Case 1:14-cv-01178-MHC Document 82-14 Filed 12/15/14 Page 1 of 62
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`Case 1:14—cv—O1178—MHC Document 82-14 Filed 12/15/14 Page 1 of 62
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`EXHIBIT N
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`EXHIBIT N
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`MTF Ex. 1008, pg. 1
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`Case 1:14—cv—O1178—MHC Document 82-14 Filed 12/15/14 Page 1 of 62
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`EXHIBIT N
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`EXHIBIT N
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`MTF Ex. 1008, pg. 1
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`Case 1:14-cv-01178-MHC Document 82-14 Filed 12/15/14 Page 2 of 62
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`UNITED STATES DISTRICT COURT
`NORTHERN DISTRICT OF GEORGIA
`ATLANTA DIVISION
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`
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`
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`MIMEDX GROUP, INC.
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`
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`
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`Civil Action No. 1:14-cv-1178-MHC
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`(JURY TRIAL DEMANDED)
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`
`
`
`
` Plaintiff
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`
`
` -vs.-
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`LIVENTA BIOSCIENCE, INC., MEDLINE
`INDUSTRIES INC., and
`MUSCULOSKELETAL TRANSPLANT
`FOUNDATION
`
`
`
` Defendants.
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`
`
`EXPERT DECLARATION OF REBECCA N. BAERGEN, M.D.
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`I, Rebecca N. Baergen, M.D., declare and state as follows:
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`I submit this Declaration at the request of, and in support of Plaintiff,
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`
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`1.
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`MiMedx Group, Inc.’s (“MiMedx”) Joint Claim Construction Statement. In
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`particular, I submit this declaration to provide my opinions regarding the meaning
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`of certain disputed claim terms in U.S. Patent Nos. 8,323,701 (“the ’701 patent”);
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`8,642,092 (“the ’092 patent”); 8,703,207 (“the ’207 patent”); 8,372,437 (“the ’437
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`patent”); 8,709,494 (“the ’494 patent”); 8,597,687 (“the ’687 patent”), (Exhibits 1-
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`6) as those terms would have been understood by a person of ordinary skill in the
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`relevant art at the relevant time frame.
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`1
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`I.
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`2.
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`QUALIFICATIONS
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`I am currently a Professor of Pathology and Laboratory Medicine and Chief of
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`Obstetric and Perinatal Pathology and Attending Pathologist at New York-
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`Presbyterian Hospital, Weill-Cornell Medical Center. I have held this position since
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`2009. Prior to holding this position, I held various positions, including Professor of
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`Clinical Pathology and Laboratory Medicine and Chief of Perinatal and Pediatric
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`Pathology.
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`3.
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`I received my Bachelors of Arts in Biology from the University of California,
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`San Diego, in 1974. I obtained my medical degree from the University of California,
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`Los Angeles, in 1983. I performed my residency at the Harbor-UCLA Medical
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`Center in Torrance, California from 1987-1991, and performed my Chief Residency
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`from 1991-1992.
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`4.
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`From 1992 to 1997, I served on the faculty of University of California, San
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`Diego, where I held various positions including Clinical Assistant Professor of
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`Pathology and Chief of Gynecologic Pathology.
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`5.
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`I was awarded the Joseph M. Didio Memorial Teaching Award in 1995
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`(University of California, San Diego), am a member of the International Federation of
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`Placental Associations (1999-present), the Society for Pediatric Pathology (1997-
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`present), International Society for Gynecological Pathologists (1994-present),
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`2
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`Gynecology Oncology Group (1992-present), and the United States and Canadian
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`Academy of Pathology (1989-present).
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`6.
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`I serve as a reviewer for numerous peer-review journals, including Placenta,
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`American Journal of Pathology, American Journal of Perinatology, American Journal
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`of Surgical Pathology, and Human Pathology, in addition to 19 others. I also serve on
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`the Editorial Board of Pediatric and Developmental Pathology, and International
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`Journal of Gynecological Pathology.
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`7.
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`I authored a book titled “Manual of Pathology of the Human Placenta,” the
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`second edition of which was published by Springer in 2011. I co-authored a book
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`titled “Pathology of the Human Placenta,” both the fifth and sixth edition published by
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`Springer in 2006 and 2012.
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`8.
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`I have published approximately 90 peer-reviewed articles in medical journals,
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`contributed eight book chapters in medical and pathology text books and about 75
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`abstracts in peer-reviewed journals and at national meetings. The majority of my
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`publications relate to the pathology of the human placenta.
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`9.
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`I have made more than 20 invited presentations at national and international
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`meetings in the area of pathology and the placenta.
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`10. Additional details of my education and experience are set forth in my
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`curriculum vitae, a copy of which is attached as Exhibit 7.
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`3
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`II.
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`FEES
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`11. The compensation paid to me for my time spent working on this matter is based
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`on my typical hourly rate of $500 per hour. My compensation is not contingent on the
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`outcome of this litigation.
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`III. PRIOR EXPERT TESTIMONY
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`12.
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`I have testified as an expert (either by submission of an expert report,
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`deposition, or appearance in court) within the last five years in matters relating to
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`medical malpractice. A complete list of matters, created to the best of my ability, is
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`attached as Exhibit 8.
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`IV. MATERIALS CONSIDERED
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`13.
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`In addition to my personal knowledge, education, and experience, including as
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`evidenced by my publications listed in my curriculum vitae, I have reviewed certain
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`documents as part of this submission. I have identified some of them in this report,
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`and others are identified at Exhibit 9 to this report. These are the materials I reviewed
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`and relied upon in connection with my opinions on claim construction as forth herein.
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`14.
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`I reserve the right to amend and/or supplement this declaration or opinions
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`therein based on additional information that is made available to me between now and
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`the time of the Markman hearing. I further reserve the right to amend and/or
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`supplement my declaration or opinions therein in response to additional discovery,
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`other events, including rebutting any positions or opinions submitted by Defendants.
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`Specifically, I reserve the right to amend and/or supplement my declaration to opine
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`further upon future court rulings, agreements between the parties, or any further
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`testimony given by any party, either by deposition, at any hearing, or at trial.
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`V. LEVEL OF ORDINARY SKILL IN THE ART
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`15. For purposes of my analysis, I have considered how the disputed terms of
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`the Patents-in-Suit would have been understood as of a particular time frame by a
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`person of ordinary skill in the art. Specifically, as for the ’701 patent, the ’092
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`patent, and the ’207 patent, I have been informed that September 2007 is the
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`relevant date for evaluating how a person of ordinary skill in the art would have
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`understood the terms being construed. As for the ’494 patent and the ’437 patent, I
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`have been informed that August 2006 is the relevant date for evaluating how a
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`person of ordinary skill in the art would have understood the terms being
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`construed.
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`16.
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`It is my opinion that a person of ordinary skill in the art would have, at least,
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`a bachelor’s degree in biology and would have taken courses in biology,
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`pathology, histology and anatomy, or related disciplines. Such a person would
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`have, based on their course work, an understanding of placental biology and
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`anatomy. Such a person would also have five years of experience in pathology
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`and/or histology, including processing of tissue to be examined, sectioning,
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`staining techniques and analysis of the results.
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`5
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`VI. BACKGROUND
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`A. The Human Placental Membranes
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`17. The human placenta is an organ that interfaces the developing fetus to the
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`maternal uterus. This organ provides nutrition, gas exchange, waste removal,
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`endocrine and immune support for the developing fetus.
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`18. The human placenta includes two membranes that exist during pregnancy:
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`the amnion and the chorion. These membranes are essentially the “bag of waters”
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`in which the fetus is enclosed.
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`19. When first formed, the amnion closely covers the body of the embryo, but
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`over time, the amniotic fluid begins to accumulate within it which causes the
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`amnion to expand and become the amniotic sac which provides a protective
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`environment for the developing embryo.
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`20. At a certain point, the amniotic fluid causes the amnion to expand and
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`ultimately to become applied (but not fused) to the inner surface of the chorion,
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`another membrane that exists during pregnancy between the developing fetus and
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`the mothers.
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`21. These features of the amnion and chorion are represented schematically
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`below. The amnion is depicted in the black dotted line; the chorion is depicted in
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`the solid blue line.
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`Amnion
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`Chorion
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`Figure 1: The Human Placental Membranes In Utero
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`B.
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`Structure of Human Placental Membranes
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`1.
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`Native Human Placental Amnion
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`22. As early as the 1960s, it was generally accepted that native human placental
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`amnion was made of several different layers. Native human placental amnion is a
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`translucent structure and can be separated from the underlying native human
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`placental chorion.
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`23. Various histological evaluations of native human placental amnion have
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`been reported. The general consensus is that native human placental amnion is
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`composed of at least several layers that can be identified histologically. These
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`layers include the layers identified below as the amniotic epithelium, the basement
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`membrane (also called the basal lamina), the compact stromal layer and the
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`fibroblast layer.
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`Figure 2: Schematic of Native Human Placental
`Amnion and Chorion
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`24. The amniotic epithelium layer is the innermost layer of the native placental
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`amnion, closest to the fetus, and is in contact with the amniotic fluid. The
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`epithelial layer consists of a single layer of flat, typically cuboidal epithelial cells,
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`which means these cells have a cube-like shape, i.e., their width is approximately
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`equal to their height in histologic section. The native amniotic epithelial cells are
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`in intimate contact with the underlying basement membrane. See, e.g., Exhibit 10,
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`Bourne et al., 1962, Postgrad, Med. J., 38:193-201 at 193-194 (“Bourne 1962”);
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`Exhibit. 11, Bourne et al., 1960, Am. J. Obstet. & Gynec., 79(6): 1070-1073
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`(“Bourne 1960”); Exhibit. 12, Rebecca N. Baergen, MANUAL OF BENIRSCHKE AND
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`KAUFMANN’S PATHOLOGY OF THE HUMAN PLACENTA (2005) Ch. 6 (“Baergen
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`2005”); Exhibit 13; Leslie P. Gartner, James L. Hiatt, COLOR TEXTBOOK OF
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`HISTOLOGY p. 87 (2nd ed. W. B. Saunders Co. 2001) (“Gartner”).
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`25. The basement membrane or the basal lamina is a thin layer composed of a
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`network of reticular fibers (a type of fiber in connective tissue) and is in contact,
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`through both chemical and physical interactions, with the base of the epithelial
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`cells. See, e.g., Exhibit 10 at pp. 194-195; Exhibit 14; Malak et al., 1993,
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`Placenta, 14:385-406 at 398 (“Malak”).
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`26. The basement membrane contains biological macromolecules, which
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`includes, for example, collagen (e.g., Collagen IV),
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`laminin, and other
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`proteoglycans.
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` See, e.g., Exhibit 14, Malak at 402.
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` These biological
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`macromolecules, by virtue of chemical interactions, provide scaffolding on to
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`which cells, such as epithelial cells, can attach.
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`27. The compact stromal layer is next. This is a relatively dense layer which is
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`virtually devoid of cells and consists of a complex network of connective tissue.
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`See, e.g., Exhibit 10, Bourne 1962 at p. 195; Exhibit 12, Baergen 2005 at pp. 88-
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`89.
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`28. Finally, the fibroblast layer consists of fibroblast cells that are embedded in a
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`dense network of extracellular matrix of the connective tissue. Fibroblast cells
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`synthesize the extracellular matrix and collagen. The main function of fibroblasts
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`is to maintain the structural integrity of the connective tissue by producing various
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`biomolecules making up the extracellular matrix, including, for example, collagen.
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`See, e.g., Exhibit 10, Bourne 1962 at p. 195; Exhibit 12, Baergen 2005at pp. 88-89;
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`Exhibit 13, Gartner at pp. 71-84, 112. The extracellular matrix (or ECM) is a
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`collection of extracellular molecules secreted by the fibroblast cells, thereby
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`providing structural support for the surrounding cells. Exhibit 13, Gartner at pp.
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`71-84, 112.
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`2.
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`Native Human Placental Chorion
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`29. The chorionic membrane consists of chorionic mesoderm (connective tissue)
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`and trophopblast layers (a placental epithelial cell). See, e.g., Exhibit 12, Baergen
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`2005 at pp. 90-91.
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`VII. THE DISPUTED CLAIM TERMS
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`30.
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`In connection with this declaration, I am providing my opinions as to the
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`meaning of certain claim terms of the Patents-in-Suit. My opinions regarding the
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`Case 1:14-cv-01178-MHC Document 82-14 Filed 12/15/14 Page 12 of 62
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`definitions of these various claim terms, and my reasoning for these opinions are
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`set forth below.
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`A. The “Exposed Basement [Membrane/Layer]” Limitation
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`1.
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` “An Exposed Basement Layer/Membrane”
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`31.
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`In this declaration, I provide my opinion as to the meaning of the term
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`“exposed basement membrane/layer” as it appears in claim 1 of the ’701 patent,
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`claim 1 of the ’092 patent, and claim 1 of the ’207 patent.
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`32.
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`In my opinion, a person of ordinary skill in the art, reading the claims in
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`light of the specification of the ’701 patent, the ’092 patent and the ’207 patent
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`(each of which is virtually identical), as well as the file history of these patents, at
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`the relevant time, would have interpreted the phrase “an exposed basement
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`[membrane/layer]” to mean a basement membrane where sufficient epithelial cells
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`have been removed such that “a sufficient amount of the basement membrane is
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`available to promote sufficient interaction between the host cells and the basement
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`membrane to support the desired purpose of the tissue graft.”
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`33.
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`I understand that an analysis of the definition of any claim term begins by
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`examining how a particular term is used in the patent claims. Thus, I begin my
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`analysis by looking to the relevant claims of the Patents-in-Suit.
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`34. Claim 1 of the ’701 patent is reproduced below and the terms at issue are
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`italicized and bolded below.
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`Claim 1 – the ’701 Patent
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`A tissue graft consisting of: a first membrane comprising
`modified amnion wherein the modified amnion has a first side
`which is an exposed basement membrane and a second side
`which is an exposed jelly-like fibroblast cellular layer;
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`
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`and one or more additional membranes sequentially layered
`such that the first additional membrane is layered adjacent to
`the exposed fibroblast layer of the first membrane,
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`wherein the at least one or more additional membranes is
`selected from the group consisting of amnion, chorion, allograft
`pericardium, allograft acellular dermis, amniotic membrane,
`Wharton's jelly, and combinations thereof.
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`35. Claim 1 of the ’092 patent is reproduced below and the terms at issue are
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`
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`italicized and bolded below.
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`Claim 1- the ’092 Patent
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`A multilayered tissue graft comprising:
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`at least one layer of isolated dehydrated chorion tissue; and
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`at least one layer of isolated dehydrated amnion tissue provided
`that at least one of said amnion layers has an exposed basement
`layer and an intact fibroblast component wherein at least one of
`the chorion layer(s) is layered directly over the fibroblast
`component of said amnion layer.
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`36. Claim 1 of the ’207 patent is reproduced below and the terms at issue are
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`italicized and bolded below.
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`Claim 1- the ’207 Patent
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`A multilayered tissue graft comprising:
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`at least one layer of isolated amnion tissue provided that at least
`one of said amnion layers has an exposed basement layer and
`an intact fibroblast component; and
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`at least one additional layer selected from the group consisting
`of amnion, chorion, allograft pericardium, allograft acellular
`dermis, amniotic membrane, Wharton's jelly, purified Type-1
`collagen, biocellulose polymers or copolymers, biocompatible
`synthetic polymer or copolymer films, purified small intestinal
`submucosa, bladder acellular matrix, cadaveric fascia, or any
`combination thereof; wherein at least one of the additional
`layer(s) is layered directly over the fibroblast component of said
`amnion layer, and further wherein the at least one layer of
`amnion tissue and the at least one additional layer are laminated
`together to form a multilayered tissue graft.
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`37. The plain language of each of these claims requires that the amnion
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`layer/tissue have “an exposed basement membrane.” There is no numerical
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`limitation recited in the claim. As such, nothing in claim language limits the
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`cellularity of the epithelial cellular layer positioned on top of the basement
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`membrane to any specific numerical amount.
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`38. The specification of each of these patents supports my opinion as to how a
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`person of ordinary skill in the art would have construed the term “an exposed
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`basement membrane/layer.” One of ordinary skill in the art, reading the
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`specification of these patents, would have understood that throughout the
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`specification the inventors describe that the goal and objective of the invention is
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`to prepare placental tissue grafts wherein a sufficient amount of the basement
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`membrane of the amnion in the placental tissue graft is exposed to allow
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`interaction between the biological macromolecules of the basement membrane and
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`the host cells of the target tissue.
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`39. For example, the specification of the ’701 patent provides:
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` The grafts are composed of at least one layer of amnion tissue
`where the epithelium layer has been substantially removed in
`order to expose the basement layer to host cells. By removing
`the epithelium layer, cells from the host can more readily
`interact with the cell-adhesion bio-active factors located onto
`top and within of the basement membrane. See e.g., Exhibit 1,
`the ’701 patent at Abstract.
`
` The grafts are composed of at least one layer of amnion tissue
`where the epithelium layer has been substantially removed in
`order to expose the basement layer to host cells. By removing
`the epithelium layer, cells from the host can more readily
`interact with the cell-adhesion bio-active factors located onto
`top and within of the basement membrane. See e.g., Exhibit 1,
`the ’701 patent at col. 1:65-col. 2:5.1
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`40. Moreover, a person of ordinary skill in the art, in light of the specification of
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`these patents would have understood that exposure of a portion of the basement
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`membrane can be sufficient to cause interaction between the biological
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`macromolecules (e.g., proteins or the bioactive agents) within the basement
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`membrane and the host cells such that the tissue grafts would achieve the
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`therapeutic goal intended. One of ordinary skill in the art, reading the specification
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`of these patents, would have understood that such interactions with the host cells
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`1 I understand the specification of the ’701 patent, the ’092 patent, and the ’207
`patent are virtually identical. As such, for convenience, I primarily provide
`citations to the ’701 patent.
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`are of significant importance in periodental applications, oral surgery to improve
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`soft tissue regeneration, bone regeneration, oral mucosa tissue regeneration, and
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`treatment of wounds and burns. See e.g., Exhibit 1, the ’701 patent at col. 11:21-
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`41; Exhibit 2, the ’092 patent at col. 11:21-41; Exhibit 3, the ’207 patent at col.
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`11:14-34.
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`41. For example, a person of ordinary skill in the art would have understood,
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`that according to the inventors, certain biological macromolecules that typically
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`reside in the amniotic basement membrane can more readily bind to the epithelial
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`cells present in the target host tissue (such as a patient’s gums, bones, or skin) and
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`promote cell attachment of the tissue graft of the invention to the host cell, if the
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`basement membrane has been sufficiently exposed. Without removal of the
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`epithelial cells positioned on the basement membrane, there would be a barrier to
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`the interaction with the host tissue epithelial cells resulting in non-attachment of
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`the host cell to the graft. See e.g., Exhibit 1, the ’701 patent at Examples.
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`42. Moreover, one of ordinary skill in the art, reading the specification of these
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`patents, would have understood that one method to expose the basement membrane
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`is by removing at least some, or in some cases, a substantial amount of the
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`epithelial cells positioned on the basement membrane to expose the basement
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`membrane. See e.g., Exhibit 1, the ’701 patent at col. 5:24-57. For example, the
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`specification provides various techniques, including chemical and physical
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`methods that would allow exposure of the basement membrane by removing some
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`of the epithelial cells.
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`43. One of ordinary skill in the art reading the specification of these patents
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`would have understood that the specification provides physical techniques such as
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`freezing the membrane or using a cell scraper to expose the basement membrane.
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`See e.g., Exhibit 1, the ’701 patent at col. 5:41-43. Such a person would have also
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`understood that the specification also provides chemical methods such as the use of
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`detergents and nucleases to expose the basement membrane. See e.g., Exhibit 1,
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`the ’701 patent at col. 5:43-46.
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`44. A person of ordinary skill in the art, in light of the specification of these
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`patents, would have understood that each of the disclosed methods, depending on
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`the particular methodology used, would have resulted in exposing varying amounts
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`of the basement membrane sufficient for the intended purpose of the tissue graft.
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`That is, depending on the method used, one of ordinary skill in the art would have
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`understood that, based on the specification of these patents, a different amount of
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`the basement membrane would be available to promote sufficient interaction
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`between the host cells and the basement membrane. The fact that the specification
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`reveals multiple methods that will expose varying amounts of the basement
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`membrane further supports my opinion that nothing in the claim language limits
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`the cellularity of the epithelial cellular layer position on top of the basement
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`membrane to any specific numerical amount.
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`45.
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`In connection with my opinion, I have also reviewed the file history for each
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`of the ’701, the ’092, and the ’207 patents and there is nothing in the file history of
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`these patents that is contrary to my opinion.
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`46. Finally, I have reviewed Defendants’ proposed construction for this term and
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`I understand they contend that the phrase “an exposed basement membrane” means
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`the side of the amnion in which greater than 90% of the epithelial cell layer has
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`been removed. I disagree with Defendants’ interpretation because, in my opinion,
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`it ignores the plain language of the claim, the specification, and the knowledge and
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`experience of a person of ordinary skill in the art.
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`47. But, as I described above, in view of the goal of the invention, one of
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`ordinary skill in the art, reading the specification, would have understood that the
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`inventors did not intend to limit the invention to exposing the basement membrane
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`solely by removal of greater than 90% of the epithelial cell layer. That is because,
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`a person of ordinary skill in the art would have known that in view of the methods
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`disclosed in the specification, the nature of biological systems in general, and the
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`limitations of the techniques for removal of the epithelial cell layer, there would
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`inherently be variation in how much epithelial cell layers would be removed.
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`Moreover, sufficient removal of epithelial cell layer was clearly contemplated by
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`Case 1:14-cv-01178-MHC Document 82-14 Filed 12/15/14 Page 19 of 62
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`the inventors so long as an adequate amount of basement membrane was available
`
`to promote sufficient interaction between the host cells and the basement
`
`membrane to support the desired function or purpose of the tissue graft.
`
`48. Furthermore, as discussed above, even though nothing in the claim language
`
`of the claims at issue limits the cellularity of the epithelial cellular layer positioned
`
`on top of the basement membrane to any specific numerical amount, Defendants’
`
`proposed construction requires a numerical limit. That is improper. Additionally,
`
`I note that dependent claim 5 in the ’207 patent specifically requires that the “at
`
`least one amnion tissue layer has had its epithelial layer substantially removed.”
`
`The fact that claim 1 of the ’701 patent, claim 1 of the ’092 patent and claim 1 of
`
`the ’207 patent do not recite a numerical limitation whereas claim 5 of the ’207
`
`patent does, further supports my opinion that a person of ordinary skill in the art
`
`would have understood that the inventors did not intend for claim 1 of the ’701
`
`patent, claim 1 of the ’092 patent and claim 1 of the ’207 patent to be limited by
`
`any numerical amount.
`
`49.
`
`In sum, in my opinion, a person of ordinary skill in the art reading the the
`
`claim language in view of the disclosures in each of the ’701, the ’092 and the ’207
`
`patents, and the file history of the patents would have understood that phrase “an
`
`exposed basement [membrane/layer]” to mean a basement membrane where
`
`sufficient epithelial cells have been removed such that “a sufficient amount of the
`
`18
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`Case 1:14-cv-01178-MHC Document 82-14 Filed 12/15/14 Page 20 of 62
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`basement membrane is available to promote sufficient interaction between the host
`
`cells and the basement membrane to support the desired purpose of the tissue
`
`graft.”
`
`2.
`
`“Wherein At Least One Amnion Tissue Layer Has Had its
`Epithelial layer Substantially Removed”
`
`In connection with this declaration, I am providing my opinion as to the
`
`50.
`
`meaning of the term “wherein at least one amnion tissue layer has had its epithelial
`
`layer substantially removed” as it appears in claim 5 of the ’207 patent.
`
`51. Claim 5 of the ’207 patent reads as follows:
`
`The multilayered tissue graft of claim 1, wherein at least one
`amnion tissue layer has had its epithelial layer substantially
`removed. (emphasis added).
`
`In my opinion, a person of ordinary skill in the art, reading this claim in light
`
`52.
`
`of the specification of the ’207 patent, at the relevant time, would have interpreted
`
`the phrase “substantially removed” with respect to the amount of epithelium
`
`removed as defined in the specification as removing greater than 90% of the
`
`epithelial cells from the amnion.
`
`53. Specifically, the specification further defines the term “substantially
`
`removed” as follows:
`
`The term “substantially removed” with respect to the amount of
`epithelium removed is defined herein as removing greater than
`90%, greater than 95%, or greater than 99% of the epithelium
`cells from the amnion.”
`
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`19
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`Case 1:14-cv-01178-MHC Document 82-14 Filed 12/15/14 Page 21 of 62
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`
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`Exhibit 3, the ’207 patent at col. 5:22-25. Nothing in the file history of the ’207
`
`patent contradicts this interpretation.
`
`54.
`
`In sum, in my opinion, a person of ordinary skill in the art reading the claim
`
`language in light of the disclosure of the ’207 patent, and the file history of the
`
`patent would have understood the phrase “substantially removed” in the phrase
`
`“wherein at least one amnion tissue layer has had its epithelial layer substantially
`
`removed” is defined in the specification as removing greater than 90% of the
`
`epithelial cells from the amnion.
`
`3.
`
`“At Least One Amnion Tissue Layer Has Had its Epithelial
`Layer Removed”
`
`55.
`
`In connection with this declaration, I am providing my opinion as to the
`
`meaning of the phrase “wherein at least one amnion tissue layer has had its
`
`epithelial layer removed” as it appears in claim 8 of the ’092 patent.
`
`56. Claim 8 of the ’092 patent reads as follows:
`
`The multilayered tissue graft of claim 1, wherein at least one
`amnion tissue layer has had its epithelial layer removed.
`
`
`In my opinion, a person of ordinary skill in the art, reading the claims in
`
`57.
`
`light of the specification of the ’092 patent, and the file history of the patent, would
`
`have interpreted the phrase “wherein at least one amnion tissue layer has had its
`
`epithelial layer removed” to mean “where sufficient amount of the at least one
`
`amnion tissue layer’s epithelial layer has been removed to expose the basement
`
`20
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`Case 1:14-cv-01178-MHC Document 82-14 Filed 12/15/14 Page 22 of 62
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`
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`membrane for purposes of promoting sufficient interaction between the host cells
`
`and the basement membrane to support the desired purpose of the tissue graft.”
`
`58. The plain language of claim 8 requires that the stated amnion tissue layer
`
`have “its epithelial layer removed.” There is no numerical or qualitative limitation
`
`stated in the claim. As such, nothing in claim language limits how much of the
`
`epithelial layer is removed and the cellularity of the epithelial cellular layer
`
`positioned on top of the basement membrane is not limited to any specific amount.
`
`59. Further, throughout the specification, the inventors describe that the goal and
`
`objective of the invention is to prepare placental tissue grafts wherein a sufficient
`
`amount of the basement membrane of the amnion in the graft is exposed to allow
`
`interaction between the biological macromolecules of the basement membrane and
`
`the host cells. See, e.g., Exhibit 2, the ’092 patent at col. 10:43-56. As discussed
`
`above, the specification provides chemical and physical means to remove a
`
`sufficient amount of the epithelial layer to expose the basement membrane. See,
`
`e.g., Exhibit 2, the ’092 patent at col. 5:26-59.
`
`60. One of ordinary skill in the art would have understood that for each of the
`
`methods identified in the specification for removing the epithelial cellular layer,
`
`there would inherently be variation in how much of the epithelial cellular layer
`
`would be removed. And, depending on the particular physical and chemical
`
`methods used, and the particular methodology employed, a varying amount of
`
`21
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`Case 1:14-cv-01178-MHC Document 82-14 Filed 12/15/14 Page 23 of 62
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`
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`epithelial cells would be removed from the epithelial cellular layer. Further, one of
`
`ordinary skill in the art would have understood that the specification does not limit
`
`the invention to a complete removal of all epithelial cells in the epithelial layer.
`
`However, one of ordinary skill in the art would have understood that the inventors
`
`clearly contemplated removal of sufficient amount of epithelial cells to expose the
`
`basement membrane for the intended purpose of the tissue grafts. Nothing in the
`
`file history contradicts this interpretation.
`
`61.
`
`I understand Defendants have taken the position that the phrase “wherein at
`
`least one amnion tissue layer has had its epithelial layer removed” means a layer of
`
`amnion tissue in which the epithelial layer has been completely removed. I
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`disagree with Defendants’ position. That is because one of ordinary skill in the art
`
`would have understood that a complete removal of all epithelial cells in the
`
`epithelial layer is physically impossible. That is because the native amniotic
`
`epithelial cells are in intimate contact with the underlying basement membrane,
`
`though chemical and physical interactions. As such, it would be virtually
`
`impossible to remove the entirety of the epithelial cells populating the epithelium
`
`layer. A person of ordinary skill in the art would ha
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