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US4761471A
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Bone morphogenetic protein composition
Assignee: University of California, San Diego
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Filing: 1986-08-22
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Granted: 1988-08-02
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Expires: 2006-08-22
Abstract
Abstract BMP compositions including the human factor and bovine factor thereof, the process of isolating BMP compositions and factors, and the use of such factors and compositions to induce bone formation in animals.
Inventors
- 👤 Marshall R. Urist
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:11
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/227; C; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/51; A61K; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/84
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
77 words
Substantially pure bone morphogenetic protein composition comprising BMP factor and at least one BMP associated protein selected from a group consisting of BMP associated proteins having molecular weights in the range of between about 14 dKa and about 34 kDa, said BMP factor being capable of inducing bone formation independent of the presence of said BMP associated proteins, and said BMP associated proteins being incapable of inducing bone formation independent of the presence of said BMP factor.
Claim 2
Dependent Claim
77 words
Substantially pure bone morphogenetic protein composition comprising BMP factor and at least one BMP associated protein selected from a group consisting of BMP associated proteins having molecular weights in the range of between about 14 dKa and about 34 kDa, said BMP factor being capable of inducing bone formation independent of the presence of said BMP associated proteins, and said BMP associated proteins being incapable of inducing bone formation independent of the presence of said BMP factor.
Claim 3
Dependent Claim
43 words
The bone morphogenetic protein composition of claim 1, wherein the BMP factor is human BMP factor having a molecular weight of 17.5±0.5 dKa, and the BMP associated proteins are human BMP associated proteins having molecular weights of about 14-, 22-, 24- and 34-kDa.
Claim 4
Dependent Claim
46 words
The bone morphogenetic protein composition of claim 1, wherein the BMP factor is bovine BMP factor having a molecular weight of 18.5±0.5 kDa, and the BMP associated proteins are bovine BMP associated proteins having molecular weights of about 14-, 16.5-, 17-, 17.5, 22-, 24-, and 34-dKa.
Claim 5
Dependent Claim
66 words
The aggregate of: (a) hBMP factor having a molecular weight in the range of about 17.5±0.5 kDa, and comprised, as determined by amino acid analysis, of lysine, histidine, arginine, aspartate, threonine, serine, glutamate proline, glycine, alanine, cystine, leucine, tyrosine and phenylalanine; and (b) at least one BMP-associated protein selected from a group consisting of BMP-associated proteins having molecular weights of about 14-, 22-, 24-, and 34-kDa.
Claim 6
Dependent Claim
66 words
The aggregate of: (a) hBMP factor having a molecular weight in the range of about 17.5±0.5 kDa, and comprised, as determined by amino acid analysis, of lysine, histidine, arginine, aspartate, threonine, serine, glutamate proline, glycine, alanine, cystine, leucine, tyrosine and phenylalanine; and (b) at least one BMP-associated protein selected from a group consisting of BMP-associated proteins having molecular weights of about 14-, 22-, 24-, and 34-kDa.
Claim 7
Dependent Claim
73 words
The aggregate of: (a) bBMP factor having a molecular weight in the range of about 18.5±0.5 kDa and and comprised, as determined by amino acid analysis, of lysine, histidine, arginine, aspartate, threonine, serine, glutamate, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, and phenylalanine; and (b) at least one BMP associated protein selected from a group consisting of BMP associated proteins having molecular weights of about 14-, 16.5-, 17.0-, 22-, 24-, and 34-kDa.
Claim 8
Dependent Claim
73 words
The aggregate of: (a) bBMP factor having a molecular weight in the range of about 18.5±0.5 kDa and and comprised, as determined by amino acid analysis, of lysine, histidine, arginine, aspartate, threonine, serine, glutamate, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, and phenylalanine; and (b) at least one BMP associated protein selected from a group consisting of BMP associated proteins having molecular weights of about 14-, 16.5-, 17.0-, 22-, 24-, and 34-kDa.
Claim 9
Dependent Claim
27 words
The aggregate of claim 5 consisting essentially of about 7 parts 22-kDa and about 1 part 14-kDa BMP associated proteins, and about 2 parts 18.5±0.5-kDa bBMP factor.
Claim 10
Dependent Claim
43 words
The aggregate of hBMP factor and 14-kDa protein of claim 4 wherein said aggregate is insoluble in 0.6 N HCl, soluble in 6M urea, soluble in 4M guanidine HCl; soluble in 0.1% SDS, soluble in 0.02N HCl and partially soluble in ethylene glycol.
Claim 11
Dependent Claim
57 words
The aggregate of claim 4, wherein said hBMP factor, as determined by amino acid analysis, is comprised, in approximate mole percentages, of lysine 4%; histidine, 1.5%; arginine, 7%; aspartate, 8%; threonine, 3%; serine, 8%; glutamate 10%; proline, 3.5%; glycine, 25%; alanine, 7%; cystine, 3%; leucine, 7%; tyrosine, 3%; phenylalanine, 2.5%; and about 3 residues/170 residues carboxyglutamic acid.
Claim 12
Dependent Claim
55 words
The aggregate of claim 8, said hBMP factor having a molecular weight in the range of about 17.5±0.5 kDa and being trypsin and chymotrypsin labile, alkali sensitive, partially degradable by pepsin and papain, and resistant to chondroitinases A, B and C; amylase; neuroamidase; hyaluronidase; alkaline phosphates; acid phosphatase; chymopapain; collagenase; tyrosinase; thermolysine; RNase and DNase.
Claim 13
Dependent Claim
46 words
The aggregate of claim 9, said hBMP factor having a molecular weight of about 17.5±0.5 kDa and being an acidic polypeptide, bindable to hydroxyapetite, having an isoelectric point of 5.0±0.2, being insoluble in chloroform, methanol, absolute alcohol, and acetone and being degraded by acid alcohol solutions.
Claim 14
Dependent Claim
54 words
The aggregate of claim 5, wherein said bBMP factor, as determined by amino acid analysis, is comprised, in approximate mole percentages, of lysine, 10%; histidine, 3.5%; arginine, 16.5%; aspartate, 16.5% threonine, 7%, serine, 17.5%; glutamate, 23.5% proline, 9% glycine, 12.5%; alanine, 14.5%; valine, 11%; methionine, 2.5%; isoleucine, 6%; leucine, 15%; tyrosine, 8%; phenylalanine, 7%.
Claim 15
Dependent Claim
52 words
The aggregate of claim 5, wherein said 22 kDa protein is comprised, in approximate mole percentages, of lysine, 2.5%; histidine, 2.5%, arginine, 6%; aspartate, 12.5%; threonine, 3.5%; serine, 5.5%; glutamate, 14.5%; proline, 6.5%; glycine, 8.5%; alanine, 6%; cystine, 3.5%; valine, 4.5%; methionine, 2%; isoleucine, 2.5%; leucine, 6.5%; tyrosine, 8.5%; and phenylalanine, 4%.
Claim 16
Dependent Claim
51 words
The aggregate of claim 5, wherein said 14-dKa protein is comprised, in approximate mole percentages, of lysine, 4.5%; histidine, 1.5%; arginine, 9%; aspartate, 11.5%; threonine, 2.5%; serine, 6.5%; glutamate, 15%; proline, 5%; glycine, 6% alanine, 8.5%; cystine, 2%; valine, 4%; methionine, 1.5%; isoleucine, 4%; leucine, 7.5%; tyrosine, 6.5%; and phenylalanine, 4%.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-08-02 | 1992-02-01 | 1992-08-02 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-08-02 | 1996-02-01 | 1996-08-02 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-08-02 | 2000-02-01 | 2000-08-02 | $7700.00 | Window Closed / Lapsed |