A method for treating a neoplasia in a subject, the method comprising: administering to said subject an effective amount of an anti-CD38 antibody and an effective amount of a pharmaceutical composition comprising an IL-15:IL-15RαSu complex, thereby treating the neoplasia.

32 . The method of claim 31 , wherein the IL-15:IL-15RαSu complex comprises a wild type IL-15 molecule.

33 . The method of claim 31 , wherein the IL-15:IL-15RαSu complex comprises an IL-15 molecule having the amino acid sequence of SEQ ID NO:3.

34 . The method of claim 31 , wherein the IL-15:IL-15RαSu complex comprises an IL-15RαSuFc fusion construct having the amino acid sequence of SEQ ID NO: 6.

35 . The method of claim 31 , wherein the IL-15:IL-15RαSu complex is Alt-803.

36 . The method of claim 31 , wherein the subject is suffering from a neoplasia and the neoplasia is selected from the group consisting of a glioblastoma, prostate cancer, hematological cancer, B-cell neoplasms, multiple myeloma, B-cell lymphoma, Hodgkin's lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, cutaneous T-cell lymphoma, T-cell lymphoma, a solid tumor, urothelial/bladder carcinoma, melanoma, lung cancer, renal cell carcinoma, breast cancer, gastric and esophageal cancer, head and neck cancer, colorectal cancer, ovarian cancer, non-small cell lung carcinoma, B cell non-Hodgkin lymphoma, and squamous cell head and neck carcinoma.

37 . The method of claim 36 , wherein the subject is suffering from multiple myeloma.

38 . The method of claim 31 , Wherein the effective amount of the IL-15:IL-15RαSu complex is administered daily.

39 . The method of claim 31 , wherein the effective amount of the IL-15:IL-15RαSu complex is between 0.1 μg/kg and 100 mg/kg.

40 . The method of claim 31 , wherein the elective amount of the IL-15:IL-15RαSu complex is administered once or twice per week.

41 . The method of claim 39 , wherein the effective amount of the IL-15:IL-15RαSu complex is between 0.1 μg/kg and 1 mg/kg.

42 . The method of claim 31 , wherein the pharmaceutical composition is administered by subcutaneous, intravenous, intraperitoneal, intramuscular, or intradermal injection, or by intravesicular instillation.

43 . The method of claim 31 , wherein the anti-CD38 antibody is daratumumab.

44 . The method of claim 31 , wherein antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody dependent cellular phagocytosis (ADCP) mediated by said antibody against tumor cells in said subject is augmented by at least 5% following said administration.

45 . The method of claim 31 , wherein said antibody and the IL-15:IL-15RαSu complex increases levels of blood NK cell, T cell, neutrophil or monocyte counts or activity.

46 . The method of claim 31 , wherein said antibody and the IL-15:IL-15RαSu complex stimulate CD4+ or CD8+ T cells to kill tumor cells.

47 . The method of claim 31 , wherein said antibody and the IL-15:IL-15RαSu complex stimulate NK cells to kill tumor cells.

48 . The method of claim 31 , wherein said antibody and the IL-15:IL-15RαSu complex stimulate neutrophils or monocytic cells to kill tumor cells.

49 . The method of claim 31 , wherein said administration results in a decrease in the number of tumor cells.

50 . The method of claim 31 , wherein said administration results in a decrease in disease progression of the neoplasia.

51 . The method of claim 31 , wherein said administration results in prolonged survival of said subjects compared to untreated subjects.

52 . The method of claim 31 wherein said subject is a human.

53 . The method of claim 31 , wherein said administration prevents future recurrence of said neoplasia.

54 . The method of claim 31 , wherein said and body and the IL-15:IL-15RαSu complex increase blood cytokine levels.

55 . The method of claim 54 , wherein said cytokine comprises IFN-γ and/or IL-6.

56 . A kit for use in the treatment of a neoplasia in a subject, the kit comprising: a first vial comprising an effective amount of an anti-CD38 antibody; a second vial comprising an effective amount of a pharmaceutical composition comprising an IL-15:IL-15αSu complex, wherein said IL-15:IL-15RαSu complex comprises an IL-15RαSu and an IL-15 molecule, wherein the contents of the first and second vials are formulated for administration to a patient in need thereof; and directions for the use thereof.

57 . The kit of claim 56 , wherein IL-15:IL-15RαSu complex comprises a stabilized IL-15RαSu fusion protein.

58 . The kit of claim 57 , wherein the stabilized IL-15RαSu fusion protein comprises an immunoglobulin Fc domain.

59 . The kit of claim 58 , wherein the IL-15:IL-15RαSu complex is Alt-803.

60 . The kit of claim 56 , wherein the anti-CD38 Ab is daratumumab.

61 . The kit of claim 56 , wherein the neoplasia is multiple myeloma.

Assignees

• Altor Bioscience Llc

Inventors

• Liu Bai
• Rhode Peter
• Xu Wenxin
• Wong Hing C

Classifications

• C07K2319/32

  fusions with soluble part of a cell surface receptor, "decoy receptors" · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/1793

  for cytokines; for lymphokines; for interferons · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title