US2021188915A1PendingUtilityA1
Hyaluronic acid-binding synthetic peptidoglycans, preparation, and methods of use
Est. expiryMay 24, 2031(~4.8 yrs left)· nominal 20-yr term from priority
C07K 14/4725C07K 14/78A61K 38/1709A61K 38/39A61K 38/10A61L 27/3654C07K 7/06A61P 19/02A61K 38/00A61P 19/08C08B 37/0069C08B 37/0072A61K 38/08A61L 27/54A61L 27/48C07K 7/08C07K 9/00A61P 29/00
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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 . A synthetic peptidoglycan comprising a synthetic peptide covalently conjugated to a glycan wherein the synthetic peptide comprises a hyaluronic acid-binding sequence.
2 . The synthetic peptidoglycan of claim 1 wherein the 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 the synthetic peptide comprises 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.
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, keratan sulfate, and hyaluronic acid.
5 . The synthetic peptidoglycan of claim 1 wherein the synthetic peptidoglycan is resistant to aggrecanase.
6 . The synthetic peptidoglycan of claim 1 wherein the peptide component of the synthetic peptidoglycan has a glycine-cysteine attached to the C-terminus of the peptide.
7 . An engineered collagen matrix comprising polymerized collagen, hyaluronic acid, and a hyaluronic acid-binding synthetic peptidoglycan comprising a peptide component and a glycan component.
8 . The engineered collagen matrix of claim 7 wherein the peptide component of the synthetic peptidoglycan 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.
9 . The engineered collagen matrix of claim 7 wherein the peptide component of the synthetic peptidoglycan comprises 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.
10 . The engineered collagen matrix of claim 7 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.
11 . The engineered collagen matrix of claim 7 wherein the synthetic peptidoglycan is resistant to aggrecanase.
12 . The engineered collagen matrix of claim 7 wherein the peptide component of the synthetic peptidoglycan has a glycine-cysteine attached to the C-terminus of the peptide.
13 . The engineered collagen matrix of claim 7 wherein the matrix further comprises an exogenous population of cells.
14 . A method of treatment for arthritis in a patient, said method comprising the step of administering to the patient a hyaluronic acid-binding synthetic peptidoglycan comprising a peptide component and a glycan component, wherein the synthetic peptidoglycan reduces a symptom associated with the arthritis.
15 . The method of claim 14 wherein the peptide component of the synthetic peptidoglycan 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 the peptide component of the synthetic peptidoglycan comprises 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.
17 . The method of claim 14 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.
18 . The method of claim 14 wherein the synthetic peptidoglycan is resistant to aggrecanase.
19 . The method of claim 14 wherein the peptide component of the synthetic peptidoglycan 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 . The synthetic peptidoglycan of claim 1 wherein the synthetic peptidoglycan is resistant to matrix metallo proteases.
23 . The engineered collagen matrix of claim 7 wherein the synthetic peptidoglycan is resistant to matrix metallo proteases.
24 . The method of claim 14 wherein the synthetic peptidoglycan is resistant to matrix metallo proteases.Join the waitlist — get patent alerts
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