Appeal No. 2003-1469 Page 3
Application No. 08/479,886
Background
“Ligand induced receptor oligomerization has been proposed as a
mechanism of signal transduction for the large family of tyrosine kinase receptors
that contain an extracellular ligand binding domain.” Specification, page 1. The
specification discloses that “growth hormones and the class of conformational
ligands to which they belong are capable of forming 1:2 complexes with their
receptor in which a first ligand site, site 1, binds to one receptor and then a
second ligand site, site 2, binds to another molecule of receptor, thereby yielding
a 1:2 complex.” Page 3.1
In “growth hormone and the homologous ligands prolactin and placental
lactogen . . . site 2 for this group of quaternary-alpha helical cytokines and
hormones principally is comprised by (a) the sequence extending from the N-
terminus to about the first 3-4 turns of helix A and (b) about the middle 4-5 turns
of helix C.” Page 9. “Site 1 also is a discontinuous site. It consists of three
segments located (a) in the middle 40% of helix A (perhaps overlapping with the
C-terminus of site 2 in helix A), (b) the C-terminal 2/3rds (preferably C-terminal
1/2) of the loop linking helices A and B, and (c) the C-terminal 1/2 (preferably 1/3)
of helix D.” Page 10.
The specification discloses that identification of the site 1 and site 2 amino
acids makes it possible “to efficiently design agonist or antagonist amino acid
sequence variants . . . by introducing amino acid sequence variation into sites 1
1 Conformationally related ligands include prolactin, placental lactogen, erythropoietin, α and β
interferon, GM-CSF, G-CSF, and interleukins 2, 3, 4, 6, and 7. See page 8.
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