Osteopharm Inc.

Gensci Regeneration Sciences, Inc.

Other

Gensci Regeneration Science, Inc.

Cherk Shing Tam

Method of ameliorating effects of aging in an animal, the method comprising administering to the animal an effective amount of a synthetic polypeptide comprising an amino acid sequence that has 10&plus;q amino acids, wherein, under physiological conditions, residues numbered n, n&plus;4, n&plus;9 are positively charged amino acids, residues numbered n&plus;3, n&plus;7 are negatively charged amino acids, wherein the remaining amino acids are nonpolar amino acids or uncharged polar amino acids, wherein n is an integer from 1 to 1&plus;q and q is a whole number greater than or equal to zero. Experiments demonstrating the effect were performed with a polypeptide having the sequence Arg-Thr-Gln-Glu-His-Thr-Ala-Glu-Cys-Lys.

Polypeptides for use in ameliorating effects of aging in mammals

Polypeptides which stimulate bone growth: Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:1) and subsequences, particularly Arg Thr Asn Glu His Thr Ala Asp Cys Lys (SEQ ID NO:24) and associated nucleotide sequences, methods of preparation and use, antibodies and kits.

Bone stimulating factor

Polypeptides which increase or promote mammalian bone growth, related nucleotide sequences, antibodies, diagnostic kits and treatments. Subsequences of the polypeptide (SEQ ID NO:2)Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser Leu Glu Val Ile Gly Lys Gly Thr His Cys Asn Gln Val Glu Val Ile Ala Thr Leu Lys Asp Gly Arg Lys Ile Cys Leu Asp Pro Asp Ala Pro Arg Ile Lys Lys Ile Val Gln Lys Lys Leu Ala Gly Asp Glu Ser Ala Asp have been shown to promote growth. Subsequences include (SEQ ID NO:11) Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser (SEQ ID NO:12); Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Glu Ser (SEQ ID NO:13); Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser and (SEQ ID NO:19) TTSGIHPK.

A polypeptide substance isolate from rat serum which, upon administration to rats incapable of producing PTH (parathyroidectomized rats), produces an increase in the observed bone mineral apposition rate. The substance has been isolated in two forms, a first layer polypeptide having a molecular weight about twice that of a second smaller polypeptide. The first eleven amino acids of the sequence of the smaller polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile (SEQ ID NO:3). The first seven amino acids of the larger polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu (SEQ ID NO:2). The lager polypeptide might be the dimer of the smaller peptide. A nucleic acid probe, based on the amino acid sequence of the rat peptide was used to screen a human liver cDNA fetal library. A polypeptide was thus chemically synthesized according to the sequence Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Pro (SEQ ID NO:11). The bone apposition rate in rats increases in a dose dependent fashion upon administration of this chemically synthesized compound. A modified polypeptide containing a cysteine&rarr;alaine substinition was carried synthesized: Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:13). Some of the bone stimulatory effects of the normal polypeptide were found for the modified polypeptide.

Polypeptides which stimulate bone growth, associated nucleotide sequences, methods of preparation and use, antibodies and kits are disclosed.

A polypeptide substance isolated from rat serum which, upon administration to rats incapable of producing PTH (parathyroidectomized rats), produces an increase in the observed bone mineral apposition rate. The substance has been isolated in two forms, a first larger polypeptide having a molecular weight twice that of a second smaller polypeptide. The first eleven amino acids of the sequence of the smaller polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile (SEQ ID NO:3). The first seven amino acids of the larger polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu (SEQ ID NO:2). The larger polypeptide might be the dimer of the smaller peptide. A nucleic acid probe, based on the amino acid sequence of the rat peptide was used to screen a human liver cDNA fetal library. A polypeptide was thus chemically synthesized according to the sequence Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:11). The bone apposition rate in rats increases in a dose dependent fashion upon administration of this chemically synthesized compound. A modified polypeptide containing a cysteine alanine substitution was carried synthesized: Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:13). Some of the bone stimulatory effects of the normal polypeptide were found for the modified polypeptide.

Polypeptides which stimulate bone growth: Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:1) and subsequences, particularly Arg Thr Asn Glu His Thr Ala Asp Cys Lys (SEQ ID NO:9) and associated nucleotide sequences, methods of preparation and use, antibodies and kits.

Polypeptides which stimulate bone growth are described based on the sequences: (a) Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val; (b) Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala; (c) Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu; and (d) Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile. The associated nucleotide sequences, methods of preparation and use, and antibodies and kits based upon them are described, as well.

Polypeptides that stimulate bone growth

A polypepide substance isolated from rat serum which, upon administration to rats incapable of producing PTH (parathyroidectomized rats), produces an increase in the observed bone mineral apposition rate. The substance bas been isolated in two forms, a first larger polypeptide having a molecular weight about twice that of a second smaller polypeptide. The first eleven amino acids of the sequence of the smaller polypepeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile (SEQ ID NO:3). The first seven amino acids of the larger polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu (SEQ ID NO:2). The larger polypeptide might be the dimer of the smaller peptide. A nucleic acid probe, based on the amino acid sequence of the rat peptide was used to screen a human liver cDNA fetal library. A polypeptide was thus chemically synthesized according to the sequence Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO: 11). The bone apposition rate in rats increases in a dose dependent fashion upon administration of this chemically synthesized compound. A modified polypeptide containing a cysteine.fwdarw.alanine substitution was carried synthesized: Glr Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gin Asn Gin Pro (SEQ ID NO: 13). Some of the bone stimulatory effects of the normal polypeptide were found for the modified polypeptide.

Bone stimulating factor, methods of isolating same, and methods of

A polypeptide isolated from human blood serum has been found to increase bone growth in rats. The peptide is thought to have the seventy-five amino acid sequence of a previously sequenced variant of NAP-2V: Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser Leu Glu Val Ile Gly Lys Gly Thr His Cys Asn Gln Val Glu Val Ile Ala Thr Leu Lys Asp Gly Arg Lys Ile Cys Leu Asp Pro Asp Ala Pro Arg Ile Lys Lys Ile Val Gln Lys Lys Leu Ala Gly Asp Glu Ser Ala Asp (SEQ ID NO:4).

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Cherk Shing Tam