# US 2018/0000934 A1 · Stable Pharmaceutical Solution Formulation of GLP-1R Antibody Fusion Protein

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- Number: US 2018/0000934 A1
- Document ID: US20180000934A1
- Status: Published application
- Kind: A1
- Application number: 15/547,727
- Filed: 2016-02-03
- Published: 2018-01-04
- Earliest claimed: 2015-02-11
- Assignees: Gmax Biopharm LLC
- Applicants: Gmax Biopharm LLC.
- Inventors: Cheng Zhang; Hua Zhang; Kesuo Fan; Yong Guo; Shuqian Jing
- Web page: https://patentgrep.com/patent/US20180000934A1

## CPC

- A61K 39/39591: {Stabilisation, fragmentation}
- A61K 9/00: Medicinal preparations characterised by special physical form {(nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 38/26: Glucagons
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- 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
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/12: Antidiarrhoeals
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/50: for increasing or potentiating the activity of insulin
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K 14/605: Glucagons
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/2869: {against hormone receptors (for antibodies against neuromediator receptors C07K16/286)}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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 stable pharmaceutical solution formulation of a GLP-1R antibody fusion protein, comprising a therapeutically effective amount of the GLP-1R antibody fusion protein, an amino acid, a surfactant and a buffer system. The final concentration of the amino acid is 1-500 mM, the final concentration of the surfactant is 0.01%-0.5%, and the pH value of the stable solution formulation is from 5.0 to 8.0. The stable solution formulation of the present invention can be used in the treatment of diabetes, obesity and conditions associated therewith.

## Claims

### Claim 1

A stable pharmaceutical solution formulation of a GLP-1R antibody fusion protein, comprising a therapeutically effective amount of the GLP-1R antibody fusion protein, an amino acid, a surfactant and a buffer system, wherein the final concentration of the amino acid is 1-500 mM, the final concentration of the surfactant is 0.01%-0.5%, and the pH of the stable solution formulation is from 5.0 to 8.0.

### Claim 2 (depends on 1)

The stable solution formulation of claim 1, wherein the stable solution formulation is stable for at least 6 months at 25° C.

### Claim 3 (depends on 1)

The stable solution formulation of claim 1, wherein the final concentration of the amino acid is 80-200 mM, the final concentration of the surfactant is 0.01%-0.2%, the buffer system is a citrate buffer, and the pH of the stable solution formulation is from 5.5 to 7.0.

### Claim 4 (depends on 3)

The stable solution formulation of claim 3, wherein the concentration of the citrate buffer is 5-30 mM.

### Claim 5 (depends on 4)

The stable solution formulation of claim 4, wherein the concentration of the citrate buffer is 20 mM.

### Claim 6 (depends on 3)

The stable solution formulation of claim 3, wherein the amino acid is L-arginine and the final concentration of L-arginine is 100-180 mM.

### Claim 7 (depends on 6)

The stable solution formulation of claim 6, wherein the final concentration of L-arginine is 138 mM.

### Claim 8 (depends on 3)

The stable solution formulation of claim 3, wherein the surfactant is TWEEN-80 and the final concentration of TWEEN-80 is 0.05%-0.15%.

### Claim 9 (depends on 8)

The stable solution formulation of claim 8, wherein the final concentration of TWEEN-80 is 0.1%.

### Claim 10 (depends on 1)

The stable solution formulation of claim 1, wherein the final concentration of the therapeutically effective amount of the GLP-1R antibody fusion protein is 0.1 mg/mL-100 mg/mL.

### Claim 11 (depends on 10)

The stable solution formulation of claim 10, wherein the final concentration of the therapeutically effective amount of the GLP-1R antibody fusion protein is 5 mg/mL-40 mg/mL.

### Claim 12 (depends on 1)

The stable solution formulation of claim 1, wherein the amino acid sequence of the light chain variable domain of the GLP-1R antibody fusion protein is one selected from: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, and the amino acid sequence of the heavy chain variable domain of the GLP-1R antibody fusion protein is one selected from: SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9.

### Claim 13 (depends on 12)

The stable solution formulation of claim 12, wherein the amino acid sequence of the light chain constant domain of the GLP-1R antibody fusion protein is SEQ ID NO: 10 or SEQ ID NO: 11, and the amino acid sequence of the heavy chain constant domain of the GLP-1R antibody fusion protein is SEQ ID NO: 12.

### Claim 14 (depends on 1)

The stable solution formulation of claim 1, wherein the concentration of the GLP-1R antibody fusion protein is 5 mg/mL-40 mg/mL, the concentration of L-arginine is 138 mM, the concentration of TWEEN-80 is 0.1%, and the pH is between 6-7.

### Claim 15 (depends on 14)

The stable solution formulation of claim 14, wherein the concentration of the GLP-1R antibody fusion protein is 5 mg/mL.

### Claim 16 (depends on 14)

The stable solution formulation of claim 14, wherein the concentration of the GLP-1R antibody fusion protein is 10 mg/mL.

### Claim 17 (depends on 14)

The stable solution formulation of claim 14, wherein the concentration of the GLP-1R antibody fusion protein is 20 mg/mL.

### Claim 18 (depends on 14)

The stable solution formulation of claim 14, wherein the concentration of the GLP-1R antibody fusion protein is 30 mg/mL.

### Claim 19 (depends on 14)

The stable solution formulation of claim 14, wherein the concentration of the GLP-1R antibody fusion protein is 40 mg/mL.

### Claim 20 (depends on 14)

The stable solution formulation of claim 14, wherein the pH is about 6.5.

### Claim 21 (depends on 1)

The stable solution formulation of claim 1, wherein the stable solution formulation is stored in a sterile syringe.

### Claim 22 (depends on 1)

A method for the treatment of diabetes or obesity in a subject, comprising administering to the subject the stable solution formulation of claim 1.

### Claim 23 (depends on 1)

A method for the treatment of irritable bowel syndrome and other diseases that benefit from lowering plasma glucose, inhibition of gastric and/or bowel movement, inhibition of gastric and/or intestinal emptying, or inhibition of food intake, comprising administering to the subject the stable solution formulation of claim 1.