UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`Dexcom, Inc.,
`Petitioner
`
`v.
`
`
`
`WaveForm Technologies, Inc.,
`Patent Owner
`
`Case No: IPR2017-01051
`U.S. Patent No. 7,529,574
`
`
`PETITIONER’S REPLY TO PATENT OWNER RESPONSE
`
`
`
`
`
`
`
`

`

`TABLE OF CONTENTS
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`
`Page
`
`
`I.
`II.
`
`Introduction ..................................................................................................... 1
`The Petition Provided Two Alternate Paths Of Combining Hagiwara
`Embodiments To Arrive At The Claimed Invention ...................................... 3
`III. The Petition Established Numerous Reasons To Combine To Support
`The Two Paths ................................................................................................ 4
`A. Hagiwara’s Disclosure Is Written To Indicate That The
`Disclosed Polarography Sensors Are Configurable For Sensing
`A Variety Of Analytes As Desired ....................................................... 5
`The Petition Provided Several Motivations For Path A
`Including Hagiwara’s Express Teaching To Add A 1(D)
`Enzyme Layer to The 1(A) Embodiment ............................................. 8
`The Petition Detailed Several Motivations For Path B Including
`An Express Teaching Of Implementing An Enzyme Sensor
`With A Side-Facing Sensor Window ................................................. 14
`IV. Patent Owner’s Remaining Arguments Are Red Herrings .......................... 17
`A.
`Patent Owner’s Primary Argument Regarding Heparin-Induced
`Thrombocytopenia (HIT) Has No Basis In Law Or Reality .............. 17
`1.
`There Is No Legal Precedent For The POSITA To
`Wholly Disregard A Reference Because Of An Allegedly
`Suboptimal Feature .................................................................. 17
`The POSITA Would Not Have Avoided Hagiwara Based
`On Its Suggested Use Of Heparin ............................................ 18
`The Response’s Complaints Regarding Unsuitability For
`Intended Purpose Are Unfounded ...................................................... 21
`1.
`There Are No Enablement Or Undue Experimentation
`Issues With Features Actually Claimed ................................... 21
`Patent Owner’s Attempt To Import Limitations Into The
`Claims Is Improper................................................................... 22
`V. Dependent Claims 2, 3, 13, and 14 ............................................................... 30
`VI. Conclusion .................................................................................................... 32
`
`B.
`
`C.
`
`B.
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`2.
`
`2.
`
`
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`
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`-i-
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`

`

`TABLE OF AUTHORITIES
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`
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`Page
`
`
`
`CASES
`
`Boston Scientific Scimed, Inc. v. Cordis Corp.,
`554 F.3d 982 (Fed. Cir. 2009) .......................................................... 12, 13, 14, 16
`
`Costco Wholesale Corp. v. Robert Bosch LLC,
`IPR2016-00039, Paper 69 (PTAB, Mar. 30, 2017) ............................................ 18
`
`DISH Network v. TQ Beta, LLC,
`IPR2015-01756, Paper 31 (PTAB, Jan. 30, 2017) ............................................. 21
`
`eBay Inc. v. Global Equity Management,
`IPR2016-01829, Paper 13 (PTAB, Apr. 21, 2017) ............................................ 22
`
`Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd.
`821 F.3d 1359 (Fed. Cir. 2016) .......................................................................... 22
`
`Plas-Pak Indus. v. Sulzer Mixpac AG,
`600 F. App’x. 755 (Fed. Cir. 2015) .............................................................. 17, 18
`
`Trustees of Columbia University v. Illumina, Inc.,
`Appeal No. 2014-1547 (Fed Cir. 2015) .............................................................. 23
`
`
`
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`-ii-
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`
`
`I.
`
`Introduction
`
`U.S. Patent No. 7,529,574 (the ’574 Patent or the ’574) is a patent on a
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`mechanical structure “innovation.” The specification states, “When dip coating
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`viscous liquids onto [a] relatively large area, it has been quite difficult to construct a
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`coating having a thickness sufficient to produce an adequate response to the presence
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`of glucose.” Ex. 1001, 1:11-14. The Patent Owner’s Response (“Response”) admits
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`that “the use of two nubs of dielectric material to support an enzyme layer is the
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`foundation of the ’574 Patent invention.” Response, 11.1
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`The ’574 has nothing to do with membrane chemistry related to analyte sensors
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`and contains zero new disclosure about the types and arrangement of membranes of
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`an analyte sensor. Instead, the patent depicts only a dip coated “material 24” (yellow
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`below) made up “of a set of layers that are constructed through a sequence of dip
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`coating operations interspersed with curing operations.” Ex. 1001, 1:65-2:1.
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`
`
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`1 Emphasis is added herein unless otherwise noted.
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`-1-
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`Petition, 3. The specification relies entirely on the Wilson prior art patent for the
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`composition of these layers and incorporates Wilson by reference for further details
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`of membrane arrangement and composition. Id., 2:1-4.
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`The Response distracts from the fact that the prior art teaches the “foundation”
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`of the invention by reading limitations into the claims that rely on the features of
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`Wilson, and by asserting that the prior art can be ignored based on an allegedly
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`dangerous feature. But regarding the real issues in this case, Patent Owner’s declarant
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`admits that the Hagiwara prior art combination shown below discloses the claimed
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`nubs and surrounding enzyme layer, i.e., the “foundation” of the invention. Ex. 1021,
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`170:16-19; 170:24-171:5.
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`Petitioner’s Illustration of Hagiwara’s Figs. 1(A) + 1(D)
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`And the reasons to combine the teachings of this single reference are solid. Thus, the
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`instituted obviousness ground is sound.
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`-2-
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`II. The Petition Provided Two Alternate Paths Of Combining Hagiwara
`Embodiments To Arrive At The Claimed Invention
`The Petition proved that it would be obvious to combine the teachings of
`
`Hagiwara 1(A) and 1(D) in two alternate ways to arrive at the claimed subject matter.
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`First, the POSITA could add 1(D)’s enzyme layer 12 to 1(A) as taught by Hagiwara
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`(Ex. 1005) 3:3-37. Petition, 47-51; Ex. 1006, ¶¶147-152, 154. Alternatively, the
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`POSITA could implement 1(D)’s glucose sensor with the side-facing sensor window
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`of 1(A) as suggested by Hagiwara 6:42-7:5. Petition, 40, 52; Ex. 1006, ¶¶48, 73, 147,
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`155.
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`The following diagram illustrates these two alternative paths. Path A starts with
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`1(A) and adds 1(D)’s enzyme layer to tailor the 1(A) generic sensor into one that can
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`sense glucose. Path B starts with 1(D) and incorporates the side-sensing window of
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`1(A) instead of an end-facing window. Both paths result in a structure that falls within
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`the scope of the claims.
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`
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`-3-
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`
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`Path A: Petition, 47-51; Ex. 1006, ¶¶ 147-152, 154. Path B: Petition, 40, 52; Ex. 1006,
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`¶¶48, 73, 147, 155.
`
`III. The Petition Established Numerous Reasons To Combine To Support
`The Two Paths
`A goal of the Patent Owner’s Response was to distract from what Hagiwara
`
`actually teaches. Thus, the following sections provide a recap of: (1) Hagiwara
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`generally to highlight the Petition-outlined context of why the reasons to combine
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`
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`-4-
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`Hagiwara in the proposed ways are so strong (Section A); (2) motivations for Path A
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`including how Hagiwara expressly suggests adding a 1(D) enzyme layer to 1(A)
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`(Section B); and (3) motivations for Path B including how Hagiwara expressly
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`suggests implementing a 1(A) side-facing window in a 1(D) enzyme sensor
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`(Section C).
`
`A. Hagiwara’s Disclosure Is Written To Indicate That The Disclosed
`Polarography Sensors Are Configurable For Sensing A Variety
`Of Analytes As Desired
`It is clear that Hagiwara intended its disclosed sensors to be modified according
`
`to the needs or desires of a user. Ex. 1006, ¶¶150, 153-155. The reference says “[i]n
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`general, the concentration of an oxidizing substance or a reducing substance contained
`
`in an aqueous solution can be measured through polarography using a measuring
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`electrode.” Id., 3:3-4. The remainder of page 3 describes how to tailor a generic
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`measuring electrode to measure a concentration of a substance. Petition, 50-52;
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`Ex. 1006, ¶¶101, 147-150.
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`Specifically, page 3, lines 5-12 describes setting up a polarography sensor for
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`detection of oxygen (an oxidizing substance), which requires applying a -0.5 to -0.7V
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`bias voltage to a generic measuring electrode functioning as a cathode. That same
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`generic measuring electrode can sense hydrogen (a reducing substance) by changing
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`-5-
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`

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`
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`the bias voltage applied to the measuring electrode to +0.1 to 0.4V such that it
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`functions as an anode, as described at lines 13-23.2
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`Hagiwara then states, “[t]his type of measuring method can also be applied to
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`oxidizing substances and reducing substances other than O2 and H2.” Ex. 1005,
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`3:23-24. Specifically, “the concentrations of substances targeted for measurement can
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`be measured… by fixing enzymes, which act in [such] substances…, on reaction
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`surfaces of measuring electrodes.” Id., 3:26-30. Hagiwara notes numerous substances
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`detectable via indirect polarography using enzymes including glucose. Id., 3:38-43.
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`Petition, 50, Ex. 1006, ¶150.
`
`Hagiwara explains how to configure a generic measuring electrode by fixing
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`glucose oxidase “on a surface made of a precious metal.” Ex. 1005, 3:30-37. Glucose
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`concentration is derivable from a measurement of either O2 or H2O2 using the enzyme-
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`coated sensor. Id., 3:33-36. Hagiwara describes the cathodic reduction method to
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`measure O2 concentration at 3:5-12 (i.e., using a bias voltage of -0.5 to -0.7V).
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`Id., 3:34-35. The reference describes measuring H2O2 concentration based on the
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`formula identified at 3:35-37 to sense electrons as for H2. Petition, 50, Ex. 1006, ¶150.
`
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`2 Dr. Smith agrees that -0.5V to -0.7V and 0.1V to 0.4V are sensible ranges for
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`measuring O2 and H2, respectively. Ex. 1021, 74:10-15; 80:7-9.
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`
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`-6-
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`Hagiwara 1(A), 1(B), and 1(C) depict different form factors for generic
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`measuring electrodes. That is, the 1(A)-1(C) measuring electrodes are presented in a
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`target-substance-agnostic manner. Hagiwara only describes the underlying structures
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`of electrodes, not the substance sensed.
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`Figure 1(A) illustrates a generic sensor having a side-facing sensor window.
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`Ex. 1005, 5:2-6:2.
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`
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`
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`The 1(D) embodiment selects features from the prior embodiments (i.e., the
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`insulating layer 4 and reference electrode configuration from 1(A) and the end-facing
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`sensor window of 1(B) and 1(C)). The 1(D) embodiment senses a desired analyte
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`through use of an enzyme layer 12 on the electrode reaction surface 2 by adjusting the
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`bias voltage for sensing oxygen or H2O2 as previously described. Id., 6:42-7:5;
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`Petition, 40-41; Ex. 1006, ¶¶73-74.
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`
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`The table below illustrates that the only differences between 1(A) and 1(D) are
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`1(A)’s use of a side-facing sensor window and 1(D)’s inclusion of an enzyme layer.
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`-7-
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`
`Configuration
`1(A)
`1(B)
`1(C)
`1(D)
`
`Missing Attributes
`Possesses Attributes3
`8,9,10,11,12
`1,2,3,4,5,6,7, side-facing
`7,10,11,12
`1,2,3,4,5,6,8,9, end-facing
`8,9,12
`1,2,3,4,5,6,7,10,11, end-facing
`1,2,3,4,5,6,7,12, end-facing
`8,9,10,11
`Feature Comparison Across Hagiwara Configurations
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`This table shows the slight adjustments that can be made to any of the configurations
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`to have attributes of one or more of the other configurations according to the needs of
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`a user. In particular, only a trivial adjustment need be made to configurations 1(A)
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`and 1(D) to arrive at the claimed subject matter (i.e., adding enzyme layer 12 to 1(A)
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`or changing 1(D)’s end-facing window to a side-facing window).
`
`B.
`
`The Petition Provided Several Motivations For Path A Including
`Hagiwara’s Express Teaching To Add A 1(D) Enzyme Layer To
`The 1(A) Embodiment
`Regarding Path A, where an enzyme layer 12 is incorporated into 1(A), page 3
`
`of Hagiwara describes polarography techniques to configure Hagiwara’s working
`
`electrodes to sense an analyte of interest. Lines 3-26 state that oxygen and hydrogen
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`can be sensed merely by setting an appropriate bias voltage to a generic (i.e., non-
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`enzyme) working electrode. Hagiwara then states:
`
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`3 Attributes here correspond to the mechanical aspects of the sensor designs as
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`labeled 1-12 on the Hagiwara figures. Like reference numbers are used across
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`embodiments to refer to common structures.
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`-8-
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`
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`In many cases, the concentrations of substances targeted for
`measurement can be measured…by fixing enzymes…on reaction
`surfaces of measuring electrodes and in the vicinities thereof…In an
`example where glucose is measured, glucose oxidase is fixed on a
`measuring electrode surface made of a precious metal, and in the
`vicinity thereof, as an enzyme.
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`Ex. 1005, 3:26-32; Petition, 48-51; Ex. 1006, ¶¶147-152, 154. Thus, page 3 of
`
`Hagiwara explicitly teaches the POSITA to start with a generic working electrode like
`
`the one depicted in 1(A):
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`Patent Owner’s Rendition of Hagiwara 1(A)
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`
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`and to add an enzyme layer (e.g., a glucose oxidase layer), like the one shown in 1(D)
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`in green:
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`-9-
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`Patent Owner’s Rendition of Hagiwara 1(D)
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`“on reaction surfaces of measuring electrodes and in the vicinities thereof” to form a
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`sensor for sensing analytes like glucose. Id., 3:26-43. Petition, 48-51; Ex. 1006,
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`¶¶147-152, 154. Incorporating the 1(D) green enzyme layer between the pink 5 and
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`purple 6 membrane layers of 1(A), as taught at 6:42-46, results in the claimed
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`structure:
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`
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`-10-
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`Petitioner’s Illustration of 1(A) + 1(D)4
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`
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`The combination would have had a reasonable expectation of success, as evidenced
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`by the arrangement of the same three membrane layers in the same order in the 1(D)
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`embodiment, with the only difference being the use of a tip-sensor window in 1(D)
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`instead of a side-sensor window. Petition, 52.
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`
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`Beyond the express instructions in Hagiwara to incorporate an enzyme layer
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`into a generic electrode to configure it to sense an analyte of interest, the Petition also
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`noted the following motivations to combine according to Path A: (1) selecting layer
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`12 from 1(D) to incorporate into 1(A) is nothing more than combining prior art
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`elements according to known methods to yield predictable results (i.e., applying the
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`4 Dr. Smith admits that this Hagiwara combination discloses the claimed nubs and
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`surrounding enzyme layer, i.e., the “foundation” of the invention. Ex. 1021,
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`170:16-19; 170:24-171:5.
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`-11-
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`
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`three membrane layers of 1(D) to the slightly different structure of insulation/sensor
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`window of 1(A)) (Petition, 51; Ex. 1006, ¶147); (2) the combination is a simple
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`substitution of one known element (the membrane arrangement of 1(D)) for another
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`(1(A)’s membrane arrangement) to obtain predictable results, where a POSITA would
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`understand that enzyme layer 12 could predictably be positioned between layers 5 and
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`6 as disclosed in 1(D) (Petition, 51; Ex. 1006, ¶151); and (3) the combination is
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`desirable “for commercial reasons, to provide a mechanism for generating clinical and
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`research data through continuous monitoring and to improve human well-being
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`through the use of real time data for analytes (e.g., glucose) critical to health”
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`(Petition, 49; Ex. 1006, ¶150; Ex. 1005, 4:1-6).
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`
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`It is noteworthy that the Federal Circuit found claims obvious in a case with
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`facts highly analogous to those here. The Boston Scientific case, cited in the Petition
`
`on page 51, also involved adding features from one embodiment to another
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`embodiment in a single-reference combination. Boston Scientific Scimed, Inc. v.
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`Cordis Corp., 554 F.3d 982, 991 (Fed. Cir. 2009). The claim there required a metallic
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`core surrounded by two layers made of first and second materials. Id., 984. As shown
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`in the excerpt from the decision below, Figure 4 of the Wolff reference depicted a
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`metallic core 22 surrounded by the first material 14. Id., 988-989. Figure 3B taught
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`an arrangement of the first material 14 surrounded by the second material 15. Id. The
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`obviousness ground proposed adding the second material 15 of Figure 3B on top of
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`
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`-12-
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`

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`the first material 14 in Figure 4, to form the claimed arrangement shown in the
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`rightmost box below.
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`Id., 989. The Court found it obvious to incorporate layer 15 from Figure 3B onto layer
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`14 in Figure 4 stating:
`
`
`
`Wolff teaches all of the limitations of claim 8… The only qualification
`to this statement of fact is that all of the limitations are found in two
`separate embodiments pictured side by side in the patent, not in one
`embodiment…Combining two embodiments disclosed adjacent to
`each other in a prior art patent does not require a leap of
`inventiveness…Just as the stent in figure 3B benefits from the two
`layers,…so would the stent in figure 4 benefit from the same two
`coating layers.
`
`Id., 991.
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`
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`Like in Boston Scientific, Hagiwara discloses all of the limitations of the claims,
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`across two embodiments. Hagiwara 1(A) and 1(D) are described just six paragraphs
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`apart. Dr. Smith admits that the figures are depicted adjacent to one another on page
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`10. Ex. 1021, 84:20-24. Just as the sensor of Hagiwara 1(D) benefits from membrane
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`
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`-13-
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`

`

`
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`layers 5, 12, 6 that includes an enzyme layer 12, allowing it to sense glucose, so would
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`the sensor of 1(A) benefit from the same membrane layers – configuring the generic
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`1(A) sensor to sense glucose as instructed by Hagiwara 3:26-37.
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`
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`Boston Scientific states that motivations to combine are strengthened when the
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`components being combined are described in the same reference. Thus Boston
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`Scientific bolsters an already strong motivation that includes Hagiwara’s explicit
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`instructions to make the combination, along with the other motivations described in
`
`the Petition.
`
`C. The Petition Detailed Several Motivations For Path B Including
`An Express Teaching Of Implementing An Enzyme Sensor With
`A Side-Facing Sensor Window
`Regarding Path B, where a 1(D) glucose sensor is implemented with a 1(A)
`
`
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`side-facing sensor window, Hagiwara explicitly teaches the POSITA to position an
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`enzyme near the electrode reaction surface of the working electrode in Figure 1(A) to
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`create a glucose sensor. Hagiwara states:
`
`FIG. 1 (D) is a polarography sensor that forms an electrode for indirect
`polarography for applying an enzymatic reaction where a porous plastic
`layer 12 is formed that homogeneously disperses and fixes an enzyme
`on the contamination inhibiting coating 5 of the electrode reaction
`surface 2 of the measuring electrode classified in the embodiment
`described in FIG. 1 (A).
`
`
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`-14-
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`

`

`
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`Ex. 1005, 6:42-45; Petition, 40, 45; Ex. 1006, ¶¶74, 95; Institution Decision, 16. Thus,
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`the express language of Hagiwara teaches a POSITA that the 1(D) glucose sensor:
`
`can alternately be implemented by fixing an enzyme on coating 5 of “the electrode
`
`reaction surface 2 of the measuring electrode classified in the embodiment described
`
`in FIG. 1(A):”
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`
`
`
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`Adjusting the 1(D) insulation 4 from an end-facing window configuration to the 1(A)
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`side-facing window configuration again results in the claimed nub-surrounded-by-
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`enzyme structure. Dr. Smith admits that this structure falls within the claims.
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`Ex. 1021, 170:16-19; 170:24-171:5. The combination would have been predictable
`
`and successful, as evidenced by the arrangement of the same three membrane layers
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`
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`-15-
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`

`

`
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`in the same order in the 1(D) embodiment, with the only difference being the sensor
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`window location. Petition, 52.
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`
`
`
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`Beyond the express instructions in Hagiwara to place an enzyme layer on top
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`of “the electrode reaction surface 2… of FIG. 1(A),” the Petition also noted the
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`following motivations to combine according to Path B: (1) The side-facing window
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`of 1(A) was a known alternative for the location of the sensor window (see, e.g.,
`
`Wilson)(Institution Decision, 16 (citing Petition, 38-40; Ex. 1006, ¶155)); (2) The
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`sensor window on the end of the sensor is “prone to wearing of the dip coated layers
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`near the sensing window 2 during insertion into a body for sensing,” where a side
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`facing sensor is less so (Institution Decision, 16 (citing Petition, 40; Ex. 1006, ¶155)).
`
`
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`Again, Boston Scientific says the appearance of 1(A) and 1(D) in the same
`
`reference bolsters the strength of Hagiwara’s explicit instructions to make the
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`combination according to path B and the other motivations of the Petition. Thus the
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`combination is solid.
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`
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`-16-
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`

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`
`
`IV. Patent Owner’s Remaining Arguments Are Red Herrings
`A.
`Patent Owner’s Primary Argument Regarding Heparin-Induced
`Thrombocytopenia (HIT) Has No Basis In Law Or Reality
`1.
`There Is No Legal Precedent For The POSITA To Wholly
`Disregard A Reference Because Of An Allegedly Suboptimal
`Feature
`Patent Owner’s primary argument is that the POSITA would completely ignore
`
`all of Hagiwara’s teaching of an indwelling analyte sensor, because it also proposes
`
`using a heparin coating that Patent Owner argues is dangerous. Patent Owner states:
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`“a person of ordinary skill in the art seeking to construct a medical device like an
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`indwelling sensor would not have been inclined to look to Hagiwara at all, considering
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`its known dangers.” Response, 17. The Response identifies no valid precedent for its
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`“get out of jail free card” legal proposition – a theory that is far divorced from
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`obviousness case law.
`
`The Response cites to the non-precedential decision in Plas-Pak Indus. Inc. v.
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`Sulzer Mixpac AG, 600 F. App’x. 755, 758 (Fed. Cir. 2015) that is directed to a
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`different theory. That case is not about ignoring teachings of the prior art based on
`
`allegedly dangerous features. Plas-Pak is about compatibility. In Plas-Pak, petitioner
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`argued that patent owner’s claims for mixing paint were obvious based on Fukuta and
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`Morris. Id., at 756-757. Fukuta provided for mixing two components that prevented
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`backflow during mixing. Id., at 758. But Morris’s systems were susceptible to
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`backflow. Id. The Federal Circuit agreed with the PTAB’s finding of non-
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`
`
`-17-
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`

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`
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`obviousness stating, “[R]eplacing… Fukuta’s system with [those] of Morris, which
`
`fail to achieve comparable backflow prevention… fundamentally alters Fukuta’s
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`‘principle of operation.’ Such a change in a reference’s ‘principle of operation’ is
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`unlikely to motivate a person of ordinary skill to pursue a combination with that
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`reference.” Id., 758-759.
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`Combining Hagiwara 1(A) with 1(D) presents no Plas-Pak compatibility
`
`issues. Hagiwara’s 1(A) and 1(D) embodiments both have the same “principle of
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`operation” (if the coagulation inhibitor is truly Hagiwara’s “principle of operation”)
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`because they both rely on the same blood coagulation inhibiting coating 6. Because
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`Hagiwara 1(A) and 1(D) are compatible, the Plas-Pak case is not on point and fails to
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`support Patent Owner’s assertion that Hagiwara can be ignored. See, Costco
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`Wholesale Corp. v. Robert Bosch LLC, IPR2016-00039, Paper 69 at 24 (PTAB,
`
`Mar. 30, 2017)(“We agree…that the proposed modification here would not
`
`fundamentally alter the principle of operation of Katlarski or Merkel, nor render them
`
`inoperable for their intended purpose.”)
`
`2.
`
`The POSITA Would Not Have Avoided Hagiwara Based On Its
`Suggested Use Of Heparin
`The Response implies that because of the “known dangers” of heparin, the
`
`POSITA would not consider a reference that suggests its use in an analyte sensor
`
`(Response, 17) – despite Hagiwara explicitly disclosing an indwelling analyte sensor,
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`and providing working examples of the device in vivo. See, Ex. 1005, 7:33-8:33;
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`Figure 3. The Response’s allegations of the dangers of heparin are a distraction. The
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`alleged “known dangers” argued by the Patent Owner do not apply to the Hagiwara
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`teachings that are relevant to the ’574 claims. Beyond being divorced to the claims,
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`Dr. Smith’s analysis is further flawed as follows.
`
`a)
`
`Smith’s Evidence Shows Rare Risk At Doses Orders Of
`Magnitude Larger Than Hagiwara’s
`Dr. Smith admits “heparin has some useful medical applications.” Ex. 2008,
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`¶41. But he argues, “in large doses it can be fatal,” citing to Exhibits 2015, 2016. Id.
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`Exhibit 2015 describes six instances of HIT in patients receiving 9,000 to 20,000 units
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`of systemic heparin per day, and Exhibit 2016 describes a 0.8% rate of HIT in patients
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`receiving greater than 10,000 units of unfractionated systemic heparin (UFH) per day.
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`Ex. 2015, 6; Ex. 2016, 2-3. Thus, the incidence rate of HIT is rare, even when high
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`doses of the specific type of heparin associated with HIT are received systemically.
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`The heparin dosages in Hagiwara are substantially lower. Hagiwara suggests
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`embedding 10 to 1,000 units in the solution into which its sensor is dipped (i.e., 0.1%-
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`11% of the amount actually administered in Exs. 2015, 2016), only a fraction of which
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`actually ends up on the sensor with release modulated by a polymer coating. A
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`POSITA would know to use proper dosages of heparin to mitigate HIT or use types
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`of heparin that are less associated with HIT. See Ex. 2016, 2958:2:45-50. Thus Patent
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`Owner’s argument fails additionally because it does not demonstrate any significant
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`risk that would dissuade a POSITA from considering heparin or Hagiwara.
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`b)
`The Art Is Replete With Indwelling Medical Devices,
`Including Glucose Sensors, That Use Heparin
`The state of the art at the time of the ’574’s filing and since corroborates that
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`the use of heparin in amounts useful for an indwelling analyte sensor is not
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`contraindicated. Dr. Smith does not provide a single example where an indwelling
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`sensor (which has a low dose and is slow-diffusing) causes these alleged “known
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`dangers.” 5 In fact, indwelling sensors using heparin were still being suggested in the
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`art well after Hagiwara but before the ’574 priority date and even after the ’574’s
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`priority date. For example, the Say reference, discussed in further detail in Dexcom’s
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`Response to the Motion to Amend, was filed in 1998 and describes a blood-vessel-
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`inserted sensor. Ex. 1022, 6:37-39. Say’s sensor is coated with heparin where the
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`“anticlotting agent may be…allowed to diffuse away from the sensor surface.”
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`Id., 26:63-27:17. Further, Dexcom’s U.S. Patent No. 8,396,528 was filed in 2008 and
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`describes an analyte sensor designed for implanting for “30 or more days” where
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`“heparin is coated on the…sensor.” Ex. 1014, 74:10-11; 159:50-53.
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`In sum, Patent Owner’s arguments regarding supposed dangers of heparin in
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`Hagiwara are not credible. Patent Owner’s expert relies on “evidence” that analyzes
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`
`5 Dr. Smith admits that Exhibit 2015 does not discuss indwelling sensors as he
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`implied when he cited to that exhibit stating “it was well known that heparin-coated
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`indwelling sensors caused…HIT.” Ex. 1021, 90:22-25; Ex. 2008, ¶42.
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`cases of HIT from systemic doses of a specific type of heparin at levels 9 to 900 times
`
`greater than the doses suggested in Hagiwara. Further, Patent Owner’s expert ignores
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`implantable analyte sensor literature that suggested use of heparin closer in time to the
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`‘574 priority dates, as well as more recent literature that still suggests using heparin.
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`The evidence shows that heparin is not contraindicated as alleged. Accordingly, a
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`POSITA would not have avoided Hagiwara based on its mere suggestion of heparin
`
`usage.
`
`B.
`
`The Response’s Complaints Regarding Unsuitability For Intended
`Purpose Are Unfounded
`1.
`There Are No Enablement Or Undue Experimentation Issues
`With Features Actually Claimed
`Patent Owner’s remaining arguments regarding the independent claims allege
`
`that it would take substantial experimentation to configure a Hagiwara 1(A) sensor to
`
`sense an analyte, like glucose, using an enzyme layer. But Hagiwara provides
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`disclosure for all of the limitations that are actually recited in the ’574 claims. In fact,
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`Hagiwara provides more disclosure than the ’574 for all of the claim limitations. The
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`only requirement is that the prior art must “sufficiently describe the claimed invention
`
`to have placed the public in possession of it.” DISH Network v. TQ Beta, LLC,
`
`IPR2015-01756, Paper 31 at 18 (PTAB, Jan. 30, 2017). The Patent Owner does not
`
`present any enablement or undue experimentation arguments with respect to the
`
`limitations that actually appear in the claims (i.e., nubs surrounded by an enzyme
`
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`layer).6 Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd. 821 F.3d 1359, 1367
`
`(Fed. Cir. 2016)(“The reasonable expectation of success requirement refers to the
`
`likelihood of success in combining references to meet the limitations of the claimed
`
`invention. Failure to consider the appropriate scope of the patent’s claimed invention
`
`in evaluating the reasonable expectation of success constitutes a legal error.”)
`
`
`
`2.
`
`Patent Owner’s Attempt To Import Limitations Into The Claims
`Is Improper
`At pages 27-40 of the Response, the Patent Owner reads several limitations into
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`
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`the claims of the ’574 that are not there. Normally one would say the Patent Owner
`
`is attempting to read limitations from the specification into the claims, but in this case,
`
`the requirements Patent Owner attempts to hold Hagiwara to are not even present in
`
`their own specification. Patent Owner admits that these “features” are not the
`
`
`6 Hagiwara’s disclosure is presumed to be enabling. eBay Inc. v. Global Equity
`
`Management, IPR2016-01829, Paper 13 at 26 (PTAB, Apr. 21, 2017).
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`invention of the ’574 because these “features” are taught by the incorporated by
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`reference Wilson prior art patent, not the present inventors. By the time of the
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`invention of the ’574, the unclaimed technology argued by Patent Owner as essential
`
`was a well-known design that was in the prior art. “[I]f novel and nonobvious
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`[technology] was needed to practice the claimed inventions, [the inventor] would have
`
`been obligated to disclose this [technology] in the patent” instead of simply relying
`
`on what was taught in the prior art. Trustees of Columbia University v. Illumina, Inc.,
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`Appeal No. 2014-1547 at 31 (Fed Cir. 2015).
`
`
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`Because the “requirements” Patent Owner reads into the claims are not actually
`
`present in those claims, the arguments at pages 27-40 of the Response should be
`
`disregarded. 7 Certain aspects of those arguments are addressed briefly here for
`
`completeness.
`
`(a) Measuring Electrode Bias Voltage
`Patent Owner argues that Hagiwara fails to disclose how to set a proper bias
`
`
`
`voltage for an enzyme-measuring electrode. Response, 30-33. This is inaccurate, and
`
`Dr. Smith admits this.
`
`
`7 Dr. Smith agrees (Exhibit 1021) that none of the “requirements” are actually recited
`
`in the claims: bias voltage (114:4-7), permselective and interferent excluding layers
`
`(175:20-25), and bioprotective layer (117:11-24).
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`Ex. 1021, 104:4-10.
`
`
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`Thus Patent Owner’s allegations regarding a lack of disclosure regarding bias
`
`voltages in Hagiwara are untrue.
`
`(b)
`Permselective And Interferent–Excluding Membranes
`Patent Owner argues that a permselective layer is required at pages 33-34 of
`
`
`
`the Response. And Patent Owner further tries to read an interferent-excluding
`
`membrane into the claims at pages 32-33 of the Response. Patent Owner argues that
`
`these layers are necessary to successfully sense glucose, even though their own expert
`
`admits that the claims are not limited to glucose sensing. Ex. 1021, 174:9-10. Neither
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`of these limitations are in the claims. So whether or not Hagiwara describes them is
`
`irrelevant.
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`
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`Dr. Smith admits that these layers are not required. The ’574 only discusses
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`permselective and interferent-excluding layers in one sentence (2:1-4) that
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`inco