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EP-4735023-A2 - COMPOSITIONS AND METHODS FOR TREATING INFLAMMATORY BOWEL DISEASE

EP4735023A2EP 4735023 A2EP4735023 A2EP 4735023A2EP-4735023-A2

Abstract

Aspects of the disclosure relate to compositions and methods for treating one or more inflammatory bowel diseases ("IBDs"), such as ulcerative colitis ("UC") and/or Crohn's disease. Some embodiments relate to a pharmaceutical dosage form comprising a core comprising an inhibitor of a protease (e.g., a bacterial protease) and a controlled release coating applied to an exterior surface of the core. In some cases, the protease inhibitor is a gliptin or a pharmaceutically acceptable salt thereof. In some cases, the controlled release coating is configured to release the protease inhibitor in the large intestine (e.g., colon) and/or small intestine of a subject to whom the pharmaceutical dosage form is administered. Some embodiments relate to methods of treating one or more IBDs comprising delivering a therapeutically effective amount of an inhibitor of a protease (e.g., a bacterial protease) to the large intestine (e.g., colon) and/or small intestine of a subject.

Inventors

  • MILLS, Robert Hardie
  • DULAI, Parambir Singh
  • MACCLANCY, Nigel James Boetius

Assignees

  • Piton Therapeutics, Inc.

Dates

Publication Date
20260506
Application Date
20240628

Claims (20)

  1. 1. A composition comprising an inhibitor of a bacterial protease and a carrier.
  2. 2. The composition of claim 1, wherein the carrier comprises a polymer that is not absorbed in a gastrointestinal tract.
  3. 3. The composition of claim 1 or 2, wherein the carrier comprises polyvinylpyrrolidone.
  4. 4. The composition of any one of claims 1-3, wherein the inhibitor of the bacterial protease is loaded into the carrier.
  5. 5. The composition of any one of claims 1-4, wherein the inhibitor of the bacterial protease is a gliptin or a pharmaceutical salt thereof.
  6. 6. The composition of any one of claim 1-5, further comprising an agent that facilitates a targeted delivery of the inhibitor of the bacterial protease and carrier to an intestinal location.
  7. 7. The composition of any one of claims 1-6, wherein the agent comprises a first material that dissolves at a pH between about 6.0 and about pH 7.6.
  8. 8. The composition of claim 7, wherein the first material dissolves at a pH 7.5.
  9. 9. The composition of any one of claims 1-8, wherein the agent comprises a second material that is susceptible to degradation by a microbial organism.
  10. 10. The composition of claim 9 wherein the second material is susceptible to degradation by a microbial organism present in a large intestine of a subject.
  11. 11. The composition of claim 10 wherein the second material is susceptible to degradation by a microbial organism present in a colon of a subject.
  12. 12. The composition of any one of claims 7-11 wherein the first material dissolves at a pH between about pH 6.0 and about pH 7.6 and the second material is susceptible to degradation by a microbial organism present in a large intestine of a subject.
  13. 13. The composition of any one of claims 6-12, wherein the agent comprises one or more layers.
  14. 14. The composition of claim 13, wherein the first material of the agent is present in a first layer.
  15. 15. The composition of claim 13 or 14, wherein the second material of the agent is present in a second layer.
  16. 16. The composition of any one of claims 1-15, wherein the bacterial protease cleaves GLP-1.
  17. 17. The composition of any one of claims 1-15, wherein the bacterial protease cleaves GLP-2.
  18. 18. The composition of any one of claims 1-17, wherein the bacterial protease is a serine protease.
  19. 19. The composition of any one of claims 1-18, wherein the bacterial protease is a dipeptidyl peptidase-4 (DPP-4).
  20. 20. The composition of claim 19, wherein the bacterial protease comprises a DPP-4 expressed by B. vulgatus and/or B. dorei.

Description

COMPOSITIONS AND METHODS FOR TREATING INFLAMMATORY BOWEL DISEASE RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 63/510,884, filed June 28, 2023, entitled “COMPOSITIONS AND METHODS FOR TREATING ULCERATIVE COLITIS” and U.S. Provisional Application No. 63/510,885, filed June 28, 2023, entitled “COMPOSITIONS AND METHODS FOR TREATING INFLAMMATORY BOWEL DISEASE,” the entire contents of each of which are incorporated herein by reference. BACKGROUND An inflammatory bowel disease (“IBD”) is a disease that is characterized by chronic inflammation of the gastrointestinal (“GI”) tract. One type of IBD is ulcerative colitis (“UC”), which causes ulcers on the inner lining of the large intestine (e.g., colon) and/or rectum. Another type of IBD is Crohn’s disease, which can cause inflammation in any part of the GI tract. IBDs can cause symptoms such as diarrhea, abdominal pain, rectal bleeding, weight loss, anemia, and fatigue, and can be associated with decreased quality of life. In some cases, IBDs can lead to complications requiring hospitalization and/or surgery. Millions of individuals around the world are affected by IBDs every year. In 2017, it was found that there were more than 6.8 million cases of IBD globally, with the highest prevalence occurring in the United States. There therefore is a need to continue developing safe, effective treatments for IBDs. SUMMARY OF INVENTION The present disclosure is related to compositions and methods for treating inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease). The subject matter of the present invention involves, in some cases, interrelated products, alternative solutions to a particular problem, and/or a plurality of different uses of one or more systems and/or articles. In some embodiments, a composition comprising an inhibitor of a protease is provided. In some embodiments, a composition comprises an inhibitor (e.g., one or more inhibitors) of a bacterial protease. In some embodiments, a composition comprises an inhibitor of a bacterial protease and an excipient. In some embodiments, provided are compositions comprising two or more protease inhibitors (e.g., 2, 3, 4, 5, or 5-10 for example). In some embodiments, provided are compositions comprising two or more bacterial protease inhibitors (e.g., 2, 3, 4, 5, or 5-10 for example). In some aspects, a pharmaceutical dosage form is described. In some embodiments, the pharmaceutical dosage form comprises a core comprising an inhibitor of a protease. In certain embodiments, the inhibitor of the protease comprises a gliptin or a pharmaceutically acceptable salt thereof. In some aspects, provided are compositions comprising two or more gliptins (e.g., 2, 3, 4, 5, or 5-10 for example). In some aspects, provided are pharmaceutical dosage forms comprising two or more gliptins (e.g., 2, 3, 4, 5, or 5-10 for example). In some embodiments, the pharmaceutical dosage form comprises a controlled release coating applied to an exterior surface of the core. In certain embodiments, the controlled release coating is configured to release the inhibitor of the protease in a large intestine and/or small intestine of a subject to whom the pharmaceutical dosage form is administered. In some aspects, a method of treating an inflammatory bowel disease is described. In some embodiments, the method comprises delivering a therapeutically effective amount of an inhibitor of a protease to a large intestine and/or small intestine of a subject. In certain embodiments, the inhibitor of the protease comprises a gliptin or a pharmaceutically acceptable salt thereof. In some aspects, a method of treating an inflammatory bowel disease is described. In some embodiments, the method comprises determining an abundance of a bacterial protease in a sample obtained from a subject. In some embodiments, the method comprises delivering a therapeutically effective amount of an inhibitor of the bacterial protease to a large intestine and/or small intestine of the subject. In certain embodiments, the inhibitor of the protease comprises a gliptin or a pharmaceutically acceptable salt thereof. Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and/or inconsistent disclosure, the present specification shall control. BRIEF DESCRIPTION OF THE DRAWINGS Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component