`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 1 of 61 PagelD #: 17927
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`EXHIBIT B
`EXHIBIT B
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`
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 2 of 61 PageID #: 17928
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`ARBUTUS BIOPHARMA CORPORATION
`and GENEVANT SCIENCES GmbH,
`
`Plaintiffs,
`
`v.
`
`MODERNA, INC. and MODERNATX, INC.,
`
`Defendants.
`
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`
`C. A. No. 22-252-MSG
`
`JURY TRIAL DEMANDED
`
`HIGHLY CONFIDENTIAL -
`OUTSIDE COUNSEL'S EYES ONLY -
`FILED UNDER SEAL
`
`AMENDED COMPLAINT FOR PATENT INFRINGEMENT
`
`Plaintiffs Arbutus Biopharma Corporation (“Arbutus”) and Genevant Sciences GmbH
`
`(“Genevant”) file this Complaint seeking patent infringement damages against Defendants
`
`Moderna, Inc. and ModernaTX, Inc. (collectively, “Moderna”) and allege the following:
`
`INTRODUCTION
`
`1.
`
`The impact of the COVID-19 pandemic, one of the greatest public health
`
`challenges in modern history, would be immeasurably worse but for the rapid, widespread
`
`availability of cutting-edge mRNA-based vaccines like Moderna’s. Moderna brought its vaccine
`
`from lab bench to arms in record speed. That unprecedented accomplishment was made possible
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`by Moderna’s use of breakthrough technology Arbutus had already created and patented—a
`
`revolutionary lipid nanoparticle (“LNP”) delivery platform that took the scientists of Arbutus
`
`years of painstaking work to develop and refine. Moderna was well aware of Arbutus’s LNP
`
`patents and licensed them for other product programs, but it chose not to do so for its COVID-19
`
`vaccine. Instead, it attempted to invalidate several of the patents before the United States Patent
`
`and Trademark Office, and when those efforts largely failed, Moderna simply used the patented
`
`
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 3 of 61 PageID #: 17929
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`
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`technology without paying for it or even asking for a license. Plaintiffs do not seek an injunction
`
`or any relief in this case that would impede the sale or manufacture of Moderna’s life-saving
`
`vaccine. They seek only fair compensation for the use of patented technology they developed
`
`with great effort and at great expense, without which Moderna’s COVID-19 vaccine would not
`
`have been successful.
`
`2.
`
`Medicines using messenger ribonucleic acid (or “mRNA”) technology, like
`
`Moderna’s COVID-19 vaccine, rely on synthetic mRNA that enters the body’s cells and instructs
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`them to make proteins they would not necessarily make on their own. Moderna’s COVID-19
`
`vaccine, in particular, uses mRNA to cause cells to make a small piece of the virus that causes
`
`COVID-19 called the “spike protein.” That small piece, which is harmless in isolation, prompts
`
`the body’s immune system to produce antibodies that will recognize the spike protein if it is
`
`encountered in the future and destroy it. In this way, the vaccine equips a person’s body ahead
`
`of time with antibodies to fight the COVID-19 virus if that person experiences a subsequent
`
`exposure.
`
`3.
`
`Ever since the vast potential for mRNA-based vaccines and other mRNA-based
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`medicines began to catch the attention of scientists more than two decades ago, the biggest
`
`technological hurdle to developing and deploying them has been devising a safe and effective
`
`way to deliver the mRNA to the cell. Without adequate protection, mRNA quickly degrades in
`
`the body. For mRNA vaccines like Moderna’s to work, they must incorporate a mechanism for
`
`protecting the fragile mRNA, delivering it through cell membranes, and then releasing it inside
`
`2
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`
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 4 of 61 PageID #: 17930
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`
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`the cell. In the words of one Nobel Prize winning scientist, the secret for making RNA-based
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`products work has always been “delivery, delivery, delivery.”1
`
`4.
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`Having vexed experts in the field for years, that problem eventually found a
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`solution in the innovative research of Arbutus scientists. Their solution was ingenious:
`
`microscopic particles built from four carefully selected types of fat-like molecules, so small that
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`they are measured in nanometers but still stable enough to shelter and protect an RNA molecule
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`on a voyage through the human body to a target cell, and then through the target cell’s
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`membrane, before finally releasing the RNA. These tiny fat-like particles are called “lipid
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`nanoparticles,” or “LNPs.” The United States Patent and Trademark Office has granted Arbutus
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`several patents for its groundbreaking LNP technologies.
`
`5.
`
`LNPs identified through Arbutus’s pioneering work have been described as
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`“crucial” to Moderna’s COVID-19 vaccine, the first mRNA product the company was able to
`
`commercialize and the keystone of its financial success.2 Without the LNPs Arbutus invented to
`
`safeguard the mRNA and deliver it into cells, the mRNA in Moderna’s vaccine would degrade
`
`before ever reaching the cells it needs to enter and the vaccine would not work.
`
`6.
`
`Moderna has long been aware of Arbutus’s LNP intellectual property and its
`
`importance as a component of mRNA-based vaccines and other mRNA-based medicines.
`
`Several years before the pandemic, Moderna obtained licenses to use Arbutus’s LNP patents for
`
`certain mRNA products directed to specific viral targets. But those licenses did not grant
`
`Moderna rights to use the technology for products targeting SARS-CoV-2, the virus that causes
`
`
`1 Erika Check, “RNA to the Rescue,” Nature 425:10-12 (2003), available at
`https://www.nature.com/articles/425010a.
`2 Nathan Vardi, “Moderna’s Mysterious Coronavirus Vaccine Delivery System,” Forbes.com,
`July 29, 2020, available at https://www.forbes.com/sites/nathanvardi/2020/07/29/modernas-
`mysterious-coronavirus-vaccine-delivery-system/.
`
`3
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`
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 5 of 61 PageID #: 17931
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`
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`COVID-19 and that the vaccines at issue here target. Before it decided to use Arbutus’s proven
`
`and patented technology as a crucial part of its COVID-19 vaccine, Moderna did not ask for a
`
`license to do so. Instead, it tried to convince the United States Patent and Trademark Office and,
`
`later, the United States Court of Appeals for the Federal Circuit to cancel several of Arbutus’s
`
`LNP-related patents. But despite the failure of Moderna’s attempts to eliminate Arbutus’s
`
`patents, and despite Plaintiffs’ efforts to resolve this dispute without litigation, Moderna has
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`remained unwilling to pay for its use of Arbutus’s technology in a vaccine that has earned
`
`Moderna billions of dollars in profits.
`
`7.
`
`Moderna’s intransigence has forced Arbutus and Genevant, a company
`
`spearheaded by former Arbutus scientists, to bring this infringement action. Plaintiffs are proud
`
`that their LNP technology has had such a profound impact on the heroic fight against the
`
`COVID-19 pandemic, and they do not seek to impede by an injunction or otherwise the
`
`production or distribution of Moderna’s COVID-19 vaccine, including boosters. All Plaintiffs
`
`seek is the compensation due to them under the patent laws of the United States and as a matter
`
`of simple fairness.
`
`NATURE OF THE ACTION
`
`8.
`
`This is a civil action under the patent laws of the United States, 35 U.S.C. § 101 et
`
`seq., seeking damages for Moderna’s infringing manufacture, use, sale, offer for sale, and/or
`
`importation of, and/or the supplying from the United States of a component or all or a substantial
`
`portion of the components of, its mRNA-1273 COVID-19 mRNA LNP vaccine product
`
`(“Moderna’s COVID-19 vaccine”) or any supplemental or booster COVID-19 mRNA LNP
`
`vaccine product (collectively, the “Accused Product”).
`
`4
`
`
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 6 of 61 PageID #: 17932
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`9.
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`As alleged herein, the manufacture, use, sale, offer to sell, and/or importation of
`
`the Accused Product, and/or the supplying from the United States of a component or all or a
`
`substantial portion of the components of the Accused Product infringes or will infringe, actively
`
`induces or will actively induce infringement of, or contributes or will contribute to the
`
`infringement of, one or more claims of the following patents relating to nucleic acid-lipid
`
`particles, compositions thereof, and their use to deliver nucleic acid-based medicines: U.S.
`
`Patent Nos. 8,058,069 (Exhibit A), 8,492,359 (Exhibit B), 8,822,668 (Exhibit C), 9,364,435
`
`(Exhibit D), 9,504,651 (Exhibit E), and 11,141,378 (Exhibit F) (collectively, the “Asserted
`
`Patents”). At all relevant times, Arbutus owned the Asserted Patents and licensed exclusive
`
`rights to sublicense, practice, and sue for infringement of them to Genevant in certain fields of
`
`use that include the vaccine application at issue in this Complaint, with certain exceptions not
`
`relevant here (hereinafter, Genevant’s “Exclusive Rights”).
`
`THE PARTIES
`
`10.
`
`Plaintiff Arbutus Biopharma Corporation is a corporation organized and existing
`
`under the laws of Canada, with its principal place of business at 701 Veterans Circle,
`
`Warminster, Pennsylvania, 18974. The company’s research and development efforts include
`
`discovering, developing, and commercializing a cure for chronic hepatitis B virus, as well as
`
`drug discovery and development efforts for treating coronaviruses, including SARS-CoV-2,
`
`which causes COVID-19.
`
`11.
`
`Plaintiff Genevant Sciences GmbH is a company organized and existing under the
`
`laws of Switzerland, with its principal place of business at Viaduktstrasse 8, 4051 Basel,
`
`Switzerland. Genevant is a technology-focused nucleic acid delivery solutions company with
`
`cutting-edge LNP platforms. Genevant owns or licenses the industry’s most important LNP
`
`5
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`
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 7 of 61 PageID #: 17933
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`
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`intellectual property—that of Arbutus—and has decades of experience and expertise in nucleic
`
`acid drug delivery and development. Genevant, together with its affiliated companies, maintains
`
`offices in Cambridge, Massachusetts and Vancouver, British Columbia, Canada. Genevant’s
`
`mission is to utilize its LNP and other technologies to deliver innovative new medicines that use
`
`mRNA or other nucleic acids.
`
`12.
`
`Defendant Moderna, Inc. is a corporation organized and existing under the laws of
`
`the State of Delaware, with its principal place of business at 200 Technology Square, Cambridge,
`
`Massachusetts, 02139. Moderna, Inc., itself and through its subsidiary ModernaTX, Inc.,
`
`develops, manufactures, imports, markets, distributes, offers to sell, and/or sells vaccines and
`
`other medicines in the State of Delaware and throughout the United States, for use in the State of
`
`Delaware and throughout the United States.
`
`13.
`
`Defendant ModernaTX, Inc. is a wholly owned subsidiary of Moderna, Inc.
`
`(collectively, “Moderna”). ModernaTX, Inc. is also a corporation organized and existing under
`
`the laws of the State of Delaware, with its principal place of business at 200 Technology Square,
`
`Cambridge, Massachusetts, 02139. ModernaTX, Inc. develops, manufactures, imports, markets,
`
`distributes, offers to sell, and/or sells vaccines and other medicines in the State of Delaware and
`
`throughout the United States, for use in the State of Delaware and throughout the United States.
`
`JURISDICTION AND VENUE
`
`A.
`
`Subject-Matter Jurisdiction
`
`14.
`
`Because this is an action for infringement under the patent laws of the United
`
`States, Title 35 of the United States Code, the Court has subject matter jurisdiction pursuant to
`
`28 U.S.C. §§ 1331 and 1338(a).
`
`6
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 8 of 61 PageID #: 17934
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`
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`B.
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`Personal Jurisdiction
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`15.
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`This Court has personal jurisdiction over Moderna because, among other things,
`
`Moderna, Inc. and ModernaTX, Inc. have purposefully availed themselves of the benefits and
`
`protections of Delaware’s laws such that they should reasonably anticipate being haled into court
`
`here. Because Defendants are organized and exist under the laws of Delaware, are qualified to
`
`do business in Delaware, and have appointed registered agents for service of process in
`
`Delaware, Moderna, Inc. and ModernaTX, Inc. have consented to general jurisdiction in
`
`Delaware.
`
`16.
`
`Additionally, Moderna, Inc. and ModernaTX, Inc., directly or through others,
`
`make, use, induce others to use, offer for sale, and/or sell the Accused Product, and/or a
`
`component, combination, or composition constituting a material part of the Accused Product,
`
`within the United States, and/or import the same into the United States, including into the
`
`District of Delaware. For example, on December 18, 2020, Moderna received Emergency Use
`
`Authorization (“EUA”) from the United States Food and Drug Administration (“FDA”) for its
`
`COVID-19 vaccine to be distributed and administered to people throughout the United States,
`
`including in the District of Delaware and, on January 31, 2022, the FDA approved Moderna’s
`
`Biologics License Application (“BLA”) for its COVID-19 vaccine. Upon information and
`
`belief, as of February 24, 2022, over 835,000 doses of Moderna’s COVID-19 vaccine have been
`
`delivered to the State of Delaware.3 Therefore, Moderna, Inc. and ModernaTX, Inc. transact
`
`business within Delaware relating to Plaintiffs’ claims and have engaged in systematic and
`
`continuous business contacts here.
`
`
`3 Delaware Environmental Public Health Tracking Network, Vaccine Tracker,
`https://myhealthycommunity.dhss.delaware.gov/locations/state/vaccine-tracker (last visited Feb.
`25, 2022).
`
`7
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 9 of 61 PageID #: 17935
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`17.
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`For the above reasons, there is nothing unreasonable or fundamentally unfair
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`about requiring Moderna, Inc. and ModernaTX, Inc. to litigate this action in this District, and the
`
`Court has personal jurisdiction over them here.
`
`C.
`
`Venue
`
`18.
`
`Venue is proper in this District under 28 U.S.C. §§ 1391(c)(2) and 1400(b)
`
`because both Moderna, Inc. and ModernaTX, Inc. are corporations organized and existing under
`
`the laws of the State of Delaware and are therefore subject to suit in this District.
`
`A.
`
`How Vaccines Work
`
`BACKGROUND
`
`19.
`
`Viruses are typically small packets of DNA or RNA. If a virus enters a living
`
`host cell—for example, after being ingested, transmitted through bodily fluids, or inhaled
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`through a person’s mouth or nose—the virus’s DNA or RNA hijacks the cell’s machinery and
`
`instructs the cell to make copies of the virus. These copies, often numbering into the millions,
`
`leave the infected cell and enter other cells where the process repeats. Infected cells can be
`
`damaged or die while hosting the virus. Left unchecked, the host organism itself can die.
`
`20.
`
`Although vaccines targeting viruses have different mechanisms of action, they
`
`traditionally work by injecting into the body a weakened or inactive form of the virus that is
`
`unable to cause infection, but nonetheless retains features of the infectious virus and can teach
`
`the immune system to recognize and attack the infectious virus if it invades in the future.
`
`B.
`
`Nucleic Acid Medicines and Delivery Technologies
`
`21. Moderna’s COVID-19 vaccine belongs to a new class of medicines that deliver
`
`nucleic acids into the cells of the body to treat diseases or, in the case of Moderna’s COVID-19
`
`vaccine, to trigger an immune response to protect a person from future infection.
`
`8
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 10 of 61 PageID #: 17936
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`22.
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`Nucleic acids are molecules that encode the genetic information essential to
`
`sustain all forms of life. One type of nucleic acid is deoxyribonucleic acid, or “DNA,” which is
`
`found in our chromosomes. In humans, each person (except identical twins) has a unique set of
`
`genetic information in the “genes” within his or her chromosomes. Among other things, these
`
`genes spell out the instructions for producing proteins that make our cells and bodies function.
`
`23.
`
`In order to make the protein encoded by a particular gene, the cell first converts
`
`the genetic code in the gene’s DNA into another type of nucleic acid known as messenger
`
`ribonucleic acid, or “mRNA.” mRNA is effectively a copy of the portion of DNA that the cell’s
`
`protein-making machinery uses as a blueprint to assemble the protein encoded by the gene.
`
`24.
`
`Vaccines and other medicines using ribonucleic acid, or “RNA,” technologies are
`
`an emerging frontier with the potential to revolutionize medicine. RNA-based medicines can
`
`employ a type of RNA called small interfering RNA (“siRNA”) to treat certain diseases by
`
`interfering with the expression of unwanted proteins to reduce the amounts produced—a process
`
`called RNA interference (“RNAi”). RNA-based medicines also can employ mRNA to cause or
`
`increase the production of certain proteins. mRNA vaccines, for example, cause cells to express
`
`a protein (or a piece of a protein) that is normally found on a particular tumor or that is part of a
`
`particular virus. The presence of that protein (or piece of a protein) teaches the body’s immune
`
`system to recognize it if it is encountered in the future and destroy it. These and other RNA-
`
`based medicines hold great promise for addressing many previously intractable diseases and, as
`
`in the present circumstances, new viruses that cause or threaten worldwide pandemics.
`
`25.
`
`Despite their promise, however, RNA-based medicines have been difficult to
`
`develop. By their nature, RNA molecules are fragile. Without adequate protection, RNA
`
`molecules are susceptible to degradation in the body, and, if and when they get to a cell, cannot
`
`9
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 11 of 61 PageID #: 17937
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`
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`cross the cell membrane to enter the cell. For decades, the need for an effective delivery
`
`technology had been the most significant challenge in the development of RNA-based products.
`
`In particular, without the means to protect mRNA and facilitate its entry into target cells,
`
`mRNA-based vaccines and other medicines have been ineffective.
`
`26.
`
`Indeed, functional RNA-based medicines eluded researchers until the pioneering
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`work by Arbutus scientists, many now at Genevant companies, resulting in the discovery and
`
`development of the leading nucleic acid delivery technology in use today. Decades ago, a group
`
`of ambitious research scientists working at a predecessor company to Arbutus began to tackle the
`
`nucleic acid delivery problem that had long stymied the field. Years of tireless effort by these
`
`scientists resulted in a solution to the problem. The solution was LNP technology that relies
`
`on fat-like molecules called lipids that encapsulate and protect nucleic acids like mRNA from
`
`degradation in the body and enable them to cross cell membranes. Once inside a cell, the LNP
`
`releases the nucleic acid it encapsulates so that, in the case of an mRNA vaccine for example, the
`
`nucleic acid can express the protein it encodes.
`
`27.
`
`The lipid components of the Arbutus technology include: structural lipids, such as
`
`phospholipids and cholesterol; “cationic” (positive charge-bearing) lipids, including “ionizable”
`
`lipids that are positive charge-bearing at certain pH levels; and conjugated lipids, which are
`
`lipids attached to a polymer such as polyethyleneglycol (“PEG”). Arbutus scientists discovered
`
`that nucleic acid-lipid particles combining particular lipid components in particular ratios could
`
`achieve much more effective delivery of nucleic acids through cell membranes and into cells.
`
`28.
`
`These Arbutus scientists spent more than a decade researching and developing
`
`this nucleic acid-lipid delivery technology. Their efforts led to the first FDA-approved RNA-
`
`based therapeutic in the form of a drug called Onpattro®, an RNAi treatment for a form of
`
`10
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 12 of 61 PageID #: 17938
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`
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`amyloidosis, a rare disease that causes certain proteins to accumulate in organs. The company
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`that developed Onpattro®, Alnylam Pharmaceuticals, did so under an LNP license from Arbutus
`
`and received FDA approval in August 2018. Building on this initial success, Arbutus has
`
`granted licenses to its LNP technology to other companies, and Genevant now has several
`
`ongoing LNP product development collaborations, some directed to COVID-19 and some
`
`directed to other diseases and disorders. Several entities developing mRNA-LNP vaccines
`
`against COVID-19 have come to Genevant for a license to Arbutus’s technology, including
`
`companies that have produced promising candidates in clinical trials. And Genevant’s COVID-
`
`19 development collaborations include efforts to provide a vaccine to parts of the developing
`
`world.
`
`C.
`
`The United States Awards Patents Recognizing Arbutus’s Innovations
`
`29.
`
`In recognition of Arbutus’s extensive and groundbreaking research and
`
`development efforts, the United States Patent and Trademark Office has granted several families
`
`of patents claiming nucleic acid-lipid particles and lipid vesicles, as well as compositions and
`
`methods of using them. The Asserted Patents are among them:
`
`a. U.S. Patent No. 8,058,069, “Lipid Formulations for Nucleic Acid Delivery,”
`
`issued on November 15, 2011 (the “’069 Patent”).
`
`b. U.S. Patent No. 8,492,359, “Lipid Formulations for Nucleic Acid Delivery,”
`
`issued on July 23, 2013 (the “’359 Patent”).
`
`c. U.S. Patent No. 8,822,668, “Lipid Formulations for Nucleic Acid Delivery,”
`
`issued on September 2, 2014 (the “’668 Patent”).
`
`d. U.S. Patent No. 9,364,435, “Lipid Formulations for Nucleic Acid Delivery,”
`
`issued on June 14, 2016 (the “’435 Patent”).
`
`11
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 13 of 61 PageID #: 17939
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`
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`e. U.S. Patent No. 9,504,651, “Lipid Compositions for Nucleic Acid Delivery,”
`
`issued on November 29, 2016 (the “’651 Patent”).
`
`f. U.S. Patent No. 11,141,378, “Lipid Formulations for Nucleic Acid Delivery,”
`
`issued on October 12, 2021 (the “’378 Patent”).
`
`30.
`
`True and correct copies of the Asserted Patents are attached hereto as Exhibits A
`
`through F. All are valid and enforceable under United States patent laws. All are assigned to
`
`and owned by Arbutus, and, at all times since Arbutus and Genevant entered into a license
`
`agreement, Genevant has held Exclusive Rights to all of the Asserted Patents in various fields of
`
`use including the vaccine application at issue here. Under the terms of the license, Genevant’s
`
`Exclusive Rights include the right to sue for the infringement alleged in this Complaint.
`
`D. Moderna’s Knowledge of, and Background with, the Asserted Patents
`
`31. Moderna has been on actual notice of Arbutus’s patents since before its
`
`development of the Accused Product and has knowingly used Arbutus’s technology as an
`
`essential component of its nucleic acid products and product candidates, including its COVID-19
`
`vaccine.
`
`32.
`
`Years before the COVID-19 pandemic, Moderna recognized that Arbutus’s LNP
`
`technology could fuel its own work in RNA-based vaccines and other medicines. Accordingly,
`
`in or about May 2015, Moderna attempted to acquire rights to Arbutus’s LNP delivery
`
`technology for four specific viral targets (none of which is COVID-19) through sublicense from
`
`a Canadian company called Acuitas Therapeutics. Although Acuitas had licensed Arbutus’s
`
`LNP technology in 2012, its license agreement expressly limited Acuitas’s ability to grant
`
`sublicenses. That limitation prohibited Acuitas from granting the sublicense that it granted to
`
`Moderna.
`
`12
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 14 of 61 PageID #: 17940
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`
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`33.
`
`In August 2016, after learning of the Moderna-Acuitas sublicense agreements,
`
`Arbutus notified Acuitas of material breach. In October 2016, Acuitas filed suit in the Supreme
`
`Court of British Columbia seeking to prevent Arbutus from terminating the Arbutus-Acuitas
`
`agreement. Arbutus counterclaimed for a declaration that the license had been terminated and
`
`sought an injunction barring Acuitas from further sublicensing Arbutus’s LNP technology.
`
`34.
`
`In February 2018, Arbutus and Acuitas settled their dispute. The settlement
`
`agreement provided that Acuitas no longer could use Arbutus’s LNP technology, with the four
`
`specific sublicenses to Moderna for vaccines targeting specific viruses remaining in effect.
`
`SARS-CoV-2, the virus that causes COVID-19 and the target of the vaccine accused of
`
`infringement in this Complaint, is not among the surviving sublicenses.
`
`35.
`
`Deprived of a broad license to Arbutus’s valuable LNP technology and hoping to
`
`make unrestricted use of that technology without having to pay royalties, Moderna began filing
`
`inter partes review (“IPR”) petitions requesting that the Patent and Trademark Office cancel
`
`certain of Arbutus’s patents, including some asserted here.
`
`36. Moderna’s first IPR petition, filed in February 2018, challenged Arbutus’s U.S.
`
`Patent No. 9,404,127 (“the ’127 Patent”), which, like the Asserted Patents, is directed to
`
`Arbutus’s LNP technology. The Patent Trial and Appeal Board (“PTAB”) ruled that all claims
`
`of the ’127 Patent should be cancelled. An appeal of that decision remains pending before the
`
`United States Court of Appeals for the Federal Circuit.
`
`37. Moderna’s IPRs against the Asserted Patents were less successful. Its second IPR
`
`petition, filed in March 2018, ended with the PTAB rejecting Moderna’s arguments challenging
`
`the validity of ten of the ’435 Patent’s twenty claims. Moderna challenged that ruling on appeal,
`
`13
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`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 15 of 61 PageID #: 17941
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`
`
`but in a December 2021 decision, the United States Court of Appeals for the Federal Circuit
`
`dismissed Moderna’s appeal for lack of standing.4
`
`38. Moderna’s third IPR petition, filed in January 2019, was even less successful.
`
`The PTAB completely rejected Moderna’s challenge to all claims of the ’069 Patent, and the
`
`United States Court of Appeals for the Federal Circuit affirmed that ruling in December 2021.
`
`E. Moderna Designs Its COVID-19 Vaccine Over a Single Weekend Aided by the
`Unauthorized Use of Arbutus’s LNP Technology
`
`39.
`
`On January 10, 2020, with the novel SARS-CoV-2 virus quickly spreading
`
`around the world, scientists identified the virus’s complete genetic sequence and posted it for
`
`free on the internet. This public disclosure revealed the complete RNA sequence that encodes
`
`the virus’s components, including its distinctive “spike protein.” With that information in the
`
`public domain, researchers around the world were able to begin designing vaccines to target the
`
`virus.
`
`40. Moderna was one of many companies that began work on a vaccine in earnest
`
`once the genetic sequence was published.
`
`41.
`
`Relying on Arbutus’s LNP technology covered by the Asserted Patents, Moderna
`
`was able to begin producing its COVID-19 vaccine within just a few days of the SARS-CoV-2
`
`genomic sequence entering the public domain. The design component of the effort was even
`
`faster: According to Moderna President Stephen Hoge, “[w]e did it in an hour, and it worked
`
`brilliantly.”5 Compared to the timelines of prior vaccine-development efforts, Moderna’s
`
`
`4 Arbutus cross-appealed the PTAB’s decision, challenging the invalidation of the ten claims of
`the ’435 Patent that were not upheld. On December 1, 2021, the Federal Circuit affirmed the
`PTAB’s decision as to those claims.
`5 “Stephen Hoge, MD ’03: Turns out, designing a COVID vaccine was easy,” UCSF Alumni,
`available at https://alumni.ucsf.edu/stories/stephen-hoge.
`
`
`14
`
`
`
`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 16 of 61 PageID #: 17942
`
`
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`accomplishment was unprecedented. In the words of Moderna’s CEO Stéphane Bancel, “11
`
`months since the DNA sequence of the virus became available, you will have two approved
`
`mRNA vaccines, which has never happened before with any technology. That is amazing.”6
`
`42. Moderna’s success was chronicled in an article first published online on June 11,
`
`2020, by individuals affiliated with the company and collaborators at the National Institutes of
`
`Health. According to this article—the “Moderna/NIH preprint”—“the release of SARS-CoV-2
`
`sequences triggered immediate rapid manufacturing of an mRNA vaccine” by Moderna.7
`
`Moderna “decide[d] on [the] mRNA-1273 sequence” on January 13, 2020, just three days after
`
`the publication of the viral sequence, and “initiate[d] cGMP production” the very next day, on
`
`January 14, 2020.8 On February 24, 2020, Moderna shipped clinical drug product, and, less than
`
`a month later, Phase I trials began.9
`
`43. Moderna’s COVID-19 vaccine could not have been developed, much less on a
`
`timeline unprecedented in human history, without Arbutus’s proven and patented LNP delivery
`
`technology—technology that had transformed vaccine design from a years-long project into one
`
`that could be performed within an hour over a January weekend.
`
`
`6 Antonio Regalado, “‘None of us were ready’ to manufacture genetic vaccines for a billion
`people,” MIT Technology Review (December 17, 2020), available at
`https://www.technologyreview.com/2020/12/17/1014989/moderna-vaccine-availability-
`stephane-bancel-ceo/.
`7 “SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness,”
`bioRvix.org (June 11, 2020) available at
`https://www.biorxiv.org/content/10.1101/2020.06.11.145920v1.full.
`8 Id.
`9 Id.
`
`
`
`15
`
`
`
`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 17 of 61 PageID #: 17943
`
`
`
`44. Moderna’s co-founder Robert Langer has been quoted as saying “I don’t think
`
`people realized just how important the delivery systems are . . . .”10 LNPs are so crucial to
`
`Moderna’s mRNA vaccines that Giuseppe Ciaramella, head of infectious diseases at Moderna
`
`from 2014 to 2018, called LNPs “the unsung hero of the whole thing,”11 while Moderna CEO
`
`Stéphane Bancel stated in December 2020 that “[w]e always said it is . . . about developing the
`
`right delivery technology. And this is something that takes years, not two weeks.”12
`
`45.
`
`The Moderna/NIH preprint detailed Moderna’s use of Arbutus’s LNP technology
`
`and its infringement of the Asserted Patents. The scientists who worked on the vaccine and
`
`contributed to the article explained that Moderna’s COVID-19 vaccine is composed of mRNA
`
`encoding a modified version of the SARS-CoV-2 spike (S) protein that was synthesized,
`
`purified, “and encapsulated into lipid nanoparticles (LNP),” with a lipid molar ratio of
`
`“50:10:38.5:1.5 (ionizable lipid:DSPC:cholesterol:PEG-lipid).” Specifically, the Moderna/NIH
`
`preprint indicates that the Accused Product includes lipid particles comprising the following
`
`lipids in the following ratio: 50 mol % of an ionizable lipid that is cationic; 10 mol % of a
`
`phospholipid (DSPC); 38.5 mol % of cholesterol; and 1.5 mol % of a conjugated lipid that
`
`inhibits aggregation of particles (PEG-lipid).
`
`46.
`
`These components are within the ranges of, among other claims of the Asserted
`
`Patents, Claim 1 of Arbutus’s ’069 Patent, which recites a “nucleic acid-lipid particle comprising
`
`(a) a nucleic acid; (b) a cationic lipid comprising from 50 mol % to 65 mol % of the total lipid
`
`
`10 Tim Loh, “Lipids Are Delivering the Vaccine Revolution,” Bloomberg (March 6, 2021),
`available at https://www.bloomberg.com/news/newsletters/2021-03-06/lipids-are-delivering-the-
`vaccine-revolution.
`11 Ryan Cross, “Without these lipid shells, there would be no mRNA vaccines for COVID-19,”
`C&EN (March 6, 2021), available at https://cen.acs.org/pharmaceuticals/drug-delivery/Without-
`lipid-shells-mRNA-vaccines/99/i8.
`12 Regalado, supra note 7.
`
`16
`
`
`
`Case 1:22-cv-00252-MSG Document 316-2 Filed 05/13/24 Page 18 of 61 PageID #: 17944
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`
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`present in the particle: (c) a non-cationic lipid