Compositions comprising IL-15-based molecules and immune checkpoint inhibitor antibodies

Patent metadata

Field	Value
Publication number	US-11992516-B2
Application number	US-202218045572-A
Country	US
Kind code	B2
Filing date	Oct 11, 2022
Priority date	Jun 30, 2014
Publication date	May 28, 2024
Grant date	May 28, 2024

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

What is claimed is:

1. A composition comprising: synergistically effective amounts of an immune checkpoint inhibitor antibody and an IL-15N72D:IL-15RαSu/Fc complex (ALT-803), wherein the immune checkpoint inhibitor antibody is a CTLA-4, PD-1, or PD-L1 antibody, wherein said ALT-803 comprises a dimeric IL-15RaSu/Fc and two IL-15N72D molecules, wherein the composition is formulated for administration to a human subject suffering from a neoplasia comprising the immune checkpoint molecule targeted by the antibody, and wherein the amounts are synergistically effective for treatment of said neoplasia.

2. The composition of claim 1 , wherein the IL-15N72D molecule comprises the amino acid sequence of SEQ ID NO: 3.

3. The composition of claim 1 , wherein the IL-15RαSu/Fc comprises the amino acid sequence of SEQ ID NO: 6.

4. The composition of claim 1 , wherein 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.

5. The composition of claim 1 , wherein the synergistically effective amount of said ALT-803 is between 0.1 μg/kg and 100 mg/kg.

6. The composition of claim 5 , wherein the synergistically effective amount of said ALT-803 is between 0.1 μg/kg and 1 mg/kg.

7. The composition of claim 1 , wherein the ALT-803 is formulated for systemic administration, intravenous administration, subcutaneous administration, intramuscular administration, intravesical administration or by instillation administration to the subject.

8. The composition of claim 1 , wherein the ALT-803 is formulated for subcutaneous administration to the subject.

9. The composition of claim 1 , wherein the antibody is formulated for intravenous administration to the subject.

10. The composition of claim 1 , wherein the antibody is selected from the group consisting of ipilimumab, nivolumab, pembrolizumab, and durvalumab.

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