Appeal No. 2001-0531 Page 3
Application No. 08/216,592
Background
Retinoic acid receptors (RARs), thyroid hormone receptors (TRs), and
retinoid X receptors (RXRs) are nuclear receptors. Specification, page 1. These
nuclear receptors bind to specific sequences of DNA, known as DNA response
elements (REs). Id., page 2. “Retinoic acid (RA) signalling involves at least two
classes of proteins, the retinoic acid receptors (RARα, RARβ, RARγ) and retinoid
X receptors (RXRα, RXRβ, RXRγ). RARs and RXRs are members of the
steroid/thyroid hormone receptor superfamily, and exhibit the modular protein
structure typical to this group, including domains which function in DNA binding,
dimerisation, ligand binding and transactivation.” Id., page 81 (citations omitted).
“Ligand binding appears to be required to induce transactivation functions
(AFs) which overlap the N-terminal and ligand binding domains of these proteins.
It has recently been shown that the affinities of RARs for their target sequences
is strongly increased when they are complexed as heterodimers with RXRs.” Id.
(citations omitted). “RXRs exhibit promiscuous heterodimerisation properties in
vitro, forming complexes with other factors including the thyroid receptor (TR)
. . ., which stimulates their cooperative and selective binding to cognate hormone
receptor elements in vitro.” Id., page 82.
Discussion
Claim 5 is directed to a method of identifying an agent capable of inducing
transactivation of a reporter gene operably linked to a DNA response element.
The claimed method begins with cells that contain the reporter gene linked to the
response element, and that have also been altered to express heterodimers
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