# US 11,111,272 B2 · α4α7 peptide monomer and dimer antagonists

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- Number: US 11,111,272 B2
- Document ID: US11111272B2
- Status: Granted
- Kind: B2
- Application number: 16/781,516
- Filed: 2020-02-04
- Published: 2020-10-01
- Granted: 2021-09-07
- Earliest claimed: 2014-10-01
- Assignees: Protagonist Therapeutics, Inc.
- Applicants: Protagonist Therapeutics, Inc.
- Inventors: Ashok Bhandari; Dinesh V. Patel; Genet Zemede; Larry C. Mattheakis; David Liu
- Web page: https://patentgrep.com/patent/US11111272B2

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- 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 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/24: Antidepressants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 29/02: without antiinflammatory effect
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- 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 7/06: having 5 to 11 amino acids
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The invention relates to peptide dimer compounds and peptide monomer compounds that potently inhibit binding of α4β7 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, possess high selectivity against α4β1 binding, and have high stability under gastrointestinal conditions.

## Claims

### Claim 1

A method for treating Celiac disease in a subject, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising a peptide dimer compound comprising two monomer subunits, wherein each monomer subunit comprises the amino acid sequence:
Pen-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homo-Glu)-(D-Lys) (SEQ ID NO:153)
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein each monomer subunit comprises a disulfide bond between the two Pen amino acids.

### Claim 3 (depends on 1)

The method of claim 1, wherein the peptide dimer compound further comprises a linker moiety.

### Claim 4 (depends on 3)

The method of claim 3, wherein the linker moiety is bound to the D-Lys amino acids of the two monomer units.

### Claim 5 (depends on 3)

The method of claim 3, wherein the linker moiety is diglycolic acid (DIG).

### Claim 6 (depends on 1)

The method of claim 1, wherein the N-terminus of each monomer subunit is acylated.

### Claim 7 (depends on 1)

The method of claim 1, wherein each monomer subunit comprises a C-terminal free amide.

### Claim 8 (depends on 1)

The method of claim 1, wherein each monomer subunit comprises a disulfide bond between the two Pen amino acids and a linker moiety bound to the D-Lys amino acid, wherein the N-terminus of each monomer subunit is acylated.

### Claim 9 (depends on 1)

The method of claim 1, wherein the peptide dimer compound consists of the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt thereof is an acetate salt of the peptide dimer compound.

### Claim 11 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is administered orally.

### Claim 12 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient.

### Claim 13 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition comprises an enteric coating.

### Claim 14 (depends on 1)

The method of claim 1, wherein the peptide dimer compound or pharmaceutically acceptable salt thereof inhibits binding of α4β7 to mucosal addressin cell adhesion molecule (MAdCAM).