`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________
`
`
`Moderna Therapeutics, Inc.
`
`Petitioner
`
`v.
`
`Arbutus Biopharma Corporation
`
`Patent Owner
`___________
`
`U.S. Patent No. 8,058,069
`
`Issued: November 15, 2011
`
`Named Inventors: Edward Yaworski, Kieu Lam, Lloyd Jeffs,
`Lorne Palmer, Ian MacLachlan
`
`Title: Lipid Formulations for Nucleic Acid Delivery
`___________
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 8,058,069
`
`
`
`
`Mail Stop: PATENT BOARD
`Patent Trial and Appeal Board
`U.S. Patent & Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`10626391
`
`
`
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`

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`TABLE OF CONTENTS
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`Page
`INTRODUCTION ........................................................................................ 1
`I.
`II. MANDATORY NOTICES .......................................................................... 4
`A. Notice of real party-in-interest (37 C.F.R. § 42.8(b)(1)) ...................... 4
`B. Notice of related matters (37 C.F.R. § 42.8(b)(2)) ............................... 4
`C. Designation of lead and back-up counsel (37 C.F.R.
`§ 42.8(b)(3)) .......................................................................................... 4
`D. Service information (37 C.F.R. § 42.8(b)(4)) ....................................... 5
`E. Payment of fees (37 C.F.R. § 42.103) .................................................. 5
`F. Certification of grounds for standing (37 C.F.R. § 42.104(a)) ............. 5
`III. CHALLENGE AND RELIEF REQUESTED.............................................. 5
`A. Ground 1: Claims 1-22 are anticipated by or obvious in
`view of Patent Owner’s prior disclosures in either the ’196
`PCT or the ’189 publication ................................................................. 5
`B. Ground 2: Claims 1-22 are obvious in view of the ’196 PCT
`or the ’189 publication in view of Lin and Ahmad .............................. 5
`C. Ground 3: Claims 1-22 are anticipated by or obvious in
`view of the ’554 publication ................................................................. 5
`IV. PRIORITY DATE ........................................................................................ 5
`V.
`PERSONS HAVING ORDINARY SKILL IN THE ART .......................... 6
`VI. BACKGROUND .......................................................................................... 6
`A. Lipid carrier particles for nucleic acid payloads .................................. 6
`B. The ’069 patent claims are directed to known lipid
`components ........................................................................................... 7
`C. The optimal lipid component proportions in a nucleic acid-
`lipid particle vary .................................................................................. 9
`the ’069 patent was granted on alleged unexpected results
`for a single formulation of lipid components ..................................... 12
`1.
`’069 patent: The prosecution history confirms patent
`owner’s reliance on unexpected results ...................................... 14
`
`D.
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`2.
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`’069 patent: Patentee tested only one formulation covered
`by the claims................................................................................ 15
`a) Example 2 shows that in vitro the 1:57 SNALP was no more
`effective than several prior art formulations .......................... 16
`b) Examples 3-4 show that the 1:57 SNALP was no more effective
`than the formulations with less than 50% cationic lipid ........ 19
`3. The ’069 patent: The testing shows that even slight
`variations of the lipid component proportions and/or the
`species of lipid component impact efficacy ................................ 21
`VII. CLAIM CONSTRUCTION ....................................................................... 23
`A. Claim 1: “Nucleic acid-lipid particle” ................................................ 23
`VIII. PRIOR ART ................................................................................................ 23
`A. Patent owner’s prior disclosures are prior art under 35
`U.S.C. § 102(b) ................................................................................... 23
`B. The ’554 publication is prior art under 35 U.S.C. § 102(b) ............... 26
`C. Lin is prior art under 35 U.S.C. § 102(b) ........................................... 27
`D. Ahmad is prior art under 35 U.S.C. § 102(b) ..................................... 29
`IX. THERE IS A REASONABLE LIKELIHOOD THAT AT LEAST
`ONE CLAIM OF THE ’069 PATENT IS UNPATENTABLE ................. 31
`A. Ground 1: Claims 1-22 are anticipated by or obvious in view
`of either the ’196 PCT or the ’189 publication ................................... 31
`1. Claim 1 ........................................................................................ 32
`a) Claim 1(a): a nucleic acid-lipid particle comprising: ........... 32
`b) Claim 1(b): a nucleic acid ..................................................... 32
`c) Claim 1(c): a cationic lipid comprising from 50 mol% to 65
`mol% of the total lipid present in the particle ........................ 32
`d) Claim 1(d): a non-cationic lipid comprising a mixture of a
`phospholipid and cholesterol or a derivative thereof, wherein
`the phospholipid comprises from 4 mol% to 10 mol% of the
`total lipid present in the particle and the cholesterol or
`derivative thereof comprises from 30 mol% to 40 mol% of the
`total lipid present in the particle............................................. 38
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`e) Claim 1(e): a conjugated lipid that inhibits aggregation of
`particles comprising from 0.5 mol% to 2 mol% of the total lipid
`present in the particle ............................................................. 39
`2. Claim 2: the nucleic acid-lipid particle of claim 1, wherein
`the nucleic acid comprises a small interfereing RNA
`(siRNA) ....................................................................................... 41
`3. Claim 3: the nucleic acid-lipid particle of claim 2, wherein
`the siRNA comprises from about 15 to about 60
`nucleotides ................................................................................... 41
`4. Claim 4: the nucleic acid-lipid particle of claim 2, wherein
`the siRNA comprises at least one modified nucleotide .............. 41
`5. Claim 5: the nucleic acid-lipid particle of claim 2, wherein
`the siRNA comprises at least one 2’-O-methyl (2’OMe)
`nucleotide .................................................................................... 42
`6. Claim 6: the nucleic acid-lipid particle of claim 2, wherein
`said siRNA is about 19 to about 25 base pairs in length ............ 42
`7. Claim 7: the nucleic acid-lipid particle of claim 2, wherein
`said siRNA comprises 3’ overhangs ........................................... 42
`8. Claim 8: the nucleic acid-lipid particle of claim 1, wherein
`the cationic lipid comprises from 52 mol% to 62 mol% of
`the total lipid present in the particle ............................................ 42
`9. Claim 9: the nucleic acid-lipid particle of claim 1, wherein
`the phospholipid comprises
`dipalmitoylphosphatidylcholine (DPPC),
`distearoylphosphatidylcholine (DSPC), or a mixture
`thereof .......................................................................................... 43
`10. Claim 10: the nucleic acid-lipid particle of claim 1,
`wherein the conjugated lipid that inhibits aggregation of
`particles comprises a polyethyleneglycol (PEG)-lipid
`conjugate ..................................................................................... 43
`11. Claim 11: the nucleic acid-lipid particle of claim 10,
`wherein the PEG-lipid conjugate comprises a PEG-
`diacylglycerol (PEG-DAG) conjugate, a PEG-
`dialkyloxypropyl (PEG-DAA) conjugate, or a mixture
`thereof .......................................................................................... 44
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`12. Claim 12: the nucleic acid-lipid particle of claim 11,
`wherein the PEG-DAA conjugate comprises a PEG-
`dimyristyloxypropyl (PEG-DMA) conjugate, a PEG-
`distearyloxypropyl (PEG-DSA) conjugate, or a mixture
`thereof .......................................................................................... 44
`13. Claim 13: the nucleic acid-lipid particle of claim 12,
`wherein the PEG has an average molecular weight of about
`2,000 daltons ............................................................................... 44
`14. Claim 14: the nucleic acid-lipid particle of claim 10,
`wherein the nucleic acid-lipid particle comprises about
`57.1 mol% cationic lipid, about 7.1 mol% phospholipid,
`about 34.3 mol% cholesterol or a derivative thereof, and
`about 1.4 mol% PEG-lipid conjugate ......................................... 45
`15. Claim 15: the nucleic acid-lipid particle of claim 1,
`wherein the conjugated lipid that inhibits aggregation of
`particle comprises from 1 mol% to 2 mol% of the total
`lipid present in the particle .......................................................... 45
`16. Claim 16: the nucleic acid-lipid particle of claim 1,
`wherein the nucleic acid in the nucleic acid-lipid particle is
`not substantially degraded after incubation of the particle
`in serum at 37°C for 30 minutes ................................................. 46
`17. Claim 17: the nucleic acid-lipid particle of claim 1,
`wherein the nucleic acid is fully encapsulated in the
`nucleic acid-lipid particle ............................................................ 47
`18. Claim 18: the nucleic acid-lipid particle of claim 1,
`wherein the nucleic acid-lipid particle has a lipid:nucleic
`acid mass ratio of from about 5 to about 15 ................................ 47
`19. Claim 19: the nucleic acid-lipid particle of claim 1,
`wherein the nucleic acid-lipid particle has a median
`diameter of from about 40 nm to about 150 nm ......................... 48
`20. Claim 20: the nucleic acid-lipid particle of claim 1,
`wherein the phospholipid comprises from 5 mol% to 9
`mol% of the total lipid present in the particle ............................. 48
`21. Claim 21: the nucleic acid-lipid particle of claim 1,
`wherein the cholesterol or derivative thereof comprises
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`from 32 mol% to 36 mol% of the total lipid present in the
`particle ......................................................................................... 48
`22. Claim 22: a pharmaceutical composition comprising a
`nucleic acid-lipid particle of claim 1 and a
`pharmaceutically acceptable carrier ............................................ 49
`B. Ground 2: Claims 1-22 are obvious in view of patent
`owner’s prior disclosures in light of Lin and Ahmad ......................... 49
`1. Claim 1(c): a cationic lipid comprising from 50 mol% to
`65 mol% of the total lipid present in the particle ........................ 49
`2. Claim 8: the nucleic acid-lipid particle of claim 1, wherein
`the cationic lipid comprises from 52 mol% to 62 mol% of
`the total lipid present in the particle ............................................ 53
`C. Ground 3: claims 1-22 are anticipated by or obvious in view
`of the ’554 publication ........................................................................ 54
`1. Claim 1 ........................................................................................ 54
`a) Claim 1(a): a nucleic acid-lipid particle comprising: ........... 54
`b) Claim 1(b): a nucleic acid ..................................................... 54
`c) Claim 1(c): a cationic lipid comprising from 50 mol% to 65
`mol% of the total lipid present in the particle ........................ 55
`d) Claim 1(d): a non-cationic lipid comprising a mixture of a
`phospholipid and cholesterol or a derivative thereof, wherein
`the phospholipid comprises from 4 mol% to 10 mol% of the
`total lipid present in the particle and the cholesterol or
`derivative thereof comprises from 30 mol% to 40 mol% of the
`total lipid present in the particle............................................. 57
`e) Claim 1(e): a conjugated lipid that inhibits aggregation of
`particles comprising from 0.5 mol% to 2 mol% of the total lipid
`present in the particle. ............................................................ 58
`2. Claim 2: the nucleic acid-lipid particle of claim 1, wherein
`the nucleic acid comprises a small interfereing RNA
`(siRNA) ....................................................................................... 59
`3. Claim 3: the nucleic acid-lipid particle of claim 2, wherein
`the siRNA comprises from about 15 to about 60
`nucleotides ................................................................................... 59
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`4. Claim 4: the nucleic acid-lipid particle of claim 2, wherein
`the siRNA comprises at least one modified nucleotide .............. 60
`5. Claim 5: the nucleic acid-lipid particle of claim 2, wherein
`the siRNA comprises at least one 2’-O-methyl (2’OMe)
`nucleotide .................................................................................... 60
`6. Claim 6: the nucleic acid-lipid particle of claim 2, wherein
`said siRNA is about 19 to about 25 base pairs in length ............ 60
`7. Claim 7: the nucleic acid-lipid particle of claim 2, wherein
`said siRNA comprises 3’ overhangs ........................................... 61
`8. Claim 8: the nucleic acid-lipid particle of claim 1, wherein
`the cationic lipid comprises from 52 mol% to 62 mol% of
`the total lipid present in the particle ............................................ 61
`9. Claim 9: the nucleic acid-lipid particle of claim 1, wherein
`the phospholipid comprises
`dipalmitoylphosphatidylcholine (DPPC),
`distearoylphosphatidylcholine (DSPC), or a mixture
`thereof .......................................................................................... 61
`10. Claim 10: the nucleic acid-lipid particle of claim 1,
`wherein the conjugated lipid that inhibits aggregation of
`particles comprises a polyethyleneglycol (PEG)-lipid
`conjugate ..................................................................................... 61
`11. Claim 11: the nucleic acid-lipid particle of claim 10,
`wherein the PEG-lipid conjugate comprises a PEG-
`diacylglycerol (PEG-DAG) conjugate, a PEG-
`dialkyloxypropyl (PEG-DAA) conjugate, or a mixture
`thereof .......................................................................................... 62
`12. Claim 12: the nucleic acid-lipid particle of claim 11,
`wherein the PEG-DAA conjugate comprises a PEG-
`dimyristyloxypropyl (PEG-DMA) conjugate, a PEG-
`distearyloxypropyl (PEG-DSA) conjugate, or a mixture
`thereof .......................................................................................... 62
`13. Claim 13: the nucleic acid-lipid particle of claim 12,
`wherein the PEG has an average molecular weight of about
`2,000 daltons ............................................................................... 63
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`14. Claim 14: the nucleic acid-lipid particle of claim 10,
`wherein the nucleic acid-lipid particle comprises about
`57.1 mol% cationic lipid, about 7.1 mol% phospholipid,
`about 34.3 mol% cholesterol or a derivative thereof, and
`about 1.4 mol% PEG-lipid conjugate ......................................... 63
`15. Claim 15: the nucleic acid-lipid particle of claim 1,
`wherein the conjugated lipid that inhibits aggregation of
`particle comprises from 1 mol% to 2 mol% of the total
`lipid present in the particle .......................................................... 63
`16. Claim 16: the nucleic acid-lipid particle of claim 1,
`wherein the nucleic acid in the nucleic acid-lipid particle is
`not substantially degraded after incubation of the particle
`in serum at 37°C for 30 minutes ................................................. 64
`17. Claim 17: the nucleic acid-lipid particle of claim 1,
`wherein the nucleic acid is fully encapsulated in the
`nucleic acid-lipid particle ............................................................ 64
`18. Claim 18: the nucleic acid-lipid particle of claim 1,
`wherein the nucleic acid-lipid particle has a lipid:nucleic
`acid mass ratio of from about 5 to about 15 ................................ 65
`19. Claim 19: the nucleic acid-lipid particle of claim 1,
`wherein the nucleic acid-lipid particle has a median
`diameter of from about 40 nm to about 150 nm ......................... 65
`20. Claim 20: the nucleic acid-lipid particle of claim 1,
`wherein the phospholipid comprises from 5 mol% to 9
`mol% of the total lipid present in the particle ............................. 66
`21. Claim 21: the nucleic acid-lipid particle of claim 1,
`wherein the cholesterol or derivative thereof comprises
`from 32 mol% to 36 mol% of the total lipid present in the
`particle ......................................................................................... 66
`22. Claim 22: a pharmaceutical composition comprising a
`nucleic acid-lipid particle of claim 1 and a
`pharmaceutically acceptable carrier ............................................ 67
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`
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`In re Clemens,
`622 F.2d 1029 (C.C.P.A. 1980) ...................................................................... 3, 34
`E.I. Dupont De Nnemours & Co. v. Synvina C.V.,
`No. 2017-1977, slip op. (Fed. Cir. Sept. 17, 2018) .....................................passim
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .................................................................... 36, 37
`Ex parte Lunsford,
`No. Appeal 2008-4023 (P.T.A.B. Nov. 26, 2008) .................................. 34, 35, 36
`In re Magnum Oil Tools Int’l, Ltd.,
`829 F.3d 1364 (Fed. Cir. 2016) ............................................................................ 3
`Moderna Therapeautics, Inc. v. Protiva Biotherapeutics, Inc.,
`IPR2018-00680 ..................................................................................................... 4
`Moderna Therapeautics, Inc. v. Protiva Biotherapeutics, Inc.,
`IPR2018-00739 ..................................................................................................... 4
`In re Patel,
`566 Fed. App’x. 1005 (Fed. Cir. 2014) .............................................................. 35
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) ............................................................ 2, 3, 33, 35
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .......................................................................... 23
`Statutes
`35 U.S.C. § 102 .................................................................................................passim
`35 U.S.C. § 103 ............................................................................................ 31, 49, 54
`35 U.S.C. §§ 311–319 ................................................................................................ 1
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`Other Authorities
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 4
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 4
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 4
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 5
`37 C.F.R. § 42.100 et seq. .......................................................................................... 1
`37 C.F.R. § 42.103 ..................................................................................................... 5
`37 C.F.R. § 42.104(a) ................................................................................................. 5
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`LIST OF EVIDENCE AND EXHIBITS RELIED UPON IN THE PETITION
`
`Exhibit
`Reference
`No.
`1001 U.S. Patent No. 8,058,069 (“’069 patent”)
`1002 U.S. Patent No. 9,364,435 (“’435 patent”)
`1003
`International Publication No. WO 2005/007196 (“’196 PCT”)
`1004 U.S. Publication No. US2006/0134189 (“’189 publication”)
`1005 U.S. Publication No. US2006/0240554 (“’554 publication”)
`1006 Lin, Alison J. et al., Three-Dimensional Imaging of Lipid Gene-Carriers:
`Membrane Charge Density Controls Universal Transfection Behavior in
`Lamellar Cationic Liposome-DNA Complexes, 84 BIOPHYSICAL JOURNAL,
`3307–16 (2003) (“Lin”)
`1007 Ahmad, Ayesha et al., New multivalent cationic lipids reveal bell curve for
`transfection efficiency versus membrane charge density: lipid-DNA complexes
`for gene delivery, 7 J GENE MED 739–48 (2005) (“Ahmad”)
`1008 Declaration of Dr. Andrew S. Janoff
`1009 Gao, Xiang et al., Nonviral Gene Delivery: What We Know and What Is Next,
`9 AAPS JOURNAL Article 9, pp. E92-E104 ( 2007) (“Gao”)
`1010 Bennett, Michael J. et al., Cholesterol Enhances Cationic Liposome-Mediated
`DNA Transfection of Human Respiratory Epithelial Cells, 15 Bioscience
`Reports, pp. 47-53 (1995) (“Bennett”)
`1011 Heyes, James et al., Cationic lipid saturation influences intracellular delivery
`of encapsulated nucleic acids, 107 JOURNAL OF CONTROLLED RELEASE 276–
`87 (2005) (“Heyes”)
`1012 U.S. Patent No. 5,753,613 (“’613 patent”)
`1013 U.S. Patent No. 7,939,505 (“’505 patent”)
`1014 U.S. Publication No. US2007/0042031 (“’031 publication”)
`1015 U.S. Publication No. US2006/0008910 (“’910 publication”)
`1016 Excerpts from ’069 Patent File History
`1017 U.S. Patent No. 5,264,618 (“’618 patent”)
`1018 Curriculum Vitae of Dr. Andrew S. Janoff
`1019 Kauffman, Kevin J. et al., Optimization of Lipid Nanoparticle Formulations
`for mRNA Delivery in Vivo with Fractional Factorial and Definitive
`Screening Designs, NANO LETTERS (2015) (“Kaufman”)
`
`
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`IPR Case No. Unassigned
`
`
`
`
`
` U.S. Patent No. 8,058,069
`
`In accordance with 35 U.S.C. §§ 311–319 and 37 C.F.R. § 42.100 et seq.,
`
`Moderna Therapeutics, Inc. (“Petitioner”) respectfully requests that the Board
`
`institute inter partes review and cancel claims 1–22 of U.S. Patent 8,058,069 (“ʼ069
`
`patent”) (Ex. 1001).
`
`I.
`
`INTRODUCTION
`The Board has already instituted inter partes review of the direct descendant
`
`of the ’069 patent, U.S. Patent No. 9,364,435 (“ʼ435 patent”) (Ex. 1002), in
`
`IPR2018-00739. The claims of both patents are directed to a composition of nucleic
`
`acid-lipid particles (e.g., particles that can be used to deliver therapeutic nucleic acid
`
`payloads to a patient) comprising four lipid components (i.e., cationic lipid,
`
`phospholipid, cholesterol and conjugated lipid), each of which fall within a claimed
`
`proportion with regard to the total lipid in the particles. See, e.g., Ex. 1001, cl. 1;
`
`Ex. 1002, cl. 1. The single independent claim in each of the two patents differ in the
`
`claimed proportion of cationic lipid (50%-65% for the ’069 patent; 50%-85% for
`
`the’435 patent) and a corresponding change to the amount of non-cationic lipid.1 Id.
`
`As with the ’435 patent, the overlapping and encompassing ranges for the lipid
`
`components are disclosed in the prior art anticipating or rending obvious the claims
`
`of the ’069 patent.
`
`
`1 The ’069 patent also delineates two types of non-cationic lipids.
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`IPR Case No. Unassigned
`
`
`
`
`
` U.S. Patent No. 8,058,069
`
`The’069 and ’435 patents belong to one iteration of unrelated patent families
`
`prosecuted by Arbutus Biopharma Corporation, some of which date back to the early
`
`2000s, that disclose substantially the same nucleic acid-lipid particles with only
`
`trivial differences in claim scope. By obtaining overlapping claims in these
`
`unrelated patent families, Patent Owner has improperly extended its patent
`
`protection. Patent Owner is using these patent families, including the ’069 patent,
`
`to improperly block the public and industry participants from using basic
`
`combinations of nucleic acid-lipid particle components explicitly described long
`
`before the ’069 patent’s priority date.
`
`For example, Patent Owner’s own disclosures in PCT Application No.
`
`PCT/CA2004/001051, Publication No. WO2005/007196 A2 (“’196 PCT”) (Ex.
`
`1003) and U.S. Patent Publication No. US2006/0134189 (“’189 publication”) (Ex.
`
`1004), and other prior art, including US Patent Publication No. 2006/0240554 A1
`
`(“’554 publication”) (Ex. 1005), show that the claimed composition of lipid
`
`components was available well before the priority date of the ’069 patent. These
`
`references disclose overlapping and encompassing ranges for each of the four lipid
`
`components with sufficient specificity to anticipate.
`
`Moreover, the disclosure of overlapping ranges for the four lipid components
`
`demonstrates a prima facie case of obviousness. In re Peterson, 315 F.3d 1325,
`
`1329 (Fed. Cir. 2003) (“[E]ven a slight overlap in range establishes a prima facie
`
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`IPR Case No. Unassigned
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`
`
`
`
` U.S. Patent No. 8,058,069
`
`case of obviousness.”); E.I. Dupont De Nnemours & Co. v. Synvina C.V., No. 2017-
`
`1977, slip op. at 18-20 (Fed. Cir. Sept. 17, 2018) (same). These disclosures, the
`
`knowledge of a POSITA and the ’069 patent’s own testing data also establish
`
`obviousness by the preponderance of the evidence. In re Magnum Oil Tools Int’l,
`
`Ltd., 829 F.3d 1364 (Fed. Cir. 2016) (petitioner’s burden of showing invalidity by
`
`preponderance of the evidence). A POSITA would appreciate that generating lipid
`
`complexes with lipid components in the ranges claimed in the ’069 patent would
`
`have been a simple matter of using prior art production methods to combine
`
`appropriate proportions of prior art lipid components. Peterson, at 1330 (“The
`
`normal desire of scientists or artisans to improve upon what is already generally
`
`known provides the motivation to determine where in a disclosed set of percentage
`
`ranges is the optimum combination of percentages.”). Thus, in the alternative, the
`
`references render the challenged claims obvious.
`
`During prosecution, Patent Owner overcame other cited prior art disclosing
`
`overlapping ranges based upon alleged unexpected test results disclosed in the ’069
`
`patent attributable to a cationic lipid proportion greater than 50%. This testing,
`
`however, was restricted to a single set of lipid components and proportions falling
`
`within the claimed ranges (e.g., the cationic lipid was fixed at 57.1 mole percent
`
`(“mol%”)). But it is well-settled that a patentee must show “unexpected results” for
`
`the entire claimed range. In re Clemens, 622 F.2d 1029, 1035 (C.C.P.A. 1980).
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`IPR Case No. Unassigned
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`
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`
`
` U.S. Patent No. 8,058,069
`
`In addition, the prior art references Lin (Ex. 1006) and Ahmad (Ex. 1007)
`
`teach that there was a recognized potential benefit in certain systems to using a
`
`cationic lipid proportion greater than 50%. A POSITA would have been motivated
`
`to combine these disclosures with the ’196 PCT or ’189 publication as described
`
`herein, further rendering the claims obvious. In addition, the skilled artisan would
`
`have had a reasonable expectation of success in doing so.
`
`II. MANDATORY NOTICES
`A. NOTICE OF REAL PARTY-IN-INTEREST (37 C.F.R. § 42.8(b)(1))
`The real party-in-interest is Moderna Therapeutics, Inc.
`
`B. NOTICE OF RELATED MATTERS (37 C.F.R. § 42.8(b)(2))
`Petitioner identifies the following related matters: Moderna Therapeautics,
`
`Inc. v. Protiva Biotherapeutics, Inc., IPR2018-00739 (’435 patent) and Moderna
`
`Therapeautics, Inc. v. Protiva Biotherapeutics, Inc., IPR2018-00680 (U.S. Patent
`
`No. 9,404,127).
`
`C. DESIGNATION OF LEAD AND BACK-UP COUNSEL (37 C.F.R.
`§ 42.8(b)(3))
`Lead Counsel: Michael Fleming
`
`(Reg. No. 67,933).
`
` Email:
`
`mfleming@irell.com.
`
`Backup Counsel: C. Maclain Wells (Reg. No. 48,991).
`
` Email:
`
`mwells@irell.com.
`
` Alan Heinrich
`
`(pro hac
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`vice TBD).
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` Email:
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`aheinrich@irell.com.
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`Address: Irell & Manella LLP, 1800 Avenue of the Stars, Suite 900, Los
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`IPR Case No. Unassigned
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` U.S. Patent No. 8,058,069
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`Angeles, CA 90067; Tel: (310) 277-1010; Fax: (310) 203-7199.
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`D.
`SERVICE INFORMATION (37 C.F.R. § 42.8(b)(4))
`Please address all correspondence to ModernaIPR@irell.com.
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`E.
`PAYMENT OF FEES (37 C.F.R. § 42.103)
`The Office is authorized to charge required fees to Deposit Account No. 09-
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`0946.
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`F. CERTIFICATION OF GROUNDS FOR STANDING (37 C.F.R. § 42.104(a))
`Petitioner certifies that the ʼ069 patent is eligible for inter partes review and
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`that Petitioner is neither barred nor estopped from requesting a review of the
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`challenged claims on the grounds identified herein.
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`III. CHALLENGE AND RELIEF REQUESTED
`Petitioner respectfully requests inter partes review and cancellation of all
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`claims of the ʼ069 patent based on the grounds in Section IX.
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`B.
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`A. GROUND 1: CLAIMS 1-22 ARE ANTICIPATED BY OR OBVIOUS IN VIEW
`OF PATENT OWNER’S PRIOR DISCLOSURES IN EITHER THE ’196 PCT
`OR THE ’189 PUBLICATION
` GROUND 2: CLAIMS 1-22 ARE OBVIOUS IN VIEW OF THE ’196 PCT
`OR THE ’189 PUBLICATION IN VIEW OF LIN AND AHMAD
`C. GROUND 3: CLAIMS 1-22 ARE ANTICIPATED BY OR OBVIOUS IN VIEW
`OF THE ’554 PUBLICATION
`IV. PRIORITY DATE
`The ʼ069 patent claims priority to provisional application No. 61/045,228,
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`filed on April 15, 2008. Ex. 1001, cover page. For purposes of this paper only,
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`IPR Case No. Unassigned
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` U.S. Patent No. 8,058,069
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`Petitioner assumes (without conceding) that the ʼ069 patent is entitled to this date.
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`V.
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`PERSONS HAVING ORDINARY SKILL IN THE ART
`A POSITA would have specific experience with lipid particle formation and
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`use in the context of delivering therapeutic nucleic acid payloads, and would have a
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`Ph.D., an M.D., or a similar advanced degree in an allied field (e.g., biophysics,
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`microbiology, biochemistry) or an equivalent combination of education and
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`experience. See Ex. 1008, Declaration of Dr. Andrew S. Janoff (“Janoff”), ¶¶29-32.
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`This level of skill is representative of the authors/inventors of prior art cited herein.
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`Id.
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`VI. BACKGROUND
`A. LIPID CARRIER PARTICLES FOR NUCLEIC ACID PAYLOADS
`Gene therapy—addressing disease at the level of the genetic cause, typically
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`with nucleic acids—is an area of intensive medical research. Therapeutic nucleic
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`acids can be used for both nucleic acid delivery and gene silencing (e.g., small
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`interfering RNA (“siRNA”)). Janoff, ¶60; see also Ex. 1009 (Gao), E92; Ex. 1006,
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`3307.
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`Long before the ’069 patent, it was known that systems comprised of
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`combinations of different types of lipids with nucleic acids could result in lipid-
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`nucleic acid particles, an accepted delivery strategy for nucleic acid therapeutics.
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`Janoff, ¶60; see also Ex. 1009, E95. The ’069 patent specification describes nucleic
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`acid-lipid carrier particles that the patentees refer to as “stable nucleic acid-lipid
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`IPR Case No. Unassigned
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`particles” or “SNALPs.” Ex. 1001, 5:51-58.
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`B.
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`THE ’069 PATENT CLAIMS ARE DIRECTED TO KNOWN LIPID
`COMPONENTS
`The ’069 patent discloses four lipid components: a cationic lipid, two non-
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`cationic lipids (a phospholipid and cholesterol), and a conjugated lipid (e.g., a
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`polyethylene glycol (“PEG”) lipid). Ex. 1001, claim 1. These lipid components
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`were known to be basic building blocks of nucleic acid-lipid particles long before
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`the ’069 patent. Janoff, ¶61; see also Ex. 1007, 740, 746 (“[cationic lipids] for
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`transfection typically consist of a mixture of cationic and neutral (helper) lipid” and
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`“strategies for optimization … could involve introducing PEG-lipids … to block …
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`unspecific interactions”); Ex. 1009, E95, 97 (cationic lipid carrier particles “are often
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`formulated with a noncharged phospholipid or cholesterol as a helper lipid … PEG-
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`lipid conjugates have been incorporated … to minimize interaction with blood
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`components ....”).
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`Cationic lipids interact with the negative charge on nucleic acid payload
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`facilitating formation of complexes. Janoff, ¶62; see also Ex. 1009, E95. Effective
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`delivery of the nucleic acid (called the “transfection efficiency”) is thought to require
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`fusion between the lipid complex and a cell membrane.2 Janoff, ¶62; see also Ex.
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`2 In the art, “[t]he term ‘fusogenic’ refers to the ability of a lipid particle … to fuse
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`with t