Polymer protein microparticles

Patent metadata

Field	Value
Publication number	US-11951216-B2
Application number	US-202217677282-A
Country	US
Kind code	B2
Filing date	Feb 22, 2022
Priority date	Nov 18, 2011
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

Abstract

Microparticles containing a core of therapeutic protein and a cortex of a biocompatible and biodegradable polymer, and methods of making and using the microparticles are provided. The extended release of a therapeutic protein from the microparticles in a physiological solution is demonstrated over an extended period of time.

First claim

What is claimed is:

1. A method of manufacturing an extended release pharmaceutical composition comprising therapeutic protein microparticles coated with a biodegradable polymer, the method comprising:
a. spray drying an aqueous therapeutic protein solution to form therapeutic protein microparticles wherein the inlet temperature of the spray dryer is set at a temperature greater than the boiling point of water and the outlet temperature that is above ambient and below the boiling point of water to form a powder comprising a population of therapeutic protein microparticles wherein the aqueous solution is pumped into the spray dryer at a rate of 2 mL/min to 15 mL/min,
b. suspending the powder comprising the population of therapeutic protein microparticles in a solution comprising polyorthoester (POE) and an organic solvent to form a suspension; and
c. spray drying the suspension to form the extended release pharmaceutical composition comprising a population of POE-coated therapeutic protein microparticles, wherein the extended release pharmaceutical composition comprises about 1 to about 500 mg/mL of therapeutic protein microparticles and releases the therapeutic protein for at least 60 days at a steady rate of release, wherein extended release pharmaceutical composition can treat conditions selected from the group consisting of cancers, cardiovascular diseases, vascular conditions, orthopedic disorders, dental disorders, wounds, autoimmune diseases, gastrointestinal disorders and ocular diseases.

2. The method of claim 1 , wherein the outlet temperature is about 54 to 55° C.

3. The method of claim 2 , wherein each therapeutic protein microparticle of the population of therapeutic protein microparticles comprises less than 3% (w/w) water.

4. The method of claim 1 , wherein the organic solvent is ethyl acetate.

5. The method of claim 1 , wherein the spray drying the suspension (c) comprises atomizing the suspension and then applying heat to the atomized suspension at a temperature greater than the flash point of the organic solvent to evaporate the organic solvent to form the population of POE-coated therapeutic protein microparticles.

6. The method of claim 5 , wherein the median diameter of the population of POE-coated therapeutic protein microparticles is about 15 microns to about 30 microns.

7. The method of claim 1 , wherein each therapeutic protein microparticle of the population of therapeutic protein microparticles has a diameter of about 2 microns to about 14 microns.

8. The method of claim 1 , wherein the condition is cancer.

9. The method of claim 1 , wherein the condition is cardiovascular disease.

10. The method of claim 1 , wherein the condition is a vascular disorder.

11. The method of claim 1 , wherein the condition is a wound.

12. The method of claim 1 , wherein the condition is an autoimmune disease.

13. The method of claim 1 , wherein the condition is an orthopedic disorder.

14. The method of claim 1 , wherein the condition is a gastrointestinal disorder.

15. The method of claim 1 , wherein the condition is an ocular disease.

16. A method of providing an extended release coating for therapeutic protein comprising:
a. atomizing an aqueous solution comprising a therapeutic protein;
b. spray drying the atomized aqueous solution at a temperature greater than the boiling point of water to remove water in the solution and form a population of therapeutic protein microparticles;
c. coating each therapeutic protein microparticle of the population therapeutic protein microparticles with a biodegradable polymer to form a population of polymer-coated therapeutic protein microparticles, wherein the biodegradable polymer is polyorthoester,
wherein the extended release pharmaceutical composition releases the therapeutic protein for at least 60 days at a steady rate of release, wherein extended release pharmaceutical composition can treat conditions selected from the group consisting of cancers, cardiovascular diseases, vascular conditions, orthopedic disorders, dental disorders, wounds, autoimmune diseases, gastrointestinal disorders and ocular diseases.

17. The method of claim 16 , wherein the population of therapeutic protein microparticles is dry.

18. The method of claim 16 , wherein the population of therapeutic protein microparticles comprises less than 3% water.

19. The method of claim 16 , wherein the aqueous solution comprises about 10 mg/mL to 100 mg/mL of the therapeutic protein.

20. The method of claim 16 , wherein the coating step (c) further comprises:
combining: (1) an organic solvent with the biodegradable polymer to a concentration of between about 10 mg/mL and 300 mg/mL; and (2) the population of therapeutic protein microparticles to a concentration of between about 10 mg/mL and 100 mg/mL to form a slurry; and spray drying the slurry to form the plurality of polymer-coated therapeutic protein microparticles at step (c).

Assignees

• Regeneron Pharma

Inventors

• Chen Hunter
• Walsh Scott

Classifications

• A61K9/5089 Primary

  Processes · CPC title

• A61K9/14

  Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} · CPC title

• A61K9/1611

  Inorganic compounds · CPC title

• A61K9/1617

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

• A61K9/1623 Primary

  Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules · CPC title