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EP0212474A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Bone morphogenetic peptides

Assignee: University of California
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Filing: 1986-08-07
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Granted: —
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Expires: 2006-08-07
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Abstract

Abstract The production and isolation of bone morphogenetic peptide agents displaying the osteoinductive and immunoreactive activity of bone morphogenetic protein (BMP) and deriving from natural, sunthetic or recombinant DNA sources, and said agents.

Inventors

  • 👤 Marshall R. Urist

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-23 19:51
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/51; A; A61; A61P; A61P43/00; A61K; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/84

Claims Analysis

Total Claims: 35
Claim 1
Independent Claim 29 words
A bone morphogenetic agent comprising a peptide displaying osteoinductive activity similar to bone morphogenetic protein (BMP), said peptides obtained from whatever source, including natural, synthetic or recombinant DNA sources.
Claim 2
Dependent Claim 29 words
A bone morphogenetic agent comprising a peptide displaying osteoinductive activity similar to bone morphogenetic protein (BMP), said peptides obtained from whatever source, including natural, synthetic or recombinant DNA sources.
Claim 3
Dependent Claim 59 words
The bone morphogenetic peptide agent of claim 1, comprising amino acid sequences of N-terminal segments of bone morphogenetic protein (BMP), said N-terminal segments of BMP having a range of relative molecular weights (M r ) from about 4K to about 7K, said peptide agent obtained from whatever source, including single or multiple amino acid additions, substitutions, deletions or insertions.
Claim 4
Dependent Claim 68 words
The bone morphogenetic peptide agent of claim 1 which are characterized by containing the following amino acid sequence: -ILE - PRO - GLN - GLN - ARG - ­ARG - TRP - ARG - ALA - LYS - VAL - GLN -ASN - ARG - ILE-, and including single or multiple amino acid additions, substitutions, deletions or insertions which provide a peptide similar in osteoinductive activity of BMP.
Claim 5
Dependent Claim 35 words
The bone morphogenetic peptide agent of claim 3, including the following amino acid sequence: -ARG - ­ASP - SER - TYR - LYS - PRO - VAL - HIS - GLU - LEV - ASN-.
Claim 6
Dependent Claim 29 words
The bone morphogenetic peptide agent of claim 4, including the following amino acid sequence: -ARG-­CYS - ALA - ASP - GLY - TYR - ARG - LEU - CYS-.
Claim 7
Dependent Claim 30 words
The bone morphogenetic peptide agents of claim 1 derived from proteolysis of BMP, and having a range of relative molecular weights (M r ) from about 4K to about 7K.
Claim 8
Dependent Claim 16 words
The bone morphogenetic peptide agent of claim 6 wherein said proteolysis of BMP is by pepsin.
Claim 9
Dependent Claim 16 words
The bone morphogenetic peptide agent of claim 6 wherein said proteolysis of BMP is by trypsin.
Claim 10
Dependent Claim 18 words
The bone morphogenetic peptide agent of claim 6, 7, or 8 wherein said proteolyzed BMP is human BMP.
Claim 11
Dependent Claim 25 words
The bone morphogenetic peptide agent of claim 9 wherein said human BMP-p has a relative molecular weight (M r ) of about 4.7K ± 0.3K.
Claim 12
Dependent Claim 18 words
The bone morphogenetic peptide agent of claim 6, 7 or 8 wherein said proteolyzed BMP is bovine BMP.
Claim 13
Dependent Claim 26 words
The bone morphogenetic peptide agent of claim 11, wherein said bovine BMP-p has a relative molecular weight (M r ) in the range of about 4.1K.
Claim 14
Dependent Claim 38 words
The bone morphogenetic peptide agent of claim 1 derived from direct chemical synthesis from constituent amino acids and wherein said peptide comprises amino acid sequences of BMP-p, including single or multiple amino acid additions, substitutions, deletions or insertions.
Claim 15
Dependent Claim 46 words
The bone morphogenetic peptide agent of claim 1 derived from expression of DNA sequences comprising sequences of codons which on expression code for a peptide similar in osteoinduction activity of BMP or BMP-p, said DNA sequences from whatever source obtained, including natural, synthetic or semi-­synthetic sources.
Claim 16
Dependent Claim 81 words
The bone morphogenetic peptide agent of claim 14, wherein said DNA expressed is characterized by a sequence of codons which on expression code for a peptide containing the amino acid sequence: -ILE - ­PRO - GLN - GLN -ARG - ARG - TRP - ARG - ALA - LYS - VAL - GLN - ASN - ARG - ILE-, including single or multiple base substitutions, additions, deletions or insertions which express a peptide similar in immunoreactive or osteoinductive activity of BMP-p.
Claim 17
Dependent Claim 110 words
A process for selecting DNA sequences coding on expression for a peptide displaying the immunoreactive or osteoinductive activity of BMP or BMP-p from a group of DNA sequences from whatever source, comprising selecting the DNA sequences that hybridize to a nucleic acid probe containing the DNA or the RNA sequences or the complements thereof that code for the amino acid sequences of BMP-p or the amino acid sequence: -ILE - PRO - GLN - GLN - ­ARG - ARG - TRP - ARG - ALA - LYS - VAL - GLN - ASN - ARG - ILE-, and said probe including single or multiple base substititions, additions, deletions or insertions.
Claim 18
Dependent Claim 110 words
A process for selecting DNA sequences coding on expression for a peptide displaying the immunoreactive or osteoinductive activity of BMP or BMP-p from a group of DNA sequences from whatever source, comprising selecting the DNA sequences that hybridize to a nucleic acid probe containing the DNA or the RNA sequences or the complements thereof that code for the amino acid sequences of BMP-p or the amino acid sequence: -ILE - PRO - GLN - GLN - ­ARG - ARG - TRP - ARG - ALA - LYS - VAL - GLN - ASN - ARG - ILE-, and said probe including single or multiple base substititions, additions, deletions or insertions.
Claim 19
Dependent Claim 71 words
A nucleic acid probe specific for selecting nucleic acid sequences coding on expression for a peptide displaying the immunoreactive or osteoinductive activity of bone morphogenetic protein (BMP) comprising the codon sequence or the complement thereof for part or all of the amino acid sequences of BMP-p, or comprising part or all of the amino acid sequence of Table IV said probe including single or multiple base substitutions, additions, deletions or insertions.
Claim 20
Dependent Claim 71 words
A nucleic acid probe specific for selecting nucleic acid sequences coding on expression for a peptide displaying the immunoreactive or osteoinductive activity of bone morphogenetic protein (BMP) comprising the codon sequence or the complement thereof for part or all of the amino acid sequences of BMP-p, or comprising part or all of the amino acid sequence of Table IV said probe including single or multiple base substitutions, additions, deletions or insertions.
Claim 21
Dependent Claim 19 words
A DNA sequence which expresses a bone morphogenetic peptide agent and which hybridizes to the probe of claim 17.
Claim 22
Dependent Claim 80 words
A process for producing a DNA sequence coding on expression for a peptide displaying the immunoreactive or osteoinductive activity of BMP or BMP-p, comprising direct chemical synthesis of DNA containing a sequence of codons for the amino acid sequence of BMP-p, including single or multiple base additions, substitutions, deletions or insertions, or comprising enzymatic synthesis of cDNA from an RNA template containing codons for the amino acid sequence of BMP-p, including single or multiple base additions, substitutions, deletions or insertions.
Claim 23
Dependent Claim 80 words
A process for producing a DNA sequence coding on expression for a peptide displaying the immunoreactive or osteoinductive activity of BMP or BMP-p, comprising direct chemical synthesis of DNA containing a sequence of codons for the amino acid sequence of BMP-p, including single or multiple base additions, substitutions, deletions or insertions, or comprising enzymatic synthesis of cDNA from an RNA template containing codons for the amino acid sequence of BMP-p, including single or multiple base additions, substitutions, deletions or insertions.
Claim 24
Dependent Claim 38 words
A method of producing a recombinant DNA molecule capable of expressing a bone morphogenetic agent comprising the step of introducing into a cloning vehicle a DNA sequence selected according to claim 16 or produced according to claim 19.
Claim 25
Dependent Claim 31 words
A recombinant DNA molecule comprising a cloning vehicle having inserted therein a DNA sequence selected according to the process of claim 16 or produced according to the process of claim 19.
Claim 26
Dependent Claim 12 words
A host transformed with a recombinant DNA molecule according to claim 21.
Claim 27
Dependent Claim 42 words
A method of producing a bone morphogenetic peptide agent displaying the immunoreactive or osteoinductive activity of BMP or BMP-p comprising the steps of transforming an appropriate host with a recombinant molecule according to claim 21, culturing said host, and collecting said peptide.
Claim 28
Independent Claim 41 words
A method of producing a bone morphogenetic peptide agent displaying the immunoreactive or osteoinductive activity of BMP comprising proteolyzing BMP for a period of time to produce BMP-p having relative molecular weights in the range from about 4K to about 7K.
Claim 29
Independent Claim 41 words
A method of producing a bone morphogenetic peptide agent displaying the immunoreactive or osteoinductive activity of BMP comprising proteolyzing BMP for a period of time to produce BMP-p having relative molecular weights in the range from about 4K to about 7K.
Claim 30
Dependent Claim 13 words
The method of claim 24, wherein said proteolysis of BMP is by pepsin.
Claim 31
Dependent Claim 13 words
The method of claim 24, wherein said proteolysis of BMP is by trypsin.
Claim 32
Independent Claim 48 words
A method for producing a bone morphogenetic peptide agent displaying the immunoreactive or osteoinductive activity of BMP comprising direct chemical synthesis of said peptide from constituent amino acids, said peptide containing the amino acid sequence of BMP-p, including single or multiple amino acid additions, substitutions, deletions or insertions.
Claim 33
Independent Claim 48 words
A method for producing a bone morphogenetic peptide agent displaying the immunoreactive or osteoinductive activity of BMP comprising direct chemical synthesis of said peptide from constituent amino acids, said peptide containing the amino acid sequence of BMP-p, including single or multiple amino acid additions, substitutions, deletions or insertions.
Claim 34
Dependent Claim 28 words
A composition for inducing bone formation which comprises a bone morphogenetic peptide agent selected from the group consisting of peptides according to any one of claims 1-8, 13-15.
Claim 35
Dependent Claim 29 words
A method for inducing bone formation in vertebrates which comprises administering to said vertebrate in a pharmaceutically acceptable manner an effective amount of a composition according to claim 28.

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