Subcutaneous anti-HER2 Antibody Formulations and Uses Thereof

Patent metadata

Field	Value
Publication number	US-2025090660-A1
Application number	US-202418635280-A
Country	US
Kind code	A1
Filing date	Apr 15, 2024
Priority date	Jul 31, 2009
Publication date	Mar 20, 2025
Grant date	—

Abstract

The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

First claim

1 . A highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody comprising:
a. about 50 to 350 mg/ml anti-HER2 antibody; b. about 1 to 100 mM of a buffering agent providing a pH of 5.5±2.0; c. about 1 to 500 mM of a stabilizer or a mixture of two or more stabilizers; d. about 0.01 to 0.08% of a nonionic surfactant; and e. an effective amount of at least one hyaluronidase enzyme.

2 . The formulation according to claim 1 , wherein the anti-HER2 antibody concentration is about 100 to 150 mg/ml.

3 . The formulation according to claim 2 , wherein the anti-HER2 antibody concentration is 120±18 mg/ml.

4 . The formulation according to claim 1 , comprising more than 150 to about 16,000 U/ml of a hyaluronidase enzyme.

5 . The formulation according to claim 4 , comprising about 2,000 U/ml to about 12,000 U/ml of a hyaluronidase enzyme.

6 . The formulation according to claim 1 , wherein the buffering agent is at a concentration of 1 to 50 mM.

7 . The formulation according to claim 6 , wherein said buffering agent is a histidine buffer.

8 . The formulation according to claim 1 , wherein the formulation includes α,α-trehalose dihydrate or sucrose as a stabilizer.

9 . The formulation according to claim 1 , wherein the stabilizer is at a concentration of 15 to 250 mM.

10 . The formulation according to claim 8 , wherein methionine is used as a second stabilizer in a concentration of 5 to 25 mM.

11 . The formulation according to claim 1 , wherein the nonionic surfactant is a polysorbate selected from the group consisting of polysorbate 20, polysorbate 80, and polyethylene-polypropylene copolymer.

12 . The formulation according to claim 11 , wherein the concentration of the polysorbate is 0.02% (w/v), 0.04% (w/v) or 0.06% (w/v), respectively.

13 . The formulation according to claim 1 , wherein the anti-HER2 antibody is selected from the group of Trastuzumab, and T-DM1 or a combination of such antibodies.

14 . The formulation according to claim 1 which is stable upon freezing and thawing.

15 . The formulation according to claim 1 , wherein the hyaluronidase enzyme is rHuPH20.

16 . The formulation according to claim 1 , wherein the buffering agent provides a pH of 5.5±0.5.

17 . The formulation according to claim 1 for subcutaneous or intramuscular administration.

18 . The formulation according to claim 1 in liquid form.

19 . The formulation according to claim 1 in lyophilized form.

20 . A highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody comprising:
a. about 50 to 350 mg/ml anti-HER2 antibody; b. about 1 to 100 mM of a buffering agent providing a pH of 5.5±2.0; c. about 1 to 500 mM of a stabilizer or a mixture of two or more stabilizers; and d. about 0.01 to 0.08% of a nonionic surfactant.

21 .- 27 . (canceled)

Assignees

• Genentech Inc

Inventors

• Adler Michael
• Grauschopf Ulla
• Mahler Hanns-Christian
• Stauch Oliver Boris

Classifications

• C12Y302/01035

  Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K38/47

  acting on glycosyl compounds (3.2), e.g. cellulases, lactases · CPC title

• A61K9/08 Primary

  Solutions {(composition of solutions A61K47/00)} · CPC title

• 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