# US 10,370,426 B2 · Triple glucagon/GLP-1/GIP receptor agonist

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,370,426 B2
- Document ID: US10370426B2
- Status: Granted
- Kind: B2
- Application number: 16/023,994
- Filed: 2018-06-29
- Published: 2019-01-03
- Granted: 2019-08-06
- Earliest claimed: 2015-12-31
- Assignees: Hanmi Pharm. Co., Ltd.
- Applicants: Hanmi Pharm. Co., Ltd
- Inventors: Euh Lim Oh; Jong Suk Lee; Young Jin Park; Chang Ki Lim; Sung Youb Jung; Se Chang Kwon
- Web page: https://patentgrep.com/patent/US10370426B2

## CPC

- C07K 14/605: Glucagons
- A61K 38/26: Glucagons
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C07K 14/47: from mammals
- C07K 14/72: for hormones {(for neuromediators C07K14/70571)}
- C07K 16/283: {against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851)}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- 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)
- 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

## Abstract

The present invention relates to a triple agonist having activities to all of glucagon, GLP-1, and GIP receptors and uses thereof.

## Claims

### Claim 1

An isolated peptide having activities to a glucagon receptor, a glucagon-like peptide-1 (GLP-1) receptor, and a glucose-dependent insulinotropic polypeptide (GIP) receptor,
wherein the isolated peptide comprises the amino acid sequence of the following Formula (1):
(SEQ ID NO: 103)
Xaa1-Xaa2-Xaa3-Gly-Thr-Phe-Xaa7-Ser-Asp-Xaa10-Ser-
Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19-
Xaa20-Xaa21-Phe-Xaa23-Xaa24-Trp-Leu-Xaa27-Xaa28-
Xaa29-Xaa30-R1
wherein, in Formula (1),
Xaa1 is His, 4-imidazoacetyl (CA), or Tyr;
Xaa2 is α-methyl-glutamic acid, or aminoisobutyric acid (Aib);
Xaa3 is Gln;
Xaa7 is Thr;
Xaa10 is Tyr;
Xaa12 is Lys;
Xaa13 is Tyr, Ala, or Cys;
Xaa14 is Leu or Met;
Xaa15 is Cys, Asp, or Glu;
Xaa16 is Gly or Glu;
Xaa17 is Gln, Arg, Ile, Glu, Cys, or Lys;
Xaa18 is Ala, Arg, or His;
Xaa19 is Ala, Gln, or Cys;
Xaa20 is Lys;
Xaa21 is Glu, Gln, Cys, or Asp;
Xaa23 is Ile or Val;
Xaa24 is Ala, Gln, Cys, or Asn;
Xaa27 is Leu or Lys;
Xaa28 is Cys, Ala, or Asp;
Xaa29 is Cys, Gly, Gln, Thr, Glu, or His;
Xaa30 is Cys, Gly, Lys, or His, or is absent; and
R1 is Cys, GKKNDWKHNIT (SEQ ID NO: 106), m-SSGAPPPS-n (SEQ ID NO: 107), or m-SSGQPPPS-n (SEQ ID NO: 108), or is absent;
wherein
m is -Cys-, -Pro-, or -Gly-Pro-; and
n is -Cys-, -Gly-, -Ser-, or -His-Gly-, or is absent.

### Claim 2 (depends on 1)

The isolated peptide of claim 1, wherein R1 is Cys, GKKNDWKHNIT (SEQ ID NO: 106), CSSGQPPPS (SEQ ID NO: 109), GPSSGAPPPS (SEQ ID NO: 110), GPSSGAPPPSC (SEQ ID NO: 111), PSSGAPPPS (SEQ ID NO: 112), PSSGAPPPSG (SEQ ID NO: 113), PSSGAPPPSHG (SEQ ID NO: 114), PSSGAPPPSS (SEQ ID NO: 115), PSSGQPPPS (SEQ ID NO: 116), or PSSGQPPPSC (SEQ ID NO: 117), or is absent.

### Claim 3 (depends on 1)

The isolated peptide of claim 1, wherein the isolated peptide is selected from the group consisting of SEQ ID NOS: 21 to 23, 30 to 32, 34, 42, 43, 50 to 52, 56, 58, 64 to 71, 73 to 78, 82, 86, 89, 93, and 95 to 102.

### Claim 4 (depends on 3)

The isolated peptide of claim 3, wherein the isolated peptide is selected from the group consisting of SEQ ID NOS: 21, 22, 23, 31, 32, 42, 43, 50, 64 to 71, 73 to 77, and 96 to 102.

### Claim 5 (depends on 1)

The isolated peptide of claim 1,
wherein, in Formula (1),
Xaa13 is Ala, Tyr, or Cys;
Xaa15 is Asp or Glu;
Xaa17 is Gln, Arg, Cys, or Lys;
Xaa18 is Ala, Arg, or His;
Xaa21 is Cys, Glu, Gln, or Asp;
Xaa23 is Ile or Val;
Xaa24 is Cys, Gln, or Asn;
Xaa28 is Cys or Asp;
Xaa29 is Gln, Cys, or His; and
Xaa30 is Cys, Lys, or His.

### Claim 6 (depends on 1)

The isolated peptide of claim 1,
wherein, in Formula (1),
Xaa1 is His or 4-imidazoacetyl;
Xaa13 is Ala or Cys;
Xaa14 is Met;
Xaa15 is Asp;
Xaa16 is Glu;
Xaa17 is Ile or Lys;
Xaa18 is Ala or His;
Xaa19 is Gln or Cys;
Xaa20 is Lys;
Xaa21 is Asp;
Xaa23 is Val;
Xaa24 is Asn;
Xaa28 is Ala;
Xaa29 is Gln or Thr; and
Xaa30 is Cys or Lys, or is absent.

### Claim 7 (depends on 1)

A pharmaceutical composition comprising the peptide of claim 1.

### Claim 8 (depends on 1)

A method of treating metabolic syndrome comprising administering the peptide according to claim 1 to a subject in need thereof,
wherein the metabolic syndrome comprises impaired glucose tolerance, hypercholesterolemia, dyslipidemia, obesity, diabetes, hypertension, arteriosclerosis due to dyslipidemia, atherosclerosis, arteriosclerosis, or coronary heart disease.

### Claim 9 (depends on 1)

The isolated peptide of claim 1, wherein the isolated peptide comprises the amino acid sequence of the following Formula (3):
(SEQ ID NO: 105)
Xaa1-Xaa2-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-
Xaa13-Leu-Asp-Glu-Xaa17-Xaa18-Xaa19-Lys-Xaa21-Phe-
Val-Xaa24-Trp-Leu-Leu-Xaa28-Xaa29-Xaa30-Xaa31-Ser-
Ser-Gly-Gln-Pro-Pro-Pro-Ser-Xaa40
wherein, in Formula (3),
Xaa1 is His or Tyr;
Xaa2 is a-methyl-glutamic acid or aminoisobutyric acid (Aib);
Xaa13 is Ala, Tyr, or Cys;
Xaa17 is Arg, Cys, or Lys;
Xaa18 is Ala or Arg;
Xaa19 is Ala or Cys;
Xaa21 is Glu or Asp;
Xaa24 is Gln or Asn;
Xaa28 is Cys or Asp;
Xaa29 is Cys, His, or Gln;
Xaa30 is Cys or His;
Xaa31 is Pro or Cys; and
Xaa40 is Cys or is absent.

### Claim 10 (depends on 9)

The isolated peptide of claim 9, wherein the isolated peptide is selected from the group consisting of SEQ ID NOS: 21, 22, 42, 43, 50, 64, 66, 67, 70, 71, 76, 77, 96, 97 and 100.

### Claim 11 (depends on 9)

The isolated peptide according to claim 9, wherein, in Formula (3), the 16th amino acid and the 20th amino acid from the N-terminus together form a ring.

### Claim 12 (depends on 9)

The isolated peptide of claim 9, wherein Xaa1 is Tyr.

### Claim 13 (depends on 9)

A pharmaceutical composition comprising the peptide of claim 9.

### Claim 14 (depends on 9)

A method of treating metabolic syndrome comprising administering the peptide according to claim 9 to a subject in need thereof,
wherein the metabolic syndrome comprises impaired glucose tolerance, hypercholesterolemia, dyslipidemia, obesity, diabetes, hypertension, arteriosclerosis due to dyslipidemia, atherosclerosis, arteriosclerosis, or coronary heart disease.

### Claim 15

An isolated peptide selected from the group consisting of SEQ ID NOS: 24, 27-29, 36, 37, 39, 53, 55, 72, 79, 81, and 88.

### Claim 16 (depends on 15)

The isolated peptide of claim 15, wherein the peptide is selected from the group consisting of SEQ ID NOS: 24, 29, 36, 37, 81, and 88.