Stable liquid pharmaceutical formulation of anti-influenza virus antibody

Patent metadata

Field	Value
Publication number	US-12065482-B2
Application number	US-201716324364-A
Country	US
Kind code	B2
Filing date	Aug 9, 2017
Priority date	Aug 10, 2016
Publication date	Aug 20, 2024
Grant date	Aug 20, 2024

Abstract

A stable liquid pharmaceutical preparation of an anti-influenza virus antibody and, more specifically, a stable liquid pharmaceutical preparation that comprises: (A) an anti-influenza virus antibody or a mixture of two or more different types of anti-influenza virus antibodies; (B) a surfactant; (C) a sugar or a sugar derivative; and (D) an amino acid. The stable liquid pharmaceutical preparation for an anti-influenza virus antibody disclosed herein has excellent storage stability at low temperature (5° C.), room temperature (25° C.), and high temperature (40° C.) and excellent long-term (12 months) storage stability, and may be administered intravenously, intramuscularly, transdermally, subcutaneously, intraperitoneally, topically, or in combinations thereof.

First claim

The invention claimed is:

1. A stable liquid pharmaceutical formulation comprising:
25 to 50 mg/mL of a mixture of two or more different anti-influenza virus (A) antibodies;
(B) 0.02 to 0.1% (w/v) of a surfactant, wherein the surfactant (B) comprises polysorbate 80;
(C) 1.0 to 5% (w/v) of a sugar or its derivative, wherein the sugar is sorbitol; and
(D) 5 to 15 mM of histidine;
wherein the pharmaceutical formulation has a pH of 6, and
wherein the mixture of two or more different anti-influenza virus antibodies (A) comprises:
i) an antibody comprising a light-chain variable region comprising a CDR1 region of SEQ ID NO: 1, a CDR2 region of SEQ ID NO: 2 and a CDR3 region of SEQ ID NO: 3, and a heavy-chain variable region comprising a CDR1 region of SEQ ID NO: 4, a CDR2 region of SEQ ID NO: 5, and a CDR3 region of SEQ ID NO: 6; and
ii) an antibody comprising a light-chain variable region comprising a CDR1 region of SEQ ID NO: 7, a CDR2 region of SEQ ID NO: 8 and a CDR3 region of SEQ ID NO: 9, and a heavy-chain variable region comprising a CDR1 region of SEQ ID NO: 10, a CDR2 region of SEQ ID NO: 11, and a CDR3 region of SEQ ID NO: 12.

2. The stable liquid pharmaceutical formulation of claim 1 , wherein the anti-influenza virus antibody (A) binds to an epitope in a hemagglutinin (HA) protein of influenza A virus, in which the epitope comprises an amino acid residue at position 318 of an HA1 polypeptide and comprises amino acid residues at positions 41, 42, 45, 48, 49, 52 and 53 of an HA2 polypeptide.

3. The stable liquid pharmaceutical formulation of claim 1 , wherein the mixture of two or more different anti-influenza virus antibodies (A) is a mixture of two different antibodies, and the ratio of the two different antibodies is 9:1 to 1:9.

4. The stable liquid pharmaceutical formulation of claim 1 , which has an antibody monomer purity of 95% or higher as measured after 6 weeks of storage at 40±2° C.

5. The stable liquid pharmaceutical formulation of claim 1 , which has an antibody monomer purity of 95% or higher as measured after 12 months of storage at 5±3° C.

6. The stable liquid pharmaceutical formulation of claim 1 , which is configured for administration intravenously, intramuscularly, transdermally, subcutaneously, intraperitoneally, topically, or a combination thereof.

7. A pre-filled syringe filled with the stable liquid pharmaceutical formulation as set forth in claim 1 .

8. An auto-injector including the pre-filled syringe of claim 7 therein.

9. A kit comprising:
a stable liquid pharmaceutical formulation set forth in claim 1 ; and
a container.

Assignees

• Celltrion Inc

Inventors

• Lee Joon Won
• Han Won Yong
• Kim Su Jung
• Oh Jun Seok
• Kim So Young
• Kim Kwang Woo
• Shin Yeon Kyeong

Classifications

• C07K16/108 Primary

  Orthomyxoviridae (F), e.g. influenza virus · CPC title

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title