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EP0723013A2
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Biosynthetic osteogenic proteins and osteogenic devices containing them
Assignee: Stryker Corp
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Filing: 1989-04-07
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Granted: —
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Expires: 2009-04-07
Abstract
Abstract Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth and cartilage in mammals using the devices; 2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.
Inventors
- 👤 Hermann Opperman
- 👤 Thangavel Kuberasampath
- 👤 David C. Rueger
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 19:16
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61L27/24; A61L27/28; A61L27/34; A61L27/36; A61L27/3604; A61L27/3608; A61L27/3641; A61L27/3645; A61L27/365; A61L27/3654; A61L27/50; A61L27/56; A61P; A61P1/00; A61P1/02; A61P43/00; C; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/51; A61C; A61C8/00; A61C8/0003; A61C8/0004; A61C8/0006; A61F; A61F2310/00; A61F2310/00005; A61F2310/00365; A61K38/00; A61L2430/00; A61L2430/02
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
148 words
A process for producing active synthetic osteogenic protein, said protein comprising a pair of polypeptide chains disulphide bonded to produce a dimeric species, the process comprising the steps of: (a) producing a consensus amino acid sequence by comparing amino acid sequences of proteins of the TGF-beta gene family; (b) constructing a synthetic gene encoding the consensus amino acid sequence of step (a), for example by assembling chemically synthesised oligonucleotides; (c) introducing the synthetic gene of step (b) into a prokaryotic or eukaryotic host cell; (d) expressing the synthetic gene to produce a putative synthetic osteogenic protein; (e) assaying the putative synthetic osteogenic protein to determine whether it is active in inducing endochondral bone formation when implanted in a mammal, and (f) repeating steps (a) to (e) (or mutagenizing the synthetic gene and repeating steps (c) to (e)) if the putative synthetic osteogenic protein is inactive when so assayed.
Claim 2
Dependent Claim
46 words
The process of claim 1 wherein in step (a) the consensus nucleic acid sequence substantially preserves the disulphide crosslinking pattern present in the sequence: (a) (b) wherein the letters indicate the amino acid residues of standard single letter code and each X represents any amino acid.
Claim 3
Dependent Claim
40 words
The process of any one of the preceding claims wherein the consensus nucleic acid sequence comprises the sequence: (a) (b) wherein the letters indicate the amino acid residues of standard single letter code and each X represents any amino acid.
Claim 4
Dependent Claim
44 words
The process of any one of the preceding claims wherein the synthetic gene of step (b) comprises a nucleotide sequence which encodes a synthetic polypeptide chain having the same number of cysteine residues in the same relative positions as COP5, COP7, COP16 or OP1.
Claim 5
Dependent Claim
53 words
The process of any one of the preceding claims wherein the synthetic gene of step (b) comprises a nucleotide sequence which encodes a synthetic polypeptide chain sharing one or more amino acids at corresponding positions in any of the sequences: Vg1, DPP, OP1, CBMP-2a, CBMP-2b, CBMP-3, COP1, COP3, COP4, COP5, COP7 or COP16.
Claim 6
Dependent Claim
96 words
The process of any one of the preceding claims wherein the synthetic gene of step (b) comprises a nucleotide sequence which encodes a synthetic polypeptide chain comprising the amino acid sequence: (a) wherein, in each position where more than one amino acid is shown, any one of the amino acids shown may be in that position; or (b) wherein, in each position where more than one amino acid is shown, any one of the amino acids shown may be in that position; or (c) (d) (e) (f) (g) (h) (i) (j) (k) (l) (m) (n) (o)
Claim 7
Dependent Claim
23 words
The process of any one of the preceding claims wherein the protein comprises a synthetic polypeptide chain of less than 200 amino acids.
Claim 8
Dependent Claim
37 words
The process of any one of the preceding claims wherein the host cell of step (c) is a prokaryotic or eukaryotic host cell, for example E. coli , bacillus, yeasts or animal cells (e.g. CHO or myeloma).
Claim 9
Dependent Claim
19 words
The process of any one of the preceding claims wherein the synthetic osteogenic protein of step (d) is unglycosylated.
Claim 10
Dependent Claim
33 words
A composition comprising a synthetic osteogenic protein, said protein comprising a pair of polypeptide chains disulphide bonded to produce a dimeric species, producible by the process of any one of the preceding claims.
Claim 11
Dependent Claim
15 words
Antibodies reactive with an epitope of the synthetic osteogenic protein as defined in claim 10.
Claim 12
Dependent Claim
19 words
An osteogenic device comprising a matrix in which is disposed the synthetic osteogenic protein as defined in claim 10.
Claim 13
Dependent Claim
61 words
An osteogenic device for implantation in a mammal, the device comprising: (a) a biocompatible, in vivo biodegradable matrix defining a scaffold of dimensions sufficient to permit the attachment, proliferation and differentiation of migratory progenitor cells from the body of said mammal, and (b) the synthetic osteogenic protein as defined in claim 10 disposed in said matrix and accessible to said cells.
Claim 14
Dependent Claim
32 words
The device of claim 12 or claim 13 wherein said matrix comprises close-packed particulate matter having a particle size within the range of 70 to 850 um (e.g. 70 to 420 um).
Claim 15
Independent Claim
86 words
The device of any one of claims 12 to 14 wherein said matrix comprises: (a) allogenic bone, e.g. demineralized, protein extracted, particulate, allogenic bone, (b) demineralized, protein extracted, particulate, deglycosylated xenogenic bone, (c) demineralized, protein extracted, particulate xenogenic bone treated with HF or a protease, (d) materials selected from collagen, hydroxyapatite, calcium phosphates (e.g. tricalcium phosphate) and polymers comprising glycolic acid and/or lactic acid monomers, (e) a shape-retaining solid of loosely adhered particulate material e.g. collagen, (f) a porous solid or (g) masticated tissue, e.g. muscle.
Claim 16
Independent Claim
18 words
The device of any one of claims 12 to 15 disposed within the marrow cavity of allogenic bone.
Claim 17
Independent Claim
40 words
The device of any of claims 12 to 16 for use in therapy, e.g. for inducing local cartilage and/or endochondral bone formation in a mammal by implanting the device in a mammal at a locus accessible to migratory progenitor cells.
Claim 18
Dependent Claim
87 words
Use of the synthetic osteogenic protein as defined in claim 10 for the manufacture of: (a) a device according to any of claims 12 to 17, or (b) a medicament, the medicament or device being for inducing local cartilage and/or endochondral bone formation in a mammal by implanting the device in a mammal at a locus accessible to migratory progenitor cells for periodontal treatment, cartilage repair and for the treatment of osteoarthritis or to correct non-union fractures, acquired or congenital craniofacial and other skeletal or dental anomalies.
Claim 19
Dependent Claim
18 words
A synthetic nucleic acid molecule for use in the process of any one of claims 1 to 9.
Claim 20
Dependent Claim
26 words
A host cell for use in the process of any one of claims 1 to 9 which contains the synthetic nucleic acid molecule of claim 19.
Claim 21
Dependent Claim
28 words
The host cell of claim 20 which is a prokaryotic or eukaryotic host cell, for example E. coli , bacillus, yeasts or animal cells (e.g. CHO or myeloma).
References Cited (Backward Citations)
No citation records indexed.
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