Anti-inflammatory compounds and methods of use

Patent metadata

Field	Value
Publication number	US-2018194820-A1
Application number	US-201815883999-A
Country	US
Kind code	A1
Filing date	Jan 30, 2018
Priority date	May 16, 2014
Publication date	Jul 12, 2018
Grant date	—

Abstract

Methods of treating or inhibiting inflammation in a subject include administering an anti-inflammatory protein to the subject. In some embodiments, the protein has at least 80% sequence identity to the amino acid sequence set forth as SEQ ID NO: 1, SEQ ID NO: 17, or fragments thereof. Isolated polypeptides, nucleic acids, and recombinant vectors including a nucleic acid encoding the anti-inflammatory protein (such as a nucleic acid encoding a protein with at least 80% sequence identity to SEQ ID NO: 1, SEQ ID NO: 17, or fragments thereof) operably linked to a heterologous promoter are also disclosed.

First claim

We claim:

1 . An isolated polypeptide comprising:
an amino acid sequence having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 11; an amino acid sequence 130-190 amino acids in length and having at least 80% identity to amino acids 1-188 of SEQ ID NO: 11, amino acids 21-188 of SEQ ID NO: 11, or amino acids 189-330 of SEQ ID NO: 11; an amino acid sequence 130-190 amino acids in length and having at least 80% identity to amino acids 1-185 of SEQ ID NO: 1, amino acids 23-185 of SEQ ID NO: 1, or amino acids 192-313 of SEQ ID NO: 1.

2 . The isolated polypeptide of claim 1 , wherein the polypeptide comprises or consists of:
the amino acid sequence of SEQ ID NO: 11; an amino acid sequence 130-190 amino acids in length and comprising amino acids 1-188 of SEQ ID NO: 11, amino acids 21-188 of SEQ ID NO: 11, or amino acids 189-330 of SEQ ID NO: 11; an amino acid sequence 120-180 amino acids in length and comprising amino acids 1-185 of SEQ ID NO: 1, amino acids 23-185 of SEQ ID NO: 1, or amino acids 192-313 of SEQ ID NO: 1.

3 . The isolated polypeptide of claim 1 , wherein the polypeptide is encoded by:
a nucleic acid comprising a nucleotide sequence at least 80% identical to the nucleic acid sequence set forth as SEQ ID NO: 17; a nucleic acid 390-570 nucleotides in length and having at least 80% identity to nucleotides 1-564 of SEQ ID NO: 17, nucleotides 61-564 of SEQ ID NO: 17, or nucleotides 565-990 of SEQ ID NO: 17; a nucleic acid 360-540 nucleotides in length and having at least 80% identity to nucleotides 1-555 of SEQ ID NO: 2, nucleotides 67-555 of SEQ ID NO: 2, or nucleotides 574-939 of SEQ ID NO: 2.

4 . The isolated polypeptide of claim 3 , wherein the polypeptide is encoded by:
a nucleic acid comprising or consisting of the nucleic acid sequence of SEQ ID NO: 17; a nucleic acid 390-570 nucleotides in length and comprising nucleotides 1-564 of SEQ ID NO: 17, nucleotides 61-564 of SEQ ID NO: 17, or nucleotides 565-990 of SEQ ID NO: 17; a nucleic acid 390-570 nucleotides in length and comprising nucleotides 1-555 of SEQ ID NO: 2, nucleotides 67-555 of SEQ ID NO: 2, or nucleotides 574-939 of SEQ ID NO: 2.

5 . An isolated nucleic acid, comprising:
a nucleic acid comprising a nucleotide sequence at least 80% identical to the nucleic acid sequence set forth as SEQ ID NO: 17; a nucleic acid 390-570 nucleotides in length and having at least 80% identity to nucleotides 1-564 of SEQ ID NO: 17, nucleotides 61-564 of SEQ ID NO: 17, or nucleotides 565-990 of SEQ ID NO: 17; a nucleic acid 360-540 nucleotides in length and having at least 80% identity to nucleotides 1-555 of SEQ ID NO: 2, nucleotides 67-555 of SEQ ID NO: 2, or nucleotides 574-939 of SEQ ID NO: 2.

6 . The isolated nucleic acid molecule of claim 5 , comprising or consisting of:
the nucleic acid sequence of SEQ ID NO: 17; a nucleic acid 390-570 nucleotides in length and comprising or consisting of nucleotides 1-555 of SEQ ID NO: 2, nucleotides 67-555 of SEQ ID NO: 2, or nucleotides 574-939 of SEQ ID NO: 17; a nucleic acid 390-570 nucleotides in length and comprising or consisting of nucleotides 1-555 of SEQ ID NO: 2, nucleotides 67-555 of SEQ ID NO: 2, or nucleotides 574-939 of SEQ ID NO: 2.

7 . A recombinant vector comprising the polynucleotide of claim 5 , operably linked to a heterologous promoter.

8 . The recombinant vector of claim 7 , wherein the heterologous promoter comprises a promoter from E. coli , a viral promoter, or a mammalian promoter.

9 . A cell comprising the recombinant vector of claim 7 .

10 . A transformed cell comprising the polynucleotide of claim 5 , operably linked to a heterologous promoter.

11 . The transformed cell of claim 10 , wherein the heterologous promoter comprises a promoter from E. coli , a viral promoter, or a mammalian promoter.

12 . A method of treating or inhibiting inflammation and/or treating or inhibiting sepsis or septic shock in a subject, comprising administering to the subject the polypeptide of claim 1 .

13 . The method of claim 12 , wherein the inflammation in the subject comprises an inflammatory disease.

14 . The method of claim 13 , wherein the inflammatory disease comprises rheumatoid arthritis, osteoarthritis, inflammatory lung disease, inflammatory bowel disease, Hirschsprung's associated enterocolitis, pelvic inflammatory disease, periodontal disease, polymyalgia rheumatica, atherosclerosis, systemic lupus erythematosus, systemic sclerosis, Sjogren's Syndrome, asthma, allergic rhinitis, psoriasis, irritable bowel syndrome, necrotizing enterocolitis, or atopy.

15 . The method of claim 12 , wherein the amount of the polypeptide administered to the subject is about 1 mg to about 5 g.

16 . The method of claim 12 , wherein the effective amount of the protein is administered to the subject daily, weekly, or monthly.

17 . The method of claim 12 , further comprising administering one or more additional anti-inflammatory therapies to the subject with inflammation or administering one or more of antibiotics, vasopressors, or intravenous fluids to the subject with sepsis or septic shock.

18 . A method of treating sepsis or septic shock in a subject, comprising administering to the subject a polypeptide comprising an amino acid sequence having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 1.

19 . The method of claim 18 , wherein the polypeptide comprises or consists of the amino acid sequence of SEQ ID NO: 1 or amino acids 23-313 of SEQ ID NO: 1.

20 . The method of claim 18 , further comprising administering one or more of antibiotics, vasopressors, or intravenous fluids to the subject.

Assignees

• Univ Oregon

Inventors

• Guillemin Karen
• Rolig Annah
• Sweeney Emily

Classifications

• C07K14/4702 Primary

  Regulators; Modulating activity · CPC title

• A61P29/00 Primary

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07K4/12

  from animals; from humans · CPC title

• C12N15/70

  Vectors or expression systems specially adapted for E. coli · CPC title