US2016222064A1PendingUtilityA1

Hyaluronic acid-binding synthetic peptidoglycans, preparation, and methods of use

47
Assignee: SYMIC IP LLCPriority: May 24, 2011Filed: Dec 4, 2015Published: Aug 4, 2016
Est. expiryMay 24, 2031(~4.9 yrs left)· nominal 20-yr term from priority
A61P 29/00A61P 19/02A61P 19/08A61K 38/1709A61L 27/3654C07K 14/78C07K 14/4725C08B 37/0072A61K 38/39A61K 38/10C08B 37/0069A61K 38/00C07K 7/06A61L 27/48C07K 7/08A61K 38/08C07K 9/00A61L 27/54
47
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Claims

Abstract

This invention pertains to the field of hyaluronic acid-binding synthetic peptidoglycans and methods of forming and using the same.

Claims

exact text as granted — not AI-modified
1 . A synthetic peptidoglycan comprising a glycan and 1 to 20 synthetic peptides conjugated to the glycan, wherein each synthetic peptide is 5 to 40 amino acids in length and comprises a hyaluronic acid-binding amino acid sequence and wherein the synthetic peptidoglycan in the peptidoglycan can bind to a hyaluronic acid. 
     
     
         2 . The synthetic peptidoglycan of  claim 1  wherein each synthetic peptide comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2,
 wherein X8 is present or is not present, 
 wherein B1 is a basic amino acid, 
 wherein B2 is a basic amino acid, and 
 wherein X1-X8 are non-acidic amino acids. 
 
     
     
         3 . The synthetic peptidoglycan of  claim 1  wherein each synthetic peptide comprises:
 (i) an amino acid sequence selected from the group consisting of: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 2) 
                 
                     
                   GAHWQFNALTVRGG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   GDRRRRRMWHRQ; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   GKHLGGKHRRSR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   RGTHHAQKRRS; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   RRHKSGHIQGSK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   SRMHGRVRGRHE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   RRRAGLTAGRPR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   RYGGHRTSRKWV; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   RSARYGHRRGVG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   GLRGNRRVFARP; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   SRGQRGRLGKTR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   DRRGRSSLPKLAGPVEFPDRKIKGRR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   RMRRKGRVKHWG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   RGGARGRHKTGR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   TGARQRGLQGGWGPRHLRGKDQPPGR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 17) 
                 
                     
                   RQRRRDLTRVEG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 18) 
                 
                     
                   STKDHNRGRRNVGPVSRSTLRDPIRR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 19) 
                 
                     
                   RRIGHQVGGRRN; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 20) 
                 
                     
                   RLESRAAGQRRA; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 21) 
                 
                     
                   GGPRRHLGRRGH; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 22) 
                 
                     
                   VSKRGHRRTAHE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 23) 
                 
                     
                   RGTRSGSTR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 24) 
                 
                     
                   RRRKKIQGRSKR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 25) 
                 
                     
                   RKSYGKYQGR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 26) 
                 
                     
                   KNGRYSISR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 27) 
                 
                     
                   RRRCGQKKK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 28) 
                 
                     
                   KQKIKHVVKLK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 29) 
                 
                     
                   KLKSQLVKRK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 30) 
                 
                     
                   RYPISRPRKR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 31) 
                 
                     
                   KVGKSPPVR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 32) 
                 
                     
                   KTFGKMKPR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 33) 
                 
                     
                   RIKWSRVSK;  
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 34) 
                 
                     
                   KRTMRPTRR, 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or 
         (ii) an amino acid sequence having at least 90% sequence identity to an amino acid sequence of (i). 
       
     
     
         4 . The synthetic peptidoglycan of  claim 1 , wherein the glycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, and keratan sulfate. 
     
     
         5 .- 13 . (canceled) 
     
     
         14 . A method of treatment for arthritis in a patient, said method comprising administering to the patient an effective amount of the synthetic peptidoglycan of  claim 1 . 
     
     
         15 . The method of  claim 14  wherein each synthetic peptide comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2,
 wherein X8 is present or is not present, 
 wherein B1 is a basic amino acid, 
 wherein B2 is a basic amino acid, and 
 wherein X1-X8 are non-acidic amino acids. 
 
     
     
         16 . The method of  claim 14  wherein each synthetic peptide comprises:
 (i) an amino acid sequence selected from the group consisting of: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 2) 
                 
                     
                   GAHWQFNALTVRGG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   GDRRRRRMWHRQ; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   GKHLGGKHRRSR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   RGTHHAQKRRS; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   RRHKSGHIQGSK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   SRMHGRVRGRHE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   RRRAGLTAGRPR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   RYGGHRTSRKWV; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   RSARYGHRRGVG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   GLRGNRRVFARP; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   SRGQRGRLGKTR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   DRRGRSSLPKLAGPVEFPDRKIKGRR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   RMRRKGRVKHWG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   RGGARGRHKTGR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   TGARQRGLQGGWGPRHLRGKDQPPGR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 17) 
                 
                     
                   RQRRRDLTRVEG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 18) 
                 
                     
                   STKDHNRGRRNVGPVSRSTLRDPIRR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 19) 
                 
                     
                   RRIGHQVGGRRN; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 20) 
                 
                     
                   RLESRAAGQRRA; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 21) 
                 
                     
                   GGPRRHLGRRGH; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 22) 
                 
                     
                   VSKRGHRRTAHE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 23) 
                 
                     
                   RGTRSGSTR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 24) 
                 
                     
                   RRRKKIQGRSKR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 25) 
                 
                     
                   RKSYGKYQGR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 26) 
                 
                     
                   KNGRYSISR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 27) 
                 
                     
                   RRRCGQKKK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 28) 
                 
                     
                   KQKIKHVVKLK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 29) 
                 
                     
                   KLKSQLVKRK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 30) 
                 
                     
                   RYPISRPRKR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 31) 
                 
                     
                   KVGKSPPVR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 32) 
                 
                     
                   KTFGKMKPR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 33) 
                 
                     
                   RIKWSRVSK;  
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 34) 
                 
                     
                   KRTMRPTRR, 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or 
         (ii) an amino acid sequence having at least 90% sequence identity to an amino acid sequence of (i). 
       
     
     
         17 . The method of  claim 14  wherein the glycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, and keratan sulfate. 
     
     
         18 . The method of  claim 14  wherein the synthetic peptidoglycan is resistant to aggrecanase. 
     
     
         19 . The method of  claim 14  wherein each synthetic peptide has a glycine-cysteine attached to the C-terminus of the peptide. 
     
     
         20 . The method of  claim 14  wherein the arthritis is selected from the group consisting of osteoarthritis and rheumatoid arthritis. 
     
     
         21 . The method of  claim 14  wherein the dosage of the synthetic peptidoglycan is in a concentration ranging from about 0.1 μM to about 10 μM. 
     
     
         22 - 24 . (canceled) 
     
     
         25 . The synthetic peptidoglycan of  claim 1 , wherein the synthetic peptide comprises the amino acid sequence GAHWQFNALTVRGG (SEQ ID NO: 2), or an amino acid sequence having at least about 90% sequence identity to GAHWQFNALTVRGG (SEQ ID NO: 2). 
     
     
         26 . The synthetic peptidoglycan of  claim 1 , wherein the synthetic peptidoglycan comprises from 2 to 20 of the synthetic peptides. 
     
     
         27 . The synthetic peptidoglycan of  claim 1 , wherein the synthetic peptidoglycan comprises from 5 to 15 of the synthetic peptides. 
     
     
         28 . The synthetic peptidoglycan of  claim 1 , wherein the synthetic peptides are covalently conjugated to the glycan. 
     
     
         29 . The synthetic peptidoglycan of  claim 28 , wherein the synthetic peptides are covalently conjugated to the glycan through a linker. 
     
     
         30 . The The synthetic peptidoglycan of  claim 1 , wherein the synthetic peptides are conjugated to backbone of the glycan.

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