IP Library › Granted Patent US 12,233,066
Granted Patent B2
US 12,233,066 · App. 17/286,026 · Granted Feb 25, 2025

Combinations of inhibitors of influenza virus replication

Inventors: Irina C. Jacobson (Sammamish, WA); Biing Yuan Lin (Bellevue, WA); Sam S K Lee (Edmonds, WA)
Assignee: COCRYSTAL PHARMA, INC.
A61K31/519A61K39/145A61K45/06
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,233,066
App. No.
17/286,026
Granted
Feb 25, 2025
Kind
B2
Abstract

Provided herein are combinations of compounds that can inhibit the replication of influenza viruses, reduce the amount of influenza viruses, and/or treat influenza.

Claims (20)

1. A method of treating influenza virus infection or reducing influenza virus replication in a subject in need thereof comprising administering to the subject a therapeutically effective amount of (1) 3-(2-(5-chloro-1 H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid or a pharmaceutically acceptable salt or solvate thereof, and (2) a second antiviral agent selected from the group consisting of baloxavir marboxil, baloxavir, oseltamivir, oseltamivir acid, and favipiravir, or a pharmaceutically acceptable salt or solvate thereof.

2. The method of any one of claim 1 , wherein the 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid or a pharmaceutically acceptable salt or solvate thereof is administered before the second antiviral agent.

3. The method of any one of claim 1 , wherein the 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid or a pharmaceutically acceptable salt or solvate thereof is administered after the second antiviral agent.

4. The method of any one of claim 1 , wherein the 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid or a pharmaceutically acceptable salt or solvate thereof and the second antiviral agent are administered at the same time.

5. The method of claim 4 , wherein the 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid or a pharmaceutically acceptable salt or solvate thereof and the second antiviral agent are co-formulated.

6. The method of claim 4 , wherein the 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid or a pharmaceutically acceptable salt or solvate thereof and the second antiviral agent are in separate formulations.

7. The method of claim 1 , wherein the second antiviral agent is oseltamivir, oseltamivir acid, or a pharmaceutically acceptable salt or solvate thereof.

8. The method of claim 1 , wherein the second antiviral agent is baloxavir marboxil, baloxavir, or a pharmaceutically acceptable salt or solvate thereof.

9. The method of claim 1 , wherein the second antiviral agent is favipiravir, or a pharmaceutically acceptable salt or solvate thereof.

10. A method for treating influenza virus infection or replication, comprising administering to a human patient having or at risk of influenza infection 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3 -d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid, or a pharmaceutically acceptable salt or solvate thereof in a dose of about 10-1,000 mg/kg and a therapeutically effective amount of a second antiviral agent selected from the group consisting of baloxavir marboxil, baloxavir, oseltamivir, oseltamivir acid, and favipiravir, or a pharmaceutically acceptable salt or solvate thereof.

11. The method of claim 10 , wherein the second antiviral agent is oseltamivir, oseltamivir acid, or a pharmaceutically acceptable salt or solvate thereof.

12. The method of claim 10 , wherein the second antiviral agent is baloxavir marboxil, baloxavir, or a pharmaceutically acceptable salt or solvate thereof.

13. The method of claim 10 , wherein the second antiviral agent is favipiravir, or a pharmaceutically acceptable salt or solvate thereof.

14. A combination comprising 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid or a pharmaceutically acceptable salt or solvate thereof and a second antiviral agent selected from the group consisting of baloxavir marboxil, baloxavir, oseltamivir, oseltamivir acid, and favipiravir, or a pharmaceutically acceptable salt or solvate thereof.

15. The combination of claim 14 , wherein the second antiviral agent is oseltamivir, oseltamivir acid, or a pharmaceutically acceptable salt or solvate thereof.

16. The combination of claim 14 , wherein the second antiviral agent is baloxavir marboxil, baloxavir, or a pharmaceutically acceptable salt or solvate thereof.

17. The combination of claim 14 , wherein the second antiviral agent is favipiravir, or a pharmaceutically acceptable salt or solvate thereof.

18. A method for treating an Influenza A or Influenza B infection in a host, reducing endonuclease activity of influenza polymerase in an influenza A or B virus in a host, or reducing influenza virus replication in a host, comprising administering to the host a therapeutic amount of the combination of claim 14 .

19. The method of claim 18 , further comprising contacting the influenza virus with or administering to the host a therapeutically effective amount of a third antiviral agent.

20. The method of claim 19 , further comprising administering to the host an influenza vaccine before, after, or concurrently with the combination.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 16, 2021
From: JACOBSON, IRINA C.; LIN, BIING YUAN; LEE, SAM SK
To: COCRYSTAL PHARMA, INC.
Reel/Frame 056567/0509 →
Continuity (2)
Provisional Application 62746884 · Oct 17, 2018
Related Publication 20210353629A1 · Nov 18, 2021
References Cited (61)
US 4079038A · Choi et al. · 1978 [cited by applicant]
US 4093709A · Choi et al. · 1978 [cited by applicant]
US 4131648A · Choi et al. · 1978 [cited by applicant]
US 4138344A · Choi et al. · 1979 [cited by applicant]
US 4180646A · Choi et al. · 1979 [cited by applicant]
US 4304767A · Heller et al. · 1981 [cited by applicant]
US 4353656A · Sohl et al. · 1982 [cited by applicant]
US 4501729A · Boucher et al. · 1985 [cited by applicant]
US 4753788A · Gamble · 1988 [cited by applicant]
US 4778054A · Newell et al. · 1988 [cited by applicant]
US 4811731A · Newell et al. · 1989 [cited by applicant]
US 4946931A · Heller et al. · 1990 [cited by applicant]
US 5035237A · Newell et al. · 1991 [cited by applicant]
US 5590645A · Davies et al. · 1997 [cited by applicant]
US 5860419A · Davies et al. · 1999 [cited by applicant]
US 5873360A · Davies et al. · 1999 [cited by applicant]
US 5968543A · Heller et al. · 1999 [cited by applicant]
US 6413536B1 · Gibson et al. · 2002 [cited by applicant]
US 6596296B1 · Nelson et al. · 2003 [cited by applicant]
US 6613355B2 · Ng et al. · 2003 [cited by applicant]
US 6632666B2 · Baust et al. · 2003 [cited by applicant]
US 6667371B2 · Ng et al. · 2003 [cited by applicant]
US 6732732B2 · Edwards et al. · 2004 [cited by applicant]
US 6749835B1 · Lipp et al. · 2004 [cited by applicant]
US 6766799B2 · Edwards et al. · 2004 [cited by applicant]
US 6848197B2 · Chen et al. · 2005 [cited by applicant]
US 6956021B1 · Edwards et al. · 2005 [cited by applicant]
US 7008644B2 · Batycky et al. · 2006 [cited by applicant]
US 7032593B2 · Johnston et al. · 2006 [cited by applicant]
US 7048908B2 · Basu et al. · 2006 [cited by applicant]
US 7146978B2 · Edwards et al. · 2006 [cited by applicant]
US 7182961B2 · Batycky et al. · 2007 [cited by applicant]
US 7252840B1 · Batycky et al. · 2007 [cited by applicant]
US 7279182B2 · Lipp et al. · 2007 [cited by applicant]
US 7384649B2 · Batycky et al. · 2008 [cited by applicant]
US 7678364B2 · Edwards et al. · 2010 [cited by applicant]
US 11014941B2 · Jacobson · 2021 [cited by examiner]
US 11040048B2 · Shishido et al. · 2021 [cited by applicant]
US 11098042B2 · Ren et al. · 2021 [cited by applicant]
CN 108276401A · 2018 [cited by applicant]
EP 69715A1 · 1983 [cited by applicant]
EP 0504263B1 · 1997 [cited by applicant]
GB 2064336A · 1981 [cited by applicant]
GB 2129691A · 1984 [cited by applicant]
GB 2169265A · 1986 [cited by applicant]
GB 2178965A · 1987 [cited by applicant]
GB 2242134A · 1991 [cited by applicant]
WO WO2005023335A2 · 2005 [cited by applicant]
WO WO2017104691A1 · 2017 [cited by applicant]
WO WO2018157830A1 · 2018 [cited by applicant]
WO WO2018200425A1 · 2018 [cited by applicant]
Chinese Patent Appliation No. 201980073306.0, Office Action and Search Report, dated Feb. 5, 2024. [cited by applicant]
Xiong et al., Design, synthesis and biological evaluation of novel, orally bioavailable pyrimidine-fused heterocycles as influenza PB2 inhibitors, European Journal of Medicinal Chemistry, 162:249-265 (2019). [cited by applicant]
Berge et al., Pharmaceutical Salts, J. Pharm. Sci., 66(1): 1-19 (Jan. 1977). [cited by applicant]
Byrn et al., Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit, Antimicrob Agents Chemother., 59(3):1569-82 (2015). [cited by applicant]
Chou et al., Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors, Adv. Enzyme Regul., 22:27-55 (1984). [cited by applicant]
Holford et al., Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models, Clin. Pharmacokinet., 6(6):429-53 (Nov.-Dec. 1981). [cited by applicant]
International Application No. PCT/US2019/056632, International Search Report and Written Opinion, mailed Jan. 28, 2020. [cited by applicant]
Liu et al., A Small-Molecule Compound Has Anti-influenza A Virus Activity by Acting as a “PB2 Inhibitor”, Mol. Pharm., 15(9):4110-4120 (2018). [cited by applicant]
Stelzmueller et al., Thoracic endovascular repair for acute complicated type B aortic dissections, J. Vasc. Surg., 69(2):318-26 (2019). [cited by applicant]
Willis et al., Therapeutic liposomal dry powder inhalation aerosols for targeted lung delivery, Lung, 190(3):251-62 (Jun. 2012). [cited by applicant]