Method of treating cancer with a pharmaceutical formulation comprising a HER2 antibody

• US 9,017,671 B2
• Filed: 10/25/2012
• Issued: 04/28/2015
• Est. Priority Date: 10/20/2004
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Andya, James, Gwee, Shiang C., Liu, Jun, Shen, Ye
• Primary Examiner(s): Kim, Yunsoo
• Application Number:
  US13/660,114
• Publication Number:
  US 20130071384A1
• Time in Patent Office: 915 Days
• Field of Search: None
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/39541 against normal tissues, cells
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 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 Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The present application describes antibody formulations, including monoclonal antibodies formulated in histidine-acetate buffer, as well as a formulation comprising an antibody that binds to domain II of HER2 (for example, Pertuzumab), and a formulation comprising an antibody that binds to DR5 (for example, Apomab).

Claims

1. A method of treating HER2-expressing cancer in a subject, comprising intravenously administering a pharmaceutical formulation to the subject in an amount effective to treat the cancer, wherein the formulation comprises an antibody that binds to domain II of HER2 in a histidine-acetate buffer at a pH from about 5.5 to about 6.5, a saccharide, and a surfactant.

2. A method of treating HER2-expressing cancer in a subject, comprising intravenously administering a pharmaceutical formulation to the subject in an amount effective to treat the cancer, wherein the formulation comprises an antibody that binds to domain II of HER2 in a histidine-acetate buffer at a pH from about 5.5 to about 6.5, a saccharide, and a surfactant, wherein the antibody concentration is from 20mg/mL to 40mg/mL, the antibody comprises the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4, respectively, the saccharide is sucrose at a concentration from about 60mM to about 250mM, and the surfactant is polysorbate 20 at a concentration from about 0.01% to about 0.1%.

3. The method of claim 2 wherein the HER2 antibody comprises a light chain amino acid sequence selected from SEQ ID No. 15 and 23, and a heavy chain amino acid sequence selected from SEQ ID No. 16 and 24.

4. The method of claim 2 wherein the pH of the formulation is from about 5.8 to about 6.2.

5. The method of claim 2 wherein the antibody binds to the junction between domains I, II and III of HER2.

6. The method of claim 2 wherein the antibody is a full length antibody.

7. The method of claim 2 wherein the formulation is aqueous and has not been subjected to prior lyophilization.

8. A method of treating HER2-expressing cancer in a subject, comprising intravenously administering a pharmaceutical formulation to the subject in an amount effective to treat the cancer, wherein the formulation comprises Pertuzumab in an amount from 20mg/mL to 40mg/mL, histidine-acetate buffer, sucrose, and polysorbate 20, wherein the pH of the formulation is from about 5.5 to about 6.5.

9. The method of claim 8 wherein the formulation comprises about 30mg/mL Pertuzumab, about 20mM histidine-acetate, about 120mM sucrose, and about 0.02% polysorbate 20, wherein the pH of the formulation is about 6.0.

10. A method of treating HER2-expressing cancer in a subject, comprising intravenously administering a pharmaceutical formulation to the subject in an amount effective to treat the cancer, wherein the formulation is an aqueous pharmaceutical formulation which has not been subjected to prior lyophilization, comprising about 30mg/mL Pertuzumab, about 20mM histidine-acetate, about 120mM sucrose, and about 0.02% polysorbate 20, wherein the pH of the formulation is about 6.0.

11. A method of treating HER2-expressing cancer in a subject, comprising intravenously administering to the subject an aqueous pharmaceutical formulation which has not been subjected to prior lyophilization in an amount effective to treat the cancer, wherein the formulation comprises an antibody that binds to domain II of HER2 in a histidine-actetate buffer at a pH from about 5.5 to about 6.5, a saccharide, and a surfactant.

12. The method of claim 11 wherein the antibody is a full length IgG1 antibody.

13. A method of treating HER2-expressing cancer in a subject, comprising intravenously administering to the subject an aqueous pharmaceutical formulation which has not been subjected to prior lyophilization in an amount effective to treat the cancer, wherein the formulation comprises an antibody comprising the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4, respectively, in a histidine-acetate buffer at a pH from about 5.5 to about 6.5, a saccharide, and a surfactant.

14. The method of claim 13 wherein the antibody is a full length IgG1 antibody.