UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`Akermin, Inc.
`Petitioner
`
`v.
`
`CO2 Solutions Inc.
`Patent Owner
`
`
`Patent No. 8,329,458
`Filing Date: June 4, 2010
`Issue Date: December 11, 2012
`Title: CARBONIC ANHYDRASE BIOREACTOR AND PROCESS FOR CO2
`CONTAINING GAS EFFLUENT TREATMENT
`
`
`
`
`Inter Partes Review No. IPR2015-00880
`
`
`
`PETITIONER’S REPLY TO PATENT OWNER’S RESPONSE
`
`

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`TABLE OF CONTENTS
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`TABLE OF ABBREVIATIONS ............................................................................. iv
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`I. 
`
`II. 
`
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`INTRODUCTION ........................................................................................... 1
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`CLAIM CONSTRUCTION ............................................................................ 1
`
`A.  “In Suspension”—The Differences Between the Parties’ Constructions
`Are Inconsequential................................................................................... 2
`
`
`III.  THE CHALLENGED CLAIMS ARE UNPATENTABLE .......................... 10
`
`
`B.  “Entrapped [in the Porous Substrates]”—Patent Owner’s Proposed
`Construction is Unreasonably Narrow and Is Irreconcilable with the
`Evidence .................................................................................................... 3
`
`A.  Ground 1: Claims 1-3, 15, 17, 24-27, 40-41, and 43 are Anticipated
`under § 102(b) by Bonaventura............................................................... 11
`
`1.  Figure 6 of Bonaventura depicts particles in suspension ............... 12
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`2.  Particles “flowing with water” are “in suspension” ..................... 13
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`3.  A mechanical agitator is not necessary for a suspension ............... 15
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`B.  Ground 2: Claims 1-3, 15-17, 24-27, and 40-43 are Unpatentable
`under § 103(a) over Bonaventura in View of the ‘416 Patent ................ 17
`
`C.  Ground 3: Claims 1, 4, 25, and 28 are Unpatentable under § 103(a)
`over Bonaventura in View of Badjic ....................................................... 20
`
`D.  Ground 4: Claims 1, 18, and 19 are Unpatentable under § 103(a) over
`Bonaventura in View of Kohl ................................................................. 21
`
`E.  Ground 5: Claims 1, 2, 15, 16, 22-26, and 40-43 are Unpatentable
`under § 103(a) over Dean in View of Rau .............................................. 22
`
`1. Dean discloses carbonic anhydrase “entrapped” in a porous
`substrate, under the proper claim construction .............................. 22
`
`2.  Motivation to combine Rau and Dean ............................................. 22
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`ii
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`IV.  THE OPINION TESTIMONY OF PO’S SENIOR EXECUTIVE IS NOT
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`IV.IV.
`CREDIBLE .................................................................................................... 24
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`THE OPINION TESTIMONY OF PO’S SENIOR EXECUTIVE IS NOTTHE OPINION TESTIMONY OF PO’S SENIOR EXECUTIVE IS NOT
`
`CREDIBLE .................................................................................................. ..24CREDIBLE .................................................................................................. ..24
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`V. 
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`V.V.
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`CONCLUSION .............................................................................................. 25 
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`CONCLUSION ............................................................................................ . .25CONCLUSION ............................................................................................ . .25
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`iii
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`iiiiii
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`

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`‘416 patent
`‘458 patent
`Akermin
`Badjic
`
`Board
`Bonaventura
`Dean
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`TABLE OF ABBREVIATIONS
`
`U.S. Patent No. 4,427,416 to Bonaventura et al. (Ex. 1005)
`
`U.S. Patent No. 8,329,458 to Parent et al. (Ex. 1001)
`
`Petitioner Akermin, Inc.
`
`Jovica D. Badjic & Nenad M. Kostic, Effects of
`Encapsulation in Sol-Gel Silica Glass on Esterase Activity,
`Conformational Stability, and Unfolding of Bovine Carbonic
`Anhydrase II, 11 Chemistry Materials 3671 (1999)
`(Ex. 1009)
`
`Patent Trial and Appeal Board
`
`U.S. Patent No. 4,602,987 to Bonaventura et al. (Ex. 1004)
`
`Douglas N. Dean et al., Batch Absorption of CO2 by Free
`and Microencapsulated Carbonic Anhydrase, 16 Indus.
`Engineering & Chemistry Fundamentals 260 (1977)
`(Ex. 1006)
`
`Institution Decision Decision Instituting Inter Partes Review under 37 C.F.R. §
`42.108 (Paper 10)
`
`Excerpts from Arthur Kohl & Richard Nielsen, Gas
`Purification (5th ed. 1997) (Ex. 1008)
`
`Corrected Petition for Inter Partes Review under 35 U.S.C.
`§§ 311-319 and 37 C.F.R. § 42.100 et seq. (Paper 5)
`
`Patent Owner CO2 Solutions Inc.
`
`Patent Owner Response (Paper 14)
`
`International Publication No. WO 00/10691 to Rau et al.
`(Ex. 1007)
`
`Excerpts from O. Zaborsky, Immobilized Enzymes, pgs. 83-
`101 (CRC Press, 1973) (Ex. 2011)
`
`
`Kohl
`
`Petition
`
`PO
`POR
`Rau
`
`Zaborsky
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`iv
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`

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`I.
`
`INTRODUCTION
`
`It is important to note what CO2 Solutions Inc. (“PO”) does not dispute. PO
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`does not dispute that the prior art taught using triphasic biocatalytic reactors
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`(having a reaction chamber, a liquid inlet, a gas inlet, a liquid outlet, and a gas
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`outlet) to treat carbon-dioxide containing gas emissions. PO also does not dispute
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`that using carbonic anhydrase immobilized in porous substrates as the biocatalyst
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`in these reactors was old. PO resorts to two primary grounds to oppose the
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`Petition. First, PO alleges that suspending the carbonic-anhydrase containing
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`porous substrates within the reactor was a new and non-obvious development.
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`Second, PO narrowly construes “entrapped” to exclude encapsulation.
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`Neither of PO’s positions is consistent with the evidence of record.
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`Suspending porous substrates containing entrapped enzymes (including carbonic
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`anhydrase) in fluidized beds, slurries, or otherwise was well known. And PO’s
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`unreasonably narrow claim construction of “entrapped” is irreconcilable with the
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`evidence. Akermin respectfully requests the Board to find claims 1-4, 15-19, 22-
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`28, and 40-43 of the ‘458 patent unpatentable.
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`II. CLAIM CONSTRUCTION
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`There are only two claim construction disputes between the parties. And
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`only one these—the broadest reasonable interpretation of “entrapped”—is of any
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`consequence in this proceeding. Akermin’s proposed constructions accord the
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`1
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`

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`claim terms their broadest reasonable interpretation in light of the intrinsic and
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`extrinsic evidence. PO’s proposed constructions, by contrast, are unreasonably
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`narrow and contradict the intrinsic evidence. And PO does not dispute Akermin’s
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`proposed constructions for “porous,” “filter”/“filtration,” “ultrafiltration,” and
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`“microfiltration.” Akermin requests the Board to adopt its proposed constructions.
`
`A.
`
`“In Suspension”—The Differences Between the Parties’
`Constructions Are Inconsequential
`
`Akermin’s Proposed Construction
`“a mixture in which particles are
`heterogeneously dispersed throughout
`the bulk of a fluid” (Petition at 10)
`
`PO’s Proposed Construction
`“substrates are a mixture of nonsettling
`particles dispersed within a liquid, the
`particles being the dispersed phase, while the
`liquid is the continuous phase” (POR at 7)
`
`PO attacks Akermin’s proposed construction as unreasonably broad,
`
`claiming that it would encompass instances in which the particles are mixed within
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`the liquid, but settled out of suspension. POR at 9. Akermin’s construction is not
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`so broad. As PO’s declarant, Dr. Fradette, acknowledged, particles that are settled
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`out of suspension would not be “dispersed throughout the bulk of a fluid,” as
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`expressly required by Akermin’s construction. Ex. 1027 at 56:22-58:17. He
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`further testified that, so long as Akermin’s construction is understood not to cover
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`settled particles, he “wouldn’t have a dispute with the definition.” Id. Akermin’s
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`simpler proposed construction should be adopted.
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`PO’s proposed claim construction injects unnecessary ambiguity and
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`complexity. For example, PO’s proposed construction requires that the particles
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`2
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`

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`dispersed within a liquid be “nonsettling” particles. As Dr. Fradette explained,
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`however, the use of the adjective, “nonsettling,” does not mean that the particles do
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`not settle. Ex. 1027 at 52:10-53:19. Rather, “nonsettling” was intended to indicate
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`that the particles will not settle while the reactor is actively operating. Id.
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`PO also includes the following phrase in its proposed construction: “the
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`particles being the dispersed phase, while the liquid is the continuous phase.” This
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`verbiage adds nothing to the definition. It simply applies the additional labels
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`“dispersed phase” and “continuous phase” to “particles” and “liquid,” respectively.
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`Finally, PO would limit a “suspension” to particles dispersed in a liquid,
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`rather than a fluid (liquid or gas). Even PO’s cited dictionary demonstrates that
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`this position is unduly narrow. Ex. 2013 at 365 (“within a liquid or gas”).
`
`B.
`
`“Entrapped [in the Porous Substrates]”—Patent Owner’s
`Proposed Construction is Unreasonably Narrow and Is
`Irreconcilable with the Evidence
`
`Akermin’s Proposed Construction
`“physically trapped within the structure
`of the substrate while retaining at least
`some of its activity”
`(Petition at 11)
`
`PO’s Proposed Construction
`“the enzyme molecules are free in solution,
`but restricted in movement within the
`interstitial confines of the porous substrate
`lattice network, and accessible to reactants
`(e.g., CO2)” (POR at 7)
`
`PO proposes a narrow construction for the phrase “entrapped in” that
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`improperly excludes “microencapsulation.” POR at 10-13, 35-41. PO asks the
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`Board to graft a limitation on the claimed “porous substrates” to further require
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`that these substrates contain “a lattice network.” The “entrapped in” claim
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`3
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`language at issue, however, modifies the carbonic anhydrase, not the porous
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`substrates.
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`The independent claims merely require that “the substrates comprise porous
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`substrates.”1 They do not specify any particular structure for the porous substrates.
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`Ex. 1001 at claims 1 and 25; Paper 10 at 11. Nowhere does the ‘458 patent
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`specification describe the porous substrates as having interstitial confines or a
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`lattice network. Paper 10 at 11; Ex. 1027 at 67:24-68:4. There is no support in the
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`intrinsic record for grafting this limitation onto the claimed “porous substrates.”
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`PO argues that its narrow construction is justified because both of the words
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`“encapsulation” and “entrapped” appear in the specification, but only “entrapped”
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`appears in the claims. POR at 10-11. But the specification uses “entrapped”
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`broadly. For example, in column 4, the specification distinguishes entrapped
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`biocatalysts from free (non-immobilized) catalysts. Ex. 1001 at 4:6-9. In column
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`6, the specification’s use of “entrapped” simply distinguishes the act of physically
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`entrapping the biocatalyst within a porous substrate from immobilizing the
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`biocatalyst on a solid packing or by chemically linking it in a network. Id. at 6:23-
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`1 There is no dispute that both lattice entrapment and microencapsulation involve
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`porous substrates. Ex. 1027 at 65:5-66:3, 146:21-147:1 (“By definition, if you
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`want the enzyme to work in such an immobilized material, the material has to be
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`porous.”); see also Ex. 1026 at Title, 1:25-48, Figs. 1-7.
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`4
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`31. And in column 8, the term “entrapped” is used when identifying exemplary
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`particles to be used as the porous substrates. Id. at 8:62-66. These passages fall
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`well short of establishing a narrow definition of “entrapped in” that excludes
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`microencapsulation. See Paper 10 at 10 (“To act as its own lexicographer, a
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`patentee must clearly set forth a definition of the disputed claim term other than its
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`plain and ordinary meaning.”) (citations omitted).
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`Contrary to PO’s assertion, its dictionary definitions for “entrap” and
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`“encapsulate” are not incompatible. See Ex. 2012 at 745, 758 (defining “entrap” as
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`“to capture and hold” and “encapsulate” as “to surround, encase, or protect in or as
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`if in a capsule”). While the dictionary definition of “encapsulate” (a term not in
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`the claims) has a narrower connotation than the entry for “entrap,” the definition of
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`“entrap” does not exclude encapsulation. It is unremarkable that a broader term
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`may encompass a narrower term—even though the reverse proposition is not true.
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`PO argues that “standard reference books on which the skilled person
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`routinely relies refer to entrapment and encapsulation as different techniques, and
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`do not state or suggest that one could encompass the other.” POR at 11 (citing
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`Exhibits 2002, 2006, and 2011). This assertion contradicts the evidence.
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`In the field of enzyme immobilization, “entrapment” is a broad classification
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`of immobilization techniques that encompasses a number of physical
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`immobilization mechanisms, notably including “encapsulation.” Multiple
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`5
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`references have graphically depicted this genus-species relationship:
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`
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`Ex. 1024 at 181 (emphasis added); Ex. 1028 at 631 (emphasis added).
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`The references cited by PO also support this conclusion. For example, in
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`Perry’s Chemical Engineers’ Handbook, three general methods of immobilizing
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`enzymes were identified: 1) adsorption, 2) covalent bonding, and 3) entrapment.
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`Ex. 2006 at 24-21. The reference goes on to discuss the following different
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`methods of entrapment: using semipermeable membranes to restrain the enzyme;
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`using polyacrylamide gel, silica gel, and other similar materials to entrap the
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`enzyme; and encapsulating the enzyme in a semipermeable material. Id. It further
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`notes that none of these entrapment methods “involve a chemical or
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`physical/chemical reaction directly with the enzyme molecules; and the enzyme
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`molecules are not altered.” Id. This is consistent with Dr. Fradette’s classification
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`of immobilization techniques as either physical (i.e., entrapped) or chemical (i.e.,
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`bound). Ex. 2004 at ¶58.
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`The Zaborsky reference (Ex. 2011) cited by PO also undermines PO’s
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`6
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`unduly narrow construction. Indeed, Zaborsky repeatedly describes enzymes
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`within microcapsules as being “entrapped.” See Ex. 2011 at 93-99 (using the term
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`“entrap”/“entrapped”/“entrapping” to describe enzymes within microcapsules,
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`including in the captions for Figures 18, 19, and 21).
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`PO also argues that “the skilled person would recognize that none of the
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`prior art on which the Petition relies uses these terms ‘entrapped’ and
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`‘encapsulation’ interchangeably.” POR at 11. To the contrary, the Badjic
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`reference applied in Ground 3 used “entrapped,” “encapsulated,” and “embedded”
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`interchangeably in reporting on encapsulation experiments with sol-gel silica glass.
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`Ex. 1009 at 1; Ex. 2017 at 157:11-158:25; Ex. 1027 at 94:24-97:7.2
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`PO accuses Akermin and Dr. DeFilippi as “misleadingly characteriz[ing]
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`Dean by stating that the carbonic anhydrase used in Dean ‘was entrapped in
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`cellulose nitrate microcapsules.’” POR at 35-36. As seen above, however,
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`“entrapped” is commonly used to describe enzymes immobilized through
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`microencapsulation, as well as other techniques. In fact, scientists skilled in the art
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`2 Notably, Dr. Fradette struggled to classify the immobilized enzyme in Badjic as
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`either “entrapped” or “encapsulated” under PO’s unduly narrow construction. Ex.
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`1027 at 147:2-148:13. Dr. Fradette ultimately concluded that Badjic disclosed
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`encapsulation, but—unlike Dean—PO did not oppose Ground 3 on this basis. Id.
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`at 148:14-151:5.
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`7
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`of enzyme immobilization have expressly described the exact Dean reference at
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`issue in this proceeding (Ex. 1006) as involving an “entrapped” enzyme. Ex. 1029
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`(Enzyme-Loaded Liposomes as Microreactors) at 290, 315 (“Dean et al. studied
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`the batch absorption of carbon dioxide by free and microencapsulated carbonic
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`anhydrase. The process was described by pseudo-steady-state model which
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`enabled to determine mass-transfer coefficients and the effectiveness factor for the
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`entrapped enzyme.”) (emphasis added). Akermin’s characterization of Dean as
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`teaching “entrapped” enzyme (within a porous microcapsule) is accurate and
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`consistent with the understanding of one of ordinary skill in the art.
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`The prior art cited during prosecution similarly describes the enzymes within
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`microcapsules as being entrapped. For example, U.S. Patent No. 5,858,746 was
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`considered during the prosecution of the ‘458 patent. See Ex. 1001 at p. 2; Ex.
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`1002 at 16. The ‘746 patent refers uses both “entrapment” and “encapsulation” to
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`describe its encapsulation technique. See Ex. 1025 at 15:60-16:7. This intrinsic
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`evidence3 further confirms Akermin’s construction.
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`PO criticizes Dr. DeFilippi as offering conclusory testimony on the
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`construction of “entrapped in” (POR at 12), but the testimony of PO’s declarant on
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`the topic is substantially more suspect. Before joining CO2 Solutions Inc. in 2013,
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`3 Prior art considered during examination is intrinsic evidence as part of the
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`prosecution history. Phillips v. AWH Corp., 415 F.3d 1301, 1317 (Fed. Cir. 2005).
`
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`8
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`none of Dr. Fradette’s work experience or research was related to immobilization
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`of enzymes in a substrate. Ex. 1027 at 11:23-19:7, 82:10-19, 146:12-20, 182:11-
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`12. Even after 2013, it appears that he has not had significant personal
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`involvement in immobilization of enzymes in a substrate. Id. at 22:2-23:18.
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`Lacking any meaningful experience in immobilizing enzymes, Dr. Fradette
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`merely parrots PO’s position. Ex. 1027 at 82:3-9 (“That’s the definition that was
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`provided as the definition we use.”), 82:23-24 (“That’s the position I have in my
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`declaration.”). Unlike Dr. Fradette, Akermin’s declarant—Dr. DeFilippi—has had
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`substantial, hands-on experience in immobilizing enzymes. Ex. 2017 at 7:10-8:19;
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`10:2-8; 160:22-161:9. Dr. DeFilippi’s testimony on this issue is also supported by
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`the numerous references discussed in this Section. Dr. DeFilippi’s testimony
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`deserves more weight than Dr. Fradette’s testimony on this subject.
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`Akermin’s proposed construction of “entrapped in” is consistent with its use
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`in both the intrinsic and extrinsic evidence. Therefore, Akermin respectfully
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`requests the Board to adopt its proposed construction. 4
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`4 The Board initially construed the term “‘entrapped in the porous substrates’ to
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`mean captured and held in the porous substrates, while retaining at least some of
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`their activity and being accessible to reactants (e.g., CO2).” Paper 10 at 11.
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`Akermin believes, however, that the intrinsic and extrinsic evidence supports
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`differentiating between physical immobilization methods (entrapment) and
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`9
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`

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`III. THE CHALLENGED CLAIMS ARE UNPATENTABLE
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`It is undisputed that triphasic (Gas-Liquid-Solid) reactors were commonly
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`used in a large variety of industrial applications before the ‘458 patent. Ex. 1001 at
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`2:10-14; Ex. 1003 at ¶24. These reactors include a reaction chamber, a liquid inlet
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`and outlet, and a gas inlet and outlet. Ex. 1027 at 46:14-19, 166:13-167:4.
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`It is also undisputed that the use of the enzyme carbonic anhydrase for
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`treating carbon-dioxide containing gas emissions was known before the ‘458
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`patent. Ex. 1001 at 2:51-55; Ex. 1003 at ¶¶12-16; Ex. 1027 at 46:20-47:6.
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`Similarly, immobilization techniques for carbonic anhydrase, including
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`entrapment, were also known. Ex. 1003 at ¶¶17-23; Ex. 1027 at 47:7-48:7.
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`Thus, there is no dispute that the reactor elements of the claims referring to
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`the configuration of the reactor vessel (highlighted green below) and the use of
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`immobilized carbonic anhydrase for treating carbon-dioxide containing gas
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`emissions (highlighted yellow below) were known in the prior art.
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`immobilization methods that depend on binding the catalyst to the substrate.
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`Therefore, Akermin contends that the portion of its proposed construction
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`requiring the catalyst to be physically trapped in the porous substrate is important.
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`Otherwise, Akermin has no dispute with the Board’s initial construction, including
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`the requirement of the catalyst “being accessible to reactants (e.g., CO2).”
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`10
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`

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`
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`The only alleged advance over the prior art described in the ‘458 patent is
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`suspending the entrapped carbonic anhydrase in the liquid within the reactor. But
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`this common reactor configuration was also well known in the prior art.
`
`A. Ground 1: Claims 1-3, 15, 17, 24-27, 40-41, and 43 are
`Anticipated under § 102(b) by Bonaventura
`
`PO does not dispute that Bonaventura discloses bioreactors using
`
`immobilized carbonic anhydrase for removing carbon dioxide. POR at 18. PO’s
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`only dispute regarding Bonaventura is whether the porous substrates are in
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`suspension. POR at 26. PO claims that in “the embodiments disclosed in
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`Bonaventura ‘987, the enzyme is held in a solid substrate, similar to the
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`Hemosponge of Bonaventura ‘416, or in a packed configuration within a
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`compartment of the reactor.” POR at 26-27.
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`11
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`

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`1.
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`Figure 6 of Bonaventura depicts particles in suspension
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`PO asserts that Figure 6 depicts “a polymeric, sponge-like material 24 in
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`which carbonic anhydrase is entrapped.” POR at 20. PO reaches this conclusion
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`based on the fact that the shading in Figure 6 of Bonaventura resembles the
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`shading used in Figures 9-11 of the ‘416 patent. See Ex. 1027 at 106:24-108:3.
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`This argument has a number of problems. First, it ignores the fact that the
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`shading used in Figure 6 is also similar to that used in Bonaventura’s Figure 4 to
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`represent features that are clearly not solid masses:
`
`
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`Ex. 1004 at Fig. 6, Fig. 4 (emphasis added). The grains (7) shown in Figure 4 are
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`described as a “complex” of an oxygen binding compound and oxygen that is
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`transported through conduit 11. Ex. 1004 at 21:9-50. If the shading used in Figure
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`4 indicated that the complex was a solid mass (as asserted by PO), rather than
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`flowable particles, it would not be able to stream through the conduit.
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`
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`Second, PO’s argument ignores Bonaventura’s express teaching that, in one
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`embodiment, immobilized enzyme 24 is a “flowable substrate,” including “gel
`
`
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`12
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`

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`particles capable of flowing with water.” Ex. 1004 at 30:26-30. This express
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`teaching forecloses PO’s interpretation based on the shading used in Figure 6.
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`
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`Third, PO incorrectly assumes that Figures 9-11 of the ‘416 patent each
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`disclose a solid sponge mass based on the use of the term “Hemosponge.” Ex.
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`1027 at 108:4-22. A closer reading of the ‘416 patent, however, reveals that
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`“Hemosponge” is merely a coined term used to describe the oxygen carrier
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`(hemoglobin) that has been immobilized (i.e., insolubilized) in one of the many
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`materials described by Bonaventura, including by using the prepolymer HYPOL.
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`Ex. 1005 at 6:56-7:10, 7:56-8:14. Once formed, this material could either be used
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`as a solid mass or ground into particles. Ex. 2017 at 159:13-165:2; Ex. 1005 at
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`6:56-64, 7:6-10, 7:33-36, Figs. 6 and 7 (depicting data achieved using the “sized-
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`gel formulation of Hemosponge”); Ex. 1027 at 110:2-112:1. In fact, Figure 9 of
`
`the ‘416 patent is described as “utilizing gel sized particles.” Ex. 1005 at 13:27-31.
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`2.
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`Particles “flowing with water” are “in suspension”
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`PO also argues that, because Bonaventura does not recite the specific words
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`“suspended” or “in suspension,” the particles were not in suspension. POR at 21.
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`But other terms of art—such as “slurry” and “fluidized”—are frequently used by
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`chemical engineers to describe reactors in which solids are suspended. Ex. 1027 at
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`43:23-44:20; see also Ex. 2017 at 84:6-18. Indeed, references cited by both parties
`
`use these other terms to describe reactors with suspended solids. See Ex. 1006 at
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`13
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`452 (“slurry”); Ex. 2007 at 6-7 (“slurry”); Ex. 2008 at 1013 (“fluidized”); Ex. 2006
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`at 23-54 (using “slurry” and “fluidized” as different “suspended catalyst beds”),
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`24-22 (“fluidized bed” of “catalytic particle[s]”).
`
`Bonaventura describes the porous substrates in Figure 6 as “gel particles
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`capable of flowing with water.” Ex. 1004 at 30:21-30. Particles that flow with
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`water (and depicted as distributed throughout the liquid, as in Figure 6) are in
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`suspension. See Ex. 1027 at 120:11-17. Further, the ‘416 patent—incorporated
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`into Bonaventura by reference— teaches that “the use of sized-gel particles allow
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`the use of fluidized bed absorption. . . .” Ex. 1005 at 7:42-45 (emphasis added),
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`12:30-41 (“FIG. 5 and FIGS. 9-11 show schematic diagrams of various laboratory
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`devices. . . making use of insolubilized hemoglobin . . . . This reactor [Fig. 5] can
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`be of the packed bed or fluidized bed type.”) (emphasis added), 16:49-51 (“The
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`method of claim 1, wherein said contacting is conducted in a fluidized bed of said
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`immobilized oxygen carrier.”) (emphasis added).
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`PO argues that “the reference in Bonaventura ‘987 to ‘gel particles capable
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`of flowing’ refers to embodiments that use relatively small gel particles in a packed
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`configuration within compartment 23, or to the potential that relatively small gel
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`particles may potentially come loose from a solid matrix.” POR at 23. This
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`argument contradicts PO’s prior representations made during prosecution.
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`During prosecution of the ‘458 patent, PO attempted to distinguish between
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`the claimed “in suspension” feature and prior-art references that taught carbonic
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`anhydrase immobilized on mounted or fixed supports. In doing so, PO represented
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`that “the cited references teach that the liquid flows over and around the supports
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`which are mounted within the reactors, while the presently claimed invention
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`requires that the substrates flow with and within the liquid.” Ex. 1002 at 72
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`(emphasis added). The Board noted this inconsistency in its Institution Decision
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`(Paper 10 at 16). But PO has made no attempt to reconcile its current position with
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`its prior representations to the Examiner.
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`3.
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`A mechanical agitator is not necessary for a suspension
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`PO also argues that “[i]f Fig. 6 had been intended to depict an immobilized
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`enzyme 24 that was in suspension in compartment 23, the skilled person would
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`expect that Fig. 6 would also depict a mechanical agitator or some other
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`mechanism for inputting mechanical energy into the system to keep the
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`immobilized enzyme 24 in suspension.” POR 21-22.
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`A number of variables are pertinent to whether particles will be suspended in
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`a particular reactor, including the density and viscosity of the liquid and the density
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`and particle size of the solid. Ex. 2014 at 549-550; Ex. 1027 at 58:23-61:3, 91:20-
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`92:15. Depending on these properties, the mechanical energy necessary to achieve
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`and maintain a suspension will vary and may be supplied by a number of different
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`sources, including liquid flow, gas flow, or a mechanical agitator. See, e.g., Ex.
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`15
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`2007 at 6-7, 333 (distinguishing mechanically agitated slurry reactors, bubble
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`column slurry reactors, and three-phase fluidized-bed reactors); Ex. 2008 at 1013.
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`PO concedes that “in some applications gas bubbles may provide
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`mechanical energy to maintain a suspension” (POR at 22), but fails to address the
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`mechanical energy introduced by the liquid flow. The flow of liquid through the
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`reactor can maintain a suspension. See, e.g., Ex. 2010 at 152 (Fig. 1); Ex. 2017 at
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`100:24-101:17 (describing utilizing down flowing liquid with buoyant particles
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`and upward flowing liquid with denser particles to force particles into suspension
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`in fluidized beds).
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`Dr. Fradette admitted that liquid flow can be a sufficient source of
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`mechanical energy to suspend particles in a reactor. Ex. 1027 at 122:7-19. But Dr.
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`Fradette concluded that in Figure 6 of Bonaventura the particles would accumulate
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`at the exit screen and form a packed configuration. Ex. 1027 at 121:8-122:6. Dr.
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`Fradette’s testimony on this point is not credible.
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`In his declaration, Dr. Fradette based his conclusion that the particles would
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`become packed based on a top-to-bottom flow: “Moreover, given the top-to-
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`bottom circulating flow of the liquid inlet-to-outlet streams in the reactor of Fig. 6,
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`any free catalyst gel particles would accumulate in stagnant regions of the reactor
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`and/or at the outlet screen 26(b).” Ex. 2004 at ¶99. But Dr. Fradette failed to
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`address the relevant variables (density and viscosity of the liquid, density and size
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`of the particles, etc.). And when confronted with the possibility of buoyant
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`particles during his deposition, Dr. Fradette abandoned his position, testifying that
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`the top-to-bottom flow (relied on in his declaration) would not work. Ex. 1027 at
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`121:8-125:13. Instead, he testified that his conclusions require reimagining the
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`reactor to have a different configuration from that actually depicted in Figure 6 or
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`addressed in his declaration. Id. at 123:12-20 (“Because the outlet in my
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`configuration, in my imagination is at the top, not at the bottom . . . .”), 125:2-13.
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`B. Ground 2: Claims 1-3, 15-17, 24-27, and 40-43 are Unpatentable
`under § 103(a) over Bonaventura in View of the ‘416 Patent
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`In Ground 2 of the Petition, Akermin relied on the reactor embodiments
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`shown in Figure 7 of Bonaventura and Bonaventura’s express teaching to use the
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`polyurethane gel particles described in the ‘416 patent as the porous substrate for
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`immobilizing the carbonic anhydrase. Petition at 29-42. As with Ground 1, PO’s
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`only basis for disputing Ground 2 is the “in suspension” limitation. POR at 27-31.
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`PO asserts that one skilled in the art would not combine the ‘416 patent’s
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`reference to a fluidized bed reactor in a two-phase system with Bonaventura’s
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`three-phase system shown in Figure 7. PO misses the point of the ‘416 patent’s
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`teaching. The ‘416 patent was cited by Bonaventura not for its reactor design, but
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`for the immobilization substrate. Ex. 1004 at 27:37-40 (“For example, the enzyme
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`of the present invention could be incorporated into and immobilized with a
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`polyurethane foam such as that described in U.S. Pat. No. 4,427,416.”). The fact
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`that these particles are shown in the ‘416 patent to be in fluidized beds merely
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`demonstrates that these particles are easily suspended.
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`PO does not dispute that “given the knowledge in the art regarding the need
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`for replacing the immobilized enzyme once it is inactivated, one skilled in the art
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`would have been motivated to use gel particles because the particles are easier to
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`replace in a reactor than a fixed substrate.” Petition at 31; see also Ex. 1003 at
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`¶97; Exhibit 1018 at 464-465; Ex. 1002 at 73-75; Paper 10 at 20. Instead, PO
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`argues that those skilled in the art would not have a reasonable expectation of
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`success in combining the reactor depicted in Figure 7 of Bonaventura with
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`fluidized-bed operations. POR at 29-30. PO bases this argument on its assertion
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`that the downwardly facing gas inlet would be incapable of delivering and
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`distributing sufficient gas flow to suspend the substrate. POR at 30. PO’s only
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`support is the conclusory testimony of Dr. Fradette. Id.; Ex. 2004 at ¶105.
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`PO’s argument (and Dr. Fradette’s testimony) is based on the assumption
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`that upward gas flow would be necessary to counteract the tendency for particles to
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`sink. This assumption is flawed when considering the characteristics of the
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`exemplary polyurethane gel particles disclosed in the ‘416 patent. In his
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`deposition, Dr. Fradette, acknowledged that the density of these polyurethane gel
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`particles is lower than that of water. Ex. 1027 at 103:19-104:20; see also Ex. 1005
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`at 10:65-67. In this case, the downward flow of the liquid is important to achieve a
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`fluidized bed. This fact was expressly noted in one of the exhibits cited by PO:
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`Three-phase fluidized-bed reactors are generally operated in a
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`cocurrent manner, but in some cases, they may also be operated i