US5948428A
Expired / Lapsed
US
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Compositions and therapeutic methods using morphogenic proteins and stimulatory factors
Assignee: MARIEL THERAPEUTICS Inc
•
Filing: 1996-12-06
•
Granted: 1999-09-07
•
Expires: 2016-12-06
Abstract
Abstract The present invention provides pharmaceutical compositions comprising a morphogenic protein stimulatory factor (MPSF) for improving the tissue inductive activity of morphogenic proteins, particularly those belonging to the BMP protein family. Methods for improving the tissue inductive activity of a morphogenic protein in a mammal using those compositions are provided. This invention also provides implantable morphogenic devices comprising a morphogenic protein and a MPSF disposed within a carrier, that are capable of inducing tissue formation in allogeneic and xenogeneic implants. Methods for inducing local tissue formation from a progenitor cell in a mammal using those devices are also provided. A method for accelerating allograft repair in a mammal using morphogenic devices is provided. This invention also provides a prosthetic device comprising a prosthesis coated with a morphogenic protein and a MPSF, and a method for promoting in vivo integration of an implantable prosthetic device to enhance the bond strength between the prosthesis and the existing target tissue at the joining site. Methods of treating tissue degenerative conditions in a mammal using the pharmaceutical compositions are also provided.
Inventors
- 👤 John C. Lee
- 👤 Lee-Chuan C. Yeh
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 18:33
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1875; A61K38/22; A61K38/30; A61L24/00; A61L24/04; A61L24/10; A61L24/108; A61P; A61P19/00; A61P43/00
Claims Analysis
Total Claims: 82
Claim 1
Independent Claim
194 words
A pharmaceutical composition for inducing tissue formation in a mammal, comprising: a) a morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell in the mammal; b) a morphogenic protein stimulatory factor (MPSF) capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell; and c) a pharmaceutically acceptable carrier; wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β, the MPSF may not be FGF, IGF-II, PDGF, estrogen, calcitonin, or vitamin D; when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β; and when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
Claim 2
Dependent Claim
194 words
A pharmaceutical composition for inducing tissue formation in a mammal, comprising: a) a morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell in the mammal; b) a morphogenic protein stimulatory factor (MPSF) capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell; and c) a pharmaceutically acceptable carrier; wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β, the MPSF may not be FGF, IGF-II, PDGF, estrogen, calcitonin, or vitamin D; when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β; and when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
Claim 3
Dependent Claim
39 words
The composition according to claim 1, wherein the morphogenic protein comprises a pair of subunits disulfide bonded to produce a dimeric species and wherein at least one of the subunits comprises a polypeptide belonging to the BMP protein family.
Claim 4
Dependent Claim
14 words
The composition according to claim 1, wherein the morphogenic protein is an osteogenic protein.
Claim 5
Dependent Claim
25 words
The composition according to any one of claims 1-3, wherein the morphogenic protein stimulatory factor comprises an agent that increases IGF-I bioactivity in the mammal.
Claim 6
Dependent Claim
22 words
The composition according to claim 4, wherein the agent that increases IGF-I bioactivity in the mammal is an altered form of IGF-I.
Claim 7
Dependent Claim
31 words
The composition according to claim 5, wherein the altered form of IGF-I is a truncated IGF-I molecule which has a decreased affinity for IGFBPs in the mammal compared to normal IGF-I.
Claim 8
Dependent Claim
16 words
The composition according to claim 6, wherein the altered form of IGF-I is des (1-3) IGF-I.
Claim 9
Dependent Claim
37 words
The composition according to any one of claims 1-3, wherein the morphogenic protein stimulatory factor is present in an amount capable of synergistically stimulating the ability of the morphogenic protein to induce tissue formation in the mammal.
Claim 10
Dependent Claim
37 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises a polypeptide selected from the group consisting of: BMP-2, BMP-4, BMP-5, BMP-6, BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, and BMP-13, COP-5, COP-7.
Claim 11
Dependent Claim
27 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises a polypeptide selected from the group consisting of OP-1, BMP-2, BMP-4 and BMP-6.
Claim 12
Dependent Claim
26 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises a polypeptide selected from the group consisting of OP-1, BMP-5 and BMP-6.
Claim 13
Dependent Claim
15 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1.
Claim 14
Dependent Claim
41 words
The composition according to any one of claims 1-3, wherein the morphogenic protein is present at a concentration of at least about 1 ng/ml, and the morphogenic protein stimulatory factor is present at a concentration of at least about 0.01 ng/ml.
Claim 15
Dependent Claim
50 words
The composition according to claim 12, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises IGF-I or an altered form of IGF-I at a concentration of from about 0.1 ng/ml to about 50 ng/ml.
Claim 16
Dependent Claim
11 words
The composition according to claim 14, comprising 200 ng/ml of OP-1.
Claim 17
Dependent Claim
205 words
A morphogenic device for implantation in a mammal, the device comprising: a) an implantable biocompatible carrier, b) a morphogenic protein disposed in the carrier, the morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell, and c) a morphogenic protein stimulatory factor (MPSF) disposed in the carrier, the MPSF capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell; wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β, the MPSF may not be FGF, IGF-II, PDGF, estrogen or calcitonin, or vitamin D; when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β; and when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
Claim 18
Dependent Claim
205 words
A morphogenic device for implantation in a mammal, the device comprising: a) an implantable biocompatible carrier, b) a morphogenic protein disposed in the carrier, the morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell, and c) a morphogenic protein stimulatory factor (MPSF) disposed in the carrier, the MPSF capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell; wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β, the MPSF may not be FGF, IGF-II, PDGF, estrogen or calcitonin, or vitamin D; when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β; and when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
Claim 19
Dependent Claim
40 words
The morphogenic device according to claim 16, wherein the morphogenic protein comprises a pair of subunits disulfide bonded to produce a dimeric species, and wherein at least one of the subunits comprises a polypeptide belonging to the BMP protein family.
Claim 20
Dependent Claim
15 words
The morphogenic device according to claim 16, wherein the morphogenic protein is an osteogenic protein.
Claim 21
Independent Claim
25 words
The device according to any one of claims 16-18, wherein the morphogenic protein stimulatory factor comprises an agent that increases IGF-I bioactivity in the mammal.
Claim 22
Independent Claim
17 words
The device according to any one of claims 16-18, wherein the carrier further comprises a biocompatible matrix.
Claim 23
Dependent Claim
15 words
The device according to claim 20, wherein the matrix comprises demineralized, protein-extracted, particulate, allogenic bone.
Claim 24
Dependent Claim
23 words
The device according to claim 20, wherein the matrix comprises mineral-free, delipidated Type I insoluble bone collagen particles, substantially depleted in noncollagenous protein.
Claim 25
Independent Claim
38 words
The device according to any one of claims 16-18, wherein the morphogenic protein comprises a polypeptide selected from the group consisting of: BMP-2, BMP-4, BMP-5, BMP-6, BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, and BMP-13, COP-5 and COP-7.
Claim 26
Independent Claim
27 words
The device according to any one of claims 16-18, wherein the morphogenic protein comprises a polypeptide selected from the group consisting of OP-1, BMP-2, BMP-4 and BMP-6.
Claim 27
Independent Claim
26 words
The device according to any one of claims 16-18, wherein the morphogenic protein comprises a polypeptide selected from the group consisting of OP-1, BMP-5 and BMP-6.
Claim 28
Independent Claim
15 words
The device according to any one of claims 16-18, wherein the morphogenic protein comprises OP-1.
Claim 29
Independent Claim
41 words
The device according to any one of claims 16-18, wherein the morphogenic protein is present at a concentration of at least about 1 ng/ml, and the morphogenic protein stimulatory factor is present at a concentration of at least about 0.01 ng/ml.
Claim 30
Dependent Claim
50 words
The device according to claim 19, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises IGF-I or an altered form of IGF-I at a concentration of from about 0.1 ng/ml to about 50 ng/ml.
Claim 31
Dependent Claim
18 words
The device according to claim 28, wherein the morphogenic protein comprises OP-1 at a concentration of 200 ng/ml.
Claim 32
Independent Claim
38 words
A method for improving the tissue inductive activity of a morphogenic protein on a mammalian progenitor cell comprising the step of coadministering to the cell a morphogenic protein stimulatory factor which comprises an agent that increases IGF-1 bioactivity.
Claim 33
Independent Claim
38 words
A method for improving the tissue inductive activity of a morphogenic protein on a mammalian progenitor cell comprising the step of coadministering to the cell a morphogenic protein stimulatory factor which comprises an agent that increases IGF-1 bioactivity.
Claim 34
Dependent Claim
22 words
The method according to claim 30, wherein the agent that increases IGF-I bioactivity in the mammal is an altered form of IGF-I.
Claim 35
Dependent Claim
31 words
The method according to claim 31, wherein the altered form of IGF-I is a truncated IGF-I molecule which has a decreased affinity for IGFBPs in the mammal compared to normal IGF-I.
Claim 36
Dependent Claim
16 words
The method according to claim 32, wherein the altered form of IGF-I is des (1-3) IGF-I.
Claim 37
Dependent Claim
29 words
The method according to claim 30, wherein the morphogenic protein comprises a disulfide bonded dimeric species comprising a polypeptide selected from the group consisting of OP-1, BMP-5 and BMP-6.
Claim 38
Dependent Claim
23 words
The composition according to claim 3, wherein the osteogenic protein is capable of inducing the progenitor cell to form endochondral or intramembranous bone.
Claim 39
Dependent Claim
28 words
The composition according to any one of claims 1-3, wherein the morphogenic protein is capable of inducing the progenitor cell to form cartilage, tendon/ligament-like tissue or neural-like tissue.
Claim 40
Dependent Claim
23 words
The composition according to claim 2, wherein the dimer is a homo- or heterodimer comprising at least one BMP-2, or OP-1 (BMP-7) subunit.
Claim 41
Dependent Claim
27 words
The composition according to any one of claims 1-3, wherein the morphogenic protein is produced by the expression of a recombinant DNA molecule in a host cell.
Claim 42
Dependent Claim
57 words
The composition according to any one of claims 1-3, wherein the morphogenic protein stimulatory factor comprises at least one compound selected from the group consisting of: insulin-like growth factor I (IGF-I), estradiol, fibroblast growth factor (FGF), growth hormone (GH), growth and differentiation factor (GDF), hydrocortisone (HC), insulin, progesterone, parathyroid hormone (PTH), vitamin D, retinoic acid and IL-6.
Claim 43
Dependent Claim
47 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises estradiol at a concentration of from about 0.05 nM to about 1000 nM.
Claim 44
Dependent Claim
48 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises growth hormone at a concentration of from about 5 ng/ml to about 1000 ng/ml.
Claim 45
Dependent Claim
47 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises hydrocortisone at a concentration of from about 0.05 nM to about 5.0 nM.
Claim 46
Dependent Claim
47 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises insulin at a concentration of from about 0.01 nM to about 1000 nM.
Claim 47
Dependent Claim
48 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises parathyroid hormone at a concentration of from about 10 nM to about 1000 nM.
Claim 48
Dependent Claim
47 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises progesterone at a concentration of from about 0.05 nM to about 1000 nM.
Claim 49
Dependent Claim
23 words
The device according to claim 18, wherein the osteogenic protein is capable of inducing the progenitor cell to form endochondral or intramembranous bone.
Claim 50
Independent Claim
27 words
The device according to any one of claims 16-18, wherein the morphogenic protein is capable of inducing the progenitor cell to form cartilage, tendon/ligament-like or neural-like tissue.
Claim 51
Dependent Claim
22 words
The device according to claim 17, wherein the dimer is a homo- or heterodimer comprising at least one BMP-2 or OP-1 subunit.
Claim 52
Independent Claim
27 words
The device according to any one of claims 16-18, wherein the morphogenic protein is produced by the expression of a recombinant DNA molecule in a host cell.
Claim 53
Dependent Claim
53 words
The device according to claim 49, wherein the morphogenic protein comprises at least one subunit comprising an amino acid sequence sufficiently duplicative of the amino sequence of COP-5 or COP-7 such that the species is capable of inducing tissue formation in a mammal when disposed in the carrier and implanted in the mammal.
Claim 54
Independent Claim
57 words
The device according to any one of claims 16-18, wherein the morphogenic protein stimulatory factor comprises at least one compound selected from the group consisting of: insulin-like growth factor I (IGF-I), estradiol, fibroblast growth factor (FGF), growth hormone (GH), growth and differentiation factor (GDF), hydrocortisone (HC), insulin, progesterone, parathyroid hormone (PTH), vitamin D, retinoic acid and IL-6.
Claim 55
Independent Claim
22 words
The device according to any one of claims 16-18, comprising a composition according to any one of claims 4-8, 14-15 or 40-45.
Claim 56
Dependent Claim
11 words
The device according to claim 46, wherein the MPSF is immobilized.
Claim 57
Dependent Claim
17 words
The device according to claim 28, wherein the IGF-I or the altered form of IGF-I is immobilized.
Claim 58
Dependent Claim
203 words
An implantable prosthetic device for repairing orthopedic defects, injuries or anomalies in a mammal, comprising: a) a prosthetic implant having a surface region implantable adjacent to a target tissue comprising a progenitor cell in the mammal; and b) a composition comprising an osteogenic protein and a morphogenic protein stimulatory factor (MPSF) disposed on the surface region in an amount sufficient to promote enhanced tissue growth into the surface; wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β, the MPSF may not be FGF, IGF-II, PDGF, estrogen, calcitonin, or vitamin D; when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β; and when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
Claim 59
Dependent Claim
203 words
An implantable prosthetic device for repairing orthopedic defects, injuries or anomalies in a mammal, comprising: a) a prosthetic implant having a surface region implantable adjacent to a target tissue comprising a progenitor cell in the mammal; and b) a composition comprising an osteogenic protein and a morphogenic protein stimulatory factor (MPSF) disposed on the surface region in an amount sufficient to promote enhanced tissue growth into the surface; wherein the MPSF is selected from the group consisting of hormones, cytokines, peptides and growth factors; and provided that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β, the MPSF may not be FGF, IGF-II, PDGF, estrogen, calcitonin, or vitamin D; when the progenitor cell is an osteoblast stimulated to form bone or cartilage and the morphogenic protein is a BMP homodimer, the MPSF may not be TGF-β; and when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
Claim 60
Dependent Claim
25 words
The prosthetic device according to claim 55, wherein the osteogenic protein is produced by the expression of a recombinant DNA molecule in a host cell.
Claim 61
Dependent Claim
55 words
The prosthetic device according to claim 55, wherein the morphogenic protein stimulatory factor comprises at least one compound selected from the group consisting of: insulin-like growth factor I (IGF-I), estradiol, fibroblast growth factor (FGF), growth hormone (GH), growth and differentiation factor (GDF), hydrocortisone (HC), insulin, progesterone, parathyroid hormone (PTH), vitamin D, retinoic acid and IL-6.
Claim 62
Dependent Claim
23 words
The prosthetic device according to claim 55, wherein the morphogenic protein stimulatory factor comprises an agent that increases IGF-I bioactivity in the mammal.
Claim 63
Dependent Claim
35 words
The prosthetic device according to claim 55, wherein the morphogenic protein stimulatory factor is present in an amount capable of synergistically stimulating the ability of the morphogenic protein to induce tissue formation in the mammal.
Claim 64
Dependent Claim
23 words
The prosthetic device according to claim 55, wherein the morphogenic protein stimulatory factor comprises an agent that increases IGF-I bioactivity in the mammal.
Claim 65
Dependent Claim
23 words
The prosthetic device according to claim 60, wherein the agent that increases IGF-I bioactivity in the mammal is an altered form of IGF-I.
Claim 66
Dependent Claim
32 words
The prosthetic device according to claim 61, wherein the altered form of IGF-I is a truncated IGF-I molecule which has a decreased affinity for IGFBPs in the mammal compared to normal IGF-I.
Claim 67
Dependent Claim
17 words
The prosthetic device according to claim 62, wherein the altered form of IGF-I is des (1-3) IGF-I.
Claim 68
Dependent Claim
35 words
The prosthetic device according to claim 55, wherein the morphogenic protein stimulatory factor is present in an amount capable of synergistically stimulating the ability of the morphogenic protein to induce tissue formation in the mammal.
Claim 69
Dependent Claim
38 words
The prosthetic device according to claim 55, wherein the osteogenic protein is capable of inducing the progenitor cell to form a tissue selected from the group consisting of endochondral bone, intramembranous bone, cartilage, tendon/ligament-like tissue and neural tissue.
Claim 70
Dependent Claim
36 words
The prosthetic device according to claim 55, wherein the osteogenic protein comprises a polypeptide selected from the group consisting of: BMP-2, BMP-4, BMP-5, BMP-6, OP-1 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, and BMP-13, COP-5 and COP-7.
Claim 71
Dependent Claim
31 words
The prosthetic device according to claim 55, wherein the osteogenic protein comprises a disulfide bonded dimeric species comprising a polypeptide selected from the group consisting of OP-1, BMP-2, BMP-4 and BMP-6.
Claim 72
Dependent Claim
30 words
The prosthetic device according to claim 55, wherein the osteogenic protein comprises a disulfide bonded dimeric species comprising a polypeptide selected from the group consisting of OP-1, BMP-5 and BMP-6.
Claim 73
Dependent Claim
13 words
The prosthetic device according to claim 55, wherein the osteogenic protein comprises OP-1.
Claim 74
Independent Claim
47 words
A method for inducing local tissue formation from a progenitor cell in a mammal comprising the step of implanting in the mammal a morphogenic device according to any one of claims 19-29 and 46-54 at a locus accessible to at least one progenitor cell of the mammal.
Claim 75
Dependent Claim
21 words
The method according to claim 70, wherein the locus is a jaw bone for use in periodontal or dental recontructive procedures.
Claim 76
Dependent Claim
30 words
The method according to claim 70, wherein the locus is a bone defect selected from the group consisting of a fracture, a non-union fracture a fusion and a bony void.
Claim 77
Dependent Claim
20 words
The method according to claim 70, wherein the locus is a joint for use in cartilage and soft tissue repair.
Claim 78
Dependent Claim
20 words
The method according to claim 70, wherein the locus is nervous system-associated tissue for use in neural regeneration and repair.
Claim 79
Independent Claim
36 words
A method of accelerating allograft repair and incorporation in a mammal, comprising the step of implanting at a locus in need of replacement bone a matrix-comprising device according to any one of claims 19-29 and 46-54.
Claim 80
Dependent Claim
15 words
The method according to claim 75, wherein the matrix of the device comprises allogenic bone.
Claim 81
Independent Claim
89 words
A method of promoting in vivo integration into a target tissue of a mammal an implantable prosthetic device, the method comprising the steps of: a) providing on a surface of the prosthetic device a composition according to any one of claims 1-15 and 35-46, and b) implanting the device in a mammal at a locus where the target tissue and the surface of the prosthetic device are maintained at least partially in contact for a time sufficient to permit enhanced tissue growth between the target tissue and the device.
Claim 82
Independent Claim
28 words
A method of treating a tissue degenerative condition in a mammal comprising the step of administering a pharmaceutical composition according to any one of claims 1-15 and 35-45.
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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) | 2002-09-06 | 2003-03-08 | 2003-09-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2006-09-06 | 2007-03-08 | 2007-09-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2010-09-06 | 2011-03-08 | 2011-09-07 | $7700.00 | Window Closed / Lapsed |