# US 11,111,271 B2 · Therapeutic peptides

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- Number: US 11,111,271 B2
- Document ID: US11111271B2
- Status: Granted
- Kind: B2
- Application number: 16/336,089
- Filed: 2017-09-27
- Published: 2020-06-11
- Granted: 2021-09-07
- Earliest claimed: 2016-09-28
- Assignees: Cohbar, Inc.
- Applicants: Cohbar, Inc.
- Inventors: Kenneth C. Cundy; Kent K. Grindstaff; Remi Magnan; Wendy Luo; Yongjin Yao; Liang Zeng Yan
- Web page: https://patentgrep.com/patent/US11111271B2

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- C07K 7/06: having 5 to 11 amino acids
- C07K 14/47: from mammals
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Provided herein are peptides and peptide analogs and methods of treating a metabolic disease, e.g., obesity, diabetes, methods of treating cancer, methods of treating a liver disease, and methods of modulating fatty acid metabolism.

## Claims

### Claim 1

A peptide comprising the amino acid sequence of formula I:
(I)
(SEQ ID NO: 1)
X1-QE-X2-X3-YI-X4-Y-X5-R-X6
wherein
X1 is absent or if present is X7—RW, wherein X7 is absent or if present is M or E;
X2 is M, A or E;
X3 is G, N or Q;
X4 is F or A;
X5 is P or A;
X6 is absent or if present is KL-X8 or X9-LR, wherein X8 is absent or if present is R or A and X9 is selected from K, A, (dA), N and Q;
wherein the amino acid sequence of formula I is selected from the group consisting of:
(SEQ ID NO: 11)
MRWQEAGYIFYPRKLR;
(SEQ ID NO: 149)
MRWQEMGYIFYPR(dA)LR;
(SEQ ID NO: 208)
MRWQEMNYIFYPR;
(SEQ ID NO: 213)
MRWQEMGYIFYPRNLR;
(SEQ ID NO: 219)
MRWQEMQYIFYPRALR;
(SEQ ID NO: 248)
RWQEMNYIFYPR;
(SEQ ID NO: 19)
MRWQEMGYIFYPRALR;
(SEQ ID NO: 21)
MRWQEMGYIFYPRKLA;
(SEQ ID NO: 17)
MRWQEMGYIFYARKLR;
(SEQ ID NO: 217)
RWQEMGYIFYPRQLR;
(SEQ ID NO: 172)
MRWQEEGYIFYPRKLR;
(SEQ ID NO: 241)
ERWQEAGYIAYPR; and
(SEQ ID NO: 211)
RWQEMQYIFYPR;
or C-terminal acids or amides, or N-acetyl derivatives thereof; or
pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

The peptide or C-terminal acids or amides, or N-acetyl derivatives thereof according to claim 1 that is isolated; or pharmaceutically acceptable salts thereof.

### Claim 3 (depends on 1)

A peptide or C-terminal acids or amides, or N-acetyl derivatives thereof of claim 1, further comprising a duration enhancing moiety.

### Claim 4 (depends on 1)

The peptide of claim 1 consisting of MRWQEMNYIFYPR (SEQ ID NO: 208); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 5 (depends on 1)

The peptide of claim 1 consisting of RWQEMNYIFYPR (SEQ ID NO: 248); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 6 (depends on 1)

The peptide of claim 1 consisting of RWQEMQYIFYPR (SEQ ID NO: 211); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 7

A peptide comprising the amino acid sequence of formula I:
X1-QE-X2—X3—YI—X4—Y—X5—R—X6 (I) (SEQ ID NO: 1)
wherein
X1 is absent or if present is X7—RW, wherein X7 is absent or if present is M or E;
X2 is M, A or E;
X3 is N or Q;
X4 is F or A;
X5 is P or A; and
X6 is absent or if present is KL-X8 or X9-LR, wherein X8 is absent or if present is R or A and X9 is selected from K, A, (dA), N and Q; or pharmaceutically acceptable salts thereof,
or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 8 (depends on 1, 7)

The peptide according to claim 1 or claim 7 that is 10-35 amino acids in length; or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 9 (depends on 4, 7)

The peptide of claim 4 or claim 7 wherein the peptide is derivatized.

### Claim 10 (depends on 9)

The peptide of claim 9 wherein the derivatization is acetylation, pegylation, biotinylation or acylation.

### Claim 11 (depends on 10)

The peptide of claim 10 wherein the derivative is PEG600, acetyl, biotin or palmityl.

### Claim 12 (depends on 1, 7)

A conjugate comprising the peptide of claim 1 or claim 7 and a heterologous moiety; or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 13 (depends on 1, 7)

A nucleic acid comprising a nucleotide sequence encoding the peptide of claim 1 or claim 7, wherein the peptide has an amino acid sequence that can be coded for by a nucleic acid.

### Claim 14 (depends on 13)

An expression vector comprising the nucleic acid of claim 13.

### Claim 15 (depends on 13)

A host cell comprising the nucleic acid of claim 13 or comprising an expression vector that comprises said nucleic acid.

### Claim 16 (depends on 1, 7)

A composition comprising the peptide of claim 1 or claim 7, and a carrier, excipient, or diluent.

### Claim 17 (depends on 16)

The composition of claim 16, wherein the peptide comprises MRWQEMNYIFYPR (SEQ ID NO: 208); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 18 (depends on 16)

The composition of claim 16, wherein the peptide comprises RWQEMNYIFYPR (SEQ ID NO: 248); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 19 (depends on 16)

The composition of claim 16, wherein the peptide comprises RWQEMQYIFYPR (SEQ ID NO: 211); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 20 (depends on 1, 7)

A kit comprising the peptide of claim 1 or claim 7, or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof, in a container or a package.

### Claim 21 (depends on 1, 7)

A method of producing the peptide or peptide analog according to claim 1 or claim 7, said method comprising:
(i) reacting a first amino acid with a second amino acid to form a covalent linkage between the first amino acid and the second amino acid, wherein the first amino acid or the second amino acid optionally is attached to another amino acid, and
(ii) repeating the reacting step of (i), whereupon the peptide or peptide analog of claim 1 or claim 7 is produced.

### Claim 22 (depends on 1, 7)

A method of treating a subject having a liver disease, comprising administering to the subject the peptide of claim 1 or claim 7 in an amount effective to treat the liver disease.

### Claim 23 (depends on 22)

The method of claim 22, wherein the liver disease is a fatty liver disease.

### Claim 24 (depends on 23)

The method of claim 23, wherein the fatty liver disease is NAFLD or NASH.

### Claim 25 (depends on 24)

The method of claim 24, wherein the peptide comprises MRWQEMNYIFYPR (SEQ ID NO: 208); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 26 (depends on 24)

The method of claim 24, wherein the peptide comprises RWQEMNYIFYPR (SEQ ID NO: 248); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 27 (depends on 24)

The method of claim 24, wherein the peptide comprises RWQEMQYIFYPR (SEQ ID NO: 211); or C-terminal acids or amides, or N-acetyl derivatives thereof; or pharmaceutically acceptable salts thereof.

### Claim 28 (depends on 27)

The method according to claim 27, wherein the peptide or C-terminal acids or amides, or N-acetyl derivatives thereof decreases free fatty acid levels in human primary adipocytes.

### Claim 29 (depends on 1, 7)

A method of reduction, remission or regression of liver disease in a subject with the liver disease, comprising administering to the subject the peptide of claim 1 or claim 7, in an amount effective to arrest the progression the liver disease.

### Claim 30

A peptide or peptide analog comprising both RWQE (SEQ ID NO: 294) and YIFY (SEQ ID NO: 295), wherein the peptide or peptide analog is 8 to 20 amino acids in length, and wherein the peptide or peptide analog:
(i) exhibits at least a 20% stability in mouse plasma for 60 minutes at 37 degrees Celsius,
(ii) decreases free fatty acid levels in human primary adipocytes, or
(iii) or both (i) and (ii).

### Claim 31 (depends on 30)

The peptide or peptide analog of claim 30 comprising the amino acid sequence of RWQEX1X2YIFY (SEQ ID NO: 319), wherein each of X1 and X2 independently is any amino acid.

### Claim 32 (depends on 31)

The peptide or peptide analog of claim 31, wherein X1X2 is Met-Asn, Met-Gln, Ala-Gly, Met-Ala, Nle-Gly, Gly-Gly, Met-(dA), (dA)-Gly, Glu-Gly, Met-Glu, Cys-Gly, Glu-Asn, or Glu-Gln.

### Claim 33 (depends on 30)

The peptide or peptide analog of claim 30, or C-terminal acids or amides, or N-acetyl derivatives thereof, that decreases free fatty acid levels in human primary adipocytes.