Claims for Patent: 9,968,676

Summary for Patent: 9,968,676

Title:	Subcutaneous anti-HER2 antibody formulations and uses thereof
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.TM.), 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. .alpha.,.alpha.-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.
Inventor(s):	Adler; Michael (Riehen, CH), Grauschopf; Ulla (Riehen, CH), Mahler; Hanns-Christian (Basel, CH), Stauch; Oliver Boris (Freiburg, DE)
Assignee:	Genentech, Inc. (South San Francisco, CA)
Application Number:	15/053,217
Patent Claims:	1. A highly concentrated, stable liquid pharmaceutical composition of pharmaceutically active anti-HER2 antibody for subcutaneous injection comprising: a. 100 to 150 mg/ml anti-HER2 antibody, wherein the anti-HER2 antibody is a combination of Trastuzumab and Pertuzumab; b. 1 to 50.+-.5% mM of a buffering agent providing a pH of 5.5.+-.2.0; c. 150 to 250.+-.5% mM of a mixture of trehalose and sucrose as a first stabilizer and 5 to 15 mM methionine as a secondary stabilizer; d. 0.01 to 0.08.+-.5% (w/v) of a nonionic surfactant; and e. 1,000 to 16,000 U/ml of at least one hyaluronidase enzyme. 2. The pharmaceutical composition of claim 1 comprising 120 mg/ml of the combination of Trastuzumab and Pertuzumab. 3. The pharmaceutical composition of claim 1, comprising 1'500 U/ml to 12,000 U/ml of the hyaluronidase enzyme. 4. The pharmaceutical composition of claim 3, comprising 2,000 U/ml of the hyaluronidase enzyme. 5. The pharmaceutical composition of claim 4, wherein the hyaluronidase enzyme is recombinant human hyaluronidase, rHuPH20. 6. The pharmaceutical composition of claim 1, wherein the buffering agent is a histidine buffer. 7. The pharmaceutical composition of claim 5, wherein the histidine buffer is a histidine chloride buffer at a pH of 5.5.+-.0.6. 8. The pharmaceutical composition of claim 6, wherein the histidine chloride buffer has a pH of 5.5. 9. The pharmaceutical composition of claim 1, wherein the nonionic surfactant is a polysorbate selected from the group consisting of polysorbate 20, polysorbate 80, and polyethylene-polypropylene copolymer. 10. The pharmaceutical composition of claim 9, wherein the nonionic surfactant is polysorbate 20. 11. An injection device comprising the highly concentrated stable ready for use pharmaceutical composition of claim 1. 12. A method of treating a disease or disorder which is amenable to treatment with an anti-HER2 antibody in a subject comprising administering to said subject a pharmaceutical composition according to claim 1 in an amount effective to treat said disease or disorder. 13. The method of claim 12, wherein the disease is cancer. 14. The method of claim 13, wherein the cancer is breast cancer. 15. The method of claim 14, wherein the cancer is HER2 overexpressing breast cancer. 16. A kit comprising a vial containing the highly concentrated stable ready for use pharmaceutical composition of claim 1 and instructions for subcutaneous administration of the composition to a patient. 17. The kit of claim 16 further comprising an injection device for subcutaneous administration of the pharmaceutical composition to the patient.

Details for Patent 9,968,676

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	05/05/2004		2029-07-31
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	12/02/2004		2029-07-31
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	10/26/2004		2029-07-31
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	10/25/2005		2029-07-31
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2029-07-31
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2029-07-31