IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`___________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
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`ARGENTUM PHARMACEUTICALS LLC,
`PETITIONER
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`v.
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`COSMO TECHNOLOGIES LIMITED,
`PATENT OWNER
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`
`___________________
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`
`CASE IPR2018-00080
`Patent 9,320,716
`___________________
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`PATENT OWNER’S PRELIMINARY PATENT OWNER RESPONSE
`UNDER 37 C.F.R. § 42.107
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`Table of Contents
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`I. 
`
`II. 
`
`Introduction ................................................................................................... 1 
`
`Background ................................................................................................... 8 
`
`A. 
`
`Technical Overview Of The Invention .............................................. 8 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`Inflammation Associated With Ulcerative Colitis ................... 8 
`
`Treatment Of Ulcerative Colitis............................................... 9 
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`Oral Colonic-Delivery Formulations ..................................... 10 
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`Uceris ..................................................................................... 14 
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`B. 
`
`Prosecution History .......................................................................... 16 
`
`C.  Mylan IPR ........................................................................................ 16 
`
`III.  Claim Construction ..................................................................................... 18 
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`A. 
`
`B. 
`
`“macroscopically homogenous structure” (All Claims) .................. 18 
`
`“to treat intestinal inflammatory disease” (All Claims) ................... 18 
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`IV.  Each of Petitioner’s Grounds Fails ............................................................. 21 
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`A.  Grounds 1 And 2: The ʼ584 Patent (Ex. 1008) Does Not
`Anticipate Nor Render Obvious Any Of The Claims ...................... 21 
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`1. 
`
`2. 
`
`3. 
`
`The ʼ584 Patent Does Not Teach “a macroscopically
`homogenous structure” (All Claims) ..................................... 24 
`
`The ʼ584 Patent Does Not Teach “wherein the
`macroscopically homogenous structure controls the
`release of the budesonide” (All Claims) ................................ 36 
`
`The ʼ584 Patent Does Not Teach How To Make A
`Formulation With “budesonide in an amount effective
`to treat intestinal inflammatory disease” (All Claims) .......... 40 
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`4. 
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`5. 
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`The ʼ584 Patent Does Not Anticipate Or Render
`Obvious Amphiphilic Claims (Claims 6-8, 12-23, 25-
`26, 28-29) ............................................................................... 42 
`
`The ʼ584 Patent Does Not Provide A Motivation Or A
`Reasonable Expectation Of Success ...................................... 46 
`
`B. 
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`Grounds 3 and 4: The ʼ388 Patent (Ex. 1009) Does Not
`Anticipate Or Render Obvious Any Of The Claims ........................ 47 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`The ʼ388 Patent Does Not Teach A Macroscopically
`Homogenous Structure (All Claims) ..................................... 48 
`
`The ʼ388 Patent Does Not Teach A Macroscopically
`Homogenous Structure Comprising “at least one
`lipophilic compound” (Claims 1-11, 22-24, 26-27, 29) ........ 51 
`
`The ʼ388 Patent Does Not Teach “wherein the
`macroscopically homogenous structure controls the
`release of the budesonide” (All Claims) ................................ 51 
`
`The ʼ388 Patent Does Not Teach How To Make A
`Formulation With “budesonide in an amount effective
`to treat intestinal inflammatory disease” (All Claims) .......... 52 
`
`The ʼ388 Patent Does Not Anticipate Or Render
`Obvious Amphiphilic Claims (Claims 6-8, 12-23, 25-
`26, 28-29) ............................................................................... 57 
`
`The ʼ388 Patent Does Not Provide A Motivation Or A
`Reasonable Expectation Of Success ...................................... 60 
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`C. 
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`Ground 5: The ʼ388 patent (Ex. 1009) In Combination With
`The ʼ584 Patent (Ex. 1008) Does Not Render Obvious
`Claims 8, 10, 18, and 20 ................................................................... 61 
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`1. 
`
`2. 
`
`Lecithin (Claims 8 and 18) .................................................... 61 
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`Stearic acid (Claims 10 and 20) ............................................. 62 
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`V. 
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`Petitioner Fails To Overcome The Objective Evidence Of
`Non-Obviousness ........................................................................................ 62 
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`A.  Others, Including The Pharma Giant In The GI Field,
`AstraZeneca, Failed To Meet The Long-Felt Need To
`Develop An Oral Formulation That Could Deliver Drug To
`The Distal Colon .............................................................................. 63 
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`B. 
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`Uceris Satisfied The Long-Felt Need ............................................... 66 
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`VI.  The Petition Should Be Denied Because the Inter Partes Review
`Process is Unconstitutional ......................................................................... 69 
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`VII.  Conclusion .................................................................................................. 70 
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`I.
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`INTRODUCTION
`Petitioner Argentum (“Petitioner”) filed this petition for inter partes review
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`after an institution decision was rendered in Mylan Pharmaceuticals, Inc. v. Cosmo
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`Technologies, Ltd., IPR2017-01035 (“Mylan IPR”).1 Petitioner raises the same
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`grounds that were instituted in the Mylan IPR, but submits a new expert
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`declaration in support. Neither Petitioner nor its new expert declaration, however,
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`addresses the evidentiary deficiencies pointed out by Patent Owner in its prior
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`preliminary response from the Mylan IPR.
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`In its institution decision in the Mylan IPR (IPR2017-01035, Paper 17),
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`hereinafter “Mylan Institution Decision” or “Decision,” the Board did not agree
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`with all of Patent Owner’s arguments. With this Preliminary Response, Patent
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`Owner now submits new evidence and arguments why institution should be
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`denied. In particular, Patent Owner submits additional evidence showing that,
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`contrary to Petitioner’s position, merely mixing and blending ingredients followed
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`by tablet compression does not result in the claimed “macroscopically homogenous
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`structure.”
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`1 Petitioner Mylan Pharmaceuticals Inc. and Patent Owner have since settled their
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`dispute and filed a joint motion for termination. See IPR2017-01035, Paper 23.
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`Patent Owner also attaches to this Preliminary Response court documents
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`from related district court litigation (“Related Litigation”)2 on the same issue of
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`whether blending, mixing, and tablet compression necessarily results in a
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`macroscopically homogenous structure. The District Court found that it does not.
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`The Court’s full analysis was not available when Patent Owner submitted its
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`preliminary response in the Mylan IPR, but the findings are available now and
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`should inform the Board’s decision for this IPR.
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`Patent Owner requests that the Board deny institution on all grounds.
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`*
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`*
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`*
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`Ulcerative colitis (“UC”)
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`is a devastating disease
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`that can cause
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`inflammation throughout the large intestine, i.e., the colon. UC patients suffer from
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`persistent diarrhea, abdominal cramps and pain, rectal bleeding, loss of appetite,
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`weight loss, and fatigue. Unfortunately, there is no cure for UC.
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`At some point during the course of their disease, most patients must resort to
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`using glucocorticosteroids (“steroids”), a class of powerful anti-inflammatories, to
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`reduce their inflammation. While these systemic steroids can reduce colon
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`inflammation, they also cause terrible toxicities that preclude their long-term use,
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`including high blood pressure, glaucoma, memory and psychological effects,
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`2 Cosmo Tech. Ltd, et al. v. Actavis Laboratories, Inc., Civ. No. 15-164 (D. Del.).
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`IPR2018-00080 (Patent No. 9,320,716)
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`increased susceptibility to infections, diabetes, adrenal gland suppression, and
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`cataracts, among others.
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`Pharmaceutical companies, including giants in the field of gastrointestinal
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`(“GI”) disease like AstraZeneca, tried for many years to develop an oral, colonic-
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`delivery formulation that could deliver locally-acting steroids, such as budesonide,
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`directly to sites of inflammation and thereby avoid the toxicities of systemic
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`administration. While some formulations, such as Entocort CR®, could deliver
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`drug to the small intestine and proximal colon (the portion of the colon
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`immediately after the small intestine), no prior art formulation delivered drug
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`throughout all the sectors of the colon, including the hard-to-reach distal colon (the
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`final portion of the colon).
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`Patent owner fulfilled this unmet need by developing a tablet formulation
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`that delivers budesonide throughout all sectors of the colon, including the distal
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`colon. This formulation is sold as Uceris®,and it is covered by the patent at issue,
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`U.S. Pat. No. 9,320,716 (“the ʼ716 patent”). As shown in a pharmaco-scintigraphy
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`study,3 Uceris® delivers budesonide “throughout the whole colon including the
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`3 A “pharmaco-scintigraphy” study allows assessment of where in the GI tract, and
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`to what extent, the drug formulation breaks up and releases the active compound.
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`See Ex. 2038 at 1201.
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`sigmoid [, i.e., the end of the distal colon].” Ex. 2039 at 34. This extraordinary
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`drug-release profile results from a novel feature of the formulation claimed by the
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`ʼ716 patent: a “macroscopically homogenous structure” comprising a hydrophilic,
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`lipophilic, and/or amphiphilic compound “wherein
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`the macroscopically
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`homogenous structure controls the release of the budesonide.”
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`None of the art cited by Petitioner taught this novel feature. Indeed, the two
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`references in Petitioner’s Grounds disclosed very different methods of colonic
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`delivery. The first reference, U.S. Pat. 5,681,584 (Ex. 1008, “the ʼ584 patent”),
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`teaches the use of discrete layers—i.e., a “delay jacket” and “semi-permeable
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`membrane”—and, optionally, a “release orifice” to control drug release. The
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`second reference, U.S. Pat. 5,811,388 (Ex. 1009, “the ʼ388 patent”), teaches a
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`bioerodible formulation that uses gum to control release through degradation by
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`microbes and enzymes present in the colon. Neither reference teaches a
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`“macroscopically homogenous structure” of hydrophilic,
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`lipophilic, and/or
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`amphiphilic excipients to control drug release.
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`Petitioner’s only argument that the prior-art references disclose the key
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`limitation of the ʼ716 patent is to conclude summarily that “blending,” “mixing,”
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`and compression of pharmaceutical ingredients to obtain a “uniform matrix tablet,”
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`without more, necessarily results in a “macroscopically homogenous structure.”
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`Not so.
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`IPR2018-00080 (Patent No. 9,320,716)
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`As discussed in detail in Section IV.A.1 below, the homogeneity of a
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`mixture depends upon many factors, including mixing time, the size and shape of
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`each component’s particles (e.g., whether particles are milled or micronized),
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`relative densities of different components, the order of mixing, mixing equipment,
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`whether the mixture is moved during the manufacturing process, and the quantity
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`of an excipient relative to the total amount of all components. If homogeneity is
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`desired for a particular product, additional steps and techniques, such as geometric
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`dilution and comilling, often are necessary. Neither the ʼ584 patent nor the ʼ388
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`patent instructs the use of any of these techniques. Indeed, neither reference says
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`anything about achieving homogeneity in any sense, much less macroscopic
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`homogeneity. Neither Petitioner nor its expert provides any underlying rationale
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`why the very limited descriptions of the formulation processes in the ʼ584 patent
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`(e.g., “mix[] together”) and the ʼ388 patent (e.g., “simply blend[]”) necessarily
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`would result in a macroscopically homogenous structure.
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`The omission of any analysis by Petitioner is glaring for at least three
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`reasons. First, conclusory assertions, unaccompanied by citation to scientific
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`literature or reasoned explanation, are entitled to no weight. In re Kahn, 441 F.3d
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`977, 988 (Fed. Cir. 2006).
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`Second, Petitioner is effectively relying on an implicit inherency theory to
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`support its argument. Without any discussion of the particular physical properties
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`IPR2018-00080 (Patent No. 9,320,716)
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`of the ingredients (e.g., particle size, density, fineness) or the specific mixing and
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`processing steps they undergo (e.g., mixing time, sequence of mixing, geometric-
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`dilution mixing), Petitioner’s argument reduces to the recognition that one can
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`obtain a homogenous blend if the right ingredients are used and the proper steps
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`are taken. But the prior art contains no direction regarding achieving macroscopic
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`homogeneity; it contains only simple directions to mix. It is Petitioner’s burden to
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`show that one following that limited direction in the art would necessarily obtain a
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`macroscopically homogenous structure, i.e., for all ingredients, under all
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`processing conditions. See Continental Can Co. v. Monsanto Co., 948 F.2d 1264,
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`1268-69 (Fed. Cir. 1991) (for inherent anticipation “evidence must make clear that
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`the missing descriptive matter is necessarily present in the thing described in the
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`reference, and that it would be so recognized by persons of ordinary skill”); W.L.
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`Gore v. Garlock, 721 F.2d 1540, 1554 (Fed. Cir. 1983) (anticipation “cannot be
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`predicated on mere conjecture respecting the characteristics of products that might
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`result from the practice of processes disclosed in references”); Ex Parte Peltz,
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`Appeal 2012-011729, 2015 WL 430562, at *2 (P.T.A.B. Jan. 13, 2015) (“Absent
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`inevitability, inherency does not follow even from a very high likelihood that a
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`prior art method will result in the claimed invention.”). Yet Petitioner provides no
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`evidence from which one can reach that conclusion.
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`IPR2018-00080 (Patent No. 9,320,716)
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`Third, Petitioner points only to lipophilic lubricants in the ʼ388 patent
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`(Grounds 3 and 4) as allegedly satisfying the “one lipophilic compound” limitation
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`in the ʼ716 patent claims. But the ʼ388 patent expressly teaches that the lubricant
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`used in its formulations is not blended uniformly with other ingredients. Ex. 1009,
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`col. 16:19-22 (“the ingredients (except for the lubricant) are simply blended
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`together to provide a uniform mixture having the active ingredient uniformly
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`dispersed throughout….”).4 Petitioner’s failure to explain why skilled artisans
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`would homogenously mix lubricants with other ingredients when the reference
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`teaches the opposite dooms Petitioner’s assertion that the ʼ388 patent anticipates or
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`renders obvious claims that require “at least one lipophilic compound” in the
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`macroscopically homogenous structure.
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`For these reasons, and other deficiencies in the Petition (as will be
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`discussed), Petitioner does not establish a reasonable likelihood of prevailing on
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`any of its Grounds.
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`4 Emphasis is added to quotes unless other noted in this Preliminary Response.
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`IPR2018-00080 (Patent No. 9,320,716)
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`II. BACKGROUND
`A. Technical Overview Of The Invention
`1.
`Inflammation Associated With Ulcerative Colitis
`Ulcerative colitis is intestinal inflammatory disease that affects the large
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`intestine. UC inflammation begins in the rectum and extends proximally
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`(backwards) in an uninterrupted pattern involving part of or the entire colon.
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`Below is an illustration of typical UC inflammation (image of large intestine
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`anatomy from Exhibit 2034, see also Ex. 2035 at 181, and the extent of
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`inflammation is shown in light and dark red shading):
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`Because UC inflammation can affect the whole colon, see Ex. 2004 at 98,
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`effective treatment must exert its anti-inflammatory effects throughout the sectors
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`of the colon. This includes the left-sided colon (right side of the illustration above)
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`IPR2018-00080 (Patent No. 9,320,716)
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`and sigmoid colon—known together as the “distal colon”—where inflammation is
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`commonly worse. See Ex. 2005 at 43 (“The most frequent localization of
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`ulcerative colitis (UC) is the distal colon.”); id. at 44 (“In treating active distal UC,
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`efficacy and targeting of the drug to the distal colon are key priorities.”); Ex. 2035
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`at 181; Ex. 2034 at 3 (“The distal colon includes the descending colon…and the
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`sigmoid colon….”).
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`Treatment Of Ulcerative Colitis
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`2.
`Non-steroidal anti-inflammatory drugs are inadequate to address UC in
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`nearly half of all UC patients. To treat UC, these individuals have historically
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`resorted to systemically-acting steroids, such as dexamethasone, taken orally or
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`administered intravenously. See Ex. 2006 at 16. Systemic steroids, which act
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`through the bloodstream, can reduce inflammation along the length of the colon.
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`The problem, however, is that maintaining the levels of systemic steroid necessary
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`to reduce inflammation is very toxic to other parts of the body. See Ex. 1009,
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`col. 1:63-66; Ex. 2007 at 1218. These toxicities affect almost all organ systems in
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`the body and include neuropsychiatric complications, osteoporosis, impaired
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`wound healing, hypertension, diabetes, weight gain, glaucoma, “moon face,” and
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`“buffalo hump.” See Ex. 2008 at 205; Ex. 2009 at 179.
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`To avoid systemic steroid toxicities, drug formulators have attempted to
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`design oral dosage forms for localized (topical) delivery in the colon, in which the
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`IPR2018-00080 (Patent No. 9,320,716)
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`active ingredient could act on the tissues it contacts while minimizing drug
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`absorption into systemic circulation. Such formulations could use locally-acting
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`steroid, such as budesonide, that has relatively low systemic absorption because of
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`high first-pass metabolism.5
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`3. Oral Colonic-Delivery Formulations
`Throughout the 1980s and 1990s, skilled artisans attempted to design orally
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`administered, colonic-delivery formulations that could deliver drug throughout the
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`colon to relieve inflammation. Artisans experimented with several different
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`colonic-release mechanisms. See Ex. 1009, col. 2:6-12 (identifying five different
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`categories of colonic-delivery formulations).
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`One example formulation used layers—a “delay jacket” and “semi-
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`permeable membrane”—and optionally a “release orifice” to control drug release.
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`Below is an illustration of this design (Figure 1 from Ex. 2011):
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`5 First-pass metabolism is a phenomenon of drug metabolism whereby the
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`concentration of a drug is greatly reduced before it reaches systemic circulation. In
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`the case of budesonide, a majority of the drug is metabolized by the liver before it
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`reaches systemic circulation.
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`IPR2018-00080 (Patent No. 9,320,716)
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`More detail about this formulation is discussed in Section IV.A when addressing
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`the ʼ584 patent (Ex. 1008).
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`Another example was a gum-based formulation that relied on bacteria in the
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`colon to enzymatically degrade (i.e., digest) the gum enveloping active drug,
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`thereby releasing drug as the gum is eroded. More details about this drug release
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`mechanism are discussed in Section IV.B when addressing the ʼ388 patent
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`(Ex. 1009).
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`IPR2018-00080 (Patent No. 9,320,716)
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`Yet another example was a multi-particulate system with individual drug
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`pellets having different controlled-release enteric (pH sensitive) coats that released
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`drug at different times. Below is an illustration of multiparticulate formulations:
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`Pellets contained different coatings to stagger the release of drug following
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`administration, such that each pellet controlled release of only that portion it
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`contained (Figure 1 from Ex. 2010):
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`IPR2018-00080 (Patent No. 9,320,716)
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`One such multiparticulate formulation, marketed by AstraZeneca as Entocort EC®,
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`was approved to treat Crohn’s disease, a gastrointestinal disease associated with
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`inflammation in the small intestines and proximal colon, but usually not the distal
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`colon. See Ex. 2004 at 98.
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`As of the priority date, no oral colonic-delivery steroid formulation had been
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`approved in the United States for UC treatment. This was because no one had been
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`able to formulate a colonic-delivery system that delivered drug throughout the
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`sectors of the colon, including the hard-to-reach distal colon where UC
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`inflammation begins and is most severe.
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`Delivering drug specifically and selectively to the sectors of the colon,
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`including the distal colon, is difficult because the oral dosage formulation has to
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`(1) traverse the stomach and small intestine to reach the colon, and (2) once in the
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`colon, release drug in a controlled manner throughout the sectors of the colon. To
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`achieve these goals, formulators must design formulations that can overcome wide
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`variations in pH, osmotic pressure, viscosity and volume of fluid, enzymatic
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`conditions, distribution of gut bacteria, mechanical force, and transit time in the
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`gastrointestinal tract. See Ex. 1008, col. 1:59-2:45.
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`Even if a dosage formulation successfully reaches the colon to begin drug
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`delivery, a big challenge in treating patients with UC is ensuring delivery
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`throughout all sectors of the colon, including and especially in the distal colon.
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`IPR2018-00080 (Patent No. 9,320,716)
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`For years, scientists tried and failed to design an oral dosage form containing
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`a topically-acting steroid for the treatment of UC.
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`Uceris
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`4.
`Patent owner solved the long-felt need by creating a novel oral formulation
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`that delivered topical steroid throughout the sectors of the colon. This unique tablet
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`formulation controls the release of its active ingredient, the steroid budesonide, by
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`using a macroscopically homogenous structure of at least one hydrophilic excipient
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`and at least one lipophilic, and/or amphiphilic excipient.6
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`Patent owner rejected prior art formulations that used multiparticulate
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`systems, bacteria-based release systems (e.g., gum-based), and delay layers to
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`control drug release. Instead, patent owner discovered that a single-unit tablet can
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`deliver drug throughout the colon if it possesses release-controlling excipients
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`contained in a macroscopically homogeneous structure. Patent Owner’s invention,
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`claimed by the ’716 patent, is commercially embodied by the FDA-approved drug
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`Uceris.® See Ex. 1060 at 2 (Orange Book listing for Uceris®)
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`6 Independent Claim 1 requires at least one hydrophilic and one lipophilic
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`compound. Independent Claim 12 requires at least one hydrophilic and one
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`amphiphilic compound. Independent Claim 22 requires at least one hydrophilic,
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`one lipophilic, and one amphiphilic compound.
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
`Uceris® is the only colonic-delivery steroid formulation approved for
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`treatment of UC. This approval was due, in part, to pharmaco-scintigraphy data
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`demonstrating that Uceris® delivered drug throughout the sectors of the colon,
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`including the hard-to-reach distal colon. Below on the left is a scintigraphy image
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`showing approximate drug dosage form breakup with Uceris® (from Figure 1 of
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`Ex. 2039), and on the right, for comparison, is figure of the large-intestine anatomy
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`(Ex. 2035 at 181):
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`
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`As illustrated above, approximate drug release from the scintigraphy image (bright
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`spots from the radioactive label) shows spread throughout the colon.
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`The FDA approved Uceris® in 2013 for the treatment of active, mild to
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`moderate ulcerative colitis. Due to the commercial and clinical success of Uceris®,
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`six generic drug manufacturers filed Abbreviated New Drug Applications seeking
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`to market generic versions of Uceris®.
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`Prosecution History
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`B.
`Petitioner’s Grounds rely on the same references that the examiner
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`considered during prosecution. The examiner withdrew an anticipation rejection
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`over the ʼ584 patent (Ground 1) after patent owner explained that the ʼ584 patent
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`does not disclose “a macroscopically homogenous” structure. See Ex. 2011 at 8.
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`The examiner also withdrew an obviousness rejection over the ʼ584 patent
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`(Ground 2). See Ex. 2012 at 7-8. Additionally, the examiner withdrew an
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`anticipation rejection over the ʼ388 patent (Ground 3). See Ex. 2013 at 5-7.
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`C. Mylan IPR
`In the Mylan IPR, the Board issued an institution decision holding that there
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`was a reasonable likelihood the ’716 patent claims were anticipated and obvious
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`over the ʼ584 patent, the ʼ388 patent, and the combination of the references
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`(Decision at 34):
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
`
`For each ground, the Board credited the petitioner’s argument that “mixing”
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`and “blending” prior to tablet compression would necessarily result in a
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`“macroscopically homogenous structure.” See Sections IV.A.1 and IV.B.1. Patent
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`Owner respectfully disagrees with that holding. In this Preliminary Response,
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`Patent Owner presents new evidence and arguments showing that mere mixing and
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`blending prior to tablet compression do not necessarily create a macroscopically
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`homogenous structure. In its prior preliminary response, for example, Patent
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`Owner was only able to rely on redacted portions of a trial transcript from the
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`District Court in Related Litigation. Since then, the District Court’s trial transcript
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`has been made publicly available, (Ex. 2025) and a subsequent memorandum
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`opinion (Ex. 2003) squarely addresses the question of whether mere mixing and
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`blending necessarily results in a “macroscopically homogenous” structure. The
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`Court held that it does not.7
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`7 Patent owner disagrees with the ultimate holding in that litigation because, inter
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`alia, there was evidence of record in that case well beyond mere blending and
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`uniformity testing. But, as discussed Section IV.A.1 below, where, as here, the
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`prior art discloses scant details beyond the bare fact of mixing, there is insufficient
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`evidence to meet the high burden of showing an alleged inherent property of the
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`prior art.
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`Other holdings from the Mylan Institution Decision are discussed later in
`
`this Preliminary Response in the applicable sections.
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`III. CLAIM CONSTRUCTION
`A.
`“macroscopically homogenous structure” (All Claims)
`In the Mylan Institution Decision, the Board held that the broadest
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`reasonable interpretation of “macroscopically homogenous structure” was “a
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`composition of uniform structure throughout, as observed by the naked eye,”
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`adopting the same construction issued by the District Court in Related Litigation.
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`See Decision at 8.
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`As will be discussed in Section IV.A.1, the District Court subsequently
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`found that the limitation of a “macroscopically homogenous” tablet could not be
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`met by mere “blending” and “mixing” of excipients, and “compression steps.”
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`“to treat intestinal inflammatory disease” (All Claims)
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`B.
`Petitioner offers no construction of this term. In the Mylan Institution
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`Decision, the Board held that although “Patent Owner proffer[ed] a construction of
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`the term ‘to treat intestinal inflammatory disease,’” the term “require[d] no
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`construction for purposes of [the institution] decision.” Decision at 8. Patent
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`Owner respectfully disagrees.
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`As defined in the specification, the term “to treat intestinal inflammatory
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`disease” requires that the claimed tablet contain budesonide in an amount effective
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`“to treat inflammatory bowel disease by targeting the large intestinal sectors.”
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`Despite the attempts of many companies, including GI giants like AstraZeneca,
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`none of the resulting prior art references taught oral colonic-release formulations
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`that were able to target all the large intestinal sectors, including the distal colon, as
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`discussed in Sections II.A and V.A. Therefore, the construction of this term is
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`relevant to whether the art taught this limitation, and whether there was a
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`reasonable expectation of success for creating a formulation that could achieve this
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`limitation given that no one had done so previously in the field.
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`Although the Board did not construe this limitation, the Mylan Institution
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`Decision implicitly relied on an unreasonably broad interpretation of the term to
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`encompass “any intestinal inflammatory disease”:
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`“[E]ven assuming that Kenyon, quoted above, shows
`testing of a formulation of the ’388 Patent, its failure to
`treat a specific inflammatory disease of the colon, distal
`ulcerative colitis, does not show necessarily on this
`treat any
`record
`that
`it would fail
`to
`intestinal
`inflammatory disease.
`Decision at 30. The specification precludes this interpretation.
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`
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`The specification recites the requirement of targeting all the large intestinal,
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`i.e., the colon, sectors:
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`The tablets according to the present invention, when
`designed to be used to treat inflammatory bowel disease,
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
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`in principle have … to target the large intestinal
`sectors,….”
`Ex. 2016, U.S. Pat. No. 8,293,273, col. 5:57-6:1, incorporated by reference into the
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`ʼ716 patent (Ex. 1001, col. 1:22-23). These sectors are the ascending colon,
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`transverse colon, descending colon, sigmoid colon, and rectum (the descending and
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`sigmoid colon are also collectively referred to as the “distal colon”). See Ex. 2033
`
`at 15.
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`As Petitioner acknowledges, “intestinal
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`inflammatory disease” and
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`“inflammatory bowel disease” are generally understood to be equivalent terms in
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`the art. See Pet. 1 (“The ʼ716 patent generally claims a composition…for the
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`treatment of inflammatory bowel disease….”); Ex. 2017 at Title, 63 (using the
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`terms “inflammatory bowel disease” and “inflammatory intestinal disease”
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`interchangeably). Because the claim term “to treat inflammatory intestinal disease”
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`is expressly defined to require treatment of inflammatory bowel disease by
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`“target[ing] the large intestinal sectors” in the specification, Patent Owner’s
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`construction should be adopted. See Martek Biosciences Corp. v. Nutrinova, 579
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`F.3d 1363, 1380 (Fed. Cir. 2009) (“When a patentee explicitly defines a claim term
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`in the patent specification, the patentee’s definition controls.”).
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`IPR2018-00080 (Patent No. 9,320,716)
`Patent Owner Preliminary Response
`IV. EACH OF PETITIONER’S GROUNDS FAILS
`To establish anticipation, each and every element in a claim, arranged as
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`recited in the claim, must be found in a single prior art reference. Net MoneyIN,
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`Inc. v. VeriSign, Inc., 545 F.3d 1359, 1369 (Fed. Cir. 2008). To prove obviousness,
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`petitioner must show “that a skilled artisan would have had reason to combine the
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`teaching of the prior art references to achieve the claimed invention, and that the
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`skilled artisan wou