Polymeric nanoparticles and methods of making and using same

Patent metadata

Field	Value
Publication number	US-10022360-B2
Application number	US-201515126894-A
Country	US
Kind code	B2
Filing date	Mar 12, 2015
Priority date	Mar 17, 2014
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

Described herein are polymeric nanoparticles that comprise 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]-triazolo-[3,4-fJ[1,6]-naphthyridin-3-one (Compound A), or a pharmaceutically acceptable salt thereof, and methods of making and using such nanoparticles. The nanoparticle comprises about 50 to about 99.8 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer or a diblock poly(lactic acid-co-glycolic acid)-poly(ethylene)glycol copolymer, wherein the total amount of poly(ethylene)glycol in the nanoparticle is about 10 to about 30 weight percent poly(ethylene)glycol and about 0.2 to about 30 weight percent of Compound A.

First claim

What is claimed is:

1. A polymeric nanoparticle comprising:
about 50 to about 99.8 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer or a diblock poly(lactic acid-co-glycolic acid)-poly(ethylene)glycol copolymer; wherein the total amount of poly(ethylene)glycol in the nanoparticle is about 10 to about 30 weight percent poly(ethylene)glycol; and
about 0.2 to about 30 weight percent of a compound that is COMPOUND A represented by the formula:

or a pharmaceutically acceptable salt thereof.

2. The nanoparticle of claim 1 , wherein the poly(lactic) acid-poly(ethylene)glycol copolymer has a poly(lactic) acid number average molecular weight fraction of about 0.7 to about 0.9.

3. The nanoparticle of claim 1 , wherein the nanoparticle comprises about 10 to about 25 weight percent poly(ethylene)glycol.

4. The nanoparticle of claim 1 , wherein the poly(lactic) acid-poly(ethylene)glycol copolymer has a number average molecular weight of about 15 kDa to about 20 kDa poly(lactic acid) and a number average molecular weight of about 4 kDa to about 6 kDa poly(ethylene)glycol.

5. The nanoparticle of claim 1 , comprising about 65 weight percent to about 85 weight percent of the copolymer.

6. The nanoparticle of claim 1 , further comprising a substantially hydrophobic acid selected from the group consisting of cholic acid and oleic acid.

7. The nanoparticle of claim 1 , further comprising about 5 to about 15 weight percent of a substantially hydrophobic acid selected from the group consisting of cholic acid and oleic acid.

8. The nanoparticle of claim 6 , wherein the molar ratio of the substantially hydrophobic acid to the compound is about 0.9:1 to about 1.1:1, wherein the acid is cholic acid or oleic acid.

9. The nanoparticle of claim 6 , wherein a pK a of the compound is at least about 1.0 pK a unit greater than a pK a of the hydrophobic acid.

10. The nanoparticle of claim 6 , wherein the substantially hydrophobic acid and the compound form a hydrophobic ion pair in the nanoparticle.

11. The nanoparticle of claim 1 , comprising about 5 to about 20 weight percent of the compound.

12. A nanoparticle comprising:
about 50 to about 97.95 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer, wherein the total amount of poly(ethylene)glycol in the nanoparticle is about 10 to about 30 weight percent poly(ethylene)glycol;
about 0.05 to about 35 weight percent of a substantially hydrophobic acid selected from the group consisting of cholic acid and oleic acid; and
about 2 to about 30 weight percent of a compound that is COMPOUND A represented by the formula:

or a pharmaceutically acceptable salt thereof.

13. The nanoparticle of claim 12 , wherein the poly(lactic) acid-poly(ethylene)glycol copolymer has a poly(lactic) acid number average molecular weight fraction of about 0.7 to about 0.9.

14. The nanoparticle of claim 12 , wherein the nanoparticle comprises about 10 to about 25 weight percent poly(ethylene)glycol.

15. The nanoparticle of claim 12 , wherein the poly(lactic) acid-poly(ethylene)glycol copolymer has a number average molecular weight of about 15 kDa to about 20 kDa poly(lactic acid) and a number average molecular weight of about 4 kDa to about 6 kDa poly(ethylene)glycol.

16. The nanoparticle of claim 12 , comprising about 65 weight percent to about 85 weight percent of the copolymer.

17. A pharmaceutically acceptable composition comprising a plurality of polymeric nanoparticles of claim 1 and a pharmaceutically acceptable excipient.

18. A method of treating cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a composition comprising the polymeric nanoparticle of claim 1 .

19. The method of claim 18 , wherein the cancer is prostate cancer.

20. The method of claim 18 , wherein the cancer is breast cancer or ovarian cancer.

Assignees

• Merck Sharp & Dohme
• Bind Therapeutics Inc
• Pfizer

Inventors

• Song Young Ho
• Troiano Greg
• Wang Hong
• Figueiredo Maria
• Lam Michael H
• Mcgregor Caroline

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4375 Primary

  the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine · CPC title

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• A61K9/5153

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title