# US 10,501,514 B2 · Cyclic galanin-analogs and uses thereof

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

- Number: US 10,501,514 B2
- Document ID: US10501514B2
- Status: Granted
- Kind: B2
- Application number: 15/557,273
- Filed: 2016-03-11
- Published: 2018-03-01
- Granted: 2019-12-10
- Earliest claimed: 2015-03-13
- Assignees: LanthioPep B.V.
- Applicants: LanthioPep B.V.
- Inventors: Anneke Kuipers
- Web page: https://patentgrep.com/patent/US10501514B2

## CPC

- C07K 14/575: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695)
- A61K 38/22: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35)
- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 1/04: on carriers {(C07K1/003, C07K1/006 take precedence)}
- C07K 1/1075: {by covalent attachment of amino acids or peptide residues}
- C07K 2319/02: containing a signal sequence
- C07K 2319/50: containing protease site
- 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 invention generally relates to the field of medicine and pharmacology. More particularly, it relates to novel analogs of galanin, and the use thereof in therapy. Provided is a cyclic peptide analog of galanin, wherein the galanin analog comprises a (methyl)Lanthionine bridge and wherein the analog has the general formula “X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-X22-”, or a truncated variant thereof lacking X1 and/or up to 11 of the C-terminal residues, wherein two residues selected from the group consisting of X3, X4, X6, X7, X10 and X13-X19 together form a Lanthionine bridge of the structure Ala-S-Ala, or a methyl Lanthionine bridge of the structure Abu-S-Ala or Ala-S-Abu.

## Claims

### Claim 1

Galanin analog selected from the group consisting of:
GWNmelanNAmelanGYLLGPHAVGNHR,
(SEQ ID NO: 6)
GWNmelanNAmelanGYLLGPHAVGNH,
(SEQ ID NO: 7)
GWNLNAAmelanYLmelanGPHAVGNHR,
(SEQ ID NO: 8)
GWNLNAAmelanYLmelanGPHAVGNH,
(SEQ ID NO: 9)
GWNLNAAlanYLLlanGPHAVGNHR,
(SEQ ID NO: 10)
GWNLNAAlanYLLlanGPHAVGNH,
(SEQ ID NO: 11)
GWNLNAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 12)
GWNLNAAGYLLGAmelanAVmelanNH,
(SEQ ID NO: 13)
GWNLNAAGYLLGAlanAVlan,
(SEQ ID NO: 14)
GWNLNAAGYLLGAlanAVlanNHR,
(SEQ ID NO: 15)
GWNLNAAGYLLGAlanAVlanNH,
(SEQ ID NO: 16)
GWNLNAAGYLLGAmelanAVGmelanHR,
(SEQ ID NO: 17)
GWNLNAAGYLLGAlanAVGlan,
(SEQ ID NO: 18)
GWNLNAAGYLLGAlanAVGlanHR,
(SEQ ID NO: 19)
GWNLNAAGYLLGAlanAVGNlanR,
(SEQ ID NO: 20)
GWNLNAAGYLLGAlanAVGNlan,
(SEQ ID NO: 21)
GWNLNAAGYLLGAlanAVGNHlan,
(SEQ ID NO: 22)
GWNLNAAGYLLGPHmelanVGmelanHR,
(SEQ ID NO: 23)
GWNLNAAGYLLGPHlanVGlan,
(SEQ ID NO: 24)
GWNLNAAGYLLGPHAmelanGNmelanR,
(SEQ ID NO: 25)
GWNLNAAGYLLGPHAlanGNlan,
(SEQ ID NO: 26)
GWNLNAAGYLLGASlanVGNHlan,
(SEQ ID NO: 27)
pEWNLNAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 28)
pEWNLNAAGYLLGAmelanAVGmelanHR,
(SEQ ID NO: 29)
pEWNLNAAGYLLGAmelanAVmelanNH,
(SEQ ID NO: 30)
pEWNLNAAGYLLGAlanAVlan,
(SEQ ID NO: 31)
pEWNLNAAlanYLLlan,
(SEQ ID NO: 32)
pEWNLNAAGYLLGPHmelanVGmelanHR,
(SEQ ID NO: 33)
GWNLNAAGYLLGmelanHAmelanG,
(SEQ ID NO: 34)
GWNLNAAGYLLGPmelanAVmelan,
(SEQ ID NO: 35)
GWNLNAAGYLLAmelanHAmelanG,
(SEQ ID NO: 36)
GWNLNAAGYLLGAmelanAVmelan,
(SEQ ID NO: 37)
pEWNLNAAGYLLAmelanHAmelanG,
(SEQ ID NO: 38)
pEWNLNAAGYLLGAmelanAVmelan,
(SEQ ID NO: 39)
pEWNLNAAGYLLAlanHAlanG,
(SEQ ID NO: 40)
pEWNLNAAGYLLAmelanHAmelanGNHR,
(SEQ ID NO: 41)
GWNLNAAmelanYLmelanGPHAVGNHR,
(SEQ ID NO: 8)
pEWNLNAAGYLLGPHAmelanGNmelanR,
(SEQ ID NO: 42)
GWNLNAAGYLLAmelanHAmelanG,
(SEQ ID NO: 36)
pEWNLNAAGYLLAmelanHAmelanG,
(SEQ ID NO: 38)
GWNLNAAGYLLGAmelanAVmelan,
(SEQ ID NO: 37)
pEWNLNAAGYLLGAmelanAVmelan,
(SEQ ID NO: 39)
GWNVNAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 43)
GWNDNAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 44)
GWNNNAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 45)
GWNLVAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 46)
GWNLKAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 47)
GWNLDAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 48)
GWNLQAAGYLLGAmelanAVmelanNHR,
(SEQ ID NO: 49)
pEWNLNAAGYLLGPlanAVlan,
(SEQ ID NO: 50)
pEWTLNAAlanYLLlan,
(SEQ ID NO: 51)
pEWNLNAAGYLLGPmelanAVmelan,
(SEQ ID NO: 52)
or
pEWTLNAAmelanYLLmelan.
(SEQ ID NO: 53)

### Claim 2 (depends on 1)

A pharmaceutical composition comprising at least one galanin analog according to claim 1.

### Claim 3 (depends on 2)

A method for treatment of Multiple Sclerosis, Alzheimer's disease, anxiety, depression, convulsions and brain injury, in a subject, said method comprising administering to the subject the pharmaceutical composition of claim 2.

### Claim 4 (depends on 1)

A method for providing a cyclic galanin analog according to claim 1, comprising the steps of
(i) providing a peptide selected from the group consisting of
GWNTNACGYLLGPHAVGNHR,
(SEQ ID NO: 58)
GWNTNACGYLLGPHAVGNH,
(SEQ ID NO: 59)
GWNLNAATYLCGPHAVGNHR,
(SEQ ID NO: 60)
GWNLNAATYLCGPHAVGNH,
(SEQ ID NO: 61)
GWNLNAASYLLCGPHAVGNHR,
(SEQ ID NO: 62)
GWNLNAASYLLCGPHAVGNH,
(SEQ ID NO: 63)
GWNLNAAGYLLGATAVCNHR,
(SEQ ID NO: 64)
GWNLNAAGYLLGATAVCNH,
(SEQ ID NO: 65)
GWNLNAAGYLLGASAVC,
(SEQ ID NO: 66)
GWNLNAAGYLLGASAVCNHR,
(SEQ ID NO: 67)
GWNLNAAGYLLGASAVCNH,
(SEQ ID NO: 68)
GWNLNAAGYLLGATAVGCHR,
(SEQ ID NO: 69)
GWNLNAAGYLLGASAVGC,
(SEQ ID NO: 70)
GWNLNAAGYLLGASAVGCHR,
(SEQ ID NO: 71)
GWNLNAAGYLLGASAVGNCR,
(SEQ ID NO: 72)
GWNLNAAGYLLGASAVGNC,
(SEQ ID NO: 73)
GWNLNAAGYLLGASAVGNHC,
(SEQ ID NO: 74)
GWNLNAAGYLLGPHTVGCHR,
(SEQ ID NO: 75)
GWNLNAAGYLLGPHSVGC,
(SEQ ID NO: 76)
GWNLNAAGYLLGPHATGNCR,
(SEQ ID NO: 77)
GWNLNAAGYLLGPHASGNC,
(SEQ ID NO: 78)
GWNLNAAGYLLGASAVGNHC,
(SEQ ID NO: 74)
QWNLNAAGYLLGATAVCNHR,
(SEQ ID NO: 79)
QWNLNAAGYLLGATAVCNH,
(SEQ ID NO: 80)
QWNLNAAGYLLGASAVC,
(SEQ ID NO: 81)
QWNLNAASYLLC,
(SEQ ID NO: 82)
QWNLNAAGYLLGPHTVGCHR,
(SEQ ID NO: 83)
GWNLNAAGYLLGTHACG,
(SEQ ID NO: 84)
GWNLNAAGYLLGPTAVC,
(SEQ ID NO: 85)
GWNLNAAGYLLATHACG,
(SEQ ID NO: 86)
GWNLNAAGYLLGATAVC,
(SEQ ID NO: 87)
QWNLNAAGYLLATHACG,
(SEQ ID NO: 88)
QWNLNAAGYLLGATAVC,
(SEQ ID NO: 93)
QWNLNAAGYLLASHACG,
(SEQ ID NO: 90)
QWNLNAAGYLLATHACGNHR,
(SEQ ID NO: 91)
GWNLNAATYLCGPHAVGNHR,
(SEQ ID NO: 60)
QWNLNAAGYLLGPHATGNCR,
(SEQ ID NO: 92)
GWNLNAAGYLLATHACG,
(SEQ ID NO: 86)
QWNLNAAGYLLATHACG,
(SEQ ID NO: 88)
GWNLNAAGYLLGATAVC,
(SEQ ID NO: 87)
QWNLNAAGYLLGATAVC,
(SEQ ID NO: 93)
GWNVNAAGYLLGATAVCNHR,
(SEQ ID NO: 94)
GWNDNAAGYLLGATAVCNHR,
(SEQ ID NO: 95)
GWNNNAAGYLLGATAVCNHR,
(SEQ ID NO: 96)
GWNLVAAGYLLGATAVCNHR,
(SEQ ID NO: 97)
GWNLKAAGYLLGATAVCNHR,
(SEQ ID NO: 98)
GWNLDAAGYLLGATAVCNHR,
(SEQ ID NO: 99)
GWNLQAAGYLLGATAVCNHR,
(SEQ ID NO: 100)
QWNLNAAGYLLGPSAVC,
(SEQ ID NO: 103)
QWTLNAASYLLC,
(SEQ ID NO: 104)
QWNLNAAGYLLGPTAVC,
(SEQ ID NO: 101)
and
QWTLNAATYLLC.
(SEQ ID NO: 102)
(ii) inducing dehydration of a Ser or Thr residue of said peptide;
(iii) inducing ring closure by coupling the dehydrated Ser or Thr to the thiol group of the Cys residue of said peptide; and
(iv) converting the N-terminal Q to pE.

### Claim 5 (depends on 4)

Method according to claim 4, wherein step (iii) comprises inducing ring closure by chemical or enzymatic means.