# US 12,214,051 B2 · Method of treating or ameliorating metabolic disorders using GLP-1 receptor agonists conjugated to antagonists for gastric inhibitory peptide receptor (GIPR)

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- Number: US 12,214,051 B2
- Document ID: US12214051B2
- Status: Granted
- Kind: B2
- Application number: 17/151,045
- Filed: 2021-01-15
- Published: 2021-05-27
- Granted: 2025-02-04
- Earliest claimed: 2017-01-17
- Assignees: Amgen Inc.
- Applicants: Amgen Inc.
- Inventors: Yuan Cheng; Chawita Netirojjanakul; Jerry Ryan Holder; Bin Wu; James R. Falsey; Bradley J. Herberich; Kelvin Sham; Leslie P. Miranda; Shu-Chen Lu; Murielle M. Venient-Ellison; Shanaka Stanislaus; Junming Yie; Jing Xu
- Web page: https://patentgrep.com/patent/US12214051B2

## CPC

- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/2869: {against hormone receptors (for antibodies against neuromediator receptors C07K16/286)}
- C07K 2317/77: Internalization into the cell
- 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

Methods of treating metabolic diseases and disorders using a composition comprising an antigen binding protein specific for the GIPR polypeptide conjugated to a GLP-1 receptor agonist are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the composition comprises an antibody or functional fragment thereof comprising a cysteine at one or more conjugation site(s) wherein the GLP-1 receptor agonist is conjugated to the antibody or functional fragment thereof through the side-chain of the cysteine residue.

## Claims

### Claim 1

A method of treating a subject with a metabolic disorder, the method comprising administering to the subject a composition comprising a monoclonal human antibody that specifically binds to a polypeptide comprising the extracellular N-terminus of human Gastric Inhibitory Peptide Receptor (“GIPR”), wherein the antibody comprises a cysteine amino acid at one or more conjugation site(s); and a Glucagon Like Polypeptide-1 (“GLP-1”) receptor agonist, wherein the GLP-1 receptor agonist is conjugated to the antibody through the side-chain of the cysteine amino acid at the one or more conjugation site(s).

### Claim 2 (depends on 1)

The method of claim 1, wherein said metabolic disorder is a disorder of glucose metabolism.

### Claim 3 (depends on 2)

The method of claim 2, wherein said disorder of glucose metabolism comprises insulin resistance and wherein said administering decreases insulin resistance in said subject.

### Claim 4 (depends on 2)

The method of claim 2, wherein said subject is obese.

### Claim 5 (depends on 4)

The method of claim 4, wherein said administering reduces body weight in said subject.

### Claim 6 (depends on 4)

The method of claim 4, wherein said administering reduces body weight gain in said subject.

### Claim 7 (depends on 4)

The method of claim 4, where said administering reduces fat mass in said subject.

### Claim 8 (depends on 4)

The method of claim 4, wherein said disorder of glucose metabolism comprises insulin resistance and wherein said administering reduces insulin resistance in said subject.

### Claim 9 (depends on 4)

The method of claim 4, wherein said subject has increased liver steatosis, and wherein said administering reduces liver steatosis in said subject.

### Claim 10 (depends on 4)

The method of claim 4, wherein said subject has increased liver fat content, and wherein said administering reduces liver fat content in said subject.

### Claim 11 (depends on 1)

The method of claim 1, wherein said subject is a mammal.

### Claim 12 (depends on 1)

The method of claim 1, wherein said subject is human.

### Claim 13 (depends on 1)

The method of claim 1, wherein said administering is by parenteral injection.

### Claim 14 (depends on 1)

The method of claim 1, wherein said administering is by subcutaneous injection.