# US 2024/0199700 A1 · Oral peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory bowel diseases

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- Number: US 2024/0199700 A1
- Document ID: US20240199700A1
- Status: Published application
- Kind: A1
- Application number: 18/527,006
- Filed: 2023-12-01
- Published: 2024-06-20
- Earliest claimed: 2014-07-17
- Assignees: Protagonist Therapeutics, Inc.
- Applicants: Protagonist Therapeutics, Inc.
- Inventors: Ashok BHANDARI; Gregory Thomas BOURNE; Xiaoli CHENG; Brian Troy FREDERICK; Jie ZHANG; Dinesh V. PATEL; David LIU
- Web page: https://patentgrep.com/patent/US20240199700A1

## CPC

- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/48: of the pancreatic hormones
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 15/14: for lactation disorders, e.g. galactorrhoea
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 7/02: Linear peptides containing at least one abnormal peptide link
- C07K 7/50: Cyclic peptides containing at least one abnormal peptide link
- C07K 7/64: Cyclic peptides containing only normal peptide links
- C07K 14/54: Interleukins [IL]
- A61K 38/00: 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)
- G01N 2800/065: Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## 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

### Claim at position 1

1-54. (canceled)

### Claim 55

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-OMe2) 5-Hydroxy-Trp, Phe(3,4-Cl2), 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;
X13 is any amino acid;
X14 is Phe, Tyr, βhPhe, 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.

### Claim 56 (depends on 55)

The peptide of claim 55, or a pharmaceutically acceptable salt or solvate thereof, wherein X1 is absent.

### Claim 57 (depends on 56)

The peptide of claim 56, or a pharmaceutically acceptable salt or solvate thereof, wherein X2 is absent.

### Claim 58 (depends on 55)

The peptide of claim 55, or a pharmaceutically acceptable salt or solvate thereof, wherein X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe.

### Claim 59 (depends on 55)

The peptide of claim 55, or a pharmaceutically acceptable salt or solvate thereof, wherein X7 is Trp.

### Claim 60 (depends on 55)

The peptide of claim 55, or a pharmaceutically acceptable salt or solvate thereof, wherein X10 is a Phe analog.

### Claim 61 (depends on 60)

The peptide of claim 60, or a pharmaceutically acceptable salt or solvate thereof, wherein X10 is Phe(4-OMe), Phe(4-CONH2), or Phe[4-(2-aminoethoxy)].

### Claim 62 (depends on 55)

The peptide of claim 55, or a pharmaceutically acceptable salt or solvate thereof, wherein X11 is Trp, 1-Nal, or 2-Nal.

### Claim 63 (depends on 55)

The peptide of claim 55, or a pharmaceutically acceptable salt or solvate thereof, wherein X12 is Aib, α-Me-Lys, α-Me-Val α-Me-Leu; Achc, Acvc, Acpc, Acpc, or THP.

### Claim 64 (depends on 55)

The peptide of claim 55, 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, Lys, Asn, Orn, or Gln.

### Claim 65 (depends on 55)

The peptide of claim 55, or a pharmaceutically acceptable salt or solvate thereof, wherein X20 is absent.

### Claim 66 (depends on 65)

The peptide of claim 65, or a pharmaceutically acceptable salt or solvate thereof, wherein X19 is absent.

### Claim 67 (depends on 66)

The peptide of claim 66, or a pharmaceutically acceptable salt or solvate thereof, wherein X18 is absent.

### Claim 68 (depends on 67)

The peptide of claim 67, or a pharmaceutically acceptable salt or solvate thereof, wherein X17 is absent.

### Claim 69 (depends on 55)

The peptide of claim 55, 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.

### Claim 70 (depends on 55)

A pharmaceutical composition comprising the peptide of claim 55, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent.

### Claim 71 (depends on 55)

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, comprising providing to the subject an effective amount of the peptide of claim 55.

### Claim 72 (depends on 71)

The method of claim 71 wherein the peptide is provided to the subject by an oral, parenteral, intravenous, peritoneal, intradermal, subcutaneous, intramuscular, intrathecal, inhalation, vaporization, nebulization, sublingual, buccal, parenteral, rectal, intraocular, inhalation, topically, vaginal, or topical route of administration.

### Claim 73 (depends on 70)

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, comprising providing to the subject an effective amount of the pharmaceutical composition of claim 70.

### Claim 74 (depends on 73)

The method of claim 73 wherein the pharmaceutical composition is provided to the subject by an oral, parenteral, intravenous, peritoneal, intradermal, subcutaneous, intramuscular, intrathecal, inhalation, vaporization, nebulization, sublingual, buccal, parenteral, rectal, intraocular, inhalation, topically, vaginal, or topical route of administration.