Compositions and methods for activating “stimulator of interferon gene”-dependent signalling

Patent metadata

Field	Value
Publication number	US-10653774-B2
Application number	US-201715665378-A
Country	US
Kind code	B2
Filing date	Jul 31, 2017
Priority date	May 18, 2013
Publication date	May 19, 2020
Grant date	May 19, 2020

Abstract

The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides induce STING-dependent type I interferon production, wherein the cyclic purine dinucleotides present in the composition are substantially pure 2′,5′,2′,5′ and 2′,5′,3′,5′ CDNs, and preferably Rp,Rp stereoisomers thereof.

First claim

The invention claimed is:

1. A method of treating cancer in a subject in need thereof, comprising:
administering to the subject one or both of a CTLA-4 pathway antagonist selected from the group consisting of Ipilimumab and tremelimumab and a PD-1 pathway antagonist selected from the group consisting of MK-3475, CT-011, AMP-224, and MDX-1106; and
administering to the subject a compound having the formula:

where R 1 and R 2 are each H,
or a pharmaceutically acceptable salt thereof, wherein the administration of the compound is directly into a tumor mass.

2. The method of claim 1 , wherein the CTLA-4 pathway antagonist is administered.

3. The method of claim 1 , wherein the PD-1 pathway antagonist is administered.

4. The method of claim 2 , wherein the PD-1 pathway antagonist is administered.

5. The method of claim 1 , wherein the compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

6. The method of claim 1 , wherein the compound and one or both of a CTLA-4 pathway antagonist and a PD-1 pathway antagonist are administered as separate administrations.

7. The method of claim 1 , wherein the compound and one or both of a CTLA-4 pathway antagonist and a PD-1 pathway antagonist are administered at different times.

8. The method of claim 1 , wherein the compound and one or both of a CTLA-4 pathway antagonist and a PD-1 pathway antagonist are administered by different routes of administration.

9. The method of claim 1 , wherein the cancer is selected from the group consisting of a colorectal cancer, an aero-digestive squamous cancer, a lung cancer, a brain cancer, a liver cancer, a stomach cancer, a sarcoma, a leukemia, a lymphoma, a multiple myeloma, an ovarian cancer, a uterine cancer, a breast cancer, a melanoma, a prostate cancer, a pancreatic carcinoma, and a renal carcinoma.

Assignees

• Aduro Biotech Inc
• Univ California

Inventors

• Dubensky Jr Thomas W
• Kanne David B
• Leong Meredith Lai Ling
• Lemmens Edward Emile
• Glickman Laura H
• Vance Russell E

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61K39/39 Primary

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K31/7084 Primary

  Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide · CPC title

• A61K2039/55511

  Organic adjuvants · CPC title