Pfenex Inc. vs GlaxoSmithKline Biologicals SA

Notice of Refund

Petitioner's Request for Refund

DECISION Denying Institution of Inter Partes Review

Galen Declaration

van Wely 2001

Mergulhao 2004

Pappenheimer 1977

Perentesis 1988

Zettlmeissl 1986

Natale 2008

Mogensen 2005

Patent Owner Preliminary Response

Patent Owner Exhibit List

Madigan 2000

Choi 2004

Hegde 2006

Bashai I 1987

Orr 1999

Papanikou 2007

Uchida 1971

Hemila 1989

Cabiaux 1988

Duffaud 1987

Bishai II 1987

Talmadge 1980

Patent Owner's Mandatory Notices

Patent Owner's Power of Attorney

Notice of Accord Filing Date

Giannini, et al., ¿¿¿The Amino-Acid Sequence of Two Non-Toxic Mutants of Diphtheria Toxin: CRM45 and CRM197,¿¿¿ Nucleic Acids Research 12(10), 4063-69 (1984) (¿¿¿Giannini-1¿¿¿)

O¿¿¿Keefe, et al., ¿¿¿Cloned Diphtheria Toxin Within the Periplasm of Escherichia coli Causes Lethal Membrane Damage at Low pH,¿¿¿ Proc. Natl. Acad. Sci. USA 86, 343-46 (Jan. 1989)

Declaration of Christopher Butler dated August 8, 2019

United States Patent No. 9,422,345 (Blais et al.) (¿¿¿the ¿¿¿345 patent¿¿¿)

Prosecution History of United States Patent No. 9,422,345 (USSN 13/500,244)

International Publication No. WO 2011/042516A2 published on April 14, 2011 (Blais, et al.)

Great Britain Patent Application No. 0917647.0 (GlaxoSmithKline Biologicals S.A.)

United States Patent No. 6,455,673 (Collier) (¿¿¿Collier-1¿¿¿)

United States Patent Application Publication No. US2003/0157093A1 (Neville, Jr., et al) (¿¿¿Neville¿¿¿)

Huber, et al., ¿¿¿Use of Thioredoxin as a Reporter to Identify a Subset of Escherichia coli Signal Sequences That Promote Signal Recognition Particle-Dependent Translocation,¿¿¿ J. Bacteriol. 187(9), 2983-91 (May 2005) (¿¿¿Huber¿¿¿)

pET-22B(+) Vector Map (https://web.archive.org/web/20030819085202/http://www.novagen.com :80/docs/NDIS/69744-000.pdf)

Oh, et al., ¿¿¿Translocation of the Catalytic Domain of Diphtheria Toxin Across Planar Phospholipid Bilayers by Its Own T Domain,¿¿¿ Proc. Natl. Acad. Sci. USA 96, 8467-70 (July 1999)

Uchida, et al., ¿¿¿Diphtheria Toxin and Related Proteins,¿¿¿ J. Biological Chem. 248(11), 3838-44 (June 10, 1973)

Mekada, et al., ¿¿¿Binding Properties of Diphtheria Toxin to Cells Are Altered by Mutation in the Fragment A Domain,¿¿¿ J. Biological Chem. 260(22), 12148-53 (Oct. 5, 1985)

Anderson, ¿¿¿Antibody Responses to Haemophilus influenzae Type b and Diphtheria Toxin Induced by Conjugates of Oligosaccharides of the Type b Capsule...,¿¿¿ Infection & Immunity 39(1), 233-38 (Jan. 1983)

HibTITER¿¿, 2007 Physicians¿¿¿ Desk Reference, 61st ed., 3426-29 (Thomson PDR, Montvale, N.J., 2007)

PREVNAR¿¿, 2008 Physicians¿¿¿ Desk Reference, 62nd ed., 3405-11 (Thomson Healthcare Inc., Montvale, N.J., 2007)

Tweten, et al., ¿¿¿Molecular Cloning and Expression of Gene Fragments from Corynebacteriophage ¿¿ Encoding Enzymatically Active Peptides of Diphtheria Toxin,¿¿¿ J. Bacteriology 156(2), 680-85 (Nov. 1983)

Terpe, ¿¿¿Overview of Bacterial Expression Systems for Heterologous Protein Production: From Molecular and Biochemical Fundamentals to Commercial Systems,¿¿¿ Appl. Microbiol. Biotechnol. 72, 211-22 (2006)

Novagen, pET System Manual, 11th ed. (2006)

Lee, et al, ¿¿¿Protein Secretion and the Pathogenesis of Bacterial Infections,¿¿¿ Genes & Development 15, 1725-52 (Cold Spring Harbor Lab. Press, 2001)

Leong, et al., ¿¿¿Cloned Diphtheria Toxin Fragment A Is Expressed from the tox Promoter and Exported to the Periplasm by the SecA Apparatus of Escherichia coli K12,¿¿¿ J. Biological Chem. 258(24), 15016-20 (Dec. 25, 1983)

Lei, et al., ¿¿¿Characterization of the Erwinia carotovora pelB Gene and Its Product Pectate Lyase,¿¿¿ J. Bacteriol. 169(9), 4379-83 (Sept. 1987)

Sletta, et al., ¿¿¿The Presence of N-Terminal Secretion Signal Sequences Leads to Strong Stimulation of the Total Expression Levels of Three Tested...", Applied & Environmental Microbiology 73(3), 906-12 (Feb. 2007)

Papini, et al., ¿¿¿Diphtheria Toxin and Its Mutant crm 197 Differ in Their Interaction with Lipids,¿¿¿ FEBS Letters 215(1), 73-78 (May 1987)

Ikemura, et al., ¿¿¿Requirement of Pro-Sequence for the Production of Active Subtilisin E in Escherichia coli,¿¿¿ J. Biological Chem. 262(16), 7859-64 (June 5, 1987) (¿¿¿Ikemura¿¿¿)

Sambrook, et al., Molecular Cloning, A Laboratory Manual, 2nd ed. (Cold Spring Harbor Laboratory Press, U.S.A., 1989)

United States Patent No. 5,917,017 (Collier, et al.) (¿¿¿Collier-2¿¿¿)

Cohen, et al., ¿¿¿Construction of Biologically Functional Bacterial Plasmids In Vitro,¿¿¿ Proc. Nat. Acad. Sci. USA 70(11), 3240-44 (Nov. 1973)

Kaczorek, et al., ¿¿¿Nucleotide Sequence and Expression of the Diphtheria tox228 Gene in Escherichia coli,¿¿¿ Science 221, 855-58 (Aug. 26, 1983)

Lees, et al., ¿¿¿Conjugation Chemistry,¿¿¿ Pneumococcal Vaccines: The Impact of Conjugate Vaccine, Chap. 11, 163-74 (ASM Press, Washington, D.C., 2008)

United States Patent Application Publication No. US2012/0289688A1 (Blais et al.)

Merriam-Webster¿¿¿s Collegiate Dictionary, 10th ed., 168 (¿¿¿capable¿¿¿) (Merriam-Webster, Incorporated, Springfield, Mass., 1997)

Zhou, et al., ¿¿¿Secretory Expression of Recombinant Diphtheria Toxin Mutants in B. Subtilis,¿¿¿ J. Tongji Med. Univ. 19(4), 253-56 (1999)

Part 1 - Alberts, et al., Molecular Biology of The Cell, 5th ed., 128, 130-31, 147, 331-39, 345, 366-69, 532, 540-41, 546-48, 550-51, 617-18 (Garland Science, Taylor & Francis Group, LLC, New York, NY, 2008)

Part 2 - Alberts, et al., Molecular Biology of The Cell, 5th ed., 128, 130-31, 147, 331-39, 345, 366-69, 532, 540-41, 546-48, 550-51, 617-18 (Garland Science, Taylor & Francis Group, LLC, New York, NY, 2008)

Part 1 - Lewin, Genes IX, 246-49 (Jones and Bartlett Publishers, Inc., Boston, Mass., 2008)

Part 2 - Lewin, Genes IX, 246-49 (Jones and Bartlett Publishers, Inc., Boston, Mass., 2008)

Tan, et al., ¿¿¿E. coli Selection of Human Genes Encoding Secreted and Membrane Proteins Based on cDNA Fusions to a Leaderless ¿¿-Lactamase Reporter,¿¿¿ Genome Research 13, 1938-43 (Cold Spring Harbor Lab. Press, 2003)

Sletta, et al., ¿¿¿Broad-Host-Range Plasmid pJB658 Can Be Used for Industrial-Level Production of a Secreted Host-Toxic Single-Chain Antibody Fragment in...¿¿¿ Applied & Environmental Microbiol. 70(12), 7033-39 (Dec. 2004)

Puigbo, et al., ¿¿¿OPTIMIZER: A Web Server for Optimizing the Codon Usage of DNA Sequences,¿¿¿ Nucleic Acids Research 35, Web Server Issue, W126-31 (2007)

American Heritage College Dictionary, 3rd ed., 207 (¿¿¿capable¿¿¿) (Houghton Mifflin Co, Boston, Mass., 2000)

DeLisa, et al., ¿¿¿Folding Quality Control in the Export of Proteins by the Bacterial Twin-Arginine Translocation Pathway,¿¿¿ Proc. Natl. Acad. Sci. USA 100(10), 6115-20 (May 13, 2003)

Bishai, et al., ¿¿¿High-Level Expression of a Proteolytically Sensitive Diphtheria Toxin Fragment in Escherichia coli,¿¿¿ J. Bacteriol. 169(11), 5140-51 (Nov. 1987) (¿¿¿Bishai¿¿¿)

Giannini, et al., ¿¿¿The Complete Nucleotide Sequence of the Gene Coding for Diphtheria Toxin in the Corynephage Omega (tox+) Genome,¿¿¿ Nucleic Acids Research 11(19), 6589-95 (1983) (¿¿¿Giannini-2¿¿¿)

United States Patent Application Publication No. US2008/0193974A1 (Coleman, et al.)

GenBank, ¿¿¿Escherichia coli Str. K-12 Substr. MG1655, Complete Genome, showing region from base 1135497 to 1136594,¿¿¿ https://www.ncbi.nlm.nih.gov/nuccore/49175990?sat=4&satkey=2239 4872 (last visited Aug. 7, 2019)

UniProt, Version 31 of FlgI Ecoli downloaded from https://www.uniprot.org/uniprot/P0A6S3.txt?version=31 (last visited Aug. 7, 2019)

Greenfield, et al., ¿¿¿Nucleotide Sequence of the Structural Gene for Diphtheria Toxin Carried by Corynebacteriophage ¿¿,¿¿¿ Proc. Natl. Acad. Sci. USA 80, 6853-57 (Nov. 1983)

Van den Berg, et al., ¿¿¿X-Ray Structure of a Protein-Conducting Channel,¿¿¿ Nature 427, 36-44 (Jan. 2004)

Barbieri, et al., ¿¿¿Expression of a Mutant, Full-Length Form of Diphtheria Toxin in Escherichia coli,¿¿¿ Infection & Immunity 55(7), 1647-51 (July 1987)

Part 2 - Madigan, et al., Brock Biology of Microorganisms, 9th ed., 108, 154-55 (Prentice Hall, Upper Saddle River, N.J., 2000)

Part 4 - Madigan, et al., Brock Biology of Microorganisms, 9th ed., 108, 154-55 (Prentice Hall, Upper Saddle River, N.J., 2000)

Paetzel, et al., ¿¿¿The Structure and Mechanism of Bacterial Type I Signal Peptidases, A Novel Antibiotic Target,¿¿¿ Pharmacology & Therapeutics 87, 27-49 (2000)

Talmadge, et al., ¿¿¿Cellular Location Affects Protein Stability in Escherichia coli,¿¿¿ Proc. Natl. Acad. Sci. USA 79, 1830-33 (Mar. 1982)

Hasenwinkle, et al., ¿¿¿Very High-Level Production and Export in Escherichia coli of a Cellulose Binding Domain for Use in a Generic Secretion-Affinity Fusion System,¿¿¿ Biotech.and Bioengineering 55(6), 854-63 (Sept. 20, 1997)

Sch¿¿ffner, et al., ¿¿¿Cosecretion of Chaperones and Low-Molecular-Size Medium Additives Increases the Yield of Recombinant Disulfide-Bridged Proteins,¿¿¿ Applied & Environmental Microbiology 67(9), 3994-4000 (Sept. 2001)

Horton et al., ¿¿¿Gene Splicing by Overlap Extension,¿¿¿ Methods in Enzymology, 217, 270-279 (1993)

Petitioner Power of Attorney

Part 1 - Madigan, et al., Brock Biology of Microorganisms, 9th ed., 108, 154-55 (Prentice Hall, Upper Saddle River, N.J., 2000)

Part 3 - Madigan, et al., Brock Biology of Microorganisms, 9th ed., 108, 154-55 (Prentice Hall, Upper Saddle River, N.J., 2000)

Bibi, ¿¿¿Co- and Posttranslational Protein Targeting to the SecYEG Translocon in Escherichia coli,¿¿¿ The Periplasm, Chap. 1, 3-15 (ASM Press, Washington, D.C., 2007)

Stephenson, ¿¿¿Sec-Dependent Protein Translocation Across Biological Membranes: Evolutionary Conservation of... (Review),¿¿¿ Molecular Membrane Bio. 22(-2), 17-28 (Jan.-Apr. 2005) (https://doi.org/10.1080/09687860500063308)

Maniatis (1982) ¿¿¿ Molecular cloning. A laboratory manual by T. Maniatis, E. F. Fritsch and J. Sambrook. Cold Spring Harbor Laboratory, New York. 1982

Prosecution History excerpt of EP App.No. 16192258.8, Aug.16, 2018 GlaxoSmithKline Reply to Apr.18, 2018 EPO Comm.(https://register.epo.org/application?number=EP16192258&d-16544-o=2&Ing=en&tab=doclist&d-16544-s=1)

Joly, et al., ¿¿¿Practical Applications for Periplasmic Protein Accumulation,¿¿¿ The Periplasm, 345-60 (ASM Press, Washington, D.C., 2007)

Chatel, et al., ¿¿¿Expression of a Lipocalin in Prokaryote and Eukaryote Cells: Quantification and Structural Characterization of Recombinant Bovine ¿¿-Lactoglobulin,¿¿¿ Protein Expression and Purification 16, 70¿¿75 (1999)

Paoletti, et al., ¿¿¿Preclinical Evaluation of Group B Streptococcal Polysaccharide Conjugate Vaccines Prepared with a Modified Diphtheria Toxin and a Recombinant Duck Hepatitis B Core Antigen,¿¿¿ Vaccine 20, 370-76 (2002)

Heckman, et al., ¿¿¿Gene Splicing and Mutagenesis by PCR-Driven Overlap Extension,¿¿¿ Nature Protocols 2(4), 924-32 (2007)

Declaration of Lorelei P. Westin dated August 9, 2019

Declaration of Joseph Oliver Falkinham, III Ph.D. in Support of Petition for Inter Partes Review of U.S. Patent No. 9,422,345

Petitioner's Explanation of Multiple Petitions Challenging Patent No. 9,422,345 and Ranking of Petitions

Petition for Inter Partes Review of US Patent 9,422,345