Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 1 of 34 PageID #: 13369
`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 1 of 34 PagelD #: 13369
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`EXHIBIT 4
`EXHIBIT 4
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`

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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 2 of 34 PageID #: 13370
`
`
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`
`
`
`
`C.A. No. 22-252 (MSG)
`
`HIGHLY CONFIDENTIAL –
`OUTSIDE COUNSEL’S EYES ONLY
`
`ARBUTUS BIOPHARMA CORPORATION
`and GENEVANT SCIENCES GmbH,
`
`Plaintiffs,
`
`v.
`
`MODERNA, INC. and MODERNATX, INC.,
`
`Defendants.
`
`MODERNA, INC. and MODERNATX, INC.,
`
`Counterclaim-Plaintiffs,
`
`v.
`
`ARBUTUS BIOPHARMA CORPORATION
`and GENEVANT SCIENCES GmbH,
`
`Counterclaim-Defendants.
`
`
`
`)
`)
`)
`)
`)
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`)
`)
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`
`
`DEFENDANTS’ FIFTH SUPPLEMENTAL OBJECTIONS AND RESPONSES TO
`PLAINTIFFS’ FIRST SET OF INTERROGATORIES (NOS. 1–10)
`
`Pursuant to Fed. R. Civ. P. 33, Defendants Moderna, Inc. and ModernaTX Inc.
`
`(collectively, “Moderna” or “Defendants”) provide their Third Supplemental Objections and
`
`Responses to Plaintiffs Arbutus Biopharma Corporation (“Arbutus”) and Genevant Sciences
`
`GmbH’s (“Genevant,” collectively “Plaintiffs”) First Set of Interrogatories (Nos. 1–10).
`
`
`
`

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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 3 of 34 PageID #: 13371
`HIGHLY CONFIDENTIAL – OUTSIDE COUNSEL’S EYES ONLY
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`SPECIFIC OBJECTIONS AND RESPONSES
`
`
`INTERROGATORY NO. 1:
`
`Do you admit that the manufacture, use, sale, offer for sale, and/or importation of the
`Accused Product would infringe, either literally or under the doctrine of equivalents, any of the
`asserted claims of the Patents-in-Suit, assuming the asserted claims to be valid and enforceable?
`If your answer is anything other than an unqualified “Yes,” then for each claim for which your
`answer is anything other than an unqualified “Yes,” state all bases on which you contend the
`asserted claim would not be infringed either literally or under the doctrine of equivalents, including
`any basis upon which you assert that Plaintiffs are estopped from asserting infringement by the
`doctrine of equivalents.
`
`RESPONSE TO INTERROGATORY NO. 1:
`
`Moderna objects to this Interrogatory as premature and unanswerable at this time because
`
`Plaintiffs have not yet served Infringement Contentions or identified Asserted Claims of the
`
`Patents-in-Suit. Moderna objects to this Interrogatory as premature and unanswerable at this time
`
`because Plaintiffs have not identified any theories under the doctrine of equivalents. Moderna
`
`objects to this Interrogatory on the ground that it seeks premature discovery in advance of the dates
`
`to be set out by the Court or agreed to by the parties because it seeks to elicit a claim construction
`
`position. Moderna objects to this Interrogatory to the extent it seeks to improperly shift the burden
`
`of proving infringement. Moderna objects to this Interrogatory to the extent it seeks information
`
`protected from discovery by the attorney-client privilege, attorney work product doctrine, or any
`
`other applicable privilege or immunity, and Moderna will not provide or produce such information.
`
`Moderna objects to this Interrogatory as premature to the extent that it calls for the rendering of an
`
`expert opinion.
`
`Subject to the General and Specific Objections, Moderna responds as follows:
`
`Because Plaintiffs have not yet identified the Asserted Claims of the Patents-in-Suit nor
`
`any theories of alleged infringement, including under the doctrine of equivalents, Moderna is
`
`unable to answer this Interrogatory completely. Regardless, Moderna does not admit that the
`
`10
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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 4 of 34 PageID #: 13372
`HIGHLY CONFIDENTIAL – OUTSIDE COUNSEL’S EYES ONLY
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`manufacture, use, sale, offer for sale, and/or importation of Moderna’s COVID-19 Vaccine would
`
`infringe, either literally or under the doctrine of equivalents, any claim of the Patents-in-Suit. See,
`
`e.g., D.I. 35.
`
`Plaintiffs bear the burden of proving that the Accused Products infringe the Asserted
`
`Claims. Plaintiffs have not met that burden. Indeed, Plaintiffs have not yet served infringement
`
`contentions. Moderna does not concede that Plaintiffs have proven direct or indirect literal
`
`infringement or infringement under the doctrine of equivalents of any element of the Asserted
`
`Claims, and Moderna reserves the right to challenge the sufficiency of proof of infringement of
`
`any and all elements of the Asserted Claims.
`
`A.
`
`No Direct or Indirect Infringement: The Asserted Claims are Invalid
`
`The Accused Products do not directly or indirectly infringe any of the Asserted Claims
`
`because an invalid claim cannot be infringed. Richdel, Inc. v. Sunspool Corp., 714 F.2d 1573,
`
`1580 (Fed. Cir. 1983) (“The claim being invalid there is nothing to be infringed.”); Prima Tek II,
`
`L.L.C. v. Polypap, S.A.R.L., 412 F.3d 1284, 1291 (Fed. Cir. 2005) (“there can be no ... induced
`
`infringement of invalid patent claims”). Moderna incorporates by reference its forthcoming
`
`Invalidity Contentions to be served according to the scheduling order and any amendments or
`
`supplementations thereto that each Asserted Claim is invalid under, inter alia, 35 U.S.C. §§ 102–
`
`103, 112. Because the Asserted Claims are invalid, the Accused Products cannot infringe.
`
`B.
`
`No Direct or Indirect Infringement: 35 U.S.C. § 271(e)(1)
`
`Moderna’s development activities relating to the Accused Products do not directly or
`
`indirectly infringe any of the Asserted Claims because they are protected under the safe harbor
`
`provision of 35 U.S.C. § 271(e)(1), which reads, in relevant part:
`
`It shall not be an act of infringement to make, use, offer to sell, or
`sell within the United States or import into the United States a
`patented invention . . . solely for uses reasonably related to the
`
`11
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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 5 of 34 PageID #: 13373
`HIGHLY CONFIDENTIAL – OUTSIDE COUNSEL’S EYES ONLY
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`development and submission of information under a Federal law
`which regulates the manufacture, use, or sale of drugs . . . .
`The Supreme Court has construed the safe harbor provision broadly, holding that the
`
`exemption “extends to all uses of patented invention that are reasonably related to the development
`
`and submission of any information under the FDCA” (original emphasis), and that the “reasonably
`
`related” requirement will be met “[a]t least where a drugmaker has a reasonable basis for believing
`
`that a patented compound may work … and uses the compound in research that, if successful,
`
`would be appropriate to include in a submission to the FDA” (emphasis added). Merck KGaA v.
`
`Integra Lifesciences I, Ltd., 545 U.S. 193, 202 (2005). Consistent with the broad construction, the
`
`safe harbor provision protects uses of patented compounds in both clinical studies and preclinical
`
`studies and research, whether or not the experiments are ultimately submitted to the FDA. Id.
`
`The Federal Circuit similarly held that the safe harbor applies “as long as there is a
`
`reasonable basis for believing that the use of the patented invention will produce the type of
`
`information that are relevant to an FDA submission.” Amgen v. Hospira, 944 F.3d 1327, 1338
`
`(Fed. Cir. 2019); see also, e.g., Momenta Pharms., Inc. v. Amphastar Pharms., Inc., 686 F.3d 1348,
`
`1360 (Fed. Cir. 2012) (“As long as the use of the patented invention is done to generate information
`
`that will be submitted pursuant to a relevant federal law, that use falls within the safe harbor.”);
`
`Classen Immunotherapies, Inc. v. Elan Pharmaceuticals, Inc., 786 F.3d 892, 897-99, 115
`
`U.S.P.Q.2d (Fed. Cir. 2015) (instructing that in some limited circumstances post-approval testing
`
`can be subject to the safe harbor of Section 271(e), and finding that accused infringer’s post-
`
`approval clinical trials and additional FDA submissions were subject to the safe harbor provision
`
`since they were necessary to obtain continued approval of the generic drug).
`
`Moderna’s development, preclinical, and clinical activities relating to FDA Emergency
`
`Use Authorization and approval of the Accused Products are exempted from infringement under
`
`12
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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 6 of 34 PageID #: 13374
`HIGHLY CONFIDENTIAL – OUTSIDE COUNSEL’S EYES ONLY
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`Section 271(e)(1). For example, Moderna has made submissions to the FDA in the following
`
`applications to the FDA relating to the Accused Products:
`
`(cid:120)
`
`IND 19745
`
`(cid:120) EUA 27073
`
`(cid:120) BLA 125752
`
`The manufacture and use of batches of the Accused Products relevant to submissions in
`
`the above FDA applications are exempted from infringement under Section 271(e)(1). Moderna’s
`
`investigation with respect to this issue is ongoing.
`
`C.
`
`28 U.S.C. § 1498
`
`Moderna incorporates by reference its briefing on its Partial Motion to Dismiss, which
`
`establishes that the Government accepted liability under 28 U.S.C. § 1498 for doses procured under
`
`Contract No. W911QY-20-C-0100 (the “’-0100 Contract”) with the U.S. Government. See, e.g.,
`
`D.I. 17 at 8; D.I. 49 at 1, 4.
`
`*
`
`*
`
`*
`
`Moderna incorporates by reference its Counterclaims for Declaratory Judgment of
`
`Noninfringement for each of the Patents-in-Suit.
`
`Moderna’s investigation is ongoing and Moderna reserves the right to supplement, revise,
`
`or amend Moderna’s Response to this Interrogatory as discovery and Moderna’s investigation in
`
`this Action proceed.
`
`FIRST SUPPLEMENTAL RESPONSE TO INTERROGATORY NO. 1 (June 12, 2023):
`
`Subject to the General and Specific Objections, Moderna further responds as follows:
`
`Moderna’s ability to respond to this Interrogatory has been prejudiced by Plaintiffs’
`
`deficient infringement contentions, which Plaintiffs have not yet rectified. For example, Plaintiffs
`
`have failed to identify or to differentiate between the different formulations of Moderna’s COVID-
`
`13
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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 7 of 34 PageID #: 13375
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`HIGHLY CONFIDENTIAL - OUTSIDE COUNSEL’S EYES ONLY
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`19 Vaccine in their contentions. Plaintiffs’ allegations of infringement under the doctrine of
`
`equivalents are conclusory at best, without any analysis as to function-way-result.
`
`See, e.g.
`
`Afinogenova May 12, 2023letter.
`
`Moderna repeats and incorporates by referenceits initial responseto this Interrogatory.
`
`A.
`
`The ’651 Patent Is Not Infringed
`
`Moderna’s COVID-19 Vaccine does not meetat least the following limitations:
`
`e Plaintiffs have not provided infringementcontentions detailing whether Modema’s COVID-
`19 Vaccine contains the recited percentages mRNAthatis allegedly “fully encapsulated.” As
`a result, Moderna’s COVID-19 Vaccine doesnotinfringe any of the Asserted Claims.
`
`e Plaintiffs have failed to show that “eachlipid vesicle is about 150 nm orless in diameter,” or
`that “eachlipid vesicle is about 100 nm orless in diameter” as required by Claims 10 and 12.
`Instead, Plaintiffs cite references that at most describe average size. As a result, Moderna’s
`COVID-19 Vaccine doesnotinfringe these claims.
`
`e Plaintiffs have not adequately explained their infringementcontentions for “wherein each lipid
`vesicle is a liposome”(claim 8) and “wherein eachlipid vesicle is a lipid-nucleic acid particle”
`(claim 9). See, e.g. Afinogenova May 12, 2023 letter. As a result, Moderna’s COVID-19
`Vaccine doesnotinfringe these claims.
`
`B.
`
`The ’069, ’359, ’668, 435, and ’?378 Patents Are Not Infringed
`
`1.
`
`No Direct or Indirect Infringement of Asserted Claims of the ’069
`°359, 7668, ’435, and 378 Patents:
`
`fF Moderna incorporates by reference its response to Interrogatory No.7.
`
`14
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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 8 of 34 PageID #: 13376
`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 8 of 34 PagelD #: 13376
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`HIGHLY CONFIDENTIAL — OUTSIDE COUNSEL’S EYES ONLY
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`The
`
`does not
`
`infringe the referenced claims under the doctrine of
`
`equivalents, applying either the function-way-result test, or the insubstantial differences test. If
`
`Plaintiffs provide adequate infringement contentions for these claim elements under the doctrine
`
`of equivalents, Moderna reserves the right to supplementthis response to address those arguments.
`
`In addition, prosecution history estoppel precludes any potential argumentby Plaintiffs that
`
`. For example, claim amendments and arguments made during
`
`prosecution of a patent application can create an estoppel, thereby preventing the patent owner
`
`from recapturing subject matter through the doctrine of equivalents that was surrendered during
`
`prosecution of the patent. Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722,
`
`736 (2002) (“[A] narrowing amendment madeto satisfy any requirement of the Patent Act may
`
`give rise to an estoppel”). Further, when an amendment is made to narrow claims in a parent
`
`application, the estoppel that is associated with the parent application applies to any continuation
`
`application that uses the same claim term. Biovail Corp. Intern. v. Andrx Pharmaceuticals, Inc.,
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`

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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 9 of 34 PageID #: 13377
`HIGHLY CONFIDENTIAL – OUTSIDE COUNSEL’S EYES ONLY
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`239 F.3d 1297, 1304, 57 U.S.P.Q.2d 1813 (Fed. Cir. 2001) (affirming bench verdict of no
`
`infringement under doctrine of equivalents where patentee added claim amendment in a
`
`grandparent application to overcome prior art and therefore prosecution history estoppel applied
`
`to the same term as used in claims issuing from a later continuation application to bar doctrine of
`
`equivalents) (post-Festo).
`
`The prosecution history of the ’069 patent clearly establishes that the applicants
`
`surrendered claim scope to overcome the examiner’s patentability rejection, which precludes the
`
`application of doctrine of equivalents. For example, during the ’069 patent prosecution, the
`
`applicants deleted “about” from the then-pending claims to narrow the ranges of lipid components
`
`in response to the examiner’s Section 102 and 103 rejections:
`
`’069 patent file history, Amdt. dated August 11, 2011 at 2. Specifically, the applicants stated:
`
`During the interview, Applicants’ representatives proposed amending the claims to
`delete the word ‘about’ form the ranges of lipid components and argued that the
`claimed ranges were not anticipated by McLachlan et al. … because that reference
`failed to disclose the claimed ranges with sufficient specificity …
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`
`
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`16
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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 10 of 34 PageID #: 13378
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`*
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`*
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`*
`
`
`In making both rejections, the Examiner alleges that the term ‘comprising from
`about’ recited in the instant embraces a broad range of lipid components. In an
`earnest effort to expedite prosecution, but without acquiescing on the merits of the
`rejection, Applicants have amended the claims to delete ‘about’ from the ranges
`of lipid components recited therein.
`
`
`Id. at 6–7 (emphasis added). Therefore, Plaintiffs are precluded from recapturing a nucleic acid-
`
`lipid particle comprising
`
` under the doctrine of equivalents
`
`based on arguments and amendments during prosecution to overcome prior art rejections.
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`Similarly, Plaintiffs are estopped from asserting doctrine of equivalents to capture
`
`
`
` for the ’359, ’668, ’435, and ’378
`
`patents. During prosecution of the ’359, ’668, and ’435 patents, for example, the applicants filed
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`preliminary amendments to delete “about” from original claims reciting “a conjugated lipid . . .
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`comprising from about 0.5 mol % to about 2 mol % of the total lipid.” See, e.g., ’359 patent file
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`history, Claims dated October 5, 2011 at 114, Amdt. dated March 28, 2012 at 4; ’668 patent file
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`history, Claims dated June 26, 2013 at 114, Amdt. dated November 6, 2013 at 5; ’435 patent file
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`history, Claims dated August 18, 2014 at 114, Amdt. dated February 26, 2015 at 2 (emphasis
`
`added). When pursuing the ’378 patent, the applicants filed claims reciting a nucleic acid-lipid
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`particle consisting essentially of a PEG-lipid conjugate consisting of “from 0.1 mol % to 2 mol %
`
`of the total lipid present in the particle,” after narrowing its claims when prosecuting the ’069,
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`’359, ’668, and ’435 patents. See, e.g., ’378 patent file history, Claims dated April 12, 2021 at 121.
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`Moreover, the disclosure in the specification demonstrates that applicants knew how to claim
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`fractional percentages of the conjugated lipid when that was their intent. E.g., ’359 patent at
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`22:40–52 (listing ranges for the conjugated lipid including fractional percentages such as from
`
`about 1.2 mol % to about 1.7 mol %, from about 1.3 mol % to about 1.6 mol %, or about 1, 1.1,
`
`17
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`1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2 mol % (or any fraction thereof or range therein) ofthe total
`
`lipid present in the particle); 57:24—35.
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`Because the ’359, ’668, ’435, and ’378 patents are issued from continuation applications
`
`of the ’069 patent and use claim terms identical to those in the 069 patent, Plaintiffs are estopped
`
`from arguing that Moderna’sDy infringes any Asserted Claims of the °359, 668,
`
`doctrine of equivalents. Biovail Corp., 239 F.3d at 1304.
`
`Plaintiffs are also estopped from recapturing[laa
`
`a6221
`
`during the IPR for the 069 patent, Plaintiffs alleged:
`
`The ’069 patent is directed to the surprising discovery that nucleic acid-lipid
`particle formulations with high levels of cationic lipids and low levels of
`conjugated lipids exhibit favorable in vivo transfection efficiencies as well as
`“improvedtolerability ofthe formulations in vivo,resulting in a significant increase
`in the therapeutic index [a measure of dosagerelative to toxic effect] as compared
`to nucleic acid-lipid particle compositions previously described.” ... Reflecting
`this discovery, the ’069patent claims nucleic acid-lipidparticleformulations with
`high levels of cationic lipids (50-65 mol %) and lowlevels of conjugatedlipids
`(0.5-2 mol %)—as well as specific levels of cholesterol/derivative (30-40 mol %)
`and phospholipid (4-10 mol %).
`
`See, e.g., IPR2019-00554, Paper 7 (Patent Owner’s Preliminary Response)at 13, 14, 45—46; id.,
`
`Paper 15 (Patent Owner’s Response)at 7, 8, 29-30, 32, 62, 64.
`
`During the IPR for the related ’435 patent, Plaintiffs again alleged:
`
`The °435 patent discloses the “surprising discovery” that nucleic acid-lipid
`particle formulations with a high level of cationic lipid and a remarkably low
`level ofconjugated lipid exhibited favorable in vivo transfection efficiencies as well
`as “improved tolerability of the formulations in vivo, resulting in a significant
`increase in the therapeutic index [a measure of dosagerelative to toxic effect] as
`
`18
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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 12 of 34 PageID #: 13380
`HIGHLY CONFIDENTIAL – OUTSIDE COUNSEL’S EYES ONLY
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`compared to nucleic acid-lipid particle compositions previously described.” . . .
`Reflective of this discovery, the ’435 patent claims nucleic acid-lipid particle
`formulations with a high level of cationic lipid (50–85 mol %) and an
`unconventionally low level of conjugated lipid (0.5–2 mol %).
`
`
`See, e.g., IPR2018-00739, Paper 12 (Patent Owner’s Preliminary Response) at 2, 6–8, 12, 24, 37;
`
`id., Paper 24 (Patent Owner’s Response) at 2, 14, 19–21, 32, 47, 59.
`
`Plaintiffs further made statements during Appeal No. 20-1184 that made it clear that
`
`Thus, Plaintiffs are estopped from recapturing
`
`
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`
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`under the ’069 and ’435 patents, as well as the ’359, ’668, and ’378 patents, which are in the same
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`family as the ’069 and ’435 patents and similarly claim
`
`
`
`Plaintiffs are further legally precluded from claiming that Moderna’s
`
`
`
`
`
`infringes any Asserted Claim of the ’069, ’359, ’668, ’435, and ’378 patents under the doctrine of
`
`equivalents based on the doctrine of vitiation. The doctrine of equivalents cannot be used to vitiate
`
`meaningful limitations from the claims, as the public is entitled to rely on such limitations to avoid
`
`infringement. Johnson & Johnston Assocs. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1054 (Fed. Cir.
`
`2002). Here, for example, vitiating the numerical limitations requiring
`
`
`
` would deprive the public of the notice function of the claims, thus rendering the
`
`claims meaningless. Mirror Worlds, LLC v. Apple Inc., 692 F.3d 1351, 1358 (Fed. Cir. 2012) (“an
`
`argument that the absence of a feature is equivalent to its presence” negates the doctrine of
`
`equivalents).
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`19
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`Case 1:22-cv-00252-MSG Document 195-5 Filed 01/16/24 Page 13 of 34 PageID #: 13381
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`Plaintiffs are also legally precluded from claiming that Moderna’s
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` infringes
`
`any Asserted Claims of the ’069, ’359, ’668, ’435, and ’378 patents under the doctrine of
`
`equivalents based on the doctrine of public dedication because the specification of the patents
`
`discloses the unclaimed subject matter such that it has been dedicated to the public. PSC Comput.
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`Prods., Inc. v. Foxconn Int’l, Inc., 355 F.3d 1353, 1360, (Fed. Cir. 2004) (“The disclosure-
`
`dedication rule requires an inventor who discloses specific matter to claim it, and to submit the
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`broader claim for examination. Otherwise, that matter is dedicated to the public and may not be
`
`recaptured under the doctrine of equivalents.”). As an example, the specification of the ’069 patent
`
`discloses embodiments that contain a conjugated lipid (e.g., PEG-lipid conjugate) comprising
`
`“about 2 mol %” of the total lipid:
`
`In certain instances, the conjugated lipid that inhibits aggregation of particles (e.g.,
`PEG-lipid conjugate) may comprise from about 0.1 mol % to about 2 mol %, from
`about 0.5 mol % to about 2 mol %, from about 1 mol % to about 2 mol %, from
`about 0.6 mol % to about 1.9 mol %, from about 0.7 mol % to about 1.8 mol %,
`from about 0.8 mol % to about 1.7 mol %, from about 1 mol % to about 1.8 mol %,
`from about 1.2 mol % to about 1.8 mol %, from about 1.2 mol % to about 1.7 mol
`%, from about 1.3 mol % to about 1.6 mol %, from about 1.4 mol % to about 1.5
`mol %, or about 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2 mol % (or any
`fraction thereof or range therein) of the total lipid present in the particle.
`
`See, e.g., ’069 patent at 22:30–42, 68:39–48. The ’069, ’359, ’668, ’435, and ’378 patents are in
`
`the same family and share the same specification. Because the ’069, ’359, ’668, ’435, and ’378
`
`patents claim a nucleic acid-lipid particle comprising a conjugated lipid consisting of “from 0.5
`
`mol % to 2 mol %” or “from 0.1 mol % to 2 mol %” of the total lipid, while the specification
`
`discloses “from about 0.1 mol % to about 2 mol %” of a conjugated lipid (emphasis added),
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`Plaintiffs are estopped from enforcing any unclaimed embodiments comprising
`
`
`
`. Moore U.S.A., Inc. v. Standard Register Co., 229 F.3d 1091, 1107 (Fed.
`
`Cir. 2000).
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`20
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`Plaintiffs is further legally precluded from claiming that Moderna’s
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`infringes any Asserted Claims of the ’069, ?359, ’668, ’435, and ’378 patents underthe doctrine
`
`of equivalents because to do so would ensnarethe priorart (see, e.g. the references in Exhibit B of
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`Moderna’s Invalidity Contentions). Ifthe claims wereto literally cover Moderna’s
`
`which containee. then the claims would encompassprior art. Wilson
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`Sporting Goods Co. v. David Geoffrey & Assocs., 904 F.2d 677, 683 (Fed. Cir. 1990). Moderna
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`incorporates by reference its Invalidity Contentions and any amendments or supplementations
`
`thereto concerning the ’069, ’359, ’668, ’435, and ’378 patents.
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`2.
`
`No Direct or Indirect Infringement of Asserted Claims of the ’069,
`°359, °668,
`’435, and ’378 Patents
`
`
`
`TheDs of the Accused Products comprising
`f| do not infringe any Asserted Claims ofthe ’069, ’359, and ’668 patents, which recite or
`incorporate a limitation requiring a nucleic acid-lipid particle comprising Po
`I 206 se
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`Claims of the ’435 patent, which recite or incorporate a limitation requiring a nucleic acid-lipid
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`particle comprising
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`Thefo do not infringe the referenced claims under the doctrine of
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`equivalents, applying either the function-way-result test, or the insubstantial differences test. If
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`Plaintiffs provide adequate infringement contentions for these claim elements under the doctrine
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`of equivalents, Modernareservesthe right to supplementthis response to address those arguments.
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`In addition, prosecution history estoppel precludes any potential argumentby Plaintiffs that
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`Moderna’sji infringe any Asserted Claimsofthe 069, ?359, ’668, and °435
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`|] under the doctrine of equivalents based on claim amendments and arguments during
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`prosecution.
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`The prosecution history of the ’069 patent clearly establishes that
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`the applicants
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`surrendered claim scope to overcome the examiner’s patentability rejection, which precludes the
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`application of doctrine of equivalents. For example, during prosecution of the ’069 patent, the
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`applicants deleted “about” from the then-pending claims to narrow the rangesoflipid components
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`in response to the examiner’s Section 102 and 103 rejections:
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`’069 patent file history, Amdt. dated August 11, 2011 at 2. Specifically, the applicants stated:
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`
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`During the interview, Applicants’ representatives proposed amending the claims to
`delete the word ‘about’ form the ranges of lipid components and argued that the
`claimed ranges were not anticipated by McLachlan et al. … because that reference
`failed to disclose the claimed ranges with sufficient specificity ….
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`*
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`*
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`*
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`In making both rejections, the Examiner alleges that the term ‘comprising from
`about’ recited in the instant embraces a broad range of lipid components. In an
`earnest effort to expedite prosecution, but without acquiescing on the merits of the
`rejection, Applicants have amended the claims to delete ‘about’ from the ranges
`of lipid components recited therein.
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`Id. at 6–7 (emphasis added). Therefore, Plaintiffs are precluded from recapturing a nucleic acid-
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`lipid particle comprising
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` under doctrine of equivalents, after
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`the applicants relinquished such claim scope to overcome prior art during prosecution.
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`Further, to overcome the examiner’s double patenting rejections, the applicants made
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`arguments alleging unexpected results of the invention arising from
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`:
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`In particular, Applicants reiterate that it is clear from the specification that the present
`invention is based, in part, on the surprising discovery that 1:57 SNALP formulations
`provide new and unexpected results when used for the in vitro or in vivo delivery of
`an active agent, such as a therapeutic nucleic acid (e.g., an interfering RNA). In fact,
`Applicants have found that SNALP formulations having increased amounts of cationic
`lipid, e.g., one or more cationic lipids comprising from 50 mol % to 65 mol % of the
`total lipid present in the particle, provide unexpectedly superior advantages when used
`for the in vitro or in vivo delivery of an active agent, such as a therapeutic nucleic acid
`(e.g., an interfering RNA).
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`*
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`*
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`*
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`It is noted that the cited references disclose the preparation and testing of SN ALP
`formulations such as the 2:30, 2:40, and 10:15 SNALP formulations as exemplified
`formulations containing the greatest amount of cationic lipid (i.e., 30 mol %, 40 mol
`%, and 15 mol % cationic lipid, respectively). As set forth in the instant specification
`and acknowledged by the Examiner, SNALP formulations having increased amounts
`of cationic lipid such as, e.g., the 1 :57 SN ALP formulation, provide unexpectedly
`superior advantages over previously exemplified SNALP formulations containing
`lower amounts of cationic lipid.
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`Id. at 9–10 (original emphasis). The applicants’ arguments, including those above, made during
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`prosecution that characterize the alleged unexpected properties of the invention, attempt to
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`distinguish the prior art, and purportedly identify critical attributes of the invention give rise to
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`argument-based estoppel and limit the available equivalents.
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`Similarly, Plaintiffs are estopped from asserting the doctrine of equivalents to capture
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` for the ’359, ’668, and ’435 patents. During prosecution of the
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`’359 and ’668 patents, the applicants filed preliminary amendments to delete “about” from original
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`claims reciting “a cationic lipid comprising from about 50 mol % to about 65 mol % of the total
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`lipid.” See, e.g., ’359 patent file history, Claims dated October 5, 2011 at 114, Amdt. dated March
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`28, 2012 at 4; ’668 patent file history, Claims dated June 26, 2013 at 114, Amdt. dated November
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`6, 2013 at 5 (emphasis added). Similarly, during prosecution of the ’435 patent, the applicants filed
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`preliminary amendments to delete “about” from original claims reciting “a cationic lipid
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`comprising from about 50 mol % to about 85 mol % of the total lipid.” See, e.g., ’435 patent file
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`history, Claims dated August 18, 2014 at 114, Amdt. dated February 26, 2015 at 2.
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`Because the ’359, ’668, and ’435 patents are issued from continuation applications of the
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`’069 patent and use claim terms identical to those in the ’069 patent, Plaintiffs are estopped from
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`arguing that Moderna’s
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`and ’435 patents requiring
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`equivalents.
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` infringe any Asserted Claims of the ’359, ’668,
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` under doctrine of
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`Plaintiffs are also estopped from recapturing
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` under
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`the doctrine of equivalents because Plaintiffs repeatedly argued in IPR the alleged unexpected
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`results and purported innovative aspects of the invention arising from
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`
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` in an attempt to distinguish prior art. For example, during the IPR for the ’069 patent,
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`Plaintiffs alleged:
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`The ’069 patent is directed to the surprising discovery that nucleic acid-lipid
`particle formulations with high levels of cationic lipids and low levels of
`conjugated lipids exhibit favorable in vivo transfection efficiencies as well as
`“improved tolerability of the formulations in vivo, resulting in a significant increase
`in the therapeutic index [a measure of dosage relative to toxic effect] as compared
`to nucleic acid-lipid particle compositions previously described.” . . . Reflecting
`this discovery, the ’069 patent claims nucleic acid-lipid particle formulations with
`high levels of cationic lipids (50–65 mol %) and low levels of conjugated lipids
`(0.5–2 mol %)—as well as specific levels of cholesterol/derivative (30-40 mol %)
`and phospholipid (4-10 mol %).
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`See, e.g., IPR2019-00554, Paper 7 (Patent Owner’s Preliminary Response) at 13, 14, 34, 45–46
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`(emphasis added); id., Paper 15 (Patent Owner’s Response) at 7, 8, 29–30, 32, 62, 64.
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`During the IPR for the ’435 patent, Plaintiffs again alleged:
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`The ’435 patent discloses the “surprising discovery” that nucleic acid-lipid
`particle formulations with a high level of cationic lipid and a remarkably low
`level of conjugated lipid exhibited favorable in vivo transfection efficiencies as well
`as “improved tolerability of the formulations in vivo, resulting in a significant
`increase in the therapeutic index [a measure of dosage relative to toxic effect] as
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