UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
`
`PHARMATECH SOLUTIONS, INC.
`Petitioner
`
`v.
`
`LIFESCAN SCOTLAND LTD.
`Patent Owner
`________________
`
`Case IPR2013-00247
`Patent 7,250,105
`________________
`
`DECLARATION OF JOHN L. SMITH REGARDING
`PATENTABILITY OF U.S. PATENT 7,250,105
`
`
`
`
`
`LIFESCAN SCOTLAND LTD. EXHIBIT 2008
`
`

`
`TABLE OF CONTENTS
`
`Page
`
`BACKGROUND AND QUALIFICATIONS.................................................. 1
`I.
`BASIC ELECTROCHEMISTRY ................................................................... 5
`II.
`III. MEASUREMENT OF GLUCOSE USING GLUCOSE OXIDASE ............ 10
`A. Meters and Disposable Test Strips ...................................................... 10
`B.
`Continuous Measurement With Implantable Electrode ...................... 14
`IV. OVERVIEW OF THE ‘105 PATENT ............................................................ 16
`THE BOARD’S DECISION INSTITUTING INTER PARTES
`V.
`REVIEW ........................................................................................................ 24
`VI. THE PRIMARY REFERENCES, NANKAI AND WINARTA .................... 25
`A. NANKAI ............................................................................................. 25
`1.
`The Board’s Discussion of Nankai ........................................... 25
`2.
`Differences Between Nankai and the ‘105 Patent Claims ........ 28
`B. WINARTA ........................................................................................... 33
`1.
`The Board’s Discussion of Winarta .......................................... 33
`2.
`Differences Between Winarta and the ‘105 Patent Claims ....... 34
`SUMMARY REGARDING PRIMARY REFERENCES ................... 40
`C.
`VII. SECONDARY REFERENCE SCHULMAN ................................................ 41
`A. Overview of Schulman ........................................................................ 41
`B. Differences Between Schulman and the ‘105 Patent Claims .............. 47
`VIII. OPINION OF NONOBVIOUSNESS ........................................................... 53
`The ‘Combination of Nankai Plus Schulman Does Not Suggest
`A.
`the Invention of Claims 1-3 of the ‘105 Patent ................................... 53
`The ‘Combination of Winarta Plus Schulman Does Not Suggest
`the Invention of Claims 1-3 of the ‘105 Patent ................................... 55
`C. One Skilled in the Art Would Not Have Looked to Schulman to
`Address the Goal of Making Accurate Glucose Measurements
`With Disposable Test Strips ................................................................ 56
`Secondary Considerations - Copying .................................................. 61
`The ‘105 Patent Claims Are Not Obvious Over Nankai Plus
`Schulman ............................................................................................. 64
`The ‘105 Patent Claims Are Not Obvious Over Winarta Plus
`Schulman ............................................................................................. 65
`
`
`
`
`
`B.
`
`D.
`E.
`
`F.
`
`

`
`I.
`
`BACKGROUND AND QUALIFICATIONS
`
`1. I, John L. Smith, make this declaration to provide expert opinions and
`
`testimony as contextual background for the Patent Trial and Appeal Board of the
`
`United States Patent and Trademark Office (“Board”) as it considers issues relating
`
`to the patentability of U.S. Patent 7,250,105, (the “105 Patent”) in an inter partes
`
`review requested by Pharmatech Solutions, Inc., Case IPR2013-00247. I have
`
`been retained by the firm of Akin Gump Strauss Hauer & Field LLP on behalf of
`
`the Patent Owner, LifeScan Scotland Ltd.
`
`2. I earned a Bachelor of Science degree in Chemistry in 1965 from Butler
`
`University in Indianapolis, Indiana and a Ph.D. in Analytical Chemistry in 1970
`
`from the University of Illinois at Urbana-Champaign, Illinois.
`
`3. From 1987 through 1998, I was employed by LifeScan, Inc. Between
`
`1987 and 1995, I held the position of Vice President of Research, Development
`
`and Engineering. From 1995 to 1998, I was the Chief Scientific Officer of
`
`LifeScan.
`
`4. In those positions, I was responsible for research and development for
`
`LifeScan’s blood glucose monitoring business. I directed fundamental and applied
`
`research into techniques for measurement of blood glucose, both in-house and
`
`through research contracts worldwide. Because of my earlier experience using and
`
`designing electrochemical instrumentation, and patents I had obtained describing
`
`
`
`

`
`fundamental advances in electrochemical measurement sensitivity, I was familiar
`
`with the advantages of electrochemical blood glucose measurements. I instituted
`
`research and development programs to convert LifeScan’s existing glucose
`
`measurement systems, which had been based on photometric (optical measurement
`
`of color changes due to glucose) systems, to electrochemical measurements. I was
`
`personally involved in the development and evaluation of electrochemical blood
`
`glucose test strips and meters at LifeScan. I have been involved in developing
`
`novel electrochemical instrumentation since 1963, when I was employed as an
`
`analytical technician at the Pitman-Moore Division of the Dow Chemical
`
`Company in Indianapolis, Indiana, and modified a commercial polarograph (a
`
`device that measures the concentration of substances in solution electrochemically)
`
`to add the capability of AC (alternating current) polarography.
`
`5. From 1991 to 1997, I also held the position of Adjunct Professor of
`
`Chemistry at San José State University in San José, CA.
`
`6. From 1984 to 1987, I was employed by Baker Instruments in Allentown,
`
`PA, as Vice President of Research, Development and Engineering for the
`
`development of clinical laboratory instrumentation. From 1978 to 1984, I was
`
`employed by the Technicon Corporation in Tarrytown, NY, as a Staff Systems
`
`Engineer and Director of Decentralized Testing
`
`for clinical
`
`laboratory
`
`instrumentation and physicians’ office testing systems. In this capacity, I
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`
`
`2
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`

`
`supervised and participated in the development of systems for glucose analysis in
`
`point-of-care applications in physicians’ offices and other decentralized testing.
`
`7. Earlier employment after graduate school included positions with
`
`Princeton Applied Research Corporation in Princeton, NJ, as senior applications
`
`chemist and manager of product development for electrochemical instrumentation
`
`from 1974-1978, and Union Carbide Corporation in Tarrytown, NY, as an
`
`analytical chemist from 1970 to 1974.
`
`8. I was employed from 2004-2006 as a consultant, then as Chief
`
`Executive Officer, and later as Chief Technical Officer for Fovioptics, a start-up
`
`company in the field of noninvasive blood glucose monitoring.
`
`9. Since 1998, I have also served as a consultant to more than twenty
`
`investors and companies in the blood glucose monitoring industry.
`
`10. I am the author of several technical publications dealing with clinical
`
`laboratory automation, clinical laboratory analytical instrumentation, and blood
`
`glucose monitoring, and I hold nine U.S. patents in the areas of electrochemical
`
`instrumentation, clinical laboratory instrumentation, and blood glucose testing. I
`
`am the author of a manuscript published on the Internet entitled The Pursuit of
`
`Noninvasive Glucose: “Hunting the Deceitful Turkey” (3rd Edition, 2013). My
`
`resume is included as Exhibit 2009.
`
`
`
`3
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`

`
`11. I am being compensated at the rate of $400.00 per hour. I own no stock
`
`from any of the parties in this action. I receive a monthly pension from Johnson &
`
`Johnson. Johnson & Johnson is the parent company of LifeScan, Inc., which is the
`
`parent company of Diabetes Diagnostics, which is the parent company of LifeScan
`
`Scotland Ltd. My pension or its amount is not dependent in any way on the
`
`outcome of this case.
`
`12. To prepare this Declaration I have reviewed a number of documents,
`
`including the ‘105 Patent, certain filings in the related patent infringement civil
`
`action captioned LifeScan, Inc. v. Shasta Techs., LLC, No. 5:11-CV-04494-EJD.
`
`(N.D.Cal), and filings by the parties and the Decision to Review by the USPTO
`
`Administrative Patent Judges in this inter partes review. I have also examined test
`
`strips from LifeScan labeled as being protected by the ‘105 Patent, and those from
`
`Pharmatech.
`
`13. I agree with the definition of person of ordinary skill in the art given by
`
`Dr. Meyerhoff in the pending litigation between the parties, namely a person of
`
`ordinary skill in the art of the '105 patent would have a bachelor degree in
`
`chemistry or electrical engineering, or an equivalent degree
`
`in
`
`the
`
`sciences/engineering fields (e.g., physics or chemical engineering), and have
`
`experience working in the field of electrochemical glucose sensors for at least five
`
`years. I am providing my opinions from that perspective.
`
`
`
`4
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`

`
`II. BASIC ELECTROCHEMISTRY
`
`14. In aspects material to this Review, the measurement of glucose by
`
`electrochemistry involves measuring the amount of current flowing in an electrical
`
`circuit.
`
`Figure A. Electrical Circuit
`
`In the circuit of Figure A, a battery provides a source of voltage (also called
`
`“potential”) designated by “E” and measured in “volts,” and a resistor, designated
`
`by “R” and measured in “ohms” provides resistance. In a completed circuit, where
`
`all the elements are connected together as shown, a flow of electrons called a
`
`current “I” and measured in “amperes” (often, just “amps”) flows through all the
`
`elements of the circuit. The relationship of these three quantities is given by
`
`Ohm’s Law, which can be written in three ways:
`
`(1) E = I x R (2) I = E ÷ R (3) R = E ÷ I
`
`These state that (1) the voltage in a circuit is equal to the current multiplied by the
`
`resistance, (2) the current is equal to the voltage divided by the resistance, and (3)
`
`the resistance is equal to the voltage divided by the current. If in this circuit, the
`
`
`
`5
`
`

`
`voltage is 1.5 volts and the resistance is 1000 ohms, then the current can be found
`
`by dividing 1.5 by 1000 to give 0.0015 amperes, or 1.5 “milliamps”—thousandths
`
`of an amp (even smaller currents, such as those found in many test strip
`
`measurements, are often expressed in “microamps,” or millionths of an ampere).
`
`Note that in a completed circuit, the same current flows through all the elements,
`
`including the battery, the resistor, and the wires that connect them together.
`
`15. If a substance is in solution, chemical reactions can be made to occur by
`
`passing electricity between a pair of electrodes placed in the solution.
`
`Figure B. An Electrochemical Circuit
`
`
`A voltage is applied to the two electrodes, an anode and a cathode, which are made
`
`of metal or other electrically conductive materials. In response to this applied
`
`voltage, chemical reactions occur in the solution at the two electrodes; these
`
`reactions are called “oxidation” at the anode (where electrons are removed from
`
`the anode material) and “reduction” at the cathode, (where electrons are added to
`
`
`
`6
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`

`
`the cathode material). Each substance has a property known as its “oxidation
`
`potential” (or conversely, as its “reduction potential”) which specifies the voltage
`
`at which the reaction for that substance begins to occur. If the applied voltage is
`
`less than the oxidation potential for the substance in solution, no current will flow,
`
`but once the voltage exceeds the oxidation potential, a current will flow which can
`
`be used to measure the concentration of the substance.
`
`16. To measure a substance using electrochemical techniques, at least the
`
`two electrodes listed above (an anode and a cathode) must be present in a
`
`conductive medium such as water with dissolved salts or blood. One of these
`
`electrodes is termed the “working electrode” where the reaction that measures the
`
`substance of interest is carried out; another is termed the “reference electrode.”
`
`The ‘105 Patent and some other prior art citations use the term “sensors” as an
`
`equivalent term for “electrodes,” and in some two-electrode systems, the reference
`
`electrode may also be referred to as a “counter/reference electrode.” In the systems
`
`of interest in blood glucose strips, the working electrode is generally the anode,
`
`which has a positive voltage applied to it, and a substance in the solution is
`
`oxidized at that electrode to create the measured current. However, in other
`
`electrochemical systems, for example the measurement of oxygen in solution, the
`
`substance being measured is reduced at the working electrode, which is in this case
`
`the cathode, and has a negative voltage applied to it.
`
`
`
`7
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`

`
`17. In order to cause the electrochemical reaction to occur, a specific voltage
`
`(equal to or higher than the oxidation potential of the substance being measured)
`
`must be applied to the working electrode. The reference electrode, rather than just
`
`being a conductive material, is specially configured to establish a reference point
`
`against which the voltage at the working electrode can be established. A suitable
`
`reference electrode for glucose measurements can be constructed using a small
`
`amount of silver metal in contact with silver chloride, or by coating a material
`
`called a “mediator” onto the surface of a conductive material such as gold or
`
`carbon. When a potential equal to or greater than the “oxidation potential” of the
`
`substance to be measured is applied to the working electrode, with respect to the
`
`reference electrode, current will flow which is proportional to the concentration of
`
`that substance.
`
`18. However, the same current that flows at the working electrode must flow
`
`throughout the completed circuit, and current flowing at the reference electrode
`
`can cause reactions to occur there that can disturb its operation as a reference
`
`electrode. To prevent this complication, electrochemists have devised a “three
`
`electrode” system that solves this problem. A circuit diagram illustrating a two
`
`electrode system, based on Figure B above, is shown in Figure C, and the
`
`arrangement of the three electrodes in an electrochemical cell is shown in Figure
`
`D:
`
`
`
`8
`
`

`
`
`
`In this scheme, an external electronic circuit is configured so that virtually all the
`
`current flows between the working electrode and a third electrode, called a
`
`“counter electrode,” leaving the reference electrode essentially out of the current-
`
`carrying part of the circuit and allowing it to perform its reference function
`
`undisturbed. This is also particularly of value in systems where the solution is
`
`poorly conducting (i.e., has a high resistance or what is termed a large “IR drop,”
`
`referring to the voltage error that would result from multiplying the current “I” by
`
`the solution resistance “R” to give the resultant voltage), which could otherwise
`
`result in errors in the voltage actually applied to the working electrode.
`
`19. It is desired to have the applied voltage, denoted in Figure C by Vapp,
`
`fully appear at the working electrode with respect to the reference electrode. Any
`
`resistance Rs in the solution is multiplied by the current I to give the voltage drop
`
`Vir = I x Rs occurring in the solution. As a result, the voltage applied to the
`
`
`
`9
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`

`
`working electrode is equal to Vapp –Vir, or less than the intended Vapp. As an
`
`example, in a system where 1.0 volts is required at the working electrode, if the
`
`solution resistance was 500 ohms and the current flowing was 1 milliamp, the “IR
`
`drop” of the solution would be 500 x 0.001, or 0.5 volts. A voltage of 1.0 volts
`
`applied between the two electrodes would result in 0.5 volts being lost to the
`
`solution resistance, and the voltage at the working electrode would be only 0.5
`
`volts instead of 1.0 volts.
`
`20. In a three-electrode arrangement (Figure D), the third “counter”
`
`electrode is configured through external electronic circuitry to carry the bulk of the
`
`current that results from the electrode reaction, and is useful when the solution
`
`resistance is high. The three-electrode measurement system prevents this “IR
`
`drop” from causing voltage errors at the same time that it protects the function of
`
`the reference electrode.
`
`III. MEASUREMENT OF GLUCOSE USING GLUCOSE OXIDASE
`
`A.
` Meters and Disposable Test Strips
`21. Systems composed of meters and disposable
`
`test strips using
`
`electrochemical methods are in use by people with diabetes to measure the amount
`
`of glucose in their blood. The test strips contain several chemical components that
`
`react with glucose in a sample of blood to produce a current at an electrode, and
`
`that current is proportional to the glucose concentration. (Other electronic circuitry
`
`
`
`10
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`

`
`and computer chips in the glucose meter convert this current to a glucose value that
`
`is displayed to the user.) These chemical components include an enzyme,
`
`frequently one called glucose oxidase, and a “mediator” that transfers electrons
`
`from the enzyme to the electrode. In many systems, this mediator is the compound
`
`“sodium ferricyanide.”
`
`22. The overall chemical reaction is written:
`
`Glucose + O2 (Oxygen) + H2O  Gluconic acid + H2O2 (Hydrogen peroxide) + e- (electrons)
`
`23. The full sequence of reactions that occurs is illustrated in Figures E:
`
`
`
`Figure E
`
`11
`
`
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`
`
`

`
`24. The sequence of reactions in Figure E can be read to say (top sequence):
`
`as glucose is oxidized to gluconic acid by the enzyme glucose oxidase, electrons
`
`are transferred from glucose to the enzyme and the enzyme is converted to a
`
`reduced form. The reduced form of the enzyme then transfers electrons to the
`
`oxidized form of the mediator, converting it to the reduced form while the enzyme
`
`is simultaneously converted back to its oxidized form. The reduced form of the
`
`mediator is then oxidized at the working electrode as it transfers electrons to the
`
`working electrode surface, causing current to flow in an external circuit. As a
`
`result of the sequence of reactions, the amount of current flowing in the external
`
`circuit is proportional to the glucose concentration.
`
`25. The second line of Figure E illustrates the complementary reaction that
`
`takes place at the counter (or counter/reference) electrode, where electrons are
`
`transferred to oxidized mediator molecules, converting them to reduced mediator
`
`and completing the circuit.
`
`26. The enzyme and mediator act as a sort of electron “bucket brigade” to
`
`transport electrons from glucose to the working electrode. As the reduced
`
`mediator (produced by the oxidation of glucose) is oxidized at the working
`
`electrode, oxidized mediator is reduced at the reference (or counter) electrode,
`
`providing the complementary electrochemical reaction at the other electrode to
`
`complete the circuit. Both the enzyme and the mediator participate in the reaction
`
`
`
`12
`
`

`
`at the working electrode as “catalysts”—materials that assist in carrying out a
`
`chemical reaction, but which are continuously recycled and not consumed in the
`
`reaction, in contrast to glucose and oxygen which are consumed. A pictorial
`
`representation of this sequence is shown in Figure F:
`
`Figure F. (Ben Feldman, Electrochemistry Encyclopedia,
`http://electrochem.cwru.edu/encycl/art-g01-glucose.htm)
`
`
`
`27. A simpler reaction scheme would result if the reduced form of the
`
`enzyme were able to interact directly with the electrode (that is, transfer electrons
`
`directly to it); but because many enzymes are large and bulky protein molecules,
`
`the site where electrons are transferred is often buried within the molecule and
`
`cannot be directly connected to an electrode surface. The mediator, being a much
`
`smaller molecule, is able to move into this buried site, transfer electrons, and then
`
`diffuse to the electrode surface to create the analytical current.
`
`
`
`13
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`

`
`B. Continuous Measurement With Implantable Electrode
`28. When an electrode is implanted within the body (in either tissue or a
`
`blood vessel), for continuous glucose monitoring, multiple measurements are made
`
`over several days with the same electrode. Because multiple measurements are
`
`required, a different approach is used to measure glucose than is used with meters
`
`and disposable test strips.
`
`29. Rather than applying blood or other body fluids to the electrode, and
`
`measuring the current generated by the reduction of mediator, glucose is measured
`
`by an extension of the initial reaction above:
`
`Glucose + O2 (Oxygen) + H20  Gluconic acid + H2O2 (Hydrogen peroxide) + e- (electrons)
`
`
`
`Here, the concentration of glucose is measured by measuring a decrease in the
`
`amount of oxygen (or by measuring the amount of hydrogen peroxide produced) as
`
`a result of the reaction. The enzyme and electrodes are kept within a membrane
`
`that allows glucose and oxygen to diffuse in, but prevents the enzyme from
`
`diffusing out into the body (if this approach were not used, the enzyme could drift
`
`away from the electrode and would not be present to react with glucose where it is
`
`needed, and also because the enzyme could react with the body to create an
`
`immune response).
`
`
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`14
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`

`
`30. When this method of measuring glucose is used, that is by measuring the
`
`decrease of oxygen due to its reaction with glucose, the resulting scheme is often
`
`termed an “oxygen electrode” or an “enzyme electrode.” In this system, the
`
`oxygen concentration is measured directly at the electrode and no mediator is used.
`
`The amount of oxygen initially present in the blood before reaction with glucose is
`
`measured, the reduced amount present after reaction is also measured, and the
`
`glucose concentration is calculated by subtracting the second oxygen concentration
`
`from the first. In order for this system to give accurate results for a single
`
`measurement of glucose, two electrodes capable of measuring oxygen must be
`
`present at two locations - one near the enzyme where the oxygen concentration is
`
`reduced by its reaction with glucose and another far enough away that the oxygen
`
`concentration is not changed by the enzyme reaction.
`
`31. While both disposable test strips and implanted electrodes use glucose
`
`oxidase as the enzyme to carry out a reaction with glucose, the method of
`
`measurement each uses is completely different. Additionally, the computation of
`
`glucose concentration is reversed — the measurement of current is directly
`
`proportional to the glucose concentration in disposable test strips, while an inverse
`
`proportion measurement based on the difference between a pair of separate oxygen
`
`measurements is used in implanted electrodes. In the former scheme, the current
`
`generated is directly proportional to the glucose in the fluid being measured so the
`
`
`
`15
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`

`
`greater the amount of glucose present, the larger the current. In the latter scheme,
`
`the more glucose present, the smaller the amount of oxygen that is present at the
`
`electrode after reaction, and the smaller the amount of current is measured with
`
`increasing glucose concentrations.
`
`IV. OVERVIEW OF THE ‘105 PATENT
`
`32. The ‘105 Patent, entitled “Measurement of Substances in Liquids,” filed
`
`May 7, 2003, was issued July 31, 2007, and lists Oliver W. H. Davies as the first
`
`named inventor. It is a continuation of application 09/521,163 filed March 8, 2000,
`
`which later issued as U.S. Patent No. 6,733,655 (“655 Patent”).
`
`33. Diabetes is a disease in which the body is unable to either manufacture
`
`or properly utilize insulin. People with diabetes need to make frequent
`
`measurements of the amount of glucose in their blood to prevent both the chronic
`
`complications of high levels (“hyperglycemia”) and the acute danger of low levels
`
`(“hypoglycemia”). A variety of blood glucose measurement systems, based on
`
`disposable test strips and electronic meters they work with, are available
`
`commercially
`
`to make
`
`those measurements.
`
` Obtaining accurate glucose
`
`measurements with these systems is of paramount importance because patients
`
`adjust their food intake and/or insulin doses based on the measurements.
`
`Inaccurate measurements can have dire results for patients.
`
`
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`16
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`

`
`34. The '105 Patent is directed generally to measurement of glucose in
`
`whole blood based on disposable test strips that use the electrochemical
`
`measurement techniques described in ¶¶21-27, supra. Electric current is measured
`
`between two sensor parts (or electrodes) called the working and reference sensor
`
`parts. (‘105 Patent, col. 1, lns. 27-29). (Note that the ‘105 Patent uses the term
`
`“sensor parts” to refer to electrodes.) The working sensor part/electrode
`
`comprises a layer of enzyme reagent, the current being generated by the transfer of
`
`electrons from the enzyme substrate, via the enzyme and an electron mediator
`
`compound, to the surface of a conductive electrode (‘105 Patent, col. 1, lns. 29-33).
`
`The current generated is proportional to both the area of the sensor part/electrode
`
`and the concentration of glucose in the test sample (‘105 Patent, col. 1, lns. 33-35).
`
`35. Inaccurate results can be obtained if the working sensor part/electrode is
`
`not fully covered with blood, since its effective area is then reduced, or if a
`
`manufacturing defect or other accident has damaged or resulted in incomplete
`
`coverage of the working sensor part/electrode (‘105 Patent, col. 1, lns. 39-64). The
`
`‘105 Patent discloses (col. 4, lns. 41-64) that the test strips are fabricated in a series
`
`of screen printing steps, and there is always the remote possibility that small pieces
`
`of foreign material could cover a part of the electrode and prevent contact there by
`
`the blood sample. Alternatively, because screen printing is done by pushing
`
`material through small holes in a screen, if one or more screen holes were blocked
`
`
`
`17
`
`

`
`by debris, there could be small voids that would reduce the area of an electrode. At
`
`the same time, there is a need to minimize the sample volume required for an
`
`accurate test, to minimize discomfort and inconvenience to the patient. The
`
`inventors sought
`
`to achieve greater reliability and accuracy
`
`in glucose
`
`measurements by providing a way to (1) ensure that an adequate volume of blood
`
`had been introduced to cover the entirety of the working electrode of a test strip,
`
`and (2) ensure the electrodes (“sensors” in the terminology of the ‘105 Patent)
`
`were not defective due to manufacturing irregularities, while (3) not increasing the
`
`volume of blood required for testing (‘105 Patent, col. 2, lns. 49-60). They did
`
`this, in material part, by (1) by providing two independent working sensor
`
`parts/electrodes at which two separate glucose measurements could be carried out,
`
`(2) by placing a common reference electrode upstream of each of the two working
`
`sensor parts/electrodes, (3) by placing
`
`the
`
`independent working sensor
`
`parts/electrodes along the flow of the blood sample so that one of the working
`
`sensor parts/electrodes can be completely covered before the other begins to be
`
`covered, and (4) developing a method in which the electric current measured at
`
`each of the working sensor parts/electrodes is compared to establish a difference
`
`parameter, and an error is indicated if the difference parameter exceeds a
`
`predetermined threshold.
`
`
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`18
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`

`
`36. Referring to the embodiment depicted in Fig. 2 of the ‘105 Patent, the
`
`test strips of the Patent employed a reference sensor part/electrode (on Element 4b
`
`of Fig. 2, referred to as a “counter/reference sensor part” (col. 4, ln. 45) and two
`
`working sensor parts/electrodes where glucose measurements are made (on
`
`Elements 6b and 8b), each of which is connected through conducting connectors
`
`(Elements 6a and 8a) to separate current measuring circuits in a blood glucose
`
`meter.
`
`
`
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`Figure G
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`37. In Figure H below (an enlargement of the top part of Fig. 2), the
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`conductive paths shown in the patent’s Fig. 2 are overlaid first with the insulating
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`mask material shown as Element 12 in the Fig. 3 (Element 12, shown in gray and
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`placed over the conductive traces in Figure H, then coated with a layer of glucose
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`oxidase enzyme (element 14 from the Fig. 4, shown in orange in Figure H):
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`The exposed areas that are defined by the opening in the insulating mask over the
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`conductive material, and that are coated with the glucose oxidase enzyme, become
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`the two working sensor parts/electrodes (shown as red rectangles in Figure H)
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`where glucose is measured. The reference sensor part/electrode area on element 4b
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`is shown in blue in Figure H.
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`38. When a drop of blood is applied to the distal end (at the top of the
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`rectangular strip as depicted in Fig. 2 in Figure G), it flows along the channel in the
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`strip, flowing across, in order, the electrodes on elements 4b, 6b, and 8b (those
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`elements are the reference electrode and the two working electrodes). After a
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`predetermined delay, the amount of current flowing in two measurement circuits
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`connected to the two electrodes is compared, and if the difference between the two
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`currents is greater than a threshold difference parameter, the system reports an
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`error condition. A difference greater than the threshold could indicate (1) that not
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`enough blood was introduced into the strip to completely cover the second working
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`electrode, (2) that the two electrodes were not of identical area, or (3) that there
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`was a defect in or debris on one of the electrodes that produced a difference in
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`current. Regardless of the cause, a test made in which the current difference
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`between the two working electrodes is greater than the threshold percentage is
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`considered erroneous, and instead of a glucose concentration value, indication of
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`an error is displayed to the user. If the difference between the two measured
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`working electrode currents is not greater than the predetermined threshold, the sum
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`of the currents or the mean value of the currents may be converted to a glucose
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`level by the measuring device (col. 4, lns. 7-13; col. 5, lns. 26-33).
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`39. The three claims in the ‘105 Patent are as follows:
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`1. A method of measuring the concentration of a substance in a sample
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`liquid comprising the steps of:
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`providing a measuring device said device comprising:
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`a first working sensor part for generating charge carriers in
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`proportion to the concentration of said substance in the sample
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`liquid;
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`a second working sensor part downstream from said first
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`working sensor part also for generating charge carriers in
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`proportion to the concentration of said substance in the sample
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`liquid wherein said first and second working sensor parts are
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`arranged such that, in the absence of an error condition, the
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`quantity of said charge carriers generated by said first working
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`sensors part are substantially identical to the quantity of said
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`charge carriers generated by said second working sensor part;
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`and
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`a reference sensor part upstream from said first and second
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`working sensor parts which reference sensor part is a common
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`reference for both the first and second working sensor parts,
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`22
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`said reference sensor part and said first and second working
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`sensor parts being arranged such that the sample liquid is
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`constrained to flow substantially unidirectionally across said
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`reference sensor part and said first and second working sensor
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`parts; wherein said first and second working sensor parts and
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`said reference sensor part are provided on a disposable test
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`strip;
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`applying the sample liquid to said measuring device;
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`measuring an electric current at each working sensor part proportional
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`to the concentration of said substance in the sample liquid;
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`comparing the electric current from each of the working sensor parts
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`to establish a difference parameter; and
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`giving an indication of an error if said difference parameter is greater
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`than a predetermined threshold.
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`2. The method as claimed in claim 1 comprising measuring the current at
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`each working sensor part after a predetermined time following application of
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`the sample.
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`3. The method as claimed in claim 1 wherein the substance to be measured
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`is glucose, and each of the working sensor parts generates charge carriers in
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`proportion to the concentration of glucose in th