Monday, May 20, 2013

Fexofenadine case: "substantially pure" has different meanings within one patent

Aventis/AMR vs. Mylan concerning fexofenadine.
The decision is by a 2-1 vote.

The initial part of the decision:

Aventis Pharmaceuticals, Inc. and Albany Molecular
Research, Inc. (AMRI) (collectively “Appellants”) appeal a
stipulated judgment of noninfringement entered by the
U.S. District Court for the District of New Jersey. The
parties stipulated to noninfringement following the district
court’s Markman opinion of January 13, 2011, which
consolidated numerous patent infringement cases and
construed terms of AMRI’s U.S. Patent No. 5,750,703
(“the ’703 patent”), among others.1 Because we conclude
that the district court’s Markman opinion misinterpreted
claim terms of the ’703 patent
, we reverse and remand.

IPBiz notes the potential procedural relationship of this case
to Gevo v. Butamax. Parties can stipulate to an outcome and challenge
claim interpretation.

Of background in the Aventis case:

Dr. Thomas E. D’Ambra,
AMRI’s president, found the prior art processes for making
piperidine derivatives inefficient. Because one goal of
Dr. D’Ambra’s work was to obtain substantially pure
piperidine derivative compounds—ultimately required for
pharmaceutical-grade end products; that is, end products
with greater than 98% purity—he recognized that the
reduced purity achieved through known teachings meant
additional purification steps were required after the
piperidine derivative was fully formed, leading to low

The commercial relevance of this case is fexofenadine/Allegra.

Footnote 5 of the decision states:

Regioisomers are chemical compounds with the
same molecular formula, but with different bonding

In the case, the relevant isomers are meta and para substituted

The difference between these regioisomeric arrangements
of constituents on both the CPK intermediate and
piperidine derivative product appears slight, but is biologically
significant—the piperidine derivative produced
using the para-CPK structure is biologically active, while
the piperidine derivative produced using the meta-CPK
structure is biologically inactive. The ’703 patent extensively
criticizes the prior art processes because each stage
of the synthesis yields an impure mixture of meta- and
para-regioisomers. But the new process invented by Dr.
D’Ambra using a CPK intermediate means that the
para/meta CPK regioisomeric mixture is more readily
separable to obtain para-CPK, resulting in a substantially
pure para-piperidine derivative end product.

[ notes: Three categories of constitutional isomers are
skeletal, positional, and functional isomers.
Positional isomers are also called regioisomers. ]

Of case history:

The district court performed a tentative claim construction
in connection with a September 20, 2005 motion
for a preliminary injunction filed after Teva began marketing
a generic fexofenadine drug. Judge Greenaway’s
January 30, 2006 opinion denied the preliminary injunc
tion request, and set forth an initial claim construction of
the ’703 patent’s disputed claim term “substantially
pure.” See Aventis Pharms., Inc. v. Barr Labs., Inc., 411
F. Supp. 2d 490, 509 (D.N.J. 2006). The district court
found that the ’703 patent’s specification used the phrase
“substantially pure” to describe both the piperidine derivative
end products and the CPK intermediate
. Id. at 498-
99. The district court also relied on statements from the
prosecution history regarding the purity of the piperidine
derivative end products to reach a tentative claim construction
that the phrase “substantially pure” in the
asserted claims of the ’703 patent means “of greater than
95% purity.” Id. at 502–03.

[Judge Greenaway is believed to be currently on CA3.]

And the earlier outcome:

In light of this claim construction,
Appellants stipulated that they could no longer prove
infringement, and the district court entered final judgment
in favor of Appellees in both cases. Appellants
timely appealed the disputed claim construction of the
’703 patent to this court.

A sign of trouble for the earlier construction:

Claims 1, 6, and 7 of the ’703 patent explicitly include
the term “substantially pure regioisomer.” The district
court construed this language to require “at least 98%
purity with respect to all impurities.” This construction,
however, conflates the purity required for the piperidine
end product with that of the CPK intermediate.


We agree with both parties that the claims themselves
are insufficient to define the term “substantially
pure.” Therefore, we must turn to other sources of intrinsic
evidence to determine “what the inventors actually
invented and intended to envelop with the claim.” Renishaw
PLC v. Marposs Societa’ per Azioni, 158 F.3d 1243,
1250 (Fed. Cir. 1998). The specification provides the “best
source” for construing a claim term and determining the
inventor’s intent regarding use. Multiform Dessicants,
Inc. v. Medzam, Ltd., 133 F.3d 1473, 1478 (Fed. Cir.
1998); see also Vitronics, 90 F.3d at 1582.


The “one-size-fits-all” construction adopted by the district
court incorrectly construes “substantially pure”
separate from the very next word--“regioisomer.” The
district court’s artificial truncation of the claim term for
the expediency of a single interpretation across different
contexts was error
. Outside of the description of the prior
art process from the ’129 patent, the specification almost
exclusively uses the term “regioisomer” to refer to the
CPK intermediate. Further, the full term, “substantially
pure regioisomer,” is used only in reference to the CPK


The district court reasoned that the
plain language of “substantially pure” must involve all
impurities, because “a solution of 25% para-CPK, 0.2%
meta-CPK, and 74.8% dirt would not be substantially
pure.” Joint App’x 55; see also Aventis, 2011 WL 2175928,
at *8. This flawed analysis again does not consider the
appropriate frame of reference for claim construction.


We hold that the modifier
“substantially pure,” when construed in light of a person
of ordinary skill in the art and in view of the claimed
improvements over the prior art, only applies regioisomeric
impurities, not all impurities.

Of the term "substantially"

With no explicit construction of the term “substantially
pure” in the claims, specification, or prosecution history,
we apply the “ordinary and customary” definition to
the claim term. In other contexts, this court has interpreted
“substantially” as a non-specific term of approximation
that avoids a numerical boundary. See, e.g.,
Playtex Prods., Inc. v. Procter & Gamble Co., 400 F.3d
901, 907 (Fed. Cir. 2005); Liquid Dynamics Corp. v.
Vaughan Co., 355 F.3d 1361, 1368 (Fed. Cir. 2004)


Therefore, we adopt the Appellants’ proposed construction
of “substantially pure regioisomer of the following formula”
as used in the ’703 patent and construe the term to
mean “largely but not wholly the para regioisomer of the
intermediate of the structure shown, as compared to the
meta isomer.”

The decision is reversed and appellants Aventis/AMR win.

Judge Bryson dissented:

The majority embraces Aventis’s proposed construction,
holding that the patent gives the term “substantially
pure” different meanings when referring to the terms
“substantially pure regioisomer” and “substantially pure
piperidine derivative.” As the district court ruled, however,
the intrinsic evidence does not distinguish between the
way “substantially pure” is used with respect to those two
terms, and for that reason I would uphold the district
court’s claim construction.


However, general principles of claim
construction are instructive here. “[W]e presume, unless
otherwise compelled, that the same claim term in the
same patent or related patents carries the same construed
meaning.” Omega Eng’g, Inc. v. Raytek Corp., 334 F.3d
1314, 1334 (Fed. Cir. 2003); see also Paragon Solutions,
LLC v. Timex Corp., 566 F.3d 1075, 1087 (Fed. Cir. 2009)
(“We apply a presumption that the same terms appearing
in different portions of the claims should be given the
same meaning unless it is clear from the specification and
prosecution history that the terms have different meanings
at different portions of the claims.”).


There is no basis for ignoring the intrinsic record and
the presumption that “substantially pure” is a discrete
claim term with a consistent meaning throughout the
patent. Aventis apparently believes that for “substantially
pure” to be construed to have the same meaning each
time it is used in the patent, the patentee would have to
explicitly “link” the purity of the para-CPK intermediate
to that of the end product. But Aventis has it backwards:
If the patentee wanted “substantially pure” to have different
meanings when applied to different elements, it
needed to explicitly “unlink” them.

Leading to

In sum, I conclude that “substantially pure” means “at
least 98% purity with respect to all impurities” and that it
has that meaning with respect to both regioisomers and
the end product. I would therefore affirm the district
court’s judgment.


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