# US 10,766,939 B2 · Amylin analogues

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- Number: US 10,766,939 B2
- Document ID: US10766939B2
- Status: Granted
- Kind: B2
- Application number: 15/074,526
- Filed: 2016-03-18
- Published: 2016-09-22
- Granted: 2020-09-08
- Earliest claimed: 2015-03-18
- Assignees: Zealand Pharma A/S
- Applicants: Zealand Pharma A/S
- Inventors: Rasmus Just; Oliver Demmer; Lise Giehm; Jesper Sloth Villadsen; Henrik Munch; Jesper Mosolff Mathiesen; Jolanta Skarbaliene; Maria Deryabina; Dieter Wolfgang Hamprecht
- Web page: https://patentgrep.com/patent/US10766939B2

## CPC

- C07K 14/575: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695)
- 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 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

The present invention relates to amylin analogs and to their use in the treatment or prevention of a variety of diseases, conditions or disorders, including obesity, excess food intake and associated metabolic diseases such as diabetes. The analogs have good physical and chemical stability, good solubility, and a long duration of action, and are well suited for use in the form of a liquid formulation.

## Claims

### Claim 1

An amylin analogue which is a compound having the formula:
R1—Z—R2
wherein
R1 is hydrogen, C1-4 acyl, benzoyl or C1-4 alkyl, or a half-life extending moiety M, wherein M is optionally linked to Z via a linker moiety L;
R2 is OH or NHR3, wherein R3 is hydrogen or C1-3-alkyl; and
Z is an amino acid sequence of formula I:
(I)
(SEQ ID NO: 3)
Arg-Cys-X3-Thr-Ala-Thr-Cys-Ala-Thr-X10-Arg-Leu-
Ala-X14-Phe-Leu-X17-Arg-X19-X20-Phe-Gly(Me)-Ala-
Ile(Me)-Leu-Ser-Ser-Thr-X31-Val-Gly-Ser-X35-Thr-
X37;
wherein
X3 is selected from the group consisting of Asn, Gly, Pro and Gln;
X10 is selected from the group consisting of Gln, Asp and Glu;
X14 is selected from the group consisting of Asp, His, Asn and Aad;
X17 is selected from the group consisting of His, Asn, Gln, Glu, Thr, Val, Lys and Aad;
X19-X20 is selected from the group consisting of Ser-Ser, Val-Val, Ser-Val and Val-Ser, or is absent;
X31 is selected from the group consisting of Asp, Glu and Asn;
X35 is selected from the group consisting of Asp, Glu, Asn, Ser, Phe, Orn, Aad, Gly and Thr; and
X37 is selected from the group consisting of Pro, Apr and Hyp;
and wherein the compound has at least one residue selected from:
X3 is Gln;
X14 is His, Asn or Aad;
X17 is Asn, Gln, Glu, Thr or Aad;
X19-X20 is Val-Ser or Ser-Val; and
X35 is Ser, Phe, Orn, Aad, Gly or Thr;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

An amylin analogue according to claim 1 wherein Z is an amino acid sequence of formula II:
(II)
(SEQ ID NO: 4)
Arg-Cys-X3-Thr-Ala-Thr-Cys-Ala-Thr-X10-Arg-Leu-
Ala-X14-Phe-Leu-X17-Arg-X19-X20-Phe-Gly(Me)-Ala-
Ile(Me)-Leu-Ser-Ser-Thr-Glu-Val-Gly-Ser-X35-Thr-
X37;
wherein
X3 is selected from the group consisting of Asn, Gly and Gln;
X10 is selected from the group consisting of Gln, Asp and Glu;
X14 is selected from the group consisting of Asp, His and Aad;
X17 is selected from the group consisting of His, Asn, Gln, Glu, Lys and Aad;
X19-X20 is Ser-Ser or is absent;
X35 is selected from the group consisting of Asp, Glu, Asn, Ser, Orn, Aad, Gly and Thr; and
X37 is selected from the group consisting of Pro and Hyp;
and wherein the compound has at least one residue selected from:
X3 is Gln;
X14 is His or Aad;
X17 is Asn, Gln, Glu or Aad; and
X35 is Ser, Phe, Orn, Aad, Gly or Thr.

### Claim 3 (depends on 1)

An amylin analogue according to claim 1 wherein Z is an amino acid sequence of formula III:
(III)
(SEQ ID NO: 5)
Arg-Cys-X3-Thr-Ala-Thr-Cys-Ala-Thr-X10-Arg-Leu-
Ala-X14-Phe-Leu-X17-Arg-X19-X20-Phe-Gly(Me)-Ala-
Ile(Me)-Leu-Ser-Ser-Thr-Glu-Val-Gly-Ser-X35-Thr-
X37;
wherein
X3 is selected from the group consisting of Asn, Gly and Gln;
X10 is selected from the group consisting of Gln, Asp and Glu;
X14 is selected from the group consisting of Asp, His and Aad;
X17 is selected from the group consisting of His and Gln;
X19-X20 is Ser-Ser or is absent;
X35 is selected from the group consisting of Asp, Glu, Asn, Aad and Gly; and
X37 is selected from the group consisting of Pro and Hyp;
and wherein the compound has at least one residue selected from:
X3 is Gln;
X14 is His or Aad;
X17 is Gln; and
X35 is Aad.

### Claim 4 (depends on 1)

An amylin analogue according to claim 1, comprising the residues:
X3 is Gly;
X10 is selected from Glu and Asp;
X14 is selected from His and Aad;
X35 is selected from Gly and Asn; and
X37 is selected from Pro and Hyp.

### Claim 5 (depends on 1)

An amylin analogue according to claim 1, comprising the residues:
Gly3+Glu10;
Asn3+Glu10;
Gln3+Glu10;
Asn3+Gln10; or
Gln3+Asp10.

### Claim 6 (depends on 1)

An amylin analogue according to claim 1, wherein X14 is selected from His and Aad, and/or X17 is Gln.

### Claim 7 (depends on 1)

An amylin analogue according to claim 1, comprising the residues:
Gln17+Glu31+Hyp37
Gly3+Glu10+His14
Asn3+Glu10+His14;
Gln3+Glu10+His14;
Gly3+Glu10+Aad14;
Gly3+Glu10+Asp14;
Asp10+Aad14;
His14+Glu31+Pro37
His14+Glu31+Hyp37
Aad14+Glu31+Pro37;
Aad14+Glu31+Hyp37;
Gly3+Glu31; or
Gly3+Glu10+Glu31+Asn35+Hyp37.

### Claim 8 (depends on 1)

An amylin analogue according to claim 1, wherein X19-X20 is Ser-Ser.

### Claim 9 (depends on 8)

An amylin analogue according to claim 8, comprising the residues:
Gly3+Ser19+Ser20+Glu31 or
Gly3+Glu10+Ser19+Ser20+Glu31+Asn35+Hyp37.

### Claim 10 (depends on 1)

An amylin analogue according to claim 1, wherein Z is:
(SEQ ID NO: 6)
RCNTATCATQRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP,
(SEQ ID NO: 7)
RCNTATCATQRLANFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP,
(SEQ ID NO: 8)
RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 9)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 10)
RCGTATCATERLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 11)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 12)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp,
(SEQ ID NO: 13)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp,
(SEQ ID NO: 14)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp,
(SEQ ID NO: 15)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp,
(SEQ ID NO: 16)
RCNTATCATQRLAHFLHRF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP,
(SEQ ID NO: 17)
RCGTATCATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 18)
RCNTATCATQRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 19)
RCGTATCATERLANFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 20)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 21)
RCGTATCATERLAHFLKRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 22)
RCNTATCATQRLAHFLHRSVF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP,
(SEQ ID NO: 23)
RCNTATCATORLAHFLHRVSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP,
(SEQ ID NO: 24)
RCGTATCATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP,
(SEQ ID NO: 25)
RCPTATCATDRLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSDTP,
(SEQ ID NO: 26)
RCNTATCATQRLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP,
(SEQ ID NO: 27)
RCPTATCATDRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSNTP,
(SEQ ID NO: 28)
RCGTATCATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP,
(SEQ ID NO: 29)
RCPTATCATDRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSDTP,
(SEQ ID NO: 30)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 31)
RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 32)
RCGTATCATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 33)
RCGTATCATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSI-Hyp,
(SEQ ID NO: 34)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp,
(SEQ ID NO: 35)
RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp,
(SEQ ID NO: 36)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP,
(SEQ ID NO: 37)
RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP,
(SEQ ID NO: 38)
RCGTATCATERLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP,
(SEQ ID NO: 39)
RCGTATCATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP,
(SEQ ID NO: 40)
RCGTATCATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP,
(SEQ ID NO: 41)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFTP,
(SEQ ID NO: 42)
RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFTP,
(SEQ ID NO: 43)
RCGTATCATERLADFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 44)
RCGTATCATERLADFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp,
(SEQ ID NO: 45)
RCGTATCATERLA-Aad-FLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 46)
RCGTATCATERLA-Aad-FLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp,
(SEQ ID NO: 47)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Apr,
(SEQ ID NO: 48)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP,
(SEQ ID NO: 49)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-TP,
(SEQ ID NO: 50)
RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp,
(SEQ ID NO: 51)
RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 52)
RCNTATCATQRLAHFL-Aad-RSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 53)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp,
(SEQ ID NO: 54)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp,
(SEQ ID NO: 55)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp,
(SEQ ID NO: 56)
RCGTATCATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 57)
RCGTATCATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 58)
RCNTATCATERLAHFLQRSSF-GIy(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 59)
RCQTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 60)
RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 61)
RCPTATCATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSNT-Hyp,
(SEQ ID NO: 62)
RCNTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSDT-Hyp,
(SEQ ID NO: 63)
RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 64)
RCNTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 65)
RCPTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 66)
RCPTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 67)
RCNTATCATQRLADFLQRSSF-GIy(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 68)
RCNTATCATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 69)
RCPTATCATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 70)
RCNTATCATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 71)
RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 72)
RCPTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 73)
RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp,
(SEQ ID NO: 74)
RCPTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp,
(SEQ ID NO: 75)
RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp,
(SEQ ID NO: 76)
RCPTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp,
(SEQ ID NO: 77)
RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp,
(SEQ ID NO: 78)
RCPTATCATERLAHFLQRSSF-GIy(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp,
(SEQ ID NO: 79)
RCGTATCATERLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 80)
RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 81)
RCNTATCATQRLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp,
(SEQ ID NO: 82)
RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGTP,
(SEQ ID NO: 83)
RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp,
(SEQ ID NO: 84)
RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTTP,
(SEQ ID NO: 85)
RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp,
(SEQ ID NO: 86)
RCNTATCATQRLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP,
(SEQ ID NO: 87)
RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP,
(SEQ ID NO: 88)
RCNTATCATQRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 89)
RCNTATCATQRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp,
(SEQ ID NO: 90)
RCQTATCATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 91)
RCQTATCATDRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
(SEQ ID NO: 92)
RCQTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp,
(SEQ ID NO: 93)
RCQTATCATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp,
(SEQ ID NO: 94)
RCQTATCATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 95)
RCQTATCATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP,
(SEQ ID NO: 96)
RCQTATCATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGTP,
(SEQ ID NO: 97)
RCQTATCATDRLA-Aad-FLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp,
or
(SEQ ID NO: 98)
RCQTATCATERLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP.

### Claim 11 (depends on 1)

An amylin analogue according to claim 1, wherein R1 is M- or M-L-.

### Claim 12 (depends on 11)

An amylin analogue according to claim 11, wherein M is an alkanoyl group.

### Claim 13 (depends on 12)

An amylin analogue according to claim 12, wherein M is selected from 15-carboxy-pentadecanoyl, 17-carboxy-heptadecanoyl and 19-carboxy-nonadecanoyl.

### Claim 14 (depends on 1)

An amylin analogue according to claim 1, wherein R1 is M-L- and L is a residue of an amino acid selected from the group consisting of Gly, Pro, Ala, Val, Leu, Ile, Met, Cys, Phe, Tyr, Trp, His, Lys, Arg, Gln, Asn, α-Glu, γ-Glu, ε-Lys, Asp, β-Asp, Ser, Thr, Gaba, Aib, β-Ala, 4-aminobutanoyl, 5-aminopentanoyl, 6-aminohexanoyl, 7-aminoheptanoyl, 8-aminooctanoyl, 9-aminononanoyl, 10-aminodecanoyl and 8Ado.

### Claim 15 (depends on 14)

An amylin analogue according to claim 14, wherein L is a γ-Glu residue.

### Claim 16 (depends on 1)

An amylin analogue according to claim 1, wherein R2 is NH2.

### Claim 17 (depends on 1)

An amylin analogue according to claim 1, wherein the amylin analogue is is selected from the group consisting of:
(SEQ ID NO: 103)
[19CD]-isoGlu-RCNTATCATQRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2,
(SEQ ID NO: 104)
[19CD]-isoGlu-RCNTATCATQRLANFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2,
(SEQ ID NO: 107)
[19CD]-isoGlu-RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 108)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 109)
[19CD]-isoGlu-RCGTATCATERLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 110)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 111)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp-NH2,
(SEQ ID NO: 112)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp-NH2,
(SEQ ID NO: 113)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp-NH2,
(SEQ ID NO: 114)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2,
(SEQ ID NO: 115)
[19CD]-isoGlu-RCNTATCATQRLAHFLHRFGIy(Me)-A-Ile(Me)-LSSTEVGSETP-NH2,
(SEQ ID NO: 116)
[19CD]-isoGlu-RCGTATCATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 117)
[19CD]-isoGlu-RCNTATCATQRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 118)
[19CD]-isoGlu-RCGTATCATERLANFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 119)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 120)
[19CD]-isoGlu-RCGTATCATERLAHFLKRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 121)
[19CD]-isoGlu-RCNTATCATQRLAHFLHRSVF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2,
(SEQ ID NO: 122)
[19CD]-isoGlu-RCNTATCATQRLAHFLHRVSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2,
(SEQ ID NO: 123)
[19CD]-isoGlu-RCGTATCATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2,
(SEQ ID NO: 124)
[19CD]-isoGlu-RCPTATCATDRLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSDTP-NH2,
(SEQ ID NO: 125)
[19CD]-isoGlu-RCNTATCATQRLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2,
(SEQ ID NO: 126)
[19CD]-isoGlu-RCPTATCATDRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSNTP-NH2,
(SEQ ID NO: 127)
[19CD]-isoGlu-RCGTATCATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2,
(SEQ ID NO: 128)
[19CD]-isoGlu-RCPTATCATDRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSDTP-NH2,
(SEQ ID NO: 129)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 130)
[19CD]-isoGlu-RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 131)
[19CD]-isoGlu-RCGTATCATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 132)
[19CD]-isoGlu-RCGTATCATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 133)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp-NH2,
(SEQ ID NO: 134)
[19CD]-isoGlu-RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp-NH2,
(SEQ ID NO: 135)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-GIy(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2,
(SEQ ID NO: 136)
[19CD]-isoGlu-RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2,
(SEQ ID NO: 137)
[19CD]-isoGlu-RCGTATCATERLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2,
(SEQ ID NO: 138)
[19CD]-isoGlu-RCGTATCATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2,
(SEQ ID NO: 139)
[19CD]-isoGlu-RCGTATCATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2,
(SEQ ID NO: 140)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFTP-NH2,
(SEQ ID NO: 141)
[19CD]-isoGlu-RCGTATCATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFTP-NH2,
(SEQ ID NO: 142)
[19CD]-isoGlu-RCGTATCATERLADFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 143)
[19CD]-isoGlu-RCGTATCATERLADFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp-NH2,
(SEQ ID NO: 144)
[19CD]-isoGlu-RCGTATCATERLA-Aad-FLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 145)
[19CD]-isoGlu-RCGTATCATERLA-Aad-FLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp-NH2,
(SEQ ID NO: 146)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Apr-NH2,
(SEQ ID NO: 147)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2,
(SEQ ID NO: 148)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-TP-NH2,
(SEQ ID NO: 149)
[19CD]-isoGlu-RCGTATCATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp-NH2,
(SEQ ID NO: 150)
[19CD]-isoGlu-RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 151)
[19CD]-isoGlu-RCNTATCATQRLAHFL-Aad-RSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 152)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp-NH2,
(SEQ ID NO: 153)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2,
(SEQ ID NO: 154)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp-NH2,
(SEQ ID NO: 155)
[19CD]-isoGlu-RCGTATCATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 156)
[19CD]-isoGlu-RCGTATCATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 157)
[19CD]-isoGlu-RCNTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 158)
[19CD]-isoGlu-RCQTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 159)
[19CD]-isoGlu-RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 160)
[19CD]-isoGlu-RCPTATCATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSNT-Hyp-NH2,
(SEQ ID NO: 161)
[19CD]-isoGlu-RCNTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSDT-Hyp-NH2,
(SEQ ID NO: 162)
[19CD]-isoGlu-RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 163)
[19CD]-isoGlu-RCNTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 164)
[19CD]-isoGlu-RCPTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 165)
[19CD]-isoGlu-RCPTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 166)
[19CD]-isoGlu-RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 167)
[19CD]-isoGlu-RCNTATCATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 168)
[19CD]-isoGlu-RCPTATCATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 169)
[19CD]-isoGlu-RCNTATCATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 170)
[19CD]-isoGlu-RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 171)
[19CD]-isoGlu-RCPTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 172)
[19CD]-isoGlu-RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2,
(SEQ ID NO: 173)
[19CD]-isoGlu-RCPTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2,
(SEQ ID NO: 174)
[19CD]-isoGlu-RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp-NH2,
(SEQ ID NO: 175)
[19CD]-isoGlu-RCPTATCATERLAHFLQRSSF-GIy(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp-NH2,
(SEQ ID NO: 176)
[19CD]-isoGlu-RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp-NH2,
(SEQ ID NO: 177)
[19CD]-isoGlu-RCPTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp-NH2,
(SEQ ID NO: 178)
[19CD]-isoGlu-RCGTATCATERLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 179)
[19CD]-isoGlu-RCGTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 180)
[19CD]-isoGlu-RCNTATCATQRLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2,
(SEQ ID NO: 181)
[19CD]-isoGlu-RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGTP-NH2,
(SEQ ID NO: 182)
[19CD]-isoGlu-RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2,
(SEQ ID NO: 183)
[19CD]-isoGlu-RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTTP-NH2,
(SEQ ID NO: 184)
[19CD]-isoGlu-RCNTATCATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp-NH2,
(SEQ ID NO: 185)
[19CD]-isoGlu-RCNTATCATQRLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2,
(SEQ ID NO: 186)
[19CD]-isoGlu-RCNTATCATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2,
(SEQ ID NO: 187)
[19CD]-isoGlu-RCNTATCATQRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 188)
[19CD]-isoGlu-RCNTATCATQRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2,
(SEQ ID NO: 189)
[19CD]-isoGlu-RCQTATCATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 190)
[19CD]-isoGlu-RCQTATCATDRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 191)
[19CD]-isoGlu-RCQTATCATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2,
(SEQ ID NO: 192)
[19CD]-isoGlu-RCQTATCATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2,
(SEQ ID NO: 193)
[19CD]-isoGlu-RCQTATCATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 194)
[19CD]-isoGlu-RCQTATCATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
(SEQ ID NO: 195)
[19CD]-isoGlu-RCQTATCATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGTP-NH2,
(SEQ ID NO: 196)
[19CD]-isoGlu-RCQTATCATDRLA-Aad-FLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2,
(SEQ ID NO: 197)
[19CD]-isoGlu-RCQTATCATERLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2,
wherein [19CD] represents [19-carboxynonadecanoyl];
and pharmaceutically acceptable salts thereof.

### Claim 18 (depends on 1)

An amylin analogue according to claim 1, comprising an intramolecular disulphide bridge formed between the cysteine residues present at positions 2 and 7 of the amino acid sequence.

### Claim 19 (depends on 1)

A pharmaceutical composition comprising an amylin analogue according to claim 1, in combination with a pharmaceutically acceptable carrier, excipient or vehicle.

### Claim 20 (depends on 1)

A device comprising an amylin analogue according to claim 1, for delivery of the amylin analogue to a subject.

### Claim 21 (depends on 1)

A kit comprising an amylin analogue according to claim 1, and optionally further comprising packaging and instructions for use.

### Claim 22 (depends on 1)

An amylin analogue according to claim 1, wherein the amylin analogue is selected from the group consisting of:
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLADFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 1) (SEQ ID NO: 102);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 2) (SEQ ID NO: 103);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLANFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 3) (SEQ ID NO: 104);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 6) (SEQ ID NO: 107);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 7) (SEQ ID NO: 108);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 8) (SEQ ID NO: 109);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 9) (SEQ ID NO: 110);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp-NH2
(Compd. 10) (SEQ ID NO: 111);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp-NH2
(Compd. 11) (SEQ ID NO: 112);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp-NH2
(Compd. 12) (SEQ ID NO: 113);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2
(Compd. 13) (SEQ ID NO: 114);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLHRF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 14) (SEQ ID NO: 115);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 15) (SEQ ID NO: 116);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 16) (SEQ ID NO: 117);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLANFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 17) (SEQ ID NO: 118);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 18) (SEQ ID NO: 119);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLKRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 19) (SEQ ID NO: 120);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLHRSVF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 20) (SEQ ID NO: 121);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLHRVSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 21) (SEQ ID NO: 122);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 22) (SEQ ID NO: 123);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATDRLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSDTP-NH2
(Compd. 23) (SEQ ID NO: 124);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 24) (SEQ ID NO: 125);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATDRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSNTP-NH2
(Compd. 25) (SEQ ID NO: 126);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSETP-NH2
(Compd. 26) (SEQ ID NO: 127);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATDRLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSDTP-NH2
(Compd. 27) (SEQ ID NO: 128);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 28) (SEQ ID NO: 129);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 29) (SEQ ID NO: 130);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 30) (SEQ ID NO: 131);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 31) (SEQ ID NO: 132);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp-NH2
(Compd. 32) (SEQ ID NO: 133);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp-NH2
(Compd. 33) (SEQ ID NO: 134);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2
(Compd. 34) (SEQ ID NO: 135);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2
(Compd. 35) (SEQ ID NO: 136);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2
(Compd. 36) (SEQ ID NO: 137);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLHRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2
(Compd. 37) (SEQ ID NO: 138);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLVRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2
(Compd. 38) (SEQ ID NO: 139);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFTP-NH2
(Compd. 39) (SEQ ID NO: 140);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLNRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFTP-NH2
(Compd. 40) (SEQ ID NO: 141);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLADFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 41) (SEQ ID NO: 142);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLADFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSFT-Hyp-NH2
(Compd. 42) (SEQ ID NO: 143);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLA-Aad-FLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 43) (SEQ ID NO: 144);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLA-Aad-FLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp-NH2
(Compd. 44) (SEQ ID NO: 145);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Apr-NH2
(Compd. 45) (SEQ ID NO: 146);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2
(Compd. 46) (SEQ ID NO: 147);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-TP-NH2
(Compd. 47) (SEQ ID NO: 148);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLTRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp-NH2
(Compd. 48) (SEQ ID NO: 149);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 49) (SEQ ID NO: 150);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAH FL-Aad-RSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 50) (SEQ ID NO: 151);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Orn-T-Hyp-NH2
(Compd. 51) (SEQ ID NO: 152);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2
(Compd. 52) (SEQ ID NO: 153);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp-NH2
(Compd. 53) (SEQ ID NO: 154);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 54) (SEQ ID NO: 155);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 55) (SEQ ID NO: 156);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 56) (SEQ ID NO: 157);
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 57) (SEQ ID NO: 158);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 58) (SEQ ID NO: 159);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTDVGSNT-Hyp-NH2
(Compd. 59) (SEQ ID NO: 160);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSDT-Hyp-NH2
(Compd. 60) (SEQ ID NO: 161);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 61) (SEQ ID NO: 162);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 62) (SEQ ID NO: 163);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 63) (SEQ ID NO: 164);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 64) (SEQ ID NO: 165);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 65) (SEQ ID NO: 166);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 66) (SEQ ID NO: 167);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 67) (SEQ ID NO: 168);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATERLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 68) (SEQ ID NO: 169);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 69) (SEQ ID NO: 170);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 70) (SEQ ID NO: 171);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2
(Compd. 71) (SEQ ID NO: 172);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2
(Compd. 72) (SEQ ID NO: 173);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp-NH2
(Compd. 73) (SEQ ID NO: 174);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp-NH2
(Compd. 74) (SEQ ID NO: 175);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp-NH2
(Compd. 75) (SEQ ID NO: 176);
[19CD]-isoGlu-R-C( )-PTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGS-Aad-T-Hyp-NH2
(Compd. 76) (SEQ ID NO: 177);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 77) (SEQ ID NO: 178);
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 78) (SEQ ID NO: 179);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2
(Compd. 79) (SEQ ID NO: 180);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGTP-NH2
(Compd. 80) (SEQ ID NO: 181);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2
(Compd. 81) (SEQ ID NO: 182);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTTP-NH2
(Compd. 82) (SEQ ID NO: 183);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSTT-Hyp-NH2
(Compd. 83) (SEQ ID NO: 184);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLERSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2
(Compd. 84) (SEQ ID NO: 185);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSSTP-NH2
(Compd. 85) (SEQ ID NO: 186);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 86) (SEQ ID NO: 187);
[19CD]-isoGlu-R-C( )-NTAT-C( )-ATQRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSST-Hyp-NH2
(Compd. 87) (SEQ ID NO: 188);
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 88) (SEQ ID NO: 189);
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATDRLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 89) (SEQ ID NO: 190);
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2
(Compd. 90) (SEQ ID NO: 191);
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGT-Hyp-NH2
(Compd. 91) (SEQ ID NO: 192);
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATDRLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 92) (SEQ ID NO: 193);
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 93) (SEQ ID NO: 194);
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSGTP-NH2
(Compd. 94); (SEQ ID NO: 195)
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATDRLA-Aad-FLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2
(Compd. 95) (SEQ ID NO: 196); and
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATERLAHFLQRF-Gly(Me)-A-Ile(Me)-LSSTEVGSNTP-NH2
(Compd. 96) (SEQ ID NO: 197);
or a pharmaceutically acceptable salt thereof;
wherein parentheses “0” indicate an intramolecular disulfide bridge between the side chains of cysteine residues at positions 2 and 7.

### Claim 23

An amylin analogue which is:
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2 (Compd. 7) (SEQ ID NO: 108), or a pharmaceutically acceptable salt thereof.

### Claim 24

An amylin analogue which is:
[19CD]-isoGlu-R—C( )-NTAT-C( )-ATQRLADFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2 (Compd. 49) (SEQ ID NO: 150), or a pharmaceutically acceptable salt thereof.

### Claim 25

An amylin analogue which is:
[19CD]-isoGlu-R-C( )-GTAT-C( )-ATERLA-Aad-FLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2 (Compd. 55) (SEQ ID NO: 156), or a pharmaceutically acceptable salt thereof.

### Claim 26

An amylin analogue which is:
[19CD]-isoGlu-R—C( )-NTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2 (Compd. 56) (SEQ ID NO: 157), or a pharmaceutically acceptable salt thereof.

### Claim 27

An amylin analogue which is:
[19CD]-isoGlu-R-C( )-QTAT-C( )-ATERLAHFLQRSSF-Gly(Me)-A-Ile(Me)-LSSTEVGSNT-Hyp-NH2 (Compd. 57) (SEQ ID NO: 158), or a pharmaceutically acceptable salt thereof.

### Claim 28 (depends on 1)

A method for the synthesis of an amylin analogue according to claim 1, comprising synthesizing the amylin analogue by solid-phase or liquid-phase methodology, optionally isolating and purifying the final product, and further optionally comprising the step of forming a disulfide bond between the thiol groups of the cysteine side chains at positions 2 and 7.

### Claim 29 (depends on 1)

A method of treating, inhibiting or reducing weight gain, promoting weight loss, reducing food intake, and/or reducing excess body weight in a subject in need, said method comprises administering to said subject a therapeutically effective amount of an amylin analogue according to claim 1.

### Claim 30 (depends on 1)

A method of treating obesity, morbid obesity, obesity prior to surgery, obesity-linked inflammation, obesity-linked gallbladder disease, obesity-induced sleep apnea and respiratory problems, degeneration of cartilage, osteoarthritis, or reproductive health complications of obesity or overweight such as infertility in a subject in need, said method comprises administering to said subject a therapeutically effective amount of an amylin analogue according to claim 1.

### Claim 31 (depends on 1)

A method of prevention or treatment of Alzheimer's disease, diabetes, type 1 diabetes, type 2 diabetes, pre-diabetes, insulin resistance syndrome, impaired glucose tolerance (IGT), disease states associated with elevated blood glucose levels, metabolic disease including metabolic syndrome, hyperglycemia, hypertension, atherogenic dyslipidemia, hepatic steatosis (“fatty liver”), kidney failure, arteriosclerosis (e.g. atherosclerosis), macrovascular disease, microvascular disease, diabetic heart (including diabetic cardiomyopathy and heart failure as a diabetic complication), coronary heart disease, peripheral artery disease or stroke, and/or combinations thereof in a subject in need, said method comprises administering to said subject a therapeutically effective amount of an amylin analogue according to claim 1.

### Claim 32 (depends on 1)

A method of lowering circulating LDL levels and/or increasing HDL/LDL ratio in a subject, said method comprises administering to said subject an amylin analogue according to claim 1.
