Amino -terminal modified parathyroid hormone (PTH) analogs
AssigneeThe Massachusetts Gerneral Hospital
InventorsF. Richard Bringhurst, Hisashi Takasu, Thomas J. Gardella
Life of this patent
Estimating the term…
Abstract
PTH derivatives having one or more amino acid substitutions that confer PTH-1/PTH-2 receptor agonist properties comprising a biologically active peptide at least 90% identical to a peptide consisting essentially of the formula: (a) X01 ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAs nSerMetGluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe (SEQ ID NO:1); (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33; (c) pharmaceutically acceptable salts thereof; or (d) N- or C-derivatives thereof; wherein: X01 is desamino Ser, desamino Ala or desamino Gly, provided that said peptide is not desamino Ser1 hPTH(1-31)NH2 or desamino Ser1 hPTH(1-34)NH2.
Claims29
A biologically active peptide at least 90% identical to a peptide consisting essentially of the formula:
- (a) X01 ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAs nSerMetGluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is desamino Ser, desamino Ala or desamino Gly, provided that said peptide is not desamino Ser1 hPTH(1-31)NH2 or desamino Ser1 hPTH(1-34)NH2.
A biologically active peptide consisting essentially of the formula:
- (a) X01 ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAs nSerMetGluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is desamino Ser, desamino Ala or desamino Gly, provided that said peptide is not desamino Ser1 hPTH(1-31 )NH2 or desamino Ser1 hPTH(1-34)NH2.
A pharmaceutical composition comprising
- (a) a biologically active peptide at least 90% identical to a peptide consisting essentially of the formula:
- X01 ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsnSerMet GluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe(SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is desamino Ser, desamino Ala or desamino Gly;
- and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- (a) a biologically active peptide consisting essentially of the formula:
- X01 ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsnSerMet GluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe(SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is desamino Ser, desamino Ala or desamino Gly;
- and a pharmaceutically acceptable carrier.
A nucleic acid molecule consisting essentially of a polynucleotide encoding a biologically active peptide which has an amino acid sequence selected from the group consisting of:
- (a) X01 ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsn SerMetGluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33;
- wherein:
- X01 is desamino Ser, desamino Ala or desamino Gly, provided that said peptide is not desamino Ser1 hPTH(1-31)NH2 or desamino Ser1 hPTH(1-34)NH2.
A recombinant DNA molecule comprising:
- (1) an expression control region, said region in operable linkage with (2) a polynucleotide sequence coding for a biologically active peptide, wherein said peptide is selected from the group consisting of:
- (a) X01 ValSerGluIleGInLeuMetHisAsnLeuGlyLysHisLeuAsn SerMetGluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33;
- wherein:
- X01 is desamino Ser, desamino Ala or desamino Gly, provided that said peptide is not desamino Ser1 hPTH(1-31)NH2 or desamino Ser1 hPTH(1-34)NH2.
A method for treating mammalian conditions characterized by decreases in bone mass, which method comprises administering to a subject in need thereof an effective bone mass-increasing amount of a biologically active peptide, wherein said peptide comprises an amino acid sequence at least 90% identical to a member selected from the group consisting essentially of:
- (a) X01 ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsn SerMetGluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is desamino Ser, desamino Ala or desamino Gly, provided that said peptide is not desamino Ser1 hPTH(1-31)NH2 or desamino Ser1 hPTH(1-34)NH2;
- and a pharmaceutically acceptable carrier.
A method for treating mammalian conditions characterized by decreases in bone mass, which method comprises administering to a subject in need thereof an effective bone mass-increasing amount of a biologically active peptide consisting essentially of the formula:
- (a) X01 ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsn SerMetGluArgValGluTrpLeuArgLysLysLeuGlnAspValHisAsnPhe (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-29, 1-30, 1-31, 1-32, or 1-33;
- (c) pharmaceutically acceptable salts thereof;
- or (d) N- or C-derivatives thereof;
- wherein:
- X01 is desamino Ser, desamino Ala or desamino Gly, provided that said peptide is not desamino Ser1 hPTH(1-31)NH2 or desamino Ser1 hPTH(1-34)NH2;
- and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.