SCHERING CORPORATION v. APOTEX INC. et al
REDACTED OPINION. Signed by Judge Peter G. Sheridan on 06/15/2012. (kam)
NOT FOR PUBLICATION
UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF NEW JERSEY
Civil Action No.:
APOTEX INC. and APOTEX CORP.,
This is an action for patent infringement and invalidity. The Court has jurisdiction pursuant
to Title 35 of the U.S. Code. More specifically, Plaintiff Schering Corporation (“Schering”) alleges
infringement of claims 1 and 11 of U.S. Patent No. 6,127,353 (’353 patent) on the product known
as Nasonex® as well as inducement to infringe, by Defendant, Apotex, Inc. (“Apotex”). Apotex
counterclaims that the ’353 patent is invalid because it was obvious and anticipated. See KSR Int'l
Co. v. Teleflex, Inc., 550 U.S. 398 (2007).
For purposes of organization, the decision is split into two major parts (Infringement and
Invalidity) and each part has a number of sections. Within Part One (Infringement), the sections are
(1) the parties, (2) the patent, (3) the issues, (4) the burden of proof,( 5) evidence and analysis of the
facts (which is further divided into subsections named (a) testing procedures; (b) XRPD analysis and;
(c) other factors) and (6) conclusion. In Part Two (Invalidity), the sections are (1) the patent history,
(2) the burden of proof, (3) anticipation, and (4) obviousness.
PART ONE – INFRINGEMENT
Section 1. The Parties
Plaintiff Schering Corporation is organized under the laws of New Jersey, with its principal
place of business located in Kenilworth, New Jersey. Schering is a wholly-owned subsidiary of
Merck & Co., Inc. Defendant Apotex, Inc. is a corporation, incorporated under the laws of Canada,
with its principal place of business located in Toronto, Ontario, Canada. It has a subsidiary, Apotex
Corp., located in Weston, Florida.
Apotex filed an abbreviated new drug application (“ANDA”) to produce a nasal spray to
reduce seasonal and perennial rhinitis symptoms in adults and children over 12 years of age. More
specifically, on or before November 6, 2009, Apotex assembled and filed (ANDA No. 91-161) with
the United States Food and Drug Administration (“FDA”) for generic mometasone furoate anhydrate
(non-water) nasal spray, 50 mcg. [SF ¶ 5]. See 21 U.S.C. § 355(j)(2).
As referred to above, Schering claims Apotex’s ANDA product is infringing on its ’353
patent. Schering sells Nasonex® as a metered-dose, manual pump spray unit containing an aqueous
suspension of mometasone furoate monohydrate (water) equivalent to 0.05% mometasone furoate
calculated on the anhydrous basis (non-water).
Apotex claims its ANDA Product is different from Nasonex® because it intends to
manufacture a nasal spray which contains mometasone furoate anhydrous (non-water). As such,
Apotex alleges that its active pharmaceutical ingredient (“API”) is different—anhydrous as opposed
Section 2. The Patent
The ’353 patent was issued from U.S. Patent Application No. 07/984,573 (“the ’573
application”) on October 3, 2000.1 The ’353 patent is directed towards a composition of matter and
focuses the novel crystalline form of mometasone furoate; as well as on various types of
pharmaceutical compositions utilizing mometasone furoate monohydrate. (T. 1291, 22). Schering
claims Apotex infringes upon Claims 1 and 11 of the ’353 patent. Claim 1 of the ’353 patent
describes the compound 9á,21-dichloro-16á-methyl-1,4-pregnadiene-11â ,17á-diol-3,20 dione-17(2-furoate) monohydrate, which is also referred to as mometasone furoate monohydrate. Claim 5
of the ’353 patent is directed to the compound 9á,21-dichloro-16á-methyl-1,4-pregnadiene-11â,17ádiol-3,20-dione-17-(2’ furoate) monohydrate as exhibiting x-ray crystallographic powder diffraction
pattern (XRPD) having certain peaks with particular spacing and intensity.
Claim 6 is directed to a pharmaceutical composition comprising mometasone furoate
monohydrate in a carrier consisting essentially of water. Claim 11 is dependent on Claim 6 and is
directed to the pharmaceutical composition of Claim 6 formulated as a nasal spray. Claim 11 of the
’353 patent specifically claims the use of mometasone furoate monohydrate in a nasal spray
In addition to the above, the ’353 patent discloses several different testing methods to
determine whether a compound or formulation contains mometasone furoate monohydrate. Among
these methods are water analysis, x-ray particle diffraction (“XRPD”), and infrared spectroscopy.
(’353 patent, col. 1, ll. 50-67).
The ’353 patent provides a graph (figure 1) showing the infrared spectrum of crystalline
mometasone furoate monohydrate and a graph of the XRPD of crystalline mometasone furoate
As noted previously, the prosecution history is set forth in Part II, infra.
monohydrate (figure 2). (PTX-2 at figs. 1 and 2).
Based on the ’353 patent data, if the monohydrate form existed in the Apotex ANDA
Product, the results of an XRPD analysis on the Apotex ANDA Product should closely correspond
to the graph in figure 2 of the ’353 patent. That is, the Apotex ANDA Product exhibited through
XRPD testing should be analyzed to determine whether it has certain peaks with particular spacing
and intensity as detailed in the ’353 patent. Figure 2 of the ’353 patent is as follows:
Section 3. The Issues
Since the ’353 patent sets forth a graph which depicts a monohydrate, the proof, at first
glance, would be to compare the XRPD graph in figure 2 to of the monohydrate to the XRPD results
of a sample of the Apotex ANDA Product. If there is a match, then infringement occurred.
Unfortunately, the proofs are not so simple for several reasons.
First, there is no allegation by Schering that Apotex used a monohydrate at the time of
manufacture. Schering’s claim is that the anhydrate in the Apotex ANDA Product converts to a
monohydrate between the date of manufacture and its expiration date (two years). Hence, to prove
infringement, Schering must show that conversion occurred within two years after manufacture (the
Second, the mometasone furoate monohydrate depicted on figure 2 of the ’353 patent was
very pure, while the Apotex ANDA Product surrounds the mometasone furoate with several
materials such as Avicel which is a “sticky” substance. Hence, in order to have a more sensitive
depiction of the mometasone furoate during XRPD testing, Schering needed to remove the other
ingredients prior to testing. This was accomplished by shaking or heating the Apotex ANDA
Product. These methods used to remove the other ingredients prior to XRPD testing gave rise to the
issue of whether Schering’s expert fundamentally changed the substance of the Apotex ANDA
The last issue concerns whether the XRPD testing results as shown in figure 2 of the ’353
patent must be matched in whole or in part to conclude that the anhydrate converted to a
Section 4. The Burden of Proof – Preponderance of the Evidence
Generally, in a non-jury case such as this, the Court must determine whether Schering met
its burden of proof. In this case, the standard is by a preponderance of the evidence. The model jury
instructions give a framework that the Court can use to guide its decision here. Paraphrasing the
model charge, Schering has to prove, in light of all the evidence, that what it claims is more likely
so than not so. To say it differently; if you were to put the evidence favorable to Schering, and the
evidence favorable to Apotex on opposite sides of the scale, Schering would have to make the scales
tip somewhat on its side. If Schering fails to meet this burden, the verdict must be for Apotex. If
one finds after considering all the evidence that a claim or fact is more likely so than not so, then the
claim or fact has been proven by a preponderance of the evidence. See Model Jury Charges §1.10,
Preliminary Instructions, Preponderance of the Evidence.
In determining whether the facts have been proven by a preponderance of evidence in this
case, the Court must consider the testimony of all witnesses, regardless of whom may have called
them, and all exhibits received in evidence, regardless of whom may have produced them. This
“standard required an analysis and weighing of all the evidence presented on both sides.” See United
States v. Montague, 40 F. 3d 1251, 1254-55 (D.C. Cir. 1994).
Section 5. Evidence and Analysis of Facts
A. Testing Procedures
Schering retained Dr. Adam Matzger2 to analyze the Apotex ANDA Product to determine
whether it converted from an anhydrate to a monohydrate within the Time Period. Apotex produced
41 bottles of its ANDA Product for Dr. Matzger to test. However, testing on the Apotex ANDA
Product did not occur until the samples were near or beyond the Time Period. That is, the contents
of the Apotex ANDA Product were manufactured in June 2008 and the testing occurred in
Adam Matzger is currently a Professor of Chemistry and of Macromolecular Science and
Engineering at the University of Michigan in Ann Arbor, MI. He is also Co-Founder, President, and
CEO of ChemXLerate, LLC, which provides analytical services, including solid state
characterization of materials and chemical characterization. Dr. Matzger’s expertise focuses on
organic materials in the solid state with a particular interest in the crystallization of pharmaceutical
compounds and related molecules. He received his Ph.D in Organic Chemistry from the University
of California at Berkeley in 1997, and has a B.A. in Chemistry from Oberlin College in Oberlin, OH
September 2010—more than two years after the manufacture date. Hence, it was critical for Dr.
Matzger to resolve how he would prepare the Apotex ANDA Product to show conversion within the
When Dr. Matzger first received the Apotex ANDA Product samples, he did not perform any
XRPD tests on the samples to see if the monohydrate appeared.3 Dr. Matzger thought that in order
to investigate the contents of the Apotex ANDA Product, he must first understand the contents of
the product, and then generally adjust his methodology to obtain the most sensitive results from an
The Apotex ANDA Product formulation is as follows:
Dr. Matzger testified that he prepared samples of the Apotex ANDA Product to accelerate
conversion from an anhydrate to a monohydrate in order to determine if the conversion occurred
within the Time Period. Dr. Matzger labeled each bottle and then he subdivided bottles into
numerous samples which were placed in glass vials. (T. 259, 2-5). About sixty samples were
According to Dr. Matzger, the ingredient most difficult to eradicate or separate from others
to determine whether monohydrate was present is Avicel. The Avicel ingredient is “sticky,” (T. 299,
3), or like the molecules are sitting inside glue, (T. 160, 22), and in order to achieve greater
sensitivity in the XRPD analysis, the Avicel must be separated from the rest of the sample. In
Such XRPD analysis may have shown that several months after the expiration date, the
Apotex ANDA Product converted to the monohydrate. If this occurred, it would most likely be
circumstantial evidence that the conversion occurred and somehow linked backward.
addition, the concentration of mometasone furoate within the Apotex ANDA Product would be
something less than one-part-in-2000, (T. 252, 4-5), and as such, Dr. Matzger recognized that the
samples must be prepared to achieve high levels of sensitivity. (T. 261, 1-10) (T. 270, 6-23) (T. 296,
17 through T. 297, 9). Hence, Dr. Matzger centrifuged some samples (1-to-3 times), and he also
shook (T. 208, 18), rotated (T. 210, 4-8) and spun (T. 208, 18-23) some samples. Other samples
were simply centrifuged 3 times (APOMOM 12242, 12245, 12246 and 12247). Dr. Matzger found
these procedures to be relatively standard techniques within his field4. (T. 252, 9).
Dr. Threlfall,5 an expert for Apotex, was critical of the tests performed by Dr. Matzger. (T.
868, 24 through T. 869, 2). Dr. Threlfall noted that other ingredients in the Apotex ANDA Product
were “thickening agents, preservatives, or protective colloids, such as pH controlling reagents,” (T.
871, 7-10), and as such, every cell is particularly important. For instance, Dr. Threlfall indicates that
a thickening agent coats both the molecules and the crystals (protective colloid) and hinders
agglomeration; the buffers control the pH of the solution to prevent API from becoming to acid; and
the benzyl conium chloride acts as an anti-coagulate upon the molecules and crystals. (T. 871, 1522). Further, Dr. Threlfall indicated that only 25 of the 60 samples tested by Dr. Matzger “were
claimed to have monohydrate,” and he disagrees whether any of them showed monohydrate.
Annexed is a chart showing the tests performed by Dr. Matzger.
Terence L. Threlfall is presently a Senior Research Fellow in the Department of Chemistry
at the University of Southampton, United Kingdom. Dr. Threlfall’s area of expertise is
polymorphism and other aspects of solid state crystal structure and behavior, and in understanding
crystallization and transformation processes. Additionally, Dr. Threlfall’s research interests are in
relating molecular structure to crystal structure using structural systematics and in applying
spectroscopy and microscopy to crystallization and to solid-solid transition processes. Dr. Threlfall
received a B.S. in Chemistry from London University in 1956, a Ph.D. in Organic Chemistry from
London University in 1971, and a L.L.B. from the University of London in 1984.
Dr. Threlfall found Dr. Matzger’s testimony troubling in four ways. Dr. Threlfall stated:
I think he went wrong at four levels: I don't think he applied proper
scientific judgment to his testing; I think that the design of his
experiments was wrong; the actual performance of experiments leads
a lot to be desired; and I think that he analyzed the data incorrectly.
(T. 909, 15-19).
Dr. Threlfall opined that Dr. Matzger had “the mindset of an advocate rather than of a
scientist. And in particular, Dr. Matzger went on the hunt for traces of material, without really
applying scientific judgment, . . . .” (T. 910, 10-14). Although Dr. Matzger found that conversion
begins to occur as soon as the Apotex ANDA Product is manufactured, Dr. Threlfall’s calculation
was far different. According to Dr. Threlfall, the “Apotex formulation would be stable against
conversion to the monohydrate for around 800 years.” (T. 922, 21-24).
Dr. Threlfall was very critical of the shaking or vortexing procedure of Dr. Matzger. Dr.
Matzger indicates that the shaking was “gentle.” Dr. Threlfall disagreed, he honed in on vortexing.
A. Vortexing is an even more energetic process. I mean it's like
creating a mini tornado within the tube. And you can imagine that
sort of -- smashes all things to pieces, it grinds the nuclei together, it
causes them to break and nascent surfaces to form, and nascent
surfaces are much more susceptible to change than the intact one
would be, because they lost their coatings basically for a moment, and
therefore they can change when they wouldn't have otherwise been
subjected to change.
(T. 925, 18 through T. 926, 1). Likewise, Threlfall was critical of the washing. He opined that Dr.
Matzger “washed out some of the essential components,” (T. 926, 8-10), and that the removal of
Avicel by shaking and washing was deleting its “protective coating.” (T. 926, 20). Threlfall likened
the removal of Avicel to an explorer sent to the Arctic, and then his clothes are “pinched, and you
leave him in his underwear.” (T. 926, 19-23). Evidently, Threlfall believes that when Dr. Matzger
washed and shaked the Apotex product, he was undermining the stability of the compound. (T. 926,
In commenting on Dr. Matzger’s procedures, Threlfall stated “I would describe this as
making scrambled eggs and then claiming you still had the eggs with the shells in the carton.” (T.
The issue is whether Schering met its burden of proof by a preponderance of the evidence
with regard to the existence of monohydrate when the samples were shaken or vortexed to the extent
that the material may have changed. Dr. Threlfall opined that Avicel “gels around the material . .
. [and] in human terms [its] like swimming through molasses.’ (T. 920, 6-9). Avicel is thixotropic,
which means “not only does it thin when you shake it . . . but it continues to thin with more shaking.”
(T. 921, 12-15). Accordingly, as shaken, “Avicel reduces its viscosity by a factor of 10,000.” (T.
Although Dr. Threlfall may have exaggerated some of his opinions through his colorful
analogies, his demeanor was truthful. Dr. Threlfall connoted that Dr. Matzger overstepped the
boundaries of a disciplined scientist. The Court gives weight to Dr. Threlfall’s testimony. With
regard to the samples that were shaken or vortexed, Schering has not met its burden of proof by a
preponderance of the evidence. If one places the evidence favorable to Schering on one side of a
scale, and all the evidence favorable to Apotex on the other, the scale does not tilt toward Schering.
As such, Schering can not meet its burden of proof on any samples that were shaken or vortexed.
B. XRPD Analysis
Putting aside the samples that were shaken, there are at least four samples which were only
centrifuged. The samples were marked as APOMOM 012242, 012245, 012246, and 012247. (T.
270, 6-23) (PTX-193 at 18-23). In order to increase sensitivity of the XRPD test for the Apotex’s
ANDA Product, it was necessary to reduce it to a solid through centrifugation. Dr. Matzger prepared
the samples (APOMOM 012242, 012245, 012246, and 012247) as follows. Each sample was
prepared “to get a better signal to noise for the samples.” Dr. Matzger centrifuged the material three
times, “trying to separate the crystalline material out in particular to gain better signal to noise.” (T.
270, 19-22). In between the centrifuging, each sample was mixed slightly “to help remove the water
soluble components” from the formulation, (T. 270, 23 through T. 271, 2), and water was added
twice. After the last centrifugation, “the water that was used as washes . . . was decanted and the
solid material at the bottom was loaded for analysis into the x-ray diffraction cell . . .” (T. 271, 5-12).
Similarly Dr. Butcher6, an expert for Apotex, conducted XRPD tests of certain samples. Dr.
Butcher undertook a similar process. Dr. Butcher centrifuged each sample four times. (T. 719, 9).
After the first centrifuge he decanted the sample and replaced it with an equal volume of distilled
water. (T. 718, 19-22). Hence, the centrifugation and washing of the samples is consistent for both
Apotex and Schering. As such, these samples are different from the major criticism of Dr. Threlfall
as set forth in the last section. In addition, Dr. Cockcroft acknowledged that he was “happy” with
the centrifugation step. (T. 827, 3-4).
Since XRPD results are a critical part of the analysis for issuance of the ’353 patent, such
Raymond Butcher is currently a Professor in the Department of Chemistry at Howard
University since 1997. Dr. Butcher has published over eight hundred publications including articles
published in journals such as Structural Chemistry, CrystEngComm, Organic & Biomolecular
Chemistry, Journal of the American Chemical Society, and Angewandte Chemie. Dr. Butcher
received a B.Sc. with Honours in Chemistry from the University of Canterbury, New Zealand in
1968, and a Ph.D. in Inorganic Chemistry and X-Ray Crystallography from the University of
Canterbury, New Zealand in 1974.
testing was conducted to determine if a monohydrate could be found in the Apotex ANDA Product.
More specifically, Schering claims that the anhydrate converts to a monohydrate prior to its
expiration of two years from manufacture date (Time Period) and as such infringes on the ’353
patent. The primary issue at trial was whether the conversion occurred.
XRPD is the standard method for looking at solid materials and polymorphs. (T. 228,
17-23).7 XRPD looks at arrangement and characteristic spacings of molecules by measuring the
intensity of refracted X-rays at different angles. (T. 230, 10-20). According to Dr. Matzger, XRPD
is relatively sensitive and excellent at being able to differentiate between different forms of the same
compounds. (T. 228, 17-23). Dr. Cockcroft found that Dr. Matzger did not find peaks due to the lack
of intensity; and at best, he found “bumps.” (T. 781, 13).
Dr. Cockcroft,8 an expert for Apotex, noted that x-ray diffraction is covered by a very simple
equation “developed by Nobel prize winner William Brack in 1913.” The Brack formula relates “to
the two-theta values in a diffraction powder” in terms of intensity. (T. 780, 13-21). Based on this
formula, the XRPD testing device (diffractometer) was created, and it depicts material on a graph
based on the intensity of its peaks. In Dr. Matzger’s testing, he used an automatic diffractometer on
XRPD and PXRD are the same test for x-ray powder diffraction. (T. 227, 18) (T. 838, 4
through T. 839, 3).
Jeremy Karl Cockcroft is presently a Senior Lecturer in the Department of Chemistry,
University College London, United Kingdom. Dr. Cockcroft’s expertise is in powder x-ray
diffraction (“XRPD”). Specifically, Dr. Cockcroft’s research has ranged from XRPD
instrumentation to the development of software for the characterization of compounds using the
technique. Recently, he established a new XRPD laboratory specialized in evaluating how
temperature differences impact upon the solid state forms of a wide range of samples from ceramics
to pharmaceuticals. Dr. Cockcroft received a B.A. in Chemistry from St. Catherine’s College,
Oxford in 1981, and a Ph.D in Chemistry from Oxford University in 1985.
which he set the scan through the two-theta angles. Once he filled a cell with the prepared sample,
the diffractometer then automatically records any peaks based on the intensity on a graph. (T. 262,
21-25). A peak is produced by a clear signal or intensity. That is, the diffractometer “measures an
intensity at each angle . . . so [there] is an intensity versus two-theta peak.” (T. 261, 3-6). Often the
prepared sample may have some different materials commingled in it during XRPD testing, and the
peak may be surrounded by noise (non-peak sound). The signal to noise factor was critical in this
case for several reasons.
First, according to Dr. Matzger there were significant overlaps between peaks of mometasone
furoate anhydrous and mometasone furoate monohydrate at 20 values above approximately 12
degrees. As a result, it would have been impractical for Dr. Matzger to collect or analyze data from
higher 20 values (T. 437, 16 through T. 438, 19), and accordingly, Dr. Matzger limited his findings
to those under the 20 values. Hence, Dr. Matzger analyzed only a portion of the peaks shown on
figure 2. of the ’353 patent.
Second, the monohydrate depicted in figure 2 was very pure, while the materials in the
prepared sample were commingled with other materials that were not separated, and this may have
created noise during Dr. Matzger’s testing. In order to determine whether a peak exists, it must rise
significantly above the noise levels in the diffractional data. (T. 781, 11-15).
Third, the signals from the XRPD conducted by Dr. Matzger must relate to the peaks of
figure 2. The issue which arises is how many peaks on figure 2 can be matched to the prepared
sample to show a monohydrate. Dr. Matzger indicates that it should be a subset of the peaks in
figure 2. (T. 620, 8-15). Dr. Matzger found that a match showing a monohydrate existed if 1 or 2
peaks were shown. Dr. Cockcroft indicates that at least three peaks must be shown to identify a
monohydrate based on practice in the field. That is, it is “accepted practice to use at least three
peaks, often more to identify material.” (T. 779, 23-24). Dr. Cockcroft noted that crystals are three
dimensional objects, and to measure these crystals, one must find length, width and depth, and each
peak must be unique. If two peaks are the same, or a factor of each other, it could be a duplication.
(T. 785, 1-7) (see below).
According to Dr. Cockcroft, the history of the three peaks standard is derived from the work
of Mr. Hanawalt. Evidently, in the 1940’s, Hanawalt was researching numerous minerals which
required him to perform XRPD tests on many minerals. Since there were so many samples,
Hanawalt devised a database of XRPD patterns so he could identify each one. In developing a card
system to identify each sample, he listed the three most intense peaks of the material on a separate
card. This format became known as the Hanawalt Search Index. (T. 788, 4-12). Due to this practice,
most scientists still use three peaks to identify a pattern. (T. 788, 4-12).
Lastly, the use of the Brack Formula recognizes that if a peak occurs at a specific level (say
7.8 degrees) and another peak occurs at a factor of 2 (say 15.6), the second peak is a duplication of
the first; and hence it is not considered a unique peak (T. 780, 19-25). Hence, duplication must be
considered in analyzing XRPD results.
All four samples were subject to XRPD analysis and recorded on a graph (PTX-451). In each
of the samples, Dr. Matzger found “evidence of conversion” with peaks at 7.8 and 11.6 as recorded
on figure 2 of the patent. (T. 272, 19-25).9 On sample 012245, Dr. Matzger found that XRPD
showed three peaks “consistent with conversion,” namely 7.8, 15.6 and 11.6. (T. 277, 13-19). With
PTX-479 was also admitted because it is another chart about APX 102242 with different
scaling. (T. 275, 7-16).
regard to the 15.6 peak, it is a factor of 2 of the 7.8 peak. Dr. Matzger noted it “illustrates . . . the
problems you can have with overlap because there is a shoulder here that is associated with the 15.6
degree peak as opposed to a “distinct peak as it did in the previous pattern.” (T. 278, 11-18) (PTX480). Despite the fact that it is a shoulder and not a peak, he opined that “its all consistent with
conversion.” (T. 278, 20). In sample 012245, Dr. Matzger fails to consider the limitation within
Brack’s formula (see above). Dr. Cockcroft had indicated that a peak at 7.8 and a peak at 15.6 were
duplicative based on the application of the Brack formula. Hence, in sample 012245, there are not
three peaks as Dr. Matzger finds, but only two in accordance with the Brack formula. Dr. Matzger
never refuted the Brack formula, as such, the limitations within the Brack formula are credible.
In reviewing samples 012242, 012246, 012246 and 012245, there are only two peaks shown.
The testimony of Dr. Cockcroft about the need to find three peaks seems more reasonable than Dr.
Matzger’s “subset” analysis. Figure 2 of the ’353 patent disclosed a graph with at least 25 peaks
showing the monohydrate. To rely on one or two peaks is insufficient upon which to find a match
to figure 2. As such, Schering failed to meet its burden of proof that a monohydrate existed in the
Apotex ANDA Product based upon the XRPD analysis considered.
C. Other Factors
Dr. Matzger opined that his XRPD tests should control because his results make sense in
light of three other items—preferred orientation, the Bodycote Report, and Raman Spectrography.
Each is discussed below.
(a) Preferred Orientation
Preferred orientation is a concept which explains why certain peaks can not be found on the
XRPD results. By example, Dr. Matzger stated rain that freezes is “spherical, hail shaped, there’s
no real orientation . . . they come down at random.” Opposed to that are “a bunch of pennies” that
fall on a table, they will adopt one orientation” that is flat. (T. 233, 1-10). This happens in
pharmaceuticals when different shapes of crystals may “lead to a different arrangement” (T. 233, 1214). Due to preferred orientation if all the crystals are laying flat, “not all of the peaks will be
observable.” In fact, “you can have cases where preferred orientation is extreme enough that peaks
are not observed.” (T. 234, 17-18).
Dr. Cockcroft disagrees. Dr. Cockcroft indicated if pennies were thrown on a table, “some
lie flat compared to some lying randomly, tilted on angels. And that’s what meant by preferred
orientation, that there is a preferential direction with regard to the crystallites.” (T. 822, 18-25). Dr.
Cockcroft was incredulous about Dr. Matzger’s finding. He stated:
Because the theory that he's advocating is one so extreme that he's
simply saying all the other peaks vanish. And as I just explained to
your Honor, you can have degrees of preferred orientation, you may
expect the majority of say the coins to lie one way up; you don't
expect a hundred percent of them to lie one way up. And therefore
you still expect to see, maybe with lower intensity, the other peaks in
the powder x-ray diffraction pattern.
(T. 825, 12-19).
Dr. Threlfall also disagreed with Dr. Matzger’s findings on preferred orientation. Dr.
Threlfall stated Dr. Matzger “ignored” some data. He stated:
A. Well, in his preferred orientation theory he suggests that he didn't
see the 14.1, 15.2, and indeed also the 17.5, the 18.7; and in one case
even as he actually went as far as 34 degrees two-theta, the 31.2
degrees peak, which is actually a substantial -- surprisingly substantial
peak in the reference monohydrate, which is actually the third order
of the 7.8 peak. So he should have observed that even in preferred
orientation circumstances, but he just ignored that. Ignored all the
things that he didn't want to see.
(T. 910, 19 through T. 911, 2). In the Court’s view, the practice of finding three peaks as per the
Hanawalt practice is very sound. The preferred orientation explanation tends to undermine the
practice of finding three peaks, and applying preferred orientation to all prepared samples appears
to be overly aggressive in light of Dr. Cockcroft and Dr. Threlfall’s testimony. Little weight is given
to the preferred orientation theory.
(b) Bodycote Report
Dr. Matzger argues that his findings are consistent with the conclusions of the Bodycote
Report, and therefore his findings should be considered reasonable. By way of background, in 2000,
Bodycote Ortech authored a report confirming that the anhydrate converted to monohydrate (T. 304,
19-22). Dr. Hui, a product manager at Novex, testified that in 2000 Bodycote had tested
mometasone furoate on behalf of Novex Pharma, a close affiliate of Apotex. Dr. Matzger focused
on the XRPD results of three different formulations of Bodycote testing. Within the Bodycote
Report, Dr. Matzger stated there were findings that “there was conversion in the formulations . . .
of anhydrous mometasone furoate anhydrate to . . . a monohydrate.” (T. 310, 1-4). More particularly,
Dr. Matzger focused on three formulations (4A, 4B and 4C) that were subject to XRPD testing
within seven weeks after production. Dr. Matzger was most impressed with the XRPD results of
formulation 4A because it is “the closest to Apotex’s ANDA Product.” (T. 328, 1-5). The “two most
important things” from the formula 4A results were “one is it shows the 7.8 degree peak . . .
consistent with conversion to a mometasone furoate monohydrate [and] that's also the only
prominent peak difference between that and anhydrous mometasone furoate. And so it shows that
you can get strong preferred orientation in this system.” (T. 330, 4-10).
In addition to Dr. Matzger’s comments, Dr. Kovacs, an Apotex representative, testified at
his deposition that the Bodycote Report found that seven weeks after production of formula 4A, it
contained both monohydrate and anhydrate forms. (Kovacs Depo. at T. 175, 2-10).
Apotex denies that formula 4A contains monohydrate. Apotex argues that the Bodycote
Report is over ten years old and therefore remote. In addition, it is likely to be either (1) “a
degradation product; or (2) the 2.5% crystal identified by Dr. Eckhart (T. 123, 19 through T. 124,
3); or (3) it lacks sufficient peaks on the XRPD test to be considered a monohydrate.
The Court finds that the Bodycote Report is relevant; but the Report itself was not supported
by any first hand testimony or evidence by a person performing or overseeing the test. Although it
may support Dr. Matzger, it does not add much weight to his testimony in light of Dr. Cockcroft’s
and Dr. Threlfall’s testimony.
(c) Raman Spectroscopy
Raman Spectroscopy provides information about the vibrational modes of bonds in a
molecule. (T. 229, 11-21). Dr. Matzger noted the difference between Raman and XRPD testing,
“with the x-ray you analyze the whole sample at once, and because this [Raman] is hooked up to a
microscope we can look at it piece by piece and actually figure out where . . . different particles, what
form they are [and] if we’re looking at, for example, mometasone furoate or other places in the
system.” (T. 229, 4-9). Since Raman gives information about vibrational modes in a molecule, you
learn “literally the way the atoms are vibrating within a molecule, which is a characteristic.” (T. 229,
11-14). In the ’353 patent, Raman Spectroscopy is not named as a testing method, but infrared
spectroscopy is so named. Dr. Matzger explained that infrared and Raman are related as a “slightly
different flavor of vibrational spectroscopy.” (T. 229, 14-20). More particularly, Raman provides
more information about spatial distribution and due to the smallness of particle size of the
monohydrate Raman provided “superior” resolution. (T. 624, 14-19). Dr. Matzger concluded that
both the XRPD and the Raman testing “showed substantial conversion in” samples 012242, ‘45, ‘46
and ‘47 as well as sample 012225. (T. 405, 23 through T. 406, 15). To the contrary, Dr. Cockcroft
and Dr. Threlfall found the same problem as they did with Dr. Matzger’s XRPD findings—there
were less than three peaks found, and therefore a monohydrate cannot be identified as a result of the
Raman testing. (T. 943, 7-13).
Dr. Matzger’s Raman findings are at odds with the results of Raman tests completed by Dr.
Spingarn10 on behalf of Apotex. Dr. Spingarn performed Raman testing on ten random particles of
the Apotex ANDA Product. He sprayed a sample onto a filter and let the liquid drain out. (T. 654,
1-3). From the solids on the filter, he focused on the “smaller particles” that were crystalline and had
sharp edges. (T. 651, 20-23). From his Raman testing he found there “was no evidence of . . . [a]
monohydrate in the sample,” and the crystals were relatively uniform in size and appearance.” (T.
The Court finds that the Raman Spectroscopy as relied upon by Dr. Matzger has little weight
because it does not identify three peaks, and there is a significant difference in test results between
Dr. Spingarn and Dr. Matzger.
Neil Elliot Spingarn is the President of S & N Laboratories, an independent testing laboratory
located in Santa Ana, California since 1984. Dr. Spingarn’s expertise is in all aspects of
microanalysis, and in particular conducting Raman Spectroscopy measurements. Dr. Spingarn
received a B.A. in Biochemistry from the University of California at Berkeley in 1974, a M.S. and
M. Phil. in Pharmacology from Yale University in 1976, and a Ph.D. in Pharmacology from Yale
University in 1978.
Section 6. Conclusion
Based upon the facts and conclusions reached above, the Court finds the complaint based
upon infringement is dismissed because Schering has failed to present credible evidence sufficient
to meet its burden of proof by a preponderance of the evidence standard.
PART TWO – INVALIDITY
Section 1. The Patent History
In the early 1980’s, Elliot Shapiro, a chemist employed by Schering, first synthesized
anhydrous mometasone furoate. (FPTO at 7). On July 29, 1982, Schering filed an application for
a patent on anhydrous mometasone furoate, and the Patent No. 4,472,393 was issued on Sept. 18,
1984 (the “Shapiro” patent). After its discovery, mometasone furoate anhydrate was placed on
Schering’s “backburner” because of very unique physical properties which created a hurdle for
development. Among these properties was the fact that mometasone furoate anhydrate was an
insoluble compound in water, and known pharmaceutically acceptable solvents were unable to
dissolve the compound. (Sequiera Depo. at T. 65, 2 through T. 66, 19).
In the early to mid-1980’s, researchers at Schering discovered that mometasone furoate could
be dissolved with one of the newer pharmaceutical solvents, hexylene glycol. (Sequiera Depo. at T.
66, 20 through T. 67, 2). After discovering that mometasone furoate could be dissolved with
hexylene glycol, Schering pursued a mometasone furoate formulation for the treatment of psoriasis,
a skin condition. (Sequiera Depo. at T. 77, 7-25).
Until the discovery of mometasone furoate monohydrate reflected in the ’353 patent, the only
known form of mometasone furoate was the anhydrous form. (PTX-2 at 1:18-28). Subsequently,
in the late 1980’s, Schering began considering other, nondermatological uses for mometasone furoate
anhydrous. (T. 60, 4-22) (T. 67, 18-23), and at that time, Dr. Pui-Ho Yuen, a formulator at
Schering,11 took responsibility for a project to develop mometasone furoate into nasal applications.
While at Schering, Dr. Yuen held the positions of Senior Scientist, Associate Principal
Scientist, Principal Scientist, and Senior Principal Scientist. (T. 31, 2-11). He is co-inventor of the
(T. 31, 22-25). It took about 2.5 years to develop the alleged invention. There were many trials and
errors. In order to develop the alleged invention, Dr. Yuen researched the literature to determine
how to formulate a suspension for nasal delivery, and gathered information that Schering had
gathered on mometasone furoate. His initial research on the background showed that there was very
little information regarding aqueous nasal suspension formulations. (T. 36, 5-8).
Dr. Yuen uncovered that nasal sprays can be formulated as both suspensions and solutions.
In 1988, only two glucocorticosteroids were approved for intranasal use in the United
States—beclomethasone dipropionate and flunisolide. (T. 974, 7-12).
One of these was a
suspension, and one was a solution. (PTX-394 at 344). In 1987, Dr. Yuen set out to formulate a
suspension12 of mometasone furoate for nasal application. (T. 31, 22-25).
Dr. Yuen concluded that to formulate a suspension of mometasone furoate, he must consider
particle size, distribution, the pH of the product, and solubility in water. (T. 34, 11-18). Dr. Yuen
recognized also that the product must not cause irritation to the user. (T. 35, 17-24). The particle
size of the active ingredient can affect the efficacy of the product. (T. 54, 9-22). The problem Dr.
Yuen confronted was that solid particles in suspension settle. This requires a thickening or
suspending agent, in order to increase the viscosity of the liquid, and slow settling. (T. 35, 9-16).
Over a period of two years, Dr. Yuen and his lab assistant, Teresa Etlinger, developed
between 30 and 40 formulations. (T. 36, 9-20). The original formulas were “to assess the stability
A suspension is a formulation in which the active ingredient remains in a solid state,
undissolved, and is suspended in a liquid vehicle. (T. 34, 11-14).
of the suspension.” (T. 38, 8 through T. 39, 14). During this time, Dr. Yuen and Ms. Etlinger noticed
that some of the formulations showed particle size growth (which is not a desirable effect). (T. 39,
12-16). As a result, Dr. Yuen and Ms. Etlinger attempted to formulate different formulations to
thwart the particle growth problem. That is, they changed the suspending agent and employed
different preservatives and antimicrobial agents. (T. 39, 17-20). None of these solutions worked.
Dr. Yuen and Ms. Etlinger regularly submitted prototype formulations for analysis. (T. 39, 17-19).
In the fall of 1988, Nancy Levine, one of the co-inventors on the ’353 patent, ran tests on
some of the samples. (PTX-322 at 76-77). The testing revealed that a new compound might be
present in at least one of these samples. As a result, additional testing occurred. (T. 94, 12 through
T. 98, 12). More specifically, Ms. Levine conducted initial stability tests, and then had the stability
samples subject to X-ray powder diffraction testing. (T. 89, 25 through T. 90, 22). As noted
previously, XRPD testing allows one to look at the solid state structure of a particular compound.
(Eckhart Depo. at T. 27, 14 through T. 28, 4). The test results on the September 22nd sample stated
that “[t]he [XRPD] and microscopic data support conversion of the original mometasone furoate
crystal structure to a second, possibly solvated, form.” (T. 92, 10-17).
Mr. Eckhart testified that the XRPD pattern he generated on the samples did not match up
with the reference standards he had seen previously for mometasone furoate. (Eckhart Depo. at T.
108, 10-17). Mr. Eckhart conducted additional testing on other formulations of mometasone furoate
nasal spray. Some, but not all, of the tests showed conversion of the anhydrous form of mometasone
furoate to the second form (the monohydrate). (T. 98, 13-100). As a result, the larger sized particle
that was appearing in some of the formulations was the active ingredient, mometasone furoate, in
a different crystalline form. (T. 41, 4-11). According to Schering, this discovery occurred in
November of 1988. (T. 41, 12-16).
Before this discovery, it was not known that mometasone furoate had different crystal forms.
(T. 41, 12-16) (T. 108, 17-20). The second form of mometasone furoate was ultimately identified
as mometasone furoate monohydrate. (T. 133, 17 through T. 134, 18). The conversion of anhydrous
mometasone furoate to the monohydrate form did not occur in all formulations, and appeared to be
unpredictable. (T. 41, 25 through T. 42, 5).
After Dr. Yuen discovered that the anhydrous mometasone furoate converted to the
monohydrate form in certain formulations, he began considering whether he could create a
formulation using the monohydrate form at the outset. (T. 41, 17-24).
In the summer of 1989, Dr. Yuen formulated several new formulations using mometasone
furoate monohydrate, (T. 42, 6-18), and developed the Nasonex® formula. Based on that
formulation, Schering undertook the patent process.
The Patent Office denied Schering’s request for a Patent at least three times over a ten year
period before its acceptance. Initially, the Patent Office did not see anything new in converting an
anhydrate to a monohydrate. Oversimplfying, according to the reviewer, it was just adding water.
On September 6, 1991, Schering filed foreign Patent Cooperation Treaty (PCT) Application
No. PCT/US91/06249 for another protective patent “mometasone furoate monohydrate, process for
making same and pharmaceutical compositions” (the “International Application”). (DTX-49 at 411).
Based on the International Application, Schering filed the ’573 application on March 5, 1993 as a
U.S. National Phase claiming priority from the International Application. (DTX-49 at 374). Claim
1 of both applications are directed to the monohydrate form of mometasone furoate. (Compare DTX48 at col. 6, ll. 31-32 with DTX-49 at 391) (see also T. 869, 10-23). In an Office Action dated
November 8, 1993, the USPTO rejected claim 1 of the ’573 application as anticipated by the Shapiro
patent. (DTX-49 at 429). In rejecting claim 1, the USPTO stated that the Shapiro patent discloses
a process involving recrystallization of mometasone furoate crystals from methanol:water, and that
the compound produced by this process (the “Recrystallization Compound”) “is inherently the
monohydrate of mometasone furoate.” (DTX-49 at 434-36 (citing Shapiro, col. 21, ll. 19-30)).
On March 9, 1994, Schering requested reconsideration of the ’573 application. (DTX-49 at
434-36). In their request for reconsideration, Schering argued that “[t]here is no teaching, disclosure,
or suggestion in the Shapiro patent itself to hydrate formation of any of the compounds claimed in
the patent.” (DTX-49 at 435-36). Additionally, Schering asserted that there is no evidence “to
support the conclusion that mometasone furoate recrystallized from methanol: water would
inherently form any hydrate molecule, much less the specific monohydrate of the subject
compound.” (DTX-49 at 436). In support of their arguments, Schering amended their application
to include claim 7, a XRPD pattern of the claimed mometasone furoate monohydrate compound.
(DTX-49 at 434, 437-38). In a Final Action dated August 1, 1994, the USPTO rejected claims 1 and
7 of the U.S. Application as anticipated by the Shapiro patent. (DTX-49 at 441). According to the
The mometasone furoate [in the Shapiro patent] is formed in a
reaction which includes reaction in a solvent followed by the addition
of 500ml of distilled water to quench the reaction. The product
formed by the addition of water would be expected to be a hydrate.
Additionally, absolute predictability is not required, only a reasonable
expectation that the monohydrate is produced.
(DTX-49 at 441).
On December 16, 1994, Schering appealed the USPTO’s July 29th decision to the Board of
Patent Appeals and Interferences, but both the appeal and the application were abandoned. (DTX-49
at 445-47). On petition from Schering, the U.S. Application was eventually reopened, and on
December 10, 1998, the USPTO issued a Second Non-Final Office Action, this time rejecting claims
1 through 7. (DTX-49 at 539-47). Claims 1, 2, 4, and 7 were rejected under 35 U.S.C. § 102(b) as
anticipated by the Shapiro patent. In rejecting these claims, the USPTO again cited to the
Recrystallization Compound, stating that it “is inherently the monohydrate of mometasone furoate.”
(DTX-49 at 545).13 Claims 3, 5, and 6 were rejected under 35 U.S.C. § 103(a) as obvious under
Shapiro. In rejecting these claims, the USPTO noted that these claims differed from the Shapiro
patent by reciting “specific organic solvent[s],” “specific formulation,” and “specific concentration
of excipients,” but determined that such differences were insubstantial. (DTX-49 at 547).
On March 15, 1999, Schering filed a reply to the USPTO’s office action. (DTX-49 at 54961). In an attempt to distinguish the Recrystallization Compound from the monohydrate form of
mometasone furoate, Schering’s reply included a declaration from Charles Eckhart, co-inventor of
the’573 application. (DTX-49 at 556-61). In his declaration, Mr. Eckhart claimed that Schering recreated the Recrystallization Compound back in May 1989 as part of its efforts to develop
mometasone furoate monohydrate. (DTX-49 at 557). According to Mr. Eckhart, a XRPD analysis
of the Recrystallization Compound conducted on June 1, 1989 revealed only the anhydrous form of
mometasone furoate. (DTX-49 at 557). In support of this claim, Mr. Eckhart attached an excerpt
The USPTO also found that the Shapiro patent “teaches [both] pharmaceutical compositions
[of mometasone furoate] and the anti-inflamatory propert[ies] of [such compositions].” (DTX-49 at
from the lab notebook that outlined the re-creation process and the corresponding XRPD pattern.
(DTX-49 at 557-61). In a Second Final Office Action dated June 28, 1999, the USPTO rejected
Schering’s claims, finding that Schering’s re-creation of the Shapiro patent process failed to follow
the process. (DTX-49 at 562-68). According to the USPTO, the Shapiro patent calls for mometasone
furoate to be mixed and dissolved in a solvent such as methanol or water. (DTX-49 at 556). The
Schering re-creation of the Shapiro patent mixed and dissolved mometasone furoate in hot
dicholoromethane. (DTX-49 at 556). The USPTO found this difference to be material and affirmed
their earlier rejection. (DTX-49 at 556-57).
After the USPTO’s Second Final Rejection, Schering reviewed the Shapiro patent files for
any evidence that the Recrystallization Compound was not the monohydrate form of mometasone
furoate. (DTX-49 at 570). Schering’s review ultimately produced an infrared IR spectrum of the
Recrystallization Compound that was generated during the development of the Shapiro patent.
(DTX-49 at 571). According to Schering, the rediscovered IR (infrared) spectrum lacked prevalent
water peaks. (DTX-49 at 591-99). On November 24, 1999, Schering officially replied to the Second
Final Office Action, notifying the USPTO of the rediscovered IR spectrum and arguing that the
absence of certain water peaks proved that the Recrystallization Compound was not a hydrate.
(DTX-49 at 591-99). The USPTO found this evidence persuasive, and on December 10, 1999, the
USPTO issued a Notice of Allowability. (DTX-49 at 600-02).
The ’353 patent was issued from ’573 application on October 3, 2000. As noted in Part I,
claim 1 of the ’353 patent is directed to the monohydrate form of mometasone furoate. (’353 patent,
col. 6, ll. 31-32) (T. 869, 15-23). Claim 11 is directed to the pharmaceutical composition comprising
mometasone furoate monohydrate in a carrier consisting essentially of water that is formulated as
a nasal spray.
On September 18, 2001, the Shapiro patent expired.
Section 2. Burden of Proof
A patent shall be presumed valid and the burden of establishing invalidity of a potent or any
claim thereof shall rest on the party asserting such invalidity. Microsoft Corp. v. i4i Ltd., 131 S. Ct.
2238, 2242 (2011). A party challenging the validity of any claim of a patent has the heavy burden
of proving invalidity by “clear and convincing” evidence. Id.; Takeda Chem. Indus. Ltd. v.
Alphapharm Party Ltd., 492 F.3d 1350, 1355 (Fed. Cir. 2007). Clear and convincing evidence is
evidence that produces in the fact finder’s mind a firm belief or conviction as to the matter at issue.
See Trans World Mfg. Corp v. Al Nyman & Sons, Inc., 750 F.2d 1552, 1560 (Fed. Cir. 1984). The
“clear and convincing” standard is an intermediate standard that lies somewhere between the
“beyond a reasonable doubt” and “preponderance of the evidence” standards of proof. Pfizer, Inc.
v. Apotex, Inc., 480 F.3d 1348, 1360 n.5 (Fed. Cir. 2007). Although an exact definition is elusive,
“clear and convincing evidence” has been described as evidence that “place[s] in the ultimate
factfinder an abiding conviction that the truth of its factual contentions are highly probable.” Id.
(citing Colorado v. New Mexico, 467 U.S. 310, 316 (1984) (internal quotations omitted)).
Clear and convincing evidence is evidence that produces in your mind a firm belief or
conviction that the allegations sought to be proved by the evidence are true. Clear and convincing
evidence involves a higher degree of persuasion than is necessary to meet the preponderance of the
evidence standard. But it does not require proof beyond a reasonable doubt, the standard applied
in criminal cases.
Section 3. Anticipation
Apotex contends that claims 1 and 11 of the ’353 patent are invalid under 35 U.S.C. § 102(b)
for anticipation. Schering argues that anticipation was not raised previously and therefore barred
under the final pretrial order. On this ground, Schering is correct. Apotex did not raise the issue of
anticipation. (FPTO 362-64 (outlining Apotex’s legal issues for trial)). When an issue, argument,
claim or defense is not raised in the pretrial order, it is deemed waived. Briglia v. Horizon Health
Care Servs., Inc., 2010 WL 4226512, at *4 n.5 (D.N.J. Oct. 21, 2010) (Hillman, J.). Thus, Schering
has waived this cause of action.
Additionally, the Court notes that Apotex fails to prove anticipation through clear and
convincing evidence. Apotex argues that the Shapiro patent anticipates the ’353 patent under 35
U.S.C. § 102(b). The statute operable statute states that “a person shall be entitled to a patent unless
. . . the invention was patented or described in a printed publication in this or a foreign country or
in public use or on sale in this country, more than one year prior to the date of the application for
patent in the United States, . . . .” 35 U.S.C. § 102(b). Apotex argues that recrystalizating
mometasone furoate from water:alcohol mixture in the ’353 patent into the monohydrate form is
described in the Shapiro patent. Despite this contention, Apotex has not shown any clear and
convincing evidence to rebut the following facts that: (1) the rediscovered IR spectrum delivered to
the USPTO in November 1999 showed an absence of water peaks and therefore recrystallization
compound was not a hydrate; and (2) the Shapiro patent does not disclose a monohydrate, hence it
is not subject to 102(b) analysis. As Dr. Trout stated, “Shapiro discusses mometasone furoate, but
it doesn’t discuss anything about the monohydrate, or the particular crystalline form that the
monohydrate would be in.” (T. 1247, 14-1). Even Dr. Mitra, Apotex’s expert, indicated that the
monohydrate was not disclosed. (T. 1056, 1-10). In light of same, the Court finds that Apotex did
not meet its burden of proof to show anticipation by clear and convincing proof.
Section 4. Obviousness
Apotex also contends that claims 1 and 11 of the ’353 patent are invalid under 35 U.S.C. §
103(a) for obviousness. A patent claim is said to be obvious if the differences between the subject
matter sought to be patent and the whole of the prior art are such that the subject matter would have
been obvious at the time the invention was made to a person having ordinary skill in the art. 35
U.S.C. § 103(a); see also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). A determination
of obviousness is a question of law based on the facts concerning: (I) the scope and content of the
prior art; (ii) the level of ordinary skill in the art; (iii) the differences between the prior art and the
claims at issue; and (iv) objective indicia of nonobviousness, such as unexpected results, failure of
others, long-felt need, commercial success, copying, and praise for the invention. See Graham v.
John Deere Co., 383 U.S. 1, 17-18 (1966); Specialty Composites v. Cabot Corp., 845 F.2d 981 (Fed.
Obviousness determinations proceed in two stages. First, the patent challenger must establish
by clear and convincing evidence that the claimed invention is prima facie obvious. See Kaufman
Co. v. Lantech, Inc., 807 F.2d 970, 974-75 (Fed. Cir. 1986). If the accused infringer fails to establish
prima facie obviousness, the analysis is over, and the asserted claims may not be found invalid for
obviousness. Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc., 231 F.3d 1339, 1345 (Fed. Cir.
2000). To establish prima facie obviousness where the invention is a chemical compound, the
challenger must prove, by clear and convincing evidence, two things: (1) that a person of ordinary
skill would have selected a particular “known compound,” and (2) there existed in the prior art a
reason to modify that lead compound “in a particular manner” so as to arrive at the compounds of
the invention. Takeda, 492 F.3d at 1357.
(1) The level of ordinary skill in the art
The Court must determine what a person having ordinary skill in the art (“PHOSITA”) would
have thought at the time of the invention, guided only by the prior art and the then-accepted wisdom
in the field. In re Kotzab, 217 F.3d 1365, 1369 (Fed. Cir. 2000). The parties agree that a PHOTISA
skilled in the art pertaining to the ’353 patent is a person actively involved in the drug development
process. (Apotex FOF ¶ 858) (Schering FOF Reply ¶ 858). The parties further agree that the process
is a multidisciplinary process that requires collaborative teamwork from persons with various
experience. (Apotex FOF ¶ 859) (Schering FOF Reply ¶ 859). The parties also agree that examples
of disciplines involved in the drug development process are those with backgrounds in medicine,
nasal pharmacology, medicinal chemistry, physical chemistry, drug formulation, and drug delivery.
(Apotex FOF ¶ 860) (Schering FOF Reply ¶ 860). The only real difference between the parties is
over whether a PHOTISA would have a specific expertise in liquid dose formulations. (Compare
Apotex FOF ¶ 861 with Schering FOF ¶ 861). Apotex, relying on the testimony of Dr. Mitra, claims
that a PHOTISA would have such specific experience, particularly in the fields of nasal liquid dose
formulations and nasal pharmacology. (T. 1022, 1-8). Conversely Schering, relying on the testimony
of Dr. Trout, claims that a PHOSITA would not require specific experience in the development of
aqueous nasal suspensions. (T. 1229, 1-12).
(2) The Scope and Content of the Prior Art
Apotex’s position regarding the scope and content of the Shapiro patent incorporates the
discussion and argument advanced in their anticipation claim—namely, that the Shapiro patent
discloses both the monohydrate form of mometasone furoate and a nasal spray developed with same.
(Apotex FOF ¶¶ 809-11, 864-66). Additionally, Apotex claims that even if the Shapiro patent did
not anticipate the ’353 patent, a skilled pharmacologist would have been motivated to develop a
nasal spray using mometasone furoate, the compound first described in the Shapiro patent.
“Determining whether there is a suggestion or motivation to modify a prior art reference is one
aspect of determining the scope and content of the prior art, . . . .” SIBIA Neurosciences, Inc. v.
Cadus Pharamceutical Corp., 225 F.3d 1349, 1356 (Fed Cir. 2000). A suggestion to modify or a
motivation to combine prior art elements may be derived from the prior art reference itself, from
knowledge of one of ordinary skill in the art, or from the nature of the problem to be solved. Id.; see
also Pro-Mold & Tool Co. v. Great Lakes Plastics, Inc., 75 F.3d 1568, 1573 (Fed. Cir. 1996).
In support of their obviousness argument, Apotex has identified five distinct articles of prior
art: (1) the Shapiro patent; (2) J. E. Carless, at al., Dissolution and crystal growth in aqueous
suspensions of cortisone acetate, 20 Journal of Pharmaceutical & Biomedical Analysis 630 (1968)
(“the Carless Paper”); (3) U.S. Patent No. 4,414,209 filed on November 8, 1983 (the “Cook Patent”);
(4) U.S. Patent No. 4,866,051 filed September 12, 1989 (“the Hunt Patent”); and (5) Chang-Jin
Wang, A competitive enzyme immunoassay for the direct determination of mometasone furoate (SCH
32088) in human plasma, 10 Journal of Pharmaceutical & Biomedical 473 (1992) (“the Wang
Paper”).14 According to Apotex, the existence and combination of these articles would have
Apotex also lists Elocon® as a prior art reference. (Apotex FOF ¶¶ 194-96). Elocon® is a
topical ointment based on the Shapiro patent. Since neither party identifies any material difference
between Elocon® and the Shapiro patent—as least as it pertains to their existence in the prior
art—the Court’s discussion of whether the ’353 Patent was obvious in light of the Shapiro patent
incorporates all references to Elocon®.
motivated an ordinary pharmacologist as of September 6, 1990 to both choose mometasone furoate
as a treatment for allergic rhinitis and to formulate mometasone furoate into an aqueous solution.
(A) Choosing mometasone furoate as a treatment for allergic rhinitis
In September 1990, skilled pharmacologists were searching for a corticosteroid that was
active as an anti-inflammatory drug with minimal unwanted side effects in order to treat rhinitis.
(Apotex FOF ¶ 870-72, 874) (Schering FOF Reply ¶ 870-72, 874). Apotex claims that mometasone
furoate “stood out” as the most effective solution. Apotex bases their conclusion on what they claim
are the two key attributes of mometasone furoate: potency and safety.
Apotex, relying on Drs. Page and Mitra, claims that mometasone furoate was known to be
a potent anti-inflammatory drug. (T. 978, 19 through T. 79, 1) (T. 1028, 5-10). Drs. Page and Mitra
further claim that knowledge of this potency extended to the mucous membrane, which includes the
nose. (T. 979, 5-9) (T. 1028, 11-18). Dr. Page also testified that during the applicable time frame,
corticosteroids were the most effective treatment of rhinitis. (T. 989, 20-22). Based on these features
Dr. Page asserts that the Shapiro patent would have taught a skilled pharmacologist that mometasone
furoate could be used to treat rhinitis. (T. 980, 6-16) (T. 973, 12-14) (T. 976, 3-5).
Apotex also claims that mometasone furoate was known to be safe. According to Apotex,
an ordinary pharmacologist would have known that mometasone furoate was safe because as of
September 6, 1990, the FDA had already approved mometasone furoate for the topical treatment of
inflammatory conditions. (T. 980, 14 through T. 981, 1). Under this argument, the safety of
mometasone furoate was particularly important due to the relative toxicity of corticosteroids.
(Apotex FOF¶¶ 869-76 (citing T. 974, 15 through T. 975, 2)).
Apotex finds further support for their claim that mometasone furoate possessed the twin
attributes of potency and safety in two articles that would have been available to an ordinary
pharmacologist in September 6, 1990. The first article is Luciano Dominguez et al., Comparison
of the Safety and Efficacy of Mometasone Furoate Cream 0.1% and Clobetasone Butyrate Cream
0.05% in the Treatment of Children with a Variety of Dermatoses, Current Therapeutic Research
128-39 (July 1990) (the “Dominguez Article”). According to Dr. Page, the Dominguez Article
concluded that mometasone furoate has a significant therapeutic advantage over a number of other
corticosteroid formulations, that it possesses superior efficacy even when applied once daily, and that
it was safe. (T. 982, 16 through T. 983, 6; DTX-407 at 129). Additionally, the parties agree that the
efficacy of once-a-day-treatments would have been important during the applicable time period given
a known patient preference for once-daily treatments. (Apotex FOF ¶ 892; Schering FOF Reply ¶
892). The second article is Renie Bressinck, M.D. et al., Comparison of the Effect of Mometasone
Furoate Ointment 0.1%, and Hydrocortisone Ointment 1%, on Adrenocortical Function in Psoriasis
Patients, Today’s Therapeutic Trends 25-35 (1988) (the “Bressinck Article”). The Bressnick Article
was a comparison of the effect of mometasone furoate ointment and hydrocortisone ointment,
another steroid available at the time. (Apotex FOF ¶ 888; Schering FOF Reply ¶ 888). According
to Dr. Page, the Bressnick Article concluded that the clinical response to mometasone was decidedly
superior to that of hydrocortisone. (T. 985, 1-9; DTX-3 at 25). Dr. Page also testified that the
Bressnick Article states that mometasone furoate is very effective clinically and has a low potential
for unwanted side effects. (T. 985, 8-9; DTX-3 at 34). Finally, Apotex cites to an expert report
drafted in 1986 by one of Schering’s physicians. (Apotex FOF ¶ 900). The report states that
“because [mometasone furoate] exhibited good topical potency with a low potential for systemic side
effects . . . this suggested that topical mometasone furoate could also have a favorable therapeutic
index for the treatment of nasal allergic diseases.” (DTX-39 at 2). According to Dr. Page, the
approach outlined in this report is consistent with what a skilled pharmacologist would have done
in 1990 and consistent with what other companies were doing at the time. (T. 988, 1-14).
In response to Apotex’s argument, Schering denies that an ordinary pharmacologist in
September 1990 would not have chosen either corticosteroids generally or mometasone furoate
specifically as a lead candidate to treat allergic rhinitis. In regard to corticosteroids generally,
Schering produced evidence that in September 1990, corticosteroids were only one type of treatment
option for allergic rhinitis. At trial Dr. Durham testified that the treatment options for allergic
rhinitis in September 1990 included corticosteroids, oral antihistamine tablets, decongestants, and
allergic immunotherapy. (T. 1076, 12-25). Dr. Durham further testified that at the same time there
was a lot of interest in the development of leukotriene synthesis inhibitors or antagonists for the
treatment of allergic reactions. (T. 1078, 22 through T. 1079, 5). In discussing these inhibitors and
antagonists, Dr. Durham cited to Victor G. Matassa, et al., Evolution of a Series of
Peptidoleukotriene Antagonists, 33 Journal of Medicinal Chemistry 1781 (1990) (the “Matassa
Article”). (T. 1049, 15-23; see also PTX-398). According to Dr. Durham, the Matassa Article
reflects that a number of companies were developing antagonists or synthesis inhibitors in 1990
because they were effective in suppressing the symptoms of allergic rhinitis. (T. 1079, 24 through
1080, 11, see also PTX-398 at 1).15 Based on the Matassa Article and on Dr. Durham’s testimony,
For their part, Apotex claims that the Matassa article would not have influenced a skilled
pharmacologist since the compounds tested in the Matassa Article were not approved for use in
humans in September 1990 and the testing performed in the Matassa paper dealt with guinea pigs.
(Apotex FOF ¶¶ 926-29 (citing T. 1095-96)).
Schering argues that since a person of skill in the art could have pursued one of the noncorticosteroid treatment options, Apotex failed to prove that it would have been obvious to select
a corticosteroid as the lead compound in a treatment for allergic rhinitis. (Schering COL ¶ 128). Dr.
Durham also testified at trial that patients preferred oral treatments to corticosteroids which often
required nasal sprays and would sometimes result in local bleeding or crusting of the nose. (T. 1084,
3-10) (T. 1085, 11-17). Based on this testimony, Schering argues that this patient preference would
have led a person of ordinary skill towards a non-steroidal once a day tablet as opposed to a
In regard to mometasone furoate, Schering produced evidence that in September of 1990 an
ordinary pharmacologist would have been ultimately dissuaded from formulating a nasal spray with
mometasone furoate because its metabolism in the liver and metabolites were unknown. In making
this argument, Schering relied on both the testimony of Dr. Durham and his review of the Wang
Paper. (T. 1086, 4 through T. 1088, 5) (DTX-28). According to Dr. Durham, the metabolism,
pharmacokinetics, and toxicokinetics of mometasone furoate had not been evaluated by September
1990. (T. 1086, 12-21 (reviewing the Wang Paper)). Dr. Durham further testified that the lack of
knowledge about the metabolism of mometasone furoate would have been a major concern for a
PHOSITA identifying a candidate to treat allergic rhinitis. (T. 1087, 2-6). Schering also challenged
those conclusions of Dr. Page which were based on the Dominquez and Bressnick Articles. As
Schering states in this argument, the Dominquez Article dealt with mometasone furoate cream and
the Bressnick Article dealt with mometasone furoate ointment. (Schering FOF ¶¶ 835, 839).
Schering further asserts that in September of 1990, if a person developing a treatment for allergic
rhinitis actually chose a corticosteroid, the delivery method would have been a nasal spray. (Schering
FOF ¶ 824 (citing T. 1085, 11-16)). Additionally, Schering asserts that the nasal delivery of a
corticosteroid would result in a large portion of the drug being swallowed and ultimately passing
through the liver. Thus, according to Schering, any conclusions reached by the Dominquez and
Bressnick articles with regards to safety or efficacy are inapposite.
(B) Formulating mometasone furoate into an aqueous solution
Apotex claims that there were express directions in the prior art teaching toward formulating
mometasone furoate into an aqueous suspension of the monohydrate form. Almost all of Apotex’s
evidence on this issue was produced at trial through the testimony of Dr. Mitra and his review of the
Shapiro patent, the Carless Paper, the Cook Patent, the Wang Patent, and the Hunt Patent. (T. 1028,
2 through T. 1039, 12) (DTX-394) (DTX-105) (DTX-162) (DTX-107). Starting with the Shapiro
patent, Dr. Mitra testified that the Shapiro patent is directed toward treating rhinitis. (T. 1028, 5-18).
Dr. Mitra also testified that the Shapiro patent specifically disclosed nasal sprays as an example of
how to deliver mometasone furoate. (T. 1028, 19-24). Dr. Mitra further testified that a PHOSITA
would have prepared a nasal spray of mometasone furoate as a suspension. (T. 1028, 25 through T.
1029-16) (T. 1033, 12 through 1034, 15). Dr. Mitra concluded that any suspension of mometasone
furoate prepared according to the Shapiro patent would be substantially similar to the seven aqueous
suspensions disclosed in the ’353 patent. (T. 1029, 10 through T. 1031, 17).
The second part of Dr. Mitra’s testimony dealt with the use of the monohydrate form of
mometasone furoate. According to Dr. Mitra, a person of ordinary skill that did not know anything
about the likelihood of crystal growth may have attempted to formulate mometasone furoate into an
aqueous solution using the anhydrous form. (T. 1032, 9-17). However, as Dr. Mitra explained in
trial, in September 1990 it was recognized in the art that pharmaceutical conversion of an anhydrate
of other steroids would lead to particle size growth. (T. 1038, 25 through T. 1039, 7). Thus, in Dr.
Mitra’s opinion, the logical choice for a PHOSITA was to preemptively avoid the particle size
growth problem by formulating with the hydrate or solvate in the first place, maintaining the particle
size that is required, and then formulating the steroid into the suspension. (T. 1038, 25 through T.
1039, 12). Importantly, Apotex claims that this process is identical to the process outlined in claims
1 and 11 of the ’353 patent. (Apotex FOF ¶ 992).
Dr. Mitra bases his opinion on preempting particle size growth on four prior art articles that
would have been available to a PHOSITA in September 1990: the Carless Paper, the Cook Patent,
the Wang Patent, and the Hunt Patent. (T. 1035, 7-9). The Carless Paper was published in 1968.
(DTX-394). According to Dr. Mitra, the Carless Paper would have taught a PHOSITA that when
cortisone acetate, a steroid similar to mometasone furoate, was formulated in an aqueous suspension,
it experienced crystal growth and particle size growth. (T. 1035, 18-24). The Cook Patent was
published in 1983. (DTX-105). According to Dr. Mitra, the Cook Patent taught a PHOSITA that
when belcometasone dipropionate, a steroid similar to mometasone furoate, was formulated with a
solvent for an inhalation formulation, it converted to the solvate crystal form and experience crystal
size growth. (T. 1036, 9-23). Further discussing the Cook Patent, Dr. Mitra testified that the Cook
Patent solved the problem of particle size growth by using the solvated crystal form and then
micronizing it to smaller particles. (T. 1036, 20-23). The Wang Patent was also published in 1983.
(DTX-162). According to Dr. Mitra, the Wang Patent taught a PHOSITA that a large number of
steroids form as monohydrates when in the presence of water. (T. 1037, 25 through 1038, 5). Dr.
Mitra further testified that the Wang Patent solved the problem of monohydrate formation by using
the monohydrate in the first place, and then micronizing it before adding it to the formulation. (T.
1038, 2-5). The Hunt Patent was issued on September 12, 1989. (DTX-107). According to Dr.
Mitra, the Hunt Patent taught a PHOSITA that beclomethasone dipropionate, the same steroid
reviewed in the Cook Patent, forms polymorphic crystals in water, which changes the particle size,
and further teaches that the steroid crystals have to be micronized. (T. 1038, 16-20). Based on the
collective message of these articles, Dr. Mitra concluded that a PHOSITA would be motivated to
formulate a nasal suspension with the hydrate form of mometasone furoate. (T. 1038, 25 through T.
Schering, for its part, denies that there were express directions in the prior art teaching toward
formulating mometasone furoate into an aqueous suspension of the monohydrate form. According
to Drs. Mitra and Trout, the Shapiro patent discloses neither a formulation for a nasal suspension nor
a formulation for a nasal spray. (T. 1057, 19-24) (T. 1240, 25 through T. 1241, 2).
Schering further claims that there significant difference between the four prior art references
relied upon by Apotex (i.e., the Carless Paper, the Cook Patent, the Wang Patent, and the Hunt
Patent) and the subject matter claimed by the ’353 patent. Most of Schering’s claims are founded
on the testimony of Dr. Trout. At trial, Dr. Trout testified first that a PHOSITA would not have look
at the four prior art references to predict the potential existence of additional forms of mometasone
furoate or properties of those forms. (T. 1234, 9-13). According to Dr. Trout, “even within a given
class, such as a similar class of steroids, one cannot predict either which form would exist, which
forms would exist . . . or which forms are stable under a given [set of] conditions. So there was no
reason that a [PHOSITA] would consider those references.” (T. 1234, 15-20) (see also T. 52, 2-18
(testifying that he did not review any patent literature when researching the properties of
mometasone furoate to develop the formulation)). Dr. Trout then testified that even if a PHOSITA
had reviewed the four prior art references in combination with the Shapiro patent, it would not have
rendered the subject matter of the ’353 patent obvious. (T. 1248, 3-7). According to Dr. Trout, none
of the four prior art references discuss mometasone furoate. (T. 1248, 10-16). Dr. Trout also testified
that none of the four prior art references discuss the monohydrate crystalline form of mometasone
furoate. (T. 1248, 9-10). Additionally, Dr. Trout testified that none of the four prior art references
discuss aqueous pharmaceutical suspensions. (T. 1236, 25 through T. 1237, 2). Based on these
assertions, Schering asserts that the prior art did not teach towards formulating mometasone furoate
into an aqueous suspension of the monohydrate form.
(3) The differences between the claimed invention and the prior art
The parties are diametrically opposed on the differences between the claimed invention and
the prior art. Apotex claims that “there are no differences between the prior art and the claimed
subject matter.” (Apotex FOF ¶ 865). Schering claims that “Apotex has not shown, by clear and
convincing evidence, that a [PHOSITA] would have been motivated to take anhydrous mometasone
furoate and modify it to a previously-unknown and unexpected monohydrate form.” (Schering COL
¶ 136). Schering also claims that “Apotex . . . suggest[s] that a [PHOSITA] would have formulated
mometasone furoate as a nasal spray, but there is little in [Apotex’s] references to support this
suggestion, and Apotex has not provided a motivation to combine.” (Schering COL ¶ 141).
(4) Objective indicia of non-obviousness
If a patent challenger makes a showing of prima facie obviousness, a patentee may rebut the
showing with evidence “that the claimed inventions exhibits some superior property or advantage
that a [PHOSITA] would have found surprising or unexpected.” Procter & Gamble Co. v. Teva
Pharms. USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009) (internal quotations and citations omitted).
Evidence showing that the invention has an unexpected superior property (sometimes called
unexpected results) compared to the prior art can rebut a prima facie case of obviousness. See in re
Mayne, 104 F.3d 1339, 1343-44 (Fed. Cir. 1997); In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995).
Prima facie obviousness may also be rebutted with objective indicia of nonobviousness (sometimes
referred to as “secondary considerations”) including the commercial success of the claimed
invention. Procter, 556 F.3d at 998. Importantly, even though the patentee has the duty of producing
such evidence, the burden of persuasion by clear and convincing evidence remains with the patent
challenger. Tech. Licensing Corp. v. Videotek, Inc., 545 F.3d 1316, 1329 (Fed. Cir. 2008).
In rebutting Apotex’s evidence of prima facie obviousness, Schering adduced the testimony
of both Dr. Petra Högger16 and Dr. Stephen Durham as evidence of unexpected results. (T. 1117, 13
through T. 1136, 20) (T. 1065, 11 through T. 1091, 16). At trial, Dr. Högger testified that furoate
moiety, a unique structural feature of mometasone furoate, imparted benefits to mometasone furoate
which directly supported the increased efficacy and safety of the drug. (T. 1132, 17 through T. 1133,
1) (T. 1135, 14-21). Dr. Högger further testified that in the early 1990s, it was unexpected and not
foreseeable that the furoate moiety would impart such benefits to mometasone furoate. (T. 1135, 1421). On the issue of unexpected results, Dr. Durham testified that mometasone furoate produced
unexpected results with regards to safety in children. (T. 1089, 6 through T. 1090, 9 (reviewing PTX-
Dr. Petra Högger is currently a Professor of Clinical Pharmacy, at Julius-MaximiliansUniversity Würzburg, Germany. There Dr. Petra Högger conducts research on pharmacokinetics and
pharmacodynamics of pulmonary and intranasally administered drugs, and pulmonary/intranasal
delivery of drugs. Dr. Högger also teaches classes relating to clinical pharmacy and therapeutics,
clinical chemistry, and pharmacotherapy. At Julius-Maximilians-University, she is a member of
Executive Committee of the Academy of Clinical Pharmacy. Dr. Högger also authored over 50
original and review articles in addition to a textbook on clinical pharmacology.
401)). Specifically, Dr. Durham testified that mometasone furoate nasal spray had no effect on the
long term growth of children, and that the absence of such growth retardation would not have been
expected in September of 1990. (T. 1089, 6-20) (T. 1090, 7-9).
Schering also adduced the testimony of Dr. Christopher Vellturo17 as evidence of commercial
success. (T. 1261, 4 through T. 1288, 3). According to Dr. Vellturo, Nasonex® nasal spray, the
product developed from the ’353 patent, is a commercial success. (T. 1268, 13-15). Notably, Dr.
Vellturo testified that over a span of thirteen years, total net U.S. sales for Nasonex® nasal spray
exceeded 5 billion dollars. (T. 1269, 13-15). Dr. Vellturo also testified that the commercial success
of Nasonex® is attributable to the formulation using mometasone furoate monohydrate in a nasal
suspension. (T. 1268, 16-23) (T. 1281, 7-13). Dr. Vellturo based this opinion on two surveys of
physicians that prescribe Nasonex® to treat allergic rhinitis. (T. 1282, 3-8). According to Dr.
Vellturo, the main attribute associated with physicians’ satisfaction in prescribing Nasonex® was
better efficacy. (T. 1285, 3-5). Finally, Dr. Vellturo reviewed the promotional expenditures, the
marketing expenditures, and the pricing for Nasonex® and determined that such features were “not
inordinately responsible for Nasonex® nasal spray’s success over the [thirteen] years in the
marketplace.” (T. 1286, 3 through T. 1287, 5).
In response, Apotex challenges both of Schering’s claims. Regarding Schering’s assertion
that the invention of the ’353 patent produced unexpected results, Apotex refutes Dr. Högger’s
Dr. Christopher A. Vellturo is the founder and president of Quantitative Economic Solutions,
LLC, an economic consulting firm. Dr. Vellturo is also employed by Boston University, in Boston,
Massachusetts, where he teaches graduate-level economics. Dr. Vellturo received a Doctor of
Philosophy degree (Ph.D.) in Economics from the Massachusetts Institute of Technology in
Cambridge, Massachusetts in 1989. My fields of specialization include industrial organization and
testimony. (Apotex FOF ¶¶ 1001-14, 1031-40). On cross examination, Dr. Högger admitted that
she never gave the opinion in her expert report that the unexpected results of mometasone furoate
were due to the monohydrate form of mometasone furoate. (T. 1145, 22-25). Dr. Högger also
admitted at trial that she never discussed the monohydrate form of mometasone furoate anywhere
in her expert report, nor had she performed any studies to determine that the unexpected results
discussed in her expert report were due to the monohydrate form of mometasone furoate. (T. 1147,
14-19). Based on this testimony, Apotex asserts that Schering failed to prove that the unexpected
results alleged by Dr. Högger have any nexus to the monohydrate form of mometasone furoate, as
opposed to mometasone furoate itself which was previously patented by the Shapiro patent. (Apotex
COL ¶ 256). Regarding Schering’s evidence of commercial success, Apotex challenges the
assertions of Schering’s expert with their own expert on commercial success, Mr. Harry Charles
Boghigian.18 (T. 1313, 23 through T. 1337, 19). Mr. Boghigian testified that the market performance
of Nasonex® had nothing to do with the ’353 patent. (T. 1320, 3-14). Rather, Mr. Boghigian asserts
that the performance of Nasonex® is entirely due to marketing and promotion. (T. 1319, 16-19).
Based on the foregoing, the Court determines that the ’353 patent would not have been
obvious to a PHOSITA in September of 1990. First, the Court agrees with Dr. Trout that the level
of ordinary skill in the art in September of 1990 would not require a PHOSITA to have specific
experience in the development of aqueous nasal suspensions. When asked if a person of skill in the
art related to the ’353 patent would have specific experience in the development of nasal suspension,
Mr. Boghigian is a pharmaceutical executive with over forty years of domestic and
international experience in the commercialization and marketing of pharmaceutical products.
Dr. Trout testified that it would not “[b]ecause the ’353 patent focuses on specific composition of
matter, mometasone furoate monohydrate . . . .” (T. 1229, 1-8). Additionally, Dr. Mitra testified that
the development process described in the ’353 patent is “a multidisciplinary process and requires
collaborative teamwork and is done in the industry routinely from various groups with various
expertise.” (T. 1021, 16-20). Based on this testimony, the Court finds that the broader definition of
a PHOSITA is appropriate.
Second, the Court finds that Apotex failed to meet their burden to prove that a PHOSITA
would have been motivated to develop a nasal spray using mometasone furoate. Dr. Durham
testified convincingly that in September of 1990, the fact that the metabolism of mometasone
furoate in the liver was unknown would have been a “major concern” about the systemic effects of
nasal delivery of the drug. (T. 1087, 2-15). Dr. Durham went on to testify that “there were questions
regarding [the] safety of the mometasone at the time . . . [e]ven though it [had] been used in the skin
effectively . . . .” (T. 1088, 3-8). Conversely, Dr. Page’s discussion of mometasone furoate’s safety
dealt with creams that did not pass through the liver. (T. 980, 6 through T. 981, 1) (T. 981, 7-12).
Dr. Durham’s testimony thus undermines the assertion that it would have been obvious to a
PHOSITA to develop a treatment for allergic rhinitis using mometasone furoate, at least to the extent
the treatment was developed as a nasal spray. Additionally, in support of the position that it would
have been obvious to develop a treatment for allergic rhinitis into a nasal spray, Apotex adduced the
testimony of Dr. Mitra. (T. 1016, 4 through T. 1040, 20). After reviewing the prior art, Dr. Mitra
testified that the “collective message” of the prior art “is if you’re taking the steroids, including
mometasone, . . . they all in water or in [the] presence of any solvent, will forma hydrate or a solvate,
and then change particle size and will grow. [T]he message is that you need to formulate . . . by
changing the particle size back to what you want, and then formulate the suspension.” (T. 1038, 25
through T. 1039, 12). This conclusion was directly contradicted by Dr. Trout. According to Dr.
Trout, “even within a given class [of steroids], one cannot predict either which form would exist,
which forms would exist . . . or which forms are stable.” (T. 1234, 15-20). Dr. Trout went on to
testify that “for several decades people have tried to develop thermodynamic theories and other
theories in order to make these predictions, but unfortunately even today the state of the art is such
that we don’t have accurate technologies to do that.” (T. 1231, 21-25). The Court found Dr. Trout
both truthful and persuasive and gives weight to his testimony. Comparatively, Dr. Mitra analysis
and conclusion appeared hamstrung by the materials and direction provided to Dr. Mitra by Apotex.
(T. 1054, 14 through T. 1055, 2).
Finally, since the Court determines that Apotex failed to make a prima facie case for obvious,
there is no need to review the objective indicia of non-obviousness. See Yamanouchi Pharm. Co. v.
Danbury Pharmacal, Inc., 231 F.3d 1339, 1345 (Fed. Cir. 2000) (“Because [Defendant] did not
show even a prima facie case for obviousness, this court has considered, but need not separately
address, the strong objective evidence of non obviousness.”).
For the reasons stated above, Schering’s complaint for infringement is dismissed because
Schering failed to present credible evidence sufficient to meet its burden of proof by a preponderance
of the evidence standard. Additionally, Apotex’s counterclaim for invalidity is dismissed because
Apotex failed to present credible evidence sufficient to meet its burden of proof by a preponderance
of the evidence standard. An appropriate form of order will follow.
s/Peter G. Sheridan
PETER G. SHERIDAN, U.S.D.J.
June 15, 2012
Disclaimer: Justia Dockets & Filings provides public litigation records from the federal appellate and district courts. These filings and docket sheets should not be considered findings of fact or liability, nor do they necessarily reflect the view of Justia.
Why Is My Information Online?