US2011250631A1PendingUtilityA1
Proteoglycan degrading mutants for treatment of cns
Est. expiryMay 16, 2023(expired)· nominal 20-yr term from priority
A61P 43/00A61P 9/00A61P 27/02A61P 25/02A61P 25/00C12N 9/2408A61K 38/51C12Y 302/01036C12Y 402/02004C12N 9/88C07K 2319/00C07K 19/00A61K 38/00C12Y 402/02001C07K 2319/10C12Y 302/01035C07K 2319/03C12Y 402/02005A61K 35/30C07K 14/005A61K 45/06
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Claims
Abstract
The present disclosure relates to the preparation and deletion mutants of chondroitinase proteins and their use in methods for promoting the diffusion of therapeutic composition into tissues and their use for neurological functional recovery after central nervous system (“CNS”) injury or disease.
Claims
exact text as granted — not AI-modified1 . An composition comprising:
an isolated nucleic acid comprising a sequence that encodes for mutant proteoglycan degrading polypeptide.
2 . The composition of claim 1 wherein the nucleic acid encodes for a proteoglycan degrading polypeptide that is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1), Chondroitinase ABC Type II, (SEQ ID NO: 27), Chondroitinase AC, (SEQ ID NO: 5), and Chondroitinase B, (SEQ ID NO: 12), hyaluronidase 1, (SEQ ID NO: 30), hyaluronidase 2, (SEQ ID NO: 31), hyaluronidase 3, (SEQ ID NO: 32), or hyaluronidase 4, (SEQ ID NO: 33).
3 . The composition of claim 1 wherein the nucleic acid encodes for a proteoglycan degrading polypeptide that is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1), Chondroitinase ABC Type II, (SEQ ID NO: 27), Chondroitinase AC, (SEQ ID NO: 5), and Chondroitinase B, (SEQ ID NO: 12)
4 . The composition of claim 1 wherein the nucleic acid encodes for a proteoglycan degrading polypeptide that is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1).
5 . The composition of claim 1 wherein the nucleic acid encodes for a proteoglycan degrading polypeptide that is a mutant of Chondroitinase ABC Type II, (SEQ ID NO: 27).
6 . The composition of claim 1 wherein the sequence of said nucleic acid is at least 80%, identical to a nucleic acid sequence encoding for a mutant proteoglycan degrading polypeptide.
7 . The composition of claim 1 wherein the nucleic acid encodes for a polypeptide that degrades a proteoglycan in a tissue of the central nervous system.
8 . The composition of claim 1 wherein the nucleic acid encodes for a polypeptide that degrades a chondroitin sulfate proteoglycan.
9 . An expression vector comprising the nucleic acid of claim 1 operably linked to an expression control sequence.
10 . The composition of claim 1 further including cells.
11 . An composition comprising:
an isolated nucleic acid consisting of a sequence a sequence that encodes for a biologically active mutant proteoglycan degrading polypeptide.
12 . The composition of claim 11 wherein the nucleic acid encodes for a proteoglycan degrading polypeptide that is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1), Chondroitinase ABC Type II, (SEQ ID NO: 27), Chondroitinase AC, (SEQ ID NO: 5), and Chondroitinase B, (SEQ ID NO: 12), hyaluronidase 1, (SEQ ID NO: 30), hyaluronidase 2, (SEQ ID NO: 31), hyaluronidase 3, (SEQ ID NO: 32), or hyaluronidase 4, (SEQ ID NO: 33).
13 . The composition of claim 11 wherein the nucleic acid encodes for a proteoglycan degrading polypeptide that is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1), Chondroitinase ABC Type II, (SEQ ID NO: 27), Chondroitinase AC, (SEQ ID NO: 5), and Chondroitinase B, (SEQ ID NO: 12)
14 . The composition of claim 11 wherein the nucleic acid encodes for a proteoglycan degrading polypeptide that is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1)
15 . The composition of claim 11 wherein the nucleic acid encodes for a proteoglycan degrading polypeptide that is a mutant of Chondroitinase ABC Type II, (SEQ ID NO: 27).
16 . The composition of claim 11 wherein the nucleic acid encodes for a polypeptide that degrades a proteoglycan in a tissue of the central nervous system.
17 . The composition of claim 11 wherein the nucleic acid encodes polypeptide that degrades chondroitin sulfate proteoglycan.
18 . The composition of claim 11 further including cells.
19 . A composition comprising:
a polypeptide comprising the amino acid sequence of a biologically active mutant proteoglycan degrading polypeptide.
20 . The composition of claim 19 wherein the proteoglycan degrading polypeptide is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1), Chondroitinase ABC Type II, (SEQ ID NO: 27), Chondroitinase AC, (SEQ ID NO: 5), and Chondroitinase B, (SEQ ID NO: 12), hyaluronidase 1, (SEQ ID NO: 30), hyaluronidase 2, (SEQ ID NO: 31), hyaluronidase 3, (SEQ ID NO: 32), or hyaluronidase 4, (SEQ ID NO: 33).
21 . The composition of claim 19 wherein the proteoglycan degrading polypeptide is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1), Chondroitinase ABC Type II, (SEQ ID NO: 27), Chondroitinase AC, (SEQ ID NO: 5), or Chondroitinase B, SEQ ID NO: 12).
22 . The composition of claim 19 wherein the proteoglycan degrading polypeptide is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1).
23 . The composition of claim 19 wherein the proteoglycan degrading polypeptide is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 27).
24 . The composition of claim 19 proteoglycan degrading polypeptide is (SEQ ID NO: 2), (SEQ ID NO: 3), or (SEQ ID NO: 4).
25 . The composition of claim 19 wherein the polypeptide degrades a proteoglycan in a tissue of the central nervous system.
26 . The composition of claim 19 wherein the polypeptide degrades a chondroitin sulfate proteoglycan.
27 . The composition of claim 19 further including cells.
28 . The composition of claim 19 and a pharmaceutically acceptable excipient.
29 . The composition of claim 19 further including molecules which block the action of neurite growth inhibitors, molecules which promote neurite adhesion, diagnostic molecules or a combination of these.
30 . A method of treating a tissue, the method comprising:
administering a mutant proteoglycan degrading polypeptide composition to the tissue, said tissue including proteoglycan molecules, said composition degrading at least a portion of the proteoglycan in the tissue.
32 . The method of claim 30 wherein the tissue is from the CNS.
33 . The method of claim 30 wherein the proteoglycan degradation promotes diffusion of molecules into the tissue.
34 . The method of claim 30 further comprising the act of identifying tissue from a contusive spinal cord injury.
35 . The method of claim 30 wherein the composition promote neurite regeneration.
36 . The method of claim 30 wherein the composition further includes molecules which block the action of neurite growth inhibitors, molecules which promote neurite adhesion, diagnostic molecules or a combination of these.
37 . The method of claim 30 wherein the plasticity of the of the nervous system is improved.
38 . The method of claim 30 wherein the proteoglycan degrading polypeptide is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1), Chondroitinase ABC Type II, (SEQ ID NO: 27), Chondroitinase AC, (SEQ ID NO: 5), and Chondroitinase B, (SEQ ID NO: 12), hyaluronidase 1, (SEQ ID NO: 30), hyaluronidase 2, (SEQ ID NO: 31), hyaluronidase 3, (SEQ ID NO: 32), or hyaluronidase 4, (SEQ ID NO: 33).
39 . The method of claim 30 wherein the proteoglycan degrading polypeptide is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1), Chondroitinase ABC Type II, (SEQ ID NO: 27), Chondroitinase AC, (SEQ ID NO: 5), or Chondroitinase B, SEQ ID NO: 12).
40 . The method of claim 30 wherein the proteoglycan degrading polypeptide is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 1).
41 . The method of claim 30 wherein the proteoglycan degrading polypeptide is a mutant of chondroitinase ABC Type I, (SEQ ID NO: 27).
42 . The method of claim 30 proteoglycan degrading polypeptide is (SEQ ID NO: 2), (SEQ ID NO: 3), or (SEQ ID NO: 4).
43 . A purified chondroitinase mutant polypeptide that degrades a proteoglycan.Cited by (0)
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