DNA encoding growth hormone antagonists
AssigneeOhio University/Edison Biotechnology Institute
InventorsJohn J. Kopchick, Wen Y. Chen
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Abstract
The present invention relates to DNA molecules which encode antagonists of vertebrate growth hormones obtained by mutation of at least the amino acid corresponding to Glu-119 in bovine growth hormone. The DNA molecules may be used to express the antagonists, either in cell culture, or in the cells of the patient of interest. The antagonist so expressed may be used to inhibit GH activity in a subject.
Claims50
A non-naturally occurring DNA molecule comprising a coding sequence encoding a vertebrate growth hormone variante comprising an amino acid substitution of an amino acid, other than glycine or alanine, for the amino acid of said vertebrate growth hormone at the position corresponding to the glycine at position 119 of bovine growth hormone, wherein the growth hormone variant has vertebrate growth hormone inhibitory activity, with the proviso that said variant does not correspond to human growth hormone with all of the following substitutions and no others:
- Y111V, L113I, K115E, D116Q, E118K, E119R, G120L, Q122E, T123G, G126L, R127I and E129S.
A non-naturally occurring DNA molecule comprising a coding sequence encoding a vertebrate growth hormone variant comprising lysine at the position corresponding to the glycine at position 119 of bovine growth hormone, wherein the growth hormone variant has vertebrate growth hormone inhibitory activity.
A non-naturally occurring DNA molecule comprising a coding sequence encoding a vertebrate growth hormone variant comprising arginine at the position corresponding to the glycine at position 119 of bovine growth hormone, wherein the growth hormone variant has vertebrate growth hormone inhibitory activity.
A non-naturally occurring nucleic acid molecule which encodes a variant of a vertebrate growth hormone, wherein the variant comprises an amino acid sequence which is at least 80% identical to the native vertebrate growth hormone amino acid sequence, and wherein the amino acid position corresponding to amino acid Gly 119 of bovine growth hormone is an amino acid other than glycine or alanine, said variant having growth hormone receptor antagonist activity, with the proviso that said antagonist is not human growth hormone having all of the following substitutions and no others:
- Y111V, L113I, K115E, D116Q, E118K, E119R, G120L, Q122E, T123G, G126L, R127I and E129S.
A non-naturally occurring nucleic acid molecule which encodes a variant of a vertebrate growth hormone, wherein the variant comprises an amino acid sequence which is at least 80% identical to the native vertebrate growth hormone amino acid sequence, and wherein the amino acid position corresponding to amino acid Gly 119 of bovine growth hormone is an amino acid other than glycine or alanine, said variant having growth hormone receptor antagonist activity, where said vertebrate growth hormone is selected from the group consisting of bovine, porcine, ovine, rat, flounder, yellowtail, tuna, salmon and chicken growth hormones.
A non-naturally occurring nucleic acid molecule which encodes a variant of a mammalian growth hormone, wherein the variant comprises an amino acid sequence which is at least 80% identical to the native mammalian growth hormone amino acid sequence, and wherein the amino acid position corresponding to amino acid Gly 119 of bovine growth hormone is an amino acid other than glycine or alanine, said variant having growth hormone receptor antagonist activity, where said variant has an alpha helix, corresponding to the third alpha helix (AAs 106-129) of bovine growth hormone, which is at least 80% identical, but not completely identical, to the alpha helix of said mammalian growth hormone which corresponds to the third alpha helix (AAs 106-129) of bovine growth hormone.
Dependencies are inferred from the claim text.