High concentration protein formulation

Patent metadata

Field	Value
Publication number	US-12036280-B2
Application number	US-201916690956-A
Country	US
Kind code	B2
Filing date	Nov 21, 2019
Priority date	Nov 21, 2018
Publication date	Jul 16, 2024
Grant date	Jul 16, 2024

Abstract

The present invention pertains to compositions and methods of making high concentration protein formulations of a therapeutic protein.

First claim

What is claimed is:

1. A non-aqueous high concentration protein formulation, comprising:
a) at least about 200 mg/mL of a therapeutic protein as a micronized solid protein formulation,
b) a hydrophobic agent comprising glyceryl tricaprylate/tricaprate, and
c) a viscosity-reducing agent selected from the group consisting of ethanol, benzyl alcohol, ethyl acetate, N-Methyl-2-pyrrolidone, or combinations thereof,

wherein the formulation has at least 25% v/v of the viscosity-reducing agent and an injection glide force of less than about 30 Newton.

2. The non-aqueous high concentration protein formulation of claim 1 , wherein the micronized solid protein formulation is produced by spray drying.

3. The non-aqueous high concentration protein formulation of claim 1 , wherein said micronized solid protein formulation has a solubility of less than about 1 mg in 10,000 mL in the hydrophobic agent and the viscosity-reducing agent.

4. The non-aqueous high concentration protein formulation of claim 1 , wherein said micronized solid protein formulation is in the form of a powder.

5. The non-aqueous high concentration protein formulation of claim 4 , wherein said powder is formulated using trileucine.

6. The non-aqueous high concentration protein formulation of claim 4 , wherein the concentration of said powder is between about 200 mg/mL to about 500 mg/mL.

7. The non-aqueous high concentration protein formulation of claim 4 , wherein the weight ratio (w/w) of said powder to the non-aqueous high concentration protein formulation is between about 0.250 and 0.700.

8. The non-aqueous high concentration protein formulation of claim 4 , wherein said powder comprises the therapeutic protein, a carbohydrate, an amino acid, or a non-ionic surfactant.

9. The non-aqueous high concentration protein formulation of claim 8 , wherein the carbohydrate is sucrose, mannitol, or trehalose.

10. The non-aqueous high concentration protein formulation of claim 8 , wherein the amino acid is histidine or proline.

11. The non-aqueous high concentration protein formulation of claim 8 , wherein the non-ionic surfactant is a polysorbate.

12. The non-aqueous high concentration protein formulation of claim 8 , wherein the concentration of the protein is at least about 70%.

13. The non-aqueous high concentration protein formulation of claim 1 , wherein said therapeutic protein is a monoclonal antibody.

14. A non-aqueous high concentration protein formulation, comprising:
at least about 200 mg/mL of a therapeutic protein as a micronized solid protein formulation,
glyceryl tricaprylate/tricaprate, and
benzyl alcohol,
wherein the formulation has at least 25% v/v of the viscosity-reducing agent and an injection glide force of less than about 30 Newton.

15. A non-aqueous high concentration protein formulation, comprising:
a) at least about 200 mg/mL of a therapeutic protein as a micronized solid protein formulation,
b) a hydrophobic agent comprising glyceryl tricaprylate/tricaprate, and
c) a viscosity-reducing agent selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, ethyl acetate, N-Methyl-2-pyrrolidone, or combinations thereof,
wherein the formulation has at least 25% v/v of the viscosity-reducing agent wherein the non-aqueous high concentration protein formulation has an injection glide force of less than about 50 Newton (N).

Assignees

• Regeneron Pharma

Inventors

• Chen Hunter
• Schlesinger Erica

Classifications

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K38/00 Primary

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title