Appeal No. 2003-1668 Page 3
Application No. 08/479,883
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. In human growth hormone, helix A (or helix 1) is made up of
amino acids 6-33, while helix C (or helix 3) is made up of amino acids 106-128.
Specification, page 15.
“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 and/or 2.” Page 3. “[T]he residues falling within the site 1 domains remain
unmodified (in the case of antagonists, in which only site 2 is disabled by
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. Specification, page 8.
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