Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 1 of 24
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`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF NEW YORK
`
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`v.
`
`Amneal Pharmaceuticals, LLC,
`
`
`Defendants.
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`v.
`
`Zydus Pharmaceuticals (USA) Inc., and Cadila
`Healthcare Ltd. (dba Zydus Cadila),
`
`
`Defendants.
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`v.
`
`Orient Pharma Co., Ltd.,
`
`
`Defendants.
`
`
`
`
`
`
`Civil Action No. 14-CV-2758 (PAC)
`
`Civil Action No. 14-CV-2760 (PAC)
`
`Civil Action No. 14-CV-2759 (PAC)
`
`

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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 2 of 24
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`Civil Action No. 14-CV-5575 (PAC)
`
`Civil Action No. 14-CV-7934 (PAC)
`
`Civil Action No. 15-CV-3935 (PAC)
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`
`v.
`
`Sawai USA, Inc., and
`Sawai Pharmaceutical Co., Ltd.,
`
`
`Defendants.
`
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`
`v.
`
`Apotex, Inc. and Apotex Corp.,
`
`
`Defendants.
`
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`
`v.
`
`Lupin Ltd. and Lupin Pharmaceuticals, Inc.,
`
`
`
`
`
`
`
`
`Defendants.
`
`
`
`
`
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`

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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 3 of 24
`Case 1:14-cv—02758—PAC Document 107 Filed 12/16/16 Page 3 of 24
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`DEFENDANTS’ PROPOSED FINDINGS AND CONCLUSIONS RE:
`DEFENDANTS’ PROPOSED FINDINGS AND CONCLUSIONS RE:
`
`INAVALIDITY BASED ON INDEFINITENESS OF ASSERTED
`INAVALIDITY BASED ON INDEFINITENESS OF ASSERTED
`
`“FORM A” CLAIMS UNDER SECTION 112 OF THE PATENT ACT
`“FORM A” CLAIMS UNDER SECTION 112 OF THE PATENT ACT
`
`
`
`PRESENTED BY SAWAI
`PRESENTED BY SAWAI
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`
`
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`

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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 4 of 24
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`
`
`I.
`
`SCIENTIFIC BACKGROUND
`A.
`Crystalline Solids and Polymorphism
`1.
`Crystalline solids contain atoms and molecules that are arranged in a long-range,
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`repeating pattern in three-dimensional space. The internal structure (called the crystal structure)
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`of a compound is determined by the position of the atoms or molecules relative to each other in
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`three dimensions. The atoms and molecules within the crystal structure are held together by
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`interactions between the atoms making up the substance.
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`2.
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`Solids that are not crystalline have no long range order of the atoms and
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`molecules that make up the solid. These materials are often referred to as amorphous solids.
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`Glass is an example of an amorphous solid, in that the silicon dioxide molecules of glass lack
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`that long-range three-dimensional order. Amorphous solids are generally less stable than
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`crystalline solids.
`
`3.
`
`For some solid substances, the atoms and molecules that make up the crystal
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`structure can be arranged in more than one configuration in three-dimensional space. That is, the
`
`atoms or molecules can pack together in more than one way to produce different crystalline
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`forms. The ability of atoms, molecules or ions to exist in more than one crystal form or structure
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`is known as polymorphism, and the various different crystal forms of the same compound are
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`known as polymorphs. The different polymorphs of a compound can have very different
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`properties despite the fact that they are made of the same molecule. A familiar related example
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`involving the different arrangement of the same atom is carbon, which exists both as graphite
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`and as diamond depending on the atoms’ three-dimensional arrangement. The different forms of
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`1
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`carbon are technically “allotropes,” not polymorphs, but the example is no less applicable for
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`this difference in nomenclature.
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`comparison of diamond (left) and graphite (right)
`
`
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`4.
`
`It is quite common for crystals of organic compounds including salt forms to have
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`different polymorphs. These different polymorphs will have different physical and chemical
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`properties. For example, different polymorphs can exhibit different melting points, solubilities,
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`chemical stabilities, hygroscopicities, X-ray crystal structures and XRPD patterns (discussed
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`below), among many other properties.
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`5.
`
`Different polymorphs can also exhibit different relative stabilities under different
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`environmental conditions. For example, one polymorph of a substance may be stable at room
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`temperature, while another is stable only at elevated temperatures. Generally, it is common for
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`organic compounds that exhibit polymorphism to have more than one form that is stable enough
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`to be isolated and stored at room temperature. Although a compound may be able to crystallize
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`into many polymorphs that are relatively stable, only one of those forms will be the most stable
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`of the group under a given set of conditions. When stable and unstable polymorphic forms are
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`present in a mixture, certain experimental conditions may promote the conversion of the less
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`stable forms to the most stable form of that group.
`
`B.
`6.
`
`Solvates and Hydrates
`Solvates are a general class of crystalline compound that incorporate solvent
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`molecules within the crystal lattice of a compound. When the particular solvent molecule
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`incorporated into the lattice is water these compounds are referred to as “hydrates”. Solvates are
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`formed by virtue of favorable interactions between the solvent and compound molecules as these
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`species are assembled to pack together in the nucleation and crystallization processes that form
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`the crystalline lattice. A solvate can be thought of as an ordered three-dimensional array
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`containing two different chemical species, one species being the compound and the other being
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`solvent molecules that initially are used to dissolve the compound.
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`7.
`
`An important feature of a solvate is that solvent molecules are incorporated within
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`the crystal lattice and not merely present as residual liquid on the surfaces of the solids or
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`trapped between solid particles that have agglomerated together. For a crystalline solvate, the
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`solvent molecules are held within the crystalline lattice through favorable bonding interactions
`
`between molecules. Generally, the solvent molecules are integral to the crystal structure, such
`
`that if they were removed the crystal structure would collapse into another crystalline form or an
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`amorphous form. Because the interactions between the compound and solvent molecules may
`
`take place at very specific locations, it is common for the solvent molecules in a solvate to
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`correspond to a specific fixed ratio with respect to the compound. For example, solvates with a
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`1:1 ratio of compound to solvent molecule are common. However, ratios such as 2:1, 3:1, 1:2,
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`etc. are also frequently observed. Solvates cease to exist when they are dissolved in solution
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`because the dissolution process breaks apart the crystal lattice and the individual molecules are
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`released to move freely about the bulk solution.
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`8.
`
`Hydrates are frequently encountered in the pharmaceutical industry as drug
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`substances in solid oral dosage forms. This is because water molecules have the ability to form
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`relatively strong hydrogen bonds between other molecules. Often crystalline hydrates have
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`favorable properties such as stability that render the compound amenable to formulation into a
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`drug product. From a drug development perspective, a key performance requirement is that the
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`solvent molecules that are present in the solvate do not present any toxicity concerns. When the
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`solvent molecules of a solvate are water (i.e., hydrates), this is not an issue.
`
`9.
`
`The crystal structures of hydrates are different than those for the corresponding
`
`single-component crystals due to the inclusion of water in the crystal structure. For a given
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`compound, it may be possible for more than one crystalline hydrate to exist. Therefore, it is not
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`uncommon for a particular compound to crystallize into different crystalline hydrates depending
`
`on the conditions used to prepare or store the material. These hydrates may differ by the relative
`
`amount of water in the crystal structure, or may have the same number of water molecules in the
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`crystal lattice, but the molecules are arranged in a differ manner when compared to other
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`hydrates with the same stoichiometry.
`
`C.
`10.
`
`Identifying and Characterizing Crystalline Forms
`There are a number of analytical techniques that can be used to identify and
`
`characterize a crystal form of a compound. One of the most useful and reliable techniques is
`
`called X-ray powder diffraction (XRPD). This technique involves exposing the solid sample to a
`
`beam of X-ray radiation. The sample causes the X-rays to diffract in a pattern that is diagnostic
`
`of the structure of the solid.
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`11.
`
`Because X-ray powder diffraction probes the nature of the packing of the
`
`molecules in three-dimensional space, the technique can be used to differentiate crystalline
`
`materials from amorphous materials, which have no long range order.
`
`12.
`
`Different crystalline forms of the same compound will exhibit differences in the
`
`XRPD patterns that arise from the different arrangements of the molecules within the crystal
`
`lattice. Therefore, comparison of the XRPD patterns obtained for different samples usually
`
`provides a method of distinguishing different solid forms of the same compound.
`
`13.
`
`X-ray diffractometers may be equipped and configured with a variety of different
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`hardware options such as different X-ray sources, detector and sample holders. Also, instrument
`
`manufacturers provide different user interfaces and software that is used to collect and process
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`the X-ray diffraction data.
`
`14.
`
`One common type of instrumental configuration used to analyze samples involves
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`exposing the material to the X-rays when the sample is aligned horizontally in the instrument. In
`
`this set-up the top of the sample is exposed to the X-ray radiation. In a typical XRPD
`
`experiment the angles of the source and detector are scanned as the intensity of the diffracted
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`radiation is measured by the detector. The output of an XRPD analysis is a pattern that contains a
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`series of peaks that are plotted on a chart with peak intensity as a function of diffraction angle
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`(plotted in units of “degrees 2θ”). This chart is referred to as an “XRPD pattern” or
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`“diffractogram.”
`
`15. X-ray powder diffraction is distinguished from X-ray crystallography, which is a
`
`related technique that involves analysis of a single crystal material. In contrast, XRPD involves
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`analysis of tens to hundreds of milligrams of bulk material. In an XRPD analysis, the sample
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 9 of 24
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`does not necessarily have to be a “powder,” which is a solid material with small-sized particles.
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`However, it is advantageous for the sample undergoing analysis to consist of relatively small and
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`uniformly sized particles, which will increase both the number and the randomness of the
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`orientation of the crystals undergoing analysis. For example, the particle size of confectioner’s
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`sugar (i.e., powdered sugar) is better suited for XRPD analysis than the granular form of table
`
`sugar.
`
`16.
`
`In a typical XRPD analysis, a portion of the sample undergoing analysis
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`(sometimes called the “specimen”) is transferred using a spatula to the well of the XRPD sample
`
`holder. A typical XRPD holder will be roughly 1-2 mm deep and have a diameter of around 1–5
`
`cm. Sample wells of this size will hold approximately 10–200 mg of material. Sample holders
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`may be made of silicon or quartz, which will not provide any background interference during
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`analysis. Alternatively, sample holders may be made of aluminum or another non-reactive
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`material provided the sample holder is designed so that it will not be in the path of the X-ray
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`beam. Once the material is transferred to the sample holder, it should be flattened and leveled
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`such that the sample well is filled completely. The sample is then placed in the path of the beam
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`or in an auto-sample tray that permits the unattended analysis of multiple samples.
`
`17.
`
`A common instrumental configuration for a powder diffractometer is the Bragg-
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`Brentano configuration, which involves rotating both the X-ray source and the detector while
`
`holding the sample at a fixed location. See R. Jenkins and R. Snyder, INTRODUCTION TO X-RAY
`
`POWDER DIFFRACTIONMETRY, 173-203 (1996)1. The X-ray source and detector follow a circular
`
`path with the sample at the center of the circle. In this type of analysis, the X-ray source and
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`1 DTX-0638
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 10 of 24
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`detector are initially set to a position such that the X-ray beam will irradiate the sample at a low
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`angle. During the analysis the angles of the X-ray source and detector are changed in a step-wise
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`fashion while the intensity of the diffracted beam is recorded.
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`XPRD analysis using as Bragg-Brentano instrument
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`
`
`18.
`
`The diffraction angle plotted as the x-axis on an XRPD pattern is expressed in
`
`degrees 2θ, which is obtained from the geometry of the source and detector in relation to the
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`sample.
`
`19.
`
`The absolute intensity of the peaks (measured “counts” of signal intensity)
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`depends on many sample and instrumental factors such as: the quality and age of the X-ray
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`source; the amount of sample in the holder; the power settings on the detector; the duration of the
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`XRPD scanning period and many other factors.
`
`20.
`
`Often the specific values for the intensity of the peaks are normalized such that
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`the largest peak is given a value of 1 or 100. In this case the numerical values for the peak
`
`intensities represent their intensities relative to the largest peak.
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`7
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 11 of 24
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`21.
`
`As discussed above, it is preferable for the sample undergoing analysis to consist
`
`of numerous particles with a relatively small particle size to assist in generating a clear
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`diffractogram.
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`22.
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`A phenomenon known as “preferred orientation” can affect the intensities of the
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`peaks that appear in a diffractogram. In an ideal XRPD experiment, the crystals present in the
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`sample are oriented completely randomly, allowing the X-rays to be diffracted from all possible
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`faces of the crystal, which would generate peaks that relate to the crystallographic planes within
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`the structure. In reality, however, the overall shapes of a particular sample of crystalline material
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`can cause the individual crystals to preferentially align in one direction when placed in the
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`sample holder of the XRPD instrument. For example, needle-shaped crystals will preferentially
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`align in a sample holder along the long axis as opposed to on their ends or at any other
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`intermediate orientation. This is known as “preferred orientation” of the crystals. See Ann W.
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`Newman and Patrick Stahly, Form Selection of Pharmaceutical Compounds, HANDBOOK OF
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`PHARMACEUTICAL ANALYSIS, 18 (L. Ohannesian, A. Streeter, eds. 2002)2.
`
`23. When preferred orientation occurs in a sample undergoing XRPD analysis, it will
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`cause certain XRPD peaks to be over-represented and certain XRPD peaks to be under-
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`represented due to the lack of a random alignment of the crystals in the path of the X-ray beam.
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`In order to combat the phenomenon of “preferred orientation” special steps sometimes must be
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`taken to increase the randomness of the orientation of the crystals. For example, grinding the
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`sample into smaller particles prior to analysis will reduce the differences in the particular
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`dimensions of a crystal (i.e., the length, width and height) such that the crystals better
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`2 DTX-0639
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 12 of 24
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`approximate round spheres and provide a more random orientation of the crystals upon filling the
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`XRPD the sample holder. However, grinding the sample imparts energy into the material and
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`therefore carries the risk of inadvertently converting the solid form of the material to another
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`form.
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`24.
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`Alternatively, preferred orientation effects may be reduced by spinning and the
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`rocking the sample during analysis. While many XRPD instruments have the ability to spin the
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`sample, this will only address preferred orientation along one axis. Therefore, this approach
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`typically does not remove all the effects associated with preferred orientation.
`
`25.
`
`Another factor that may affect the intensities of XRPD peaks is related to the
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`particle size of the sample. Smaller particles of material permit the analysis of a greater absolute
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`number of particles while maintaining the same mass of the sample. It is advantageous to
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`analyze a greater number of particles in an XRPD experiment because this increases the
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`likelihood that all orientations of the crystal are represented.
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`26.
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` Conversely, if the sample undergoing XRPD analysis contains relatively few
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`crystals, the intensities of the XRPD peaks may not be truly representative of the structure
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`because not all of the orientations of the sample will have been exposed to the X-ray beam. This
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`situation is referred to as a sample exhibiting poor “particle statistics”. See R. Jenkins and R.
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`Snyder, INTRODUCTION TO X-RAY POWDER DIFFRACTIOMETRY, 231-259 (1996)3.
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`27.
`
`The practical outcome of XRPD analyses carried out on organic compounds is
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`that the intensities of the XRPD peaks can vary between samples of the same polymorph. See
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`U.S. PHARMACOPEIA 25, Chapter 941, X-Ray Diffraction 2088 (24th rev. 2002)4.
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`3 DTX-0638
`4 DTX-0640
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 13 of 24
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`28.
`
`Once the XRPD pattern for a particular crystal form of a particular compound is
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`known, that crystal form can then be identified in a later sample by comparing the XRPD
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`diffractograms of the sample with a reference pattern for that crystal form. In theory, all the
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`peaks found in the the XRPD pattern of the sample will match those present in the reference
`
`pattern, and there should be no additional peaks.
`
`II.
`
`LEVEL OF ORDINARY SKILL IN THE ART - ‘993 PATENT
`
`29.
`
`A person of ordinary skill in the art (POSA) as of February 12, 2003, would have
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`either: 1) a high level of education with such a person holding an advanced degree (i.e., Ph.D. or
`
`Master’s Degree) or 2) a bachelor’s degree in chemistry, chemical engineering, or related
`
`disciplines and at least several years of experience related to organic synthesis and/or evaluation
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`of solid state forms in the pharmaceutical industry, and an appreciation for the various factors
`
`that relate to drug development, including an understanding of solvate chemistry. Such a person
`
`would understand that the process requires a multi-disciplinary approach, and would draw upon
`
`not only his or her own skills, but could also take advantage of certain specialized skills of
`
`others, to solve any given problem.
`
`30.
`
`A POSA would understand the principles of X-ray powder diffraction (“XRPD”)
`
`as it relates to the analysis of organic compounds and the methods and instrumental parameters
`
`used to analyze them. That person would also have some familiarity with maintenance,
`
`calibration, and operation of an X-ray powder diffractometers. The POSA would have an
`
`understanding of how XRPD patterns may be compared to patterns of other samples and
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`reference standards for the purpose of polymorph characterization, gained through industry
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`experience, or in an academic or government research laboratory.
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 14 of 24
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`A.
`
`31.
`
`The Asserted Claims of the ‘993 Patent Are Indefinite
`
`“The Patent Act requires that a patent specification conclude with one or more
`
`claims particularly pointing out and distinctly claiming the subject matter which the applicant
`
`regards as [the] invention.’” Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120, 2124
`
`(2014) (citation omitted, emphasis in original). “[A] patent is invalid for indefiniteness if its
`
`claims, read in light of the specification delineating the patent, and the prosecution history, fail to
`
`inform, with reasonable certainty, those skilled in the art about the scope of the invention.” Id.
`
`32.
`
`"Even if a claim term's definition can be reduced to words, the claim is still
`
`indefinite if a person of ordinary skill in the art cannot translate the definition into meaningfully
`
`precise claim scope." GE Lighting Solutions, LLC v. Lights of Am. Inc., 2016 U.S. App. LEXIS
`
`19362 (Fed. Cir. Oct. 27, 2016)(“elongated” is a term of degree and indefinite in the absence of
`
`any disclosure about how to measure that degree).
`
`33.
`
`The asserted claims, when viewed in light of the specification and prosecution
`
`history, fail to inform one of the ordinary level of skill in the art about the scope of the invention
`
`with reasonable certainty, and are therefore indefinite under 35 U.S.C. §112.
`
`34.
`
`Claim 1 of the ’993 patent contains a list of characteristic peaks for each of the
`
`claimed polymorphs, which are defined by both the positions of the peaks in degrees 2θ and the
`
`intensities of the peaks which are expressed with qualitative descriptors. The qualitative
`
`descriptors are relative, and Claim 1 defines them as follows: “for each of said polymorphs, (vs)
`
`stands for very strong intensity; (s) stands for strong intensity; (m) stands for medium intensity;
`
`(w) stands for weak intensity; (vw) stands for very weak intensity.” 5
`
`
`5 DTX-0059, Col. 10:50-11:37
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`11
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 15 of 24
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`35.
`
`The XPRD patterns provided in Figures 1 -7 of the ’993 patent provide a scale
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`that contains the measured intensity of thee XRPD peaks (measured in counts of signal). Often,
`
`the intensity scale of an XRPD pattern is adjusted such that the largest peak of an XRPD pattern
`
`is given a value of 1 or 100% for the maximum height of that peak. The other peaks in the
`
`diffractogram are then represented as a fraction (or percentage fraction) of that largest peak.
`
`Peaks reported in this manner are characterized by their “relative intensity” values.6
`
`36.
`
`The ’993 patent describes the XRPD peak intensity values using qualitative
`
`descriptors (vs, s, m, w, vw) instead of numerical values. Unlike the 2θ peak positions, the patent
`
`provides no further guidance on how these qualitative peak intensities should be interpreted.
`
`37.
`
`A POSA would understand from Tables 1 – 6 in the ’993 patent that these
`
`descriptors represent peak relative intensities and not absolute intensities. 7
`
`38.
`
`A POSA would notice that data tables in the specification contain the same XRPD
`
`peak information as found in claim 1concerning peak position and intensity. 8
`
`39.
`
`A skilled person would also notice from the column headings in the tables
`
`containing the intensity descriptors are listed as “Rel. Intensity”, which means “Relative
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`Intensity”.
`
`40.
`
`A skilled person would not find any guidance in the ‘993 patent as to the
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`meaning and scope of the relative intensity descriptors beyond what is given in the claims:
`
`“...wherein (vs) stands for very strong intensity,(s) stands for strong intensity,(m) stands for
`
`medium intensity, (w) stands for weak intensity, and (vw) stands for very weak intensity.” Thus,
`
`
`6 DTX-0059, pp. 3-11
`7 DTX-0059, Col. 2:35-5:50
`
`8 DTX-0059, Col. 10:50-11:37
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`12
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 16 of 24
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`this descriptors do not provide any objective boundaries of the upper and lower limits of each of
`
`the claimed relative intensities. Liberty Ammunition, Inc. v. United States, 835 F.3d 1388, 1396
`
`(Fed. Cir. 2016) (“we have recognized that claims having terms of degree will fail for
`
`indefiniteness unless they "provide objective boundaries for those of skill in the art" when read
`
`in light of the specification and the prosecution history.”), citing Interval Licensing LLC v. AOL,
`
`Inc., 766 F.3d 1364, 1370-71 (Fed. Cir. 2014), cert. denied, 136 S. Ct. 59, 193 L. Ed. 2d 207
`
`(2015).
`
`41.
`
`Nowhere in the ’993 patent are the relative terms (vs) very strong intensity, (s)
`
`strong intensity, (m) medium intensity, (w) weak intensity, and (vw) very weak intensity defined
`
`in an absolute sense or relative to each other in a way that meaningfully conveys the scope of the
`
`asserted claims.9 Standard Oil Co. v. Am. Cyanamid Co., 774 F.2d 448, 453 (Fed Cir. 1985)
`
`(holding “partially soluble” was too vague to “particularly point out and distinctly claim” the
`
`subject matter of the invention).
`
`42.
`
`There is no clear boundary separating, for example a strong intensity peak from a
`
`medium intensity peak or a very strong intensity peak. None of the XRPD patterns correlate
`
`those terms of intensity with specific peaks, and nowhere does the ’993 patent define those terms
`
`with respect to the intensity counts of the y-axis of each XRPD patterns, or by any other means.
`
`43.
`
`Absent guidance in the patent itself, a POSA is left to determine these boundaries
`
`from the XRPD data itself, which is limited to the XRPD figures. A POSA would find such
`
`information inadequate for this purpose.
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`9 DTX-0059
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 17 of 24
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`44.
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`There are different procedures that a POSA would recognize are used to express
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`the relative intensities of the peaks provided in an XRPD analysis. These procedures range from
`
`a rigorous mathematical analysis of the experimental data to determine the size of each peak
`
`expressed as a peak area, to simply measuring the height of apex of the XRPD peak.
`
`45.
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`First, relative intensities can be determined by assigning the largest peak in each
`
`diffraction pattern a value of 100% and scaling all other peaks to the largest peak accordingly.
`
`This method provides values for peak relative intensities that could then be related to the
`
`qualitative descriptors provided in the patent.
`
`46.
`
`In a second method, the signals (peaks) are separated from the noise(baseline) for
`
`each of the XRPD patterns. To do this, a region of the XRPD diffractogram that contained no
`
`peaks is first identified to determine the amount of measured intensity corresponds to
`
`“background.” Then, this background intensity value is subtracted from the peak intensities that
`
`are measured, and the differences are the peak intensities that can be compared.
`
`47.
`
`Comparing the values for the peak heights measured using the two methods
`
`described above with the corresponding descriptors that are provided for each peak in the claims
`
`of the patent, provides a rational basis to analyze the metes and bounds of the claimed qualitative
`
`descriptors for XRPD peak intensity.
`
`48.
`
`There are no discrete boundaries between the various intensity descriptors that the
`
`inventors provided for the pitavastatin XRPD peaks. Every single one of the intensity terms
`
`contains a range of intensity values that overlaps with another terms.
`
`49.
`
`Even when the intensity ranges for the claimed forms are considered together, all
`
`of them overlap with another:
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 18 of 24
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`
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`50.
`
`As seen in the chart above, in some cases the patentees have characterized a peak
`
`
`
`as being “very weak” that is more intense than another peak characterized as “strong”.
`
`51.
`
`In another example, certain peaks used to define Form A in Claim 1 that are
`
`labelled as “strong” peaks actually have peak intensity values lower than peaks labelled as
`
`“medium” for the same form. This result contradicts the plain and ordinary meaning of the terms
`
`“strong” and “medium” as understood by a POSA and confirms the ambiguity in these claim
`
`terms as used in the asserted claims. 10
`
`52.
`
`A POSA would also be confused by the fact that there are no peaks with “very
`
`strong” relative intensity for Form C. The intensity descriptors found in the claims are clearly
`
`relative intensity descriptors as disclosed in the specification. However, it makes no sense that
`
`
`10 DTX-0059, Col. 10:50-11:37
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 19 of 24
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`the peak in Form C with a relative intensity value of 100% is not a “very strong” peak as that
`
`peak corresponds by definition to the maximum intensity peak.
`
`53.
`
`Although it would be expected that all peaks labelled as “strong” would fall
`
`within a common range of relative intensities across all the form, the range of intensities is
`
`highly variable depending on the solid form. For example, the peaks labelled as “strong” in
`
`Claim 1 for Form A fall within a range of 42-68% as derived from Figure 1, while the “strong”
`
`peaks claimed for Form B fall within a range of 49-82% as determined from analysis of Figure 2.
`
`Therefore, a POSA would have no understanding of what constitutes a “strong” peak as opposed
`
`to a “medium” peak when interpreting the XRPD patterns for the various polymorphs disclosed
`
`in the 993 patent.11 Exxon Research & Eng’g Co. v. U.S., 265 F.3d 1371, 1381 (Fed Cir. 2001)(
`
`When a word of degree is used the district court must determine whether the patent’s
`
`specification provides some standard for measuring that degree.”); Hearing Components, Inc. v.
`
`Shure Inc., 600 F.3d 1357, 1367 (Fed. Cir. 2010); Enzo Biochem, Inc., v. Applera Corp., 599
`
`F.3d 1325, 1332 (Fed. Cir. 2010).
`
`54.
`
`Even if a POSA did not subtract out baseline data and considered only the
`
`diffractograms coupled with the arbitrary assignment of relative intensities by the patentees,
`
`anomalous results immediately frustrate a POSA’s ability to understand the scope of what is
`
`claimed.
`
`55.
`
`The arbitrary assignment of vs, s, m, w, vw, provide no objective criteria to assist
`
`a POSA in determining how to determine whether a XRPD peak is, e.g., vs or s, s or m, etc. As
`
`a result, persons of ordinary skill in the art could not determine the scope of the claims with any
`
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`11 DTX-0059, Col. 10:50-11:37
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 20 of 24
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`certainty, let alone with reasonable certainty, because the patent does not describe how to tell
`
`what the relative intensity of a claimed peak may be. See also, Bayer Intellectual Prop. GmbH v.
`
`Warner Chilcott Co., LLC, 2016 WL 4363485 (D. Del. Apr. 21, 2015) (Sleet, J.) (finding various
`
`terms of degree indefinite -- “high contraceptive reliability, low incidence of follicular
`
`development, and satisfactory cycle control, with reliable avoidance of intracyclic menstrual
`
`bleeding and undesirable side-effects.” The court observed that the words of degree, such as
`
`“high,” “low,” “satisfactory,” and “reliable” had no standards against which to draw
`
`comparisons, and the patent offered no suggestions for how to measure them.); Graphics Props.
`
`Holdings v. Asus Computer Int’l, Inc., 70 F. Supp.3d. 654 (D. Del. Sept. 29, 2014) (Stark, C.J.)
`
`(finding term “high information content” indefinite because there was no standard in the
`
`specification for measuring what differentiates "high information content" from "information
`
`content" generally).
`
`56.
`
`The XRPD pattern of Form A (Fig. 1) is illustrative:
`
`
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`Case 1:14-cv-02758-PAC Document 107 Filed 12/16/16 Page 21 of 24
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`20.8 vs
`
`21.1 m
`
`24.2 s
`
`57.