On Jul 13, 2018, Federal Circuit upheld two patents covering testosterone
replacement therapy (Aveed®) & rejected
a generics maker’s argument that the patents were invalid for obviousness.
Endo Pharmaceuticals Solutions, Inc. holds NDA for Aveed®, a
testosterone undecanoate (TU) intramuscular injection. Aveed® is a long-acting
injectable testosterone replacement therapy for men suffering from
physiologically low levels of testosterone, also known as hypogonadism. Custopharm
Inc.’s predecessor-in-interest, Paddock Laboratories, LLC, submitted an ANDA to
USFDA for approval of generic version of Aveed®. Claim 2 of US 7,718,640
patent and claim 18 of US 8,338,395 patent which were the sole issues cover
Aveed®’s formulation and injection regimen. Specifically, claim 2 of the ’640
patent covers a 750 mg dosage of TU in the composition & claim 18 of
the ’395 patent covers a 750 mg dosage of TU & a vehicle containing
castor oil (42% or less) and a co-solvent, benzyl benzoate.
The case proceeded to a bench trial on the sole issues of
whether claim 2 of the ’640 patent and claim 18 of the ’395 patent would have
been obvious to a skilled artisan in view of the prior art, which consisted
primarily of three scientific articles: Behre,
Nieschlag, and von Eckardstein (Articles). These Articles describe small
clinical studies involving 1000 mg TU injections. The Articles report a
composition of 250 mg/ml TU in castor oil. The parties agreed that the Articles
do not disclose or describe the use of a co-solvent. District court found that
the prior art did not disclose the 750 mg TU injection dosage, and that
Custopharm had not shown, by clear and convincing evidence, that a skilled
artisan would have been motivated to lower the dosage of TU from 1000 mg to
750 mg due to concerns patients were being overdosed. Further, the district
court found that the Articles do not inherently disclose benzyl benzoate as
a co-solvent or the particular ratio of solvent to co-solvent claimed by
the patents-in-suits. Custopharm appealed.
During appeal, Custopharm contended that a skilled artisan
would have recognized that these patients were being overdosed and would have
been motivated to reduce the dose from 1000 mg to 750 mg by injecting patients
with 3 ml instead of 4 ml of solution at a TU concentration of 250 mg/ml. Court
however, rejected the arguments & found that Custopharm had not shown, by
clear and convincing evidence, that a skilled artisan would have recognized
that patients injected with 1000 mg TU were being overdosed. To meet its
burden, Custopharm needed to do more than merely show that the prior art does
not preclude lowering the dose of TU. Custopharm needed to affirmatively
demonstrate that a skilled artisan would have been motivated to lower the dose
of TU despite no clear evidence of overdosing under the FDA Guidelines which disclosed
300 to 1000 ng/dl ranges.
Regarding the vehicle formulation, Custopharm argued that
the vehicle formulation was inherently disclosed because the Articles provide a
detailed recitation of the TU injection composition’s pharmacokinetic
performance, from which a skilled artisan could derive that the vehicle consisted
of 40% castor oil and 60% benzyl benzoate. The district court reasonably
found that this was not enough “to establish that the Articles barred the
possibility of an alternative vehicle being used in the prior art compositions”
to meet the rigorous standard of inherency. Because first, Custopharm has
not demonstrated that a skilled artisan could extrapolate the vehicle
formulation used in the Articles from pharmacokinetic performance data. Second,
the prior art was replete with potential co-solvents such that a skilled
artisan, reviewing the Articles, would not have necessarily recognized that the
Articles’ authors used benzyl benzoate as a co-solvent for their reported
clinical studies. Third, the cases Custopharm cited to support their inherency
arguments are inapposite.
Thus, Federal Circuit concluded that the district court did
not commit reversible error in finding that claim 2 of the ’640 patent and
claim 18 of the ’395 patent were not proven to be obvious over the prior art.
No comments:
Post a Comment