Appeal No. 1999-1732
Application No. 08/308,879
receptor, and human breast cancer cell lines have been shown to respond to both prolactin
and growth hormone when grown as solid tumors in nude mice. See id. at page 5.
Growth hormone and the class of conformational ligands to which they belong form
a 1:2 complex with their receptor, with a first ligand binding site, which the specification
refers to as site 1, binds to a first receptor, and then a second receptor binds to the
hormone at the second ligand site, site 2. See id. at page 6. Coupled with the knowledge
of the conformational structure of the ligand, the specification states that one can design
hormone agonists or antagonists by introducing amino acid variations into sites 1 and/or 2.
See id. at pages 6-7. The specification states that
[i]n particular, antagonists for polypeptide ligands are provided which
comprise an amino acid sequence mutation in site 2 which reduces or
eliminates the affinity of the ligand for the receptor at site 2. Ideally, the
ligand antagonist analog will have low or no affinity for receptor at site 2 and
will have elevated affinity for receptor at site 1.
Id. at page 7.
The claimed invention is drawn to a method for inhibiting growth of breast cancer
cells through the use of a growth factor antagonist, wherein the antagonist has an amino
acid variation that reduces ligand binding at site 2 by at least two-fold. Also claimed is a
preferred antagonist, wherein the glycine at position 120 of human growth hormone has
been mutated to arginine (G120R).
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