Granted Patent B2

US 12,673,974 · App. 18/527,006 · Granted Jul 7, 2026

Inventors: Ashok Bhandari (Pleasanton, CA); Gregory Thomas Bourne (Brisbane, AU); Xiaoli Cheng (Mountain View, CA); Brian Troy Frederick (Ben Lomand, CA); Jie Zhang (Salisbury, AU); Dinesh V. Patel (Fremont, CA); David Liu (San Francisco, CA)

Assignee: Protagonist Therapeutics, Inc.

C07K7/08C07K7/02C07K7/50C07K7/64C07K14/54A61K38/00G01N2800/065

Abstract

Claims (55)

1 . A peptide, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide comprises the amino acid sequence of Formula (Xa):

X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20  (Xa)

wherein

X1 is any amino acid or absent;

X2 is any amino acid or absent;

X3 is any amino acid or absent;

X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Sec, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3-chloro-isobutyric acid, Abu, β-azido-Ala-OH, propargylglycine, 2-(3′-butenyl)glycine, 2-allylglycine, 2-(3′-butenyl)glycine, 2-(4′-pentenyl)glycine, 2-(5′-hexenyl)glycine, or absent;

X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, α-MeOrn, α-MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn, or Gln;

X6 is any amino acid;

X7 is any amino acid;

X8 is any amino acid;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, Ser, Sec, Abu, β-azido-Ala-OH, propargylglycine, 2-2-allylglycine, 2-(3′-butenyl)glycine, 2-(4′-pentenyl)glycine, Ala, hCys, Met, MeCys, (D) Tyr, or 2-(5′-hexenyl)glycine;

X10 is Phe, Tyr, a Phe analog, or a Tyr analog;

X11 is Trp, 1-Nal, 2-Nal, Phe (3,4-OMe 2 ) 5-Hydroxy-Trp, Phe (3,4-Cl 2 ), or Tyr (3-t-Bu);

X12 is His, Phe, Arg, N-Me-His, or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, α-MeLys, α-MeLys (Ac), α-Me-Leu, α-MeOrn, α-MeSer, α-MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X 13 is Cit, Asp, Dab, Dap, Phe, His, Dap (Peg 2 -Ac), Dap (pyroglutaric acid), hArg, Lys, Lys (Ac), Lys (Benzoic acid), Lys (glutaric acid), Lys (IVA), Lys (Peg 4 - isoGlu-Palm), Lys (pyroglutaric acid), Lys (succinic acid), Asn, Orn, Gln, Arg, Thr or Val, wherein Lys (IVA) is

X14 is Phe, Tyr, BhPhe, Asn, Arg, Gln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is any amino acid,

X16 is any amino acid or absent;

X17 is any amino acid or absent;

X18 is any amino acid or absent;

X19 is any amino acid or absent; and

X20 is any amino acid or absent,

wherein the peptide is cyclized via a bond between two amino acid residues within the peptide.

2 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X1 is absent.

3 . The peptide of claim 2 , or a pharmaceutically acceptable salt or solvate thereof, wherein X2 is absent.

4 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe.

5 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X7 is Trp.

6 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X10 is a Phe analog.

7 . The peptide of claim 6 , or a pharmaceutically acceptable salt or solvate thereof, wherein X10 is Phe (4-OMe), Phe (4-CONH 2 ), or Phe [4-(2-aminoethoxy)].

8 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X11 is Trp, 1-Nal, or 2-Nal.

9 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X12 is Aib, α-Me-Lys, α-Me-Val, α-Me-Leu, Achc, Acvc, Acpc, or 4-amino-4-carboxy-tetrahydropyran.

10 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val, bhAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Asn, Orn, or Gln.

11 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X20 is absent.

12 . The peptide of claim 11 , or a pharmaceutically acceptable salt or solvate thereof, wherein X19 is absent.

13 . The peptide of claim 12 , or a pharmaceutically acceptable salt or solvate thereof, wherein X18 is absent.

14 . The peptide of claim 13 , or a pharmaceutically acceptable salt or solvate thereof, wherein X17 is absent.

15 . The peptide of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide is cyclized via an amide bond, a disulfide bond, a thioether bond, or a triazole ring.

16 . The peptide of claim 1 , wherein the peptide is a pharmaceutically acceptable salt.

17 . The peptide of claim 16 , wherein X1 is absent.

18 . The peptide of claim 17 , wherein X2 is absent.

19 . The peptide of claim 16 , wherein X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe.

20 . The peptide of claim 16 , wherein X7 is Trp.

21 . The peptide of claim 16 , wherein X10 is a Phe analog.

22 . The peptide of claim 21 , wherein X10 is Phe (4-OMe), Phe (4-CONH 2 ), or Phe [4-(2-aminoethoxy)].

23 . The peptide of claim 16 , wherein X11 is Trp, 1-Nal, or 2-Nal.

24 . The peptide of claim 16 , wherein X12 is Aib α-Me-Lys, α-Me-Val, α-Me-Leu, Achc, Acvc, Acpc, Acbc, or 4-amino-4-carboxy-tetrahydropyran.

25 . The peptide of claim 16 , wherein X13 is Thr, Phe, Lys, Val, Lys (Ac), Cit, Asp, Dab, Dap, hArg, Asn, Orn, or Gln.

26 . The peptide of claim 16 , wherein X20 is absent.

27 . The peptide of claim 26 , wherein X19 is absent.

28 . The peptide of claim 27 , wherein X18 is absent.

29 . The peptide of claim 28 , wherein X17 is absent.

30 . The peptide of claim 16 , wherein the peptide is cyclized via an amide bond, a disulfide bond, a thioether bond, or a triazole ring.

31 . A pharmaceutical composition comprising the peptide of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent.

32 . The pharmaceutical composition of claim 31 , wherein the peptide is a pharmaceutically acceptable salt.

Continuity (8)

References Cited (400)