UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________________________________
`
`
`
`
`
`ALERE INC.,
`Petitioner
`
`v.
`
`REMBRANDT DIAGNOSTICS, LP
`Patent Owner
`U.S. Patent No. 8,623,291
`
`Case No. IPR2016-___
`
`
`
`DECLARATION OF ROBERT C. BOHANNON IN SUPPORT OF
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT
`NO. 8,623,291 UNDER 35 U.S.C. § 312 AND 37 C.F.R. § 42.104
`
`
`
`
`
`ALERE EXHIBIT NO. 1003
`Page 1 of 117
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`TABLE OF CONTENTS
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`Page
`Introduction ...................................................................................................... 5 
`I. 
`Qualifications ................................................................................................... 6 
`II. 
`In Vitro Device Design Process ....................................................................... 9 
`III. 
`IV.  Overview of Technology ............................................................................... 10 
`A. 
`Commercial Devices for Drug Testing Were Known in the Art ........ 14 
`B. 
`Testing Multiple Analytes With Multi-Strip Devices Was
`Known in the Art ................................................................................. 16 
`Test Strip Construction Was Known in the Art .................................. 19 
`C. 
`D.  Windows For Viewing Test And/Or Control Zones Were
`Known in the Art ................................................................................. 28 
`Caps For Protecting Test Strips Were Known in the Art .................... 31 
`E. 
`V.  Applicable Legal Principles ........................................................................... 33 
`VI.  Person of Ordinary Skill in the Art ................................................................ 36 
`VII.  The ’291 Patent And Its Prosecution History ................................................ 37 
`VIII.  Claim Construction ........................................................................................ 42 
`A. 
`“Sample Addition Pad” ....................................................................... 42 
`B. 
`“Transparent Window” ....................................................................... 43 
`C. 
`“A First Transparent Window” ........................................................... 44 
`D. 
`“A Second Transparent Window” ....................................................... 45 
`IX.  Summary of Select Prior Art ......................................................................... 45 
`A.  Overview of DE (Ex. 1004) ................................................................ 45 
`B. 
`Overview of May (Ex. 1005) .............................................................. 48 
`C. 
`Overview of Charm (Ex. 1008) ........................................................... 49 
`D.  Overview of Cipkowski (Ex. 1006) .................................................... 52 
`E. 
`Overview of Sun (Ex. 1007) ............................................................... 57 
`X.  Grounds of Invalidity ..................................................................................... 58 
`A.  Ground I: Claims 1, 2, and 9 Are Obvious Over DE In View of
`May ...................................................................................................... 59 
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`1. 
`2. 
`
`Independent Claim 1 ................................................................. 59 
`Dependent Claim 2: “the device according to claim 1 further
`comprising a second transparent window formed within the
`cover through which the test strips can be viewed.” ................ 68 
`Independent Claim 9: “A method for detecting a multiplicity of
`analytes which comprises removing the cap from the device of
`claim 1 and inserting the protruding ends of the test strips into a
`sample to be analyzed and observing the effect of the sample on
`the test and control zones of the test strips contained in the
`device.” ..................................................................................... 72 
`Ground II: Claims 1 and 9 Are Obvious Over DE In View of
`Charm and May ’871 ........................................................................... 73 
`1. 
`Claim 1 ...................................................................................... 73 
`2. 
`Claim 9 ...................................................................................... 77 
`Ground III: Claim 2 Is Obvious over DE In View of May,
`Shuler, and Eisinger ............................................................................ 78 
`D.  Ground IV: Claims 1 and 2 Are Obvious Over Cipkowski In
`View of May ........................................................................................ 81 
`1. 
`Independent Claim 1 ................................................................. 81 
`2. 
`Dependent Claim 2: “the device according to claim 1 further
`comprising a second transparent window formed within the
`cover through which the test strips can be viewed.” ................ 91 
`Independent Claim 9: “A method for detecting a multiplicity of
`analytes which comprises removing the cap from the device of
`claim 1 and inserting the protruding ends of the test strips into a
`sample to be analyzed and observing the effect of the sample on
`the test and control zones of the test strips contained in the
`device.” ..................................................................................... 93 
`Ground V: Claims 1 and 9 Are Obvious Over Cipkowski in
`View of Charm and May ’871 ............................................................. 94 
`1. 
`Claim 1 ...................................................................................... 94 
`2. 
`Claim 9 ...................................................................................... 97 
`Ground VI: Claim 2 Is Obvious Over Cipkowski in View of
`May, Shuler, and Eisinger ................................................................... 98 
`
`B. 
`
`C. 
`
`E. 
`
`F. 
`
`3. 
`
`3. 
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`3. 
`
`G.  Ground VII: Claims 1, 2, and 9 Are Obvious Over Sun in View
`of May ................................................................................................. 99 
`1. 
`Independent Claim 1 ................................................................. 99 
`2. 
`Dependent Claim 2: “the device according to claim 1 further
`comprising a second transparent window formed within the
`cover through which the test strips can be viewed.” ..............108 
`Independent Claim 9: “A method for detecting a multiplicity of
`analytes which comprises removing the cap from the device of
`claim 1 and inserting the protruding ends of the test strips into a
`sample to be analyzed and observing the effect of the sample on
`the test and control zones of the test strips contained in the
`device.” ...................................................................................109 
`H.  Ground VIII: Claims 1 and 9 Are Obvious Over Sun in View of
`Charm and May ’871 ......................................................................... 111 
`1. 
`Independent Claim 1 ...............................................................111 
`2. 
`Independent Claim 9 ...............................................................113 
`Ground IX: Claim 2 Is Obvious Over Sun in View of May,
`Shuler, and Eisinger .......................................................................... 113 
`XI.  Materials Relied Upon ................................................................................. 115 
`XII.  Conclusion ................................................................................................... 115 
`XIII.  Availability for Cross-Examination ............................................................ 115 
`XIV.  Right to Supplement .................................................................................... 115 
`
`
`I. 
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`I.
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`I, Robert C. Bohannon, declare as follows:
`
`Introduction
`1. My name is Robert C. Bohannon.
`
`2.
`
`I have been retained by Alere Inc. (“Petitioner”) as an expert to
`
`provide my opinions concerning claims 1, 2, and 9 of U.S. Patent No. 8,623,291
`
`(“the ’291 Patent”).
`
`3.
`
`As discussed below, I have many years of experience in the field of
`
`designing, developing and marketing immunoassays in various different formats
`
`and for various different types of analytes, including immunoassays used in
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`detecting drugs of abuse in urine samples.
`
`4.
`
`In forming my opinions, I reviewed the ’291 Patent including its
`
`disclosure and claims, the prosecution history of the ’291 Patent and the petition
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`for inter partes review of the ’291 Patent, including the exhibits (“the Petition”).
`
`5.
`
`I am being compensated at my normal consulting rate of $620 per
`
`hour. My compensation is not dependent on the outcome of this proceeding and in
`
`no way affects the substance of my statements in this Declaration.
`
`6.
`
`I have no financial interest in Petitioner (or its subsidiaries, including
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`Alere Toxicology Services, Inc., Amedica Biotech, Inc., Ameditech, Inc.,
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`Innovacon, Inc., Instant Technologies, Inc., Instant Tech Subsidiary Acquisition
`
`Inc. d/b/a US Diagnostics, and Branan Medical Corp.), and have no financial
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`interest in the ’291 Patent or in Rembrandt Diagnostics, LP. I have had no contact
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`with the named inventor of the ’291 Patent.
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`II. Qualifications
`7.
`I received a Bachelor of Arts degree in Molecular Biology from the
`
`University of Colorado at Boulder in 1986, and a Ph.D. in Molecular Virology
`
`from Baylor College of Medicine in 1991.
`
`8.
`
`I have been the President and Lab Director of Catalloid Products, Inc.
`
`and Chief Scientific Officer of EKF Life Sciences since April 2013.
`
`9.
`
`Before that, I managed research and development for a variety of
`
`private companies. My background and experience is set forth in greater detail in
`
`my C.V., which is attached as Appendix A.
`
`10.
`
`I am an inventor on over 15 issued or pending patents and have
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`published articles in leading academic journals.
`
`11. My expertise spans many fields, and includes the development of
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`assays for lateral flow, EIA (enzyme immunoassays), and molecular tests.
`
`12. By the mid- to late- 1990s, I already had years of experience with
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`drug testing, assay development, and other relevant skills because I worked for
`
`Onasco Companies, a public biotech company, while earning my Ph.D, then held
`
`several other positions in both the public and private sectors. I developed twelve
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`diagnostic kits and vaccines for Onasco Companies. Also in the mid- 1990s, I was
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`licensed as a researcher by the Drug Enforcement Administration, and developed
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`two anti-cocaine vaccines for my own lab, Anarco. From November 1994 to June
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`1997, I worked as a Project Officer for the U.S. Army, where I spent most of my
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`time developing assays. Among other responsibilities, I supervised and managed a
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`crew of 17 technicians assaying up to 9000 field samples per day. I also
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`implemented automation of sample handling, counting, and reporting of biological
`
`assays. From June 1997, to November 1998, I served as the Director of Research
`
`and Development and Lab Director for Epitope, Inc. My responsibilities included
`
`evaluating new technologies and competitive products, as well as developing rapid
`
`diagnostic tests, including for drugs of abuse. I managed dozens of R&D projects
`
`with multi-million dollar budgets.
`
`13. Since the late 1990s, I have held director and C-suite level positions
`
`with a variety of companies, and was involved in managing numerous R&D
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`projects with multi-million dollar budgets, and supervising dozens of scientists and
`
`technicians. Despite my managerial responsibilities, I consistently maintained
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`active bench time developing tests.
`
`14.
`
`I have more than twenty years of experience designing and developing
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`test devices, including strip and cup test devices, systems for testing drugs of
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`abuse, and systems for testing HIV, HCV, HBV, and small molecules. For
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`example, I was Vice President of Technology, Research and Development, and
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`Lab Director, at MedTox Diagnostics, Inc. (“MedTox,” now Labcorp) in
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`Burlington, North Carolina from October 2003 to January 2005. While at
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`MedTox, I led the redesign of over a dozen products in MedTox’s FDA-cleared
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`SURE-SCREEN® product line, including dip strip tests for assaying drugs of
`
`abuse in urine samples. Some of these products were multipanel tests, and some
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`included integrated cups for urine testing. An example of the type of the MedTox
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`SURE-SCREEN® cup I worked on is discussed in a Quick Reference Guide
`
`attached as Appendix B. My work at MedTox led to several issued patents,
`
`including U.S. Patent No. 7,458,942 (“Systems and Methods for Collecting,
`
`Testing and Transporting Liquid Biological Specimens”), U.S. Patent No.
`
`7,285,426 (“Bulking Materials Containing Starch Reagent For Use in Test
`
`Devices”), and U.S. Patent No. 7319,032 (“Non-Sugar Sweeteners for Use in Test
`
`Devices”).
`
`15.
`
`I also worked as Director of Research and Development, and Lab
`
`Director, at Epitope, Inc. (now OraSure Technologies, “OraSure”) in Beaverton,
`
`Oregon, during June 1997 to November 1998. For OraSure, I developed the
`
`Intercept® drug of abuse system, which was oral fluid drug test for screening drugs
`
`of abuse. My experience at OraSure also included developing tests for infectious
`
`diseases such as urine-based HIV tests, the OraQuickTM HIV saliva test, and an
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`oral cancer test using enzyme immunoassay (EIA) and lateral flow strips for saliva
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`samples, among others.
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`III.
`
`In Vitro Device Design Process
`16. The design process for in vitro devices generally involves considering
`
`the problem(s), challenge(s), or need(s) to be addressed. For example, the process
`
`might start by identifying a target for the assay, and considering various
`
`requirements and design constraints, such as user needs, regulatory requirements,
`
`and availability of reagents or other materials. The process usually involves
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`looking at existing solutions, options, and design choices in the field. These may
`
`be found in existing commercial devices, prototypes, literature, and patents in the
`
`field. It sometimes becomes apparent that the market has changed over the years
`
`in such a way that previous inventions do not satisfy market requirements. For
`
`example, new isotypes of viruses might have emerged that require a new test, or
`
`there might be an increased need for different test formats (such as an over-the-
`
`counter version of an existing test). Competition in the marketplace creates
`
`incentives to design new or improved products. Most often, new or improved
`
`products are designed by combining two or more existing features in the art. Many
`
`new or improved products involve implementing straightforward design choices
`
`that do not require much experimentation and are therefore likely to be
`
`implemented successfully.
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`IV. Overview of Technology
`17. By July 14, 1998, a wide variety of systems and methods for detecting
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`the presence or absence, and/or quantifying the amount of, analytes in biological
`
`fluid samples were known in the art. Analytes have long included drugs of abuse
`
`(such as cocaine, opiates, and marijuana) or disease molecules, or indicators of
`
`pregnancy or fertility. The field has seen many advancements since the 1960s,
`
`when researchers first developed systems and methods for testing biological
`
`samples such as urine in addition to or instead of serum. For decades, testing had
`
`to be conducted in a laboratory, with techniques such as radioimmunosorbent
`
`techniques, mass spectrometry and enzyme-linked immunosorbent assays
`
`(ELISAs), and other similar techniques, due to the size, cost, and lack of portability
`
`of the equipment required.
`
`18. Early on, many assays were conducted as “competition” assays, in
`
`which an enzyme labeled antigen or antibody competed with the antigen or
`
`antibody to be detected for a reaction site on a surface to which one member of an
`
`immunologically coupled pair was attached. See, e.g., Ex. 1009, 1:57-64
`
`(explaining that “early ELISAs” were competitive assays). In these assays, the
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`absence of a line in a test zone indicates a positive result, and the presence of the
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`drug. Competition assays were and are frequently used for testing drugs of abuse.
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`See, e.g., U.S. Patent No. 6,808,682 (“Bates”)(Ex. 1013), 1:13-15 (“On-site drug
`
`tests generally use an immunoassay method called antigen-antibody competitive
`
`binding to screen for the presence of drugs.”). Later, researchers developed a
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`“sandwich” assay, in which the antibody or antigen to be detected was
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`“sandwiched” by an immunochemical reaction between a solid surface treated with
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`an immunological species reactive with the species to be detected, and the same or
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`a different reactive immunological species which has been coupled to an enzyme
`
`label. See, e.g., Ex. 1009,1:64-2:6 (explaining sandwich assays). In sandwich
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`assays, the presence of a line in a test zone indicates a positive result.
`
`19.
`
`In the 1980s, researchers developed the first assay devices with test
`
`strips, which yielded much faster results (in minutes, rather than days) more
`
`cheaply. Because assay devices with test strips were smaller, they were portable,
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`and enabled testing in the field and/or at home. Although samples were typically
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`sent to a laboratory for rigorous confirmation of results, portable testing was an
`
`important breakthrough because it allowed prompt testing while samples were
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`fresh. For example, as a 1977 article explains, such “on-site” or “near-patient”
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`testing “has a number of advantages over laboratory-based testing, including the
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`almost immediate availability of results.” Brown E R S, Jarvie D R, Simpson D,
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`Evaluation of Bionike One-Step Tests For The Detection of Drugs of Abuse in
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`Urine, 34 ANN. CLIN. BIOCHEM. 1997, at 74 (“Brown”)(Ex. 1012). The greater
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`convenience and decreased cost made analyte testing a much more prevalent
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`practice in both medicine and law enforcement. As testing became more popular,
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`economies in scale enabled further improvements in assay devices and methods.
`
`20. Numerous assay approaches were developed, including “dipstick,”
`
`“lateral flow,” and “flow-through” devices and methods involving test strips
`
`comprised of a matrix material (e.g., paper, nitrocellulose, etc.). The dipstick
`
`approach typically involves applying a sample to a device with a test strip (such as
`
`by dipping the device itself into a sample), and the presence of the analyte is
`
`indicated by a visually detectable signal such as a change in color. The flow-
`
`through approach typically involves applying a sample to a porous material such
`
`that the sample flows through the porous material and then the analyte in the
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`sample reacts with one or more reagents in the material to produce a detectable
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`signal. The lateral flow approach also typically involves applying a sample to
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`porous material. Instead of drawing the sample through the porous material
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`perpendicularly, however, the sample flows laterally from an application zone to a
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`test or reaction zone, and the captured analyte can be detected by a variety of
`
`protocols, including direct visualization. Many variations of these approaches
`
`were known in the art. The use of color bars and other methods to produce
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`visually observable assay results on test strips contributed to the speed and
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`convenience of prior art assay devices.
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`21. Over time, devices were developed that required fewer steps (e.g., to
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`reduce or eliminate intermediate steps such as washing steps to remove unbound
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`antibody or antigen), further improving the convenience of the devices, and
`
`making them even more accessible to users without significant training or
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`background in the field, and reducing the likelihood of errors caused by incorrectly
`
`performed intermediate steps.
`
`22. The ’291 patent explicitly recognizes that the prior art includes
`
`“chromatographic analyte devices [that] permit an assay to be performed in a
`
`single step (application of an analyte sample to the device)” to produce “visually
`
`observable assay results (such as… those indicated by colored bars on the test
`
`strip).” ‘291 patent (Ex. 1001), 1:11-24. The ‘291 patent also states that the test
`
`strips used in the claimed devices are “conventional in form: therefore because
`
`those of ordinary skill in the art will be abundantly familiar with the design of such
`
`test strips, they will not be described in detail here.” Id., 5:16-19. The ’291 patent
`
`also refers the reader to other prior art patents that “provide a representative sample
`
`of test strip designs known in the art,” including U.S. Patent No. 5,602,040
`
`(“May,” Ex. 1005 hereto, discussed further below) and others. Id., 5:54-6:3.
`
`23. Safety and security were also drivers of innovation in the field. In
`
`testing for drugs of abuse, for example, prevention of tampering has long been an
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`important concern. See, e.g., German Utility Model No. DE 297 02 825
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`(“DE”)(Ex. 1004), 3:19-21, 5:12-13.1 In medical testing, testing personnel often
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`needed to be protected from exposure to the sample, for example to avoid
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`infection. Id., 2:9-10. Many devices with test strips protected the strips via a
`
`housing, casing, or other enclosure. See, e.g., May (Ex. 1005), 3:60-65.
`
`A. Commercial Devices for Drug Testing Were Known in the Art
`24. As discussed above, by July 14, 1998, and well before then, cost and
`
`convenience were strong drivers of innovation in analyte testing. The need for
`
`convenient, safe, simple, and secure drug testing led to the development of a
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`variety of commercial devices that a POSITA would have been familiar with at the
`
`time of the alleged invention. For example, in the 1990s, the Bionike A/QTM Dip-
`
`stick Test detected drugs of abuse by dipping the end of a test strip into a urine
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`sample. Brown (Ex. 1012), 74-75.
`
`
`1 All citations to DE are to Petitioner’s certified English translation. That
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`translation is attached to the original German document in Ex. 1004.
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`The appearance or absence of a control band and a test band indicated whether the
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`test worked correctly, and whether a particular drug was present in the sample. Id.,
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`75, Fig. 1. Drugs of abuse testable via Bionike include amphetamine,
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`methamphetamine, benzodiazepines, cannabinoids, methadone, and opiates. Id.,
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`75. Brown concluded that “the Bionike tests for the detection of drugs of abuse are
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`rapid, simple to use and reliable,” and the “dip-stick tests could be performed
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`without the need to transfer the urine to the sample cup supplied by the
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`manufacturer.” Id., 78. Results could be read in minutes, and “in most cases [the
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`result] was unambiguous.” Id.
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`25. As further reported in the Brown article (Ex. 1012), other commercial
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`devices for on-site drug screening available by July 14, 1998 included the EZ-
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`SCREEN urine test from Environmental Diagnostics, which was based on
`
`antibody-coated cards, the Abuscreen ONTRAK system from Roche Diagnostics,
`
`which was a qualitative latex agglutination immunological slide test, the ONTRAK
`
`TESTCUP from Roche Diagnostics, which was a multi-analyte
`
`immunochromatographic screening method, and the Triage Screening Cassette
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`from Merck, which was based on a competitive immunoassay that simultaneously
`
`detected seven or eight groups of abused drugs. Ex. 1012, 74. Each of these tests
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`were “rapid, reliable, and useful for on-site screening for suspected drug-abuse and
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`for checking for compliance,” but Brown found that Bionike’s products had better
`
`sensitivity and specificity, with fewer false positives. Id., 74-75.
`
`B.
`
`Testing Multiple Analytes With Multi-Strip Devices Was Known
`in the Art
`26. The development of assay devices with test strips opened up new
`
`possibilities for testing multiple analytes simultaneously, either on multiple regions
`
`of a single strip, or on different strips. Devices for testing multiple analytes
`
`simultaneously (e.g., testing a single urine sample for multiple drugs of abuse)
`
`were known in the art by July 14, 1998. DE 297 02 825 (“DE”), 1-2; U.S. Patent
`
`No. 5,976,895 (“Cipkowski”), 1:63-2:10; U.S. Patent No. 5,962,336 (“Sun”), 1:4-
`
`22. Some of these devices also employed a “dipstick” design, with more than one
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`test strip protruding from a housing. As explained in detail below, each primary
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`reference in Petitioner’s Grounds teaches multi-strip devices to be dipped into a
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`urine sample to simultaneously test for more than one type of drug of abuse:
`
`Ex. 1004, Fig. 3.
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`
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` Ex. 1006, Fig. 9.
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`Ex. 1007, Fig. 8.
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`C. Test Strip Construction Was Known in the Art
`27.
`In addition, the ’291 patent discloses that test strip construction was
`
`known in the art. The ‘291 patent acknowledges that the test strips used in its
`
`claimed devices are “conventional in form,” that they are prepared using “means
`
`known in the art,” and use test binders and means for attaching the binders to
`
`porous test strips that are “well-known to those of ordinary still in the art.” Ex.
`
`1001, 5:16-19 & 5:45-60. The ’291 patent even refers the reader to prior art
`
`patents that “provide a representative sample of test strip designs known in the
`
`art.” Id., 5:54-6:30. The incorporated patents disclose assay devices with a variety
`
`of configurations, and were aimed at detecting a variety of analytes— confirming
`
`that, by the time of the alleged invention, a POSITA would have recognized that
`
`teachings in this field could readily be applied across devices. Thus, for example,
`
`changes or improvements in test strip construction disclosed in connection with
`
`one type of assay device could often readily be applied to test strip construction in
`
`connection with a different type of assay device.
`
`28. One of the patents incorporated by reference into the ’291 patent is
`
`U.S. Patent No. 5,602,040 (“May”)(Ex. 1005). Ex. 1001, 5:64-6:4. May, filed
`
`May 12, 1994 and issued Feb. 11, 1997, is an important patent in the field because
`
`(among other things) it teaches one of the first “pee-on strips,” in which a sample
`
`could be applied simply by placing the device under a urine stream, and employed
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`a sealed casing. May discloses using two or more strips side by side in a
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`windowed housing to simultaneously test different samples or reagents for a wide
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`range of uses, including detecting drugs of abuse in urine. Ex. 1005, Abstract,
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`1:37-45, 6:26-39, 15:9-11, Figs. 1-5, 13-14.
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`29. Binders could be specific for each analyte. May teaches the use of
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`labelled and unlabeled “specific binding reagent[s]” on test strips in either
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`“competition” or “sandwich” assays. Ex. 1005, 2:3-3:7. May also teaches a zone
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`showing “the result of the assay” and a “control zone” showing “whether the assay
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`has been completed.” Ex. 1005, 3:65-4:9, 5:8-26, 12:47-53, 12:62-67, 13:27-30,
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`13:55-58.
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`30. Each of the primary references discussed below (DE, Cipkowski and
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`Sun) contain similar teachings regarding test strip construction. DE teaches that
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`each test strip has “T” and “C” zones, which a POSITA would understand to mean
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`“test” and “control” respectively.
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`Ex. 1004, Fig. 3.
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`31. Cipkowski teaches that in the embodiment of Fig. 9, “third ply 41 is
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`provided with an opening 42 through which the test and control lines may be
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`seen.” Id., 4:66-5:7.
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`Fig. 9 shows “T” and “C” zones for each strip, which a POSITA would understand
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`refer to test and control zones. Cipkowski also teaches that:
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`These test strips indicate the presence or absence of the
`following specific drugs of abuse: PCP (P), cocaine (C),
`amphetamines (A), marijuana (M) and opiates (O). Test
`strips 26-30 may be of the type as made by Bionike of
`South San Francisco, Calif. and Applied Biotech, Inc. of
`San Diego, Calif. Such test strips are characterized as
`immunoassay strips and employ colloidal gold chemistry.
`Id., 3:61-67; see also id., 5:51-55 (“The test card thus comprises a number of
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`individual test strips of the immunoassay type and each strip is responsive or
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`indicative to a particular drug of abuse.”).
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`32. Sun teaches that “each strip contains a different antibody at a
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`predetermined site on the strip” so that “a different test may be conducted on each
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`strip.” Ex. 1007, 3:36-39.
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`“If the sample contains the antigen which conjugates with the antibody, colored
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`particles contained within the strip serve as a visual indicator from the specific
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`antigen/antibody reaction” and “[t]he result of the test may be seen through
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`window 128a.” Id., 4:11-35.
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`33. A secondary reference discussed below, U.S. Patent No. 4,943,522,
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`issued July 24, 1990 (“Eisinger”)(Ex. 1009)—also incorporated by reference into
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`the’291 patent (Ex. 1001, 6:1-4)—teaches a “method and apparatus for conducting
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`specific binding pair assays, such as immunoassays” with a “porous membrane
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`capable of non-bibulous lateral flow.” Ex. 1009, Abstract; see also id., 11:45-48
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`(“Multiple analytes in a single sample can be determined with a single apparatus
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`by providing multiple indicator zones so that each indicator binds only one
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`analyte.”), 11:45-48, 16:60-63, 17:51-53, 19:30-34.
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`The membrane has “at least one indicator zone” in which “is affixed a member of a
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`binding pair” and “the sample contains an analyte which is its complementary
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`binding member or an analyte which can be derivatized so as to bind the fixed
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`member.” Id., 4:42-52. Indicator zones 106a and 106b may be viewed through
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`apertures 146a and 146b. Id., 10:62-67, 11:24-29, 12:23-26, Figs. 1, 3.
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`And, as discussed below, multiple indicator zones may be used on a single strip to
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`view the assay results for different analytes. Id., 5:12-18, 11:45-48, 12:23-31,
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`16:60-62, 17:51-53, 19:30-33.
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`34. U.S. Patent No. 5,798,273 (“Shuler”)(Ex. 1010), filed September 25,
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`1996, teaches “a method and assay device for detecting small analytes,” wherein
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`“[t]he results of the assay can be directly read from the device, which is a lateral
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`flow device.” Ex. 1010, Abstract. The assay may be a “competitive inhibition
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`assay.” Id., 1:34-37. In one embodiment, “a sample… suspected of containing
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`specific analyte is added to a preparation of anti-analyte antibody which, with [the]
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`analyte[,] constitutes a specific binding pair.” Id., 1:58-63. Analytes detectable by
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`the assay include hormones and “drugs of abuse.” Id., 2:37-44.
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`35. Figure 1 of Shuler depicts an embodiment with “[a] solid support 1”
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`such as a nitrocellulose membrane, with “a sample addition area 8; a capture area 2
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`having analyte or analyte analog immobilized thereon; and a read-out area 3, with
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`three zones.” Id., 2:45-50. “The solid support employed in the assay is preferably
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`in sheet form, with the substrate in sheet form, generally being in the form of a
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`card, a test strip or dip stick, etc.” Id., 3:39-41. The “read-out area... contains at
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`least one or more zones to provide the desired results and can contain more than
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`three zones or less than three zones if so desired.”