US5750651A
Expired / Lapsed
US
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Cartilage and bone-inducing proteins
Assignee: Stryker Corp
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Filing: 1993-11-01
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Granted: 1998-05-12
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Expires: 2013-11-01
Abstract
Abstract Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth 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 Oppermann
- 👤 Thangavel Kuberasampath
- 👤 David C. Rueger
- 👤 Engin Ozkaynak
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 22:03
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; 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; A61L2430/06; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/84
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
112 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR25## or a naturally occurring mammalian variant thereof comprising at least 96 amino acids and having a molecular weight of approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, said dimeric protein having a conformation sufficient to induce cartilage and bone formation when combined with a matrix and implanted in a mammal.
Claim 2
Dependent Claim
112 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR25## or a naturally occurring mammalian variant thereof comprising at least 96 amino acids and having a molecular weight of approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, said dimeric protein having a conformation sufficient to induce cartilage and bone formation when combined with a matrix and implanted in a mammal.
Claim 3
Dependent Claim
112 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR26## or a naturally occurring mammalian variant thereof comprising at least 96 amino acids and having a molecular weight of approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in an unglycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, said dimeric protein having a conformation sufficient to induce cartilage and bone formation when combined with a matrix and implanted in a mammal.
Claim 4
Dependent Claim
112 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR26## or a naturally occurring mammalian variant thereof comprising at least 96 amino acids and having a molecular weight of approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in an unglycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, said dimeric protein having a conformation sufficient to induce cartilage and bone formation when combined with a matrix and implanted in a mammal.
Claim 5
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR27## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-1.
Claim 6
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR27## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-1.
Claim 7
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR28## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-3.
Claim 8
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR28## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-3.
Claim 9
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR29## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-4.
Claim 10
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR29## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-4.
Claim 11
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR30## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-5.
Claim 12
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR30## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-5.
Claim 13
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR31## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-7.
Claim 14
Dependent Claim
129 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR31## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as the six cysteine residues in COP-7.
Claim 15
Dependent Claim
125 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR32## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as in COP-16.
Claim 16
Dependent Claim
125 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce cartilage or bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains having less than about 200 amino acids and a sequence comprising ##STR32## or a biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having at least six cysteine residues in the same relative positions as in COP-16.
Claim 17
Dependent Claim
115 words
A protein produced by expression of recombinant DNA comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation which can induce cartilage or bone formation when combined with a matrix, wherein one of said polypeptide chains forming said dimeric species comprises the sequence ##STR33## or a naturally-occuring or biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having six cysteines residues in the same relative positions as the six cysteine residues in OP1.
Claim 18
Dependent Claim
115 words
A protein produced by expression of recombinant DNA comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation which can induce cartilage or bone formation when combined with a matrix, wherein one of said polypeptide chains forming said dimeric species comprises the sequence ##STR33## or a naturally-occuring or biosynthetic conservative amino acid substitution variant thereof comprising at least 96 amino acids and having a molecular weight approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, and having six cysteines residues in the same relative positions as the six cysteine residues in OP1.
Claim 19
Dependent Claim
85 words
An isolated protein comprising a pair of polypeptide chains disulfide bonded to form a dimeric protein having a conformation competent to induce cartilage and bone formation when implanted in a mammal in association with a matrix, each polypeptide chain having less than 200 amino acids and encoded by a DNA retrievable from a mammalian cDNA library by hybridization with a nucleic acid encoding an amino acid sequence comprising ##STR34## wherein said hybridization is performed in 5× SSPE, 10× Denhardt's mix, 0.5% SDS at 50° C.
Claim 20
Dependent Claim
85 words
An isolated protein comprising a pair of polypeptide chains disulfide bonded to form a dimeric protein having a conformation competent to induce cartilage and bone formation when implanted in a mammal in association with a matrix, each polypeptide chain having less than 200 amino acids and encoded by a DNA retrievable from a mammalian cDNA library by hybridization with a nucleic acid encoding an amino acid sequence comprising ##STR34## wherein said hybridization is performed in 5× SSPE, 10× Denhardt's mix, 0.5% SDS at 50° C.
Claim 21
Dependent Claim
20 words
The protein of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 further characterized as being glycosylated.
Claim 22
Dependent Claim
166 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains of said pair having at least 96 amino acids and less than about 200 amino acids, and having a molecular weight of approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, wherein each of said polypeptide chains is encoded by a DNA, one strand of which hybridizes selectively to: ##STR35## in 5× SSPE, 10× Denhardt's mix, 0.5% SDS at 50° C., and further wherein each of said polypeptide chains is further characterized as having at least six cysteine residues in the same relative positions as the six cysteine skeleton sequence: ##STR36## wherein each said X is an amino acid.
Claim 23
Dependent Claim
166 words
A protein, produced by expression of recombinant DNA in a host cell, comprising a pair of polypeptide chains disulfide bonded to form a dimeric species having a conformation competent to induce bone formation when combined with a matrix and implanted in a mammal, each of said polypeptide chains of said pair having at least 96 amino acids and less than about 200 amino acids, and having a molecular weight of approximately 14-16 kDa in an unglycosylated form or a molecular weight of approximately 16-18 kDa in a glycosylated form as determined by polyacrylamide gel electrophoresis under reducing conditions, wherein each of said polypeptide chains is encoded by a DNA, one strand of which hybridizes selectively to: ##STR35## in 5× SSPE, 10× Denhardt's mix, 0.5% SDS at 50° C., and further wherein each of said polypeptide chains is further characterized as having at least six cysteine residues in the same relative positions as the six cysteine skeleton sequence: ##STR36## wherein each said X is an amino acid.
Claim 24
Dependent Claim
40 words
The protein of claim 12 wherein each said polypeptide chains is further characterized as having at least seven cysteine residues in the same relative positions as the seven cysteine skeleton sequence: ##STR37## wherein each said X is an amino acid.
Claim 25
Dependent Claim
22 words
The protein of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 or 13 wherein said protein is unglycosylated.
Claim 26
Dependent Claim
11 words
The protein of claim 14 produced in a prokaryotic host cell.
Claim 27
Dependent Claim
14 words
The protein of claim 15, wherein said host cell is an E. coli cell.
Claim 28
Dependent Claim
27 words
The protein of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, wherein the protein is produced in an eukaryotic host cell.
Claim 29
Dependent Claim
17 words
The protein of claim 17 wherein said host cell is a mammalian cell or a Saccharomyces cell.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 2001-05-11 | 2001-11-10 | 2002-05-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-05-11 | 2005-11-10 | 2006-05-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-05-11 | 2009-11-10 | 2010-05-12 | $7700.00 | Window Closed / Lapsed |