Compositions and methods for treating celiac sprue disease

Patent metadata

Field	Value
Publication number	US-9289473-B2
Application number	US-201214131601-A
Country	US
Kind code	B2
Filing date	Aug 10, 2012
Priority date	Aug 10, 2011
Publication date	Mar 22, 2016
Grant date	Mar 22, 2016

Abstract

The invention provides compositions and methods for treating celiac sprue.

First claim

We claim:

1. A polypeptide comprising an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO:35 residues 1-378, wherein
(a) the polypeptide degrades a PQPQLP (SEQ ID NO:34) peptide at pH 4;
(b) residue 278 is Ser, residue 78 is Glu, and residue 82 is Asp; and
(c) the polypeptide comprises an amino acid change from SEQ ID NO: 67 residues 1-378 at one or more residues selected from the group consisting of amino acid residues 73, 102, 103, 104, 130, 165, 168, 169, 172, and 179, wherein if the amino acid change is at residue 73, the residue 73 amino acid is changed to either K or G.

2. The polypeptide of claim 1 , comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 35 residues 1-378.

3. The polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO:35 residues 1-378.

4. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence of any one of SEQ ID NO:36-66 residues 1-378.

5. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 66 residues 1-378.

6. A nucleic acid encoding the polypeptide of claim 1 .

7. A nucleic acid expression vector comprising the isolated nucleic acid of claim 6 .

8. A recombinant host cell comprising the nucleic acid expression vector of claim 7 .

9. A pharmaceutical composition, comprising the polypeptide of claim 1 , and a pharmaceutically acceptable carrier.

10. A method for treating celiac sprue, comprising administering to an individual with celiac sprue an amount effective to treat the celiac sprue of the polypeptide of claim 1 .

11. A method for treating celiac sprue, comprising administering to an individual with celiac sprue an amount effective of the pharmaceutical composition of claim 9 to treat the celiac sprue.

12. The method of claim 10 , wherein the polypeptide is administered orally.

13. The method of claim 10 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:66 residues 1-378.

14. The polypeptide of claim 1 , wherein the one or more amino acid changes are selected from the group consisting of:
residue 73: K, and G;
residue 102: D,
residue 103: S;
residue 104: A, T, and N;
residue 130: S;
residue 165: N;
residue 168: A;
residue 169: N, and G;
residue 172: D; and
residue 179: S, and H.

15. The method of claim 10 , wherein the one or more amino acid changes are selected from the group consisting of:
residue 73: K, and G;
residue 102: D,
103: S;
104: A, T, and N;
residue 130: S;
165: N;
residue 168:A;
residue 169:N, and G;
residue 172: D; and
residue 179: S, and H.

16. The method of claim 10 , wherein the polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 35 residues 1-378.

17. The method of claim 10 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 35 residues 1-378.

18. The method of claim 10 , wherein the polypeptide comprises the amino acid sequence of any one of SEQ ID NO: 36-66 residues 1-378.

19. The method of claim 13 wherein the polypeptide is administered orally.

20. The method of claim 17 wherein the polypeptide is administered orally.

Assignees

• Siegel Justin
• Baker David
• Gordon Sydney Rin Anna
• Pultz Ingrid Swanson
• Stanley Elizabeth Joy
• Wolf Sarah Jane
• Univ Washington Ct Commerciali

Inventors

• Siegel Justin
• Baker David
• Gordon Sydney Rin Anna
• Pultz Ingrid Swanson
• Stanley Elizabeth Joy
• Wolf Sarah Jane

Classifications

• A61P37/08

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title

• C12N9/52

  derived from bacteria {or Archaea} · CPC title