DCT

1:24-cv-00512

GlaxoSmithKline Biologicals SA v. Pfizer Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00512, D. Del., 08/14/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because several defendant entities are organized under Delaware law and reside in the district. For non-resident defendants, venue is based on their status as non-U.S. residents and their alleged consent to venue in other litigations involving the same accused products.
  • Core Dispute: Plaintiff alleges that Defendant’s Comirnaty® COVID-19 vaccines infringe eight patents related to mRNA vaccine formulations using lipid nanoparticles and methods of administering the same.
  • Technical Context: The technology involves using lipid nanoparticles (LNPs) to encapsulate and deliver messenger RNA (mRNA) encoding a viral immunogen, a platform that gained significant market prominence during the COVID-19 pandemic for enabling rapid vaccine development.
  • Key Procedural History: The complaint alleges that Defendants were aware of the inventors' work long before developing the accused products, citing Defendants’ own statements in European opposition proceedings and U.S. Inter Partes Review (IPR) proceedings. These statements are used by the Plaintiff to define key technical terms and to assert Defendants' knowledge of the patented technology.

Case Timeline

Date Event
2010-07-06 Earliest Priority Date Asserted for Patents-in-Suit
2020-12-11 First FDA Emergency Use Authorization for Accused Product
2023-05-02 Issue Date for U.S. Patent No. 11,638,693
2023-05-02 Issue Date for U.S. Patent No. 11,638,694
2023-05-23 Issue Date for U.S. Patent No. 11,655,475
2023-06-06 Issue Date for U.S. Patent No. 11,666,534
2023-09-19 Issue Date for U.S. Patent No. 11,759,422
2023-09-26 Issue Date for U.S. Patent No. 11,766,401
2023-10-17 Issue Date for U.S. Patent No. 11,786,467
2023-12-26 Issue Date for U.S. Patent No. 11,851,660
2024-08-14 Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 11,638,693 - "Vaccine for Eliciting Immune Response Comprising RNA Encoding an Immunogen and Lipid Formulations Comprising Mole Percentage of Lipids," issued May 2, 2023

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of employing messenger RNA (mRNA) in vaccines, noting that mRNA is chemically fragile, prone to degradation, and needs a method for protected delivery into a patient's cells to be effective (Compl. ¶30).
  • The Patented Solution: The invention utilizes liposomes to encapsulate and protect immunogen-encoding RNA from the external environment, facilitating its in vivo delivery to cells where it can be translated to produce an immunogen and elicit an immune response ('693 Patent, col. 1:58-61, col. 2:2-5). The liposomes are defined by a specific composition of four lipid types in claimed molar percentage ranges, including a cationic lipid with a tertiary amine and a specific pKa range (’693 Patent, Abstract).
  • Technical Importance: This LNP-based delivery system provides a versatile "platform" technology, enabling the rapid formulation of mRNA encoding a wide range of immunogens to address new viral threats (Compl. ¶¶3-4).

Key Claims at a Glance

  • The complaint asserts at least Claim 1 (Compl. ¶105).
  • Independent Claim 1 requires:
    • A formulation comprising ribonucleic acid (RNA) molecules that encode an immunogen.
    • A lipid composition comprising: (a) 20-70 mole % cationic lipid, (b) an anionic or a zwitterionic lipid, (c) a polyethylene glycol (PEG)-conjugated lipid, and (d) 5-80 mole % cholesterol.
    • A requirement that the lipids encapsulate at least half of the RNA molecules.
    • A functional requirement that the formulation is immunogenic in vivo by eliciting an antibody response.
    • A requirement that the cationic lipid comprises a tertiary amine and has a pKa between 6.07 and 7.6.
    • A detailed, 14-step procedural definition for how the pKa is to be determined.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 11,638,694 - "Vaccine for Eliciting Immune Response Comprising Lipid formulations and RNA Encoding Multiple Immunogens," issued May 2, 2023

The Invention Explained

  • Problem Addressed: Similar to the '693 Patent, this invention addresses the technical hurdles of delivering fragile mRNA for vaccination purposes (Compl. ¶30).
  • The Patented Solution: This invention adapts the LNP platform to create bivalent or multivalent vaccines by encapsulating two or more distinct species of RNA molecules, each encoding a different immunogen, within a single lipid formulation (’694 Patent, Abstract, col. 40:7-14). The lipid composition and properties, including the specific pKa range and its detailed measurement method, are substantially similar to those in the '693 Patent.
  • Technical Importance: The technology enables the development of vaccines that can target multiple viral strains or pathogens simultaneously, potentially offering broader protective immunity (Compl. ¶61).

Key Claims at a Glance

  • The complaint asserts at least Claim 1 (Compl. ¶135).
  • Independent Claim 1 requires:
    • A formulation comprising a first species of RNA molecules encoding a first immunogen and a second species of RNA molecules encoding a second immunogen.
    • A lipid composition comprising: (a) a cationic lipid, (b) an anionic or zwitterionic lipid, (c) a PEG-conjugated lipid, and (d) a cholesterol.
    • A requirement that the lipids encapsulate at least half of both the first and second species of RNA molecules.
    • A functional requirement that the formulation elicits an antibody response in vivo against both immunogens.
    • A requirement that the cationic lipid comprises a tertiary amine and has a pKa between 6.07 and 7.6, determined by the same 14-step procedural definition recited in the '693 Patent.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

Multi-Patent Capsule: U.S. Patent No. 11,666,534

  • Patent Identification: U.S. Patent No. 11,666,534, "Methods of Administering Lipid Formulations with Viral Immunogens," issued June 6, 2023 (Compl. ¶159).
  • Technology Synopsis: This patent claims methods of eliciting an immune response by administering a unit dose of a formulation. The formulation comprises RNA encoding one of several specified viral immunogens (including a coronavirus spike polypeptide) encapsulated in lipids that include a tertiary amine cationic lipid, a PEG-conjugated lipid, and cholesterol (Compl. ¶164).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶163).
  • Accused Features: The accused features are the FDA-authorized uses of the Comirnaty® vaccines, which involve administering a unit dose containing mRNA for a coronavirus spike polypeptide within a lipid formulation alleged to meet the claim limitations (Compl. ¶¶165-171).

Multi-Patent Capsule: U.S. Patent No. 11,766,401

  • Patent Identification: U.S. Patent No. 11,766,401, "Methods of Administering Lipid Formulations with Immunogens," issued September 26, 2023 (Compl. ¶184).
  • Technology Synopsis: This patent claims a method of eliciting an immune response in a human or a cow by administering an immunologically effective unit dose of a formulation. The claimed formulation is structurally similar to that of the ’534 Patent, comprising RNA encapsulated in lipids including a tertiary amine cationic lipid, a PEG-conjugated lipid, and cholesterol (Compl. ¶189).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶188).
  • Accused Features: The administration of Comirnaty® vaccines to humans is alleged to infringe the claimed method (Compl. ¶¶190-196).

Multi-Patent Capsule: U.S. Patent No. 11,786,467

  • Patent Identification: U.S. Patent No. 11,786,467, "Lipid Formulations with Immunogens," issued October 17, 2023 (Compl. ¶209).
  • Technology Synopsis: This patent claims a product-by-process style formulation comprising RNA encoding an immunogen and lipids. The lipids include a tertiary amine cationic lipid, a PEG-conjugated lipid, and cholesterol. The formulation is defined by the functional properties of being immunogenic in vivo and having at least half the RNA encapsulated (Compl. ¶215).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶214).
  • Accused Features: The Comirnaty® vaccine products themselves are alleged to be the infringing formulations, containing the claimed lipid and RNA components and exhibiting the claimed functional properties (Compl. ¶¶216-222).

Multi-Patent Capsule: U.S. Patent No. 11,759,422

  • Patent Identification: U.S. Patent No. 11,759,422, "PEGylated Liposomes for Delivery of Immunogen-Encoding RNA," issued September 19, 2023 (Compl. ¶235).
  • Technology Synopsis: This patent claims a method for raising a protective immune response by administering a liposome containing encapsulated RNA. A key feature of the claim is the requirement that the liposome includes a PEG moiety with an average molecular mass between 1 kDa and 3 kDa, and that this PEG-lipid is not a specific type (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)]) (Compl. ¶240).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶239).
  • Accused Features: The administration of Comirnaty® vaccines is alleged to infringe. The complaint asserts that the PEG-lipid in the vaccines (ALC-0159) has a PEG moiety with a molecular mass of ~2 kDa (2000), falling within the claimed range, and is not the specifically excluded lipid type (Compl. ¶¶73, 244).

Multi-Patent Capsule: U.S. Patent No. 11,655,475

  • Patent Identification: U.S. Patent No. 11,655,475, "Immunisation of Large Mammals with Low Doses of RNA," issued May 23, 2023 (Compl. ¶259).
  • Technology Synopsis: This patent claims a method of eliciting an antibody response in a large mammal (including a human) by administering at least two sequential unit doses of a composition. The claimed method requires each unit dose to comprise between 2 µg and 100 µg of mRNA that is encapsulated in liposomes containing a tertiary amine cationic lipid (Compl. ¶264).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶263).
  • Accused Features: The accused infringing activity is the administration of the Comirnaty® vaccines to humans according to FDA-authorized dosing regimens, which allegedly involve sequential doses containing between 2 µg and 100 µg of mRNA (Compl. ¶¶268, 270).

Multi-Patent Capsule: U.S. Patent No. 11,851,660

  • Patent Identification: U.S. Patent No. 11,851,660, "Immunisation of Large Mammals with Low Doses of RNA," issued December 26, 2023 (Compl. ¶283).
  • Technology Synopsis: This patent claims a method of eliciting an antibody response against a coronavirus spike polypeptide in a large mammal by administering at least two intramuscular unit doses of a composition. The composition comprises lipid particles and mRNA, with each dose containing between 2 µg and 100 µg of the mRNA. The lipid particles are defined as comprising four specific types of lipids, including a tertiary amine cationic lipid (Compl. ¶288).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶287).
  • Accused Features: The intramuscular administration of the Comirnaty® vaccines to humans according to the approved multi-dose schedule is alleged to meet all limitations of the claimed method (Compl. ¶¶289-296).

III. The Accused Instrumentality

Product Identification

  • The accused products are all dosage forms of the Pfizer-BioNTech Comirnaty® COVID-19 vaccines, including the original monovalent, the bivalent BA.1 variant, the bivalent BA.4/5 variant, and the monovalent XBB.1.5 variant (collectively, the "Accused Products") (Compl. ¶8).

Functionality and Market Context

  • The Accused Products are mRNA-based vaccines designed to elicit an immune response against the spike protein of the SARS-CoV-2 coronavirus (Compl. ¶¶58, 60). The active ingredient is a nucleoside-modified messenger RNA (mRNA) that encodes a specific viral spike protein variant (Compl. ¶108). This mRNA is formulated in lipid nanoparticles (LNPs) composed of four specific lipid ingredients: ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) ("ALC-0315"), 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide ("ALC-0159"), 1,2-distearoyl-sn-glycero-3-phosphocholine ("DSPC"), and cholesterol (Compl. ¶73). The bivalent versions contain two different mRNA active substances to target multiple viral strains (Compl. ¶¶62-63, 66). The complaint alleges that the Accused Products have generated billions of dollars in revenue for the Defendants (Compl. ¶¶6, 97).
    No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'693 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A formulation comprising: ribonucleic acid (RNA) molecules comprising a sequence that encodes an immunogen The Accused Products are formulations containing nucleoside-modified messenger RNA (mRNA) that encodes a viral spike glycoprotein of SARS-CoV-2. ¶108 col. 9:29-32
lipids comprising: (a) from 20 mole % to 70 mole % cationic lipid The Accused Products contain the cationic lipid ALC-0315, which allegedly constitutes 46.3 mole % of the lipids present. ¶¶110, 113 col. 2:29-34
(b) an anionic or a zwitterionic lipid The Accused Products contain DSPC, which is alleged to be a zwitterionic phospholipid. ¶111 col. 2:29-34
(c) a polyethylene glycol-conjugated (PEG-conjugated) lipid The Accused Products contain ALC-0159, which is alleged to be a PEGylated lipid. ¶112 col. 2:55-59
(d) from 5 mole % to 80 mole % cholesterol The Accused Products contain cholesterol, which allegedly constitutes 42.7 mole % of the lipids present. ¶114 col. 2:29-34
the lipids encapsulate at least half of the RNA molecules The lipids in the Accused Products are formulated into lipid particles that allegedly enable delivery of the mRNA into host cells with an encapsulation efficiency typically greater than 90%. ¶115 col. 2:2-9
the formulation is immunogenic in vivo by eliciting an antibody response against the immunogen in vivo The Accused Products are vaccines that elicit both neutralizing antibody and cellular immune responses to the spike (S) antigen when administered according to authorized indications. ¶116 col. 1:58-61
the cationic lipid comprises a tertiary amine and has a pKa from 6.07 to 7.6; and whereby the pKa is determined at standard temperature and pressure by the following:… The cationic lipid ALC-0315 allegedly contains a tertiary amine. The complaint cites scientific literature reporting a pKa for ALC-0315 between 6.09 and 6.284 when measured in a TNS assay. ¶¶110, 117 col. 40:7-50

'694 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A formulation comprising: a first species of ribonucleic acid (RNA) molecules … that encodes a first immunogen The bivalent Accused Products contain "tozinameran," an mRNA encoding the spike protein of the original SARS-CoV-2 strain. ¶138 col. 40:7-10
a second species of RNA molecules … that encodes a second immunogen The bivalent Accused Products also contain either "riltozinameran" (encoding the Omicron BA.1 spike protein) or "famtozinameran" (encoding the Omicron BA.4/5 spike protein). ¶139 col. 40:11-14
lipids comprising: (a) a cationic lipid, (b) an anionic lipid or a zwitterionic lipid, (c) a polyethylene glycol-conjugated (PEG-conjugated) lipid, and (d) a cholesterol The bivalent Accused Products contain the same four-lipid combination as the monovalent versions: ALC-0315 (cationic), DSPC (zwitterionic), ALC-0159 (PEG-conjugated), and cholesterol. ¶140 col. 40:15-19
the lipids encapsulate at least half of the first species of RNA molecules and at least half of the second species of RNA molecules The lipids in the bivalent Accused Products are formulated into lipid particles that allegedly encapsulate both mRNA species with an efficiency greater than 90%. ¶144 col. 40:20-23
the formulation is immunogenic in vivo by eliciting an antibody response against the first immunogen and the second immunogen in vivo The bivalent Accused Products are alleged to elicit neutralizing antibody responses against both the original and the relevant Omicron variant spike proteins. ¶146 col. 41:1-4
the cationic lipid comprises a tertiary amine and has a pKa from 6.07 to 7.6; and whereby the pKa is determined by the following: … The cationic lipid ALC-0315 allegedly contains a tertiary amine and has a pKa falling between 6.07 and 7.6, based on scientific literature cited in the complaint. ¶¶141, 145 col. 41:5-50

Identified Points of Contention:

  • Procedural Questions: A primary point of contention may arise from the detailed, 14-step procedure for determining the pKa of the cationic lipid, which is recited in full in the asserted claims of both the '693 and '694 patents. The complaint cites scientific literature to allege that the pKa of the accused ALC-0315 lipid falls within the claimed range (Compl. ¶¶117, 145). This raises the evidentiary question of whether the methods used in the cited literature are identical to the specific procedural steps required by the claims.
  • Scope Questions: The term "liposome" is used in the patents ('693 Patent, col. 2:2), while the complaint and cited documents often refer to the accused delivery vehicle as "lipid nanoparticles" or "LNPs" (Compl. ¶¶33, 107). The complaint alleges that Defendants themselves have equated these terms in other legal proceedings (Compl. ¶33). The case may involve a dispute over whether the accused "LNPs" fall within the scope of the claimed "liposomes."

V. Key Claim Terms for Construction

  • The Term: "whereby the pKa is determined … by the following: [14-step process]"

    • Context and Importance: This lengthy procedural limitation, appearing at the end of independent Claim 1 in both the '693 and '694 patents, defines the sole method by which the critical pKa range must be measured. Infringement requires not just that the accused lipid has a pKa within the 6.07-7.6 range, but that it has such a pKa when measured by this exact method. Practitioners may focus on this term because it appears to be a potential avenue for a non-infringement defense if the plaintiff cannot produce evidence showing the pKa was determined using this precise method.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The parties may dispute whether minor deviations from the recited steps (e.g., buffer concentrations, measurement wavelengths) are material. The specification's general description of pKa as "the pH at which 50% of the lipids are charged" ('693 Patent, col. 2:35-38) could be cited to argue that the purpose of the steps is simply to find this value, and functionally equivalent methods should suffice.
      • Evidence for a Narrower Interpretation: The claim language uses the definitive phrase "whereby the pKa is determined...by the following," which suggests this is the exclusive and required method of measurement. The patentee's choice to include such a detailed, multi-step process directly in the claim, rather than merely describing it as a preferred method in the specification, may suggest an intent to be strictly bound by its terms.

  • The Term: "lipids comprising: (a) from 20 mole % to 70 mole % cationic lipid …" (and other specified mole percentages)

    • Context and Importance: These limitations define the formulation by the relative molar quantities of its constituent lipids. The complaint relies on a third-party scientific publication to allege that the Accused Products meet these percentage ranges (Compl. ¶¶113-114). The dispute will likely center on whether the composition of the commercially manufactured and sold products consistently and accurately reflects these specific ratios.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification provides examples with varying lipid ratios, such as 40% or 60% cationic lipid ('693 Patent, col. 2:50-52), suggesting some flexibility. A party might argue that the ranges should be interpreted to accommodate normal manufacturing variances.
      • Evidence for a Narrower Interpretation: The claims recite specific numerical ranges. The prosecution history (not provided, but likely to be reviewed by the parties) may reveal arguments made by the patentee to distinguish prior art based on these specific percentages, which could be used to argue for a strict interpretation of the claimed boundaries.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement on the basis that Defendants provide the Accused Products with packaging, package inserts, and other supporting materials that instruct and encourage healthcare practitioners to administer the vaccines in a manner that directly infringes the asserted method claims (Compl. ¶¶103, 118-119). Contributory infringement is alleged on the grounds that the Accused Products are not staple articles of commerce and are especially made for an infringing use (Compl. ¶104).
  • Willful Infringement: The willfulness allegations are based on both pre- and post-suit knowledge. The complaint alleges pre-suit knowledge stemming from Defendants' long-standing awareness of the inventors' work and the associated patent families, including through citations in their own patent applications and in communications with GSK (Compl. ¶¶45-51). Post-suit willfulness is alleged based on continued infringement after receiving specific notice of the patents-in-suit via communications from GSK beginning on or about April 24, 2024 (Compl. ¶¶52, 126-127).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A central strategic issue will be one of judicial estoppel and party admissions: to what extent will Defendants' prior statements in IPRs and foreign litigations, which the complaint uses to define key technical concepts such as the equivalence of "liposomes" and "LNPs," be binding or persuasive in establishing the scope and meaning of the asserted claims?
  • A critical evidentiary question will be one of methodological compliance: can the Plaintiff prove that the pKa of the accused ALC-0315 lipid falls within the claimed range when measured by the explicit and detailed 14-step process recited in the claims themselves, or will there be a dispositive mismatch between the claim's procedural requirements and the available scientific evidence?
  • A key factual question for damages will be one of apportionment and contribution: given the complexity of the accused mRNA vaccines, the case will likely involve a dispute over the contribution of the patented LNP formulation technology to the overall value and success of the Comirnaty® products, which will be central to determining a reasonable royalty.