`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`BUTAMAXTM ADVANCED BIOFUELS LLC
`Petitioner
`
`V.
`
`GEVO, INC.
`Patent Owner
`
`CASE IPR: IPR2013-00539
`Patent 8,273,565
`
`BUTAMAXTM ADVANCED BIOFUELS LLC’S
`DEMONSTRATIVES FOR ORAL ARGUMENT
`(INTER PARTES REVIEW OF U.S. PATENT NO. 8,273,565)
`
`Mail Stop "PATENTBOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`BUTAMAX 1026
`
`
`
`BUTAMAX ADVANCED BIOFUELS, LLC,
`Petitioner,
`v.
`GEVO, INC.,
`Patent Owner.
`____________
`
`IPR2013-00539 (Patent No. 8,273,565)
`
`October 28, 2014
`
`1
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`BUTAMAX 1026
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`Gevo does not contest …
`
`• Jurisdiction
`
`• Claim construction
`
`• Dr. Thiele’s testimony is not rebutted by an
`expert
`
`Paper 19
`
`2
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`Ground 1: Gevo does not contest …
`
`Ground 35 U.S.C.
`1
`§ 102(e)
`
`Claims
`1-4, 6-8 and 11-19
`
`Index of References
`Flint (BMX1003)
`
`• Flint (and its ‘333 provisional application) discloses
`every element of claims 1‐4, 6‐8, and 11‐19
`
`Paper 4, pg. 26; BMX1002, pgs. 26‐27; Paper 9, pgs. 16‐18; Paper 19, pg. 15.
`
`3
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`U.S. Patent 8,273,565 B2, Claim 1
`
`What is claimed is:
`
`1. A recombinant yeast microorganism comprising a
`recombinantly overexpressed polynucleotide encoding a
`dihydroxy acid dehydratase (DHAD),
`
`wherein said recombinant yeast microorganism is engineered to
`comprise at least one inactivated monothiol glutaredoxin
`selected from the group consisting of monothiol glutaredoxin-3
`(GRX3) and monothiol glutaredoxin-4 (GRX4),
`
`and wherein said inactivated monothiol glutaredoxin results from
`the deletion of one or more nucleotides of an endogenous gene
`encoding said monothiol glutaredoxin, the insertion of one or
`more nucleotides into an endogenous gene encoding said
`monothiol glutaredoxin, or combinations thereof.
`
`BMX1001, col. 91, ll. 15‐26.
`
`4
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`Ground 1: Flint anticipates claims 1-4, 6-8, & 11-19
`
`• All claims encompass inactivating GRX3/4 by deleting one
`or more nucleotides, inserting one or more nucleotides or
`both
`• Provisional applications do not support full scope
`• Gevo relies upon:
`• “…‘engineer’ refers to … mutating a polynucleotide and/or
`polypeptide native to the microorganism. …” ‘952 application,
`¶[0067] and ‘209 application, ¶[0073].
`• “… Mutations include, for example, point mutations, deletions, or
`insertions of single or multiple residues in a polynucleotide, …”
`‘952 application, ¶[0068] and ‘209 application, ¶ [0074].
`• “a deletion of part or all of a gene.” ‘952 application, ¶[0068].
`• “… alteration, disruption, deletion or knocking‐out of a gene or
`polynucleotide …” ‘952 application, ¶[00213] and ‘209 application,
`¶[00244].
`
`Paper 4, page 24; BMX1002 at ¶49; Paper 19, pgs. 7‐8 and 10‐11.
`
`5
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`Ground 2: Gevo does not contest …
`
`Ground
`
`35 U.S.C.
`
`Index of References
`Claims
`Anthony (BMX1005), Puig
`1-4, 6-8 and
`2
`§ 103(a)
`11-19
`(BMX1006) and Ojeda (BMX1007)
`• Anthony, Puig, and Ojeda are prior art
`• Anthony teaches a recombinant yeast overexpressing
`DHAD and having reduced activity of Fe‐S cluster
`proteins
`• Puig teaches that Aft induces expression of the iron
`regulon, including Cth2, and Cth2 is responsible for
`downregulating Fe‐S cluster genes
`• Ojeda teaches that deleting GRX3 and GRX4 decreases
`enzymatic activity of several Fe‐S proteins
`
`Paper 4, pgs. 29, 30, 35, 37, and 39; BMX1002 at ¶¶ 75, 79, 81; BMX1005 ¶¶[003], [006], [0013], [0074, [0075]; BMX1006
`pp. 99‐101, 103, 104, 108, Suppl. Table S2; BMX1007, pgs. 17661‐63; Paper 9, pgs. 20‐21; Paper 19, pgs. 15‐17, and 20
`
`6
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`Ground 2: Gevo argues:
`
`• Anthony does not teach inactivating GRX3/4
`• But, Ground 2 is based on a combination of art
`
`• Anthony and Puig teach against overexpressed DHAD
`• But, Puig teaches downregulation of endogenous DHAD
`
`• Ojeda teaches away from the claims
`• But, Ojeda teaches that deleting GRX3 and 4 decreases activity
`of endogenous Fe‐S proteins
`
`• But, claims are directed to recombinantly overexpressed
`DHAD
`
`Paper 4, pages 37, 38, 45‐47; Paper 19, pgs. 15‐17 and 20‐21; Paper 21, pgs. 5‐6, 9‐10, 12‐13
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`7
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`Ground 2: Recombinant DHAD lacking endogenous 3’ UTR
`
`• Puig teaches Cth2‐mediated targeted mRNA
`degradation of endogenous Fe‐S cluster proteins
`
`• Puig teaches the nucleotide sequences that are
`targeted by Cth2
`• Puig teaches that the 3’UTR of endogenous DHAD
`contains putative AREs [nucleotide sites] targeted by
`Cth2
`
`• A POSA would have been motivated to construct a
`recombinant DHAD that would be encoded by
`mRNA that lacks the Cth2‐mRNA binding sequence
`found in the 3’ UTR of mRNA that encodes
`endogenous DHAD.
`
`Paper 4, pgs. 37, 38, 45‐47; BMX1002 at ¶¶ 80, 102, 103, 105, 107, 108, 109; Paper 9, pg. 20; Paper 19, pg. 17; Paper
`21, pgs. 9‐10
`
`8
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`Grounds 3 and 4: Gevo does not contest …
`
`Ground
`
`35 U.S.C.
`
`Claims
`
`3
`
`4
`
`§ 103(a)
`
`§ 103(a)
`
`5
`
`9
`
`Index of References
`Anthony (BMX1005), Puig (BMX1006), Ojeda
`(BMX1007) and Li (BMX1015)
`Anthony (BMX1005), Puig (BMX1006), Ojeda
`(BMX1007) and van Maris (BMX1008)
`
`• Li and van Maris are prior art
`• Li teaches KARI enzymes that use NADH as a co‐factor
`• van Maris teaches deleting PDC
`
`Paper 4, pgs. 47, 48, and 50‐51; BMX1002 at ¶¶ 94, 97; BMX1015 ¶¶[0006], [0127]‐[0133]; BMX1008, Abstract, p. 159,
`Figure 1, Table 2, and p. 163; Paper 9, pgs. 25 and 26; Paper 19, pg. 22
`
`9
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`No secondary considerations support patentability
`
`• Gevo’s alleged unexpected result is not commensurate
`in scope with the ‘565 patent claims
`
`• DHAD + GRX3 complete gene deletion
`
`• But claim encompasses deletion of one or more
`nucleotides, insertion of one or more nucleotides, or
`combinations thereof for GRX3, GRX4 or both
`
`Paper 4, pgs. 57‐58; Paper 21, pg. 14.
`
`10
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`Figure A from Petition
`
`High Iron
`
`Low Iron
`
`Aft1/2
`activation
`complex
`dissociation
`
`Aft 1/2
`
`Grx 3/4
`Fra 1/2
`
`Aft 1/2
`
`complex
`
`Mrs4
`
`Isu1
`
`Fre1
`
`Fet3
`
`Fe uptake
`Fe-S cluster formation/assembly
`
`Cth2 (Tis11)
`
`Cth2
`
`exemplary iron regulon genes
`
`LEU1
`
`DHAD/
`ILV3
`
`AOO1
`
`cytosol
`
`nucleus
`
`exemplary Fe-S cluster proteins
`
`Paper 4, pg. 32, Figure A; BMX1002, pg. 44, Figure A
`
`11
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`
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`Flint, Fig. 10
`
`Figure 10
`
`Apo-DHAD
`
`Holo-DHAD
`
`Mitochondria
`
`CIA2
`
`[2Fe=2S]
`
`Vacuole
`
`Fe
`
`CCC1
`
`Fe
`
`Fe
`
`Aft1
`
`Aft1
`Aft1
`
`Grx3/4
`
`Fra2
`
`Nucleus
`
`Aft1
`
`activation
`Fe regulon
`
`BMX1003, Fig. 10.
`
`12
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`BUTAMAX 1026
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`CERTIFICATION OF SERVICE (37 C.F.R. § 42.6(e))
`
`The undersigned hereby certifies that the above-captioned "Buta maxTM
`
`Advanced Biofuels LLC’s Demonstratives for Oral Argument" were served
`
`electronically in their entirety on October 23, 2014, upon the following party:
`
`IPR2013-00539@cooley.com
`Cooley LLP
`1229 Pennsylvania Avenue, N.W.
`Washington, DC 20004-2400
`
`Respectfully submitted,
`STERNE, KESSLER, GOLDSTEIN & Fox P.L.L.C.
`
`Deboizait Sterling, Ph.D.
`Lead Attorney for Petitioner
`Registration No. 62,732
`
`Date: October 23, 2014
`
`1100 New York Avenue, N. W.
`Washington, D.C. 20005-3934
`(202) 371-2600
`
`1920154_I .DOCX