US6180606B1
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Compositions with enhanced osteogenic potential, methods for making the same and uses thereof
Assignee: Isotis Orthobiologics Inc
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Filing: 1998-01-13
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Granted: 2001-01-30
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Expires: 2018-01-13
Abstract
Abstract Osteogenic compositions, and methods for preparing same, which compositions comprise a porous or semi-porous matrix, an osteogenic factor and an agent such as growth factors, nutrient factors, drugs, calcium-containing compounds, blood products, large molecular weight proteins, or combinations thereof. These materials can be used in a wide range of clinical procedures to replace and restore osseous or periodontal defects.
Inventors
- 👤 Charles C. Chen
- 👤 Steven R. Jefferies
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 04:01
CPC Classifications
A; A61; A61L; A61L31/00; A61L31/14; A61L31/16; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1841; A61K38/1875; A61K6/00; A61K6/80; A61K6/802; A61K6/831; A61K6/833; A61K6/838; A61K6/884; A61K6/891; A61L31/04; A61L31/043; A61L31/044; A61L31/047; A61L31/12; A61L31/125; A61L31/127; A61L31/146; A61L2300/00; A61L2300/40; A61L2300/412; A61L2300/414; A61L2300/45; Y; Y10; Y10S; Y10S128/00; Y10S128/08; Y10S530/00; Y10S530/827; Y10S530/84
Claims Analysis
Total Claims: 60
Claim 1
Independent Claim
61 words
An osteogenic composition having enhanced osteogenic potential, the composition comprising a porous or semi-porous matrix; at least one osteoinductive factor; and, at least one growth factor, nutrient factor, drug, calcium-containing compound, anti-inflammatory agent, antimicrobial agent, blood product, large molecular weight protein, or combination thereof present on or within the porous or semi-porous matrix or present on or within the osteoinductive factor.
Claim 2
Dependent Claim
61 words
An osteogenic composition having enhanced osteogenic potential, the composition comprising a porous or semi-porous matrix; at least one osteoinductive factor; and, at least one growth factor, nutrient factor, drug, calcium-containing compound, anti-inflammatory agent, antimicrobial agent, blood product, large molecular weight protein, or combination thereof present on or within the porous or semi-porous matrix or present on or within the osteoinductive factor.
Claim 3
Dependent Claim
16 words
The composition of claim 1 , wherein the porous or semi-porous matrix is resorbable or non-resorbable.
Claim 4
Dependent Claim
29 words
The composition of claim 1 , wherein the porous or semi-porous matrix comprises a form of a sponge, a membrane, a fibrous structure, a powder, a fleece, or particles.
Claim 5
Dependent Claim
20 words
The composition of claim 1 , wherein the at least one osteoinductive factor comprises mineralized, partially mineralized or remineralized bone.
Claim 6
Dependent Claim
15 words
The composition of claim 1 , wherein the at least one osteoinductive factor is particulate.
Claim 7
Dependent Claim
15 words
The composition of claim 1 , wherein the at least one osteoinductive factor is freeze-dried.
Claim 8
Dependent Claim
17 words
The composition of claim 1 , comprising a growth factor, which comprises a cytokine or a prostaglandin.
Claim 9
Dependent Claim
18 words
The composition of claim 1 , wherein the growth factor is of natural origin or is recombinantly produced.
Claim 10
Dependent Claim
15 words
The composition of claim 1 , comprising a combination of two or more growth factors.
Claim 11
Dependent Claim
20 words
The composition of claim 1 , wherein the at least one osteoinductive factor is the at least one growth factor.
Claim 12
Dependent Claim
41 words
The composition of claim 1 , wherein the matrix comprises collagen and the osteoinductive factor comprises demineralized bone particles, and wherein weight ratio of demineralized bone particles to collagen is 10% to 90% collagen, to 90% to 10% demineralized bone particles.
Claim 13
Dependent Claim
24 words
The composition of claim 1 , further comprising a glycoprotein, carbohydrate, cell culture media, a Bone Morphogenetic Factor, or combination of Bone Morphogenetic Factors.
Claim 14
Dependent Claim
56 words
The composition of claim 1 , wherein the matrix comprises human collagen and the osteoinductive factor comprises demineralized bone particles, and wherein the weight percent ratio of human collagen to demineralized bone particles is in a range of about 60% human collagen to 40% demineralized bone particles, to 10% human collagen to 90% demineralized bone particles.
Claim 15
Dependent Claim
40 words
The composition of claim 1 comprising a nutrient factor, wherein the nutrient factor is a vitamin, hormone, individual or combination of amino acids, carbohydrate or derivative thereof, fat or derivative thereof, alcohol or derivative thereof, inorganic salt, or trace element.
Claim 16
Dependent Claim
15 words
The composition of claim 1 comprising a nutrient factor, wherein the nutrient factor is glycerol.
Claim 17
Dependent Claim
29 words
The composition of claim 1 comprising a drug, wherein a weight ratio of the drug to the matrix is about 0.1 weight percent drug to 1 weight percent matrix.
Claim 18
Dependent Claim
22 words
The composition of claim 1 , comprising a blood product, wherein the blood product is fibrin, fibronectin, or a blood clotting factor.
Claim 19
Dependent Claim
27 words
The composition of claim 1 comprising a calcium-containing compound, wherein the calcium-containing compound is calcium hydroxide, calcium lactate, an inorganic calcium salt, or an organic calcium salt.
Claim 20
Dependent Claim
12 words
The composition of claim 1 , wherein the nutrient factor is collagen.
Claim 21
Dependent Claim
12 words
The composition of claim 1 , further comprising inorganic fillers or particles.
Claim 22
Dependent Claim
37 words
The composition of claim 20 , where the inorganic fillers or particles are hydroxyapatite, tri-calcium phosphate, ceramic glass, amorphous calcium phosphate, porous ceramic particles or powders, mesh titanium or titanium alloy, or particulate titanium or titanium alloy.
Claim 23
Dependent Claim
29 words
The composition of claim 1 , wherein the osteoinductive factor comprises demineralized bone particles, a Bone Morphogenetic Protein, an osteoinductive extract of demineralized bone matrix, or a combination thereof.
Claim 24
Dependent Claim
46 words
The composition of claim 22 , wherein the osteoinductive factor comprises a Bone Morphogenetic Protein which is Bone Morphogenetic Protein-2 (BMP-2), Bone Morphogenetic Protein-2a (BMP-2a), Bone Morphogenetic Protein-4 (BMP-4), Bone Morphogenetic Protein-5 (BMP-5), Bone Morphogenetic Protein-6 (BMP-6), Bone Morphogenetic Protein-7 (BMP-7), or Bone Morphogenetic Protein-8 (BMP-8).
Claim 25
Dependent Claim
59 words
The composition of claim 1 , comprising a growth factor wherein the growth factor is selected from the group consisting of: Transforming Growth Factor-Beta (TGF-β), Transforming Growth Factor-Alpha (TGF-α), Epidermal Growth Factor (EGF), Insulin Like Growth Factor-I or II, Interleukin-I (IL-I), Interferon, Tumor Necrosis Factor, Fibroblast Growth Factor (FGF), Platelet Derived Growth Factor (PDGF), and Nerve Growth Factor (NGF).
Claim 26
Dependent Claim
30 words
The composition of claim 24 , wherein the growth factor is Transforming Growth Factor-Beta (TGF-β), which is Transforming Growth Factor-Beta-1 (TGF-β1), Transforming Growth Factor-Beta-2 (TGF-β2), or Transforming Growth Factor-Beta-3 (TGF-β3).
Claim 27
Dependent Claim
37 words
The composition of claim 1 , wherein the porous or semi-porous matrix comprises the at least one growth factor, nutrient factor, drug, calcium-containing compound, anti-inflammatory agent, antimicrobial agent, blood product, large molecular weight protein, or combination thereof.
Claim 28
Dependent Claim
18 words
The composition of claim 26 , wherein the porous or semi-porous matrix is at least one nutrient factor.
Claim 29
Dependent Claim
17 words
The composition of claim 1 comprising a drug, wherein the drug is tetracycline or an antimicrobial agent.
Claim 30
Dependent Claim
18 words
The composition of claim 28 comprising an antimicrobial agent, wherein the antimicrobial agent is chlorahexadine or zinc citrate.
Claim 31
Dependent Claim
21 words
The composition of claim 1 comprising an anti-inflammatory agent, wherein the anti-inflammatory agent is a steroidal agent or a nonsteroidal agent.
Claim 32
Dependent Claim
17 words
The composition of claim 30 comprising a nonsteroidal anti-inflammatory agent, where the nonsteroidal anti-inflammatory agent is flurbiprofen.
Claim 33
Dependent Claim
24 words
The composition of claim 1 comprising a large molecular weight protein, wherein the large molecular weight protein is an enzyme or extracellular matrix protein.
Claim 34
Dependent Claim
21 words
The composition of claim 32 wherein the large molecular weight protein is an extracellular matrix protein which is laminin or fibronectin.
Claim 35
Dependent Claim
20 words
The composition of claim 1 , wherein the porous or semi-porous matrix is an organic material or an inorganic material.
Claim 36
Dependent Claim
19 words
The composition of claim 34 , wherein the porous or semi-porous matrix comprises a ceramic or a synthetic polymer.
Claim 37
Dependent Claim
29 words
The composition of claim 35 , wherein the porous or semi-porous matrix comprises a synthetic polymer which comprises polylactic acids, polyglycolic acids, or combinations of polylactic and polyglycolic acids.
Claim 38
Dependent Claim
23 words
The composition of claim 34 , wherein the porous or semi-porous matrix comprises an organic material which is polyamino acids, gelatin, or collagen.
Claim 39
Dependent Claim
19 words
The composition of claim 37 , wherein the porous or semi-porous matrix comprises collagen which is allogeneic or xenogeneic.
Claim 40
Dependent Claim
20 words
The composition of claim 37 , wherein the porous or semi-porous matrix comprises collagen which is atelopeptide or telopeptide collagen.
Claim 41
Dependent Claim
26 words
The composition of claim 37 , wherein the porous or semi-porous matrix comprises collagen, and wherein the collagen is human, bovine, equine, porcine or ovine collagen.
Claim 42
Dependent Claim
38 words
The composition of claim 40 wherein the collagen is bovine, and wherein the weight percent ratio of bovine collagen to demineralized bone particles is in a range of about 75% bovine collagen to about 25% demineralized bone particles.
Claim 43
Dependent Claim
63 words
The composition of claim 40 wherein the matrix comprises human collagen and the osteoinductive factor comprises Bone Morphogenetic Protein, and wherein the weight percent ratio of human collagen to Bone Morphogenetic Protein is in a range of about 1 weight unit Bone Morphogenetic Protein to 1 weight unit human collagen, to 1 weight unit Bone Morphogenetic Protein to 1000 weight units human collagen.
Claim 44
Dependent Claim
65 words
An osteogenic composition having enhanced osteogenic potential, the composition comprising a porous or semi-porous matrix of collagen; at least one osteoinductive factor which is demineralized bone particles, Bone Morphogenetic Protein-2 (BMP-2), Bone Morphogenetic Protein-7 (BMP-7) or a combination thereof; and, at least one growth factor wherein the growth factor is present on or within the matrix and/or is present on or within the osteoinductive factor.
Claim 45
Dependent Claim
65 words
An osteogenic composition having enhanced osteogenic potential, the composition comprising a porous or semi-porous matrix of collagen; at least one osteoinductive factor which is demineralized bone particles, Bone Morphogenetic Protein-2 (BMP-2), Bone Morphogenetic Protein-7 (BMP-7) or a combination thereof; and, at least one growth factor wherein the growth factor is present on or within the matrix and/or is present on or within the osteoinductive factor.
Claim 46
Dependent Claim
35 words
The composition of claim 43 , wherein the osteoinductive factor is bone particles, and wherein a weight ratio of collagen to demineralized bone is 10% to 90% collagen and 90% to 10% demineralized bone particles.
Claim 47
Dependent Claim
41 words
An osteogenic composition having enhanced osteogenic potential, the composition comprising a porous or semi-porous matrix of collagen; at least one osteoinductive factor; and, a Transforming Growth Factor-Beta (TGF-β) present on or within the matrix or on or within the osteoinductive factor.
Claim 48
Dependent Claim
41 words
An osteogenic composition having enhanced osteogenic potential, the composition comprising a porous or semi-porous matrix of collagen; at least one osteoinductive factor; and, a Transforming Growth Factor-Beta (TGF-β) present on or within the matrix or on or within the osteoinductive factor.
Claim 49
Dependent Claim
19 words
The composition of claim 45 wherein the porous or semi-porous matrix of collagen comprises the form of a sponge.
Claim 50
Dependent Claim
110 words
An osteogenic composition of claim 45 , the composition comprising: a porous or semi-porous matrix of collagen in the form of a sponge, wherein the collagen matrix in sponge form is about 75 weight percent of the composition; an osteoinductive factor which is demineralized bone powder, wherein the demineralized bone powder is about 25 weight percent of the composition; and, a Transforming Growth Factor-Beta (TGF-β) is sorbed into or onto the matrix at a weight ratio of about 2.5 μg to 5 μg of TGF-β per 40 mg of sponge, whereby a combination of the matrix, the osteoinductive factor and the TGF-β add to 100 weight percent of the composition.
Claim 51
Dependent Claim
14 words
The composition of claim 45 wherein the porous or semi-porous matrix comprises human collagen.
Claim 52
Dependent Claim
16 words
The composition of claim 45 wherein the osteoinductive factor comprises a plurality of demineralized bone particles.
Claim 53
Dependent Claim
74 words
A method for preparing an osteogenic composition in accordance with claim 45 , said method comprising: providing a porous or semi-porous matrix of human collagen; providing a plurality of demineralized bone particles, whereby the bone particles serve as an osteoinductive factor; combining the matrix and the particles; and, sorbing Transforming Growth Factor-Beta-2 (TGF-β2) into or onto the matrix, or into or onto the particles, or into or onto a combination of matrix and particles.
Claim 54
Dependent Claim
60 words
The method of claim 50 , wherein the sorbing step comprises sorbing an aqueous solution of Transforming Growth Factor-Beta-2 (TGF-β2), and the weight percent ratio of aqueous TGF-β2 to demineralized bone particles is in a range of about 1 weight unit aqueous TGF-β2 to 1 weight unit collagen, to about 1 weight unit aqueous TGF-β2 to 1,000,000 weight units collagen.
Claim 55
Dependent Claim
16 words
The composition of claim 45 wherein the Transforming Growth Factor-Beta (TGF-β) is Transforming Growth Factor-Beta-2 (TGF-β2).
Claim 56
Dependent Claim
25 words
The composition of claim 52 , wherein the amount of the TGF-β2 is about 50 pg to 500 mg TGF-β2 per 40 mg of sponge.
Claim 57
Dependent Claim
26 words
The composition of claim 53 , wherein the amount of the TGF-β2 sponge is about 5 ng to 100 mg TGF-β2 per 40 mg of sponge.
Claim 58
Dependent Claim
25 words
The composition of claim 54 , wherein the amount of the TGF-β2 is about 50 ng to 5 mg TGF-β2 per 40 mg of sponge.
Claim 59
Dependent Claim
96 words
An improved osteogenic composition having enhanced osteogenic potential, the composition comprising: a bone graft material of about 65 to about 95 weight percent of a porous or semi-porous matrix of reconstituted collagen; and about 35 to about 5 weight percent of an osteoinductive factor which is demineralized bone particles, solubilized bone morphogenetic protein, or mixtures of demineralized bone particles and solubilized bone morphogenetic protein; wherein the improvement comprises, at least one growth factor, nutrient factor, drug, calcium-containing compound, anti-inflammatory agent, blood product, calcium-containing compound, large molecular weight protein, or combination thereof is added to the composition.
Claim 60
Dependent Claim
96 words
An improved osteogenic composition having enhanced osteogenic potential, the composition comprising: a bone graft material of about 65 to about 95 weight percent of a porous or semi-porous matrix of reconstituted collagen; and about 35 to about 5 weight percent of an osteoinductive factor which is demineralized bone particles, solubilized bone morphogenetic protein, or mixtures of demineralized bone particles and solubilized bone morphogenetic protein; wherein the improvement comprises, at least one growth factor, nutrient factor, drug, calcium-containing compound, anti-inflammatory agent, blood product, calcium-containing compound, large molecular weight protein, or combination thereof is added to the composition.
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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) | 2004-01-30 | 2004-07-31 | 2005-01-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2008-01-30 | 2008-07-31 | 2009-01-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2012-01-30 | 2012-07-31 | 2013-01-30 | $7700.00 | Window Closed / Lapsed |