Appeal 2007-0852
Application 09/919,195
Xiao-Chun Xu et al., Suppression of Retinoic Acid Receptor ß in Non-Small-
Cell Lung Cancer In Vivo: Implications for Lung Cancer Development, 89 (9)
Journal of the National Cancer Institute 624 (1997).
Cong Yan et al., Retinoic acid-receptor activation of SP-B gene
transcription in respiratory epithelial cells, 275 The American Physiological
Society L239-L246 (1998).
Manely Ghaffari et al., Inhibition of hSP-B promoter in respiratory
epithelial cells by a dominant negative retinoic acid receptor, 276 The American
Journal of Physiology L398-L404 (1999).
DISCUSSION
Background
The present invention is directed to methods and compositions for
promoting the formation of alveoli in mammalian lung tissue. (Specification 4.)
In one embodiment, the invention comprises a therapeutic method for inducing the
formation of alveoli in mammalian lung tissue by administration of a composition
comprising a therapeutically effective amount of a ligand that is an RAR (retinoic
acid receptor) β antagonist. (Specification 4-5.) The retinoid receptors are part of
the steroid/thyroid/vitamin D superfamily of nuclear receptors. (Specification 8.)
In a preferred aspect of this embodiment, the RAR β receptor antagonist or inverse
agonist has specific RAR modulating activity at the RAR receptor, and is not
specific to the RARα receptor. (Specification 6-7.)
By "specific RAR modulating activity" in the claim, it is meant that such a
compound has a disassociation constant (KD) (the ligand concentration at which
50% of the RAR receptors are complexed with the ligand) at an RAR receptor at
least 10 times, preferably at least 25 times, even more preferably at least 50 times,
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