US5344654A
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Prosthetic devices having enhanced osteogenic properties
Assignee: Creative Biomolecules Inc
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Filing: 1992-06-16
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Granted: 1994-09-06
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Expires: 2012-06-16
Abstract
Abstract A prosthetic device comprising a prosthesis coated with substantially pure osteogenic protein is disclosed. A method for biologically fixing prosthetic devices in vivo is also disclosed. In this method, a prosthesis is implanted in an individual in contact with a substantially pure osteogenic protein, enhancing the strength of the bond between the prosthesis and the existing bone at the joining site.
Inventors
- 👤 David C. Rueger
- 👤 Thangavel Kuberasampath
- 👤 Hermann Oppermann
- 👤 Engin Ozkaynak
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 05:06
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/24; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1875; A61K6/00; A61K6/20; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024; A61L27/227; A61L27/28; A61L27/34; A61L27/50; A61L27/56; A61P; 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; A61L2430/00; A61L2430/02; Y; Y10; Y10S; Y10S525/00; Y10S525/937
Claims Analysis
Total Claims: 38
Claim 1
Independent Claim
149 words
A method for promoting in vivo osseointegration of an implantable, prosthetic device, the method comprising the steps of: providing on a surface of the prosthetic device substantially pure osteogenic protein, and implanting the device in a mammal at a site wherein bone tissue and said surface are maintained at least partially in contact for a time sufficient to permit enhanced bone tissue growth between said tissue and said device; wherein said osteogenic protein is a basic protein comprising a pair of polypeptide chains, one of said polypeptide chains comprising an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation when disposed in a matrix and implanted in a mammal.
Claim 2
Independent Claim
149 words
A method for promoting in vivo osseointegration of an implantable, prosthetic device, the method comprising the steps of: providing on a surface of the prosthetic device substantially pure osteogenic protein, and implanting the device in a mammal at a site wherein bone tissue and said surface are maintained at least partially in contact for a time sufficient to permit enhanced bone tissue growth between said tissue and said device; wherein said osteogenic protein is a basic protein comprising a pair of polypeptide chains, one of said polypeptide chains comprising an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation when disposed in a matrix and implanted in a mammal.
Claim 3
Dependent Claim
171 words
In the method of repairing the skeletal system of a mammal comprising surgically implanting in contact with bone tissue a prosthetic device, and permitting the device and the bone tissue to integrate to form a weight bearing skeletal component, the improvement comprising: providing substantially pure osteogenic protein on a surface of said device prior to its implantation thereby to promote enhanced bone tissue growth into said device and to improve the tensile strength of the junction between the bone and said device; wherein said protein is an osteogenically active protein, characterized in that the protein is a basic protein comprising a pair of polypeptide chains, one of said polypeptide chains comprising an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation when disposed in a matrix and implanted in a mammal.
Claim 4
Dependent Claim
171 words
In the method of repairing the skeletal system of a mammal comprising surgically implanting in contact with bone tissue a prosthetic device, and permitting the device and the bone tissue to integrate to form a weight bearing skeletal component, the improvement comprising: providing substantially pure osteogenic protein on a surface of said device prior to its implantation thereby to promote enhanced bone tissue growth into said device and to improve the tensile strength of the junction between the bone and said device; wherein said protein is an osteogenically active protein, characterized in that the protein is a basic protein comprising a pair of polypeptide chains, one of said polypeptide chains comprising an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation when disposed in a matrix and implanted in a mammal.
Claim 5
Dependent Claim
43 words
The method of claim 1 or 2 wherein said surface of said prosthetic device further comprises hydroxylapatite, collagen, homopolymers or copolymers of glycolic acid, lactic acid or butyric acid and derivatives thereof, tricalcium phosphate or other calcium phosphate, metal oxides or combinations thereof.
Claim 6
Independent Claim
16 words
The method of claims 1 or 2 wherein the prosthetic device comprises a porous, metallic material.
Claim 7
Dependent Claim
25 words
The method of claim 1 or 2 wherein said dimeric osteogenic protein is produced by recombinant DNA in a host cell and is isolated therefrom.
Claim 8
Dependent Claim
110 words
The method of claim 1 or 2 wherein the osteogenic protein is an osteogenically active dimeric protein expressed from recombinant DNA in a host cell, further characterized in that the protein comprises a pair of oxidized subunits disulfide bonded to produce a dimeric species, one of said subunits having an amino acid sequence encoded by a nucleic acid capable of hybridizing to a nucleic acid encoding OPS (residues 335 to 431 of Seq. ID No. 1) under stringent hybridization conditions, such that the disulfide bonded dimeric species comprising said subunit has a conformation capable of inducing endochondral bone formation in a mammal when disposed on the surface of said device.
Claim 9
Dependent Claim
12 words
The method of claim 5 wherein said dimeric osteogenic protein is unglycosylated.
Claim 10
Dependent Claim
32 words
The method of claim 1 or 2 wherein each said polypeptide chain of said protein comprises an amino acid sequence sharing greater than 65% identity with an amino acid sequence comprising OPS.
Claim 11
Dependent Claim
31 words
The method of claim 8 wherein the amino acid sequence of one of said polypeptide chains comprises the amino acid sequence defined by residues 335-431 of Seq. ID No. 1 (OPS).
Claim 12
Dependent Claim
25 words
The method of claim 8 wherein both said polypeptide chains comprise the amino acid sequence defined by residues 335-431 of Seq. ID No. 1 (OPS.)
Claim 13
Dependent Claim
25 words
The method of claim 10 wherein both said polypeptide chains comprise the amino acid sequence of residues 318-431 of Seq. ID No. 1 (OP1-16 Val.)
Claim 14
Dependent Claim
146 words
An improved prosthetic device for repairing mammalian skeletal defects, injuries, or anomalies comprising a rigid prosthetic implant having a porous or non-porous surface region for implantation adjacent bone tissue, wherein the improvement comprises: substantially pure osteogenically active osteogenic protein disposed on said surface region in an amount sufficient to promote enhanced bone tissue growth into said surface; wherein said protein is an osteogenically active protein, characterized in that the protein is a basic protein comprising a pair of polypeptide chains, one of said polypeptide chains comprising an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation when disposed in a matrix and implanted in a mammal.
Claim 15
Dependent Claim
146 words
An improved prosthetic device for repairing mammalian skeletal defects, injuries, or anomalies comprising a rigid prosthetic implant having a porous or non-porous surface region for implantation adjacent bone tissue, wherein the improvement comprises: substantially pure osteogenically active osteogenic protein disposed on said surface region in an amount sufficient to promote enhanced bone tissue growth into said surface; wherein said protein is an osteogenically active protein, characterized in that the protein is a basic protein comprising a pair of polypeptide chains, one of said polypeptide chains comprising an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation when disposed in a matrix and implanted in a mammal.
Claim 16
Dependent Claim
15 words
The device of claim 12 wherein said surface of said prosthetic device further comprises hydroxylapatite.
Claim 17
Dependent Claim
23 words
The device of claim 12 wherein said dimeric osteogenic protein is produced by recombinant DNA in a host cell and is isolated therefrom.
Claim 18
Dependent Claim
12 words
The device of claim 14 wherein said dimeric osteogenic protein is unglycosylated.
Claim 19
Dependent Claim
68 words
The device of claim 12 wherein one of said polypeptide chains comprises an amino acid sequence encoded by a nucleic acid capable of hybridizing to a nucleic acid encoding OPS (residues 335-431 of Seq. ID No. 1), such that the disulfide bonded dimeric species comprising said polypeptide chain has a conformation capable of inducing endochondral bone formation in a mammal when disposed on the surface of said device.
Claim 20
Dependent Claim
38 words
The device of claim 12 wherein each of said polypeptide chains comprises an amino acid sequence sharing greater than 65% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS).
Claim 21
Dependent Claim
23 words
The device of claim 17 wherein one of said polypeptide chains of said protein comprises residues 335-431 of Seq. ID No. 1 (OPS).
Claim 22
Dependent Claim
25 words
The device of claim 17 wherein both said polypeptide chains comprise the amino acid sequence defined by residues 335-431 of Seq. ID No. 1 (OPS).
Claim 23
Dependent Claim
26 words
The device of claim 19 wherein both said polypeptide chains comprise the amino acid sequence defined by residues 318-431 of Seq. ID No. 1 (OP1-16 Val.)
Claim 24
Dependent Claim
13 words
The device of claim 12 wherein the prosthesis comprises a porous metallic material.
Claim 25
Dependent Claim
26 words
The device of claim 12 wherein the prosthesis comprises a contoured implantable portion for insertion into an orifice having plural indentations transverse to its longitudinal axis.
Claim 26
Dependent Claim
9 words
The device of claim 22 comprising a dental implant.
Claim 27
Independent Claim
190 words
A method for promoting in vivo osseointegration of a prosthetic device into an orifice of a bone, comprising the steps of: providing a prosthetic device having a contoured implantable portion for insertion into said orifice, said contoured portion having plural indentations transverse to its longitudinal axis, and implanting into the orifice the contoured portion of the prosthetic device and a bond growth composition comprising a substantially pure osteogenic protein combined with a matrix material which induces bone growth in said indentations, osseointegration between the bone and the prosthetic device, and osseointegration of new bone induced by said composition and said bone; wherein said protein is an osteogenically active protein, characterized in that the protein is a basic protein comprising a pair of polypeptide chains, one of said polypeptide chains comprising an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation when disposed in a matrix and implanted in a mammal.
Claim 28
Independent Claim
190 words
A method for promoting in vivo osseointegration of a prosthetic device into an orifice of a bone, comprising the steps of: providing a prosthetic device having a contoured implantable portion for insertion into said orifice, said contoured portion having plural indentations transverse to its longitudinal axis, and implanting into the orifice the contoured portion of the prosthetic device and a bond growth composition comprising a substantially pure osteogenic protein combined with a matrix material which induces bone growth in said indentations, osseointegration between the bone and the prosthetic device, and osseointegration of new bone induced by said composition and said bone; wherein said protein is an osteogenically active protein, characterized in that the protein is a basic protein comprising a pair of polypeptide chains, one of said polypeptide chains comprising an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation when disposed in a matrix and implanted in a mammal.
Claim 29
Dependent Claim
14 words
The method of claim 24 wherein the contoured portion comprises a porous metallic material.
Claim 30
Dependent Claim
15 words
The method of claim 25 wherein the osteogenic protein enhances bone ingrowth into said pores.
Claim 31
Dependent Claim
22 words
The device of claim 24 or 29 wherein said protein is produced by recombinant DNA in a host and is isolated therefrom.
Claim 32
Dependent Claim
10 words
The device of claim 27 wherein said protein is unglycosylated.
Claim 33
Independent Claim
179 words
A device for promoting in vivo osseointegration of a prosthesis into an orifice of a bone, comprising a rigid prosthetic implant having a contoured portion for insertion into said orifice, said contoured portion having plural indentations transverse to its longitudinal axis, and a bone growth composition comprising a substantially pure osteogenic protein combined with a matrix material which induces bone growth in said indentations, osseointegration between the bone and the prosthetic implant and osseointegration of new bone induced by said composition and said bone; wherein said protein is an osteogenically active protein characterized in that the protein is a basic, dimeric protein and comprises a pair of polypeptide chains, one of said polypeptide chains having an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation in association with said contoured portion of said prosthesis when implanted in a mammal.
Claim 34
Independent Claim
179 words
A device for promoting in vivo osseointegration of a prosthesis into an orifice of a bone, comprising a rigid prosthetic implant having a contoured portion for insertion into said orifice, said contoured portion having plural indentations transverse to its longitudinal axis, and a bone growth composition comprising a substantially pure osteogenic protein combined with a matrix material which induces bone growth in said indentations, osseointegration between the bone and the prosthetic implant and osseointegration of new bone induced by said composition and said bone; wherein said protein is an osteogenically active protein characterized in that the protein is a basic, dimeric protein and comprises a pair of polypeptide chains, one of said polypeptide chains having an amino acid sequence sharing greater than 60% identity with the amino acid sequence defined by residues 335 to 431 of Seq. ID No. 1 (OPS) such that said pair of polypeptide chains, when disulfide bonded to produce a dimeric species, has a conformation capable of inducing endochondral bone formation in association with said contoured portion of said prosthesis when implanted in a mammal.
Claim 35
Dependent Claim
14 words
The device of claim 29 wherein the contoured portion comprises a porous metallic material.
Claim 36
Dependent Claim
15 words
The device of claim 30 wherein the osteogenic protein enhances bone ingrowth into said pores.
Claim 37
Dependent Claim
44 words
The device of claim 29 wherein said matrix material is selected from the group consisting of hydroxylapatite, collagen, polymers or copolymers of glycolic acid, lactic acid or butyric acid, tricalcium phosphate or other calcium phosphates, metal oxides, demineralized guanidine extracted bone and combinations thereof.
Claim 38
Dependent Claim
9 words
The device of claim 29 comprising a dental implant.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-09-05 | 1998-03-07 | 1998-09-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-09-05 | 2002-03-07 | 2002-09-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-09-05 | 2006-03-07 | 2006-09-06 | $7700.00 | Window Closed / Lapsed |