UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
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`ACTAVIS LLC
`Petitioner,
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`v.
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`ABRAXIS BIOSCIENCE, LLC
`Patent Owner
`________________
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`IPR2017-001101; IPR2017-01103; IPR2017-01104
`U.S. Patent Nos. 7,820,788; 7,923,536; and 8,138,229
`________________
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`DECLARATION OF NICHOLAS A. PEPPAS, SC.D.
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`I, Nicholas A. Peppas, Sc.D., hereby declare and state as follows:
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`1.
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`I submit this declaration on behalf of Abraxis Bioscience, LLC (“Abraxis” or
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`“Patent Owner”), Patent Owner of U.S. Pat. Nos. 7,820,788 (“the ’788 patent”),
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`7,923,536 (“the ’536 patent”), and 8,138,229 (“the ’229 patent”) (collectively, “the
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`Abraxis Patents”) in connection with the petitions for inter partes reviews filed by
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`Actavis LLC (“Actavis” or “Petitioner”) in case nos. IPR2017-01101, IPR2017-
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`01103, and IPR2017-01104 (collectively, the “Actavis IPR Petitions”).
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`I.
`2.
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`Qualifications
`I am the Cockrell Family Regents Chair (i.e., Chaired Professor) in
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`Engineering at The University of Texas at Austin with appointments in the
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`Departments of Chemical Engineering, Biomedical Engineering of the Cockrell
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`College of Engineering, and the Division of Pharmaceutics of the College of
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`Pharmacy of the University of Texas at Austin since January 1, 2003. I am also a
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`tenured full professor with joint appointment in the Department of Pediatrics at the Dell
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`Medical School of the same University. From September 2009 to August 2015, I was
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`also the Chairman of the Biomedical Engineering Department in the same
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`University.
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`3.
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`Previously, I was the Showalter Distinguished Professor of Chemical and
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`Biomedical Engineering at Purdue University, in West Lafayette, Indiana, with joint
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`appointments in the School of Chemical Engineering and in the Department of
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`Biomedical Engineering. I joined Purdue University in 1976. I have degrees in
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`chemical engineering from the National Technical University of Athens, Greece
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`(Dipl. Eng., 1971) and the Massachusetts Institute of Technology - MIT (Sc.D.,
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`1973). I did one year of postdoctoral work with Professors Clark Colton, Kenneth
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`Smith and Robert Lees at the Arteriosclerosis Center of the Massachusetts Institute
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`of Technology (1975–76).
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`4.
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`I am an elected member of the (US) National Academy of Engineering, the
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`(US) National Academy of Medicine, the American Academy of Arts and Sciences,
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`the National Academy of Inventors, the Academy of Engineering, Medicine and
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`Sciences of Texas, the National Academy of Pharmacy of France, the Royal
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`Academy of Pharmacy of Spain and the Academy of Athens, Greece.
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`5.
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`I have received honorary doctorate degrees from the University of Ghent,
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`Belgium (1999), the University of Parma, Italy (1999), the University of Athens
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`(2000), and the University of Ljubljana, Slovenia (2012), granted by their respective
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`Faculties of Pharmacy. The doctorate from the University of Parma also carries the
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`title “Doctor of Pharmacy”. I have also received an honorary doctorate (in Chemical
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`Engineering) from the University of Patras (2015).
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`6.
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`I have served as a Visiting Professor at the Faculty of Pharmacy of the
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`University of Geneva, Switzerland (Fall 1982), the Department of Chemical
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`Engineering of the California Institute of Technology (Spring 1983), the Faculty of
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`Pharmacy of the University of Paris-Sud (Fall 1986), the Department of Pharmacy of
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`the University of Parma, Italy (Fall 1987), the School of Pharmacy of the Hoshi
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`University of Tokyo, Japan (Spring 1994), the School of Pharmacy of the Hebrew
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`University of Jerusalem, Israel (Spring 1994), the Departments of Pharmacy and
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`Materials Science of the University of Naples, Italy (May 1996), the Department of
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`Pharmacy of the Free University of Berlin, Germany (January-March 2001), the
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`Department of Pharmacy of the Complutense University of Madrid, Spain (March-
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`May 2001) and the Department of Materials Science of the Nanyang Technological
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`Institute of Singapore (2006).
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`7. My teaching assignments at the University of Texas in the past ten years have
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`been courses on “Introduction to Polymer Science and Engineering”, Advances in
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`Biomedical Engineering”, “Advances in Biomaterials Science and Engineering”,
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`“Bionanotechnology”, and “Kinetics and Reaction Engineering”.
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`8.
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`Starting in 1979, I have developed and taught, along with Professors Robert
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`Langer of MIT, Frank Szoka of the University of California at San Francisco and
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`others, the course “Advances in Controlled Release Technology” offered every
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`summer at MIT. This is a five-day course offered to industrial and university
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`researchers who do not have a sufficient background in the field. In my lectures, I
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`teach the theory of diffusion of polymers and liquids, the utilization of polymer
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`micro- and nanoparticles as carriers in drug delivery, as well as the preparation and
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`characterization of drug delivery systems such as tablets, films, capsules,
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`microspheres, nanospheres and related pharmaceutical systems. The past summer
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`(2017) was the 39th year I taught this course.
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`9. My research contributions have been in several areas of drug and protein
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`delivery including therapeutic agents for treatment of diabetes, cancer, autoimmune
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`diseases and cardiovascular problems, biomaterials, bionanotechnology, mass
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`transfer, kinetics and reaction engineering, polymers and biomedical engineering.
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`10. Since 1979, I have also worked on the design, development and investigation
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`of the pharmaceutical and medical applications of micro- and nanoparticulate
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`polymers and drug delivery formulations. I have published numerous papers on the
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`design and use of polymers as micro- and nanoparticles and I have participated in the
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`development of a number of products that incorporated micro- and nanoparticles in
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`order to achieve desirable release properties.
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`11. For over forty one years I have been involved with the preparation,
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`characterization and evaluation of the behavior of hydrophilic and hydrophobic
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`polymers and devices, especially in controlled delivery of drugs, peptides and
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`proteins. My laboratory pioneered the use of many of these polymer carriers in drug
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`delivery applications and I have extensive experience in formulation, preparation and
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`testing of polymer formulations, including sustained release formulations. I received
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`the 2012 National Academy of Engineering Founders Award in recognition of this
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`pioneering work in the field of drug delivery. The National Academy of Engineering
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`citation for the Founders Award lists “For contributions to biomedical and drug
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`delivery applications of polymer networks and hydrogels and for leadership in the
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`bioengineering community”.
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`12.
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`I am the author of approximately 1,300 publications, 450 abstracts, and
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`approximately 35 issued or pending US and international patents.
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`13.
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`I am the coauthor or coeditor of 37 books and volumes, including the three-
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`volume monograph “Hydrogels in Medicine and Pharmacy” (CRC Press, 1987).
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`14.
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`I am an Associate Editor of the journal “Cell and Molecular Bioengineering ”,
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`the journal “Regenerative Engineering and Translational Medicine”, and the
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`Biomedical Engineering Book Series of Cambridge University Press.
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`15.
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`I sit on the editorial boards of numerous journals, including the “Journal of
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`Controlled Release”, “Advanced Drug Delivery Reviews”, “International Journal of
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`Pharmaceutics”, “Journal of Applied Polymer Science”, “Journal of Biomedical
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`Materials Research”, “Journal of Biomaterials Science”, “Journal of Drug Delivery
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`Science and Technology”, “European Journal of Pharmaceutics and
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`Biopharmaceutics”, and “Nanomedicine”.
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`16. From 2008–2016, I was the President of the 26,000-member International
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`Union of Societies of Biomaterials Science and Engineering.
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`17. Since 1981, I have been one of the leaders of the 4,000-member Controlled
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`Release Society (CRS). I guided it as its President in 1987–88, and organized the
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`1985 (Geneva) and 1993 (Washington) meetings of the Society as well as many
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`other conferences and workshops. The Controlled Release Society is the world’s
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`leading Society for technical information in the field of controlled release; it is a
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`leading group addressing controlled release and bioadhesive controlled release
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`systems. This July I received the CRS Distinguished Service Award.
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`18. Since 1975, I have been also active in the Society for Biomaterials. I was
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`elected as President-elect in April 2002 and I took over as its President in April 2003
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`by automatic succession. The Society for Biomaterials is the world’s premier
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`scientific and technical organization for the dissemination of knowledge related to
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`biomaterials for medical devices, and polymers in pharmaceutical technology.
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`19.
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`I am Past-Chair of the Engineering section of the American Association for
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`the Advancement of Science (AAAS). I have received numerous US and
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`international awards that are awarded by the leading world organizations of scientific
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`and technical excellence. These include the 2012 Founders Award of the National
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`Academy of Engineering, the 2010 Acta Biomaterialia Gold Medal; the 2010
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`Maurice-Marie Janot Award, of the French and German Pharmaceutical Associations
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`APGI and APV; the 2002 Dale Wurster Award in Pharmaceutics of the American
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`Association of Pharmaceutical Scientists (the highest research recognition of the
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`most important pharmaceutical association of the USA); the 2002 Eurand Award for
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`Life Achievements in Oral Drug Delivery (the highest scientific recognition in oral
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`delivery by the Controlled Release Society); the 2010 Distinguished Achievement
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`Award of the Biomedical Engineering Society; the 2010 Acta Biomaterialia Gold
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`Medal ; the 2010 Distinguished Scientist of the Southern Universities Research
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`Association; the 2008 Pierre Galletti Award of the American Institute of Medical and
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`Biological Engineering; the 2008 Institute Lecturer Award of the American Institute
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`of Chemical Engineers; the 2008 Jay Bailey Award of the Biological Engineering
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`Society; the 2000 General Electric Senior Research Award of ASEE recognizing the
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`best engineering researcher of the U.S.; the 1999 Research Achievement Award in
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`Pharmaceutical Technology of the American Association of Pharmaceutical
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`Scientists (the highest scientific recognition in pharmaceutical technology); the 1995
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`International Pharmaceutical Technology Medal of the International Pharmaceutical
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`Association (APV); the 1994 Pharmaceutical and Bioengineering Award of the
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`American Institute of Chemical Engineers, and many others.
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`20.
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`I have supervised the theses of 107 Ph.D. students, including 54 current
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`professors in other Universities, and many other students, postdoctoral fellows and
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`visiting scientists. My former students include many industrial leaders in chemical,
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`pharmaceutical or medical companies. Several of them are in senior administrative
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`positions. A copy of my curriculum vitae, including a list of publications I authored
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`is attached to this declaration as Appendix A.
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`II. Materials Considered
`21.
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`In preparing this declaration, I have reviewed the Actavis IPR Petitions as
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`well as the other documents identified below and listed in the attached Appendix
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`B.
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`III. Hypothetical Person of Ordinary Skill in the Art
`22.
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`I understand that Actavis contends in the Actavis IPR Petitions that a
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`“hypothetical person of ordinary skill in the art” (“POSA”) would have an
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`advanced degree in chemistry, chemical engineering, pharmaceutics, pharmacy, or
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`a related discipline, and/or having experience formulating compounds for use in
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`pharmaceutical compositions, including nanoparticle suspensions, for several
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`years. I further understand that for the Actavis IPR Petitions Actavis uses
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`December 9, 2002, as the relevant date for analyzing the level of skill and
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`knowledge of a hypothetical POSA. For purposes of this declaration, I have been
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`asked to use Actavis’s definition of a POSA and to use December 9, 2002 as the
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`relevant date for analyzing the level of skill and knowledge of a hypothetical
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`POSA.
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`IV. Statements
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`A. Expected loss of paclitaxel
`23. Paclitaxel, a type of taxane that is sold under the brand name Taxol®,
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`among others, is a chemotherapeutic medication that was first isolated in the late
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`1960’s as part of a National Cancer Institute (NCI) program that screened
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`medicinal plants for potential chemotherapeutic activity. The structure of
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`paclitaxel was published in 1971. (EX2021.)
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`24. Paclitaxel is an extremely hydrophobic compound, i.e., it is highly insoluble
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`in water. (See, e.g., EX2043, 54 (“Paclitaxel is highly hydrophobic (water
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`insoluble, with water solubility ≤0.5 mg/l)”).) Due to its high hydrophobicity, an
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`adjuvant such as Cremophor EL was historically required to solubilize the drug for
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`use in its clinical administration, even though the Cremophor EL was known to
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`cause serious side effects. (See e.g., EX1001, 4:38–45; EX1006, 13:6–12, 26:2–
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`5,29:19–22.)
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`25. Also due to its high hydrophobicity and other properties, paclitaxel rapidly
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`and nonspecifically adsorbs (sticks and accumulates on the surface) to most
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`surfaces, including plastic, glass, and metal. (See, e.g., EX2031, 109 (“taxol
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`adsorbs rapidly and non-specifically to plastic and glass surfaces.”); EX2032
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`(“Taxol … is a notorious example” of a compound that “stick[s] to the sides of
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`various containers like crazy.”); EX2033, 5372-5373, 5379-5383 (“Paclitaxel
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`(PAT), an anti-restenotic drug, has strong adhesion towards a variety of material
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`surfaces. . . . PAT has been shown to strongly adsorb onto different materials
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`including glass, polypropylene, silicones, and polytetrafluoroethylene.”); EX2034,
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`2186 (“Paclitaxel adheres strongly to most surfaces.”); EX2035, 2290 (teaching
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`“paclitaxel adheres to the surface of [a metal] stent”); EX2036, 329-330
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`(“Hydrophobic drugs (paclitaxel, verapamil and digoxin) were highly adsorbed to
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`conventional plastic microplates. . . . [H]ydrophobic adsorption (van der Waals
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`adsorption) is an interaction of a hydrophobic surface (e.g., plastic) and
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`hydrophobic drugs (e.g., paclitaxel, digoxin, verapamil). . . . The adsorption rates
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`of digoxin, verapamil and paclitaxel [to conventional (non-treated) plastic and
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`glass containers] exceeded 10%, and the adsorption rate of paclitaxel was the
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`highest among the probe drugs.”).)
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`26.
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`I am familiar with the method of making the CapxolTM nanoparticles that is
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`described in Example 1 (“Preparation of Nanoparticles by High Pressure
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`Homogenization”) of Desai et al., WO 1999/000113, “Novel Formulations of
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`Pharmacological Agents, Methods for the Preparation thereof and Methods for the
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`Use thereof” (published Jan. 7, 1999) (“Desai”).
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`27. The method of making the CapxolTM nanoparticles that is described in
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`Desai’s Example 1 requires at least the following eight steps: 1) dissolution of 30
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`mg paclitaxel in 3.0 ml methylene chloride; 2) addition of the paclitaxel solution to
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`27 ml an aqueous human serum albumin solution (1% w/v); 3) 5 minutes low-
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`speed homogenization in a Virtis homogenizer, model: Tempest I.Q.; 4) transfer of
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`the crude emulsion into an Avestin high pressure homogenizer; 5) at least five
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`cycles of high-pressure homogenization (emulsification) at 9000–40,000 psi; 6)
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`transfer of the mixture to a flask for rotary evaporation; 7) 20–30 minutes of rotary
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`evaporation at elevated temperature (40º C); and 8) transfer of the mixture to a
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`glass volumetric cylinder after evaporation.
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`28.
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`In my opinion, a POSA would understand and expect that these
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`manufacturing steps described in Example 1 of Desai would lead to a significant
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`loss of paclitaxel in the final composition obtained from practicing the example.
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`This loss would have been fully expected by a POSA as of December 9, 2002, due
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`to paclitaxel’s well-known properties, including its hydrophobicity. Indeed, a
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`POSA would have understood that loss of paclitaxel could occur by a variety of
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`phenomena, processes or mechanisms during processing, including epimerization
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`or other degradation or transformations, binding to processing vessels and other
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`equipment, and precipitation. (EXS2028–2030.)
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`29.
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` As noted above, paclitaxel is highly adsorbed to glass vessels. (See, e.g.,
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`EX2031, 109 (“taxol adsorbs rapidly and non-specifically to plastic and glass
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`surfaces.”); see also EX2036.) Therefore, by processing paclitaxel in a glass
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`vessel, a POSA would expect sticking and loss of paclitaxel to the walls of the
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`vessel. During steps 1 (dissolution of paclitaxel), 3 (low-speed homogenization)
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`and 7 (rotary evaporation) as indicated above, glass vessels are typically used to
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`hold the albumin/paclitaxel mixture, which would result in a loss of paclitaxel due
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`to adsorption. The transfer of the mixture in steps 4, 6 and 8 also occurs in glass
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`vessels. For example, the product of the high-pressure-homogenization process is
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`typically collected in a glass sample cylinder, and the product would then be
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`transferred to a glass round-bottom flask for rotary evaporation. A POSA would
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`thus expect loss of paclitaxel to occur in the transfer from the glass sample
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`collection cylinder to a round-bottom flask. An example of a rotary evaporator
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`including the glass round-bottom flask is shown in Appendix C to this declaration.
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`30. Likewise, during the at least 5 cycles of high-pressure homogenization (step
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`5), a metal sample chamber houses the mixture in the Avestin high pressure
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`homogenizer. Thus, a POSA would expect sticking and loss of paclitaxel to the
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`walls of the chamber.
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`31. Paclitaxel would also be expected to be lost to the different probes and
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`component parts that contact the solution during the eight step process. For
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`example, during step 3, a Virtis homogenizer, which has a metal impeller with
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`multiple openings, is used during the low speed homogenization process. (Desai at
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`60:27–28.) Paclitaxel will stick to the open sides of the impeller and fill into the
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`multiple openings of the impeller. An example of a Virtis homogenizer and a
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`close-up image of the impeller are shown in Appendix D to this declaration.
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`32. Likewise, paclitaxel would also be expected to be lost to the different
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`components parts of the Avestin high-pressure homogenizer (Desai at 60:30) —
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`which includes a pump, valves, filter membranes, heat exchanger, lines, tubing,
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`and plastic, PFTE (Teflon), and metal fitting and seals—because paclitaxel binds
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`nonspecifically to the materials from which these components are made. An
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`example of an Avestin high-pressure homogenizer is shown in Appendix E to this
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`declaration.
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`33. Plastic tubing and lines that are used in a high-pressure homogenizer have
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`high affinity to paclitaxel. Hunz et al. reported that “Paclitaxel showed
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`pronounced adsorption to the microdialysis membrane as well as to the outlet
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`tubes. The amount bound to the equipment exceeded that recovered in the
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`perfusate.” (See, e.g., EX2037, 660.)
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`34.
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`In addition to the above, paclitaxel precipitation is also a potential reason for
`
`paclitaxel loss. (See e.g. EX2038; EX2039; EX2040, 135S; EX2041.) Due to the
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`poor water solubility of paclitaxel (paclitaxel having a reported water solubility of
`
`0.0003 mg/mL)1, loss of paclitaxel in the manufacturing process of Capxol™
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`would be expected to occur through precipitation as a result of the drug’s inability
`
`to solubilize in aqueous solution. Indeed, precipitation of paclitaxel has been
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`observed in clinical settings when organic paclitaxel formulations were infused
`
`into aqueous solutions and when high-shear mechanical forces were applied to
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`paclitaxel dispersions in water. (EX2040, 135S.) Thus, homogenization of a
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`mixture of starting ingredients as described in Example 1 would be expected to
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`1 (See EX2042, 1024.)
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`result in precipitation of paclitaxel for the reasons described above. (See id.)
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`35. Based on the known hydrophobic nature of paclitaxel, at least the references
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`cited above, and my knowledge as a skilled artisan, it my opinion that the process
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`of Example 1 would result in a significant loss of paclitaxel during the processing
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`steps described above, and a POSA on December 9, 2002 would have understood
`
`and expected such paclitaxel loss to occur. Likewise, the processes described in
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`Examples 47–49 of the Abraxis Patents would similarly be expected to result in a
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`loss of paclitaxel during the processing steps described in those examples.
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`36. Clearly then, given the expected loss of paclitaxel during processing, a
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`POSA would have known that the ratio of albumin-to-paclitaxel in the final
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`composition would be expected to be higher than the ratio calculated from the
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`starting ingredients, since the amount of paclitaxel (denominator in the ratio
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`“albumin-to-paclitaxel”) would be lower. Accordingly, a POSA would have
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`known that to determine the claimed weight ratio of albumin to paclitaxel, as
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`opposed to deriving only an approximated “calculated ratio,” it would be necessary
`
`to measure the amounts of albumin and paclitaxel in the finished composition.
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`37. Methods for measuring the amount of albumin and paclitaxel in
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`pharmaceutical compositions, by techniques such as high performance liquid
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`chromatography (“HPLC”), were well-known in the art at the time. (See, e.g.,
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`EXS2023–2027, EX2051.) In fact, Desai describes using HPLC analysis to
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`determine the amount of paclitaxel in pharmaceutical formulations. (See, e.g.,
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`Desai, at 74:20–24; 104:18–107:16.)
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`B. Kadima does not teach the claimed albumin-to-paclitaxel weight
`ratios
`38. Upon reading Kadima et al., WO 2000/006152, “Pharmaceutically
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`Acceptable Composition Comprising an Aqueous Solution of Paclitaxel and
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`Albumin” (“Kadima”), I have concluded that Kadima does not teach a range of
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`albumin-to-paclitaxel weight “ratio[s] of about 0.5:1 to about 10:1.” In addition,
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`nowhere does Kadima even disclose albumin-to-paclitaxel weight ratios; Kadima
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`discloses only albumin-to-paclitaxel molar ratios. (See, e.g., Kadima Figs. 1–3, 6–
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`8, 11, 12; Id. at 8:6–8, 31:8–10.) Kadima states: “[I]n order to produce a
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`commercially available, pharmaceutically acceptable albumin-bound drug, the
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`drug must be bound reversibly to the albumin in a high molar ratio.”); id. at 11:7–8
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`(“The molar ratio of paclitaxel:albumin and the final concentration of paclitaxel in
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`the albumin solution are optimized.”); id. at 32:1–5 (Table showing estimation of
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`cost at “different binding molar ratios”).) Kadima’s table (Kadima at p. 32),
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`reproduced below, illustrates this point. While this table includes “Molar ratios”
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`and quantities of human serum albumin (HSA) and paclitaxel in grams, no explicit
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`weight ratio of these two compounds is reported.
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`39. Clearly, a POSA would have understood that weight ratios and molar ratios
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`are distinct and different. A molar ratio is the ratio of the moles (a unit for
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`measuring quantities of atoms or molecules) in any two compounds in a chemical
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`reaction. The weight ratio is the ratio between the mass (e.g., number of grams) of
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`two components.
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`40. From the information contained in Kadima’s table above (i.e., the stated
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`amounts of albumin (g) and paclitaxel (mg)), a POSA could calculate the weight
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`ratio of albumin-to-paclitaxel. It is clear that this ratio will not be the same as the
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`“molar ratio”. For example, a 1:10 paclitaxel to albumin molar ratio, shown in the
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`left-most column, is equivalent to a paclitaxel-to-albumin weight ratio of 30 mg
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`paclitaxel (first number in second column of the Table above) divided by 23,400
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`mg (i.e., 23.4 grams) human serum albumin (HSA). Conversely, the albumin-to-
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`paclitaxel weight ratio in the composition is 23,400 mg divided by 30 mg
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`paclitaxel, i.e., a calculated weight ratio of 780:1. The table below shows the
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`calculated weight ratios for each of the examples shown in Kadima’s table above.
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`I also added two additional rows (shaded) illustrating the weight ratios of CapxolTM
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`and Abraxane® for comparison.
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`Molar Ratio
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`1:10
`1:5
`1:2
`1:1
`1:0.5
`1:0.17
`1:0.12
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`Paclitaxel (mg) HSA (g)
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`Weight Ratio
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`30
`30
`30
`30
`30
`30
`100
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`23.4
`11.7
`4.7
`2.34
`1.17
`0.4 (CapxolTM)
`0.9 (Abraxane®)
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`23400/30 = 780:1
`11700/30 = 390:1
`4700/30 = 157:1
`2340/30 = 78:1
`1170/30 = 39:1
`400/30 = 13.33:1
`900/100 = 9:1
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`41. As illustrated in the table above, the lowest albumin-to-paclitaxel weight
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`ratio disclosed in Kadima is 39:1 and the highest is 780:1.
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`42.
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`I declare that all statements made herein on my own knowledge are true and
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`that all statements made on information and belief are believed to be true, and
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`further, that these statements were made with the knowledge that willful false
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`statements and the like so made are punishable by fine or imprisonment, or both,
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`under Section 1001 of Title 18 of the United States Code.
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`Date: July 7, 2017
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`/s/
`Nicholas A. Peppas, Sc.D.
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`APPENDIX A
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`CURRICULUM VITAE OF NICHOLAS A. PEPPAS
`
`Cockrell Family Regents Chair in Engineering #6
`McKetta Department of Chemical Engineering, Department of Biomedical Engineering,
`Departments of Pediatrics, and Surgery and Perioperative Care, Dell Medical School, and
`Division of Pharmaceutics, College of Pharmacy
`The University of Texas at Austin
`
`Web site: http://www.che.utexas.edu/research/biomat/index.htm
`E-mail: peppas@che.utexas.edu
`
`
`Born
`August 25, 1948, Athens, Greece
`
`Education
`
`Dipl. Eng. (Chem. Eng.), National Technical University of Athens, Greece, 1971.
`Sc. D. (Chem. Eng.), Massachusetts Institute of Technology, 1973.
`
`Honorary Doctorates
`
`Doc. Hon. Causa, University of Ghent, Belgium, 1999.
`Pharm. D. Hon. Causa, University of Parma, Italy, 1999.
`Doc. Hon. Causa, University of Athens, Greece, 2000.
`Hon. Prof., Sichuan University, People’s Republic of China, 2012
`Doc. Hon. Causa, University of Ljubljana, Slovenia, 2012.
`Doc. Hon. Causa, University of Patras, Greece, 2015.
`Doc. Hon. Causa, National Technical University of Athens, Greece, 2016.
`
`Professional Experience
`
`University of Texas, Department of Chemical Engineering, Cockrell Family Regents Chair #6, 2014-.
`University of Texas, Department of Biomedical Engineering, Cockrell Family Regents Chair #6, 2014-.
`University of Texas, Department of Chemical Engineering, Fletcher Stuckey Pratt Chair, 2003-14.
`University of Texas, Department of Biomedical Engineering, Fletcher Stuckey Pratt Chair, 2003-14.
`University of Texas, Department of Surgery and Perioperative Care, Dell Medical School, 2016- .
`University of Texas, Department of Pediatrics, Dell Medical School, 2017- .
`University of Texas, Division of Pharmaceutics, College of Pharmacy, Professor, 2003- .
`University of Texas, Department of Biomedical Engineering, Chair of the Department, 2009-15.
`University of Texas, Texas Materials Institute, Professor, 2003- .
`
`Purdue University, School of Chemical Engineering, Showalter Distinguished Professor, 1993-2002.
`Purdue University, Department of Biomedical Engineering, Showalter Distinguished Professor, 1999-2002.
`Purdue University, School of Chemical Engineering, Professor, 1982-2002.
`Purdue University, School of Chemical Engineering, Associate Professor, 1978-82.
`Purdue University, School of Chemical Engineering, Assistant Professor, 1976-78.
`
`Peking Union Medical College, People’s Republic of China, Honorary Professor, March 2017- present.
`Sichuan University, Chengdu, People’s Republic of China, Honorary Professor, June 2012-present.
`Nanyang Technological University, Singapore, Visiting Professor, January 2005.
`Free University of Berlin, Germany, Mercator Visiting Professor, Jan-June 2001.
`University of Santiago de Compostela, Spain, Visiting Professor, February-March 2001.
`Complutense University, Madrid, Spain, Visiting Professor, March-April 2001.
`University of Naples, Italy, Visiting Professor, Department of Materials Engineering, May 1996.
`1
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`Hoshi University, Tokyo, Japan, Visiting Professor, Jan.-March 1994; March 1995; March 1997.
`Hebrew University, Jerusalem, Israel, Visiting Professor, March-May 1994.
`University of Parma, Italy, Faculty of Sciences, Adjunct Professor, 1987-88; 1993-94.
`University of Paris XI, France, Faculty of Pharmacy,Visiting Professor, May-December 1986.
`California Institute of Technology, Department of Chemical Engineering, Visiting Professor, March-July 1983.
`University of Geneva, Switzerland, Faculty of Sciences, Visiting Professor, Sept.1982-Feb. 1983.
`
`M.I.T., Department of Chemical Engineering and Arteriosclerosis Center, Research Associate, 1975-76.
`Research Center for National Defense, Research Associate, 1974-75.
`Shell Co., Rotterdam, The Netherlands, Summer 1970.
`Beso Co., Patras, Greece, Summers 1968 and 1969.
`
`
`Member of Academies
`
`National Academy of Engineering (2006)
`National Academy of Medicine (2008)
`American Academy of Arts and Sciences (2017)
`National Academy of Inventors (2014)
`French Academy of Pharmacy (Académie Nationale de Pharmacie) (2005)
`Royal Academy of Spain (Academia Real) (2011)
`Academy of Athens, Greece (2013)
`Academy of Medicine, Engineering and Science of Texas (2006)
`International Academy of Medical and Biological Engineering (2016)
`
`
`
`Awards and Honors
`
`2017 Elected Honorary Professor, Peking Medical Union Univer