EXHIBIT 1021
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`DECLARATION OF DONALD A. WIEBE
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`lnfopia Ex. 1021 pg. 1 A
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`DECLARATION OF DONALD A. WIEBE
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`lnfopia Ex. 1021 pg. 1 A
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`IN THE‘UNITED STATES PATENT AND TRADEMARK OFFICE
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`In re
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`Inter Partes Review '
`of,U.S. Pat. No.: 7,087,397
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`Trial No.: TO BE ASSIGNED '
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`Inventors: Sunil G. Anaokar;
`Gena Lynn Antonopoulos and
`Alexandria Muchnik,
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`For:
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`Atty Docket No. 522493 .2
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`Serial No: 10/329,044
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`Filed: December 23, 2002
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`Issued: August 8, 2006
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`Customer No.2 27128
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`‘ Attn: Mail Stop “Patent Board, PTAB”
`Commissioner for Patents
`P. O Box 1450
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`Alexandria, VA 22313-1450
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`DECLARATION OF DR. DONALD ALAN WIEBE
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`I, Dr. Donald A. Wiebe, hereby declare that thefollowing is true and correct _
`under penalty ofperjury. I am otter the age of_18, competentto make this
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`declaration, and I am familiar with the facts below. I offer this declaration in,
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`support‘ofthe Petition for Inter Partes Review of claims 1-18 ofUS Patent No.
`'7,087,397 (the ‘397 Patent). All reference to Exhibit numbers1n this Declaration
`refer to the documents attached to the Declarationin support thereofand the
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`PAGE 1’
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`Infolcia Ex. 1021 pg. 2
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`Exhibits associated with the Petition for Inter Partes Review filed
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`contemporaneously herewith.
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`Personal Background Information
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`1.
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`I. I obtained a Bachelor’s Degree in Chemistry from the University of
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`Wisconsin — La Crosse in 1967. I obtained a Masters and a PhD. in Organic
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`Chemistry from The University of Iowa, Iowa City in 1970 and 1973, respectively.
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`From 1967~1970, I was a teaching assistant in the Department of
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`Chemistry at the University ofIowa, Iowa City. Inthis capacity, Itaught
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`laboratory classes for undergraduate students that were majors in chemistry,
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`nursing students, or pre—med students in subjects pertaining to general and organic
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`chemistry. In addition, I taught laboratory sessions for undergraduate students
`taking qualitative organic chemistry where the laboratory experience gave students
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`the ability to perform tests to identity of specificcompounds present inan
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`unknown that contained a mixture of chemicals. Finally, I was available to provide
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`students assistance when general guidance or tutoring was required to help them
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`understand key concepts from the lectures ofvarious general or organic chemistry.
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`classes.
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`From 1970-1972, I was a Research Assistant in the Department of
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`Chemistry at the UniversityofIowa, Iowa City. In that capacity, my duties and
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`responsibilities included maintenance and service on a Hitachi time-of—flight
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`lnfopia Ex. 1021- pg. 3
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`magnetic sector mass spectrometer. Chemistry faculty or graduate students from
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`the University of Iowa Chemistry Department requesting analysis by mass -
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`spectrometry to assist in identification ofthe specimen(s) in question submitted
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`research specimens.
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`4.
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`From 1972-1978, I was the Director of the Lipid Research Laboratory
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`in the Department ofInternal Medicine at the University of Iowa, Iowa City (my
`: academic appointment was as an Assistant Research Scientistf In that capacity,
`my duties and responsibilities included acquiring laboratory equipment, reagents,
`supplies, ‘and hire/train laboratory personnel to preform cholesterol, triglyceride,
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`and HDL—cholesterol analysis for patient specimens received for the NIH funded
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`Lipid ReSearch Clinic (LRC) study. The directors of the LRC laboratories (12
`laboratories located throughout the US and Canada) had regular meetings at least
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`once a year to discuss or resolve issues related to lipid and lipoprotein issues and
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`this meeting included Centers for Disease Control .(CDC) personnel. All the lipid
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`' and lipoprotein measurements in the LRC laboratories were standardized to CDC’s
`specifications and requirements.
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`From 1978—1980,‘I was a post-doctoral fellowship in the Department
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`ofPathology at the University ofIowa, Iowa City. In that capacity, my duties and
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`responsibilities included rotation through the various clinical chemistry and
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`toxicology laboratory sections to learn about the automated laboratory techniques
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`and quality control schemes used to ensure laboratoryresults acquired on patient
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`Infopia Ex. 1021 pg. 4
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`specimens were valid. The fellowship program was atWO-year program certified
`by the Commission onAccreditation in Clinical Chemistry (COMACC) is an
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`independent non-profit organization that accredits training programs in clinical
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`chemistry at the postdoctoral level. This process is intended to, assure the. trainee
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`that the standards of education and training are consistent with the progress in
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`medicine and clinical laboratory sciences.
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`6.
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`From 1980-1984, I was a visiting and research scientist in the. Clinical
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`Chemistry Division at the Center for Environmental Health, Centers for Disease
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`Controlpin Atlanta, Georgia. In these capacities, my duties and responsibilities
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`included developing criteria for collection ofhuman serum for the preparation of
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`controls and standards for clinical laboratories. Most of these materials were
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`‘ focused on lipid and lipoprotein products, such as cholesterol, triglyceride and
`HDL—cholesterol measurements. Duties were expanded to include programs and
`activities associated with superfimd issues and “agent orange” studies.
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`From1984tothepresent,IhavebeenanAssistantProfessorinthe
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`Departmentnof.Pathology & Laboratory Medicine, School ofMedicine at the
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`University of Wisconsin — Madison with promotion to Associate Professor in 1990
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`with tenure. Over my career at the University of Wisconsin, I have taught Clinical
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`Laboratory Science (CLS) classes relating to the principals and practice of blood
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`separation mechanisms including dry chemistry systems as well as clinical
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`laboratmy testing methods and procedures, all ofwhich are applicable to the
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`Infopia Ex. 1021 pg.” 5 ,
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`subject matter of US. Patent No. 7,087,397. These classes include: CLS-525, a
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`clinical chemistry ISt semester class for seniors in the CLS program that included a
`4 series oflectures and laboratory sessions with a’focus on lipids and lipoprotein
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`techniques.
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`8.
`' During my tenure as an Associate Professor in the School of Medicine
`I at the University of Wisconsin, I have also held a number of different positions.
`Since 1985 to thepresent, I have been the Director ofthe Toxicology Laboratory
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`Services at the University of Wisconsin Hospital and Clinics. In this capacity, my
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`duties and responsibilities included oversight of all the analysis ofpatient
`specimens received for the analysis oftherapeutic drug monitoring or toxicology
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`testing. Most ofthe technology involved in the toxicology laboratory included
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`automated chromatography techniques, such as gas chromatography, high
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`performance liquid ‘chromatography with both UV and mass spectrometer
`detection systems. From 1984 to 2002, I was the Associated Director of Clinical
`Chemistry and promoted to Director ofthe Clinical Chemistry Laboratory in 2002
`until 2014 at the University ofWisconsin Hospital and Clinics. In this capacity,
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`my duties and responsibilities included all functions associated with testing patient
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`specimens in a high volume, complex laboratory that involved lipid and lipoprotein
`testing (cholesterol, triglyceride andHDL-cholesterol). The clinical chemistry ‘
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`laboratory utilizes automated high volume clinical chemistry analyzers functioning
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`lnfopia Ex. 1021 pg. 6
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`24/7 and 365 days ofthe year to provided services to both inpatients and '
`outpatients for a Wide variety oflaboratory services.
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`9.
`I have also published numerous papers in various journals and I have
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`Written and contributed to various chapters in'various books as identified in my CV
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`attached hereto as Exhibit 1022. As stated in Exhibit 1022, many of these
`publicationsrelate to cholesterol and HDL testing in a clinical laboratory setting,
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`including publications relating to cholesterol and triglyceride concentrations in
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`serum/plasma pairs; precipitation procedures for estimation ofhigh density
`lipoprotein cholesterol; various cholesterol measurement methods; testing
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`cholesterol accuracy-performance of several common laboratory instruments;
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`standardization of cholesterol measurements and performance specifications
`relating to HDL and LDL cholesterol With‘operating specifications based on
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`clinical and analytical goals. These and other publications, invited papers
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`published in conference proceedings, chapters in books, contributed papers and/or
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`abstracts, technical reports, invited seminars and research presentations and other
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`publications are all identified in my CV attached as Exhibit 1022 hereto.
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`10.
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`These are publications having particular pertinence to the issues I will
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`be discussing. They are:
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`a. First: John J. Albers, G. Russell Warnick, Donald Wiebe, et al.:
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`‘ Multi-laboratory comparison of three heparin-MnJmL precipitation
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`procedures for estimation ofhigh density lipoprotein cholesterol.
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`Infopi-a Ex. 1021 pg. 7
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`gin. (Eh—em. fit 853—856 (lé78). Itspertinence is HDL—cholesterol
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`analysis, because it demonstrates experience with HDL-cholesterol
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`analysis du'ring‘the 1970is.
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`. Second: Donald A. Wiebe and Thomas Bernert: The influence of
`incomplete cholesterol ester hydrolysis on cholesterol
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`measurement by enzymatic methods. gin. Chem. _3__()_: 352-356
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`(1984). Its pertinence is cholesterol analysis, because it
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`demonStrates an expertise in cholesterol analysis.
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`. Third: Donald A. Wiebe and S. Jay Smith: COmparison of six
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`high-density lipoprotein isolation methods using the cholesterol
`reference method for quantitation. @. C_h§rn. fl: 746-750
`(1985). Its pertinence is HDL—cholesterol analysis, because it
`demonstrates an expertise in HDL—cholesterol analysis.’
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`H
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`. Fourth: James H Stein, Cynthia M. Carlsson, Kristi Papcke—
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`Benson, Jean A. Emerson, Patrick E McBride, and Donald A.
`Wiebe. Inaccuracy ofportable lipid analysis in patients with
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`hyperlipidemia. gin; m. 48: 284—290(2002). Its pertinence is
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`lipid analysis by point ofcare methods, because it concerns the
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`usefulness in management of patient care.
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`. Fifth: Donald A. Wiebe and G. Russell Warnick:’Measurement‘of 7
`high-density lipoprotein cholesterol concentration. In Laboratory
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`Measurement of Lipids, Lipoproteins and Apolipoprotcins Risk
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`Factors. Eds. Nader Rifai and G. Russell Warnick, AACC Press,
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`Wash DC,' 1994, pp 91—105. Its pertinence is the coauthor ship of a
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`chapter written on HDL—cholesterol measurement and subsequent
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`2 additional editions, because it further documents my expertise in
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`HDL-cholesterol measurements.
`‘My CV is attached hereto as Exhibit 1022.
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`11‘
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`The Level of Ordinary Skill in-the Art
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`12.
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`I am informed that the relevant art in question pertains to the testing
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`and measurement of HDL cholesterol concentration from a serum such as whole
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`. blood or plasma.
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`13.
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`' I am informed that a person of ordinary skill in the art is a
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`hypothetical person who is presumed to have known the relevant art at the time of
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`the invention I ampfurther informed that factors that may be considered in
`_ determining the level of ordinary skill in the art may include: (A) type ofproblems
`encountered in the art; (B) prior art solutions to those problems; (C) rapidity with
`which innovations are made; (D) sophistication ofthe technology; and (E)
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`"educational level of active workers in the field. I was told to assume that in a given
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`. case, every factor may not be present, and oneor more factors may predominate. I 7
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`am. also informed that a person of ordinary skill in the art is also a person of
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`; ordinary Creativity, not an automaton, and‘in many cases a person of ordinary skill
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`Infopia Ex. 1021 pg. 9
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`will be able to fit the teachings of multiple patents together like pieces of a puzzle.
`. Finally, I am told to assume that the hypothetical person having ordinary skill in
`the art to which the claimed subject matter pertains would, ofnecessity have the ‘
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`capability of understanding the scientific and engineering principles applicable to
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`the pertinent art. ,
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`i 14.
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`Considering the factors in paragraph 11 above, I believe that a person
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`‘ having ordinary skill in the art on or before 2000 would have a detailed knowledge
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`ofthe chemistry'and processes associated with the testing ofHDL [in clinical
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`laboratory settings, and that such a person would have many years of experience
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`i with clinical laboratory testing for HDL and the techniques in the laboratory used 7
`to measure HDL through manual methods.
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`15 ..
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`Preferably, this person would typically have atleast a bachelor’s
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`degree in chemistry, biochemistry or clinical chemistry with at least four to five
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`years of experience in a clinical laboratoryvsetting testing for HDL. It would be
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`preferred that the person of ordinary skill have a PhD. degree in chemistry or a
`similar degree. As is the case in many professions, a lack ofhigher education can
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`be made up for by hands-on—work experience in the field, while the need for real~
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`world experience may be somewhat lower with a higher education level.
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`I believe that I am aperson having atleast Ordinary skill in the art at
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`present, and before 2000. During the 2000 time frame, I had already achieVed my
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`PhD. Degree (in 1973) and had worked in the field of cholesterol and HDL testing
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`lnfopia Ex. 1021 pg. 10
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`in a clinical laboratory setting for many years (as set forth in my work history and
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`positions held set forth in my ‘CV attached hereto as Exhibit 1022). As noted
`above, from 1972-1978 I was the Directorofthe Lipid Research Laboratory in the 7
`Department ofInternalMedicine at the University ofIowa, Iowa City wherein I
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`worked on a daily basis in a clinical laboratory setting wherein I was intimately
`involved with testing for triglycerides and cholesterol concentrations, LDL and
`HDL, in ‘whole blood including using various methods for testing, using various
`instruments for testing, and analyzing standardization proceduresfor cholesterol '
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`measurements and testing. Thus, prior to the invention at issue in the ‘397 Patent,
`1 had a PhD in organic chemistry as well as almost thirty (30) years ofexperience
`in HDL testing in the clinical laboratory setting.
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`17.
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`From 1980-1996 I likewise had hands-on experience as a visiting and
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`research scientist in the Clinical Chemistry Division, Center for Environmental
`Health, Centers for Disease Control in Atlanta, Georgia and from 1984-1996, I was
`Assistant Director for the Clinical Chemistry Laboratory at the University of
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`Wisconsin Hospitals and Clinics. All of this experience predated the 2000
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`timeframe relating to the ‘397 Patent. I am therefore appropriately positioned to
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`opine as to What a person having ordinary skill in the art at the time of the
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`invention would understand and do.
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`18.
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`In addition to the above experiences pertinentto the art, my
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`V qualifications further include general clinical laboratory experience acquired
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`Infopia Ex. 1021 pg: 11
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`throughout my over 40—year career in laboratory medicine by attending national
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`meetings and conferences and professional activities that contributed to my overall
`understanding ofanalytical issues andprinciples, highly relevant to the invention
`. at issue.
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`‘The Technology At Issue
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`19.
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`The principals and practiceofusing dry chemistry systems for urine
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`and blood tests date back to the 19803. In this regard, I attach hereto. a chapter
`entitled “Principals and Practice ofDry Chemistry Systems” from a book entitled
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`“Recent Advances’in Clinical Biochemistry”, edited by OR Price and KG. M.M.
`Alberti and published by Churchill Livingstone in 1985. This chapter di5closes the
`use ofanalytical testing devices and so-called “new diagnostic procedures” that
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`were known at the time the book was published (1985). The publication describes
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`procedures uSing analytical principals that had been employed successfully‘in the
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`clinical laboratory for twenty-«five (25) years in the form of the familiar urine and
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`blood test strips. See generally, p. 273 ofExhibit 1023. The term “dry chemistry”
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`means that all the reagents and auxiliary substances necessary for the reaction are
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`embedded in a paper or plastic matrix in their dry state, thus obviating the need to
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`prepare reagent solutions. 'As I quote from page 273 ofExhibit 1023:
`“in order to initiate the reaction, however, these new
`procedures still require a solvent in which the substance
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`to be determined is dissolved; in the clinical laboratory
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`lnfopia Ex. .1021 pg. 12
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`the solvent would be the sample, namely, urine, serum,
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`plasma or whole blood.”
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`V 20.
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`Further aspects concerning the l<nown aspects ofthe art at the time is
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`explained in the introduction section ofExhibit 1023 on pages 273’ and 274:
`“in the past the results were evaluated purely visually
`by comparingthe reaction colours that develop with a
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`table of referenced colors; more recently the use ofreflectance ‘
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`. photometry has enabled the production of quantitative results
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`that are comparable with those of the classic photometric
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`methods-with respect to precision and accuracy (Drucker
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`et al, 1993).” Exhibit 1023 sets forth the historical
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`development ofdry chemistry systems and clearly discloses
`the use ofblood test strips for visual interpretation .
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`although the emphasis, in the 19803, was primarily on glucose.
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`' 21.
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`The basic principles for constructing a dry reagent carrier useful in of
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`I measuring cholesterol and HDL are set forth on page 277 ofExhibit 1023 and in a
`basic form, includes a reagent part, a reflective part and a support part; “Thus a '
`dry chemistry system may comprise just three basic layers, or may be
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`supplemented by‘further layers such as a spreading layer or a plasma separation
`layer.” The use ofvertical flow methods and spreading layers to measure HDL
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`and cholesterol vvere well—knovvn in the art at least as early as the publication date
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`PAGE 12
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`'Infopia Ex. 1021 pg. 13
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`ofExhibit 1023 andsuch methods are clearly illustrated in diagrams b) and c) on
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`page 289 of Exhibit 1023.
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`22.. Exhibit 1023 also discusses the‘theoretical principles ofreflectance
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`spectroscopy starting on page. 280, and then further discusses the technical details
`and performance data associated with the dry chemistry systems-known at that
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`time. Such known systems included the Ames System, the Eastman Kodak System
`and the Reflotron System,all ofwhich used techniques similar to those disclosed
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`in the ‘397 Patent for testing blood samples to measure HDL cholesterol. All of
`these systems/techniques are based on similar reaction principles wellknown prior
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`‘ to the 2000 timeframe, including the use of several reaction layers and a plasma
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`separation system that consists of different layers of glass fiber material and serves
`to separate the erythrocytes when the sample material is blood. &, p. 290 of
`Exhibit 1023.
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`23. Arranging layers in avertical stack so as to allow a sample, such as
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`blood, to flow vertically downward in the stack to a reaction layer is well—known in
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`the clinical laboratory setting. For example, Exhibit 1023 at pp. 275, 278 and 289
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`discloses various'layers of a dry chemistry system, or test strip, arranged in a
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`vertical stack wherein blood, serum or plasma samples flow vertically downward
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`in the stack through, at least, a spreading layer, a reagent layer and an indicator 1
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`layer as clearly shown on‘pp. 278 and 289 ofExhibit 1023. Glass fiber layers are
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`also disclosed in the layered structure illustrated in Exhibit 1023.
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`lnfopia Ex. 1021 pg. 14
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`24.
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`The Connolly reference (U.S. PatentNo. 5,597,532) disclOses a test.
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`strip having layers arranged in a vertical stack as best shown in Fig. 2 including a
`disbursement) layer 28, a separating layer 30, and a test reaction membrane 32 on
`Which dry chemicals and reactants are contained for generating a visible signal in
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`the presence ofserum analytes. Connolly, EX. 1015, at 4:44-62.
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`25.
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`The Patel reference (U.8. Patent No. 5,215,886) likewise discloses a
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`test strip device ofvertically stacked membranes having a polymeric membrane 14
`for removing red blood cells, and filter layers ~l6 and 18 for removing VLDL and
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`LDL, while allowing HDL to pass there through. Patel, EX. 1014, at 6:48-55
`26.
`The Kozak reference (U.S. Patent No. 5,460,974) likewise discloses a
`test strip device 80 of vertically stacked layers including a first filter pad 90 for
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`removing cellular components from a Whole blood‘sample, a second filter pad 88
`including a precipitating reagent for removing LDL and VLDL fractions from'a
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`Whole blood sample, a third separating filter 86 to further remove the cellular
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`components and the LDL and VLDL fractions from the whole blood sample, and a '
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`test pad-84 containing reagents for producing‘a detectable response that can be .
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`examined through the transparent strip 82. Kazak, EX. 1007, at 24:16—50.
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`The Carroll reference (U.S. Patent No. 6,040,195) discloses atest strip
`27.
`10 having vertically stacked layers including a spreading layer 20,, a separating ‘
`layer 30 for filtering and a pre-conditioned membrane 40. Carroll, EX 1008, at
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`3:48—50.
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`.ln'fopia Ex. 1021* pg; 15
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`28.
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`The Kitajima reference (US. Patent No. 5,876,605) likewise discloses
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`a plasma or serum separating filter unit having vertically stacked layers as
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`illustrated in Fig. 1 including two glass fiber.filter layers 10, a cellulose filter layer
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`11, and a membrane 13. Kitajimcz, EX. 1016, at 10:20-35.
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`29.
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`Thus, the Connolly, Patel, Kozak, Carroll and ‘Kitajima references as 7
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`well as Exhibit 1023 teach test strips having vertically stacked layers and whole
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`blood samples which flow vertically downwardly through the various layers of
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`these prior art test strips. These references all Show that the vertical downward
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`flow of a blood sample through vertically stacked layers of atest strip was known I
`before .2000, which is consistent with my own knowledge at the time.
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`The ‘397 Patent, Ex. 1001
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`30.
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`The ‘397 Patent relates generally to a multi—layered test strip 20 and ,
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`method ofusing the test strip for determining the concentration ofHDL cholesterol
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`in a whole blood sample. The test strip 20 of the ‘397 Patent includes a vertically
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`stacked test strip having, in one disclosed example, three distinct layers, namely, a"
`red blood cell separation layer 38, a non-HDL separation chemistry layer 40, and
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`an HDL reaction layer 42 as shown in Fig. l reproduced below.
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`V PAGE 15
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`Infopia Ex; 1021 pg. 16
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`(‘3 97 Patent, Anaokar, EX. 1001, Figure 1)
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`The non—HDL cholesterol separation chemistry layer 40 contains non-HDL
`cholesterol separation chemicals for separating the non-HDL blood components
`from the HDL blood components [so that the non-HDL components 'do not
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`precipitate inthe reaction in the HDL reaction layer. ‘In essence, the ‘397 patented
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`test strip includes a two~stage blood separation mechanism wherein the first red
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`blood cell separation layer 3 8 separates most of the blood cells and the second non-
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`HDL separation layer 40 separates the remainder oftheblood cells. It is preferred-
`that both ofthese layers include glass fibers or a glass fiber matrix as is well-
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`known in the prior art as described above.
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`lnfopia Ex. 1021 pg. 17
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`31.
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`The HDL reaction layer 42 as illustrated in ‘397 Patent, Fig. 1
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`contains dry chemicals and reactants for generating a visible colour change in the
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`presence of cholesterol, identified in the patent as commercially available CHAPS,
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`or 3—[(3-cholamidopropyl) dimethylammonio]-l~propanesulfonate. Layer 42 is
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`positioned beneath and influid communication with layer 40 as again shown in
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`Fig. 1. This reaction layer produces a colour, the intensity ofwhich is proportional
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`to the Concentration of HDL cholesterol in the blood sample that is applied to the
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`test strip.
`32. As illustrated in Fig. l ofthe ‘397 Patent, in another example, a
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`disbursement layer 36 is placed on top of the vertically stacked layers and acts as a
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`top layer for spreading or disbursing the blood sample laterally across the
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`disbursement layer before it begins to flow vertically downwardly in the stack
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`through the other layers, Ex. 1001 at 8:40—51. Claim 1 ofthe ’397 Patent identifies
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`a vertically stacked three layer test strip whereas claim 19 of the ‘397 patent
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`identifies a vertically stacked four layer test strip.
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`33.
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`The multi-layered test strip is held in a test strip holder which is
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`likewise disclosed in Fig. lofthe #397 Patent. The test strip holder includes an end
`portion 26 which is described as preferably attached by hinge 28 to a second end
`portion 30 as best shown in Fig. 1. Portion 26 is folded about hinge 28 over
`portion 30 such that end portion 26 resides on top ofthe vertically stacked test strip I
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`,
`
`’
`
`2 layers and end portion 30 lies at the bottom ofthe stacked layers. Top holder
`
`~ PAGE 17
`
`lnfopia Ex. 1021 pg. 18
`
`
`
`
`
`
`
` r t :
`
`- portion 26 includes an opening 32 and the bottom holder portion 30 includes an
`
`opening 34. The openings 32 and 34 are aligned with eachother when the test
`holder is folded as illustrated in Fig. 1. Opening 32 shows an application window
`for depositing a Whole blood sample While Opening 34 defines a test reading
`
`window wherein a visible colour produced by the HDL reaction layer can be
`
`viewed. EX. 1001 at 8:55-67; 9:1-3. 1
`
`34.
`
`The background section of the ‘397 Patent shows that test strips for
`
`I precipitation and separation of non-HDL cholesterol and blood cells from plasma
`to determine the level ofHDL cholesterol have been well-known in the field of
`
`blood diagnostics dating back at least to the early 19803. EX. 1001 at 1:54-67; 2:1-
`
`67; 3:1-67; 4:1-37. The use of glass fibers for separating red blood cells from
`
`whole blood is likewise well-known in the art again dating back to the early 1980s,
`
`as shown in the same reference. Id.
`
`35.
`
`I am informed that allowance of the ‘397 Patent was based upon the
`
`Declaration ofJames J. Sutor, a senior scientist at l’olymer Technology Systems.
`
`36.
`
`I have reviewed this Declaration and it appears that the Declaration of
`
`Mr. Sutor (EX. 1012) is directed largely to the Thakore reference (Exhibit 1006)
`
`and that Mr. Sutor merely addresses the lateral and upward flow associated with
`the Thakore reference. Mr. Sutor goes on to state that lateral and upward flow
`
`have disadvantages and that vertical flow‘works better in test strips in which'one or
`
`‘ more cholesterol—varying lipoproteins are segregated. S_ee, para. 9 of Exhibit 1012.
`
`PAGE 18
`
`“Infopia‘Ex. 1021. pg. 19
`
`
`
`Mr. Sutor’s declaration notwithstanding, reference to vertical flow had already
`
`been disclosed and knovvn in the art. Namely, the Connolly reference (Ex. 1015),
`
`the Patel reference (EX. 1014); the Carroll reference (EX. 1008); and the Clinical
`
`Biochemistry reference (Exhibit 1023) all show vertical flow‘ through stacked
`
`multi—layers‘ of a test strip.
`
`Claim 1 states that the blood fluid flows vertically downWard in the
`37.
`stack to the HDLreaction layer without substantial lateral migration ofthe fluid
`below the red blood cell separation layer (claim 1). I believe that a person having
`
`ordinary skill in the art of measuring and determining HDL concentration from
`
`whole blood samples at the time ofthe invention ofthe ‘397 Patent, and at the time
`
`of its priority date, would have interpreted “without lateral migration of fluid
`
`below said red blood cell separation layer” as follows. I base my opinion in part
`
`on the prosecution history ofthe ‘397 Patent and on the definitionscited in the
`
`b ‘397 Patent. For those that are not clearly defined or described in the ‘397 Patent or
`its file wrapper, 1 base my opinion on the plain and ordinary meaning as
`
`conventionally used in the art and understood by a person having ordinary skill in
`
`the art. In claim 1, the red blood cell separation layer 38 (Fig. 1) is the top layer of
`the test strip. Below the red blood cell separation layer 38, the test strip of Claiml
`
`'
`
`includes a non-HDL separation layer 40 and an HDL reaction. layer 42 again as
`illustrated in Fig. 1 ofthe ‘397 Patent. 1 interpret the term “without substantial
`
`lateral migration of fluid below the red blood cell separation layer” to mean that g
`
`PAGE 19
`
`' Infopia Ex. 1021 pg. 20
`
`
`
`
`
`
`
`
`
`It E
`
`once the whole blood sample has penetrated the red blood cell separation layer 3 8,
`
`the remaining fluid from the whole blood sample moving downwardly into layers
`
`40 and 42 will move in a vertical downward direction and will have some fluid
`movement and spreading in all directions from one side oflayers 40 and 42 to the
`
`other side respectively. In claim 1 b) of the ‘397 Patent, the term “substantial”
`
`qualifies the subsequent words “lateral migration.” That is, “substantial” refers to
`
`the idea that there is some lateral migration in the blood flow. “Substantial” is
`
`based upon Applicant’s own statements in the ‘397 Patent that “[O]fcourse, there
`
`is fluid movement, especially spreading, in all directions in applicant’s inventive
`test strips”, there will be some lateral migration ofthe blood fluid as it flows
`downward past layer 38. gee, EX. 1001 at 5:32-34. This definition is consistent
`
`with the definition of prior art lateral flow devices defined in the ‘397 Patentlas
`
`being devices where the “presence of a sample application point that is laterally
`offset (along the axis ofthe test Strip) from the sample reading area ofthe test
`
`strip)”. fie, EX. 1001 at 2 :14-17. This definition is also consistent With
`
`, applicant’s proffered definition at Ex. 1001, 23:61—64.
`
`3 8. A person having ordinary skill in the art would understand that using
`
`the term without substantial lateral migration of fluid below the red blood cell
`
`separation layer simply means that the blood sample will continue to migrate
`
`downwardly through the respective layers and that some lateral migration, by its
`
`Very nature, will occur based upon the thickness of the various layers and based ‘
`
`v PAGE 20
`
`lnfopia Ex. 1021 pg. 21
`
`
`
`
`
`upon the size of the whole blood sample. Basic physics tells you that some lateral
`
`migration will occur in a vertically downward oriented flow. No numerical
`quantification ofthis term is set forth in the ‘397 Patent. Instead, the Applicant
`
`distinguishes its flow pattern from the prior art lateral flow devices by defining the
`
`‘ features associated with a lateral flow device and by further-defming its vertical '
`
`flow device as a device wherein there is no need to allow for any net lateral
`
`movement of fluid from one side of a layer to the other as required by prior art
`
`devices. . .Sfl’ Ex. 1001 at 5:34-36. Applicant explains this feature and advantage
`as follows:
`
`“Advantageously, Applicants’ test strip can be made more
`compact because the large surface area oftransport media
`
`needed in prior art devices for lateral movement has been
`
`eliminated. In otherwords, the test layers can be vertically '
`
`aligned with one another and made smaller, thereby enabling
`
`a smaller and more compact test strip which requires a smaller
`blood samplei’. §§§,»Ex. 1001 at 5 :37-43.
`
`39.
`
`I also note that Applicants’ amended claim 1 dining prosecution to
`
`specifically state that the “without substantial lateral migration of fluid” took place
`below the red blood cell separation layer. This amendment was made .to overcome
`
`and distinguish over the prior art Thakore reference wherein the bloodflows
`
`vertically upward and, according to Applicant, therefore has a tendency to spread
`
`PAGE: 2 l
`
`.Infopia Ex. 1021 pg. .22
`
`
`
`
`
`laterally much more when the flow is upward thereby resulting in more blood
`
`being required to do the test. &, BX. 101 l, p. 6.
`40.
`Based on the recitations in the ‘397 Patent and in the file history as set
`forth above in paragraphs 32-34, it is clear to me, and it would be clear to a person
`
`.
`
`having ordinary skill in the art, that the term “without substantial lateral migration
`
`of fluid below said red blood cell separation layer”? simply means that some fluid
`movement and spreading may take place in the vertically stacked layers below the
`
`red blood cell separation layer because as explained above, the laws of governing .
`
`physics dictate that a quantum of lateral migration will necessarily occur in a
`vertically
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