Peptides Having Anti-Inflammatory Properties

Abstract

Aspects of the present invention relate to peptides having anti-inflammatory activity, compositions containing one or more of the peptides, and use of the peptides to treat conditions associated with excessive inflammation in animals, particularly humans and other mammals.

1 .- 34 . (canceled) 
     
     
         35 . A method of modulating macrophage activity, the method comprising:
 contacting a macrophage with a CD206-binding agent to modulate activity of the macrophage.   
     
     
         36 . The method according to  claim 35 , wherein the CD206-binding agent binds to a mannose-binding site to modulate binding of signal regulatory protein (SIRP)-mannose to CD206. 
     
     
         37 . The method according to  claim 35 , wherein the CD206-binding agent binds to CD206 with a binding energy of at least −650 kcal/mol. 
     
     
         38 . The method according to  claim 35 , wherein the CD206-binding agent directly contacts at least one amino acid residue of CD206 selected from Phe-708, Thr-709, Trp-710, Pro-714, Glu-719, Asn-720, Trp-721, Ala-722, Glu-725, Tyr-729, Glu-733, Asn-747, Asp-748, Ser-1691, Cys-1693, Phe-1694 and Phe-1703. 
     
     
         39 . The method according to  claim 35 , wherein the macrophage activity that is modulated is macrophage polarization. 
     
     
         40 . The method according to  claim 35 , wherein viability of the macrophage is reduced. 
     
     
         41 . The method according to  claim 35 , wherein the macrophage is a M2 macrophage or a tumor associated macrophage (TAM). 
     
     
         42 . The method according to  claim 35 , wherein the CD206-binding agent inhibits macrophage activity. 
     
     
         43 . The method according to  claim 35 , wherein the CD206-binding agent is an anti-inflammatory peptide. 
     
     
         44 . The method according to  claim 35 , wherein the macrophage is in vitro. 
     
     
         45 . The method according to  claim 35 , wherein the macrophage is in vivo. 
     
     
         46 . A method of treating a subject for a condition associated with chronic inflammation, the method comprising:
 administering an effective amount of a CD206-binding agent to the subject to treat the subject for the condition associated with chronic inflammation.   
     
     
         47 . The method according to  claim 46 , wherein the condition associated with chronic inflammation is selected from the group consisting of scleroderma or multiple sclerosis, irritable bowel disease, ulcerative colitis, colitis, Crohn's disease, idiopathic pulmonary fibrosis, asthma, keratitis, arthritis, osteoarthritis, rheumatoid arthritis, auto-immune diseases, a feline or human immunodeficiency virus (FIV or HIV) infection, cancer, age-related inflammation and/or stem cell dysfunction, graft-versus-host disease (GVHD), keloids, obesity, diabetes, diabetic wounds, other chronic wounds, atherosclerosis, Parkinson's disease, Alzheimer's disease, macular degeneration, gout, gastric ulcers, gastritis, mucositis, toxoplasmosis, and chronic viral or microbial infections. 
     
     
         48 . The method according to  claim 46 , wherein the CD206-binding agent is administered in conjunction with another drug known to be effective in treating the condition. 
     
     
         49 . The method according to  claim 46 , wherein the condition is cancer. 
     
     
         50 . The method according to  claim 49 , further comprising administering an effective amount of a chemotherapeutic agent or cell therapy to the subject. 
     
     
         51 . The method according to  claim 50 , wherein the chemotherapeutic agent or cell therapy is selected from steroids, anthracyclines, thyroid hormone replacement drugs, thymidylate-targeted drugs, checkpoint inhibitor drugs, Chimeric Antigen Receptor/T cell therapies, and other cell therapies. 
     
     
         52 . The method according to  claim 46 , wherein the condition associated with chronic inflammation is a fibrosis or scleroderma. 
     
     
         53 . The method according to  claim 46 , wherein the CD206-binding agent is an immunomodulatory peptide of 18 amino acid residues or less in length, wherein the peptide comprises a sequence defined by one of the formulae:
   [Y 1a Y 1b ]-[X 1a X 1b ]-[Y 2a Y 2b ]-[X 2a X 2b ]-[Y 3a ]-[X 3a ]; and     [X 3a ]-[Y 3a ]-[X 2b X 2a ]-[Y 2b Y 2a ]-[Y 1b X 1a ]-[X 1b X 1a ]-[Y 1b Y 1a ];   wherein:   Y 1a , Y 1b , Y 2a , Y 2b  and Y 3a  are each phenylalanine; and   X 1a , X 1b , X 2a , X 2b  and X 3a  are each independently selected from lysine and arginine.   
     
     
         54 . The method according to  claim 46 , wherein the CD206-binding agent is an immunomodulatory peptide of 18 amino acid residues or less in length, wherein the peptide comprises a sequence selected from SEQ ID NO:121-124, SEQ ID NO:148, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 120.