Modified growth hormones
First Claim
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1. A pharmaceutical composition, comprising a modified growth hormone polypeptide containing an amino acid replacement in an unmodified growth hormone polypeptide at a position corresponding to amino acid Y42 of a mature human growth hormone polypeptide, wherein:
- the growth hormone polypeptide is modified in its primary sequence only by the amino acid replacement at Y42;
the amino acid replacement is Y42H, whereby the modified growth hormone polypeptide retains an activity and exhibits increased resistance to proteolysis in the serum or gastrointestinal tract compared to the unmodified growth hormone polypeptide that does not comprise the amino acid replacement, and is rendered orally available;
the unmodified human growth hormone polypeptide comprises the sequence of amino acids set forth in SEQ ID NO;
1 or the sequence of amino acid residues set forth as amino acid residues 27-217 in SEQ ID NO;
712, or allelic or species variants, alternative splice variants or an active portion thereof that includes the position corresponding to Y42; and
the pharmaceutical composition is formulated for oral administration.
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Abstract
Provided are modified growth hormone polypeptides, nucleic acid molecules encoding modified growth hormone polypeptides and methods of generating modified growth hormone polypeptides. Also provided are methods of treatment using modified growth hormone polypeptides.
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Citations
12 Claims
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1. A pharmaceutical composition, comprising a modified growth hormone polypeptide containing an amino acid replacement in an unmodified growth hormone polypeptide at a position corresponding to amino acid Y42 of a mature human growth hormone polypeptide, wherein:
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the growth hormone polypeptide is modified in its primary sequence only by the amino acid replacement at Y42; the amino acid replacement is Y42H, whereby the modified growth hormone polypeptide retains an activity and exhibits increased resistance to proteolysis in the serum or gastrointestinal tract compared to the unmodified growth hormone polypeptide that does not comprise the amino acid replacement, and is rendered orally available; the unmodified human growth hormone polypeptide comprises the sequence of amino acids set forth in SEQ ID NO;
1 or the sequence of amino acid residues set forth as amino acid residues 27-217 in SEQ ID NO;
712, or allelic or species variants, alternative splice variants or an active portion thereof that includes the position corresponding to Y42; andthe pharmaceutical composition is formulated for oral administration. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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Specification