	US 12,122,815 B2
	GIP receptor agonist peptide compounds and uses thereof
Hiroshi Imoto, Fujisawa (JP); Mari Adachi, Fujisawa (JP); Yoko Kanematsu, Fujisawa (JP); Taiji Asami, Fujisawa (JP); Ayumu Niida, Fujisawa (JP); Naoki Nishizawa, Fujisawa (JP); Derek Cecil Cole, San Diego, CA (US); Mack Flinspach, San Diego, CA (US); Nick Scorah, San Diego, CA (US); and Abhijit Suresh Bhat, Cambridge, MA (US)
Assigned to TAKEDA PHARMACEUTICAL COMPANY LIMITED, Osaka (JP)
Appl. No. 17/279,266
Filed by TAKEDA PHARMACEUTICAL COMPANY LIMITED, Osaka (JP)
PCT Filed Sep. 24, 2019, PCT No. PCT/JP2019/038441 § 371(c)(1), (2) Date Mar. 24, 2021, PCT Pub. No. WO2020/067557, PCT Pub. Date Apr. 2, 2020.
Claims priority of provisional application 62/735,548, filed on Sep. 24, 2018.
Prior Publication US 2022/0135638 A1, May 5, 2022
Int. Cl. C07K 14/575 (2006.01); A61K 9/00 (2006.01); A61K 9/08 (2006.01); A61K 9/20 (2006.01); A61K 38/00 (2006.01); A61K 47/02 (2006.01); A61P 1/08 (2006.01)

CPC C07K 14/575 (2013.01) [A61K 9/0019 (2013.01); A61K 9/08 (2013.01); A61K 9/2013 (2013.01); A61K 9/2018 (2013.01); A61K 9/2059 (2013.01); A61K 47/02 (2013.01); A61P 1/08 (2018.01); A61K 38/00 (2013.01)]

29 Claims

1. A GIP receptor agonist peptide represented by formula (I): P¹-A1-A2-A3-A4-A5-A6-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-A25-A26-A27-A28-A29-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-A40-A41-P²(SEQ ID NO: 4), or a salt thereof;

wherein

P¹represents a group represented by formula

—R^A1,

—CO—R^A1,

—CO—OR^A1,

—CO—COR^A1,

—SO—R^A1,

—SO₂—R^A1,

—SO₂—OR^A1

—CO—NR^A2R^A3,

—SO₂—NR^A2R^A3,

—C(═NR^A1)—NR^A2R^A3, or

is absent,

wherein R^A1, R^A2, and R^A3each independently represent a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group;

P²represents —NH₂or —OH;

A1 represents Tyr, 3,5-Dix Tyr, D-Tyr, 3,5 di-Br-Tyr, Phe, αMethyl-Phe, mono-halo-Phe, bis-halo-Phe, -Tyr, -D-Phe, -D-Tyr, des-amino-Phe, or des-amino-Tyr;

A2 represents Aib;

A3 represents Glu or Pro;

A4 represents Gly, or Ser;

A5 represents Thr, D-Iva, Glu, Iva, or Ser;

A6 represents Phe, or Val;

A7 represents Ile, or Val;

A8 represents Ser;

A9 represents Asp, Leu, or Phe;

A10 represents Tyr;

A11 represents Aib or Ser;

A12 represents Ile, Ala, or Aib;

A13 represents Aib, Ala, Gln, Leu, or D-Iva;

A14 represents Leu;

A15 represents Asp, Lys, Ser, or Tyr;

A16 represents Arg, or Lys;

A17 represents Aib, or Gln;

A18 represents Ala or His;

A19 represents Gln or Ser;

A20 represents Aib, Ala or Gln;

A21 represents Asn, Asp, Glu, Leu, or Ser;

A22 represents Phe or αMePhe;

A23 represents Ile or Val;

A24 represents Arg, Asn, Asp, Lys, or Lys(Ac);

A25 represents Trp;

A26 represents Aib, Iva, or Leu;

A27 represents Leu;

A28 represents Ala, Arg, Lys, or Lys(Ac);

A29 represents Gln or Gly;

A30 represents Arg or Gly;

A31 represents Pro, Gly ψ, or a deletion;

A32 represents Ser, Gly, ψ, or a deletion;

A33 represents Ser, Gly, ψ, or a deletion;

A34 represents Gly, ψ or a deletion;

A35 represents Ala, Ser, ψ, or a deletion;

A36 represents Pro, Gly, ψ, or a deletion;

A37 represents Pro, Gly, ψ, or a deletion;

A38 represents Pro, Gly, ψ, or a deletion;

A39 represents Ser, Gly, ψ, or a deletion;

A40 represents, Ser, ψ, or a deletion;

A41 represents Gly, ψ, or a deletion;

and wherein any one or two amino acids selected from A31 to A41 represent ψ, wherein ψ is a residue independently selected from Lys, Orn, and Cys and wherein the side chain of said residue is substituted.