Thursday, September 24, 2015

Defendants do not make out well in Shire v. Amneal, et al. in Vyvanse® case

The outcome:

Because defendants have failed to raise a genuine issue of material
fact that the asserted claims are obvious, we affirm the
district court’s judgment of nonobviousness.

Because the district court did not abuse its discretion in denying
defendants’ motion to amend their invalidity contentions
to include an on-sale bar claim, we affirm that ruling.

Because in the circumstances of this case Johnson Matthey
cannot be liable for induced infringement prior to the
grant of FDA approval of the application filed by the
ANDA defendants, we reverse the district court’s judgment
that Johnson Matthey has induced infringement of
the asserted compound claims and remand the case for
further proceedings consistent with this opinion.

Some of the history

Shire is the assignee of the patents-in-suit and markets
LDX dimesylate capsules. These capsules are approved
by the Food and Drug Administration (“FDA”) and
distributed under the brand name Vyvanse®. The FDA’s
Approved Drug Products with Therapeutic Equivalence
Evaluations (commonly known as the “Orange Book”) lists
all the patents-in-suit for Vyvanse®.
The ANDA defendants filed Abbreviated New Drug
Applications (“ANDAs”) for their generic versions of
Vyvanse® seeking approval prior to the expiration of the
patents-in-suit. The ANDAs included certifications
pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV) (2012) (commonly
referred to as “Paragraph IV certifications”) stating
that the claims of the patents-in-suit are invalid and/or
not infringed. Pursuant to § 355(j)(2)(B), the ANDA
defendants notified Shire of the Paragraph IV certifications.
In response, Shire sued the ANDA defendants for
infringing the asserted claims, along with certain other
claims not at issue in this appeal, under 35 U.S.C.
§ 271(e) (2012). In each suit, Shire also sued Johnson
Matthey. Johnson Matthey supplied LDX dimesylate to
the ANDA defendants and correspondingly filed a drug
master file with the FDA, see 21 C.F.R. § 314.420, but did
not itself file an ANDA. The district court consolidated all
the lawsuits

As to the obviousness defense:

The district court concluded that (1) the prior art did
not disclose LDX or make it obvious; (2) even if it did, the
prior art did not disclose that LDX was known as an
active drug substance; (3) even if it did, the prior art
provided no motivation to pick LDX as a starting compound;
and (4) even if it did, the prior art provided no
motivation to make mesylate salts of LDX. Op. at *15–17.
Shire did not introduce and the district court did not
analyze any secondary considerations.
Defendants maintain that there is a genuine issue of
material fact whether Australian Patent Application No.
54,168/65 (“AU ’168”), actually discloses LDX. Specifically,
they claim that page 7 of AU ’168 identifies 18 amino
acids by name, including lysine, and states a preference
for L-amino acids and d-amphetamine. Upon reading this
passage, defendants argue, a person of skill in the art
would immediately envisage LDX. Defendants also claim
that Formula IV and Example 24 of AU ’168 disclose
LDX. Defendants also contend that there is a genuine
issue of material fact whether the prior art as a whole
rendered the mesylate salts of LDX obvious. There is also
a genuine issue of material fact, defendants argue,
whether mesylate salts of LDX were obvious and whether
there was a reasonable expectation of success that the
mesylate salt of LDX would serve its intended purpose.
In addition to AU ’168, defendants rely on several other
pieces of prior art, including U.S. Patent No. 3,843,796
(“Miller”), to bolster their obviousness argument.
Shire denies that AU ’168 discloses LDX. Shire
claims that the record fails to show that a person of skill
in the art would: “(i) start with d-amphetamine, (ii) chemically
modify d-amphetamine, (iii) make a prodrug of damphetamine,
(iv) synthesize [LDX] while ignoring other
conjugates of d-amphetamine, (v) make a salt of [LDX]
instead of using the freebase form, and finally (vi) specifically
choose a mesylate salt rather than any other salt.”
Resp. Br. at 19.

The matter of deference to the USPTO for consideration of
a reference of record arises:

On this record, there is no genuine issue of material
fact that the prior art did not disclose or make obvious the
mesylate salt of LDX. Defendants’ primary reference is
AU ’168. AU ’168 is listed on the face of the patents-insuit
and therefore the examiner is presumed to have
considered it.
Defendants therefore “ha[ve] the added
burden of overcoming the deference that is due to a qualified
government agency presumed to have properly done
its job, which includes one or more examiners who are
assumed to have some expertise in interpreting the
references and to be familiar from their work with the
level of skill in the art and whose duty it is to issue only
valid patents.” PowerOasis, Inc. v. T-Mobile USA, Inc.,
522 F.3d 1299, 1304 (Fed. Cir. 2008) (citations omitted).

Here, a generic disclosure is not enough to render
the species obvious:

AU ’168 discloses combining amphetamine, in any of
its stereochemical forms, with numerous amino acids, in
various stereochemistries and with many potential protecting
groups. Nothing in AU ’168 specifically suggests
combining d-amphetamine with L-lysine. Page 7 of AU
’168, relied on heavily by defendants, lists 18 amino acids
“and the like,” and states they can belong to the D- or Lseries.
Even this list, therefore, does not limit itself to 18
amino acids. AU ’168 expressly suggests posttranslational
modifications of the amino acids, see id. at 8,
thus further increasing the potential amino acid groups to
be utilized. While page 7 states that “[a]cids of the Lseries
are preferred,” AU ’168 actually describes numerous
D-series amino acids. Read in context of the whole
reference, a person of skill in the art would, therefore, not
focus exclusively on amino acids with the L stereochemistry.


There is no genuine issue of material fact that AU ’168 does not
disclose L-lysine as part of a limited class of compounds
for ‘A’. AU ’168 suggests that ‘A’ can be selected from one
of three lists, and as defendants’ expert candidly admitted,
Formula IV “does not indicate any preference” among
the different options. Thus, Formula IV discloses all the
compounds from all three lists, the first of which lists 17
amino acids (including lysine), the second of which teaches
over a hundred possible combinations of amino acids
and protecting groups and the third of which does not
even provide a definite list of compounds. This too is not
a definite and limited class. Further, as described above,
AU ’168 does not meaningfully describe a preference for
the L stereochemistry of its amino acids.

As to induced infringement:

Shire counters by asserting that Johnson Matthey is
properly in the suit and can be liable for induced infringement.
According to Shire, this court’s decision in
Forest Laboratories, Inc. v. Ivax Pharmaceuticals, Inc.,
501 F.3d 1263 (Fed. Cir. 2007), held that a party can be
liable “under section 271(e)(2) for its future infringement
under section 271(b) as the ANDA-filers’ API supplier.”
Resp. Br. at 52. Shire contends that on the facts before us
“Forest cannot be distinguished.” Id. at 55 (capitalization
altered). Finally, Shire argues that under the reasoning
of Forest Labs., Johnson Matthey can be enjoined.
Johnson Matthey is correct that it cannot be liable for
the API it sold the ANDA defendants up to this point.
Johnson Matthey, as an API supplier, has thus far done
nothing more than provide material for use by the ANDA
defendants in obtaining FDA approval. As the district
court found, these sales, and the ANDA defendants’ use of
the API for filing the ANDA, were “reasonably related to
the submission of an ANDA.” Op. at *12. As such, Johnson
Matthey’s activities are protected by the safe harbor
of § 271(e)(1), and the district court erred by entering
judgment that Johnson Matthey has induced infringement
of the compound claims at issue.



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