UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`MYLAN PHARMACEUTICALS INC.
`MYLAN LABORATORIES LIMITED
`Petitioner
`
`v.
`
`QUALICAPS CO. LTD.
`Patent Owner
`
`
`U.S. Patent No. 6,649,180
`Filing Date: April 13, 2000
`Issue Date: November 18, 2003
`Title: HARD CAPSULE FORMED OF CELLULOSE ETHER FILM WITH A
`SPECIFIC CONTENT OF METHOXYL AND HYDROXYPROPOXYL
`GROUPS
`________________
`
`Inter Partes Review No. Unassigned
`
`
`
`DECLARATION OF ARTHUR H. KIBBE IN SUPPORT OF PETITION
`
`FOR INTER PARTES REVIEW OF U.S. PATENT NO. 6,649,180
`
`
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 1
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`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`MYLAN PHARMACEUTICALS INC.
`MYLAN LABORATORIES LIMITED
`Petitioner
`
`v.
`
`QUALICAPS CO. LTD.
`Patent Owner
`
`
`U.S. Patent No. 6,649,180
`Filing Date: April 13, 2000
`Issue Date: November 18, 2003
`Title: HARD CAPSULE FORMED OF CELLULOSE ETHER FILM WITH A
`SPECIFIC CONTENT OF METHOXYL AND HYDROXYPROPOXYL
`GROUPS
`________________
`
`Inter Partes Review No. Unassigned
`
`
`
`DECLARATION OF ARTHUR H. KIBBE IN SUPPORT OF PETITION
`
`FOR INTER PARTES REVIEW OF U.S. PATENT NO. 6,649,180
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 1
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`
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`TABLE OF CONTENTS
`
`SCOPE OF THE REPORT .................................................................. 1
`
`QUALIFICATIONS AND EXPERIENCE ......................................... 3
`
`
`
`I.
`
`II.
`
`III. TECHNOLOGY BACKGROUND OF CLAIMED SUBJECT
`MATTER OF THE ’180 PATENT ...................................................... 7
`
`A.
`
`B.
`
`Thermal Gelling ......................................................................... 8
`
`Additive Gelling ....................................................................... 10
`
`IV. OVERVIEW OF THE ’180 PATENT ............................................... 13
`
`V.
`
`PERSON OF ORDINARY SKILL IN THE ART ............................. 15
`
`VI.
`
`IDENTIFICATION OF THE PRIOR ART ....................................... 15
`
`A. Yamamoto ................................................................................ 15
`
`B.
`
`C.
`
`The Japanese Pharmacopeia ..................................................... 16
`
`Greminger ................................................................................. 16
`
`VII. CLAIM CONSTRUCTION ............................................................... 17
`
`A.
`
`B.
`
`“gelling agent”.......................................................................... 17
`
`“gelling aid” ............................................................................. 18
`
`VIII. STATEMENT OF LEGAL PRINCIPLES ........................................ 18
`
`IX. UNPATENTABILITY OF THE ’180 PATENT CLAIMS ............... 19
`
`A. Ground 1: Claims 1 and 4 are Unpatentable as Obvious
`in View of Yamamoto in Combination with Japanese
`Pharmacopeia ........................................................................... 19
`
`1.
`
`Claim 1 ........................................................................... 19
`
`i.
`
`Limitation [1.1] “A hard capsule formed of a
`film composition comprising a
`
`i
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 2
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`ii.
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`hydroxypropyl methyl cellulose as a base, a
`gelling agent, and a gelling aid.” ......................... 19
`
`Limitation [1.2] wherein said hydroxypropyl
`methyl cellulose has a content of
`hydroxypropoxyl groups of at least 4% by
`weight of the hydroxypropyl methyl
`cellulose and a content of methoxyl groups
`and hydroxypropoxyl groups combined of
`23 to 37.6% by weight of the hydroxypropyl
`methyl cellulose. .................................................. 21
`
`2.
`
`Claim 4 ........................................................................... 30
`
`i.
`
`Limitation [4.1] The hard capsule formed of
`a film of claim1, wherein the content of
`methoxyl and hydroxypropoxyl groups
`combined is 29 to 37% by weight of the
`hydroxypropyl methyl cellulose. ......................... 30
`
`B.
`
`Ground 2: Claims 1 and 4 are Unpatentable as Obvious
`in View of Greminger .............................................................. 38
`
`1.
`
`Claim 1 ........................................................................... 38
`
`i.
`
`ii.
`
`Limitation [1.1] “A hard capsule formed of a
`film composition comprising a
`hydroxypropyl methyl cellulose as a base, a
`gelling agent, and a gelling aid.” ......................... 38
`
`Limitation [1.2] wherein said hydroxypropyl
`methyl cellulose has a content of
`hydroxypropoxyl groups of at least 4% by
`weight of the hydroxypropyl methyl
`cellulose and a content of methoxyl groups
`and hydroxypropoxyl groups combined of
`23 to 37.6% by weight of the hydroxypropyl
`methyl cellulose. .................................................. 41
`
`2.
`
`Claim 4 ........................................................................... 44
`
`ii
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 3
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`i.
`
`Limitation [4.1] The hard capsule formed of
`a film of claim1, wherein the content of
`methoxyl and hydroxypropoxyl groups
`combined is 29 to 37% by weight of the
`hydroxypropyl methyl cellulose. ......................... 44
`
`C.
`
`The Proposed Grounds for Rejection Address Patentee’s
`Asserted Unexpected Benefit of Shell Clarity and
`Stability .................................................................................... 47
`
`1.
`
`2.
`
`Yamamoto ...................................................................... 48
`
`Greminger ...................................................................... 49
`
`X.
`
`CONCLUSION .................................................................................. 51
`
`
`
`
`
`iii
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`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 4
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`
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`I, Arthur H. Kibbe, being over the age of 18 and competent to make
`
`the statements herein, hereby declare the following:
`
`I. SCOPE OF THE REPORT
`1.
`I have been retained on behalf of Petitioner Mylan
`
`Pharmaceuticals Inc. (“Petitioner” or “Mylan”) as an independent expert
`
`consultant to analyze and provide my opinions on the invalidity of U.S.
`
`Patent No. 6,649,180 (the “’180 Patent”), and such other topics as addressed
`
`in this report.
`
`2.
`
`As part of this work, I have been requested by counsel for
`
`Petitioner to study Claims 1 and 4 of the ’180 Patent and opine on their
`
`invalidity.
`
`3.
`
`I understand based on information and belief, including
`
`assignment information available in the United States Patent and Trademark
`
`Office Patent Assignment Database, the ’180 Patent was initially assigned to
`
`Shionogi Qualicaps Co., Ltd. and is currently assigned to Qualicaps Co.,
`
`Ltd. Upon information and belief, Warner Chilcott Company, LLC has an
`
`exclusive license to manufacture a drug called DELZICOL® under the ’180
`
`Patent.
`
`4.
`
`In this declaration, I will discuss the technology related to the
`
`’180 Patent, including an overview of that technology as it was known at the
`
`
`
`1
`ETITIONER MYLAN EXHIBIT 1010
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 5
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`time of the earliest filing date of April 13, 2000. This overview of the
`
`relevant technology provides some of the bases for my opinions with respect
`
`to the ’180 Patent.
`
`5.
`
`In forming my opinions, I have relied upon the ’180 Patent, the
`
`prosecution history of the ’180 Patent, the Exhibits to the Petition for Inter
`
`Partes Review of the ’180 Patent, and my own experience and expertise in
`
`the relevant technologies and systems that were already in use prior to, and
`
`within the timeframe of the earliest priority date of the claimed subject
`
`matter in the ’180 Patent – April 13, 2000.
`
`6.
`
`This declaration is based on the information currently available
`
`to me. To the extent that additional information becomes available, I reserve
`
`the right to continue my investigation and study, which may include a
`
`review of documents and information that may be produced, as well as
`
`testimony from depositions that may not yet be taken.
`
`7. My opinions and conclusions are set forth below. If called
`
`upon to testify, I am prepared to do so.
`
`8.
`
`I am being compensated at my standard rate of $750 per hour
`
`for the time I spend on this matter. No part of my compensation is
`
`dependent upon the outcome of this proceeding, and I have no financial or
`
`other economic interest in this matter.
`
`2
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 6
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`II. QUALIFICATIONS AND EXPERIENCE
`9.
`I am an emeritus Professor of Pharmaceutical Sciences at the
`
`Wilkes University School of Pharmacy, Wilkes University, as well as the
`
`former Chair of the Department of Pharmaceutical Sciences in the School of
`
`Pharmacy. I earned a Bachelor of Science degree in Pharmacy from
`
`Columbia University in 1966, a Master of Science degree in
`
`Pharmacy/Pharmaceutics from the University of Florida in 1968, and my
`
`Ph.D. in Pharmaceutics from that institution in 1973. My areas of
`
`concentration at that time were Pharmaceutics, Pharmacokinetics and
`
`Biopharmaceutics. My dissertation was on the stability of solid dosage
`
`forms. I joined the faculty of the Department of Pharmaceutical Sciences at
`
`Wilkes University as its Chair in 1994. In that capacity, I oversaw the
`
`construction of the laboratory and research space in the then new School of
`
`Pharmacy, and continue to direct the faculty and teach undergraduate and
`
`professional courses in pharmaceutics (dosage form design and
`
`manufacture) and pharmacokinetics.
`
`10.
`
`I have held a variety of positions in academia, industry, and the
`
`government over the course of my career. My work has been largely
`
`concentrated in the fields of pharmaceutical formulation development;
`
`pharmacokinetics; and the pharmaceutical testing, regulatory and approval
`
`3
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 7
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`processes. I served as the Chief of Pharmaceutical Development Services
`
`for the National Institutes of Health (NIH) from 1984-1985. In that position,
`
`I directed a staff of 15 scientists, developed delivery systems for Phase I
`
`clinical trials, and supported the internal NIH clinical research program. As
`
`the Senior Director of Professional and Scientific Affairs for the American
`
`Pharmaceutical Association from 1987-1992, my responsibilities included
`
`the development of policy statements on relevant scientific issues; the
`
`representation of the Association before Congress and the Food and Drug
`
`Administration (FDA); the development and management of symposia on
`
`scientific issues; the management of various professional staff; and the
`
`management of the Journal of Pharmaceutical Science. My experience also
`
`extends to the pharmaceutical industry. I was the Director of Client Services
`
`for BioResearch Laboratories, Ltd. from 1985-87, where I negotiated the
`
`protocol design and contracts for hundreds of Phase I studies and
`
`bioequivalency studies. I was also the Director of Marketing for Pharmakon
`
`Research International, Inc. from 1992-94, where I negotiated the protocol
`
`design and contracts for numerous preclinical trials.
`
`11. From 1972 to 1984, I was an Assistant/Associate Professor of
`
`Pharmaceutics at the School of Pharmacy of the University of Mississippi.
`
`While at the University of Mississippi, I taught undergraduate and graduate
`
`4
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`level courses in the areas of formulation design and development,
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`pharmacokinetics, and the physical chemistry of heterogenous systems;
`
`conducted research in those areas, among others; and served as a thesis
`
`advisor to Ph.D. candidates. I also taught continuing education courses to
`
`licensed pharmacists while on faculty at the University of Mississippi, and
`
`was Chair of the School of Pharmacy’s Curriculum Committee.
`
`12.
`
`I am a Fellow of the Academy of Pharmaceutical Research and
`
`Science, and have served on various editorial boards. I presently serve on
`
`the Editorial Review Panel of the Journal of Drug Development and
`
`Industrial Pharmacy, and as a Reviewer for the Journal of Pharmaceutical
`
`Science and the Journal of the American Pharmacists Association.
`
`13.
`
`I was the Chair of the Food and Drug Administration’s (FDA)
`
`Pharmaceutical Sciences Advisory Committee (2002 to 2004) and its
`
`subcommittee on cGMP and PAT. I continued as a member of this
`
`Advisory Committee and as a special employee of the FDA consulting on
`
`formulation issues that affect FDA policy. I have also serve as a scientific
`
`consultant to the Subcommittee on Oversight and Investigations of the
`
`Committee on Energy and Commerce of the United States House of
`
`Representatives. I have also served as a member of the FDA’s Generic Drug
`
`Advisory Committee. I am the past chair of the PA Governor’s Advisory
`
`5
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 9
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`Panel on Renal Disease having served for over ten years on the committee.
`
`While with the American Pharmaceutical Association, I served as the Chair
`
`of a special panel appointed by the Commissioner of FDA to investigate the
`
`generic drug approval process which produced a report entitled “Fairness in
`
`the Generic Drug Approval Process,” sometimes referred to as “the Kibbe
`
`Report.”
`
`14.
`
`I have authored or co-authored numerous papers in refereed
`
`journals, have written a number of essays and articles published in the
`
`professional press, and have made a number of presentations before national
`
`and international professional societies.
`
`15.
`
`I co-authored the “Generic Drugs and Generic Equivalency”
`
`chapter in the Encyclopedia of Pharmaceutical Technology (1st Ed. 1993)
`
`and authored that chapter in the two subsequent editions of the Encyclopedia
`
`of Pharmaceutical Technology. As an invited guest speaker, I have lectured
`
`on the generic drug approval process.
`
`16.
`
` I served as the Editor-in-Chief of the Handbook of
`
`Pharmaceutica1 Excipients (3rd Ed. 2000), and authored a number of the
`
`monographs contained therein. I serve on the Steering Committee for all the
`
`subsequent editions of the Handbook of Pharmaceutical Excipients, and
`
`have authored a number of monographs for those editions. I have also
`
`6
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 10
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`authored a chapter entitled “Theory of Dissolution” in the book “Dissolution
`
`Theory, Technology & Methods” edited by Anthony Palmieri III. (ISBN 0-
`
`9761519-1-X)
`
`17. During the course of my career, I have received several awards
`
`and honors, including recognition for my contributions to the training of
`
`pharmacy students.
`
`18. My complete curriculum vitae is attached hereto as
`
`Attachment A.
`
`III. TECHNOLOGY BACKGROUND OF CLAIMED SUBJECT
`MATTER OF THE ’180 PATENT
`19. Medicinal capsules have been around for more than a century.
`
`Originally, the capsules were made out of gelatin, which is derived from
`
`collagen from animal by-products. It is essentially the same material used to
`
`make foods such as marshmallows and JELL-O.
`
`20. The manner in which gelatin was made into capsules is similar
`
`in many regards to processes used today, using other materials. First, one
`
`makes a mixture of approximately 30% gelatin and 70% hot water. This
`
`forms a viscous hot mixture. For opaque and/or colored capsules an
`
`opacifying agent, dye, pigment, and other addenda are added. Room
`
`temperature stainless steel pins then are dipped into the hot liquid. Gelatin
`
`adheres to the surface of the pins forming a film for use as the hard capsule.
`
`7
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 11
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`The film is dried to remove excess water and stripped off the pin, forming
`
`the cap and body of the capsule. The body and cap of the capsule are filled
`
`with a pharmaceutical compound and joined together.
`
`21. A temperature difference resulting from heating the mixture and
`
`then cooling the mixture by introducing the cooler, room temperature pins
`
`allows the gelatin molecules to cross-link and bind to one another.
`
`22. There were several problems with the use of gelatin. One
`
`concern is that gelatin capsule were made from animal products. The
`
`pharmaceutical industry identified cellulose ethers as one material that could
`
`replace gelatin capsules. Cellulose ethers are derived from plant materials
`
`and can be manipulated into plastic films that make up capsule caps and
`
`bodies. One such cellulose ether is hydroxypropylmethylcellulose
`
`(“HPMC”). Two common, but vastly different, ways of creating HPMC
`
`capsules were developed: thermal gelling and additive gelling.
`
`A. Thermal Gelling
`
`23.
`
`In this method, no additives are utilized to form capsule films.
`
`U.S. Patent No. 3,493,407 (“Greminger”), a prior art reference relied upon in
`
`the petition, also discloses a method of thermal gelling in which pins are
`
`dipped into a warmed aqueous solution and transferred to an oven for
`
`several minutes until dry. Ex. 1006 at col. 3, line 60-col. 4, line 70.
`
`8
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 12
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`24. Likewise, in a method primarily utilized by Capsugel Belgium
`
`NV, the stainless steel pins used to form and shape the HPMC capsule films
`
`are preheated above HPMC’s gelation temperature. The pins are dipped into
`
`a cooler solution of HPMC dispersed in the solvent water. The pins are
`
`removed from the aqueous solution, with an HPMC film having formed on
`
`the surface of the pins. The gel capsule pieces are dried at a particular
`
`temperature and humidity to allow the HPMC to gel and dry on the pin. The
`
`HPMC capsule shells are then removed.
`
`25. HPMC-only capsules form gels that can be made into capsule
`
`films when HPMC is dissolved in water and then heated. No other
`
`chemicals or reagents are added to the system. Water is present in the
`
`system as the solvent to disperse the HPMC. The heat needed to cause the
`
`HPMC to gel is added to the system by dipping pins that are heated above
`
`the gelling temperature of the HPMC dispersed in the water solvent. The
`
`energy around the pins then leads to the HPMC molecules exposing their
`
`hydrophobic units. The HPMC molecules then organize by aligning their
`
`hydrophobic units. This organization leads to the gelling of HPMC.
`
`26. The HPMC-only capsules formed from this thermal gelation
`
`process possess many advantages over gelatin capsules. Because they are
`
`derived from vegetable sources, they may be more widely accepted by
`
`9
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 13
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
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`customers, including those in cultures that rely primarily on vegetable
`
`sources for nutrition or that have strict regulations on materials from animal
`
`sources.
`
`B. Additive Gelling
`
`27. As discussed above, capsule films made from gelatin include
`
`animal products and there was a desire to remove animal products from
`
`capsule films. However, the thermal gelling process used for pure-HPMC
`
`films requires modification to the existing capsule forming equipment, such
`
`as the use of heated dipping pins versus the room temperature pins used for
`
`gelatin based capsules.
`
`28. As described in the ’180 Patent, the capsule films made using
`
`the described additive gelling process made use of existing equipment. See
`
`Ex. 1001 at col. 4, lines 54-59 (“for example, the film can be prepared in the
`
`form of capsule shells by a well-known dipping method as in the
`
`manufacture of conventional gelatin capsules.”).
`
`29. Unlike the pure HPMC capsule films described above, the
`
`capsule film of the ’180 patent comprises three main ingredients: a specific
`
`HPMC base, a gelling agent, and a gelling aid. Id. at col. 2, lines 54-57. As
`
`the patent describes, a composition of these ingredients “prevents the gelling
`
`aid from precipitating out and maintains a favorable outer appearance during
`
`10
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 14
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`long-term storage.” Id. at col. 2, lines 13-15. The specific HPMC base
`
`(made up of specified functional substitutions of hydroxyproypl and
`
`methoxy groups), which gels via promotion by the gelling agent, ensures
`
`that the gelling aid stays in ion form in the film to keep it from precipitating
`
`out. Id. at col. 2, lines 46-49.
`
`30. Unlike the pure HPMC capsule film where the film solution is
`
`roughly at room temperature and the pins dipped into the solution are heated,
`
`the films formed according to the ’180 Patent involve dipping room
`
`temperature pins into a heated dispersion of the necessary ingredients. The
`
`’180 Patent states “the cellulose ether [HPMC base], gelling agent, gelling
`
`aid[,] and optional additives are dissolved in water in appropriate amounts . .
`
`. to form a dipping solution, capsule-forming pins are dipped in the dipping
`
`solution, then drawn out of the solution.” Id. at col. 4, lines 59-64.
`
`31. The ’180 Patent does not describe thermal gelling films. The
`
`described films instead make use of the gelling mechanism akin to that of
`
`gelatin through the use of gelling agents that enhance the gelling properties
`
`of HPMC.
`
`32. The method described in the ’180 Patent begins with dissolving
`
`HPMC in the solvent water at about room temperature. To that aqueous
`
`solution, a gelling agent, such as the family of compounds listed in the ’180
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`11
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`Patent, including carrageenan, is added. Also added to the aqueous solution
`
`are potassium ions in the form of potassium chloride. The potassium ions
`
`serve as the gelling aid as described in the specification. The temperature of
`
`the solution is raised, just as it is for gelatin. Then, cooler, room-
`
`temperature pins are lowered into the solution. The film solution adheres to
`
`the outside of the pins and, as the solution cools, the carrageenan molecules
`
`associate –association that is facilitated by the potassium ions – and serve as
`
`the lattice on which the HPMC solution gels and forms a film.
`
`33. The underlying chemistry in the shell of the ’180 Patent differs
`
`from a pure-HPMC base film. As detailed above, in the pure-HPMC base
`
`film, the HPMC molecules cross-link to form the gel. In the ’180 Patent
`
`system, the carrageenan molecules begin to gel as the temperature of the
`
`solution drops just as gelatin does, and, in doing so, forms a substrate that
`
`orients and constrains the HPMC molecules so that the film as a whole can
`
`gel. The ’180 Patent explains that the gel is easier to control because of the
`
`action of the gelling agent and gelling aid. See Ex. 1001 at col. 3, lines 62-
`
`66.
`
`34. The resulting film is dried and used as a hard capsule film to
`
`contain an active ingredient in a pharmaceutical dosage form. The ’180
`
`Patent makes this clear. Id. at col. 4, line 67-col. 5, line 4 (“The shells are
`
`12
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`then cut . . . and mated to construct hard capsules of the cellulose ether film
`
`according to the invention.”); col. 6, lines 26-28.
`
`35. The claims of the ’180 Patent further confirm that the described
`
`invention is a composition that makes up the final hard capsule. Id. at Claim
`
`1 (“[a] hard capsule formed of a film composition comprising . . . .”).
`
`36. The presence of the gelling agent in the finished capsule is
`
`important because the ’180 Patent makes clear that too little gelling agent
`
`“may achieve a lower degree of gelation and fail to produce a film of
`
`sufficient thickness to enable shell formation by the dipping method.” Id. at
`
`col. 4, lines 11-14. Similarly, the presence of the gelling aid in the finished
`
`capsule is important in that if too little gelling aid is used, the gelling aid
`
`“may promote gelation of the gelling agent to a less extent and fail to
`
`produce a film of a sufficient thickness to enable shell formation by the
`
`dipping method.” Id. at col. 4, lines 40-43. And while the amount of the
`
`“gelling agent” and “gelling aid” is stated as “not critical”, the ’180 Patent
`
`makes clear that both have important and necessary purposes in the
`
`composition. Id. at col. 4, lines 4-48.
`
`IV. OVERVIEW OF THE ’180 PATENT
`37. The ’180 Patent was filed on April 13, 2000, and claims priority
`
`to an application filed in Japan, JP 11-106689, filed on April 14, 1999.
`
`13
`
`
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 17
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`
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
`
`
`Ex. 1001. For purposes of this Petition only, I assume the earliest priority
`
`date for the ’180 Patent is April 14, 1999.
`
`38. The ’180 Patent describes a cellulose ether film suited for use in
`
`forming pharmaceutical and food hard capsules. The Abstract of the ’180
`
`Patent describes the cellulose ether film as “formed of a composition
`
`comprising a cellulose ether as a base in which some of the hydrogen atoms
`
`of cellulosic hydroxyl groups are replaced by alkyl groups and/or
`
`hydroxyalkyl groups, a gelling agent, and a gelling aid.” Id. at Abstract.
`
`The Abstract, moreover, describes the “the total content of alkoxyl and
`
`hydroxyalkoxyl groups in the cellulose ether [as] limited to 23-37.6% by
`
`weight, which is effective for preventing the gelling aid from precipitating
`
`out and maintaining a favorable outer appearance during long-term storage.”
`
`Id.
`
`39. Claim 1 of the ’180 Patent describes the claimed composition,
`
`and is reproduced below:
`
`A hard capsule formed of a film composition comprising a
`hydroxypropyl methyl cellulose as a base,
`a gelling agent,
`and a gelling aid,
`wherein said hydroxypropyl methyl cellulose has a content of
`hydroxypropoxyl groups of at least 4% by weight of the
`hydroxypropyl methyl cellulose and a content of methoxyl gropus and
`hydroxypropoxyl groups combined of 23 to 37.6% by weight of the
`hydroxypropyl methyl cellulose.
`
`14
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 18
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`
`
`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
`
`
`Id. at 6:38-45.
`
`40. Claim 4 of the ’180 Patent recites a variation of the film,
`
`“wherein the content of methoxyl and hydroxypropoxyl groups combined is
`
`29 to 37% by weight of the hydroxypropyl methyl cellulose.” Id. at 6:55-58.
`
`V. PERSON OF ORDINARY SKILL IN THE ART
`41. One of ordinary skill in the art at time of the earliest effective
`
`filing date of the ’180 Patent would have been someone with at least a
`
`bachelor’s degree in chemistry, chemical engineering, material engineering,
`
`pharmacy, or the equivalent technical degree, and at least two years of
`
`industry experience in pharmaceutical formulation.
`
`VI.
`
`IDENTIFICATION OF THE PRIOR ART
`
`A. Yamamoto
`
`42. United States Patent No. 5,756,123 (“Yamamoto”) was issued
`
`on May 26, 1998. See Ex. 1004. I understand that Yamamoto is thus prior
`
`art to the ’180 Patent pursuant to § 102(a) and § 102(e).
`
`43.
`
`I understand that Yamamoto is a reference that was not cited
`
`during prosecution of the ’180 Patent. It generally discloses “[a] capsule
`
`shell comprising 79.6-98.7% by weight of a hydroxypropylmethyl cellulose,
`
`0.03-0.5% by weight of carrageenan, and 0.14-3.19% by weight of a
`
`potassium ion and/or a calcium [ion]....” Ex. 1004 at Abstract.
`
`15
`
`
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 19
`
`
`
`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
`
`
`
`B. The Japanese Pharmacopeia
`
`44. The Japanese Pharmacopeia (The Society of Japanese
`
`Pharmacopeia, 13th ed. 1996) (“Japanese Pharmacopeia”) was published on
`
`April 1, 1996. See Ex. 1005. I understand that Japanese Pharmcopeia is
`
`thus prior art to the ’180 Patent pursuant to § 102(a) and § 102(b).
`
`45.
`
`I understand that Japanese Pharmacopeia is a reference that was
`
`not cited during prosecution of the ’180 Patent. It generally discloses three
`
`types of HPMC. Id. at 800-804. The Japanese Pharmacopeia was expressly
`
`referenced and pointed to by Yamamoto in describing the capsule films
`
`described therein. See Ex. 1001 at col. 3, lines 27-34; col. 7 at lines 29-31;
`
`col. 7 at lines 45-47; col. 8 at lines 23-26; col. 8 at lines 45-47.
`
`C. Greminger
`
`46. United States Patent No. 3,493,407 (“Greminger”) was issued
`
`on February 3, 1970. See Ex. 1006. I understand that Greminger is thus
`
`prior art to the ’180 Patent pursuant to § 102(a) and § 102(b).
`
`47.
`
`I understand that Greminger is a reference that was not cited
`
`during prosecution of the ’180 Patent. It generally discloses “[i]mproved
`
`cellulose ether medicinal capsules are prepared by forming the capsules
`
`from a solution containing about 10-30 weight percent of a
`
`16
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 20
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`
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
`
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`hydroxyalkylmethylcellulose and having an operational viscosity of about
`
`1000-12,000 cps.” Ex. 1006 at col. 1, lines 15-19.
`
`VII. CLAIM CONSTRUCTION
`48.
`I have reviewed the legal section of the Petition filed
`
`concurrently and, in particular, the description provided there of the claim
`
`construction standard. I accept Petitioner’s summary as accurate and have
`
`used that legal framework in my evaluation of the prior art presented in this
`
`matter. I understand that pursuant to 37 C.F.R. § 42.100(b), the claim terms
`
`of an unexpired patent subject to inter partes review shall receive the
`
`broadest reasonable construction in light of the specification of the patent in
`
`which they appear.
`
`A. “gelling agent”
`
`49. The ’180 Patent discloses that the function or purpose of the
`
`gelling agent is to improve the amount of gelation above and beyond the
`
`impact that the solvent has on HPMC’s inherent gelling properties. See
`
`Ex. 1001 at col. 3, lines 60-66 (“[C]arrageenan is especially preferred
`
`because it has a high gel strength and exhibits good gelling properties in the
`
`co-presence of a specific ion so that it may achieve effective gelation even
`
`when added in small amounts.”); col. 4, lines 11-17 (“When capsule shells
`
`are formed by the well-known dipping method, for example, it is
`
`17
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 21
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`
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
`
`
`recommended to use about 0.05 to 25 parts, and especially about 0.25 to 15
`
`parts by weight of the gelling agent per 100 parts by weight of the cellulose
`
`ether. Less than 0.05 part of the gelling agent may achieve a lower degree
`
`of gelation and fail to produce a film of a sufficient thickness to enable
`
`shell formation by the dipping method. More than 25 parts of the gelling
`
`agent may achieve a too high degree of gelation and provide a dipping
`
`solution with a viscosity higher than necessity, making it difficult to form a
`
`uniform coat or film.”) (emphasis added).
`
`50. Accordingly, I understand that Petitioner contends in this
`
`proceeding, and I agree with and have employed, the following claim
`
`construction of “gelling agent” as the “broadest reasonable construction”: a
`
`substance that increases the amount of gelation.
`
`B. “gelling aid”
`
`51. The patent applicant acted as his own lexicographer in stating
`
`that the “gelling aid” is “any substance that can promote gelation by the
`
`gelling agent” and thus I have applied that definition. See Ex. 1001 at col. 4,
`
`lines 18-20.
`
`VIII. STATEMENT OF LEGAL PRINCIPLES
`52.
`I understand that in this type of proceeding in the U.S. Patent
`
`Office, a claim receives the broadest reasonable interpretation in light of the
`
`18
`
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1011 - Page 22
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`
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`Petition for Inter Partes Review of U.S. Patent No. 6,649,180
`
`
`drawing(s), specification, and prosecution history of the patent as evaluate
`
`from the perspective of a person of ordinary skill in the art at the time of the
`
`invention.
`
`53.
`
`I also understand that generally claim terms are given their
`
`ordinary and customary meaning as would be understood by one of ordinary
`
`skill in the art at the time of the i
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