Patent US5763416A successfully refreshed from Google Patents.
US5763416A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Gene transfer into bone cells and tissues
Assignee: University of Michigan (System)
•
Filing: 1994-02-18
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Granted: 1998-06-09
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Expires: 2014-02-18
Abstract
Abstract Disclosed are methods, compositions and devices for use in transferring nucleic acids into bone cells in situ. The transfer of an osteotropic gene into bone progenitor cells is described, which event is shown to stimulate the progenitor cells and to promote bone growth, repair and regeneration in vivo. These gene transfer protocols are suitable for use in transferring various nucleic acid materials into bone, and have many uses, for example, in treating various bone-related diseases and defects, such as, in promoting fracture repair, use in connection with implants, and in treating osteoporosis and osteogenesis imperfecta.
Inventors
- 👤 Jeffrey Bonadio
- 👤 Steven A. Goldstein
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 21:06
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024; A61K38/00; A61K38/16; A61K38/17; A61K38/22; A61K38/29; A61K47/00; A61K47/50; A61K47/69; A61K47/6953; A61K48/00; A61P; A61P19/00; A61P19/08; C; C07; C07K; C07K14/00; C07K14/435; C07K14/46; C07K14/47; C07K14/475; C07K14/51; C07K14/575; C07K14/635; C07K14/705; C07K14/72; C07K14/78; C12; C12N; C12N15/00; C12N15/09; C12N15/87; C07K2319/00; C12N2799/00; C12N2799/02; C12N2799/021; C12N2799/022
Claims Analysis
Total Claims: 84
Claim 1
Independent Claim
65 words
A method for transferring a nucleic acid segment into bone progenitor cells located within a bone progenitor tissue site of an animal, comprising contacting said tissue site with a composition comprising a nucleic acid segment and a structural bone-compatible matrix so as to transfer said nucleic acid segment into said cells, wherein said nucleic acid segment expresses a transcriptional or translational product in said cells.
Claim 2
Independent Claim
65 words
A method for transferring a nucleic acid segment into bone progenitor cells located within a bone progenitor tissue site of an animal, comprising contacting said tissue site with a composition comprising a nucleic acid segment and a structural bone-compatible matrix so as to transfer said nucleic acid segment into said cells, wherein said nucleic acid segment expresses a transcriptional or translational product in said cells.
Claim 3
Dependent Claim
42 words
The method of claim 1, wherein the contacting process comprises bringing said nucleic acid segment into contact with said structural bone-compatible matrix to form a matrix-nucleic acid segment composition and bringing said matrix-nucleic acid segment composition into contact with said tissue site.
Claim 4
Dependent Claim
14 words
The method of claim 1, wherein said nucleic acid segment is a DNA molecule.
Claim 5
Dependent Claim
14 words
The method of claim 1, wherein said nucleic acid segment is an RNA molecule.
Claim 6
Dependent Claim
16 words
The method of claim 1, wherein said nucleic acid segment is an antisense nucleic acid molecule.
Claim 7
Dependent Claim
29 words
The method of claim 1, wherein said nucleic acid segment is a linear nucleic acid molecule, a plasmid or a recombinant insert within the genome of a recombinant virus.
Claim 8
Dependent Claim
25 words
The method of claim 1, wherein said nucleic acid segment encodes a polypeptide or protein that stimulates bone progenitor cells when expressed in said cells.
Claim 9
Dependent Claim
33 words
The method of claim 1, wherein said structural bone-compatible matrix is a collagenous, metal, hydroxyapatite, bioglass, aluminate, bioceramic, acrylic ester polymer, lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 10
Dependent Claim
14 words
The method of claim 8, wherein said structural bone-compatible matrix is a titanium matrix.
Claim 11
Dependent Claim
17 words
The method of claim 9, wherein said structural bone-compatible matrix is a titanium matrix coated with hydroxylapatite.
Claim 12
Dependent Claim
14 words
The method of claim 8, wherein said structural bone-compatible matrix is a collagen preparation.
Claim 13
Independent Claim
45 words
A method of stimulating bone progenitor cells located within a bone progentor tissue site of an animal, comprising contacting said tissue site with a composition comprising an osteotropic gene and a structural bone-compatible matrix so as to promote expression of said gene in said cells.
Claim 14
Independent Claim
45 words
A method of stimulating bone progenitor cells located within a bone progentor tissue site of an animal, comprising contacting said tissue site with a composition comprising an osteotropic gene and a structural bone-compatible matrix so as to promote expression of said gene in said cells.
Claim 15
Dependent Claim
21 words
The method of claim 12, wherein expression of said gene in said cells stimulates said cells to promote bone tissue growth.
Claim 16
Dependent Claim
37 words
The method of claim 12, wherein the contacting process comprises bringing said osteotropic gene into contact with said structural bone-compatible matrix to form a matrix-gene composition and bringing said matrix-gene composition into contact with said tissue site.
Claim 17
Dependent Claim
49 words
The method of claim 12, wherein said osteotropic gene is in the form of plasmid DNA, a DNA insert within the genome of a recombinant adenovirus, a DNA insert within the genome of a recombinant adeno-associated virus (AAV) or a DNA insert within the genome of a recombinant retrovirus.
Claim 18
Dependent Claim
38 words
The method of claim 12, wherein said osteotropic gene is a parathyroid hormone (PTH) gene, a bone morphogenetic protein (BMP) gene, a growth factor gene, a growth factor receptor gene, a cytokine gene or a chemotactic factor gene.
Claim 19
Dependent Claim
55 words
The method of claim 16, wherein said osteotropic gene is a transforming growth factor (TGF) gene, a fibroblast growth factor (FGF) gene, a granulocyte/macrophage colony stimulating factor (GMCSF) gene, an epidermal growth factor (EGF) gene, a platelet derived growth factor (PDGF) gene, an insulin-like growth factor (IGF) gene, or a leukemia inhibitory factor (LIF) gene.
Claim 20
Dependent Claim
16 words
The method of claim 15, wherein said osteotropic gene is a TGF-α, TGF-β1 or TGF-β2 gene.
Claim 21
Dependent Claim
13 words
The method of claim 16, wherein said osteotropic gene is a PTH gene.
Claim 22
Dependent Claim
21 words
The method of claim 16, wherein said osteotropic gene is a BMP-2A, BMP-2B, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7 or BMP-8 gene.
Claim 23
Dependent Claim
15 words
The method of claim 20, wherein said osteotropic gene is a BMP-2 or BMP-4 gene.
Claim 24
Dependent Claim
33 words
The method of claim 12, wherein said structural bone-compatible matrix is a collagenous, metal, hydroxylapatite, bioglass, aluminate, bioceramic, acrylic ester polymer, lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 25
Dependent Claim
14 words
The method of claim 22, wherein said structural bone-compatible matrix is a titanium matrix.
Claim 26
Dependent Claim
17 words
The method of claim 23, wherein said structural bone-compatible matrix is a titanium matrix coated with hydroxylapatite.
Claim 27
Dependent Claim
14 words
The method of claim 22, wherein said structural bone-compatible matrix is a collagen preparation.
Claim 28
Dependent Claim
19 words
The method of claim 13, wherein said matrix-gene composition is applied to a bone fracture site in said animal.
Claim 29
Dependent Claim
19 words
The method of claim 13, wherein said matrix-gene composition is implanted within a bone cavity site in said animal.
Claim 30
Dependent Claim
24 words
The method of claim 27, wherein said bone cavity site is the result of dental or periodontal surgery or the removal of an osteosarcoma.
Claim 31
Dependent Claim
14 words
A composition comprising a nucleic acid segment in association with a structural bone-compatible matrix.
Claim 32
Dependent Claim
14 words
A composition comprising a nucleic acid segment in association with a structural bone-compatible matrix.
Claim 33
Dependent Claim
14 words
The composition of claim 29, wherein said nucleic acid segment is a DNA molecule.
Claim 34
Dependent Claim
14 words
The composition of claim 29, wherein said nucleic acid segment is an RNA molecule.
Claim 35
Dependent Claim
16 words
The composition of claim 29, wherein said nucleic acid segment is an antisense nucleic acid molecule.
Claim 36
Dependent Claim
29 words
The composition of claim 29, wherein said nucleic acid segment is a linear nucleic acid molecule, a plasmid or a recombinant insert within the genome of a recombinant virus.
Claim 37
Dependent Claim
25 words
The composition of claim 29, wherein said nucleic acid segment encodes a polypeptide or protein that stimulates bone progenitor cells when expressed in said cells.
Claim 38
Dependent Claim
35 words
The composition of claim 29, wherein said structural bone-compatible matrix is a collagenous, titanium, hydroxylapatite, hydroxylapatite-coated titanium, bioglass, aluminate, bioceramic, acrylic ester polymer lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 39
Dependent Claim
14 words
The composition of claim 35, wherein said structural bone-compatible matrix is a collagen preparation.
Claim 40
Dependent Claim
32 words
A composition comprising an osteotropic gene in association with a structural bone-compatible matrix, said composition being capable of stimulating bone growth when administered to a bone progenitor tissue site of an animal.
Claim 41
Dependent Claim
32 words
A composition comprising an osteotropic gene in association with a structural bone-compatible matrix, said composition being capable of stimulating bone growth when administered to a bone progenitor tissue site of an animal.
Claim 42
Dependent Claim
49 words
The composition of claim 37, wherein said osteotropic gene is in the form of plasmid DNA, a DNA insert within the genome of a recombinant adenovirus, a DNA insert within the genome of a recombinant adeno-associated virus (AAV) or a DNA insert within the genome of a recombinant retrovirus.
Claim 43
Dependent Claim
32 words
The composition of claim 37, wherein said osteotropic gene is a PTH, BMP-2A, BMP-2B, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, TGF-α, TGF-β1, TGF-β2, FGF, GMCSF, EGF, PDGF, IGF or a LIF gene.
Claim 44
Dependent Claim
18 words
The composition claim 39, wherein said osteotropic gene is a TGF-α, TGF-β1, TGF-β2, PTH, BMP-2 or BMP-4 gene.
Claim 45
Dependent Claim
33 words
The composition of claim 37, wherein said structural bone-compatible matrix is a collagenous, metal, hydroxyapatite, bioglass, aluminate, bioceramic, acrylic ester polymer, lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 46
Dependent Claim
14 words
The composition of claim 41, wherein said structural bone-compatible matrix is a titanium matrix.
Claim 47
Dependent Claim
17 words
The composition of claim 42, wherein said structural bone-compatible matrix is a titanium matrix coated with hydroxylapatite.
Claim 48
Dependent Claim
14 words
The composition of claim 41, wherein said structural bone-compatible matrix is a collagen preparation.
Claim 49
Dependent Claim
50 words
An osteotropic device, comprising an osteotropic gene capable of expression in bone progenitor cells, the gene associated with an amount of a structural bone-compatible matrix effective to absorb said gene, wherein said device is capable of stimulating bone formation when implanted within a bone progenitor tissue site of an animal.
Claim 50
Dependent Claim
50 words
An osteotropic device, comprising an osteotropic gene capable of expression in bone progenitor cells, the gene associated with an amount of a structural bone-compatible matrix effective to absorb said gene, wherein said device is capable of stimulating bone formation when implanted within a bone progenitor tissue site of an animal.
Claim 51
Dependent Claim
16 words
The device of claim 45, wherein said device is a titanium or a hydroxylapatite-coated titanium device.
Claim 52
Dependent Claim
19 words
The device of claim 45, wherein said device is shaped to join a bone fracture site in said animal.
Claim 53
Dependent Claim
19 words
The device of claim 45, wherein said device is shaped to fill a bone cavity site in said animal.
Claim 54
Dependent Claim
12 words
The device of claim 45, wherein said device is an artifical joint.
Claim 55
Dependent Claim
21 words
The method of claim 1, wherein said bone progenitor cells are stem cells, macrophages, fibroblasts, vascular cells, osteoblasts, chondroblasts or osteoclasts.
Claim 56
Dependent Claim
12 words
The method of claim 50, wherein said bone progenitor cells are fibroblasts.
Claim 57
Dependent Claim
17 words
The method of claim 2, wherein said nucleic acid segment is absorbed in said structural bone-compatible matrix.
Claim 58
Dependent Claim
17 words
The method of claim 2, wherein said nucleic acid segment is adsorbed to said structural bone-compatible matrix.
Claim 59
Dependent Claim
17 words
The method of claim 2, wherein said nucleic acid segment is impregnated within said structural bone-compatible matrix.
Claim 60
Dependent Claim
24 words
The method of claim 8, wherein said structural bone-compatible matrix is a lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 61
Dependent Claim
21 words
The method of claim 12, wherein said bone progenitor cells are stem cells, macrophages, fibroblasts, vascular cells, osteoblasts, chondroblasts or osteoclasts.
Claim 62
Dependent Claim
12 words
The method of claim 56, wherein said bone progenitor cells are fibroblasts.
Claim 63
Dependent Claim
17 words
The method of claim 14, wherein said nucleic acid segment is absorbed in said structural bone-compatible matrix.
Claim 64
Dependent Claim
17 words
The method of claim 14, wherein said nucleic acid segment is adsorbed to said structural bone-compatible matrix.
Claim 65
Dependent Claim
17 words
The method of claim 14, wherein said nucleic acid segment is impregnated within said structural bone-compatible matrix.
Claim 66
Dependent Claim
24 words
The method of claim 22, wherein said structural bone-compatible matrix is a lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 67
Independent Claim
64 words
A method of delivering a nucleic acid segment to a fibroblast cell located within a repair tissue site of an animal, comprising contacting said tissue site with a composition comprising a nucleic acid segment and a structural bone-compatible matrix to effect uptake of the nucleic acid segment into the fibroblast cell and to promote expression of a transcriptional or translational product in said cell.
Claim 68
Independent Claim
64 words
A method of delivering a nucleic acid segment to a fibroblast cell located within a repair tissue site of an animal, comprising contacting said tissue site with a composition comprising a nucleic acid segment and a structural bone-compatible matrix to effect uptake of the nucleic acid segment into the fibroblast cell and to promote expression of a transcriptional or translational product in said cell.
Claim 69
Independent Claim
84 words
A method of delivering at least one selected nucleic acid segment to a fibroblast cell located within a repair tissue site of an animal, comprising the steps of: (a) preparing a matrix-nucleic acid composition comprising at least one nucleic acid segment and a structural bone-compatible matrix; and (b) contacting said repair tissue site with the matrix-nucleic acid composition to effect uptake of the nucleic acid segment by the fibroblast cell wherein said nucleic acid segment expresses a transcriptional or translational product in said cell.
Claim 70
Independent Claim
84 words
A method of delivering at least one selected nucleic acid segment to a fibroblast cell located within a repair tissue site of an animal, comprising the steps of: (a) preparing a matrix-nucleic acid composition comprising at least one nucleic acid segment and a structural bone-compatible matrix; and (b) contacting said repair tissue site with the matrix-nucleic acid composition to effect uptake of the nucleic acid segment by the fibroblast cell wherein said nucleic acid segment expresses a transcriptional or translational product in said cell.
Claim 71
Dependent Claim
29 words
The method of claim 63, wherein said nucleic acid segment is a linear nucleic acid molecule, a plasmid or a recombinant insert within the genome of a recombinant virus.
Claim 72
Dependent Claim
35 words
The method of claim 63, wherein said structural bone-compatible matrix is a collagenous, metal, hydroxylapatite, hydroxylapatite-coated metal, bioglass, aluminate, bioceramic, acrylic ester polymer, lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 73
Dependent Claim
14 words
The method of claim 65, wherein said structural bone-compatible matrix is a collagenous matrix.
Claim 74
Dependent Claim
24 words
The method of claim 65, wherein said structural bone-compatible matrix is a lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 75
Dependent Claim
17 words
The composition of claim 29, wherein said nucleic acid segment is absorbed in said structural bone-compatible matrix.
Claim 76
Dependent Claim
17 words
The composition of claim 29, wherein said nucleic acid segment is adsorbed to said structural bone-compatible matrix.
Claim 77
Dependent Claim
17 words
The composition of claim 29, wherein said nucleic acid segment is impregnated within said structural bone-compatible matrix.
Claim 78
Dependent Claim
24 words
The composition of claim 35, wherein said structural bone-compatible matrix is a lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 79
Dependent Claim
16 words
The composition of claim 37, wherein said osteotropic gene is absorbed in said structural bone-compatible matrix.
Claim 80
Dependent Claim
16 words
The composition of claim 37, wherein said osteotropic gene is adsorbed to said structural bone-compatible matrix.
Claim 81
Dependent Claim
16 words
The composition of claim 37, wherein said osteotropic gene is impregnated within said structural bone-compatible matrix.
Claim 82
Dependent Claim
24 words
The composition of claim 41, wherein said structural bone-compatible matrix is a lactic acid polymer, glycolic acid polymer or lactic acid/glycolic acid polymer matrix.
Claim 83
Dependent Claim
13 words
The method of claim 19, wherein said osteotropic gene is a PTH1-34 gene.
Claim 84
Dependent Claim
13 words
The composition of claim 40, wherein said osteotropic gene is a PTH1-34 gene.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 2001-06-08 | 2001-12-08 | 2002-06-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-06-08 | 2005-12-08 | 2006-06-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-06-08 | 2009-12-08 | 2010-06-09 | $7700.00 | Window Closed / Lapsed |