Peptide hormone analogues

Patent metadata

Field	Value
Publication number	US-12516095-B2
Application number	US-202017618375-A
Country	US
Kind code	B2
Filing date	Jun 12, 2020
Priority date	Jun 12, 2019
Publication date	Jan 6, 2026
Grant date	Jan 6, 2026

Abstract

The invention provides novel compounds which are peptide hormone analogues, and which are useful in treating disorders such as diabetes and obesity. The compounds of the general sequence recited in the specification possess a tailored profile with regards to potency properties at the glucagon and GLP-1 receptors. With regard to in vivo properties, administration of example peptides of the invention have been shown, in animal models, to result in increased weight loss. Preferred compounds achieve this without reducing food intake significantly.

First claim

The invention claimed is:

1 . A compound of Formula (I):
X-W-Y1-Y2  Formula (I)
or a derivative or salt thereof; wherein X is an amino acid sequence:

(SEQ ID NO: 742)

His1-Xaa2-Xaa3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-

Xaa10-Ser11-Xaa12-Xaa13-Leu14-Xaa15-Xaa16-Xaa17-

Xaa18-Xaa19-Xaa20-Xaa21-Phe22-Xaa23-Xaa24-Trp25-

Leu26-Xaa27-Xaa28-Xaa29-

wherein
Xaa2 is AlB;
Xaa3 is His, Glu, or Gln;
Xaa10 is Leu, or Tyr;
Xaa12 is Arg, or Lys;
Xaa13 is Tyr, or Gln;
Xaa15 is Asp or Glu;
Xaa16 is Ala, Gln, Glu, or Ser;
Xaa17 is Arg, Glu, or Lys;
Xaa18 is Ala, Arg or Lys;
Xaa19 is Ala or Val;
Xaa20 is Arg, Gln or His;
Xaa21 is Asp, Leu, or Glu;
Xaa23 is Ile or Val;
Xaa24 is Gln or Glu;
Xaa27 is Leu or Lys;
Xaa28 is Ala, Asn, Gln, His, or Thr; and
Xaa29 is Gly, Ser or Thr;
W is an amino acid sequence:

(SEQ ID NO: 743)

-Xaa30-Xaa31-Xaa32-Xaa33-Xaa34-;

wherein
Xaa30 is His, Gln, or Gly;
Xaa31 is His, Gln, Glu, Gly, or Pro;
Xaa32 is His, Gln, Gly, Glu, Pro, or Ser;
Xaa33 is Ala, His, Gln, Glu, Gly, Pro, or Ser; and
Xaa34 is Ala, His, Gln, Glu, Gly, Pro or Ser;
Y1 is an amino acid sequence:

(SEQ ID NO: 744)

-Xaa35-Xaa36-Xaa37-Xaa38-Xaa39-Xaa40-Xaa41-Lys42-

Xaa43-Xaa44

wherein
Xaa35 is Pro, His, Glu, Ser or Ala;
Xaa36 is Ser, Gly, Pro or Thr;
Xaa37 is Pro, Ala, Ser, Glu, Gly or absent;
Xaa38 is Pro, Ala, Gly, Ser or absent;
Xaa39 is Pro, Gly, Ala, Ser or absent;
Xaa40 is Pro, Gly, Ser or absent;
Xaa41 is Gly, Ser or absent
Xaa43 is Ser or absent;
Xaa44 is Trp or absent;
and the lysine residue at position 42 is substituted at its ε-amino group with a group Y2 and Y2 is:

(SEQ ID NO: 745)

Z-Xaa45-Xaa46-Xaa47-Xaa48-

wherein:
Xaa45 is Gly, Thr or absent;
Xaa46 is Ser, Gly, Thr or absent;
Xaa47 is Gly, Asn, Ser, Gln, Thr, His Tyr, Ala or absent;
Xaa48 is Ser, Thr, His, Gln, Gly, Asn or absent;
and Z is a group of formula:

wherein R is a C 8 -C 28 alkylene or alkenylene group and
R 1 is CO 2 H.

2 . The compound of claim 1 , or the derivative or salt thereof, wherein:
Xaa2 is AlB; Xaa3 is His, Gln or Glu; Xaa10 is Leu or Tyr; Xaa12 is Arg or Lys; Xaa13 is Tyr or Gln; Xaa15 is Asp or Glu; Xaa16 is Ala, Gln, Glu or Ser; Xaa17 is Arg, Glu or Lys; Xaa18 is Ala, Arg or Lys; Xaa19 is Ala or Val; Xaa20 is Arg, Gln or His; Xaa21 is Asp, Glu or Leu; Xaa23 is Ile or Val; Xaa24 is Gln or Glu; Xaa27 is Leu or Lys; Xaa28 is Ala, Asn, Gln or His; and Xaa29 is Gly, Ser or Thr.

3 . The compound of claim 2 , or the derivative or salt thereof, wherein:
Xaa2 is AlB; Xaa3 is His; Xaa10 is Tyr; Xaa12 is Lys; Xaa13 is Tyr; Xaa15 is Asp; Xaa16 is Ala; Xaa17 is Lys; Xaa18 is Arg; Xaa19 is Ala; Xaa20 is Arg, Gln or His; Xaa21 is Glu; Xaa23 is Ile; Xaa24 is Glu; Xaa27 is Leu; Xaa28 is Gln; and Xaa29 is Ser.

4 . The compound of claim 1 , or the derivative or salt thereof, wherein W has an amino acid sequence selected from:

(SEQ ID NO: 752)

-Gly30-His31-His32-His33-His34-,

(SEQ ID NO: 753)

-His30-His31-His32-His33-His34-,

(SEQ ID NO: 754)

-His30-His31-Gln32-His33-His34-,

(SEQ ID NO: 755)

-His30-Gln31-Gln32-GIn33-His34-,

(SEQ ID NO: 756)

-His30-Gln31-His32-Pro33-Ser34-,

(SEQ ID NO: 757)

-His30-Gln31-His32-Glu33-Ser34-,

(SEQ ID NO: 758)

-His30-His31-Gln32-Glu33-Ser34-,

(SEQ ID NO: 759)

-His30-His31-Gln32-Ser33-Pro34-,

(SEQ ID NO: 760)

-His30-Glu31-Pro32-Ser33-Pro34-,

(SEQ ID NO: 761)

-His30-Glu31-Glu32-Ser33-Pro34-,

(SEQ ID NO: 762)

-His30-Gln31-Gln32-Glu33-Ser34-,

(SEQ ID NO: 763)

-Gln30-His31-Gln32-His33-Gln34-,

Assignees

• Ip2Ipo Innovations Ltd

Inventors

• Bloom Stephen Robert

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61K38/00

  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) · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title