US2019330276A1PendingUtilityA1
Hyaluronic acid-binding synthetic peptidoglycans, preparation, and methods of use
Est. expiryMay 24, 2031(~4.9 yrs left)· nominal 20-yr term from priority
A61P 29/00A61P 19/08A61P 19/02A61K 38/10A61K 38/00C08B 37/0072A61K 38/1709A61L 27/48C07K 7/08A61K 38/39C07K 14/4725A61L 27/54C07K 14/78C07K 7/06C08B 37/0069A61K 38/08A61L 27/3654C07K 9/00
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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-modified1 . (canceled)
2 . A pharmaceutical composition comprising 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, wherein the glycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid;
wherein each 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; wherein the composition does not comprise a collagen-binding synthetic peptidoglycan.
3 . A pharmaceutical composition comprising a synthetic peptidoglycan of the formula (P n L) x G
wherein n is 1 to 20; x is 1 to 20; L is a linker having an approximate molecular weight of about 20 to about 500 Da; and P is a synthetic peptide of: (i) amino acid sequence:
(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;
or
(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 pharmaceutical composition of claim 2 , 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).
5 . The pharmaceutical composition of claim 2 , comprising 1 to 10 synthetic peptides conjugated to the glycan, wherein each 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).
6 . The pharmaceutical composition of claim 2 , wherein the synthetic peptidoglycan comprises from 2 to 20 of the synthetic peptides.
7 . The pharmaceutical composition of claim 2 , wherein the synthetic peptidoglycan comprises from 5 to 15 of the synthetic peptides.
8 . The pharmaceutical composition of claim 2 , wherein the synthetic peptides are covalently conjugated to the glycan.
9 . The pharmaceutical composition of claim 8 , wherein the synthetic peptides are covalently conjugated to the glycan through a linker having an approximate molecular weight of about 20 to about 500 Da.
10 . The pharmaceutical composition of claim 2 , wherein each synthetic peptide is separately conjugated to the glycan.
11 . A pharmaceutical composition comprising a glycan and 1 to 10 synthetic peptides conjugated to the glycan, wherein each synthetic peptide has the sequence of GAHWQFNALTVRGG (SEQ ID NO: 2) or an amino acid sequence having at least 90% sequence identity to GAHWQFNALTVRGG (SEQ ID NO: 2), wherein the glycan is chondroitin sulfate.
12 . A method of treatment for arthritis in a patient, said method comprising administering to the patient an effective amount of the pharmaceutical composition of claim 2 .
13 . The method of claim 12 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).
14 . The method of claim 12 wherein the synthetic peptidoglycan is resistant to aggrecanase.
15 . The method of claim 12 wherein each synthetic peptide has a glycine-cysteine attached to the C-terminus of the peptide
16 . The method of claim 12 wherein the arthritis is selected from the group consisting of osteoarthritis and rheumatoid arthritis.
17 . The method of claim 12 wherein the dosage of the synthetic peptidoglycan is in a concentration ranging from about 0.1 μM to about 10 μM.
18 . A method of treatment for arthritis in a patient, said method comprising administering to the patient an effective amount of a pharmaceutical composition comprising a glycan and 1 to 10 synthetic peptides conjugated to the glycan, wherein each synthetic peptide has the sequence of GAHWQFNALTVRGG (SEQ ID NO: 2) or an amino acid sequence having at least 90% sequence identity to GAHWQFNALTVRGG (SEQ ID NO: 2), wherein the glycan is chondroitin sulfate; and wherein the composition does not comprise a collagen-binding synthetic peptidoglycan.
19 . The method of claim 18 , wherein the synthetic peptides are covalently conjugated to the glycan through a linker having an approximate molecular weight of about 20 to about 500 Da.Cited by (0)
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