DCT

3:23-cv-01048

Promosome LLC v. Pfizer Inc.

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:23-cv-01048, S.D. Cal., 06/06/2023
  • Venue Allegations: Venue is alleged against Pfizer based on its regular and established places of business in the Southern District of California, including a La Jolla campus, and alleged acts of infringement within the district. Venue is alleged against the BioNTech entities on the basis that they are foreign entities.
  • Core Dispute: Plaintiff alleges that Defendants’ method for manufacturing the Comirnaty® COVID-19 vaccine infringes a patent related to reengineering mRNA sequences to improve protein expression efficiency.
  • Technical Context: The technology concerns methods for modifying mRNA to increase the amount of a desired protein produced from it, a critical factor for the efficacy and safety of mRNA-based therapeutics and vaccines.
  • Key Procedural History: The complaint alleges that Plaintiff disclosed the patented technology to Dr. Katalin Karikó, then a Senior Vice President at BioNTech, in 2015 and 2016. It further alleges that Plaintiff contacted Pfizer in early 2023 to discuss licensing before filing suit. These allegations form the basis for a claim of willful infringement.

Case Timeline

Date Event
2009-02-24 Earliest Priority Date for ’179 Patent (Provisional Application filing)
2014-10-07 U.S. Patent No. 8,853,179 issues
2015-12-21 Plaintiff's Dr. Mauro allegedly spoke with BioNTech's Dr. Karikó about the technology
2016-04-XX BioNTech's Dr. Karikó allegedly inquired further about the technology
2020-01-11 SARS-CoV-2 genomic sequence published online
2020-12-11 FDA grants Emergency Use Authorization (EUA) for BNT162b2 (Comirnaty®)
2021-08-23 FDA approves Biologics License Application (BLA) for Comirnaty®
2023-02-08 Plaintiff allegedly sent letter to Pfizer's General Counsel regarding the patent
2023-03-10 Plaintiff allegedly sent email to Pfizer employees with copy of the patent
2023-06-06 Complaint Filed

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

U.S. Patent No. 8,853,179 - "Reengineering mRNA Primary Structure for Enhanced Protein Production"

  • Issued: October 7, 2014

The Invention Explained

  • Problem Addressed: In the cellular process of translating mRNA into protein, the ribosome is supposed to start at an "authentic" initiation codon. However, the ribosome can be diverted to other "secondary" initiation codons located further down the mRNA sequence (Compl. ¶31). This "ribosomal diversion" reduces the yield of the desired full-length protein and can lead to the production of unwanted, potentially harmful "cryptic peptides" ('179 Patent, col. 1:24-col. 2:2; Compl. ¶4-5).
  • The Patented Solution: The patent describes a method for reengineering an mRNA sequence to solve this problem. The method involves identifying and mutating the secondary initiation codons so they are no longer recognized by the ribosome. Crucially, this is done by substituting synonymous codons—different three-letter nucleotide sequences that code for the exact same amino acid—which ensures that the final, full-length protein's amino acid sequence is not changed ('179 Patent, col. 2:38-51; Compl. ¶38-39). This modification channels more ribosomes to the correct starting point, increasing the expression efficiency of the desired protein ('179 Patent, col. 10:5-9).
  • Technical Importance: Increasing protein expression efficiency allows for smaller, safer, and more effective doses of mRNA vaccines and therapeutics (Compl. ¶43).

Key Claims at a Glance

  • The complaint asserts infringement of Claim 1, the only claim in the patent (Compl. ¶47).
  • The essential elements of independent Claim 1 are:
    • A method comprising:
    • a) providing a polynucleotide that includes: i) a coding sequence for a full-length protein, ii) a primary initiation codon upstream of that sequence, and iii) one or more secondary initiation codons within the coding sequence.
    • b) mutating the secondary initiation codons, which results in a decrease in protein synthesis starting at those secondary sites, thereby increasing the expression efficiency of the full-length protein.
    • The mutation step must involve changing one or more nucleotides in such a way that the amino acid sequence of the protein remains unaltered.

III. The Accused Instrumentality

Product Identification

The accused products are Defendants' BNT162b2/Comirnaty® COVID-19 Vaccine, its bivalent versions (Original/Omicron BA.1 and BA.4/BA.5), and all related foreign or domestic equivalents (the "Accused Products") (Compl. ¶91).

Functionality and Market Context

  • The Accused Products are mRNA vaccines designed to cause human cells to produce the SARS-CoV-2 spike protein, thereby generating an immune response (Compl. ¶23). The complaint alleges that to create the Accused Products, Defendants performed the patented method on the polynucleotide (cDNA or pDNA) that encodes the spike protein (Compl. ¶92, ¶94). Specifically, it is alleged that Defendants "mutated numerous secondary initiation codons" within the spike protein's coding sequence to increase expression efficiency, without altering the underlying amino acid sequence (Compl. ¶94). Figure 2 of the complaint illustrates the problem of ribosomal diversion to various downstream start sites that the patented method aims to solve. (Compl. ¶31, Fig. 2).
  • The Comirnaty® vaccine has generated tens of billions of dollars in revenue for the Defendants and is a cornerstone of the global response to the COVID-19 pandemic (Compl. ¶13, ¶73-74).

IV. Analysis of Infringement Allegations

’179 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a) providing a polynucleotide comprising: i) a coding sequence for the full-length protein; ii) a primary initiation codon...; and iii) one or more secondary initiation codons located within the coding sequence... The Accused Products are derived from a cDNA or pDNA polynucleotide that contains the coding sequence for the COVID-19 spike protein. The native protein sequence contains a primary initiation codon and numerous secondary initiation codons. ¶94 col. 2:39-44
b) mutating the one or more secondary initiation codons located within the coding sequence... Defendants are alleged to have "mutated numerous secondary initiation codons" located within the coding sequence of the polynucleotide that encodes the spike protein. ¶94 col. 2:44-49
wherein the mutation results in a decrease in initiation of protein synthesis at the one or more secondary initiation codons, thereby increasing expression efficiency of the full-length protein... By mutating the secondary initiation codons, Defendants' method allegedly reduces ribosomal diversion and increases the expression efficiency of the full-length spike protein. This effect is depicted in the complaint's Figure 4, which contrasts pre- and post-modification protein yields. ¶40, ¶94, Fig. 4 col. 10:5-9
wherein mutating the one or more secondary initiation codons... comprises mutating one or more nucleotides such that the amino acid sequence of the protein remains unaltered. The complaint alleges that Defendants mutated the secondary codons "without altering the amino acid sequence of the spike protein." ¶94 col. 2:50-51

Identified Points of Contention

  • Scope Questions: The claim is to a method of improving... efficiency. A potential dispute is whether Defendants' modifications were made for the claimed purpose of reducing secondary initiation, or for other reasons such as general "codon optimization," which the complaint itself distinguishes from the patented method (Compl. ¶34, ¶38). The defense may argue that any effect on secondary initiation was an unintended byproduct of a different, non-infringing optimization strategy.
  • Technical Questions: The complaint states that the accused vaccine's amino acid sequence is identical to the native protein "save for two amino acids that were modified to achieve additional stability for reasons separate from the '179 Patent" (Compl. ¶94, n.10). This raises the question of whether the claim limitation "the amino acid sequence of the protein remains unaltered" is met. The court will have to determine if this limitation applies to the entire protein sequence or only to the amino acid positions corresponding to the mutated codons.

V. Key Claim Terms for Construction

  • The Term: "the amino acid sequence of the protein remains unaltered"
  • Context and Importance: This term is critical because the complaint concedes the final accused protein contains two amino acid changes for stability reasons, unrelated to the patented method (Compl. ¶94, n.10). The entire infringement case may hinge on whether these two unrelated changes preclude a finding that the sequence "remains unaltered" as required by the claim. Practitioners may focus on this term because its construction could be dispositive.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation (Plaintiff's likely view): The specification repeatedly frames the invention in the context of using synonymous codons to replace existing codons without changing the corresponding amino acid (e.g., ’179 Patent, col. 2:50-51, "mutating one or more nucleotides such that the amino acid sequence remains unaltered"). A party could argue the "unaltered" limitation is tied directly to the "mutating" step and is intended to mean that the specific mutations of secondary codons do not themselves alter the amino acid sequence at those positions.
    • Evidence for a Narrower Interpretation (Defendant's likely view): The plain language of the claim is absolute. A party could argue that if the final protein's amino acid sequence is different from the original protein's sequence for any reason, it does not "remain unaltered," and the claim is not infringed. The specification does not appear to explicitly contemplate or carve out exceptions for other, unrelated modifications.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges Defendants induced infringement by contract manufacturers who perform the patented method, and also by third parties (e.g., healthcare providers) who use the resulting vaccines. The alleged inducement is based on sales, education, and advertising efforts (Compl. ¶96-97).
  • Willful Infringement: The complaint alleges both pre- and post-suit willfulness. It asserts that BioNTech knew of the patented method as early as 2015 through detailed technical discussions between Plaintiff's inventor and Dr. Katalin Karikó, then a BioNTech Senior Vice President (Compl. ¶54-55, ¶95). It further alleges that Pfizer was put on direct notice through a series of letters and emails in February and March 2023, which included a copy of the patent and a specific allegation of infringement, prior to the lawsuit being filed (Compl. ¶78-81, ¶101).

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

  • A core issue will be one of claim construction: does the limitation "the amino acid sequence of the protein remains unaltered" require the entire protein sequence to be identical, or does it only require that the specific mutations of secondary codons be synonymous? The resolution of this question in light of the two stability-enhancing amino acid changes in the Comirnaty® vaccine could determine the outcome of the infringement analysis.
  • A key evidentiary question will be one of intent and knowledge: can the Plaintiff prove that the alleged 2015-2016 communications with a single BioNTech executive constitute pre-suit knowledge of the patented method by the corporate defendants? This will be central to the high-stakes issue of willful infringement.
  • A central factual dispute will likely be the reason for mutation: can Plaintiff prove that Defendants' modifications to the spike protein's mRNA sequence were performed for the specific purpose of the claimed invention—reducing secondary initiation—as opposed to being the result of a more general, conventional codon optimization process aimed at different goals?