IP Library › Granted Patent US 12,018,057
Granted Patent B2
US 12,018,057 · App. 17/149,544 · Granted Jun 25, 2024

Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases

Inventors: Chengzao Sun (Horsham, PA); Brian Troy Frederick (Newark, CA); Sandeep Somani (Horsham, PA); Ashok Bhandari (Newark, CA); Raymond Patch (Horsham, PA); Stephanie Barros (Horsham, PA); Raffaele Ingenito (Pomezia, IT); Roberto Costante (Pomezia, IT); Danila Branca (Pomezia, IT); Elisabetta Bianchi (Pomezia, IT)
Assignees: Janssen Biotech, Inc.; Protagonist Therapeutics, Inc.
C07K14/4703A61K47/60A61K38/00
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Quick Facts
Patent No.
US 12,018,057
App. No.
17/149,544
Granted
Jun 25, 2024
Kind
B2
Abstract

The present invention provides novel 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 diseases.

Claims (167)

1. A peptide that is:

(SEQ ID NO: 3)

[Propionic_acid]-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-

Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-N-

[alpha-MePhe]-NH 2 ;

(SEQ ID NO: 4)

[Propionic_acid]-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-

[Phe(4-OMe)]-[2-Nal]-[THP]-E-N-[THP]-NH 2 ;

(SEQ ID NO: 5)

[3,3,3-Trifluoropropionic acid]-[(D)Arg]-[Pen]-

Q-T-W-Q-[Pen]-Phe[4-(2-aminoethoxy)]-[2-Nal]-

[THP]-E-N-[THP]-NH 2 ;

SEQ ID NO: 6)

[Propionic_acid]-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-

Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-

[Lys(COCF 3 )]-N-[THP]-NH 2 ;

(SEQ ID NO: 7)

[Propionic_acid]-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-

Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-

[Lys(COtBu)]-N-[THP]-NH 2 ;

(SEQ ID NO: 8)

[Propionic_acid]-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-

Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-N-

[N-Me-beta-Ala]-NH 2 ;

(SEQ ID NO: 9)

[Pentanoic acid]-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-

Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-N-

[THP]-NH 2 ;

(SEQ ID NO: 10)

[Propionic_acid]-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-

Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-N-

[THP]-NH 2 ;

(SEQ ID NO: 13)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[THP]-NH 2 ;

(SEQ ID NO: 14)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[N-Me-beta-

Ala]-NH 2 ;

(SEQ ID NO: 15)

pr-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-Q-N-[THP]-NH 2 ;

(SEQ ID NO: 18)

[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-[Phe(4-OMe)]-

[2-Nal]-[THP]-E-N-[THP]-NH 2 ;

(SEQ ID NO: 26)

pr-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COtBu)]-

N-F-NH 2 ;

(SEQ ID NO: 33)

pr-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(CO2Allyl)]-

N-F-NH 2 ;

(SEQ ID NO: 51)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COcPr)]-

N-[THP]-NH 2 ;

(SEQ ID NO: 52)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COPr)]-

N-[THP]-NH 2 ;

(SEQ ID NO: 53)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(Ac)]-N-F-NH 2 ;

(SEQ ID NO: 54)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COEt)]-

N-F-NH 2 ;

(SEQ ID NO: 55)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COcPr)]-

N-F-NH 2 ;

(SEQ ID NO: 56)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(Ac)]-

N-[THP]-NH 2 ;

(SEQ ID NO: 57)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COEt)]-

N-[THP]-NH 2 ;

(SEQ ID NO: 58)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COPr)]-

N-F-NH 2 ;

(SEQ ID NO 59)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COPent)]-

N-F-NH 2 ;

(SEQ ID NO: 60)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COCF 3 )-

N-F-NH 2 ;

(SEQ ID NO: 61)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-[Lys(COiPr)]-

N-F-NH 2 ;

(SEQ ID NO: 105)

Ac-[(D)Arg]-[Pen]-N-T-W-[Lys(Ac)]-[Pen]-

Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-

N-[THP]-NH 2 ;

(SEQ ID NO: 106)

Ac-[(D)Arg]-[Pen]-N-T-W-[Lys(Ac)]-[Pen]-

Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-

N-[alpha-MePhe]-NH 2 ;

(SEQ ID NO: 125)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-

Ph)Asn]-NH 2 ;

(SEQ ID NO: 126)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-(2-

aminophenyl))Asn]-NH 2 ;

(SEQ ID NO: 127)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-

Pip)Asn]-NH 2 ;

(SEQ ID NO: 128)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-

Pyr)Asn]-NH 2 ;

(SEQ ID NO: 129)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-(4-

aminophenyl))Asn]-NH 2 ;

(SEQ ID NO: 130)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-(3-

aminophenyl))Asn]-NH 2 ;

(SEQ ID NO: 131)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-(4-

Pyz))Asn]-NH 2 ;

(SEQ ID NO: 132)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-(5-

indolyl)Asn]-NH 2 ;

(SEQ ID NO: 133)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-(3-

Pyz))Asn]-NH 2 ;

(SEQ ID NO: 134)

pr-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-THP]-E-N-[THP]-NH 2 ;

(SEQ ID NO: 135)

pr-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[(alpha-

Me)-4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-N-

[THP]-NH 2 ;

(SEQ ID NO: 136)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-

propylamido)Asn]-NH 2 ;

or

(SEQ ID NO: 137)

Ac-[(D)Arg]-[Pen]-Q-T-W-Q-[Pen]-Phe[4-(2-

aminoethoxy)]-[2-Nal]-[THP]-E-N-[(N-

(imidazol-2-yl)methyl)Asn]-NH 2 ;

wherein the peptide is cyclized via a Pen-Pen disulfide bond;

or a pharmaceutically acceptable salt thereof.

2. The peptide of claim 1 , wherein said peptide is Ac-[(D)Arg]-[Pen]-N-T-W-[Lys(Ac)]-[Pen]-Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-N-[THP]—NH 2 (SEQ ID NO:105) or a pharmaceutically acceptable salt thereof.

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

4. The pharmaceutical composition of claim 3 , wherein said peptide is Ac-[(D)Arg]-[Pen]-N-T-W-[Lys(Ac)]-[Pen]-Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-N-[THP]—NH 2 (SEQ ID NO:105) or a pharmaceutically acceptable salt thereof.

5. A method for treating an Inflammatory Bowel Disease (IBD), ulcerative colitis, Crohn's disease, Celiac disease (nontropical Sprue), enteropathy associated with seronegative arthropathies, microscopic colitis, collagenous colitis, eosinophilic gastroenteritis, colitis associated with radio- or chemo-therapy, colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1, chronic granulomatous disease, glycogen storage disease type 1b, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Wiskott-Aldrich Syndrome, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, psoriasis, psoriatic arthritis, or graft versus host disease in a subject in need thereof, comprising administering an effective amount of the peptide or a pharmaceutically acceptable salt thereof of claim 1 to the subject.

6. The method of claim 5 , wherein the method is for treating an Inflammatory Bowel Disease (IBD).

7. The method of claim 5 , wherein the method is for treating ulcerative colitis.

8. The method of claim 5 , wherein the method is for treating Crohn's disease.

9. The method of claim 5 , wherein the method is for treating psoriasis.

10. The method of claim 5 , wherein the method is for treating psoriatic arthritis.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2023
From: BIANCHI, ELISABETTA; BRANCA, DANILA; COSTANTE, ROBERTO; INGENITO, RAFFAELE
To: IRBM S.P.A.
Reel/Frame 065440/0638 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2023
From: IRBM S.P.A.
To: JANSSEN BIOTECH, INC.
Reel/Frame 065440/0750 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 5, 2021
From: PATCH, RAYMOND; SOMANI, SANDEEP; SUN, CHENGZAO; BARROS, STEPHANIE
To: JANSSEN BIOTECH, INC.
Reel/Frame 057097/0536 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 5, 2021
From: FREDERICK, BRIAN TROY; BHANDARI, ASHOK
To: PROTAGONIST THERAPEUTICS, INC.
Reel/Frame 057098/0037 →
Continuity (2)
Provisional Application 62961618 · Jan 15, 2020
Related Publication 20220402983A1 · Dec 22, 2022