US2016083443A1PendingUtilityA1

Immunomodulatory compositions and methods for treating disease with modified host defense peptides

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Assignee: UNIV SASKATCHEWANPriority: Jun 28, 2007Filed: Jul 1, 2015Published: Mar 24, 2016
Est. expiryJun 28, 2027(~0.9 yrs left)· nominal 20-yr term from priority
Inventors:Scott NapperKenneth Jason KindrachukSamuel Kwadwo Attah-Poku
A61K 39/002A61K 39/02A61K 2039/572A61K 2039/55516C07K 14/4723A61K 39/39A61K 38/00A61K 39/0008A61P 37/04C07K 2319/00A61P 31/00A61K 39/0002A61P 33/00
47
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Claims

Abstract

Compositions and methods are provided for modulating an immune response in a vertebrate subject. Compositions and methods can comprise administering a modified host defense peptide to the vertebrate subject in an amount effective to activate the immune response in the vertebrate subject, wherein the modified host defense peptide is inverted in amino acid sequence from an amino terminus to a carboxy terminus or modified to one or more D -amino acids, or both modifications, when compared to a host defense peptide. Compositions and methods are provided which comprise administering a modified host defense peptide to the vertebrate subject in an amount effective to modify an immune response in the vertebrate subject.

Claims

exact text as granted — not AI-modified
What is claimed: 
     
         1 . A method for modulating an immune response in a vertebrate subject in need thereof comprising,
 administering a modified host defense peptide in an amount effective to activate the immune response in the vertebrate subject, wherein the modified host defense peptide is modified by at least one of: inversion in amino acid sequence from an amino terminus to a carboxy terminus, or modification to one or more  D -amino acids, when compared to a host defense peptide.   
     
     
         2 . The method of  claim 1  wherein the modified host defense peptide is modified by all  D -amino acids. 
     
     
         3 . The method of  claim 1  wherein the modified host defense peptide is modified by inversion in amino acid sequence from an amino terminus to a carboxy terminus and by one or more  D -amino acids. 
     
     
         4 . The method of  claim 1  wherein the host defense peptide is BMAP-28. 
     
     
         5 . The method of  claim 4  wherein the host defense peptide comprises an amino acid sequence of SEQ ID NO: 1. 
     
     
         6 . The method of  claim 1  wherein the modified host defense peptide has between 27 and about 50 amino acids and comprises an amino acid sequence of SEQ ID NO:2. 
     
     
         7 . The method of  claim 1  wherein the modified host defense peptide comprises between 8 and about 12 amino acids of an amino acid sequence of SEQ ID NO:2. 
     
     
         8 . The method of  claim 1  wherein the modified host defense peptide consists of an amino acid sequence of SEQ ID NO:2. 
     
     
         9 . The method of  claim 1 , wherein the modified host defense peptide is optionally modified, said modification selected from a group consisting of glycosylation, reduction of one or more amide bonds, methylation of one or more nitrogens, esterification of one or more carboxylic acid groups, and modification at the amino terminus, carboxy terminus, or both amino and carboxy termini with a moiety independently selected from the group consisting of CH 3 CO, CH 3 (CH 2 ) n CO, C 6 H 5 CH 2 CO and H 2 N(CH 2 ) n CO, wherein n=1-10. 
     
     
         10 . The method of  claim 1 , wherein the modified host defense peptide is optionally modified as a fusion protein or a polypeptide conjugated to carbohydrate or lipid. 
     
     
         11 . The method of  claim 1 , wherein the vertebrate subject is mammalian, avian, reptilian, amphibian, osteichthyes, or chondrichthyes. 
     
     
         12 . The method of  claim 1  wherein the modified host defense peptide decreases cytotoxicity to host cells in the mammalian subject compared to cytotoxicity of a naturally-occurring host defense peptide. 
     
     
         13 . The method of  claim 1  wherein the modified host defense peptide stimulates an immune response against an infectious disease in the mammalian subject. 
     
     
         14 . The method of  claim 1  wherein the modified host defense peptide has an adjuvant activity to stimulate an immune response against an infectious disease in the mammalian subject. 
     
     
         15 . The method according to  claim 14 , wherein the infectious disease is a bacterial infectious disease. 
     
     
         16 . The method of  claim 15  wherein the bacterial infectious disease is a Gram-negative bacterial disease or a Gram positive bacterial disease. 
     
     
         17 . The method according to  claim 15 , wherein the bacterial infectious disease is an antibiotic resistant bacterial infectious disease. 
     
     
         18 . The method according to  claim 14 , wherein the infectious disease is a viral disease. 
     
     
         19 . The method according to  claim 14 , wherein the infectious disease is a fungal disease. 
     
     
         20 . The method according to  claim 14 , wherein the infectious disease is a parasitic disease. 
     
     
         21 . A method for modulating an immune response in a vertebrate subject in need thereof comprising,
 administering a modified host defense peptide in an amount effective to inhibit the immune response and reduce host cell toxicity in the vertebrate subject, wherein the modified host defense peptide is modified by at least one of: inversion in amino acid sequence from an amino terminus to a carboxy terminus, or modification to one or more  D -amino acids, when compared to a host defense peptide.   
     
     
         22 . The method of  claim 21  wherein the modified host defense peptide is modified by all  D -amino acids. 
     
     
         23 . The method of  claim 21  wherein the modified host defense peptide is modified by inversion in amino acid sequence from an amino terminus to a carboxy terminus and by one or more  D -amino acids. 
     
     
         24 . The method of  claim 21  wherein the host defense peptide is BMAP-28. 
     
     
         25 . The method of  claim 24  wherein the host defense peptide comprises an amino acid sequence of SEQ ID NO:1. 
     
     
         26 . The method of  claim 21  wherein the modified host defense peptide has between 27 and about 50 amino acids and comprises an amino acid sequence of SEQ ID NO:2. 
     
     
         27 . The method of  claim 21  wherein the modified host defense peptide consists of an amino acid sequence of SEQ ID NO:2. 
     
     
         28 . The method of  claim 21  wherein the modified host defense peptide comprises between 8 and about 12 amino acids of an amino acid sequence of SEQ ID NO:2. 
     
     
         29 . The method of  claim 21  wherein the vertebrate subject is mammalian, avian, reptilian, amphibian, osteichthyes, or chondrichthyes. 
     
     
         30 . The method of  claim 21  wherein the modified host defense peptide decreases cytotoxicity to host cells in the mammalian subject compared to cytotoxicity of the host defense peptide. 
     
     
         31 . The method of  claim 21  wherein the modified host defense peptide reduces endotoxin activity in the vertebrate subject. 
     
     
         32 . The method of  claim 31  wherein the modified host defense peptide reduces inflammatory disease or sepsis in the vertebrate subject. 
     
     
         33 . The method of  claim 32  wherein the inflammatory disease is caused by arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease, irritable bowel syndrome. 
     
     
         34 . The method of  claim 32  wherein the inflammatory disease is associated with acute or chronic pain.

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