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US4843063A Expired / Lapsed US ⏱️ 0.0 years remaining

Polypeptide cartilage-inducing factors found in bone

Assignee: Celtrix Pharmaceuticals Inc
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Filing: 1988-06-08
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Granted: 1989-06-27
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Expires: 2008-06-08
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Abstract

Abstract Two proteins that are found in bone and that have in vivo chondrogenic/osteogenic activity in combination with a co-factor are described. Both proteins also were active in combination with EGF in the in vitro TGF-β assay. Each has a molecular weight of approximately 26,000 daltons by SDS-PAGE. Each is reduced to a single polypeptide indicating that the proteins are probably homodimers. One has an N-terminal sequence identical to that of human placenta-derived TGF-β whereas the other has an N-terminal sequence that is different from that of TGF-β derived from human placenta. The two proteins may be purified to hmogeneity using RP-HPLC or acetic acid-urea gel electrophoresis.

Inventors

  • 👤 Saeid Seyedin
  • 👤 Thomas Thomas
  • 👤 Hanne Bentz
  • 👤 Larry Ellingsworth
  • 👤 Rosa Armstrong

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 14:59
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/495; A; A61; A61K; A61K35/00; A61K35/12; A61K35/32; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/841; Y10S930/00; Y10S930/01; Y10S930/12

Claims Analysis

Total Claims: 11
Claim 1
Independent Claim 89 words
A method of promoting proliferation of cells in an animal comprising administering to the animal a composition comprising a TGF-beta activating agent, a pharmaceutically acceptable carrier, and a polypeptide that (a) is found in mammalian bone, (b) is active in the TGF-beta assay, (c) is a co-factor for inducing cartilage formation in vivo, (d) is a dimer having an approximate molecular weight of 26,000 daltons as determined by SDS-PAGE, and (e) is substantially pure, wherein said polypeptide and activating agent are present in amounts sufficient to promote bone growth.
Claim 2
Independent Claim 89 words
A method of promoting proliferation of cells in an animal comprising administering to the animal a composition comprising a TGF-beta activating agent, a pharmaceutically acceptable carrier, and a polypeptide that (a) is found in mammalian bone, (b) is active in the TGF-beta assay, (c) is a co-factor for inducing cartilage formation in vivo, (d) is a dimer having an approximate molecular weight of 26,000 daltons as determined by SDS-PAGE, and (e) is substantially pure, wherein said polypeptide and activating agent are present in amounts sufficient to promote bone growth.
Claim 3
Dependent Claim 17 words
The method of claim 1 wherein each chain of said dimer has the following N-terminal sequence: Ala-Leu-Asp-Thr-Asn-Tyr-Cys-Phe-Ser-(Ser)-Thr-Glu-Lys-Asn-Cys-Cys-Val-Arg-Gln-Leu-Tyr-Ile-Asp-Phe-Arg-Lys-Asp-Leu-Gly-Trp-.
Claim 4
Independent Claim 109 words
A method for inducing cartilage and bone formation for repairing, replacing, and or augmenting cartilage and bone tissue in animals, which method comprises: administering to a mammal in need of bone repair, replacement, or augmentation a composition comprising a TGF-beta activating agent, a pharmaceutically acceptable excipient, and a polypeptide the (a) is found in mammalian bone, (b) is active in the TGF-beta assay, (c) is a co-factor for inducing cartilage formation in vivo, (d) is a dimer having an approximate molecular weight of 26,000 daltons as determined by SDS-PAGE, and (e) is substantially pure, wherein said polypeptide and activating agent are present in amounts sufficient to promote bone growth.
Claim 5
Independent Claim 109 words
A method for inducing cartilage and bone formation for repairing, replacing, and or augmenting cartilage and bone tissue in animals, which method comprises: administering to a mammal in need of bone repair, replacement, or augmentation a composition comprising a TGF-beta activating agent, a pharmaceutically acceptable excipient, and a polypeptide the (a) is found in mammalian bone, (b) is active in the TGF-beta assay, (c) is a co-factor for inducing cartilage formation in vivo, (d) is a dimer having an approximate molecular weight of 26,000 daltons as determined by SDS-PAGE, and (e) is substantially pure, wherein said polypeptide and activating agent are present in amounts sufficient to promote bone growth.
Claim 6
Dependent Claim 17 words
The method of claim 3 wherein each chain of said dimer has the following N-terminal sequence: Ala-Leu-Asp-Thr-Asn-Tyr-Cys-Phe-Ser-(Ser)-Thr-Glu-Lys-Asn-Cys-Cys-Val-Arg-Gln-Leu-Tyr-Ile-Asp-Phe-Arg-Lys-Asp-Leu-Gly-Trp-.
Claim 7
Independent Claim 89 words
A method for treating osteoporosis or osteopetrosis, which comprises: systemically administering an effective amount of a composition comprising a TGF-beta activating agent, a pharmaceutically acceptable excipient, and a polypeptide that (a) is found in mammalian bone, (b) is active in the TGF-beta assay, (c) is a co-factor for inducing cartilage formation in vivo, (d) is a dimer having an approximate molecular weight of 26,000 daltons as determined by SDS-PAGE, and (e) is substantially pure, wherein said polypeptide and activating agent are present in amounts sufficient to promote bone growth.
Claim 8
Independent Claim 89 words
A method for treating osteoporosis or osteopetrosis, which comprises: systemically administering an effective amount of a composition comprising a TGF-beta activating agent, a pharmaceutically acceptable excipient, and a polypeptide that (a) is found in mammalian bone, (b) is active in the TGF-beta assay, (c) is a co-factor for inducing cartilage formation in vivo, (d) is a dimer having an approximate molecular weight of 26,000 daltons as determined by SDS-PAGE, and (e) is substantially pure, wherein said polypeptide and activating agent are present in amounts sufficient to promote bone growth.
Claim 9
Dependent Claim 17 words
The method of claim 5 wherein each chain of said dimer has the following N-terminal sequence: Ala-Leu-Asp-Thr-Asn-Tyr-Cys-Phe-Ser-(Ser)-Thr-Glu-Lys-Asn-Cys-Cys-Val-Arg-Gln-Leu-Tyr-Ile-Asp-Phe-Arg-Lys-Asp-Leu-Gly-Trp-.
Claim 10
Dependent Claim 17 words
The method of claim 3 wherein each chain of said dimer has the following N-terminal sequence: Ala-Leu-Asp-Ala-Tyr-Cys-Phe-Arg-Asn-Val-Gln-Asp-Asn-Cys-Cys-Leu-Arg-Pro-Leu-Tyr-Ile-Asp-Phe-Lys-Arg-Asp-Leu-Gly-Trp.
Claim 11
Dependent Claim 17 words
The method of claim 5 wherein each chain of said dimer has the following N-terminal sequence: Ala-Leu-Asp-Ala-Ala-Tyr-Cys-Phe-Arg-Asn-Val-Gln-Asp-Asn-Cys-Cys-Leu-Arg-Pro-Leu-Tyr-Ile-Asp-Phe-Lys-Arg-Asp-Leu-Gly-Trp.

References Cited (Backward Citations)

US3458397A Cited
US4294753A Cited
US4455256A Cited
US4394370A Cited
WO1984001106A1 Cited
US4434094A Cited
EP0128849A1 Cited
US4563350A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1992-06-26 1992-12-26 1993-06-27 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1996-06-26 1996-12-26 1997-06-27 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2000-06-26 2000-12-26 2001-06-27 $7700.00 Window Closed / Lapsed

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