UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BLUEBIRD BIO, INC.,
`Petitioner,
`
`v.
`
`SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH,
`Patent Owner.
`____________
`
`Case No. IPR2023-00070
`Patent No. 7,541,179
`____________
`
`
`DECLARATION OF DR. JAMES RILEY
`IN SUPPORT OF PATENT OWNER’S RESPONSE
`
`
`
`
`
`
`
`
`SKI Exhibit 2056
`Page 1 of 189
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`Case IPR2023-00070
`Patent 7,541,179
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`
`Table of Contents
`
`Qualifications .................................................................................................. 4
`I.
`Relevant Field and Level of Ordinary Skill in the Art ................................... 6
`II.
`III. Materials Reviewed ........................................................................................ 8
`IV. The Understandings Applied to My Analysis .............................................. 14
`V.
`State of the Art .............................................................................................. 20
`A.
`Background ........................................................................................ 20
`B.
`The β-globin gene was intensely studied ........................................... 22
` While the LCR had been well-characterized, it was not
`high-level expression ............................................................... 24
`C. Methods for assembling expression vectors were known .................. 27
`Restriction Endonucleases ....................................................... 27
`
`
`PCR .......................................................................................... 30
`
`known which regions were needed to provide consistent
`
`
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`D. Despite all that was known about the β-globin gene, gene therapy
`vectors remained elusive .................................................................... 37
`VI. Vector Development and Testing is Slow .................................................... 40
`VII. The Claimed Lentiviral Vector Represented a Major Advancement
`Towards Genetic Treatment of Disorders such as Hemoglobinopathies ..... 42
`VIII. The ’179 and ’061 Patents ............................................................................ 45
`A.
`The Disclosures of the ’179 Patent .................................................... 46
`B.
`The Priority Date of the ’179 Patent .................................................. 52
`C.
`Prosecution History ............................................................................ 64
`IX. The Asserted Art ........................................................................................... 64
`A.
`Summary of the Asserted Art ............................................................. 64
` May Abstract ............................................................................ 64
`
`The Nature Article ................................................................... 68
`
`The May Thesis ........................................................................ 70
`Use of the Asserted Art ...................................................................... 73
`
`B.
`
`
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`in the Asserted Art or (ii) that the Clams Were Obvious in View of that
`
`The Nature Article Does Not Anticipate Claims 1, 19, and 22 of the
`
`Claim Construction ....................................................................................... 74
`X.
`XI. Petitioner Fails to Show that (i) Each Limitation of the Claims is Disclosed
`Art ................................................................................................................. 75
`A.
`’179 Patent .......................................................................................... 77
`
`generate the disclosed HS fragments ....................................... 77
`
`
`A POSA would have understood that PCR could be used to
`
`None of the HS fragments generated using restriction
`
`enzymes are the sizes of the HS fragments disclosed in the
`
`Nature Article ........................................................................... 84
`XII. The Asserted Art Fails to Render the Challenged Claims Obvious ........... 104
`The Nature Article Does Not Render the Claims Obvious.... 104
`
`
`Obvious. ................................................................................. 110
`
`The May Abstract Does Not Render the Challenged Claims
`
`
`
`
`
`
`
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`Case IPR2023-00070
`Patent 7,541,179
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`I, James Riley, declare as follows:
`
`1.
`
`I am over the age of 21 years and am fully competent to make this
`
`Declaration. I make the following statements based on personal knowledge and, if
`
`called to testify to them, could and would do so.
`
`2.
`
`I understand these patents are being challenged in inter partes reviews
`
`in front of the Patent Trial and Appeal Board of the United States Patent and
`
`Trademark Office.
`
`3.
`
`I understand that the validity of certain claims of U.S. Patent No.
`
`7,541,179 (“the ’179 Patent”) and U.S. Patent No. 8,058,061 (“the ’061 Patent”)
`
`have been challenged in inter partes review (IPR) proceedings in front of the Patent
`
`Trial and Appeal Board of the United States Patent and Trademark Office.
`
`Specifically, in IPR2023-00070 the validity of claims 1, 10, 19, and 22 of the ’179
`
`Patent have been challenged, and in IPR2023-0074 the validity of claims 1, 2, 5-8,
`
`11, and 15 of the ’061 Patent have been challenged. I make this declaration in support
`
`of Patent Owner’s Preliminary Response in the above-captioned inter partes review.
`
`I.
`
`Qualifications
`
`4.
`
`I received my B.S. from Vanderbilt University in Molecular Biology in
`
`1989. I received my Ph.D. from Emory University in Genetics and Molecular
`
`Biology in 1994 under the supervision of Dr. Jeremy Boss. I did my postdoctoral
`
`
`
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`work at the Walter Reed Army Institute of Research in the Division of Retrovirology
`
`under the supervision of Dr. Carl June.
`
`5.
`
`I am currently employed by the University of Pennsylvania’s Perelman
`
`School of Medicine, where I am a Professor of Microbiology. I am also a member
`
`of the Immunology and Cell & Molecular Biology Graduate Groups as well as the
`
`Institute for Immunology, Center for Cellular Immunotherapies, and Diabetes
`
`Research Center. I also currently serve on the Scientific Advisory Board at the Johns
`
`Hopkins Translational ImmunoEngineering Center at Johns Hopkins University.
`
`6.
`
`I have also published approximately 10 papers that have examined how
`
`to best control expression of inserted genes in lentiviral vectors or DNA plasmids.
`
`7.
`
`In 1999, I joined the faculty at the University of Pennsylvania School
`
`of Medicine, where I am currently still a professor.
`
`8.
`
`Since 2000, I have served as an editorial reviewer for the Human Gene
`
`Therapy journal. Around that time, and since then, I have also been an editorial
`
`reviewer for the journals Cell, Science, and Nature and their more specialized sister
`
`journals, Clinical Immunology, Journal of Clinical Investigation, the Journal of
`
`Immunology, and Molecular Therapy, among others.
`
`
`
`5
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`9.
`
`Between 1992 and 1996, I published a series of articles that described
`
`the promoter elements required to regulate MHC class II genes in a B-cell-specific
`
`manner:
`
` In early 2001, I presented a lecture on the use of lentiviruses for
`HIV-1 immunotherapy.
`
` In 2013, I presented a lecture on “Gene Therapy Approaches to
`Treat and Cure HIV-1 Infection” as part of Nobel Forum:
`Towards an HIV-1 Cure, in Stockholm, Sweden.
`
` In 2015, I co-founded a cell and gene therapy company called
`Tmunity Therapeutics, which was recently acquired by
`Gilead/Kite.
`
` Since 2016, I have lectured on Genome Engineering as part of
`the Cell and Gene Therapy course offered to University of
`Pennsylvania graduate students.
`
` In 2021, I coauthored a peer reviewed review entitled “Genetic
`Engineering of T cells for Immunotherapy” that was published
`in Nature Reviews Genetics.
`
`10. A copy of my current CV is attached as Appendix A.
`
`II. Relevant Field and Level of Ordinary Skill in the Art
`
`11.
`
`I have reviewed the ’179 Patent and portions of its prosecution history
`
`with the United States Patent and Trademark Office. Specifically, I have reviewed
`
`
`
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`the ’179 Patent and its prosecution history in relation to the asserted prior art and
`
`arguments at issue in the present inter partes review.
`
`12.
`
`I have reviewed Dr. Jörg Bungert’s declaration, submitted in support of
`
`the Petition, which I understand to be Ex. 1002. I understand Dr. Bungert has taken
`
`the position that a person of ordinary skill in the art at the time of the invention
`
`(“POSA”) would have had at least an advanced degree (e.g., a Master’s or Ph.D.) in
`
`biochemistry, biotechnology, protein chemistry, genetics, molecular and structural
`
`biology, bioengineering, or similar disciplines. (Ex. 1002 at ¶14.) He also opines that
`
`a POSA would also have had several years of post-graduate training or related
`
`experience in one or more of these areas, which would have given them an
`
`understanding of vector design and the effect of LCR fragments on gene expression,
`
`including how the LCR regulates gene expression. (Id. at ¶15.) I disagree with Dr.
`
`Bungert in that several years of post-graduate training would be required to a POSA
`
`understanding of vector design and the effect of LCR fragments on gene expression,
`
`including how the LCR regulates gene expression.
`
`13. Based on my experience described above and contained in my C.V., I
`
`have an established understanding of the relevant field in the relevant timeframe,
`
`and the knowledge that would have been known by a POSA, as defined above and
`
`during the relevant time frame (late 1990s to very early 2000s).
`
`
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`III. Materials Reviewed
`
`14.
`
`I have reviewed the Petition and supporting evidence. I have also
`
`reviewed all challenged claims of the ’179 Patent (Claims 1, 10, 19, and 22), as well
`
`as the ’179 Patent and parts of its file history. I have examined the prior art references
`
`asserted against the ’179 Patent in the Petition. I have also reviewed the transcript
`
`produced from Dr. Bungert’s deposition on July 10, 2023. (Ex. 2055.) I will use the
`
`exhibit numbers listed on the “List of Exhibits” on pages vi-ix of the Petition and
`
`the exhibit numbers listed in Patent Owner’s Exhibit List, which I have included for
`
`ease of reference below:
`
`Description
`
`Exhi
`bit
`No.
`2001 Exclusive Licensee Agreement Between Sloan Kettering Institute for
`Cancer Research and San Rocco Therapeutics, LLC
`January 2023 Declaration of Dr. James Riley
`2002
`2003 October 2020 Declaration of Dr. Michel Sadelain
`2004 Petitioner’s October 2020 Letter Submitting Dr. Sadelain’s October 2020
`Declaration in New York State Court
`Joint Defense Agreement
`2005
`January 2023 Declaration of Michel Sadelain
`2006
`January 2023 Declaration of Chad May
`2007
`January 2023 Declaration of Stefano Rivella
`2008
`January 2023 Declaration of Lucio Luzzatto
`2009
`2010 Sorrentino, B., One Step Closer to Gene Therapy for
`Hemoglobinopathies, Blood (2004) 104(12):3419.
`2011 Caterina J., et al., Human Beta-Globin Locus Control Region: Analysis
`of the 5’ DNase I Hypersensitive Site HS2 in Transgenic Mice, Proc.
`Nat’l. Acad. Sci. USA. (1991) 88(5):1626-30.
`
`
`
`8
`
`SKI Exhibit 2056
`Page 9 of 189
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`Case IPR2023-00070
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`
`Description
`
`Exhi
`bit
`No.
`2012
`
`2013
`
`Judson, H., The Glimmering Promise of Gene Therapy, MIT Tech. Rev.
`(Nov. 1, 2006),
`https://www.technologyreview.com/2006/11/01/227582/the-glimmering-
`promise-of-gene-therapy/.
`Jackson, J., et al. Role of DNA Sequences Outside the Cores of DNase
`Hypersensitive Sites (HSs) in Functions of the β-globin Locus Control
`Region: Domain Opening and Synergism Between HS2 and HS3, J. Biol.
`Chem. (1996) 271(20):11871-8.
`2014 Philipsen, S., et al. The β-globin Dominant Control Region:
`Hypersensitive Site 2, EMBO J. (1990) 9(7):2159-67.
`2015 Hardison, R., et. al., Locus Control Regions of Mammalian β-globin
`Gene Clusters: Combining Phylogenetic Analyses and Experimental
`Results to Gain Functional Insights, Gene (1997) 205(1-2):73-94.
`2016 Persons, D. & Nienhuis, A., Gene Therapy for the Hemoglobin
`Disorders: Past, Present, and Future, Proc. Nat’l. Acad. Sci. USA
`(2000) 97(10):5022-24.
`2017 Kafri, T. et al., Lentiviral Vectors: Regulated Gene Expression,
`Molecular Therapy (2000) 1(6): 516-521.
`2018 Amado, R. & Chen, I., Lentiviral Vectors — the Promise of Gene
`Therapy within Reach? Science. (1999) 285(5428):674-76.
`2019 Chada, K., et al., Specific Expression of a Foreign β-globin Gene in
`Erythroid Cells of Transgenic Mice, Nature (1985) 314(6009):377-80.
`2020 Townes, T., et al., Expression of Human β-globin Genes in Transgenic
`Mice: Effects of a Flanking Metallothionein-Human Growth Hormone
`Fusion Gene, Mol. Cell. Biol. (1985) 5(8):1977-83.
`2021 Dzierzak, E., et al., Lineage-Specific Expression of a Human β-globin
`Gene in Murine Bone Marrow Transplant Recipients Reconstituted with
`Retrovirus-Transduced Stem Cells, Nature (1988) 331(6151):35-41.
`2022 Bodine, D., et. al., Combination of Interleukins 3 and 6 Preserves Stem
`Cell Function in Culture and Enhances Retrovirus-Mediated Gene
`Transfer into Hematopoietic Stem Cells, Proc. Nat’l. Acad. Sci. USA
`(1989) 86(22):8897-901.
`2023 Bender, M., et al., A Majority of Mice Show Long-Term Expression of a
`Human β-globin Gene After Retrovirus Transfer into Hematopoietic
`Stem Cells, Mol. Cell. Biol. (1989) 9(4):1426-34.
`9
`
`
`
`SKI Exhibit 2056
`Page 10 of 189
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`

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`Case IPR2023-00070
`Patent 7,541,179
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`Description
`
`Exhi
`bit
`No.
`2024 Sadelain, M., et al., Generation of a High-Titer Retroviral Vector
`Capable of Expressing High Levels of the Human B-globin Gene, Proc.
`Nat’l Acad. Sci. (USA) (1995) 92(15):6728-32.
`2025 GenBank Accession No. Z84721 (Mar. 19, 1997).
`2026 NCBI RefSeq Gene HBA2, RefSeq:NM_000517.6 (data last updated
`Oct. 28, 2022).
`2027 Hardison, R., et al., Sequence and Comparative Analysis of the Rabbit α-
`Like Globin Gene Cluster Reveals a Rapid Mode of Evolution in a G +
`C-rich Region of Mammalian Genomes, J. Mol. Biol. (1991) 222(2):233-
`49.
`2028 Huisman, T., et al., A Syllabus of Human Hemoglobin Variants (1996),
`published by The Sickle Cell Anemia Foundation in Augusta, Georgia,
`2029 GenBank Accession No. J00179 (1993).
`2030 Tagle, D., et al., The β Globin Gene Cluster of the Prosimian Primate
`Galago crassicaudatus: Nucleotide Sequence Determination of the 41-kb
`Cluster and Comparative Sequence Analyses, Genomics (1992)
`13(3):741-60.
`2031 Li, Q. et al., Development of Viral Vectors for Gene Therapy of β-Chain
`Hemoglobinopathies: Optimization of a γ-Globin Gene Expression
`Cassette, Blood (1999) 93(7):2208-16.
`2032 Slightom, J., et al., Human Fetal Gγ- and Aγ-Globin Genes: Complete
`Nucleotide Sequences Suggest that DNA Can Be Exchanged Between
`These Duplicated Genes, Cell (1980) 21(3):627-38.
`2033 Excerpts from Inventor Notebooks
`2034 Excerpts from Inventor Notebooks
`2035 October 2020 Affidavit of Dr. Isabelle Rivière
`2036 Verma, I. & Weitzman, M., Gene Therapy: Twenty-First Century
`Medicine, Annu. Rev. BioChem. (2005) 74:711-38.
`2037 Blau, H. & Springer, M., Molecular Medicine, Gene Therapy – A Novel
`Form of Drug Delivery, N. Engl. J. Med. (1995) 333(18):1204-07.
`2038 Morris, A., et al., MHC Class II Gene Silencing in Trophoblast Cells is
`Caused by Inhibition of CIITA Expression, Am. J. Reproductive
`Immunology (1998) 40(6):385-94.
`2039 Bernards, R., et al. Physical Mapping of the Globin Gene Deletion in β-
`thalassemia, Gene (1979) 6(3):265-80.
`10
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`

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`Case IPR2023-00070
`Patent 7,541,179
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`Description
`
`Exhi
`bit
`No.
`2040 Ryan, T., et al., A Single Erythroid-Specific DNase I Super-
`Hypersensitive Site Activates High Levels of Human β-globin Gene
`Expression in Transgenic Mice, Genes & Dev. (1989) 3(3): 314-23.
`2041 Pasceri, P., et al., Full Activity from Human β-globin Locus Control
`Region Transgenes Requires 5'HS1, Distal β-globin Promoter, and 3’ β-
`globin Sequences, Blood (1998) 92(2):653-63.
`2042 Hardison, R., et al., Locus Control Regions of Mammalian β-globin Gene
`Clusters: Combining Phylogenetic Analyses and Experimental Results to
`Gain Functional Insights, Gene (1997) 205(1-2):73-94.
`2043 Hacein-Bey-Abina, S., et. al., “A Serious Adverse Event after Successful
`Gene Therapy for X-Linked Severe Combined Immunodeficiency, N.
`Engl. J. Med. (2003) 348(3):255-256.
`2044 Pfeifer, A., & Verma, I., Gene Therapy: Promises and Problems, Annu.
`Rev. Genomics Hum. Genet. (2001) 2:177-211.
`2052 Bungert, J., et al., Synergistic Regulation of Human β-globin Gene
`Switching by Locus Control Region Elements HS3 and HS4, Genes and
`Development (1995) 9:3083-3096
`2053 Duplicate of Ex. 2014.
`2054 Liu, Q., et al., Mutation of Gene-proximal Regulatory Elements Disrupts
`Human ε-, γ-, and β-globin Expression in Yeast Artificial Chromosome
`Transgenic Mice, Proc. Natl. Acad. Sci. USA (1996) 94:169-174
`2055 Transcript of Deposition of Dr. Jӧrg Bungert on July 10, 2023
`
`2057 McInerney, J., et al. Slow and Steady Wins The Race? Progress in the
`Development of Vectors for Gene Therapy of β-Thalassemia and Sickle
`Cell Disease, Hematology (2000) 4(5):437-455.
`2058 Grosveld, F., et al., The Dynamics of Globin Gene Expression
`and Gene Therapy Vectors, Ann. NY Acad. Sci. (1998) 850:18-27.
`2059 Fraser, P., et al., DNaseI Hypersensitive Sites 1, 2 and 3 of the Human β-
`globin Dominant Control Region Direct Position-Independent
`Expression, Nucleic Acids Res. (1990) 18(12):3503-8.
`2060 Fraser, P., et al., Each Hypersensitive Site of the Human β- globin Locus
`Control Region Confers a Different Developmental Pattern of
`Expression on the Globin Genes, Genes & Dev. (1993) 7(1):106-13.
`
`11
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`SKI Exhibit 2056
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`Case IPR2023-00070
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`Description
`
`Exhi
`bit
`No.
`2061 Kulozik, A., et al., The Proximal Element of the β Globin Locus Control
`Region Is Not Functionally Required In Vivo, J. Clin. Invest. (1991)
`87(6):2142-46.
`2062 Milot, E., et al., Heterochromatin Effects on the Frequency and Duration
`of LCR-Mediated Gene Transcription, Cell (1996) 87(1):105-14.
`2063 Peterson, K., et al., Effect of Deletion of 5’HS3 or 5’HS2 of the Human
`β-globin Locus Control Region on the Developmental Regulation of
`Globin Gene Expression in β-globin Locus Yeast Artificial Chromosome
`Transgenic Mice, Proc. Nat’l. Acad. Sci. USA (1996) 93(13):6605-09.
`2064 Bungert, J., et al., Hypersensitive Site 2 Specifies a Unique Function
`within the Human β-Globin Locus Control Region To Stimulate Globin
`Gene Transcription, Mol. Cell. Biol. (1999) 19(4):3062–3072.
`2065 Tuan, D., et al., An Erythroid-Specific, Developmental-Stage-
`Independent Enhancer far Upstream of the Human “β-like Globin”
`Genes, Proc. Nat’l. Acad. Sci. USA (1989) 86(8):2554-58.
`2066 Collis, P., et al., Definition of the Minimal Requirements Within the
`Human β-globin Gene and the Dominant Control Region for High Level
`Expression, EMBO J. (1990) 9(1): 233-40.
`2067 Costa, G., et al., Cloning and Analysis of PCR-Generated DNA
`Fragments, PCR Methods Appl. (1994) 3(6):338-45.
`2068 Clive Newton & Alex Graham, PCR (Introduction to Biotechniques
`Series) (2nd Ed. 1997).
`2069 Safety of Gene Therapy, CSPAN (Feb. 2, 2000), https://www.c-
`span.org/video/?155137-1/safety-gene-therapy.
`2070 Press Briefing by Scott McClellan, The White House (Aug. 9, 2001),
`https://georgewbush-
`whitehouse.archives.gov/news/briefings/20010809.html#Scott,%20back
`%20on%20stem%20cells (last visited July 27, 2023).
`2071 Robert Cooke, New Gene Therapy Hopes / Experiments Point to Cures
`for Blood Diseases, Newsday (July 6, 2000),
`https://www.sfgate.com/health/article/New-Gene-Therapy-Hopes-
`Experiments-point-to-2714623.php.
`2072 Malik, P., Toward Gene Therapy for β-thalassemia; New Models, New
`Approaches, Blood (2003) 101(8): 2902-03.
`
`
`
`12
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`SKI Exhibit 2056
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`Case IPR2023-00070
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`Description
`
`Exhi
`bit
`No.
`2073 Stamatoyannopoulos, M., Prospects for Developing a Molecular Cure
`for Thalassemia, Hematology (2005) 10 (Supplement 1): 255-57.
`2074 Malech, H., et al., Evolution of Gene Therapy, Historical Perspective,
`Hematol. Oncol. Clin. N. Am. (2022) 36(4):627-45.
`2075 Stoeckert, C. & Cheng, H., Partial Repression of Human γ-Globin Genes
`by LCR Element HS3 When Linked to β-Globin Gens and LCR Element
`HS2 in MEL Cells, Am. J. Hematology (1996) 51(3):220-28.
`2076 Ryan, T., et al., Knockout-Transgenic Mouse Model of Sickle Cell
`Disease, Science (1997) 278(5339):873-76.
`2077 Walsh, C., et al., Regulated High Level Expression of Human γ-Globin
`Gene Introduced into Erythroid Cells by an Adeno-Associated Virus
`Vector, Proc. Nat’l. Acad. Sci. USA (1992) 89(15):7257-61.
`2078 Arcasoy, M., et al., High Levels of Human γ-Globin Gene Expression in
`Adult Mice Carrying a Transgene of Deletion-Type Hereditary
`Persistence of Fetal Hemoglobin, Mol. Cell. Biol. (1997) 17(4):2076-89.
`2079 McCune, S., et al., Recombinant Human Hemoglobins Designed for
`Gene Therapy for Sickle Cell Disease, Proc. Nat’l. Acad. Sci. USA
`(1994) 91(21): 9852-56.
`2080 Adachi, K., et al., Role of γ87 Gln in the Inhibition of Hemoglobin S
`Polymerization by Hemoglobin F, J. Bio. Chem. (1994) 269(13): 9562-
`9567.
`2081 Himanen, J-P., et al., Participation and Strength of Interaction of Lysine
`95(β) in the Polymerization of Hemoglobin S as Determined by its Site-
`Directed Substitution by Isoleucine, J. Biol. Chem. (1995)
`270(23):13885-91.
`2082 Wallace, R., et al., Oligonucleotide Directed Mutagenesis of the Human
`β-globin Gene: A General Method for Producing Specific Point
`Mutations in Cloned DNA, Nucl. Acid Res. (1981) 9(15):3647-56.
`2083 Eckert, K. & Kunkel, T., DNA Polymerase Fidelity and the Polymerase
`Chain Reaction, PCR Methods Appls. (1991) 1(1):17-24.
`2084 Second Amended and Supplemental Complaint, San Rocco
`Therapeutics, LLC v. Bluebird Bio, Inc. and Third Rock Ventures, C.A.
`No. 21-1478-RGA (D. Del.)
`
`
`
`
`
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`SKI Exhibit 2056
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`
`15.
`
`I reserve the right to supplement this exhibit list.
`
`IV. The Understandings Applied to My Analysis
`
`16.
`
`I understand that IPR proceedings were instituted and that the Petitioner
`
`has challenged certain claims of the ’179 and ’061 patents as summarized in the
`
`following table:
`
`Ground # Claims
`
`Asserted Basis
`
`IPR2023-00070 (US 7,541,179)
`
`1
`
`2
`
`3
`
`4
`
`1, 19, 22
`
`1, 19, 22
`
`1, 19, 22
`
`Anticipated by the May Thesis (Ex. 1004)
`
`Anticipated by the May Article (Ex. 1005)
`
`Obvious based on the May Article (Ex. 1005)
`
`1, 10, 19, 22
`
`Obvious based on the May Abstract (Ex. 1006)
`
`IPR2023-00074 (US 8,058,061)
`
`1
`
`2
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`3
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`4
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`5
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`
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`1, 2, 6, 7, 11
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`Anticipated by the May Thesis (Ex. 1004)
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`5
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`Obvious based on May Thesis (Ex. 1004) and
`Himanen (Ex. 1047)
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`1, 2, 6, 7, 11
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`Anticipated by the May Article (Ex. 1005)
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`1, 2, 6, 7, 11
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`Obvious based on the May Article (Ex. 1005)
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`5
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`Obvious based on May Article (Ex. 1005) and
`Himanen (Ex. 1047)
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`14
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`SKI Exhibit 2056
`Page 15 of 189
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`6
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`7
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`
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`1, 2, 6, 7, 8, 11, 15 Obvious based on the May Abstract (Ex. 1006)
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`5
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`Obvious based on the May Abstract (Ex. 1006)
`and Himanen (Ex. 1047)
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`17.
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`I understand that in an IPR proceeding, claims should be construed as
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`having their ordinary and customary meaning as understood by a POSA at the time
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`of the invention. I understand that claim terms should be read in the context of the
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`claim language of which they are a part. I further understand that the patent
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`specification and file history can also inform the meaning of claim terms and the
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`scope of the claims. If, after a review of this evidence, the construction is not
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`apparent, I understand that extrinsic evidence, such as dictionary definitions,
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`treatises, and trade journals, may be consulted to discern the meaning of a term. For
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`terms where no construction is necessary, I have simply read the terms according to
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`their ordinary and customary meaning. My understandings herein are made in light
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`of how a person of ordinary skill in the art in or around 2000 would view the ordinary
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`and customary meaning of the claim terms. I reserve the right to supplement my
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`declaration, should any claim terms be given different constructions.
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`18.
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`I understand that a claim is anticipated if a single prior art reference
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`discloses each and every limitation of the claimed invention. I understand that a
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`limitation can be expressly disclosed by the reference or be inherent. I further
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`
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`15
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`SKI Exhibit 2056
`Page 16 of 189
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`understand that for a feature to be inherently disclosed, a POSA would understand
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`the inherent feature would necessarily and inevitably be present when the teaching
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`of the reference is practiced. That is, I understand that if a feature is not necessarily
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`and inevitably present, it is not inherently disclosed.
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`19.
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`I understand that a patent claim may be unpatentable for obviousness if
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`the difference between the claimed subject matter and the prior art is such that the
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`subject matter as a whole would have been obvious at the time the invention was
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`made to a person having ordinary skill in the art. I understand that a finding of
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`obviousness requires a determination of: (1) the scope and content of the prior art;
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`(2) the difference(s) between the claimed invention and the prior art; (3) the level of
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`skill of the ordinary artisan in the pertinent art. I understand this analysis looks at
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`whether the differences are such that the claimed invention as a whole would have
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`been obvious to one of ordinary skill in the art at the time the invention was made. I
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`further understand that any obviousness analysis must consider objective evidence
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`of non-obviousness, where such evidence is present.
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`20.
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`I understand that objective evidence of non-obviousness includes (1)
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`copying, (2) long-felt but unsolved need, (3) failure of others, (4) commercial
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`success of the invention, (5) unexpected results created by the claimed invention, (6)
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`unexpected properties of the claimed invention, (7) licenses showing industry
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`
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`16
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`SKI Exhibit 2056
`Page 17 of 189
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`respect for the invention, (8) skepticism of skilled artisans before the invention, (9)
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`recognition of the invention’s advancement, and (10) contemporaneous invention by
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`others or absence thereof. In general, there must be a connection between the factor
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`and the claimed invention. For instance, the “commercial success” of a product
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`practicing the claimed invention is relevant to the obviousness analysis only if the
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`commercial success is attributable to advantages from the use of the invention that
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`were not available to the purchasing public before the invention was made.
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`21. My understanding is that the obviousness inquiry is not limited to just
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`the prior art references being applied, but includes the knowledge and understanding
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`of one of ordinary skill in the art.
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`22. However, I understand that merely demonstrating that each element,
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`independently, was known in the prior art is, by itself, insufficient to establish a
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`claim was obvious. My understanding is that the test for obviousness is not whether
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`the features of one reference can be incorporated into the structure of another
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`reference, but rather what the combined teachings would have suggested to those of
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`ordinary skill in the art. I further understand that a party seeking to invalidate a patent
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`must show that a person of ordinary skill in the art would have been motivated to
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`combine the teachings of the prior art references to achieve the claimed invention
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`with a reasonable expectation of success.
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`
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`17
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`SKI Exhibit 2056
`Page 18 of 189
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`23.
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`It is my understanding that each prior art reference must be considered
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`as a whole, including the portions that would lead away from the claimed invention.
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`I have been informed that some prior art combinations are improper, or not
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`combinable. For instance, the reference cannot be non-analogous art. In order for a
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`reference to be used to show obviousness, the reference must be analogous art to the
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`claimed invention. I understand that to be analogous, the art must be from the same
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`field of endeavor or be reasonably pertinent to the problem – and therefore logically
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`would command the artisan’s attention in considering her/his problem. I also
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`understand that when (1) the combination of prior art references teaches away from
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`the claimed invention or from each other, (2) the combination makes one invention
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`unsatisfactory for its intended purpose, or (3) when the combination would change
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`the principle of operation of prior art reference, such a combination is improper and
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`does not show obviousness of the claimed invention.
`
`24.
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`I understand that a combination of old, familiar, or known elements
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`according to known methods is likely to be obvious when it does no more than yield
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`predictable results. Predictable variations of a work from one field are likely to be
`
`obvious, even if the variation is in another field. For example, where a technique has
`
`been used to improve a device, use of the same technique to improve similar devices
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`is a predictable variation and likely obvious. Likewise, if the use of prior art for
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`
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`18
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`SKI Exhibit 2056
`Page 19 of 189
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`improvements is simply done according to the prior art’s established functions, a
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`person of ordinary skill in the art has simply implemented a predictable variation. If
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`there existed at the time of invention a known problem for which there was an
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`obvious solution, a patent claim encompassing that solution is not patentable.
`
`25.
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`I understand that claims must be enabled by the original disclosure of
`
`the patent. For the claims to be enabled, the information contained in the disclosure
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`must be sufficient to inform those skilled in the relevant art how to make and use the
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`claimed invention without undue experimentation. I also understand the original
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`disclosure must contain a written description of the claimed invention. I understand
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`that the written description requirement is separate and distinct from the enablement
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`requirement. To satisfy the written description requirement, the original disclosure
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`must describe (in writing or drawings) the claimed invention in sufficient detail that
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`one skilled in the art can reasonably conclude the inventor had possession of the
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`claimed invention. I understand that a genus can find written description support
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`when the disclosure includes representative species of the genus and/or when one
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`skilled in the art would understand that the species disclosed had a correlation
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`between the structure and function of other species within the genus. In other words,
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`the question is whether one of skill in the art can discern or visualize, from the
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`
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`19
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`SKI Exhibit 2056
`Page 20 of 189
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`original disclosure, that the named inventor actually invented the subject matter later
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`claimed.
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`26. The following background and analysis is based on my own
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`experiences, education, and opinions. I have provided citations in support of this
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`understanding. Although the following analysis cites to particular pages, lines,
`
`paragraphs, or figures of many of the references discussed, these citations are
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`intended to assist in understanding the various bases of my conclusions, and prior
`
`art teachings used to reach them. These citations are not intended to be an exhaustive
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`recitation of every page, line number, or paragraph in which these teachings may be
`
`found. Similar teachings or disclosures may be found at other pages, lines, or
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`paragraphs, as well as in other references, and it is to b