Patent US2644983A successfully refreshed from Google Patents.
US7045141B2
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US
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Allograft bone composition having a gelatin binder
Assignee: Musculoskeletal Transplant Foundation
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Filing: 2002-05-20
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Granted: 2006-05-16
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Expires: 2022-05-20
Abstract
Abstract The invention is directed toward an osteoimplant for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing composition of demineralized allograft bone material mixed with an aqueous phosphate buffered gelatin which when lyophilized to remove water from the composition cross links the gelatin to form a solid structure.
Inventors
- 👤 Barbara L. Merboth
- 👤 Moon Hae Sunwoo
- 👤 Arthur A. Gertzman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 01:57
CPC Classifications
A; A61; A61K; A61K35/00; A61K35/12; A61K35/32; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1875; A61K6/00; A61K6/80; A61K6/884; A61L; A61L24/00; A61L24/0005; A61L24/001; A61L24/0031; A61L24/0047; A61L24/0073; A61L24/0094; A61L27/00; A61L27/14; A61L27/20; A61L27/22; A61L27/222; A61L27/36; A61L27/3604; A61L27/3608; A61L27/3641; A61L27/3645; A61L27/365; A61L27/3683; A61L27/3691; A61L27/3695; A61L27/40; A61L27/44; A61L27/446; A61L27/46; A61L27/48; A61L27/50; A61L27/52; A61L27/54; C; C08; C08L; C08L5/00; C08L5/08; A61F; A61F2/00; A61F2/02; A61F2/30; A61F2002/30001; A61F2002/30003; A61F2002/30004; A61F2002/30059; A61L2300/00; A61L2300/40; A61L2300/404; A61L2300/406; A61L2300/412; A61L2300/414; A61L2300/428; A61L2430/00; A61L2430/02
Claims Analysis
Total Claims: 47
Claim 1
Independent Claim
114 words
A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising a mixture of allograft osteoinductive bone material which is at least partially demineralized in a carrier forming a composition, the bone material ranging from about 20% to about 65% of the weight of the composition and the carrier comprising a gelatin component dissolved in an aqueous solution containing a hydrogel, said composition being lyophilized to achieve a crosslinking of the gelatin to obtain a structural stability which is maintained after application to said bone defect site, said gelatin comoonent ranting from about 10% to about 50% by weight of the composition after lyophilization.
Claim 2
Dependent Claim
114 words
A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising a mixture of allograft osteoinductive bone material which is at least partially demineralized in a carrier forming a composition, the bone material ranging from about 20% to about 65% of the weight of the composition and the carrier comprising a gelatin component dissolved in an aqueous solution containing a hydrogel, said composition being lyophilized to achieve a crosslinking of the gelatin to obtain a structural stability which is maintained after application to said bone defect site, said gelatin comoonent ranting from about 10% to about 50% by weight of the composition after lyophilization.
Claim 3
Dependent Claim
27 words
A sterile bone repair composition as claimed in claim 1 wherein said mixture includes bone morphogenic protein in excess of the amount naturally occurring in allogeneic bone.
Claim 4
Dependent Claim
24 words
A sterile bone repair composition as claimed in claim 1 wherein said osteoinductive bone material is demineralized with a calcium content below about 1%.
Claim 5
Dependent Claim
27 words
A malleable bone composition as claimed in claim 1 wherein said gelatin carrier includes a phosphate buffered saline with a pH ranging from 7.0 to about 7.4.
Claim 6
Dependent Claim
26 words
A malleable bone composition as claimed in claim 1 wherein said bone material is partially mineralized with a calcium content between about 4% to about 8%.
Claim 7
Dependent Claim
28 words
A sterile bone repair composition as claimed in claim 1 wherein said aqueous solution comprises at least one ofa group consisting of water, saline and phosphate buffered saline.
Claim 8
Dependent Claim
34 words
A sterile bone repair composition as claimed in claim 1 wherein said hydrogel is selected from the group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
Claim 9
Dependent Claim
25 words
A sterile bone repair composition as claimed in claim 1 wherein said allograft aqueous solution has a pH ranging from about 7.0 to about 7.4.
Claim 10
Dependent Claim
26 words
A sterile bone repair composition as claimed in claim 1 wherein said bone material includes bone particles ranging from 100 microns to 850 microns in size.
Claim 11
Dependent Claim
36 words
A sterile bone repair composition as claimed in claim 1 wherein said bone material contains growth factors transforming growth factor (TGF-beta), platelet derived growth factor (PDGF), osteopontin, fibroblast growth factor (FGF) and insulin-like growth factor (IGF-1).
Claim 12
Dependent Claim
149 words
A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising a mixture of allogeneic osteoinductive bone material which is partially demineralized and has a residual calcium content ranging from about 4.0% to about 8.0% in an aqueous gelatin carrier, said aqueous gelatin carrier contains a gelatin component and a hydrogel component, said hydrogel component comprising at least one of a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC) which is lyophilized to remove the water content leaving a crosslinked gelatin bone structure having a structural stability which is maintained alter application to said bone repair site, with said bone material ranging from about 30% to about 60% of the weight of the composition and said gelatin component ranging from about 30% to about 60% by weight of the composition.
Claim 13
Dependent Claim
149 words
A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising a mixture of allogeneic osteoinductive bone material which is partially demineralized and has a residual calcium content ranging from about 4.0% to about 8.0% in an aqueous gelatin carrier, said aqueous gelatin carrier contains a gelatin component and a hydrogel component, said hydrogel component comprising at least one of a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC) which is lyophilized to remove the water content leaving a crosslinked gelatin bone structure having a structural stability which is maintained alter application to said bone repair site, with said bone material ranging from about 30% to about 60% of the weight of the composition and said gelatin component ranging from about 30% to about 60% by weight of the composition.
Claim 14
Dependent Claim
28 words
A sterile bone repair composition as claimed in claim 11 wherein said aqueous gelatin contains a phosphate buffered saline with a pH ranging from 7.0 to about 7.4.
Claim 15
Dependent Claim
33 words
A sterile bone repair composition as claimed in claim 12 wherein phosphate in said phosphate buffered saline includes at least two phosphate ions HPO 4 −2 and H 2 PO 4 −1 .
Claim 16
Dependent Claim
33 words
A sterile bone repair composition as claimed in claim 11 including antimicrobial and/or antibiotics erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracycline, viomycin, chloromycetin and streptomycin, cefazolin, ampicillin, azactam, tobramycin, clindamycin, gentamycm and vitamins.
Claim 17
Dependent Claim
27 words
A sterile bone repair composition as claimed in claim 11 wherein said composition includes bone morphogenic proteins in excess of the amount naturally occurring in allogeneic bone.
Claim 18
Dependent Claim
21 words
A sterile bone repair composition as claimed in claim 11 wherein said composition has a pH ranging from 6.8 to 7.4.
Claim 19
Dependent Claim
36 words
A sterile bone repair composition as claimed in claim 11 wherein said bone material contains growth factors transforming growth factor (TGF-beta), platelet derived growth factor (PDGF), osteopontin, fibroblast growth factor (FGF) and insulin-like growth factor (IGF-1).
Claim 20
Dependent Claim
128 words
A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising new bone growth inducing partially demineralized lyophilized allograft bone material having a particle size ranging from about 100 to about 850 microns mixed in an aqueous gelatin carrier, containing a hydrogel component ranging from 5% to 10% by weight to form a composition which is lyophilized to remove water content leaving a crosslinked gelatin bone structure having a structural stability which is maintained after application to said bone defect site with said bone material ranging from about 30% to about 50% of the weight of the composition of the structure and the crosslinked gelatin ranging from 30% to 60% by weight of the composition of the structure.
Claim 21
Dependent Claim
128 words
A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising new bone growth inducing partially demineralized lyophilized allograft bone material having a particle size ranging from about 100 to about 850 microns mixed in an aqueous gelatin carrier, containing a hydrogel component ranging from 5% to 10% by weight to form a composition which is lyophilized to remove water content leaving a crosslinked gelatin bone structure having a structural stability which is maintained after application to said bone defect site with said bone material ranging from about 30% to about 50% of the weight of the composition of the structure and the crosslinked gelatin ranging from 30% to 60% by weight of the composition of the structure.
Claim 22
Dependent Claim
36 words
A sterile bone repair composition as claimed in claim 18 wherein said hydrogel component comprises at least one ofa group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
Claim 23
Dependent Claim
167 words
A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing compound of partially demineralized lyophilized allograft bone material with a calcium content greater than 4% and less than 8% dry weight and a particle size ranging from about 100 to about 850 microns mixed in an aqueous gelatin carrier having a hydrogel component comprising a glycosaminoglycan ranging from about 5.0% to about 15.0% by weight of the composition and having a molecular weight of at least 700,000 Daltons, said mixture being lyophilized to remove water content with the water content after lyophilization ranging from about 0.1% to about 1.0% leaving a crosslinked gelatin bone structure having a structural stability which is maintained after application to said bone repair site with said bone material ranging from about 30% to about 50% of the weight of the composition and the crosslinked gelatin ranging from 30% to 60% by weight of the composition.
Claim 24
Dependent Claim
167 words
A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing compound of partially demineralized lyophilized allograft bone material with a calcium content greater than 4% and less than 8% dry weight and a particle size ranging from about 100 to about 850 microns mixed in an aqueous gelatin carrier having a hydrogel component comprising a glycosaminoglycan ranging from about 5.0% to about 15.0% by weight of the composition and having a molecular weight of at least 700,000 Daltons, said mixture being lyophilized to remove water content with the water content after lyophilization ranging from about 0.1% to about 1.0% leaving a crosslinked gelatin bone structure having a structural stability which is maintained after application to said bone repair site with said bone material ranging from about 30% to about 50% of the weight of the composition and the crosslinked gelatin ranging from 30% to 60% by weight of the composition.
Claim 25
Dependent Claim
19 words
A sterile bone repair composition as claimed in claim 20 wherein said glycosaminoglycan is sodium hyaluronate and its derivatives.
Claim 26
Dependent Claim
20 words
A sterile bone repair composition as claimed in claim 20 wherein said aqueous gelatin carrier includes a phosphate buffered saline.
Claim 27
Dependent Claim
31 words
An osteoimplant as claimed in claim 20 wherein said glycosaminoglycan is selected from a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
Claim 28
Dependent Claim
110 words
An osteoimplant for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing compound of demineralized allograft osteoinductive bone material mixed in a phosphate buffered aqueous gelatin carrier which is lyophilized to remove water content leaving a crosslinked gelatin bone structure having a structural stability which is maintained after application to said bone repair site, said bone material ranging from about 30% to about 60% of the weight of the structure and the crosslinked gelatin ranging from 30% to 60% by weight of the structure with the water content of said structure ranging from about 0.1% to about 1.0%.
Claim 29
Dependent Claim
110 words
An osteoimplant for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing compound of demineralized allograft osteoinductive bone material mixed in a phosphate buffered aqueous gelatin carrier which is lyophilized to remove water content leaving a crosslinked gelatin bone structure having a structural stability which is maintained after application to said bone repair site, said bone material ranging from about 30% to about 60% of the weight of the structure and the crosslinked gelatin ranging from 30% to 60% by weight of the structure with the water content of said structure ranging from about 0.1% to about 1.0%.
Claim 30
Dependent Claim
24 words
A method as claimed in claim 24 wherein said osteoinductive bone material is powdered bone ranging from about 100 microns to about 850 microns.
Claim 31
Dependent Claim
27 words
A method as claimed in claim 24 wherein said osteoinductive bone material is powdered bone with a residual calcium content ranging from about 4% to about 8%.
Claim 32
Dependent Claim
30 words
A method as claimed in claim 24 wherein said osteoinductive bone material is powdered bone which has been deniineralized to have a residual calcium content which is less than 1%.
Claim 33
Dependent Claim
16 words
A method as claimed in claim 24 wherein said osteoinductive bone material includes mineralized bone chips.
Claim 34
Independent Claim
86 words
A method of constructing a crosslinked osteoinductive bone repair construct comprising the steps of: a. dissolving a gelatin in an aqueous solution; b. mixing osteoinductive bone material in an aqueous solution and gelatin mixture to obtain a formulation; c. shaping said formulation into a specific shape; and d. subjecting said shaped formulation to lyophilization at a negative temperature to remove at least 90% of water from said aqueous gelatin osteoinductive bone mixture crosslinking said gelatin and osteoinductive bone material contained therein to form a solid structure.
Claim 35
Independent Claim
86 words
A method of constructing a crosslinked osteoinductive bone repair construct comprising the steps of: a. dissolving a gelatin in an aqueous solution; b. mixing osteoinductive bone material in an aqueous solution and gelatin mixture to obtain a formulation; c. shaping said formulation into a specific shape; and d. subjecting said shaped formulation to lyophilization at a negative temperature to remove at least 90% of water from said aqueous gelatin osteoinductive bone mixture crosslinking said gelatin and osteoinductive bone material contained therein to form a solid structure.
Claim 36
Dependent Claim
26 words
A method as claimed in claim 29 wherein said aqueous solution comprises at least one of a group consisting of phosphate buffered saline, saline and water.
Claim 37
Dependent Claim
21 words
A method as claimed in claim 29 wherein said aqueous solution includes a hydrogel component of less than 10% by weight.
Claim 38
Dependent Claim
34 words
A method as claimed in claim 31 wherein said hydrogel component comprises at least one of a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
Claim 39
Dependent Claim
21 words
A method as claimed in claim 29 wherein said aqueous solution has a pH ranging from about 7.0 to about 7.4.
Claim 40
Independent Claim
133 words
A method of constructing a crosslinked osteoinductive bone repair construct comprising the steps of: a. dissolving a gelatin in an aqueous solution; b. mixing from about 20% to about 50% by weight osteoinductive bone material in an aqueous gelatin and hydrogel mixture to obtain a bone repair formulation, said hydrogel being less than 10% by weight of said formulation; c. shaping said bone repair formulation into a specific shape for; and d. lyophilizing said shaped bone repair formulation below 0° C. for a period of time sufficient to leave from 0.01 to 0.8% water in said aqueous gelatin osteoinductive bone formulation and crosslink said gelatin with said osteoinductive bone material contained therein to form a solid structure with said gelatin ranging from about 30% to about 60% fo the weight of the structure.
Claim 41
Independent Claim
133 words
A method of constructing a crosslinked osteoinductive bone repair construct comprising the steps of: a. dissolving a gelatin in an aqueous solution; b. mixing from about 20% to about 50% by weight osteoinductive bone material in an aqueous gelatin and hydrogel mixture to obtain a bone repair formulation, said hydrogel being less than 10% by weight of said formulation; c. shaping said bone repair formulation into a specific shape for; and d. lyophilizing said shaped bone repair formulation below 0° C. for a period of time sufficient to leave from 0.01 to 0.8% water in said aqueous gelatin osteoinductive bone formulation and crosslink said gelatin with said osteoinductive bone material contained therein to form a solid structure with said gelatin ranging from about 30% to about 60% fo the weight of the structure.
Claim 42
Dependent Claim
26 words
A method as claimed in claim 34 wherein said aqueous solution comprises at least one of a group consisting of phosphate buffered saline, saline and water.
Claim 43
Dependent Claim
18 words
A method as claimed in claim 34 wherein said lyophilization is at −40° C. for about 4 hours.
Claim 44
Independent Claim
110 words
A method of constructing a crosslinked osteoinductive bone repair construct comprising the steps of: a. dissolving a gelatin in an aqueous solution containing a glycosaminoglycan; b. mixing osteoinductive demineralized bone material having a size ranging from 100 microns to 2 mm and 30% to 60% by weight in said aqueous gelatin solution to obtain a formulation; c. shaping said formulation into a specific shape; and d. subjecting said shaped formulation to lyophilization at a temperature of at least −40° C. to remove at least 92% of water from said aqueous gelatin osteoinductive bone mixture crosslinking said gelatin, glycosaminoglycan and osteoinductive demineralized bone material contained therein to form a solid structure.
Claim 45
Independent Claim
110 words
A method of constructing a crosslinked osteoinductive bone repair construct comprising the steps of: a. dissolving a gelatin in an aqueous solution containing a glycosaminoglycan; b. mixing osteoinductive demineralized bone material having a size ranging from 100 microns to 2 mm and 30% to 60% by weight in said aqueous gelatin solution to obtain a formulation; c. shaping said formulation into a specific shape; and d. subjecting said shaped formulation to lyophilization at a temperature of at least −40° C. to remove at least 92% of water from said aqueous gelatin osteoinductive bone mixture crosslinking said gelatin, glycosaminoglycan and osteoinductive demineralized bone material contained therein to form a solid structure.
Claim 46
Dependent Claim
51 words
A method as claimed in claim 37 wherein said lyophilization of step d, is conducted for at least 4 hours after which the temperature is raised to about +35° C. for 20 to 28 hours with the formulation at the higher temperature being placed under a vacuum of about 350 mTorr.
Claim 47
Dependent Claim
24 words
A method as claimed in claim 37 wherein about 0.1 to about 8% of the original water is left in the formulization after lyophilization.
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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) | 2009-05-15 | 2009-11-14 | 2010-05-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2013-05-15 | 2013-11-14 | 2014-05-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2017-05-15 | 2017-11-14 | 2018-05-16 | $7700.00 | Window Closed / Lapsed |