# US 9,517,266 B2 · Liquid formulation containing a protein drug

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- Number: US 9,517,266 B2
- Document ID: US9517266B2
- Status: Granted
- Kind: B2
- Application number: 14/231,580
- Filed: 2014-03-31
- Published: 2014-10-09
- Granted: 2016-12-13
- Earliest claimed: 2013-03-29
- Assignees: Samsung Electronics Co., Ltd.
- Applicants: Samsung Electronics Co., Ltd.
- Inventors: In Hwan Lim; Dong Uk Kim; Geun Woong Kim; Hee Kyung Sung; Yun Ju Jeong
- Web page: https://patentgrep.com/patent/US9517266B2

## CPC

- A61K 39/39591: {Stabilisation, fragmentation}
- A61K 9/0019: {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)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- 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
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/53: Hinge
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Disclosed is a method of preparing a stabilized liquid formulation of a protein drug, comprising admixing a protein drug with a composition for stabilization, wherein the composition for stabilization comprises a surfactant, a buffer, and a liquid medium, and has a pH from about 5 to about 8.

## Claims

### Claim 1

A method for stabilizing a protein drug, comprising admixing a protein drug with a composition for stabilization, wherein the composition for stabilization comprises a surfactant, a buffer, and a liquid medium, and has a pH from about 5 to about 8, wherein the protein drug is an anti-c-Met antibody or antigen-binding fragment thereof comprising a CDR-H1 comprising SEQ ID NO: 1, a CDR-H2 comprising SEQ ID NO: 2, a CDR-H3 comprising SEQ ID NO: 3, a CDR-L1 comprising SEQ ID NO: 10, a CDR-L2 comprising SEQ ID NO: 11, and a CDR-L3 comprising SEQ ID NO: 13; and the buffer comprises succinic acid, citric acid, or a combination thereof.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the surfactant comprises one or more selected from the group consisting of polysorbate, poloxamer, polyethylene-polypropylene glycol, polyoxyethylene, and sodium dodecyl sulphate.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the surfactant comprises one or more selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, and polysorbate 80.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the amount of the surfactant in the composition for stabilization is about 0.01% to about 1% (w/v) based on the total amount of the composition for stabilization.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the composition for stabilization has a pH from about 5 to about 7.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the amount of the buffer in the composition for stabilization is about 0.1 to about 1% (w/v) based on the total amount of the composition for stabilization.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the composition for stabilization has an osmotic pressure of about 250 to about 400 milliosmole (mOsm).

### Claim 8 (depends on 1)

The method according to claim 1, wherein the composition for stabilization further comprises an osmoregulating agent selected from the group consisting of a pharmaceutically acceptable salt, a sugar, an amino acid, and any combination thereof.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the osmoregulating agent comprises one or more selected from the group consisting of sodium chloride, sodium succinate, sodium sulfate, potassium chloride, magnesium chloride, magnesium sulfate, trehalose, sucrose, mannitol, sorbitol, fructose, maltose, lactose, dextran, proline, alanine, arginine, asparagine, aspartic acid, glycine, serine, lysine, and histidine.

### Claim 10 (depends on 8)

The method according to claim 8, wherein the amount of the osmo-regulating agent in the composition for stabilization is about 0.01 to about 1% (w/v) based on the total amount of the composition for stabilization.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the amount of the protein drug in the liquid formulation is about 1 mg/ml to about 200 mg/ml.

### Claim 12 (depends on 1)

The method according to claim 1, wherein about 5% or less of the initial protein drug content of the liquid formulation aggregates or degrades after the liquid formulation has been stored at about 40° C. to about 50° C. for three months.

### Claim 13 (depends on 1)

The method of claim 1, wherein the anti-c-Met antibody comprises a heavy chain comprising the amino acid sequence from the 18th to 460th positions of SEQ ID NO: 66 and a light chain comprising the amino acid sequence from the 21st to 240th positions of SEQ ID NO: 68.