Heterocyclic compounds and uses thereof

• US 10,675,286 B2
• Filed: 08/09/2017
• Issued: 06/09/2020
• Est. Priority Date: 03/19/2014
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Kutok, Jeffery L., Winkler, David G., Palombella, Vito J.
• Primary Examiner(s): Jean-Louis, Samira J
• Application Number:
  US15/672,964
• Publication Number:
  US 20180055852A1
• Time in Patent Office: 1,035 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 39/0005 Vertebrate antigens from snakes A61K39/38
• CPC Class Codes: A61K 39/39533 against materials from animals
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 39/39566 against immunoglobulins, e.g. anti-idiotypic antibodies
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 : for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/12 : for electrolyte homeostasis
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 16/2827 : against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Claims

1. A method of treating a solid tumor in a subject, comprising administering to the subject a therapeutically effective amount of a compound of the formula:

2. The method of claim 1, wherein the anti-PD-1 antibody is pembrolizumab.

3. The method of claim 1, wherein the anti-PD-1 antibody is nivolumab.

4. The method of claim 1, wherein the solid tumor is melanoma.

5. The method of claim 4, wherein the melanoma is relapsed after or refractory to a prior therapy, and wherein the prior therapy is an immune checkpoint therapy.

6. The method of claim 1, wherein the solid tumor is gall bladder cancer.

7. The method of claim 1, wherein the solid tumor is triple negative breast cancer.

8. The method of claim 7, wherein the triple negative breast cancer is naive to immune checkpoint therapy.

9. The method of claim 8, wherein the immune checkpoint therapy is a treatment by a PD-1 or PD-L1 inhibitor.

10. The method of claim 1, wherein the solid tumor is adrenal gland cancer.

11. The method of claim 1, wherein the solid tumor is mesothelioma.

12. The method of claim 11, wherein the mesothelioma is epithelioid mesothelioma, sarcomatoid mesothelioma, or biphasic mesothelioma.

13. The method of claim 1, wherein the compound is administered at a dose of about 1-60 mg once daily.

14. The method of claim 1, wherein the compound is administered at a dose of about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, or about 60 mg once daily.

15. The method of claim 14, wherein the compound is administered at a dose of about 30 mg once daily.

16. The method of claim 14, wherein the compound is administered at a dose of about 40 mg once daily.

17. The method of claim 1, wherein the anti-PD-1 antibody is administered at a dose of 1 to 5 mg/kg every 2 weeks.

18. The method of claim 17, wherein the anti-PD-1 antibody is administered at a dose of about 3 mg/kg every 2 weeks.

19. The method of claim 1, wherein the subject has a high number of MDSC, compared to a reference value.