# US 2024/0190938 A1 · Gip derivatives and uses thereof

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- Number: US 2024/0190938 A1
- Document ID: US20240190938A1
- Status: Published application
- Kind: A1
- Application number: 18/105,419
- Filed: 2023-02-03
- Published: 2024-06-13
- Earliest claimed: 2018-05-04
- Assignees: Novo Nordisk A/S
- Applicants: Novo Nordisk A/S
- Inventors: Wouter Frederik Johan Hogendorf; Henning Thoegersen; Nicholas Raymond Cox; Patrick J. Knerr; Richard DiMarchi; Brian Finan; Jesper F. Lau; Steffen Reedtz-Runge; Fa Liu
- Web page: https://patentgrep.com/patent/US20240190938A1

## CPC

- C07K 14/605: Glucagons
- C07K 14/645: Secretins
- A61K 38/22: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35)
- A61K 38/2235: {Secretins}
- A61K 38/26: Glucagons
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C07K 14/575: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695)
- 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)
- 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 novel peptides that are derivatives of glucose-dependent insulinotropic polypeptide (GIP) analogues having improved physical stability in solution and a protracted profile of action. More particular the invention relates to such peptides that are agonists at the GIP receptor and to their use in weight management or for treatment of diseases such as obesity, diabetes or non-alcoholic steatohepatitis (NASH).

## Claims

### Claim 1

A method for reducing weight by administering a pharmaceutical composition to a subject in need thereof,
wherein pharmaceutical composition comprises a glucose-dependent insulinotropic polypeptide (GIP) analogue derivative and a glucagon-like peptide-1 (GLP-1) receptor agonist;
wherein the GIP analogue derivative comprises a GIP analogue and a modifying group;
wherein the GIP analogue is (SEQ ID NO: 48):
X1-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Aa-X14-Asp-X16-Ile-X18-Gln-X20-Asp-Phe-Val-Lys-Trp-Leu-Leu-Ala-Gln-Lys-X31;
wherein
X1 is Tyr, D-Tyr, Ac-Tyr, or Ac-D-Tyr;
X2 is Aib, Ala, or D-Ala;
X14 is Leu, Nle, Asp or Met;
X16 is Lys or Ala;
X18 is Arg or His;
X20 is Gln, Glu or Aib;
X31 is Gly or Pro;
wherein the modifying group is A-B-C;
wherein A is
wherein p is an integer in the range of 14-20, and
wherein * denotes the position of an amide bond connecting A- and B-;
wherein B is
wherein q is an integer in the range of 0-1,
wherein r is an integer in the range of 1-3,
wherein * denotes the position of the amide bond connecting A- and B-,
wherein ** denotes the position of an amide bond connecting B- and C-; and
wherein C is
wherein s is an integer in the range of 1-3,
wherein t is an integer in the range of 1-4,
wherein u is an integer in the range of 1-3,
wherein ** denotes the position of the amide bond connecting B- and C-, and
wherein *** denotes the position of an amide bond connecting C- and the epsilon amino group of the lysine at position 24.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the GLP-1 receptor agonist is semaglutide.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the subject is suffering from obesity.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the GIP analogue derivative is selected from the group consisting of:
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 1; SEQ ID NO: 6)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Lys24]-hGIP(1-31) (Compound 2; SEQ ID NO: 7)
N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino) methyl]cyclohexanecarbonyl]amino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib2,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 3; SEQ ID NO: 8)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 4; SEQ ID NO: 9)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Aib2,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 5; SEQ ID NO: 10)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Aib2,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 6; SEQ ID NO: 11)
N{1}-acetyl,N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 7; SEQ ID NO: 12)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]-butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 8; SEQ ID NO: 13)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Glu20,Lys24]-hGIP(1-31) (Compound 9; SEQ ID NO: 14)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]-butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Glu20,Lys24]-hGIP(1-31) (Compound 10; SEQ ID NO: 15)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Aib20,Lys24]-hGIP(1-31) (Compound 11; SEQ ID NO: 16)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]-butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Aib20,Lys24]-hGIP(1-31) (Compound 12; SEQ ID NO: 17)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Ala16,Arg18,Lys24]-hGIP(1-31) (Compound 13; SEQ ID NO: 18)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]-butanoyl]amino]butanoyl]-[Aib2,Nle14,Ala16,Arg18,Lys24]-hGIP(1-31) (Compound 14; SEQ ID NO: 19)
N{1}-acetyl,N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[D-Tyr1,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 15; SEQ ID NO: 20)
N{1}-acetyl, N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[D-Tyr1,Nle14,Arg18,Glu20,Lys24]-hGIP(1-31) (Compound 16; SEQ ID NO: 21)
N{1}-acetyl, N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]-butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[D-Tyr1,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 17; SEQ ID NO: 22)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 18; SEQ ID NO: 23)
N{1}-acetyl,N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[D-Tyr1,Asp14,Arg18,Glu20,Lys24]-hGIP(1-31) (Compound 19; SEQ ID NO: 24)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-amino]butanoyl]-[Aib2,Nle14,Glu20,Lys24]-hGIP(1-31) (Compound 20; SEQ ID NO: 25)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]-amino]butanoyl]-amino]butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Glu20,Lys24]-hGIP(1-31) (Compound 21; SEQ ID NO: 26)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]-amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Glu20,Lys24]-hGIP(1-31) (Compound 22; SEQ ID NO: 27)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]-amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Arg18,Glu20,Lys24]-hGIP(1-31) (Compound 23; SEQ ID NO: 28)
N{1}-acetyl,N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]-amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Aib20,Lys24]-hGIP(1-31) (Compound 24; SEQ ID NO: 29)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]-9 amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Arg18,Aib20,Lys24]-hGIP(1-31) (Compound 25: SEQ ID NO: 30)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]-butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Lys24,Pro31]-hGIP(1-31) amide (Compound 26; SEQ ID NO: 31)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]-9 butanoyl]amino]butanoyl]-[Aib2,Nle14,Lys24,Pro31]-hGIP(1-31) amide (Compound 27; SEQ ID NO: 32)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]-amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Arg18,Lys24,Pro31]-hGIP(1-31) amide (Compound 28; SEQ ID NO: 33)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]-amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Lys24,Pro31]-hGIP(1-31) amide (Compound 29; SEQ ID NO: 34)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]-amino]butanoyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 30; SEQ ID NO: 35)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]-amino]butanoyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Aib2,Nle14,Arg18,Lys24,Pro31]-hGIP(1-31) amide (Compound 31; SEQ ID NO: 36)
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]-amino]butanoyl]amino]butanoyl]-[D-Tyr1,Aib2,Nle14,Lys24,Pro31]-hGIP(1-31) amide (Compound 32; SEQ ID NO: 37)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Lys24,Glu33]-hGIP (Compound 33; SEQ ID NO: 38)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Lys24,Glu33]-hGIP (Compound 34; SEQ ID NO: 39)
N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib2,Nle14,Lys24,Glu33,Glu34]-hGIP (Compound 35; SEQ ID NO: 40)
N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib2,Nle14,Lys24,Glu33,Asp34]-hGIP (Compound 36, SEQ ID NO: 41)
N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib2,Nle14,Arg18,Lys24,Glu33,Glu34]-hGIP (Compound 37; SEQ ID NO: 42)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Lys24,Glu33,Glu34]-hGIP (Compound 38; SEQ ID NO: 43)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Lys24,Glu33,Asp34]-hGIP (Compound 39; SEQ ID NO: 44)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Lys24,Glu33,Glu34]-hGIP (Compound 40; SEQ ID NO: 45)
N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoyl-amino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib2,Nle14,Arg18,Lys24,Glu33,Glu34]-hGIP (Compound 41; SEQ ID NO: 46)
N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]-[Aib2,Nle14,Arg18,Lys24,Glu33,Glu34]-hGIP (Compound 42; SEQ ID NO: 47)
N{1}-acetyl,N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[D-Tyr1,Nle14,Arg18,Aib20,Lys24]-hGIP(1-31) (Compound 43; SEQ ID NO: 59)
N{1}-acetyl,N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[D-Tyr1,Aib2,Nle14,Arg18,Lys24,Pro31]-hGIP(1-31) amide (Compound 44; SEQ ID NO: 60)
N{Epsilon-24}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib2,Leu14,Lys24]-hGIP (Compound 45; SEQ ID NO: 61)
and
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Aib2,Nle14,Arg18,Lys24,Pro31]-hGIP(1-31) amide (Compound 46; SEQ ID NO: 62)

### Claim 5 (depends on 4)

The method according to claim 4, wherein the GIP analogue derivative is:
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Aib2,Nle14,Arg18,Lys24]-hGIP(1-31) (Compound 5; SEQ ID NO: 10)

### Claim 6 (depends on 5)

The method according to claim 5, wherein the GLP-1 receptor agonist is semaglutide.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the subject is suffering from obesity.

### Claim 8 (depends on 4)

The method according to claim 4, wherein the GIP analogue derivative is:
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]amino]butanoyl]-amino]butanoyl]amino]butanoyl]-[D-Tyr1,Nle14,Arg18,Aib20,Lys24]-hGIP(1-31) (Compound 25; SEQ ID NO: 30)

### Claim 9 (depends on 8)

The method according to claim 8, wherein the GLP-1 receptor agonist is semaglutide.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the subject is suffering from obesity.

### Claim 11 (depends on 4)

The method according to claim 4, wherein the GIP analogue derivative is:
N{1}-acetyl, N{Epsilon-24}-[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[4-[(19-carboxynonadecanoylamino)methyl]cyclohexanecarbonyl]-amino]butanoyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]-[D-Tyr1,Aib2,Nle14,Arg18,Lys24,Pro31]-hGIP(1-31) amide (Compound 31; SEQ ID NO: 36)

### Claim 12 (depends on 11)

The method according to claim 11, wherein the GLP-1 receptor agonist is semaglutide.

### Claim 13 (depends on 12)

The method according to claim 12, wherein the subject is suffering from obesity.