IP Library › Granted Patent US 11,884,748
Granted Patent B2
US 11,884,748 · App. 17/161,370 · Granted Jan 30, 2024

Oral peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory bowel diseases

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
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Quick Facts
Patent No.
US 11,884,748
App. No.
17/161,370
Granted
Jan 30, 2024
Kind
B2
Abstract

Peptide inhibitors of the interleukin-23 receptor, and related compositions and methods of using these peptide inhibitors to treat or prevent a variety of diseases and disorders, including inflammatory bowel disease, are disclosed.

Claims (126)

1. A pharmaceutical composition comprising a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent,

wherein the peptide inhibitor of an interleukin-23 receptor is selected from the group consisting of:

(SEQ ID NO: 702)

Ac-[Abta]-QTWQC-[Phe(4-OMe)]-[2-Nal]-[α-Me-Lys]-

ENG-NH 2 ; 

(SEQ ID NO: 704)

Ac-[Abta]-QTWQCY-[2-Nal]-[α-Me-Lys]-ENG-NH 2 ; 

(SEQ ID NO: 782)

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]-W-

[α-Me-Lys]-ENG-NH 2 ;

(SEQ ID NO: 861)

Ac-[Abta]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[α-Me-Lys]-[Lys(isovaleric acid)]-NG-NH 2 ; 

(SEQ ID NO: 877)

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]

AiN-QNG-NH 2 ;

(SEQ ID NO: 880)

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[AibMLys(Ac)]-NA-NH 2 ; 

(SEQ ID NO: 900)

Ac-[Abu]-QTWQC-[Phe[4-(2-(acetyl-aminoethoxy)]]-

[2-Nal]-[α-Me-Lys(Ac)]-[Lys(Ac)]-NG-NH 2 ; 

(SEQ ID NO: 911)

Ac-[Abta]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[α-Me-Lys]-ENQ-NH 2 ; 

(SEQ ID NO: 912)

Ac-[Abta]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[α-Me-Lys]-ENN-NH 2 ; 

(SEQ ID NO: 915)

Ac-[Abta]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[α-MeVal]-[Lys(Ac)]-NG-NH 2 ;

(SEQ ID NO: 954)

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[α-Me-Leu]-[Cit]-NN-NH 2 ; 

(SEQ ID NO: 970)

Ac-[(D)Phe]-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-

[2-Nal]-[α-Me-Lys]-ENN-NH 2 ; 

(SEQ ID NO: 972)

Ac-T-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[α-Me-Lys]-ENN-NH 2 ; 

(SEQ ID NO: 976)

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-

[2-Nal]-[acbc]-ENN-NH 2 ;

(SEQ ID NO: 980)

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-

[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-

ENN-NH 2 ;

(SEQ ID NO: 984)

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[alphα-methyl-L-Leucine]-QN-[betaAla]-NH 2 ;

(SEQ ID NO: 992)

Ac-(D)Phe-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-

[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]- 

ENN-NH 2 ;

(SEQ ID NO: 993)

Ac-[(D)Arg]-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-

[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-

ENN-NH 2 ; 

(SEQ ID NO: 1043) 

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-

[acpc]-ENN-NH 2 ; 

or

(SEQ ID NO: 1047)

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]

achc]-ENN-NH 2 ;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

2. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe(4-OMe)]-[2-Nal]-[α-Me-Lys]-ENG-NH 2 (SEQ ID NO:702) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

3. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQCY-[2-Nal]-[a-Me-Lys]-ENG-NH 2 (SEQ ID NO: 704 ) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

4. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]-W-[α-Me-Lys]-ENG-NH 2 (SEQ ID NO:782) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

5. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[α-Me-Lys]-[Lys(isovaleric acid)]-NG-NH 2 (SEQ ID NO:861) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

6. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[Aib]-QNG-NH 2 (SEQ ID NO:877) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

7. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[Aib]-[Lys(Ac)]-NA-NH 2 (SEQ ID NO:880) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

8. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-(acetyl-aminoethoxy)]]-[2-Nal]-[α-Me-Lys(Ac)]-[Lys(Ac)]-NG-NH 2 (SEQ ID NO:900) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

9. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[α-Me-Lys]-ENQ-NH 2 (SEQ ID NO:911) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

10. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-( 2 -aminoethoxy)]]-[2-Nal]-[α-Me-Lys]-ENN-NH 2 (SEQ ID NO:912) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

11. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[α-MeVal]-[Lys(Ac)]-NG-NH 2 (SEQ ID NO:915) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

12. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-8 2-Nal]-[α-Me-Leu]-[Cit]-NN-NH 2 (SEQ ID NO:954) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

13. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[(D)Phe]-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[α-Me-Lys]-ENN-NH 2 (SEQ ID NO: 970) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

14. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-T-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[α-Me-Lys]-ENN-NH 2 (SEQ ID NO:972) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

15. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]acbc]-ENN-NH 2 (SEQ ID NO:976) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

16. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe [4-(2-aminoethoxy)]]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH 2 (SEQ ID NO:980) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

17. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe [4-(2-aminoethoxy)]]-[2-Nal]-[alpha-methyl-L-Leucine]-QN-[betaAla]-NH 2 (SEQ ID NO:984) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

18. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-(D)Phe-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH 2 (SEQ ID NO:992) or a pharmaceutically acceptable salt thereof;

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

19. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[(D)Arg]-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]-[4-amino-4-carboxy-tetrahydropyran]-ENN-NH 2 (SEQ ID NO:993) or a pharmaceutically acceptable salt thereof,

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

20. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]acpc]- ENN-NH 2 (SEQ ID NO:1043) or a pharmaceutically acceptable salt thereof,

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

21. The pharmaceutical composition of claim 1 , wherein the peptide inhibitor of an interleukin-23 receptor is:

Ac-[Abu]-QTWQC-[Phe[4-(2-aminoethoxy)]]-[2-Nal]achc]-ENN-NH 2 (SEQ ID NO:1047) or a pharmaceutically acceptable salt thereof,

wherein the peptide inhibitor is cyclized via a thioether bond between Abu and C.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 14, 2021
From: BOURNE, GREGORY THOMAS; BHANDARI, ASHOK; CHENG, XIAOLI; FREDERICK, BRIAN TROY; ZHANG, JIE; PATEL, DINESH V.; LIU, DAVID
To: PROTAGONIST THERAPEUTICS, INC.
Reel/Frame 056251/0461 →
Continuity (7)
Continuation 16217864 · Dec 12, 2018
Continuation 15442229 · Feb 24, 2017
Division 14800627 · Jul 15, 2015
Provisional Application 62119685 · Feb 23, 2015
Provisional Application 62119688 · Feb 23, 2015
Provisional Application 62025899 · Jul 17, 2014
Related Publication 20210363185A1 · Nov 25, 2021
Cited By (1)
US 12,673,974