Paper No. 30
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
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`------------------
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`------------------
`
`ABS GLOBAL, INC.,
`Petitioner,
`
`v.
`
`CYTONOME/ST, LLC,
`Patent Owner.
`
`------------------
`Case No. IPR2017-02097
`Patent No. 8,529,161 B2
`------------------
`
`PETITIONER'S REPLY
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`------------------
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`------------------
`
`ABS GLOBAL, INC.,
`Petitioner,
`
`v.
`
`CYTONOME/ST, LLC,
`Patent Owner.
`
`------------------
`Case No. IPR2017-02097
`Patent No. 8,529,161 B2
`------------------
`
`PETITIONER'S REPLY
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`
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`IPR2017-02097
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`Petitioner's Reply
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`TABLE OF CONTENTS
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`I.
`II.
`
`Introduction ...................................................................................................... 1
`Claim Construction .......................................................................................... 3
`A.
`"Adjusting" ............................................................................................ 3
`B.
`"Focusing" (Claims 6, 7, 14, 15) ........................................................... 7
`i.
`Focusing Does Not Require "Accelerating Sheath Fluid" .......... 8
`ii.
`Focusing Does Not Require "Aligning the Particle Stream" .... 13
`"Orienting" (claims 8 and 16) ............................................................. 14
`C.
`III. Claims 1-20 Are Anticipated by Wada ......................................................... 15
`A. Wada Describes Adjusting (Claims 1 and 9) ...................................... 15
`B. Wada Describes Focusing (Claims 6-7, 14-15) .................................. 16
`C. Wada Describes Orienting (Claims 8, 16) .......................................... 23
`D. Wada Describes Positioning One or More Particles
`(Claims 18, 20) .................................................................................... 24
`E. Wada Describes a Sample Inlet (Claims 17, 19) ................................ 24
`F. Wada Describes the Remaining Dependent Limitations .................... 25
`IV. Claims 1 to 20 Would Have Been Obvious ................................................... 25
`V.
`Conclusion ..................................................................................................... 27
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`i
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`IPR2017-02097
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`Petitioner's Reply
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`TABLE OF AUTHORITIES
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` Page(s)
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`Cases
`Aspex Eyewear, Inc. v. Marchon Eyewear, Inc.,
`672 F.3d 1335 (Fed. Cir. 2012) .......................................................................... 13
`Brown v. 3M,
`265 F.3d 1349 (Fed. Cir. 2001) ............................................................................ 3
`Hewlett-Packard Co. v. Bausch & Lomb Inc.,
`909 F.2d 1464 (Fed. Cir. 1990) .......................................................................... 18
`Luminara Worldwide v. Liown Elecs. Co.,
`814 F.3d 1343 (Fed. Cir. 2016) .......................................................................... 12
`Rambus Inc. v. Infineon Techs. AG,
`318 F.3d 1081 (Fed. Cir. 2003) .......................................................................... 12
`TriVascular, Inc. v. Samuels,
`812 F.3d 1056 (Fed. Cir. 2016) ............................................................................ 7
`
`
`
`
`ii
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`IPR2017-02097
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`I.
`
`Introduction
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`Petitioner's Reply
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`The Board correctly found that Wada anticipates claims 1, 4, 8, 9, 12 and 16
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`to 20 because Wada describes a microfluidic system comprising a primary flow
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`channel and at least two regions in which hydrodynamic flows adjust a sample.
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`Paper 11 ("Dec."), 21-25. The Board, however, initially found claims 2-3, 5-7, 10-
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`11 and 13-15 not anticipated by Wada based largely on erroneous testimony from
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`Patent Owner's expert, finding these claims to have added requirements putatively
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`not described in Wada. Patent Owner's Response disputes the Board's findings of
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`anticipation, and seeks to extend the Board's findings regarding claims 2-3, 5-7,
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`10-11 and 13-15. Throughout, Patent Owner strains to read new requirements into
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`the claims and distorts Wada.
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`For claims the Board found anticipated, Patent Owner attempts to add
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`requirements found nowhere in the claims. For example, it asserts that the claims
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`require adjustments to an intact "suspended core sample" comprised of some
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`undefined multiplicity of particles. But that conflicts with the literal claim
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`language specifying that a sample can contain a single particle ("a sample having
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`one or more particles") and that adjustments can be made to "one or more particles
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`in the sample."
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`The Board's initial findings of no anticipation of claims 2-3, 5-7, 10-11 and
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`13-15 contain similar errors. Most notably, the Board misread the claims to require
`
`1
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`IPR2017-02097
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`Petitioner's Reply
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`the "secondary adjustment" to occur before detection or sorting of particles. Dec.,
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`26. There is no such requirement in the claims. This error was compounded by
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`Patent Owner's and its expert's unsupported assertions that "focusing" does not
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`occur in the second region of Wada's device in Figure 23 because the "purpose" of
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`that region was to "direct" a particle to one of two final destinations. But Wada
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`describes using the same microfluidic techniques in both regions, and the Board
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`found the first region performs "focusing." It thus cannot be correct that "focusing"
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`occurs in the first but not the second region of Wada's system.
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`The Board also misapprehended Petitioner's obviousness grounds, which
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`explained, by reliance on Micronics 2001, that a skilled person, when
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`implementing a microfluidic system, engages in an iterative process that involves
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`adapting the physical structure of a microfluidic system to yield a desired flow
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`pattern. Because the claims are directed to the use of conventional microfluidic
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`structures to achieve an entirely functional outcome, Petitioner presented
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`Micronics 2001 to foreclose the possibility that Patent Owner would contend some
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`unspecified configuration of the claimed system would render them patentable.
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`The skilled person would have found each claim obvious because each simply
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`specifies the predictable result of well-known configurations to the physical
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`structure of microfluidic systems. Di Carlo ¶¶92-94.
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`2
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`IPR2017-02097
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`Petitioner's Reply
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`Patent Owner's arguments all ultimately rest on illusory distinctions that
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`require the Board to adopt strained clam interpretations that conflict with the
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`claims and disclosure, and with admissions from named '161 patent inventors.
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`Each claim should be held unpatentable over Wada alone or with Micronics 2001.
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`II. Claim Construction
`The claim construction disputes concern "adjusting," "focusing," and
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`"orienting" a "sample." Patent Owner's assertions on each must be rejected as
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`inconsistent with the claims and the plain meaning of each term.
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`"Adjusting"
`
`A.
`The patent uses "adjust" with its plain and ordinary meaning, which the
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`Board correctly found is "to move." Dec., 8. Nothing in the specification suggests
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`otherwise. See Brown v. 3M, 265 F.3d 1349, 1352 (Fed. Cir. 2001) (affirming plain
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`meaning for claim limitations that "are not technical terms of art, and do not
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`require elaborate interpretation"). Nevertheless, Patent Owner presents two
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`alternative constructions for "adjusting" that improperly import numerous
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`limitations.
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`Patent Owner first contends that "in addition to 'moving,'" "adjusting"
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`requires "at least preserv[ing] (i.e., not disrupt[ing]) the suspended sample core."
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`Paper 25 ("POR"), 28-29. But this construction contradicts the claims, which
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`nowhere refer to a "suspended sample core" and consistently state that only a
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`3
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`IPR2017-02097
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`Petitioner's Reply
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`single particle need be the object of an "adjustment." For example, claims 1 and 9
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`require "flowing a sample having one or more particles," which expressly
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`includes adjustments to a sample having a single particle. Ex. 1031 ("Di Carlo")
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`¶53.
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`The dependent claims also make clear that the object of an "adjustment" can
`
`be a single particle. See, e.g., claim 3 ("…aligning the sample includes aligning
`
`one or more particles in the sample"); claim 4 ("…adjusting the sample…includes
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`adjusting a spatial characteristic of one or more particles in the sample."); claim
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`10 ("…aligning the sample includes aligning one or more particles in the
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`sample"); Claim 11 ("…adjusting the sample…includes adjusting a spatial
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`characteristic of one or more particles in the sample."). The claim language thus
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`rules out Patent Owner's assertion that the claims require adjustments to be made to
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`some unspecified multiplicity of particles that are spatially positioned in some
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`manner in a sample (i.e., within a "sample core").1
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`
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`1
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`Patent Owner's proposed "suspended sample core" requirement cannot be
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`reconciled with the skilled person's understanding that when a samples contains a
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`multiplicity of particles, the particles are randomly dispersed in the suspension
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`medium. See Ex. 1003 ¶128.
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`4
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`IPR2017-02097
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`Petitioner's Reply
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`Patent Owner's alternative theory is that "adjusting" means moving "into
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`proper position for use." POR, 29. But none of the claims require a sample to be
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`positioned in any particular manner. The two dependent claims that mention
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`"positioning" allow the sample to be positioned anywhere "within the primary flow
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`channel." Ex. 1001, cls. 18, 20. The specification likewise allows that the sample
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`"may or may not be at center of the primary sheath flow channel…." Id., 7:60-62,
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`8:1-2. It also makes clear that the sample may be passed to any "component in
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`fluid communication with an outlet," not just one with a detector or sensor as
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`Patent Owner suggests. Id., 5:15-18, 1:48-50. There is thus no basis for importing
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`positioning requirements into the claims, POR, 29, including that the sample be
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`positioned "in-line with a detector or sensor for a microfluidic system."
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`The claims also do not require a subjectively "desirable change" in the
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`sample size or shape to form a "narrow sample core" (POR, 29) and the
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`specification provides no objective basis for gauging such a limitation.2 Indeed,
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`incorporating such a meaning into the claims would render them indefinite, as each
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`"proper position for use" would depend on the configuration of each system being
`
`used. See, e.g., Ex. 1001, 7:6-7, 5:46-48, 7:14-15, 8:15-16, 7:34-37 (allowing
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`
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`2
`
`Although a sample width is reported in the specification ('161 patent at
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`10:27-29), no range is provided, nor are any metrics for sample height or shape.
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`5
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`IPR2017-02097
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`Petitioner's Reply
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`introduction of sheath fluid from any suitable direction, inlets in any suitable
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`location, and channels shaped in any suitable manner).
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`The Board also correctly rejected Patent Owner's assertion that the "sample
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`as a whole must be adjusted in all claims" because it is "not entirely clear." Dec., 7.
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`Dr. Kapur's testimony that "a 'sample' remains a single sample even if portions of
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`the sample have been split into separate flows or into separate channel [sic]"
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`simply perpetuates this confusion. Ex. 2005 ¶11. Critically, the claims require only
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`a single particle to be adjusted. Di Carlo ¶¶53-54.
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`Other theories advanced by Patent Owner's expert are likewise contrary to
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`the claim language and the intrinsic evidence. For example, Dr. Kapur suggests
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`that "adjusting" does not require moving the sample at all, stating that "the
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`percentage of sample fluid relative to sheath fluid could be 'adjusted' by reducing
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`the percentage of sample fluid." Ex. 2005 ¶12. But the claims make clear that
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`"introducing additional suspension medium into the primary flow channel" adjusts
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`the sample direction, not its percentage. Di Carlo ¶55.
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`The Board should therefore maintain its construction of "adjust" as having
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`its plain and ordinary meaning of "move."3
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`
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`3 While Patent Owner complains this dictionary definition was "cherry-picked," a
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`review of the other definitions shows they are irrelevant, and concern unrelated
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`6
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`IPR2017-02097
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`Petitioner's Reply
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`"Focusing" (Claims 6, 7, 14, 15)
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`B.
`As the Board recognized, a "focused particle stream" was well-understood in
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`the art to mean "a particle stream that is substantially focused, pinched, narrowed,
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`or otherwise confined…." Dec., 15 (quoting Wada, 8:22-25, 10:26-29). The same
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`focusing language is found in the specification. Ex. 1001, 1:32-34 ("pinch"), 1:34-
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`36 ("narrowed"), 2:9-11 ("confined"). To the extent a construction of "focusing" is
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`needed, this plain and ordinary meaning—"pinching, narrowing, or otherwise
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`confined"—is appropriate.
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`At Patent Owner's urging, the Board included two additional requirements
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`for "focusing": (i) use of an "accelerating sheath fluid to exert a force on the
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`particles" and (ii) "aligning the particle stream." Neither limitation comports with
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`the claim language or the plain meaning of "focusing" as it is used in the
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`disclosure.4 TriVascular, Inc. v. Samuels, 812 F.3d 1056, 1068 (Fed. Cir. 2016); Di
`
`Carlo ¶14-51.
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`
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`contexts (e.g., adjusting expenses, insurance, and environmental adaptation). See
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`Ex. 1009 at 25.
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`4
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`The Board's preliminary construction also requires that "focusing" occur "in
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`a desired direction relative to the boundaries of the channel" and "while achieving
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`or maintaining laminar flow." The claims, however, separately specify that
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`7
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`IPR2017-02097
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`Petitioner's Reply
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`i. Focusing Does Not Require "Accelerating Sheath Fluid"
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`A skilled person reading the '161 patent would not have concluded that
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`"focusing" requires "accelerating sheath fluid to exert a force on the particles. "
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`Nothing in the patent disclosure compels that conclusion, and two named inventors
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`testified that "focusing" as used in the '161 patent and understood in the field does
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`not require an accelerating sheath fluid.5 Di Carlo ¶¶ 14-48.
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`First, Dr. John Gilbert, a named inventor and the founder of Cytonome,
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`testified that "focusing"—both with its ordinary meaning and as it is used in his
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`patents—does not require an accelerating sheath fluid:
`
`Q. Does the term "focusing," as you use it in your patent, require
`accelerating the sheath fluid?
`A.
`So - no, it doesn't require it. It might happen anyway, but it's
`not required.
`
`
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`focusing occurs in at least two different directions, such that additional recitation
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`of the direction would be superfluous. And flow is laminar in microfluidic devices
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`regardless of whether focusing occurs. Di Carlo ¶¶85-86, 89.
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`5
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`The testimony of these two inventors is probative because it reflects
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`contemporaneous views of those working in the field of the patent on the plain and
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`ordinary meaning of "focusing" and confirms that "focusing" as used in the '161
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`patent did not have a special definition at odds with its plain meaning.
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`8
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`IPR2017-02097
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`Petitioner's Reply
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`…
`Just in terms of your own personal experience at the time you
`Q.
`filed your patent application, was it understood in the field at the time
`that focusing required accelerating the sheath fluid?
`A.
`So I don't believe people would even agree that that was true.
`
`Ex. 1026, Gilbert Tr., 229:43-8, 229:25-230:6; see also id., 47:3-5; Di Carlo ¶41-
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`42.
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`Dr. Bernard Bunner, another named inventor, likewise testified that sheath
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`fluid "acceleration" occurs only in a tapered primary focusing region and only in a
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`horizontal dimension:
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`Q. So in your devices, the only acceleration is going to be in the
`horizontal dimension and in the area where the device tapers the flow
`channel; right?
`A. Yes.
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`Ex. 1027, Bunner Tr., 151:7-152:5; Di Carlo ¶43.
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`The inventors' testimony reflects how microfluidic systems function. In
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`them, sheath fluid is conventionally injected into the primary flow channel at a
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`higher flow rate than the sample fluid. Di Carlo ¶38 (citing sheath-to-sample flow-
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`9
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`IPR2017-02097
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`Petitioner's Reply
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`rate ratios ranging from 2.5:1 to 120:1).6 This produces a "difference in velocity"
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`between the sheath and sample fluids that causes the sample fluid to be narrowed,
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`pinched, or otherwise confined by the sheath fluid. Sheath fluid itself does not need
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`to be "accelerating" in a particular region to exert a force on particles in a sample
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`because it is already moving at a higher rate than the sample fluid layer. Di Carlo
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`¶38. Consequently, as Patent Owner's expert acknowledged, "focusing" can be
`
`achieved with a "difference in fluid velocity between sheath fluid and sample
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`fluid" and thus does not require an "accelerating sheath fluid." Ex. 2002 ¶12.
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`The specification likewise makes clear that an "accelerating" sheath fluid is
`
`not required for "focusing." Notably, the specification explains that the primary
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`focusing region may be configured in a manner that preferably "accelerates and
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`focuses the sheath fluid" (Ex. 1001, 4:63-65 (emphasis added)), whereas the
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`secondary focusing region simply focuses (see, e.g., id., 2:12-17, 6:17-31). Pet. 25.
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`This distinction recurs throughout the specification, where several examples reflect
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`no "acceleration" even in the primary focusing region. See, e.g., id., 8:21-26, 2:6-
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`12, 2:36-41, 3:22-27, 4:63-5:6; Di Carlo ¶¶39-40.
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`
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`6
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`The '161 patent itself recites a flow-rate ratio of "45:1," such that prior to
`
`entering the focusing regions, the sheath fluid flows at a rate 45 times greater than
`
`the sample fluid. '161 patent at 9:46-47; Di Carlo ¶38
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`10
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`IPR2017-02097
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`Petitioner's Reply
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`Dr. Bunner's testimony reinforces this point, as he testified that some
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`focusing regions in his alleged invention may both accelerate and focus, but others
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`only focus:
`
`Q. So, in your view, the primary focusing region includes accelerating
`and focusing steps; right?
`[Attorney Objections]
`A. Yes.
`Q. Now, in the second focusing region, is there both accelerating and
`focusing in the secondary focusing region as well?
`A. No.
`Q. So some regions have [acceleration] and some regions don't in your
`devices; right?
`A. The primary focusing region has -- the primary focusing region
`uses accelerating of the flow, for horizontal focusing.
`Q. And the secondary focusing reason does not use accelerating;
`right?
`A. No.
`Q. Okay. And that's your understanding of how your devices work;
`right?
`A. Yes.
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`Ex. 1027, 377:14-378:12; Di Carlo ¶ 44.
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`The specification in conjunction with this testimony makes clear that the
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`inventors did not act as their own lexicographer – they did not "clearly set forth a
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`definition" of "focusing" or "clearly express an intent to redefine the term."
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`11
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`IPR2017-02097
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`Petitioner's Reply
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`Luminara Worldwide v. Liown Elecs. Co., 814 F.3d 1343, 1353 (Fed. Cir. 2016);
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`Di Carlo ¶45.
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`Patent Owner also never made a "clear and unmistakable disavowal" of
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`claim scope to exclude focusing that occurs without accelerating sheath fluid. Id.
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`Indeed, a skilled person would have regarded the prosecution argument Patent
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`Owner relies on – that "focusing requires acceleration and removal of sheath fluid
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`from around a particle" – as facially inaccurate. See Rambus Inc. v. Infineon Techs.
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`AG, 318 F.3d 1081, 1090 (Fed. Cir. 2003) (an "incorrect statement in the
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`prosecution history does not govern the meaning of the claims"; the "claim
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`language itself controls the bounds of the claim, not a facially inaccurate remark
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`during prosecution"); Di Carlo ¶46. Ohki discloses "focusing" even under Patent
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`Owner's construction of the term. Di Carlo ¶¶20-35, 47-48. And as to whether
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`focusing requires "removal of sheath fluid," Dr. Gilbert testified unequivocally:
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`"[I]t doesn't require it" and "we don't teach removal of sheath fluid in this patent."
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`Ex. 1026, 234:6-9, 234:24-235:3.
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`Importantly, Patent Owner did not distinguish the claims over the examiner's
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`asserted prior art reference (Ex. 3001, "Ohki") by relying on the construction for
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`"focusing" it now advances. Dec., 16-17. Patent Owner could not contend that the
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`Ohki devices do not "focus" a sample. Di Carlo ¶¶20-35. The field had
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`acknowledged that these devices produce "sample sheathing and hydrodynamic
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`12
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`IPR2017-02097
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`Petitioner's Reply
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`focusing on all four sides." Di Carlo ¶33 (quoting Ex. 1028, 236). Patent Owner
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`distinguished Ohki as showing only one focusing region. Ex. 2001, 49.
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`The intrinsic and extrinsic evidence thus demonstrate "focusing" does not
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`require "accelerating sheath fluid."
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`ii. Focusing Does Not Require "Aligning the Particle Stream"
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`The Board's conclusion that "focusing" requires "aligning the particle
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`stream" is similarly inconsistent with the claims and inventor testimony.
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`Dependent claims 2, 3, 10 and 11 make clear that "aligning" a sample is
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`distinct from "focusing" a sample. See, e.g., claim 2, ("wherein adjusting the
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`sample … includes aligning the sample."). "[W]hen different words are used in
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`separate claims, they are presumed to have different meanings." Aspex Eyewear,
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`Inc. v. Marchon Eyewear, Inc., 672 F.3d 1335, 1349 (Fed. Cir. 2012).
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`The Board also did not have the benefit of inventor testimony when it found
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`"focusing" to require "aligning the particle stream." Dr. Gilbert testified that
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`focusing may result in aligning the particle stream if the particle-stream diameter is
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`narrowed to "approach the diameter…of the particles," but that otherwise the
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`particle stream will be distributed across the sample stream. Ex. 1026, 233:15-
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`234:5. Thus, "aligning" a sample is not a necessary feature of "focusing" a sample
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`according to the patent. Di Carlo ¶¶49-51.
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`13
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`IPR2017-02097
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`Petitioner's Reply
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`"Orienting" (claims 8 and 16)
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`C.
`Claims 8 and 16 specify that "adjusting" a sample includes "orienting" it. In
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`its preliminary response, Patent Owner did not dispute that "orienting the sample"
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`means "moving the…sample into a specified position." Paper 9, 30; Dec., 30-31.
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`Patent Owner has now changed course and contends that "orienting the sample"
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`requires "providing directionality to asymmetric particles within a sample," that
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`such directionality must be provided "in the entire sample," and that all particles
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`have the same directionality. POR, 37-38.
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`Patent Owner's proposed construction should be rejected because it conflicts
`
`with the claims and requires reading unsupported requirements into the claims.
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`First, as explained above, the claims state that a sample can contain a single
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`particle. Requiring a multiplicity of particles in the sample contradicts the claims.
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`Second, no claim requires a sample to contain "asymmetric" particles; the
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`only example of a "sample having one or more particles" in the specification
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`contains symmetric, spherical particles. Ex. 1001, 9:44-46 (specifying "6 micron
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`yellow beads from Spherotech"); Di Carlo ¶58-59. As Dr. Di Carlo testified,
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`"particles that are spherical have no directionality." Ex. 2004, 75:25-76:1. There is
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`thus no basis for limiting a "sample" to a multiplicity of "asymmetric particles."
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`Finally, Patent Owner's expert's testimony on this term relies on a mistaken
`
`reading of the claims and should be disregarded. Di Carlo ¶¶56-57. Dr. Kapur
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`14
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`IPR2017-02097
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`Petitioner's Reply
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`apparently understood the term "orienting the sample" to mean that "the entire
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`sample directionally orients asymmetrical particles." Ex. 2005 ¶13. But the claim
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`clearly states that "introducing additional suspension medium" orients the particles,
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`not that the sample itself orients the particles.
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`The Board's preliminary construction of the "orienting" was therefore correct
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`and should be maintained. Di Carlo ¶60.
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`III. Claims 1-20 Are Anticipated by Wada
`A. Wada Describes Adjusting (Claims 1 and 9)
`The Board correctly found claims 1 and 9 anticipated. Dec., 22-25. Wada
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`describes microfluidic systems in which a sample comprising at least one particle
`
`is moved in a first direction in a first hydrodynamic focusing region and then is
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`moved in a different direction in a second hydrodynamic focusing region. Pet., 35-
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`55; see, e.g., Wada, 9:8-26, 11:34-12:37, 13:1-33, 23:18-24, Figs. 1, 22-23; see
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`also id., cl. 6. Nothing more is required by the claims, which compels a finding of
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`anticipation.
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`Patent Owner's response relies entirely on its implausible alternative claim
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`constructions, all of which should be rejected. See supra Section II. Patent Owner
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`also mischaracterizes what Wada actually shows, contending that the offset
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`focusing microchannels in Wada Figure 23 split the sample into separate flows or
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`into separate channels. That is incorrect. Wada describes adjusting a sample stream
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`15
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`IPR2017-02097
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`Petitioner's Reply
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`containing one or more particles first to the left and then to the right using distinct
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`hydrodynamic focusing regions. As explained in the Petition, this two-step
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`focusing process directs a sample containing selected particles—still surrounded
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`by sheath fluid—into the right-hand collection channel. Pet., 66. The entirety of
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`that sample containing those particles at each adjustment region is thus adjusted in
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`the specified direction, exactly as the claims specify. Di Carlo ¶¶62-68.
`
`B. Wada Describes Focusing (Claims 6-7, 14-15)
`Based on Patent Owner's assertions about how the second adjustment region
`
`in Wada Figure 23 functions, the Board concluded that the Wada Figure 23 device
`
`does not anticipate claims 6, 7, 14 and 15. That conclusion cannot be reconciled
`
`with the claim language or Wada's descriptions.
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`Initially, the Board found that the first region in Wada Figure 23 performs
`
`"focusing," even under its preliminary construction. Dec., 26 ("Thus, Wada
`
`describes that focusing occurs in Petitioner's blue shaded region…"). The Board
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`also acknowledged that "…Wada discloses the aspects of horizontal and vertical
`
`focusing and different flow structure embodiments, which may focus a sample
`
`within a flow channel." Dec., 27 (citing Pet. 63 (citing Ex. 1006, 9:8-22, 9:60-10:4,
`
`Fig. 1A, Figs. 21-23)).
`
`The Board, however, found that the second region (in green) in Wada Figure
`
`23 does not perform focusing. Dec., 26. It did so by crediting Patent Owner's
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`16
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`IPR2017-02097
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`Petitioner's Reply
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`assertions that because this second region "is for
`
`sorting, not focusing" it does not perform
`
`"focusing." Dec., 24-25. The Board also cited
`
`Patent Owner's expert testimony that the "sorting
`
`Wada teaches in Petitioner's green shaded region
`
`of Figure 23 does not constitute focusing because
`
`it does not narrow and align the particle stream
`
`within a laminar flow" and his assertions that particles in the Wada device are
`
`forced "out of focused laminar flow … and causes the sheath and sample fluids to
`
`mix." Dec., 26-27 (citing Ex. 2002 ¶14).
`
`Patent Owner's and its expert's assertions about how the Wada systems
`
`function are simply incorrect, which led the Board to incorrectly conclude that the
`
`second region in Figure 23 does not focus. Di Carlo ¶¶69-71. Critically, the
`
`Board's conclusion that the first region (blue) in Wada's Figure 23 device performs
`
`"focusing" compels the conclusion that the second region (green) does, too. That is
`
`because the two regions have the same structure and function in the identical
`
`manner – each uses the same offset microchannel design to introduce a sheath flow
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`17
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`IPR2017-02097
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`Petitioner's Reply
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`into the primary flow channel that moves one or more particles within a sample in
`
`a different direction.7 Di Carlo ¶¶72-76; Wada, 13:17-33.
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`More specifically, Wada applies the same "hydrodynamic flow 2302" to the
`
`selected particles (represented by black circles) through each focusing
`
`microchannel in the series. E.g., Pet., 50-55, 62-65. The second focusing
`
`microchannel is the same size, shape and proportion, and is depicted in Figure 23
`
`as introducing the same "hydrodynamic flow 2302" to force particles away from
`
`the primary flow channel walls as the first focusing microchannel. Wada, 13:17-
`
`33, Fig. 23; see also Wada, 11:34-13:33 (describing "Use of Focusing to Sort
`
`Particles"); Di Carlo ¶¶77-81; Ex. 2004, 54:23-64:21, 71:7-20. By doing so, each
`
`region necessarily causes a narrowing and alignment of the particle stream in a
`
`particular direction, and each creates a laminar flow wherein the introduced sheath
`
`fluid surrounds the fluid layer containing the particles. Di Carlo ¶¶82-89; Wada,
`
`11:34-13:33, 23:19-24. Thus, as Wada itself states, its system uses "a series of
`
`offset focusing microchannels to achieve focusing by serial introduction of fluids
`
`
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`7
`
`See Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469 (Fed.
`
`Cir. 1990) ("[A]pparatus claims cover what a device is, not what a device does.")
`
`(original emphasis).
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`IPR2017-02097
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`Petitioner's Reply
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`from the offset channels." Pet., 38-39, 46-47 (quoting Wada, 9:13-17) (emphasis
`
`added).
`
`Patent Owner's expert also incorrectly portrayed how Wada's Figure 23
`
`device functions, asserting, inter alia, that it mixes the sample and sheath flows
`
`within the green-shaded region of Figure 23. See Ex. 2002 ¶¶14-16; Ex. 2005
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`¶¶14-16. That is incorrect – the two flows only mix when combined further
`
`downstream in the collection wells (2312) not upstream at the claimed secondary
`
`adjustment region where laminar flow is maintained. Di Carlo ¶73. Moreover, as
`
`Figure 23 itself illustrates, the secondary focusing region focuses the entire
`
`selected particle stream toward the right side of the primary flow channel so that
`
`particles in the stream flow through the desired collection channel and into the
`
`collection well. Di Carlo ¶77.
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`The second, green-shaded region of Figure 23 also narrows and aligns the
`
`particle stream within a laminar flow – that is the necessary consequence of the
`
`introduction of sheath fluid in the identical manner as in the first focusing region,
`
`which the Board found meets the "focusing" requirement. Indeed, the only
`
`difference between the two regions is the direction in which the hydrodynamic
`
`focusing flows are introduced into the primary flow channel, as required by the
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`contested claims. Both focusing microchannels thus apply hydrodynamic flows
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`that meet the Board's interpretation of "focusing" of a sample containing one or
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`Petitioner's Reply
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`more particles, as well as the plain and ordinary meaning of "focusing." Di Carlo
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`¶¶81-90.
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`Wada's use of the word "direct" rather than "focusing" to describe the
`
`purpose of the focusing in the second region (Wada, 13:21-31) may have led the
`
`Board to improperly credit Patent Owner's argument that Wada's second focusing
`
`microchannel does not perform "focusing" when used to process a sample
`
`containing some "selected" and some "unselected" particles. The defect in Patent
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`Owner's position, however, is shown by a single example: when used to process a
`
`sample containing only one or more "selected" particles, the device described in
`
`Figure 23 continuously focuses the entire sample into the right-hand collection
`
`channel. Ex. 2004, Di Carlo Tr., 72:19-73:4; Di Carlo ¶68.
`
`Regardless, as the figures in Wada identified in the Petition show,
`
`"directing" is the result of "focusing," not a different phenomenon. Di Carlo ¶¶ 74-
`
`77. For example, Wada describes Figure 22—identified in the Petition as another
`
`example of "a series of offset focusing channels" (Pet. 39-40)—employs "at least
`
`two sets of opposing microchannels for focusing and/or otherwise directing the
`
`flow of cells." Wada, 13:2-5 (emphasis added); see also id., 7:30-33 ("Fig. 22 is a
`
`schematic illustration of a particle sorting configuration utilizing sets of opposing
`
`microchannels to focus and/or otherwise direct the flow of the members of, e.g., a
`
`cell population to achieve cell sorting.").
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`IPR2017-02097
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`Petitioner's Reply
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`The prosecution history and issued claims of Wada reinforce that Wada uses
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`"focusing" to "direct" a sample and the particles in it. Di Carlo ¶¶78-80. For
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`example, the Wada applicants cited Figure 23 and its description as providing
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`"ample support" for claims in which "directing" is the consequence "focusing"
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`applied by the hydrodynamic flows shown in the figure. See Ex. 1018, 142-43.
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`Claim 6 of Wada likewise recites "focusing the particles" in a first region "such
`
`that the particles are directed toward a first side of at least opposing first and
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`se
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