On Nov. 19, 2019, Federal Circuit affirmed PTAB’s decision
& found formulation patents covering insulin glargine (Lantus®)
invalid under obviousness.
Sanofi-Aventis Deutschland GMBH’s owns U.S. Patent Nos.
7,476,652 and 7,713,930, which describe and claim certain formulations of a
particular kind of insulin ie —insulin glargine. Mylan filed IPR petitions
& board finally concluded that the subject matter of the claims is unpatentable
for obviousness. Sanofi appealed.
Claim 7 of the ’652 patent is illustrative for present action:
7. A pharmaceutical formulation comprising Gly(A21), Arg(B31),
Arg(B32)-human insulin, at least one chemical entity chosen from polysorbate
and poloxamers; at least one preservative; and water, wherein the
pharmaceutical formulation has a pH in the acidic range from 1 to 6.8.
Sanofi first commercially sold glargine in the U.S. in May
2001 (before priority), under the trade name Lantus®, whose product label
identifies, among other things, a pH of 4. Some patients soon began reporting
problems with turbidity in the vials, i.e., before injection. Sanofi determined
that the turbidity was caused by undesirable “non-native” aggregation of the
glargine protein while still in solution. Sanofi then resolved the
vial-turbidity problem by adding a nonionic surfactant to the glargine
formulation to prevent non-native aggregation.
During appeal Sanofi challenged the Board’s finding based on
(1) KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), required the
Board to find that the prior art disclosed an aggregation problem for glargine
specifically (not just insulins in general); (2) the Board improperly relied on
each patent’s own (shared) specification in finding a motivation to combine;
and (3) substantial evidence does not support the Board’s finding because key
evidence cited by the Board concerned insulins in general rather than glargine
specifically.
With respect to first point, Sanofi argued that the Board
was required, under KSR, to find in the prior art a recognition of an
aggregation problem for glargine specifically, not just for insulins generally.
But Federal Circuit said that in KSR, the Supreme Court criticized a rigid
approach to determining obviousness based on the disclosures of individual
prior-art references, with little recourse to the knowledge, creativity, and
common sense that an ordinarily skilled artisan would have brought to bear when
considering combinations or modifications. Nothing in KSR demands the kind of
prior-art identifications of a problem at the level of specificity that Sanofi
urges. The Board thus properly examined the evidence in this particular case to
determine whether a relevant artisan would have recognized an insulin
aggregation problem in the prior art and expected glargine to share that
problem.
With respect to second point, Federal Circuit also rejected
Sanofi’s contention that the Board committed legal error when it cited the
shared patent specification, specifically background section. Sanofi challenged
the Board’s reliance on this material as legally improper, invoking court’s
longstanding recognition that a tribunal should not “look to knowledge taught
by the inventor . . . and then use that knowledge against its teacher.” But
Federal Circuit said that the Board did not violate that principle, because it
did not use the specification for its teachings about the inventor’s discovery.
Rather, it used the specification for its teachings about prior-art knowledge,
and that use of a specification is not just common, given patent drafters’
standard practice of reciting prior art in setting out the background of the
invention, but permissible. Moreover, the Board used the cited material not as
the sole support for any finding but in conjunction with support from other
sources. The Board found evidence of insulin aggregation on hydrophobic
surfaces and at air/water interfaces in a handful of other prior-art
references.
With respect to third point, Federal Circuit said that the
Board’s findings with respect to the motivation to combine are detailed and
well supported. The Board correctly found that insulins “had a known tendency
to aggregate in the presence of hydrophobic surfaces” and at air-water
interfaces and that a relevant artisan would have expected glargine to behave
similarly to other insulins when in contact with hydrophobic surfaces and at
air-water interfaces. The Board also found that nonionic surfactants, including
the claimed ones, were well known and had been used successfully to stabilize
insulin formulations, and so would have been looked to by a relevant artisan
concerned about aggregation in glargine. Sanofi argued that the prior art
discloses aggregation only in insulin pumps, but the Board disagreed, finding
instead that “it is the air-water interfaces and interactions with hydrophobic
surfaces that promote insulin aggregation, and not the type of device used to
deliver the insulin formulation.” Prior
art & expert testimony supports the Board’s determination. The evidence
also supports the Board’s finding that the prior art taught use of nonionic
surfactants like those claimed in the present patents to address the
aggregation problem.
Sanofi also challenged the Board’s finding that a relevant
artisan would have had a reasonable expectation of success in adding the
claimed surfactants to the existing glargine preparation in the way claimed in
the patents at issue here. Sanofi specifically argued that, although
surfactants were known to stabilize insulins generally, a relevant artisan
would not have expected the same result for glargine specifically because its
mechanism of action depends on some favorable native aggregation. Federal
Circuit said that nonionic surfactants—were shown in the prior art to have been
successfully used to prevent aggregation of various types of insulins and other
peptides. Moreover, presence of phenols in a glargine formulation would not
have dissuaded a relevant artisan from expecting success in using nonionic
surfactants. Therefore, Board’s finding is supported by substantial evidence.
Finally, Federal Circuit also rejected Sanofi challenge with respect to commercial
success.
Federal Ciruit thus affirmed the Board’s decisions that all
claims of the ’652 and ’930 patents are unpatentable for obviousness.
