Appeal No. 2003-1019 Page 3
Application No. 09/524,132
Townsend, the PDR and the FDA Memorandum.
We reverse each of these rejections.
BACKGROUND
Premarin® (conjugated estrogens, USP)[, derived from the urine of
pregnant mares,] has been known to contain a mixture of estrogens
obtained exclusively from natural sources, occurring as the sodium salts of
water-soluble estrogen sulfates blended to represent the average
composition of material derived from pregnant mares’ urine . . . [and] is
generally believed to contain a number of estrogenic compounds.
However, despite numerous attempts to characterize Premarin® [ ] over
the past several decades, the essential estrogenic compounds present in
Premarin® [ ] have remained a mystery.
Specification, pages 1-2.
According to appellants, however, “the essential estrogenic compounds present
in naturally derived equine conjugated estrogens have now been determined”
(specification, page 4), using “[t]wo fundamental criteria” (specification, page 14). First,
components of Premarin® “with a [lot-to-lot] variability of ± 50% were eliminated” from
consideration as essential components (id., page 15); second, “[a] structure-function
approach to defining estrogenicity was taken” (id.) in order to avoid the conflicting
results observed in various biological assays and estrogen receptor binding assays “due
to differences in tissue-specific responses[,] metabolic activation or degradation of
specific estrogens,” and “the existence of at least two receptor subtypes” (id.).
Consequently, “essential estrogenic compounds” present in Premarin® and other
conjugated estrogen preparations obtained from natural sources were “defined as
estrogenic compounds that are consistent and controlled (i.e. less than +/- 50%
variation between lots), are present in concentrations >0.1% by weight of the mixture of
estrogenic compounds, and have a chemical structure that has the potential to have a
meaningful estrogenic activity (i.e. has a phenolic A ring (at carbon 3) and a $-hydroxyl
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