Case 1:21-cv-01736-UNA Document1 Filed 12/10/21 Page 1 of 18 PagelD #: 1
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`IN THE UNITED STATES DISTRICT COURT
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`FOR THE DISTRICT OF DELAWARE
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`C.A. No.
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`JURY TRIAL DEMANDED
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`GENZYME CORPORATION and
`AVENTISINC.,
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`Plaintiffs,
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`v.
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`NOVARTIS GENE THERAPIES, INC.,
`NOVARTIS PHARMACEUTICALS
`CORPORATION, and NOVARTIS AG
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`Defendants.
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`COMPLAINT
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`Plaintiffs Genzyme Corporation (“Genzyme”) and Aventis Inc. (“Aventis”) (collectively,
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`“Plaintiffs”), for their Complaint against Defendants Novartis Gene Therapies, Inc., Novartis
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`Pharmaceutical Corporation, and Novartis AG (collectively, “Novartis” or “Defendants”), allege
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`as follows:
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`Nature of the Action
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`1. This is a civil action under the Patent Act, 35 U.S.C. § 1 ef seq., for infringement of
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`United States patents. Specifically, Plaintiffs allege that Defendants infringe United States Patent
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`No, 6,596,535 (the “’535 Patent”); United States Patent No. 7,125,717 (the “’717 Patent”); United
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`States Patent No. 7,785,888 (the “888 Patent”), United States Patent No. 7,846,729 (the “’729
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`Patent”), and United States Patent No. 8,093,054 (the “’054 Patent”’) (collectively, the “Asserted
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`Patents”) through the unauthorized manufacture, use, and sale of recombinant adeno-associated
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`virus vectors (“tAAVvectors”) for their gene therapy drug Zolgensma®.
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`The Parties
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`2. Plaintiff Genzyme is a corporation organized and existing under the laws of the
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`Commonwealth of Massachusetts, having its principal place of business at 50 Binney Street,
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`Cambridge, Massachusetts 02142.
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`3. Plaintiff Aventis is a limited liability company organized and existing underthe laws
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`of the State of Delaware withits principal place of business at 55 Corporate Drive, Bridgewater,
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`New Jersey 08807. Genzymeis a wholly-owned subsidiary of Aventis.
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`4. Oninformation and belief, Novartis Gene Therapies, Inc. is a corporation organized
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`and existing under the laws of Delaware, having its corporate offices and principal place of
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`business at 2275 Half Day Road, Suite 203, Bannockburn,Illinois 60015. On information and
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`belief, Novartis Gene Therapies may be served via its registered agent, Corporation Service
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`Company, 251 Little Falls Drive, Wilmington, Delaware 19808.
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`5. On information and belief, Novartis Pharmaceuticals Corporation is a corporation
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`organized and existing under the laws of Delaware, having its corporate offices and principal
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`place of business at a principal place of business at
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`1 Health Plaza, East Hanover, New
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`Jersey 07936. On information and belief, Novartis Pharmaceuticals Corporation may be served
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`via its registered agent Corporation Service Company, 251 Little Falls Drive, Wilmington,
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`Delaware 19808. On information and belief, Novartis Pharmaceuticals Corporation is the direct
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`or indirect parent of Novartis Gene Therapies, Inc. and hasat all times directed and controlled the
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`infringing actionsofits subsidiary.
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`6. On information and belief, Novartis AG is a corporation organized and existing under
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`the laws of Switzerland, having its corporate offices and principal place of business at
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`Fabrikstrasse 2, 4056 Basel, Switzerland. On information and belief, Novartis AG is the direct
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`or indirect parent of Novartis Pharmaceuticals Corporation and Novartis Gene Therapies, Inc. and
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`has at all times directed and controlled the infringing actions of its subsidiaries.
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`Jurisdiction and Venue
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`7. This Court has subject matter jurisdiction over this action under 28 U.S.C. §§ 1331
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`and 1338(a).
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`8. This Court has personal jurisdiction over Novartis Gene Therapies, Inc. for at least the
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`reasons that Novartis Gene Therapies, Inc.
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`is incorporated in Delaware, knowingly transacts
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`business in Delaware, maintains a registered agent in Delaware, and, on information and belief,
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`has engaged in, and made meaningful preparations to engagein, infringing conduct in Delaware.
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`9, This Court has personal jurisdiction over Novartis Pharmaceuticals Corporation
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`because Novartis Pharmaceuticals Corporation is incorporated in Delaware, knowingly transacts
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`business in Delaware, maintains a registered agent in Delaware, avails itself of this Court in
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`numerous lawsuits that
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`it and/or its related entities have filed before this Court, and, on
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`information andbelief, has engaged in, and made meaningful preparations to engage in,infringing
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`conduct in Delaware.
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`10. On information and belief, this Court may exercise personal jurisdiction over Novartis
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`AG because of its contacts with this forum,
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`including its regularly and intentionally doing
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`business here, availing itself of this Court in numerous lawsuits that it and/or its related entities
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`havefiled before this Court, and/or committing acts giving rise to this lawsuit here. Alternatively,
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`on information and belief, this Court may exercise personal jurisdiction over Novartis AG under
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`Federal Rule of Civil Procedure 4(k)(2).
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`11. Venueis properin this district pursuant to 28 U.S.C. § 1400(b) with respect to Novartis
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`Gene Therapies, Inc. for at least the reason that it resides inthis district.
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`12, Venue is properinthis district pursuant to 28 U.S.C. § 1400(b) with respect to Novartis
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`Pharmaceuticals Corporationfor at least the reason thatit resides in this district.
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`13. Venue is properin this district pursuant to at least 28 U.S.C. § 1391(b) and (c) with
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`respect to Novartis AG.
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`Statement of Facts
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`Background of the Technology at Issue
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`14. The Asserted Patents relate to recombinantviral vectors useful in gene therapy (among
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`other things), as well as methods for the preparation and use of such vectors. Gene therapyis a
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`groundbreaking medical technique to treat or cure disease by modifying a person’s own genes.
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`One mechanism by which gene therapy can work is by introducing functional copies of a gene
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`(called a “‘transgene”’) into a patient’s cells that have a faulty or missing natural version of the
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`gene. By doing so, gene therapy cantreat, or even cure, a genetic disorder.
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`15. Gene therapy can be performed by packaging and delivering a transgeneto the cells
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`of a patient using recombinantviral vectors, such as recombinant adeno-associated virus (rAAV)
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`vectors that are incorporated into adeno-associated virus (AAV). However, obtaining sufficient
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`levels of transgene expression can be a hurdle for effective gene therapy.
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`In some cells,
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`expression of the transgene necessary to provide a therapeutic effect can be slow to initiate or
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`does not initiate atall.
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`16. When an AAV virus containing a rAAV vector is administered to a patient, a single-
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`stranded viral vector DNAcontaining the transgeneis transferred into a target cell. The incoming
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`single-stranded DNA must then be converted to a double-stranded DNA molecule by the target
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`cell’s own cellular mechanisms. This formation of double-stranded DNAis a key rate-limiting
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`step in the transfer of genetic material from the rAAV vector and the ultimate ability for
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`expression of the transgene in a cell. Thus, double-stranded DNA formation is needed for
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`efficient expression of a therapeutic protein and for functional gene therapy.
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`17. The inventor of the Asserted Patents, Dr. Barrie J. Carter, discovered thatrAAV vector
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`DNA canbe engineered to self-adopt a double-stranded conformation upon delivery to a target
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`cell, and can be packaged in a mannerto facilitate this conformation so that the cellular processes
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`needed to express the therapeutic protein encoded by the vectortransgene can begin immediately
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`once the vector is introduced into the cell.
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`In other words, the vectors described in the Asserted
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`Patents eliminate the need for the target cell to convert single-stranded DNA to double-stranded
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`DNA. The Asserted Patents refer to this technology as “intrastrand base pairing” vectors, which
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`are also widely knownin thefield as “self-complementary vectors.” Using the intrastrand base
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`pairing technology of the Asserted Patents, the onset of gene expression is increased, so more
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`cells can receive genetic material at a given dose of rAAV vector or the rAAV vector can be
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`effective at a lower dose as compared to conventional rAAV vectors. This discovery formed the
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`basis for later improvements on different ways to generate self-complementary vectors, which
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`have now beenincorporated into important gene therapy platforms. Thus, the Asserted Patents
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`represent a significant leap forward that allows functional gene therapy.
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`The Asserted Patents were Licensed
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`18. Building upon the technology of the Asserted Patents, Dr. Richard Samulski’s
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`laboratory at the University of North Carolina identified one way to form the intrastrand base
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`pairing vectors described by the Asserted Patents.
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`In May 2013, Asklépios BioPharmaceutical,
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`Inc (“AskBio”’), which was co-founded by Dr. Samulski, entered into a license agreement with
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`Genzyme, whereby AskBio received certain nghts to the Asserted Patents. The rights that
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`Genzymelicensed to AskBio included a limited right to sublicense. Notably, the rights Genzyme
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`licensed to AskBio expressly excluded the field of treating spinal muscular atrophy (SMA).
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`AskBio therefore could not have sublicensed rights related to treating SMA.
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`19. In June 2015, upon information and belief, AskBio entered into a sublicensing
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`agreement with AveXis, Inc. (now Novartis Gene Therapies, Inc.), which granted AveXis, Inc.
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`certain rights to the technology of the Asserted Patents. On informationand belief, the AskBio-
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`AveXis, Inc. sublicense made Novartis Gene Therapies, Inc. aware of the Asserted Patents before
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`it began marketing Zolgensma®. Because AskBio hadnorights to the Asserted Patents in relation
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`to SMA, however, its sublicense could not include any rights related to the treatment of SMA.
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`20.
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`Despite the express carve-out of SMA from the Genzyme-AskBio license (and
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`therefore the AskBio-AveXis, Inc. sublicense), on information and belief AveXis, Inc. used the
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`technology licensed from AskBio to generate Zolgensma® for treatment of SMA.
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`Zolgensma®
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`21. On April 9, 2018, Novartis AG announced that it had entered into an agreementto
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`acquire AveXis, Inc. On May 15, 2018, the transaction closed and AveXis, Inc. became a wholly-
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`ownedindirect subsidiary of Novartis AG. Theclosing of the transaction was accompanied by a
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`press release quoting the CEOs of Novartis AG and Novartis Pharmaceuticals Corporation
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`regarding the relationship with AveXis,Ine.
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`22. On May 24, 2019, AveXis, Inc. obtained FDA approval to market Zolgensma®
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`(onasemnogene abeparvovec-xioi) as a gene therapy product intended to treat certain children
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`less than two years of age with SMA. On September 2, 2020, Novartis AG announcedthat
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`AveXis, Inc. had been renamed and rebranded as Novartis Gene Therapies,Inc.
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`23. Following FDA approval of Zolgensma®, AveXis, Inc. promptly began sales and
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`active promotion of the productin the United States for the treatment of SMA,and has continued
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`sales and promotion after being renamed Novartis Gene Therapies, Inc. Zolgensma® is a gene
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`therapy product indicated for use in certain children less than two years old with SMA. A true
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`and correct copy of the current Zolgensma® package insert dated October 2021 is attached as
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`Exhibit A.
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`24. Zolgensma® is an adeno-associated virus (AAV)-based gene therapy product that
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`delivers a copy of the humansurvival motor neuron (SMN) geneinto target motor neuroncells
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`of the child, which results in expression of the SMN protein in the motor neuron cells. The
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`Zolgensma® drug productinfringes the Asserted Patents by using AskBio’s self-complementary
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`tAAV vectors, which are covered by and based on the fundamental innovation of the Asserted
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`Patents.
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`25. On information and belief, Zolgensma® has been and is currently manufactured by
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`Novartis Gene Therapies,
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`Inc.
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`in Libertyville,
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`Illinois and Durham, North Carolina. On
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`information and belief, Zolgensma® was previously also manufactured in Longmont, Colorado.
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`Patents-in-Suit
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`26. The °535 Patent, entitled “Metabolically Activated Recombinant Viral Vectors and
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`Methods for the Preparation and Use,” issued on July 22, 2003 to inventor Dr. Barrie J. Carter.
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`The 535 Patent was originally assigned to Targeted Genetics Corporation, then was subsequently
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`assigned to Genzyme Corporation. A true and correct copy of the ’535 Patent is attached as
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`Exhibit B.
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`27. The ‘535 Patent issued from U.S. Patent Application No. 09/634,126, which claims
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`priority to U.S. Provisional Patent Application No. 60/160,080, which wasfiled on August 9,
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`1999,
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`28. The ‘535 Patent expired on August 8, 2020.
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`It was valid and enforceable under United
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`States Patent Laws during its term and whenthe infringement occurred.
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`29. The °717 Patent, entitled ‘“Metabolically Activated Recombinant Viral Vectors and
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`Methodsforthe Preparation and Use,”issued on October24, 2006 to inventor Dr. Barrie J, Carter.
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`The ’717 Patent issued from a continuation of the ’535 Patent. The ’717 Patent was originally
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`assigned to Targeted Genetics Corporation,
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`then was subsequently assigned to Genzyme
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`Corporation. A true and correct copy of the ’717 Patent is attached as Exhibit C,
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`30. The ’717 Patent expires on March 29, 2022.
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`It has been valid and enforceableat all
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`times since issued, and remains valid and enforceable.
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`31. The ’888 Patent, entitled ““Metabolically Activated Recombinant Viral Vectors and
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`Methodsfor the Preparation and Use,” issued on August 31, 2010 to inventor Dr. Barrie J. Carter.
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`The ’888 Patent issued from a continuation of the ’717 Patent. The ’888 Patent was originally
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`assigned to Targeted Genetics Corporation,
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`then was subsequently assigned to Genzyme
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`Corporation. A true and correct copy of the ’888 Patent is attached as Exhibit D.
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`32. The 888 Patent expired on August 8, 2020. It was valid and enforceable under United
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`States Patent Laws during its term and whenthe infringement occurred.
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`33. The ’729 Patent, entitled ‘“‘Metabolically Activated Recombinant Viral Vectors and
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`Methodsfor the Preparation and Use,”issued on August 28, 2008 to inventor Dr. Barrie J. Carter.
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`The ’729 Patent issued from a continuation of the ’888 Patent. The °729 Patent wasoriginally
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`assigned to Targeted Genetics Corporation,
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`then was subsequently assigned to Genzyme
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`Corporation. A true and correct copy of the ’729 Patent is attached as Exhibit E.
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`34. The °729 Patent expired on August 8, 2020. It was valid and enforceable under United
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`States Patent Laws during its term and whenthe infringement occurred.
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`35. The ’054 Patent, entitled ‘“Metabolically Activated Recombinant Viral Vectors and
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`Methods for the Preparation and Use,” issued on January 10, 2012 to inventor Barrie J. Carter.
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`The ’054 Patent issued from a continuation of the ’729 Patent. The ’054 Patent was originally
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`assigned to Targeted Genetics Corporation,
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`then was subsequently assigned to Genzyme
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`Corporation. A true and correct copy of the ’054 Patent is attached as Exhibit F.
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`36. The 054 Patent expired on August 8, 2020. It was valid and enforceable under United
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`States Patent Laws during its term and whenthe infringement occurred.
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`37.
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`On information and belief, Defendants had knowledge of the ’535 Patent, the ’717
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`Patent, the ’888 Patent, ’729 Patent, and the ’054 Patentat least as early as when Novartis Gene
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`Therapies, Inc. entered into the license agreement with AskBio.
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`Count I: Infringement of U.S. Patent No. 6,596,535
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`38. Plaintiffs repeat and reallege the allegationsset forth in paragraphs | through 37 above
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`as thoughfully set forth herein.
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`39.
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`Oninformation and belief, Defendants commercial manufacture, importation, use,
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`offerto sell, or sale of Zolgensma®infringes one or moreclaimsof the ’535 Patent, including but
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`not limited to claim 1, under 35 U.S.C. § 271 (a).
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`40. Although the *535 Patent expired on August 8, 2020, prior to expiry Defendants
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`infringed the °535 Patent in violation of 35 U.S.C. § 271(a) at least by making, using, and/or
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`selling Zolgensma®in the United States.
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`41. On informationand belief, Defendants’ pre-expiration manufacture, use, and/or sale
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`of Zolgensma®infringedat least claim 1 of the ’535 Patent.
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`42. The ’535 patent has one independent claim, claim 1. Claim1recites:
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`A recombinant adeno-associated virus (rAAV) vector comprising a single-stranded
`heterologous nucleotide sequence comprising a region which formsintrastrand base pairs
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`suchthat expression of a coding region of the heterologous sequence is enhancedrelative
`to a second rAAV vector that lacks sufficient intrastrand base pairing to enhance said
`expression, wherein the region which formsintrastrand base pairs is in a coding region.
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`43. On information and belief, Zolgensma®contains a rAAV vector that comprises a
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`coding region of the SMW gene(i.e., a heterologous sequence) that forms intrastrand base pairs
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`by utilizing intrastrand base pairing vector technology to increase the efficacy of the drug. See
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`Exhibit A (11. Description” (“[Zolgensma®]
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`is a recombinant self-complementary AAV9
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`containing a transgene encoding the humansurvival motor neuron (SMN)protein.”)).
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`44. Plaintiffs have suffered damages as a result of Defendants’ infringement of the 535
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`Patent.
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`45. On information and belief, Defendants’ infringement has been willful. Since having
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`knowledge of the *535 Patent, Defendants knew or should know that their actions infringe the
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`°535 Patent.
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`CountII: Infringement of U.S. Patent No. 7,125,717
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`46. Plaintiffs repeat and reallege the allegations set forth in paragraphs 1 through 45 above
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`as though fully set forth herein.
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`47.
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`On information and belief, Defendants commercial manufacture, importation, use,
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`offerto sell, or sale of Zolgensma® infringes one or more claims of the ’717 Patent, including but
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`not limited to claims | and 2, under 35 U.S.C. §§ 271(a) and/or(b).
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`48. On information and belief, Defendants’ manufacture, use, and/or sale of Zolgensma®™
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`infringes at least claims | and 2 of the ’717 Patent.
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`49, On information and belief, Defendants have induced infringement of the ’717 Patent
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`of at least claim | of the ’717 Patent under 35 U.S.C. § 271(b). Defendants knew of the ’717
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`Patent, and that their conduct and communications induces users of Zolgensma® to directly
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`-10-
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`®
`infringe the *717 Patent. For instance, by means of the Zolgensma™ label provided by Defendants
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`and through other communications, Defendants instruct, direct, and encourage users of
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`Zolgensma® and others with respect to the use of Zolgensma® with the knowledge that such use
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`according to the label infringed the ’717 Patent, intending that physicians and/or health care
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`providers in the United States performed the directly infringing activities. On information and
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`belief, such conduct by Defendants was intended to cause, and actually resulted in, direct
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`infringementin the United States.
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`50. The ’717 patent has two independent claims, claim 1 and claim 2. Claim | recites:
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`A method for introducing a polynucleotide into a cell, comprising contacting the
`cell essentially in the absence of an AAV helpervirus with a recombinant adeno-
`associated virus (rAAV)particle comprising an rAAV vector under conditions that
`allow uptake of the rAAV vector, whereby the rAAV vector is introduced into the
`cell, wherein the rAAV vector comprises a single-stranded heterologous nucleotide
`sequence comprising a coding region which forms intrastrand base pairs suchthat
`expression of the coding region of the heterologous sequence is enhancedrelative
`to a second rAAV vectorthat lacks sufficient intrastrand base pairing to enhance
`said expression, wherein the rAAV vector comprises one or more inverted terminal
`repeat (ITR) sequence flanking said heterologous sequence
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`51. Claim2 recites:
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`A method for expressing a polynucleotide coding region in a cell, comprising
`subjecting the cell to conditions which allow expression of the coding region,
`whereby the coding region is expressed, wherein the polynucleotide coding region
`is introduced into the cell by contacting the cell essentially in the absence of an
`AAVhelpervirus with an rAAVparticle comprising an rAAV vector, wherein the
`rAAV vector comprises a single-stranded heterologous nucleotide sequence
`comprising the coding region which forms intrastrand base pairs such that
`expression of the coding region of the heterologous sequence is enhanced relative
`to a second rAAV vector that lacks sufficient intrastrand base pairing to enhance
`said expression, wherein the rAAV vector comprises one or moreinverted terminal
`repeat (ITR) sequences flanking said heterologous sequence.
`
`®
`52. On information and belief, Zolgensma® contains a functional copy of the SMN gene
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`(i.e., a heterologous sequence) packaged in rAAV9. Oninformation and belief, Zolgensma*
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`-ll-
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`contains arAAV vectorthat contains a coding region of the SMW genethat forms intrastrand base
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`pairs by utilizing intrastrand base pairing vector technology to increase the efficacy of the drug.
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`See Exhibit A (“11. Description.”’). On information and belief, Zolgensma
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`® contains a rAAV
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`vector that contains one or more ITR sequences flanking the SMWN sequence.
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`53. On information and belief, when administered to a patient, Zolgensma®delivers a
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`copy of the coding region of the SMN geneto a cell where the SMN protein is expressed. On
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`information and belief, Zolgensma®is administered withouta helpervirus.
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`54. Plaintiffs have suffered damages as a result of Defendants’ infringement of the ’717
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`Patent and will continue to suffer damages as long as those infringing activities continue.
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`55. On information and belief, Defendants’ infringement has been willful. Since having
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`knowledge of the °717 Patent, Defendants knew or should knowthat their actions infringe the
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`"717 Patent.
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`Count ILI: Infringement of U.S. Patent No. 7,785,888
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`56. Plaintiffs repeat and reallege the allegations set forth in paragraphs | through 55 above
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`as thoughfully set forth herein.
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`57. On information and belief, Defendants commercial manufacture, importation, use,
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`offerto sell, or sale of Zolgensma®infringes one or moreclaims of the ’888 Patent, including but
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`not limited to claim 1, under 35 U.S.C. § 271 (a),
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`58. Although the ’888 Patent expired on August 8, 2020, prior to expiry Defendants
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`infringed the *888 Patent in violation of 35 U.S.C. § 271(a) at least by making, using, and/or
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`selling Zolgensma® in the United States.
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`59. On information and belief, Defendants’ pre-expiration manufacture, use, and/or sale
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`of Zolgensma”infringedat least claim 1 of the ’888 Patent.
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`-12-
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`60. The ’888 patent has one independentclaim, claim 1. Claim | recites:
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`A recombinant adeno-associated virus (rAAV) preparation, which rAAV virus
`preparation is essentially free of helper virus, comprising an rAAV particle,
`wherein the rAAV particle comprises an rAAV genome, wherein the rAAV
`genome comprises a heterologous nucleotide sequence comprising a coding region
`and one or more inverted terminal
`repeat
`(ITR)
`sequences
`flanking said
`heterologous sequence, wherein the total amount of unique sequencepresent in the
`heterologous sequenceis about one-half of the heterologous sequence and wherein
`the heterologous sequence forms intrastrand base pairs along most or all of its
`length such that expression of the coding region is enhanced relative to an rAAV
`vector that lacks sufficient intrastrand base pairing to enhance expression.
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`61. On information andbelief, Zolgensma® contains a functional copy of the SMN gene
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`(ie., a heterologous sequence) packaged in AAV9. Oninformation and belief, Zolgensma®
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`contains a rAAV vector that contains arAAV genome and a coding region of the SMN genethat
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`formsintrastrand basepairs by utilizing intrastrand base pairing vector technologyto increase the
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`efficacy of the drug. See Exhibit A (11. Description.”). On information and belief, Zolgensma”
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`contains a rAAV vectorthat contains one or more ITR sequences flanking the SMN sequence.
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`62. On information andbelief, Zolgensma® does not contain a helpervirus.
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`63. Plaintiffs have suffered damages as a result of Defendants’ infringement of the ’888
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`Patent.
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`64. On information and belief, Defendants’ infringement has been willful. Since having
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`knowledge of the ’888 Patent, Defendants knew or should know that their actions infringe the
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`888 Patent.
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`Count IV: Infringement of U.S. Patent No. 7,846,729
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`65. Plaintiffs repeat and reallege the allegations set forth in paragraphs 1 through 64 above
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`as though fully set forth herein.
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`-13-
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`66. On information and belief, Defendants commercial manufacture, importation, use,
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`offerto sell, or sale of Zolgensma® infringes one or more claims ofthe ’729 Patent, including but
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`not limited to claim 1, under 35 U.S.C. § 271 (a).
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`67. Although the ’729 Patent expired on August 8, 2020, prior to expiry Defendants
`
`infringed the *729 Patent in violation of 35 U.S.C. § 271 (a) at least by making, using, and/or
`
`selling Zolgensma® in the United States.
`
`68. On information and belief, Defendants’ pre-expiration manufacture, use, and/or sale
`
`of Zolgensma®infringed at least claim 1 of the ’729 Patent.
`
`69. The ’729 patent has one independent claim, claim 1. Claim | recites:
`
`A method for preparing a recombinant adeno-associated virus (rAAV),
`method comprising:
`1) incubating a host cell under conditions that allow AAV replication and
`encapsidation, wherein said host cell comprises:
`(a) arAAV vector comprising a heterologous nucleotide sequence
`and one or more AAV inverted terminal repeat (ITR) sequences flanking
`said heterologous sequence, wherein the vector is less than about 2.5 kb,
`and
`
`the
`
`(b) AAV rep function, AAV cap function, and helpervirus function
`for AAV; and
`2) purifying rAAVparticles produced from the host cell, wherein the rAAV
`particles comprise a rAAV genome which forms intrastrand base pairs along its
`length, such that expression of a coding region of the heterologous sequenceis
`enhancedrelative to arAAV vectorthat lacks sufficient intrastrand base pairing to
`enhancesaid expression
`
`70. On information and belief, Zolgensma® has been and is prepared using a hostcell
`
`under conditions that allow AAV replication and encapsidation and then purifying the rAAV
`
`particles produced from the hostcell to select for rAAVparticles containing vectors encoding the
`
`SMN transgene.
`
`71. On information and belief, Zolgensma® contains a functional copy of the SMN gene
`
`(i.e., a heterologous sequence) packaged in rAAV9.
`
`Oninformation and belief, Zolgensma®
`
`-14-
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`

`

`Case 1:21-cv-01736-UNA Document1 Filed 12/10/21 Page 15 of 18 PagelD #: 15
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`contains a rAAV vector that contains arAVV genomeand a coding region of the SMN genethat
`
`formsintrastrand basepairs along its length by utilizing intrastrand base pairing vector technology
`
`to increase the efficacy of the drug. See Exhibit A (11. Description.”). On information and
`
`belief, Zolgensma® contains a rAAV vectorthat contains one or more ITR sequencesflanking the
`
`SMN sequence.
`
`72.
`
`Oninformationand belief, Zolgensma® contains a rAAV vectorthat is less than
`
`about 2.5 kb.
`
`73. Plaintiffs have suffered damages as a result of Defendants’ infringement of the ’729
`
`Patent.
`
`74. On information and belief, Defendants’ infringement has been willful. Since having
`
`knowledge of the ’729 Patent, Defendants knew or should know that their actions infringe the
`
`°729 Patent.
`
`Count V: Infringement of U.S. Patent No. 8,093,054
`
`75. Plaintiffs repeat and reallege the allegations set forth in paragraphs 1 through 74 above
`
`as thoughfully set forth herein.
`
`76. On information and belief, Defendants commercial manufacture, importation, use,
`
`offer to sell, or sale of Zolgensma® infringes one or more claims of the 054 Patent, including but
`
`not limited to claims 1 and 19, under 35 U.S.C. §§ 271(a) and/or (b).
`
`77. Although the ’054 Patent expired on August 8, 2020, prior to expiry Defendants
`
`infringed the ’054 Patent in violation of 35 U.S.C. § 271(a) at least by making, using, and/or
`
`selling Zolgensma® in the United States.
`
`78. On information and belief, Defendants’ pre-expiration manufacture, use, and/or sale
`
`of Zolgensma® infringedat least claims 1 and 19 ofthe ’054 Patent.
`
`= 15s
`
`

`

`Case 1:21-cv-01736-UNA Document1 Filed 12/10/21 Page 16 of 18 PagelD #: 16
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`79. On information and belief, Defendants have induced infringementprior to the expiry
`
`of the ’054 Patent of at least claim 1 of the ’054 Patent under 35 U.S.C. § 271(b). Defendants
`
`knew of the ’054 Patent, and that their conduct and communications induced users of Zolgensma™
`
`to directly infringe the 054 Patent. Forinstance, by means ofthe Zolgensma® label provided by
`
`Defendants and through other communications, Defendants instructed, directed, and encouraged
`
`users of Zolgensma® and others with respect to the use of Zolgensma® with the knowledgethat
`
`such use accordingto the label infringed the ’054 Patent, intending that physicians and/orhealth
`
`care providers in the United States performed the directly infringing activities. On information
`
`and belief, such conduct by Defendants was intended to cause, and actually resulted in, direct
`
`infringement in the United States.
`
`80. The ’054 patent has two independentclaims, claim | and claim 19. Claim 1 recites:
`
`A composition comprising a purified recombinant adeno-associated virus (rAAV)
`particle comprising an AAV capsid and a single-stranded rAAV vector genome,
`wherein the rAAV vector genome comprises in the 5' to 3' direction: a 5’ AAV
`inverted terminal repeat (ITR) sequence, a first heterologous nucleotide sequence,
`an internal AAV ITR sequence, a second heterologous nucleotide sequence, and a
`3' AAV ITR sequence, whereinthefirst heterologous nucleotide sequence can form
`intrastrand base pairs with the second nucleotide sequence along mostorall ofits
`length.
`
`8l.
`
`Claim 19 recites:
`
`A method of expressing a polynucleotide coding sequence in a cell, comprising
`subjecting the cell to conditions which allow expression of the coding sequence,
`wherein the coding sequence is introduced into the cell by contacting the cell
`essentially in the absence of an AAV helper virus with a composition comprising a
`purified recombinant adeno-associated virus (rAAV) particle, wherein the rAAV
`particle comprises an AAV capsid and a single-stranded rAAV vector genome,
`wherein the rAAV vector genome comprises in the 5' to 3’ direction: a 5’ AAV
`inverted terminal repeat (ITR) sequence, a first heterologous nucleotide sequence,
`an internal AAV ITR sequence, a second heterologous nucleotide sequence, and a
`3' AAV ITR sequence, whereinthe first heterologous nucleotide sequence can form
`intrastrand base pairs with the second nucleotide sequence along mostorall ofits
`length, and wherein the first or the second heterologous nucleotide comprises the
`coding sequence.
`
`-16-
`
`

`

`Case 1:21-cv-01736-UNA Document1 Filed 12/10/21 Page 17 of 18 PagelD #: 17
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`82. Oninformationand belief, Zolgensma® contains a functional copy of the SMN gene
`
`(i.e., a heterologous sequence) packaged in rAAV9. Oninformation and belief, Zolgensma®
`
`contains a single-stranded rAAV vector genomethat contains a coding region of the SMN gene
`
`that formsintrastrand base pairs byutilizing intrastrand base pairing vector technologyto increase
`
`the efficacy of the drug. See Exhibit A (“11. Description.”). On information and belief,
`
`Zolgensma® contains an AAV capsid. On information and belief, Zolgensma® contains a rAAV
`
`vector that contains one or more ITR sequences flanking the SMN sequence.
`
`83.
`
`84.
`
`On information and belief, Zolgensma® doesnot contain a helpervirus.
`
`On information and belief, when administered to a patient, Zolgensma® delivers a
`
`copy of the SMN gene to a motor neuron cell where the