On Feb
04, 2020, Judge Stanley R. Chesler of New Jersey found claims of alogliptin
compound patent valid & infringed.
Takeda (Plaintiff) own U.S. Patent No. 7,807,689 (compound),
which is listed in the Orange Book as protecting Plaintiffs’ alogliptin
benzoate formulations, marketed under the brand names Nesina®, Kazano®, and
Oseni®. Indoco & Torrent (Defendants) filed ANDAs seeking approval to
market generic products. The defendants stipulated infringement of claims 4 and
12 of the ’689 patent & contested invalidity challenge. Claim 4 covers
alogliptin & claim 12 covers specific benzoate salt.
Defendants presented case on obviousness-type double
patenting and on obviousness. Specifically, Defendants’ invalidity theories
relied heavily on a chemistry technique termed “scaffold hopping” or “scaffold
replacement” and “isosteric replacement theory”. For this defendants relied on “Böhm”
reference. Bohm states that,
“Scaffold hopping approach
requires the availability of a template
– a chemical structure displaying the desired biological activity, and it is based
on the assumption that the same biological activity can be exerted by other compounds
that maintain some essential features of the template but are structurally
different otherwise”.
Defendants argued that claims 4 and 12 are invalid, under
the doctrine of obviousness-type double
patenting, because they are not patentably distinct from F162, the compound
disclosed in claim 162 of the ’344 patent. Defendants argued that the POSA
would have been motivated to replace the scaffold of the claim 162 compound
with the goal of developing a new DPP-IV inhibitor for the treatment of Type 2
diabetes, because ‘scaffold replacement’ is one of ‘a range of strategies’ used
by medicinal chemists to design and identify novel structures.”
But court said that Defendants has offered no support for
the proposition that the POSA would have been motivated to choose scaffold
replacement to develop a novel compound from F162. Defendants have not yet
identified some reason which would have led a POSA to select scaffold
replacement to modify F162 to make F162u with a reasonable expectation of
success. As of the Priority Date, the art did not have available the structural
information needed to perform scaffold replacement to produce a non-peptidic
molecule that was active as a DPP-IV inhibitor with a reasonable expectation of
success. The cited testimony says no more than that scaffold replacement was one
of a “range” of options. Furthermore, Defendants relies substantially on the
testimony of Dr. Rotella, whose credibility was damaged on cross-examination.
During the direct examination, Dr. Rotella stated that the substituents of F162
and alogliptin are the same, but the scaffolds differ. On cross-examination,
Dr. Rotella agreed that F162 contained a fluorine atom as a substituent, while
alogliptin does not. Dr. Rotella’s credibility also suffered from inconsistent
testimony. Court also did not find second isosteric replacement theory
convincing & denied the challenge.
With respect to obviousness
theory, Defendants argued that POSA searching for a promising drug development
candidate would have focused on non-peptidic inhibitors and specifically on xanthine-based
compounds, which a POSA would recognize as “particularly promising.” Defendants
argued that, in short, two references suggest DCAX as lead compound, the WO
’496 patent and the CA ’730 patent. Plaintiffs contended that Defendants’
theory is based on hindsight. Plaintiffs argued that Defendants rely
principally on the testimony of their expert, Dr. Ferraris, but that his
credibility is undermined by, and is inconsistent with, his own work. Dr.
Ferraris testified that a POSA seeking a candidate for drug development would
have ignored peptidic inhibitors, but his own work during this time was on
peptidic inhibitors. His actual work thus contradicts his opinions in this
case. Next, Plaintiffs point to the fact that Dr. Ferraris admitted that he did
not actually do an independent lead compound analysis. Dr. Ferraris testified
that the choice of DCAX and the two references supporting that choice, the WO
’496 and CA ’730 patents, were given to him by Defendants’ counsel; he did not
search through the prior art to find them.
Court next said that, Defendants’ path to the selection of
DCAX is unpersuasive. Defendants argue, in short, that there are eight
compounds that are mentioned in both the WO ’496 and the CA ’730 patents and
that, of those eight compounds, DCAX has the greatest potency. Defendants did
not explain why a POSA would believe that a compound mentioned in two patents
is more worthy of development than a more potent compound listed in one. The
prior art did not supply a POSA with a reason to select DCAX as a lead compound
over other compounds in the prior art. Court said that the Defendant’s argument
has a number of major gaps, missing connections or steps with inadequate
support. This is a theory with major defects and does not come close to meeting
the clear and convincing standard for successful validity challenges.
The Court thus concluded that Defendants have failed to
prove, by clear and convincing evidence, that claims 4 and 12 of the ’689
patent are invalid under their theories based on § 103 obviousness or the
doctrine of obviousness-type double patenting.
