Nucleic acids encoding modified parathyroid hormone
AssigneeThe General Hospital Corporation
InventorsF. Richard Bringhurst, Hisashi Takasu, Thomas J. Gardella, John T. Potts JR.
Life of this patent
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Abstract
Synthetic and/or recombinant biologically active peptide derivatives of PTH(1-28), comprising a biologically active peptide at least 90% identical to a peptide consisting essentially of the formula: (a) X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsnSer MetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1); (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27; (c) pharmaceutically acceptable salts thereof; or (d) N- or C-derivatives thereof; wherein: X01 is Ser, Ala or Gly; and X02 is Glu or Arg, provided that said peptide is not hPTH(1-26)NH2, hPTH(1-27)NH2 or hPTH(1-28)NH2.
Claims32
A biologically active peptide at least 90% identical to a peptide consisting essentially of the formula:
- (a) X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsn SerMetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is Ser, Ala or Gly;
- and
- X02 is Glu or Arg,
- provided that said peptide is not hPTH(1-26)NH2, hPTH(1-27)NH2 or hPTH(1-28)NH2.
A biologically active peptide consisting essentially of the formula:
- (a) X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsn SerMetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is Ser, Ala or Gly;
- and
- X02 is Glu or Arg,
- provided that said peptide is not hPTH(1-26)NH2, hPTH(1-27)NH2 or hPTH(1-28)NH2.
A pharmaceutical composition comprising
- (a) a biologically active peptide at least 90% identical to a peptide consisting essentially of the formula:
- X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsnSerMet
- X02ArgValGluTrpLeuArgLysLysLeu(SEQ ID NO:
- 1);
- (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is Ser, Ala or Gly;
- and
- X02 is Glu or Arg;
- and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- (a) a biologically active peptide consisting essentially of the formula:
- X01ValSerGluIleGInLeuMetHisAsnLeuGlyLysHisLeuAsnSerMet
- X02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is Ser, Ala or Gly;
- and
- X02 is Glu or Arg;
- 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) X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsn SerMetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1);
- or
- (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27;
- wherein:
- X01 is Ser, Ala or Gly;
- and
- X02 is Glu or Arg.
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) X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsn SerMetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1);
- or
- (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27;
- wherein:
- X01 is Ser, Ala or Gly;
- and
- X02 is Glu or Arg.
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) X01ValSerGluIleGInLeuMetHisAsnLeuGlyLyslisLeuAsn SerMetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is Ser, Ala or Gly;
- and
- X02 is Glu or Arg,
- provided that said peptide is not hPTH(1-26)NH2, hPTH(1-27)NH2 or hPTH(1-28)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) X01ValSerGluIleGInLeuMetHisAsnLeuGlyLysfisLeuAsn SerMetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1);
- (b) fragments thereof containing amino acids 1-24, 1-25, 1-26, or 1-27;
- (c) pharmaceutically acceptable salts thereof;
- or
- (d) N- or C-derivatives thereof;
- wherein:
- X01 is Ser, Ala or Gly;
- and
- X02 is Glu or Arg,
- provided that said peptide is not HPTH(1-26)NH2, hPTH(1-27)NH2 or hPTH(1-28)NH2;
- and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.