UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_________________
`
`
`BIONTECH SE and PFIZER INC.
`Petitioner
`
`v.
`
`MODERNATX, INC.
`Patent Owner
`
`_________________
`
`U.S. Patent No. 10,702,600
`_________________
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 10,702,600
`
`

`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`TABLE OF CONTENTS
`
`I.
`INTRODUCTION ........................................................................................... 1
`II. MANDATORY NOTICES ............................................................................. 3
`III.
`PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15 AND 42.103 ................. 4
`IV. STANDING ..................................................................................................... 4
`V.
`RELIEF REQUESTED AND GROUNDS RAISED ...................................... 4
`VI. BACKGROUND ............................................................................................. 5
`A.
`Technology Overview ........................................................................... 5
`1.
`Use of Vaccines to Induce an Immune Response ....................... 5
`2.
`Nucleic Acid Vaccines ................................................................ 7
`3.
`Evolution of mRNA Therapeutics, Including mRNA
`Vaccines ...................................................................................... 9
`Formulation of mRNA Therapeutics in Lipid Carriers ............ 12
`4.
`’600 Patent Overview .......................................................................... 13
`B.
`VII. LEVEL OF ORDINARY SKILL .................................................................. 15
`VIII. OVERVIEW OF THE PRIOR ART ............................................................. 16
`A.
`Schrum ................................................................................................. 16
`B.
`Geall .................................................................................................... 18
`C.
`Yang .................................................................................................... 19
`D. Altmeyer .............................................................................................. 20
`IX. CLAIM CONSTRUCTION .......................................................................... 21
`X. DETAILED EXPLANATION OF GROUNDS ............................................ 22
`A. Ground 1: Schrum Anticipates Claims 1, 2, 4-6, 8-12, 16, 17,
`20, 21, and 26 of the ’600 Patent ......................................................... 22
`1.
`Claim 1 ...................................................................................... 22
`2.
`Claim 2: “The composition of claim 1, wherein the open
`reading frame encodes a BetaCoV S protein.” ......................... 28
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`Patent No. 10,702,600
`Claim 4: “The composition of claim 1, wherein the
`mRNA further comprising a 5′ untranslated region (UTR)
`and a 3′ UTR.” .......................................................................... 28
`Claim 5: “The composition of claim 4, wherein the
`mRNA further comprises a poly(A) tail.” ................................ 29
`Claim 6: “The composition of claim 4, wherein the
`mRNA further comprises a 5′ cap analog.” .............................. 29
`Claim 8: “The composition of claim 1, wherein the
`mRNA comprises a chemical modification.” ........................... 30
`Claim 9: “The composition of claim 8, wherein the
`chemical modification is a 1-methylpseudouridine
`modification or a 1-ethylpseudouridine modification.” ............ 31
`Claim 10: “The composition of claim 8, wherein at least
`80% of the uracil in the open reading frame has a
`chemical modification.” ............................................................ 31
`Claim 11: “The composition of claim 1, wherein the lipid
`nanoparticle comprises an ionizable cationic lipid, a
`neutral lipid, a sterol, and a PEG-modified lipid.” ................... 32
`10. Claim 12: “The composition of claim 11, wherein the
`lipid nanoparticle comprises 20-60% ionizable cationic
`lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-
`15% PEG-modified lipid.” ........................................................ 34
`11. Claim 16 .................................................................................... 35
`12. Claim 17: “The composition of claim 16, wherein the
`open reading frame encodes a BetaCoV S protein.” ................ 36
`13. Claim 20: “The composition of claim 16, wherein at least
`80% of the uracil in the open reading frame has a
`chemical modification.” ............................................................ 36
`14. Claim 21: “The composition of claim 20, wherein the
`chemical modification is a 1-methylpseudouridine
`modification or a 1-ethylpseudouridine modification.” ............ 37
`15. Claim 26 .................................................................................... 37
`Ground 2: Schrum in View of Geall Renders Claims 1, 2, 4-6,
`8-12, 16, 17, 20, 21, and 26 Obvious .................................................. 38
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`4.
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`5.
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`6.
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`4.
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`Claim 1 ...................................................................................... 38
`Claim 2: “The composition of claim 1, wherein the open
`reading frame encodes a BetaCoV S protein.” ......................... 42
`Claim 4: “The composition of claim 1, wherein the
`mRNA further comprising a 5′ untranslated region (UTR)
`and a 3′ UTR.” .......................................................................... 42
`Claim 5: “The composition of claim 4, wherein the
`mRNA further comprises a poly(A) tail.” ................................ 42
`Claim 6: “The composition of claim 4, wherein the
`mRNA further comprises a 5′ cap analog.” .............................. 42
`Claim 8: “The composition of claim 1, wherein the
`mRNA comprises a chemical modification.” ........................... 43
`Claim 9: “The composition of claim 8, wherein the
`chemical modification is a 1-methylpseudouridine
`modification or a 1-ethylpseudouridine modification.” ............ 43
`Claim 10: “The composition of claim 8, wherein at least
`80% of the uracil in the open reading frame has a
`chemical modification.” ............................................................ 44
`Claim 11: “The composition of claim 1, wherein the lipid
`nanoparticle comprises an ionizable cationic lipid, a
`neutral lipid, a sterol, and a PEG-modified lipid.” ................... 44
`10. Claim 12: “The composition of claim 11, wherein the
`lipid nanoparticle comprises 20-60% ionizable cationic
`lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-
`15% PEG-modified lipid.” ........................................................ 44
`11. Claim 16 .................................................................................... 45
`12. Claim 17: “The composition of claim 16, wherein the
`open reading frame encodes a BetaCoV S protein.” ................ 46
`13. Claim 20: “The composition of claim 16, wherein at least
`80% of the uracil in the open reading frame has a
`chemical modification.” ............................................................ 46
`14. Claim 21: “The composition of claim 20, wherein the
`chemical modification is a 1-methylpseudouridine
`modification or a 1-ethylpseudouridine modification.” ............ 47
`
`8.
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`9.
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`C.
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`4.
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`5.
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`Patent No. 10,702,600
`15. Claim 26 .................................................................................... 47
`Ground 3: Schrum in view of Yang Renders Claims 1, 2, 4-6,
`8-12, 16, 17, 20, 21, and 26 Obvious .................................................. 48
`1.
`Claim 1 ...................................................................................... 48
`2.
`Claim 2: “The composition of claim 1, wherein the open
`reading frame encodes a BetaCoV S protein.” ......................... 52
`Claim 4: “The composition of claim 1, wherein the
`mRNA further comprising a 5′ untranslated region (UTR)
`and a 3′ UTR.” .......................................................................... 52
`Claim 5: “The composition of claim 4, wherein the
`mRNA further comprises a poly(A) tail.” ................................ 53
`Claim 6: “The composition of claim 4, wherein the
`mRNA further comprises a 5′ cap analog.” .............................. 53
`Claim 8: “The composition of claim 1, wherein the
`mRNA comprises a chemical modification.” ........................... 53
`Claim 9: “The composition of claim 8, wherein the
`chemical modification is a 1-methylpseudouridine
`modification or a 1-ethylpseudouridine modification.” ............ 53
`Claim 10: “The composition of claim 8, wherein at least
`80% of the uracil in the open reading frame has a
`chemical modification.” ............................................................ 53
`Claim 11: “The composition of claim 1, wherein the lipid
`nanoparticle comprises an ionizable cationic lipid, a
`neutral lipid, a sterol, and a PEG-modified lipid.” ................... 54
`10. Claim 12: “The composition of claim 11, wherein the
`lipid nanoparticle comprises 20-60% ionizable cationic
`lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-
`15% PEG-modified lipid.” ........................................................ 54
`11. Claim 16 .................................................................................... 54
`12. Claim 17: “The composition of claim 16, wherein the
`open reading frame encodes a BetaCoV S protein.” ................ 55
`13. Claim 20: “The composition of claim 16, wherein at least
`80% of the uracil in the open reading frame has a
`chemical modification.” ............................................................ 56
`
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`8.
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`9.
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`iv
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`3.
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`4.
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`5.
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`6.
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`7.
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`14. Claim 21: “The composition of claim 20, wherein the
`chemical modification is a 1-methylpseudouridine
`modification or a 1-ethylpseudouridine modification.” ............ 56
`15. Claim 26 .................................................................................... 56
`D. Ground 4: Schrum in View of Altmeyer Renders Claims 1, 2,
`4-6, 8-12, 16, 17, 20, 21, and 26 Obvious ........................................... 57
`1.
`Claim 1 ...................................................................................... 57
`2.
`Claim 2: “The composition of claim 1, wherein the open
`reading frame encodes a BetaCoV S protein.” ......................... 61
`Claim 4: “The composition of claim 1, wherein the
`mRNA further comprising a 5′ untranslated region (UTR)
`and a 3′ UTR.” .......................................................................... 61
`Claim 5: “The composition of claim 4, wherein the
`mRNA further comprises a poly(A) tail.” ................................ 61
`Claim 6: “The composition of claim 4, wherein the
`mRNA further comprises a 5′ cap analog.” .............................. 62
`Claim 8: “The composition of claim 1, wherein the
`mRNA comprises a chemical modification.” ........................... 62
`Claim 9: “The composition of claim 8, wherein the
`chemical modification is a 1-methylpseudouridine
`modification or a 1-ethylpseudouridine modification.” ............ 62
`Claim 10: “The composition of claim 8, wherein at least
`80% of the uracil in the open reading frame has a
`chemical modification.” ............................................................ 62
`Claim 11: “The composition of claim 1, wherein the lipid
`nanoparticle comprises an ionizable cationic lipid, a
`neutral lipid, a sterol, and a PEG-modified lipid.” ................... 62
`10. Claim 12: “The composition of claim 11, wherein the
`lipid nanoparticle comprises 20-60% ionizable cationic
`lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-
`15% PEG-modified lipid.” ........................................................ 63
`11. Claim 16 .................................................................................... 63
`12. Claim 17: “The composition of claim 16, wherein the
`open reading frame encodes a BetaCoV S protein.” ................ 64
`
`9.
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`8.
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`13. Claim 20: “The composition of claim 16, wherein at least
`80% of the uracil in the open reading frame has a
`chemical modification.” ............................................................ 65
`14. Claim 21: “The composition of claim 20, wherein the
`chemical modification is a 1-methylpseudouridine
`modification or a 1-ethylpseudouridine modification.” ............ 65
`15. Claim 26 .................................................................................... 65
`XI. DISCRETIONARY DENIAL IS NOT APPROPRIATE ............................. 66
`A.
`Fintiv Does Not Justify Denial ............................................................ 66
`B.
`Discretionary Denial Under 35 U.S.C. § 325(d) Is Not
`Appropriate .......................................................................................... 68
`XII. CONCLUSION .............................................................................................. 70
`
`
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`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`LIST OF EXHIBITS
`
`
`
`Exhibit No. Document
`Ex. 1001
`U.S. Patent No. 10,702,600
`
`Ex. 1002
`
`Declaration of Daniel O. Griffin, M.D., Ph.D.
`
`Ex. 1003
`
`Curriculum Vitae of Daniel O. Griffin, M.D., Ph.D.
`
`Ex. 1004
`
`Declaration of James J. Moon, Ph.D.
`
`Ex. 1005
`
`Curriculum Vitae of James J. Moon, Ph.D.
`
`Ex. 1006
`
`Ex. 1007
`
`Reserved
`
`Reserved
`
`Ex. 1008
`
`File History for U.S. Patent No. 10,702,600
`
`Ex. 1009
`
`U.S. Patent App. Publication 2013/0266640 (“Schrum”)
`
`Ex. 1010
`
`International Patent App. Pub. No. WO 2012/006369 (“Geall”)
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`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`Exhibit No. Document
`Andrew J. Geall et al., RNA: The new revolution in nucleic acid
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`Exhibit No. Document
`“Katalin Karikó and Drew Weissman awarded Horwitz Prize for
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`Katalin Karikó et al., Increased eythropoiesis in mice injected with
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`Reserved
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`
`ModernaTX, Inc. et al v. Pfizer Inc. et al. (D. Mass. 22-11378-
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`
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`Exhibit No. Document
`Notice of Allowance of U.S. Patent No. 10,933,127 (Application
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`
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`
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`
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`
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`
`Excerpts from Bruce Alberts et al., Chapters 1, 3, 5-7, 24, and 25
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`Exhibit No. Document
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`
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`
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`
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`Exhibit No. Document
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`
`Reserved
`
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`
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`
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`
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`
`Reserved
`
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`
`Excerpts from Kenneth Murphy, JANEWAY’S IMMUNOBIOLOGY,
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`
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`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`Exhibit No. Document
`Muthusamy Jayaraman et al., Maximizing the potency of siRNA
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`
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`
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`
`Alex K. K. Leung et al., Chapter Four – Lipid nanoparticles for
`short interfering RNA delivery, in ADVANCES IN GENETICS, Vol.
`88, (2014)
`
`Sean C. Semple et al., Efficient encapsulation of antisense
`oligonucleotides in lipid vesicles using ionizable aminolipids:
`Formation of novel small multilamellar vesicle structures, 1510
`BIOCHIMICA ET BIOPHYSICA ACTA 152 (2001)
`
`Ex. 1085
`
`Rosemary Kanasty et al., Delivery materials for siRNA
`therapeutics, 12 NATURE MATERIALS 967 (2013)
`
`Ex. 1086
`
`Reserved
`
`Ex. 1087
`
`Ex. 1088
`
`Shutao Guo & Leaf Huang, Nanoparticles escaping RES and
`endosome: Challenges for siRNA delivery for cancer therapy,
`2011 JOURNAL OF NANOMATERIALS 1 (2011)
`
`Philip L. Felgner et al., Lipofection: A highly efficient, lipid-
`mediated DNA-transfection procedure, 84 PROC. NATL. ACAD.
`SCI. USA 7413 (1987)
`
`Ex. 1089
`
`Erick J. Dufourc, Sterols and membrane dynamics, 1 J. CHEM.
`BIOL. 63 (2008)
`
`
`
`xiv
`
`

`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`
`I.
`
`INTRODUCTION
`This inter partes review is about Patent Owner’s attempt to coopt an entire
`
`field of mRNA technology. As the Board is no doubt aware, Petitioner BioNTech
`
`designed a vaccine against SARS-CoV-2, a virus which did not exist before 2019,
`
`and partnered with Petitioner Pfizer to bring the vaccine (Comirnaty®) to
`
`patients. Patent Owner obtained the patent at issue, during the pandemic, with
`
`unimaginably broad claims directed to a basic idea that was known long before the
`
`asserted priority date of 2015 – compositions of mRNA encoding any spike protein
`
`or spike protein subunit of any betacoronavirus, formulated in a broadly claimed
`
`lipid delivery system.
`
`Scientists first demonstrated in 1990 that injecting mRNA encoding for a
`
`protein caused expression of that protein in vivo. (Ex. 1013 at 1465-66.) This
`
`discovery opened a world of possible medical applications, including using mRNA
`
`for vaccination to protect against disease. (Id. at 1468.) Within three years,
`
`scientists demonstrated that an mRNA vaccine encoding a protein as the “antigen”
`
`(a portion of a foreign pathogen, such as a protein on a virus) delivered via a lipid
`
`carrier (a delivery system of a combination of lipids that protects the mRNA payload
`
`during circulation in the body) induced a protective immune response in vivo.
`
`(Ex. 1014.)
`
`1
`
`

`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`Following the 1993 publication of the use of antigen-encoding mRNA,
`
`scientists in the field worked to optimize mRNA vaccines. Before 2015, that work
`
`led to mRNA vaccines which improved upon the 1993 iteration with respect to the
`
`(1) mRNA (including using naturally occurring uridine modifications, untranslated
`
`regions, and caps/tails); (2) encoded antigen used to induce an immune response;
`
`and (3) lipid-based carrier. The specific combination of these features claimed in
`
`the ’600 patent had been disclosed in scientific and patent publications by 2015.
`
`The challenged patent claims priority to nine provisional applications that
`
`Patent Owner filed in 2015, with no data, directed to these same basic ideas. (See,
`
`e.g., Ex. 1037, 1038.) In October 2016, Patent Owner then filed a non-provisional
`
`application containing two examples of betacoronavirus (specifically, MERS-CoV)
`
`mRNA vaccines tested in mice and rabbits: Application No. PCT/US2016/058327.
`
`The mRNA structure of the specific vaccines was not disclosed. After numerous
`
`continuations, Patent Owner eventually obtained, in July 2020, the subject of this
`
`petition, U.S. Patent No. 10,702,600 (“the ’600 patent”).
`
`The ’600 patent has, by Patent Owner’s own arguments, unimaginably broad
`
`claims reciting an mRNA composition encoding any spike protein or spike protein
`
`subunit of any betacoronavirus (whether in existence or arising at any later point in
`
`time), formulated in a lipid delivery system. Its broad claims encompass subject
`
`2
`
`

`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`matter disclosed in the art before October 22, 2015, the earliest date to which the
`
`’600 patent claims priority.
`
`Petitioner therefore requests that this Petition be granted and that the
`
`challenged claims be found unpatentable and canceled.
`
`II. MANDATORY NOTICES
` Pursuant to 37 C.F.R. § 42.8(b)(1), Petitioner identifies the following as real
`
`parties-in-interest: BioNTech SE, BioNTech US Inc., BioNTech Manufacturing
`
`GmbH, and Pfizer Inc.
`
`Related Matters: The ’600 patent is asserted in the following civil action:
`
`ModernaTX, Inc., et al. v. Pfizer Inc, BioNTech SE, et al., 1:22-cv-11378-RGS (D.
`
`Mass.).
`
`The ’600 patent issued in July 2020 from Application No. 16/805,587 (“the
`
`’587 application”). Thereafter, Application No. 16/880,829 was filed as a
`
`continuation of the ’587 application and issued in March 2021 as U.S. Patent No.
`
`10,933,127 (“the ’127 patent”). The ’127 patent is asserted in the above-cited district
`
`court case and is the subject of a separate inter partes review petition concurrently
`
`filed by Petitioner.
`
`Counsel and Service Information: Lead counsel is David Krinsky (Reg. No.
`
`72,339). Backup counsel are (1) Stanley Fisher (Reg. No. 55,820), (2) Naveen Modi
`
`(Reg. No. 46,224), (3) Bruce Wexler (Reg. No. 35,409), (4) Eric Dittmann (Reg. No.
`
`3
`
`

`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`51,188), (5) Chetan Bansal (Reg. No. 81,590), (6) Rebecca Hilgar (pro hac vice to
`
`be filed), and (7) Ryan Meuth (pro hac vice to be filed). Service information is
`
`Williams & Connolly LLP, 680 Maine Avenue SW, Washington, D.C. 20024, Tel.:
`
`202.434.5000, Fax: 202.4345029, email: COVIDPatentPfizer@wc.com and
`
`BioNTech-Moderna-IPR@paulhastings.com. Petitioner consents to electronic
`
`service.
`
`III. PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15 AND 42.103
`The PTO is authorized to charge any fees due during this proceeding to
`
`Deposit Account No. 50-6403.
`
`IV. STANDING
`Petitioner certifies under 37 C.F.R. § 42.104(a) that the ’600 patent is
`
`available for review and Petitioner is not barred or estopped from requesting review
`
`on the grounds identified herein.
`
`V. RELIEF REQUESTED AND GROUNDS RAISED
`Petitioner respectfully requests review of claims 1, 2, 4-6, 8-12, 16-17, 20-21,
`
`and 26 of the ’600 patent and cancellation of these claims as unpatentable. The
`
`challenged claims should be found unpatentable based on the following grounds:
`
`Ground 1: Claims 1, 2, 4-6, 8-12, 16-17, 20-21, and 26 are unpatentable
`
`under 35 U.S.C. § 102(a) as anticipated by US 2013/026640 (“Schrum”) (Ex. 1009).
`
`4
`
`

`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`Ground 2: Claims 1, 2, 4-6, 8-12, 16-17, 20-21, and 26 are unpatentable
`
`under 35 U.S.C. § 103 as being obvious based on Schrum in view of WO
`
`2012/006369 (“Geall”) (Ex. 1010).
`
`Ground 3: Claims 1, 2, 4-6, 8-12, 16-17, 20-21, and 26 are unpatentable
`
`under 35 U.S.C. § 103 as being obvious based on Schrum in view of Yang et al., A
`
`DNA Vaccine Induces SARS Coronavirus Neutralization and Protective Immunity
`
`in Mice, 428 NATURE 561 (2004) (“Yang”) (Ex. 1011).
`
`Ground 4: Claims 1, 2, 4-6, 8-12, 16-17, 20-21, and 26 are unpatentable
`
`under 35 U.S.C. § 103 as being obvious based on Schrum in view of WO
`
`2005/118813 (“Altmeyer”) (Ex. 1012).
`
`VI. BACKGROUND
`A. Technology Overview
`
`1.
`
`Use of Vaccines to Induce an Immune Response
`
`Vaccines are pharmaceutical compositions administered to stimulate (or
`
`“induce”) the body’s immune response against diseases. (Ex. 1002, ¶¶32-41.)
`
`Vaccines rely upon introduction of an “antigen,” a portion of a disease-causing agent
`
`(“pathogen”). In the context of viruses, the antigen may be a single protein. Vaccine
`
`administration mobilizes the body’s cells, which identify and neutralize the antigen,
`
`generating protective antibodies and T cells to fight infection. Upon subsequent
`
`5
`
`

`

`Petition for Inter Partes Review
`Patent No. 10,702,600
`exposure to the live virus, the body recognizes the antigen and is able to fight
`
`infection more efficiently. (Id., ¶36.)
`
` Antigen selection can determine the protection achieved by vaccination.
`
`Certain portions of pathogens represent better targets for vaccine development.
`
`(Id., ¶44.) Therefore, vaccine development is guided by scientific knowledge
`
`reg