Treatment of gluten intolerance and related conditions

Patent metadata

Field	Value
Publication number	US-10982201-B2
Application number	US-201916357191-A
Country	US
Kind code	B2
Filing date	Mar 18, 2019
Priority date	Nov 21, 2012
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

Abstract

Provided herein are compositions, foods comprising nepenthesin or a derivative thereof and methods of using nepenthesin or a derivative thereof for modulating gluten intolerance and related conditions, such as celiac disease. Further provided herein are pharmaceutical compositions comprising nepenthesin or a derivative thereof and methods of using nepenthesin or a derivative thereof to treat bacterial infections of the gastrointestinal tract, such as C. difficile or H. pylori. Further provided herein are compositions comprising recombinant nepenthesin I or nepenthesin II, or homologous proteins, and methods for making the same.

First claim

What is claimed is:

1. A composition for treating or attenuating gluten intolerance comprising:
(a) an effective amount of nepenthesin, the nepenthesin comprising an amino acid sequence that is at least 85% identical to the amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7, without a plant signal sequence and having aspartic protease activity; and
(b) an effective amount of a buffer to maintain the pH of said composition at a pH of 5 or above, wherein said nepenthesin is inactive prior to administration;
wherein said effective amount of nepenthesin is sufficient to degrade gluten upon oral administration of said solid composition to a patient suffering from gluten intolerance.

2. The composition of claim 1 , wherein said effective amount of nepenthesin is between about 1 mg and about 1 g, wherein about refers to a variation of up to ±5%.

3. The composition of claim 1 , further comprising at least one additional agent selected from the group consisting of an inhibitor of a transglutaminase, an anti-inflammatory agent, a COX-2 inhibitor, a p38 MAP kinase inhibitor, a mast cell-stabilizing agent, an anti-ulcer agent, an anti-allergy agent, and an anti-TNF-α agent.

4. The composition of claim 1 , further comprising at least one additional enzyme selected from the group consisting of a gastric protease, an aspartic protease, and a prolyl endopeptidase.

5. The composition of claim 1 , wherein said composition is formulated to release said nepenthesin in a patient's stomach.

6. The composition of claim 2 , wherein said effective amount of said nepenthesin is between about 1 mg and about 500 mg.

7. The composition of claim 2 , wherein said effective amount of said nepenthesin is between about 1 mg and about 200 mg.

8. The composition of claim 1 , wherein the gluten intolerance is celiac disease, wheat allergy, gluten sensitivity, or dermatitis herpetiformis.

9. The composition of claim 1 , wherein the nepenthesin comprises an amino acid sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 3.

10. The composition of claim 1 , wherein the nepenthesin comprises an amino acid sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 4.

11. The composition of claim 1 , wherein the nepenthesin comprises an amino acid sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 5.

12. The composition of claim 1 , wherein the nepenthesin comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of set forth in SEQ ID NO: 6.

13. The composition of claim 1 , wherein the nepenthesin comprises an amino acid sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 7.

14. The composition of claim 1 , wherein the nepenthesin comprises an amino acid sequence that is at least 90% identical to the amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7.

15. The composition of claim 1 , wherein the nepenthesin comprises an amino acid sequence that is at least 95% identical to the amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7.

16. The composition of claim 1 , wherein the nepenthesin is recombinant nepenthesin.

17. The composition of claim 1 , wherein the nepenthesin comprises the amino acid sequence set forth in SEQ ID NO: 3.

18. The composition of claim 1 , wherein the nepenthesin comprises the amino acid sequence set forth in SEQ ID NO: 4.

19. The composition of claim 1 , wherein the nepenthesin comprises the amino acid sequence set forth in SEQ ID NO: 5.

20. The composition of claim 1 , wherein the nepenthesin comprises the amino acid sequence of set forth in SEQ ID NO: 6.

21. The composition of claim 1 , wherein the nepenthesin comprises the amino acid sequence set forth in SEQ ID NO: 7.

Assignees

• Codexis Inc

Inventors

• Schriemer David C
• Man Petr
• Mrazek Hynek
• Rey Martial

Classifications

• C12Y304/23012

  Nepenthesin (3.4.23.12) · CPC title

• C12N9/63 Primary

  derived from plants · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title