IP Library › Granted Patent US 12,202,849
Granted Patent B2
US 12,202,849 · App. 17/885,883 · Granted Jan 21, 2025

Crystalline forms of tenofovir alafenamide

Inventors: Chiajen Lai (Livermore, CA); Bing Shi (Redwood City, CA); Robert G. Strickley (San Mateo, CA)
Assignee: Gilead Sciences, Inc.
C07F9/65616A61K9/0019A61K31/675A61K45/06C07B2200/13
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 12,202,849
App. No.
17/885,883
Granted
Jan 21, 2025
Kind
B2
Abstract

The present invention relates to novel crystalline forms of salts and/or co-crystals of tenofovir alafenamide, the pharmaceutical formulations, and the therapeutic uses thereof in treating viral infections.

Claims (22)

1. Crystalline Tenofovir Alafenamide Napsylate Form I, characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 3.9°, 7.8°, 13.6°, 15.3°, and 19.2° 2-θ±0.2° 2-θ.

2. The crystalline form of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern has further peaks at about 19.4°, 19.8°, 20.6°, 23.8°, and 27.2° 2-θ±0.2° 2-θ.

3. The crystalline form of claim 2 , wherein the X-ray powder diffraction (XRPD) pattern has further peaks at about 9.8°, 13.2°, 15.5°, 16.5°, 17.8°, 23.0°, 24.1°, and 26.0° 2-θ±0.2° 2-θ.

4. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern as set forth in FIG. 7 .

5. The crystalline form of claim 1 , characterized by a differential scanning calorimetry (DSC) pattern as set forth in FIG. 8 .

6. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline Tenofovir Alafenamide Napsylate of claim 1 and a pharmaceutically acceptable excipient.

7. The pharmaceutical composition of claim 6 , further comprising one to three additional therapeutic agents.

8. The pharmaceutical composition of claim 7 , wherein the additional therapeutic agents are each active against HIV.

9. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is in a unit dosage form.

10. The pharmaceutical composition of claim 9 , wherein the unit dosage form is a subcutaneous injection.

11. A method for treating a virus infection in a human, the method comprising administering to a human in need thereof a therapeutically effective amount of the crystalline Tenofovir Alafenamide Napsylate of claim 1 .

12. The method of claim 11 wherein the virus infection is caused by HIV.

13. The pharmaceutical composition of claim 9 , wherein the unit dosage form is an injection.

14. The pharmaceutical composition of claim 9 , wherein the unit dosage form is an intramuscular injection.

15. The pharmaceutical composition of claim 9 , wherein the crystalline Tenofovir Alafenamide Napsylate is in a suspension.

16. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Napsylate is administered by injection.

17. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Napsylate is administered by intramuscular injection.

18. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Napsylate is administered by subcutaneous injection.

19. The method of claim 18 , wherein the crystalline Tenofovir Alafenamide Napsylate is in a suspension.

20. The method of claim 12 , wherein the crystalline Tenofovir Alafenamide Napsylate is in a long-acting formulation.

21. The method of claim 20 , wherein the long-acting formulation is active for at least 30 days.

22. The method of claim 21 , wherein the long-acting formulation maintains a concentration minimum (Cmin) above the efficacious level for HIV treatment.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 14, 2024
From: LAI, CHIAJEN; SHI, BING; STRICKLEY, ROBERT G.
To: GILEAD SCIENCES, INC.
Reel/Frame 066774/0620 →
Continuity (4)
Continuation 16360763 · Mar 21, 2019
Division 15882784 · Jan 29, 2018
Provisional Application 62452428 · Jan 31, 2017
Related Publication 20230091736A1 · Mar 23, 2023
References Cited (95)
US 9908908B2 · Zhang et al. · 2018 [cited by applicant]
US 10287307B2 · Lai et al. · 2019 [cited by applicant]
US 11440928B2 · Lai et al. · 2022 [cited by applicant]
US 20120149708A1 · Kashanchi · 2012 [cited by applicant]
US 20130065856A1 · Liu et al. · 2013 [cited by applicant]
US 20160237073A1 · Hamblin et al. · 2016 [cited by applicant]
US 20170050932A1 · Lynch et al. · 2017 [cited by applicant]
CN 104558036A · 2015 [cited by applicant]
CN 105085571A · 2015 [cited by applicant]
EP 0903341A1 · 1999 [cited by applicant]
KR 1020150025993A1 · 2015 [cited by applicant]
WO WO2002008241A2 · 2002 [cited by applicant]
WO WO2004087720A1 · 2004 [cited by applicant]
WO WO2010101967A2 · 2010 [cited by applicant]
WO WO2012030927A2 · 2012 [cited by applicant]
WO WO2012032067A1 · 2012 [cited by applicant]
WO WO2013025788A1 · 2013 [cited by applicant]
WO WO2013095684A1 · 2013 [cited by applicant]
WO WO2014172243A1 · 2014 [cited by applicant]
WO WO2014195724A1 · 2014 [cited by applicant]
WO WO2015002434A1 · 2015 [cited by applicant]
WO WO2015040640A2 · 2015 [cited by applicant]
WO WO2015107451A2 · 2015 [cited by applicant]
WO WO2015176602 · 2015 [cited by examiner]
WO WO2015176602A1 · 2015 [cited by applicant]
WO WO2016081940A1 · 2016 [cited by applicant]
WO WO2016192692A1 · 2016 [cited by applicant]
WO WO2016205141 · 2016 [cited by examiner]
WO WO2016205141A1 · 2016 [cited by applicant]
WO WO2017004012A1 · 2017 [cited by applicant]
WO WO2018144390A1 · 2018 [cited by applicant]
Anderson, B. et. al. (1996) “Preparation of Water-Soluble Compounds Through Salt Formation” [cited by applicant]
Bastin et al., (Organic Process Research & Development 200, 4, 427-435). [cited by applicant]
Chrzanowski et al., “The preparation and evaluation of salt forms of linogliride with reducedsolubilities as candidates for extended release,” Drug Development and Industrial Pharmacy (2017) 43:3 pp. 421-431. [cited by applicant]
Communication pursuant to Rules 161(1) and 162 EPC dated Oct. 11, 2019 for European Appl. No. 18705239.4. [cited by applicant]
Elder, D. et al. (2010) “The Utility of Sulfonate Salts in Drug Development” [cited by applicant]
Exam Report dated Jan, 27, 2022 for Australian Application No. 2021200857. [cited by applicant]
Exam Report dated Mar. 11, 2022 for European Appl. No. 18705239.4. [cited by applicant]
Examination Report dated Feb. 18, 2020 for Australian Appl. No. 2018216738. [cited by applicant]
Examination Report dated Mar. 19, 2020 for Indian Appl. No. 201917032116. [cited by applicant]
Final Rejection dated Jun. 10, 2021 for Korean Appl. No. 10-2019-7025206. [cited by applicant]
International Preliminary Report on Patentability Issued 2019-08-06 for PCT App No. PCT/US2018/015770; 7pgs. [cited by applicant]
International Search Report and Written Opinion for PCT/US2018/015770, dated Mar. 23, 2018, 12 pages. [cited by applicant]
Kojima, T. (2008) “Effective Solid Form Selection for the Pharmaceutical Development” [cited by applicant]
Li, C.J. et al. (2017) “In vitro and in vivo release of dinalbuphine sebacate extended release formulation: Effect of the oil ratio on drug release” [cited by applicant]
Notice of Preliminary Rejection dated Feb. 23, 2021 for Korean Appl. No. 10-2019-7025206. [cited by applicant]
Office Action dated Dec. 10, 2018 for Taiwanese App. No. 107102293, 6pgs. [cited by applicant]
Office Action dated Aug. 12, 2019 for Taiwanese App No. 107102293; 3pgs. [cited by applicant]
Office Action dated Jun. 29, 2020 for Canadian Appl. No. 3049028. [cited by applicant]
Office Action dated Aug. 25, 2020 for Japanese Appl. No, 2019-541123. [cited by applicant]
Office Action dated Apr. 28, 2021 for Japanese Appl. No. 2019-541123. [cited by applicant]
Office Action dated May 5, 2021 for Canadian Appl. No. 3049028. [cited by applicant]
Office Action dated May 26, 2021 for Chinese Appl. No. 201880009292.1. [cited by applicant]
Office Action dated Feb. 23, 2021 for Korean Appl. No. 10-2021-7034440. [cited by applicant]
Office Action dated Jan. 5, 2022 for Korean Appl. No. 10-2021-7012232. [cited by applicant]
Office Action dated Jan. 20, 2022 for Taiwanese Appl. No. 109143905. [cited by applicant]
Office Action dated Jan. 28, 2022 for Argentinian Appl. No. 20180100144. [cited by applicant]
Office Action dated Feb. 1, 2022 for Japanese Application No. 2020-195169. [cited by applicant]
Office Action dated Feb. 15, 2022 for Chinese Appl. No. 201880009292.1. [cited by applicant]
Patel, A. et al. (2009) “Pharmaceutical salts: A formulation trick or a clinical conundrum?” [cited by applicant]
Sarma, B. et al. (2011) “Solid forms of pharmaceuticals: Polymoprhs, salts and cocrystals” [cited by applicant]
Second Final Rejection dated Aug. 20, 2021 for Korean Appl. No. 10-2019-7025206. [cited by applicant]
Stahl et al. (eds., Handbook of Pharmaceutical Salts. Properties, Selection and Use (Wiley-VCH, 2008), pp. 265-327). [cited by applicant]
Stahl, P.H. et al. (2008) Handbook of Pharmaceutical Salts: Properties, Selection, and Use: 1-7, 103-104, 109-110, 120, 154-157, 163, 164-170, 192-220. [cited by applicant]
Swarbrick et al. (Encyclopedia of Pharmaceutical Technology 13 (Marcel Dekker, NY 1996) pp. 453-499). [cited by applicant]
Third Party Observation dated May 31, 2019 for PCT Appl. No. PCT/US2018/015770. [cited by applicant]
Verbeeck, R.K. et al. (2006) “Generic Substitution: The Use of Medicinal Products Containing Different Salts and Implications for Safety and Efficacy” [cited by applicant]
Office Action dated Aug. 1, 2022 for Chinese Application No. 201880009292.1. [cited by applicant]
Office Action dated Aug. 5, 2022 for Korean Application No. 10-2021-7012232. [cited by applicant]
Office Action dated Aug. 5, 2022 for Korean Application No. 10-2021-7034440. [cited by applicant]
Pre-Appeal Examination Report dated Nov. 29, 2022 for Japanese Application No. 2019- 541123. [cited by applicant]
Office Action dated Jan. 5, 2023 for Korean Application No. 10-2021-7034440. [cited by applicant]
Gunawardana et al. (2015) “Antimicrob Agents Chemother”, 59(7): 3913-3919. [cited by applicant]
Office Action dated Feb. 15, 2023 for Korean Appl. No. 10-2021-7012232, 7 pages. [cited by applicant]
Office Action dated Feb. 3, 2023 for Taiwanese Appl. No. 111140896, 11 pages. [cited by applicant]
Examination Report dated Oct. 12, 2023 for Australian Appl. No. 2022283687, 3 pages. [cited by applicant]
Notice of Allowance dated Mar. 11, 2019 for U.S. Appl. No. 15/882,784. [cited by applicant]
Non-Final Office Action dated Mar. 10, 2020 for U.S. Appl. No. 16/360,763. [cited by applicant]
Notice of Allowance dated Jul. 2, 2020 for U.S. Appl. No. 16/360,763. [cited by applicant]
Non-Final Office Action dated Nov. 23, 2020 for U.S. Appl. No. 16/360,763. [cited by applicant]
Final Office Action dated Apr. 20, 2021 for U.S. Appl. No. 16/360,763. [cited by applicant]
Non-Final Office Action dated Nov. 9, 2021 for U.S. Appl. No. 16/360,763. [cited by applicant]
Examination Report dated Nov. 26, 2021 for Indian Appl. No. 202018054920. [cited by applicant]
Final Office Action dated Mar. 28, 2022 for Japanese Appl. No. 2019-541123. [cited by applicant]
Notice of Allowance dated May 13, 2022 for U.S. Appl. No. 16/360,763. [cited by applicant]
Office Action dated Oct. 4, 2022 for Japanese Appl. No. 2021-176746, 3 pages. [cited by applicant]
Final Office Action dated Nov. 16, 2022 for Japanese Application No. 2020-195169. [cited by applicant]
Notice of Opposition dated Jan. 10, 2024 for Indian Appl. No. 202018054920. [cited by applicant]
Examination Report dated Jan. 29, 2024 for Canadian Appl. No. 3168042, 4 pages. [cited by applicant]
Pre-Grant Hearing Notice dated Apr. 16, 2024 for Indian Appl. No. 202018054920. [cited by applicant]
Office Action dated May 10, 2024 for Taiwanese Appl. No. 112137480. [cited by applicant]
Office Action dated May 31, 2024 for Chinese Appl. No. 202211484773.2. [cited by applicant]
Notice of Acceptance dated Aug. 22, 2024 for AU Appl. No. 2022283687. [cited by applicant]
Extended European Search Report dated Oct. 8, 2024 for EP Appl. No. 24173808.7. [cited by applicant]
Savjani, K et al. (2012) “Drug Solubility: Importance and Enhancement Techniques”, ISRN Pharm; 2012:195727, 10 pages. [cited by applicant]