High-concentration monoclonal antibody formulations

Patent metadata

Field	Value
Publication number	US-2016176986-A1
Application number	US-201514752670-A
Country	US
Kind code	A1
Filing date	Jun 26, 2015
Priority date	May 18, 2012
Publication date	Jun 23, 2016
Grant date	—

Abstract

The present application discloses high-concentration monoclonal antibody formulations suitable for subcutaneous administration, e.g. via a pre-filled syringe. In particular, it discloses a formulation comprising a spray dried monoclonal antibody at a concentration of about 200 mg/mL or more suspended in a non-aqueous suspension vehicle where the viscocity of the suspension vehicle is less than about 20 centipoise. Also disclosed are: a subcutaneous administration device with the formulation therein, a method of making the formulation, a method of making an article of manufacture comprising the suspension formulation, use of the formulation in the preparation of a medicament, and a method of treating a patient with the formulation.

First claim

What is claimed is:

1 . A suspension formulation comprising a spray dried monoclonal antibody at a concentration of about 200 mg/mL or more suspended in a non-aqueous suspension vehicle, wherein the viscocity of the suspension vehicle is less than about 20 centipoise.

2 . The formulation of claim 1 wherein the viscosity of the suspension vehicle is less than about 10 centipoise.

3 . The formulation of claim 2 wherein the viscosity of the suspension vehicle is less than about 5 centipoise.

4 . The formulation of claim 1 wherein the injection glide force of the formulation is about 20 newton or less.

5 . The formulation of claim 4 wherein the injection glide force of the formulation is about 15 newton or less.

6 . The formulation of claim 1 wherein the average particle size in the formulation is from about 2 microns to about 30 microns.

7 . The formulation of claim 6 wherein the average particle size in the formulation is from about 2 microns to about 10 microns.

8 . The formulation of claim 1 wherein the antibody concentration in the formulation is from about 200 mg/mL to about 500 mg/mL.

9 . The formulation of claim 8 wherein the antibody concentration in the formulation is from about 200 mg/mL to about 350 mg/mL.

10 . The formulation of claim 1 further comprising a saccharide.

11 . The formulation of claim 10 wherein the saccharide is trehalose or sucrose.

12 . The formulation of claim 10 wherein the molar ratio of saccharide: monoclonal antibody is from about 50 to about 400:1.

13 . The formulation of claim 12 wherein the molar ratio of saccharide: monoclonal antibody is from about 100 to about 250:1.

14 . The formulation of claim 1 further comprising a surfactant.

15 . The formulation of claim 14 wherein the surfactant is polysorbate 20 or polysorbate 80.

16 . The formulation of claim 1 which is suitable for subcutaneous administration.

17 . The formulation of claim 1 wherein the monoclonal antibody is a full length monoclonal antibody.

18 . The formulation of claim 17 wherein the monoclonal antibody is a human IgG1.

19 . The formulation of claim 1 wherein the monoclonal antibody is a chimeric, humanized, or human antibody.

20 . The formulation of claim 1 wherein the monoclonal antibody binds an antigen selected from the group consisting of: CD20, HER2, VEGF, IL6R, beta7, Abeta, HER3, EGFR, and M1′.

21 . The formulation of claim 20 wherein the antibody is rituximab, trastuzumab, or bevacizumab.

22 . The formulation of claim 1 wherein the non-aqueous suspension vehicle comprises propylene glycol dicarprylate/dicaprate, benzyl benzoate, ethyl lactate, or mixtures thereof.

23 . The formulation of claim 22 wherein the non-aqueous suspension vehicle comprises ethyl lactate.

24 . The formulation of claim 22 wherein the non-aqueous suspension vehicle comprises a mixture of propylene glycol dicarprylate/dicaprate and ethyl lactate.

25 . A subcutaneous administration device with the formulation of claim 1 therein.

26 . The device of claim 25 which comprises a pre-filled syringe.

27 . A method of making a suspension formulation comprising suspending a spray dried monoclonal antibody in a non-aqueous suspension vehicle with a viscosity less than about 20 centipoise, wherein the monoclonal antibody concentration in the suspension formulation is about 200 mg/mL or more.

28 . A method of making an article of manufacture comprising filling a subcutaneous administration device with the formulation of claim 1 .

29 . A suspension formulation comprising a spray dried full length human IgG1 monoclonal antibody at a concentration from about 200 mg/mL to about 400 mg/mL suspended in a non-aqueous suspension vehicle with a viscocity less than about 20 centipoise, wherein the formulation has an average particle size from about 2 microns to about 10 microns, and injection glide force less than about 15 newton.

30 . The formulation of claim 29 which further comprises saccharide wherein the molar ratio of saccharide: monoclonal antibody is from about 100 to about 250:1.

31 . The formulation of claim 29 wherein the antibody is rituximab, trastuzumab, or bevacizumab.

32 . The formulation of claim 1 for use in treating a disease or disorder in a patient.

33 . Use of the formulation of claim 1 in the preparation of a medicament for treating a patient in need of treatment with the monoclonal antibody in the formulation.

34 . A method of treating a patient comprising administering the formulation of claim 1 to a patient in need of treatment with the monoclonal antibody in the formulation.

35 . The method of claim 34 wherein the formulation is administered subcutaneously to the patient.

36 . The method of claim 34 wherein the formulation is administered by a pre-filled syringe containing the formulation therein.

Assignees

• Genentech Inc

Inventors

• Armstrong Nicholas J
• Bowen Mayumi N
• Maa Yuh-Fun

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title