DCT
1:23-cv-00578
Alnylam Pharma Inc v. Pfizer Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Alnylam Pharmaceuticals, Inc. (Delaware)
- Defendant: Pfizer Inc. (Delaware) and Pharmacia & Upjohn Co. LLC ( Delaware)
- Plaintiff’s Counsel: McDermott Will & Emery LLP
- Case Identification: 1:23-cv-00578, D. Del., 05/26/2023
- Venue Allegations: Venue is asserted in the District of Delaware based on both Defendants being Delaware corporations.
- Core Dispute: Plaintiff alleges that Defendant’s COVID-19 Vaccine (COMIRNATY®) infringes four patents related to a class of protonatable, biodegradable lipids used to form lipid nanoparticle delivery systems for RNA-based therapeutics.
- Technical Context: The technology concerns lipid nanoparticles (LNPs), which serve as microscopic vehicles to protect and deliver fragile RNA molecules, such as mRNA, into human cells, a foundational technology for modern RNA vaccines.
- Key Procedural History: The four patents-in-suit were all issued in February, March, and April of 2023, shortly before the complaint was filed. The complaint notes Plaintiff’s history of licensing its intellectual property but does not detail any specific licensing negotiations or prior litigation between the parties concerning this technology.
Case Timeline
| Date | Event |
|---|---|
| 2011-12-07 | Priority Date for ’229, ’657, ’479, and ’480 Patents |
| 2020-03-17 | Defendants announce plan to jointly develop COVID-19 vaccine |
| 2020-04-22 | Defendants announce first clinical trial of mRNA vaccine candidates |
| 2020-12-11 | FDA grants Emergency Use Authorization for Defendants' vaccine |
| 2021-08-23 | FDA approves vaccine under the tradename COMIRNATY® |
| 2023-02-28 | U.S. Patent No. 11,590,229 Issues |
| 2023-03-28 | U.S. Patent No. 11,612,657 Issues |
| 2023-04-25 | U.S. Patent No. 11,633,479 Issues |
| 2023-04-25 | U.S. Patent No. 11,633,480 Issues |
| 2023-05-26 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,590,229 - "Biodegradable Lipids for the Delivery of Active Agents"
Issued February 28, 2023. (Compl. ¶23).
The Invention Explained
- Problem Addressed: The patent addresses the long-standing challenge of delivering fragile, negatively charged RNA therapeutics (like siRNA and mRNA) into the body’s cells in a safe, effective, and non-toxic manner (Compl. ¶17; ’229 Patent, col. 1:36-42). Early lipid-based delivery systems suffered from toxicity issues, especially at the high doses required for efficacy (Compl. ¶18).
- The Patented Solution: The invention is a class of novel, synthetic cationic lipids containing biodegradable groups within their lipidic structure. These lipids are designed to form nanoparticles that encapsulate and protect RNA during transit in the body, facilitate its entry into target cells, and then metabolize and clear from the body quickly to enhance safety and avoid dose-limiting toxicity (’229 Patent, col. 2:1-11; Compl. ¶21).
- Technical Importance: This approach of using biodegradable lipids was a key innovation enabling the development of potent and safe RNA delivery systems, which became foundational to the success of mRNA-based vaccines (Compl. ¶1).
Key Claims at a Glance
- The complaint asserts independent claim 27 (Compl. ¶25, 85).
- Essential elements of independent claim 27 include:
- A vaccine comprising a lipid particle and a pharmaceutically acceptable diluent, excipient, or carrier.
- The lipid particle comprises: (i) a nucleic acid comprising RNA; (ii) 35-65 mol% of a protonatable lipid compound; (iii) 3-12 mol% distearoylphosphatidylcholine (DSPC); (iv) 15-45 mol% cholesterol; and (v) 0.5-10 mol% of a PEG-modified lipid.
- The protonatable lipid compound comprises a head group, two hydrophobic tails, and a central nitrogen atom moiety.
- Each hydrophobic tail has the formula -R¹²-M¹-R¹³, with specific chemical definitions for each group, including that R¹³ is a C₁₀-C₂₀ branched alkyl branched at the alpha position relative to the ester group.
- Each hydrophobic tail has a specified chain length of 17 atoms and a total carbon atom content of 21 to 26 carbons.
- The complaint also asserts dependent claim 28 (Compl. ¶85).
U.S. Patent No. 11,612,657 - "Biodegradable Lipids for the Delivery of Active Agents"
Issued March 28, 2023. (Compl. ¶27).
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the ’229 Patent: the need for a potent, safe, and effective delivery system for RNA therapeutics that overcomes the fragility of RNA and the toxicity of earlier delivery vehicles (Compl. ¶¶17-19; ’657 Patent, col. 1:24-58).
- The Patented Solution: The invention provides a pharmaceutical composition containing a lipid particle made from a specific class of biodegradable, protonatable lipids. As described in the patent, the incorporation of biodegradable groups leads to faster metabolism and removal of the lipid from the body after delivery of the RNA, resulting in lower toxicity (’657 Patent, col. 2:1-11).
- Technical Importance: This technology provides a specific formulation for lipid nanoparticles that enables the creation of viable RNA-based therapeutics and vaccines (Compl. ¶1).
Key Claims at a Glance
- The complaint asserts independent claim 15 (Compl. ¶29, 89).
- Essential elements of independent claim 15 include:
- A pharmaceutical composition comprising a lipid particle and a pharmaceutically acceptable diluent.
- The lipid particle comprises: (i) a nucleic acid comprising RNA; (ii) about 45-65 mol % of a protonatable lipid compound; (iii) about 5-10 mol % DSPC; (iv) about 25-40 mol % of cholesterol; and (v) 0.5-5 mol % of a PEG-modified lipid.
- The protonatable lipid compound comprises a head group, two identical hydrophobic tails, and a central nitrogen atom moiety.
- Each hydrophobic tail has the formula -R¹²-M¹-R¹³, with specific chemical definitions for each group, including that R¹³ is a C₁₀-C₂₀ alkyl group branched at the α-position relative to M¹.
- Each hydrophobic tail has a specified chain length of 17 to 24 atoms and a total carbon atom content of 21 to 26 carbons.
- The complaint also asserts dependent claims 16-19, 22, 23, 26, 28, and 29 (Compl. ¶89).
U.S. Patent No. 11,633,479 - "Biodegradable Lipids for the Delivery of Active Agents"
Issued April 25, 2023. (Compl. ¶31).
Technology Synopsis
The ’479 Patent claims the chemical structure of the lipid compound itself, rather than a composition containing it. The patent describes a class of lipid compounds with a central nitrogen moiety, two identical hydrophobic tails with specific structural features (e.g., branching, chain length, carbon count), and a head group, designed for use in RNA delivery systems. (Compl. ¶¶32-33).
Asserted Claims & Accused Features
- Asserted Claims: Independent claim 10 and dependent claim 11. (Compl. ¶¶93-94).
- Accused Features: The specific protonatable lipid compound ALC-0315, which is alleged to be a core component of the lipid nanoparticles in Defendants' COVID-19 Vaccine. (Compl. ¶¶2, 73).
U.S. Patent No. 11,633,480 - "Biodegradable Lipids for the Delivery of Active Agents"
Issued April 25, 2023. (Compl. ¶36).
Technology Synopsis
The ’480 Patent claims a lipid particle composition for delivering an active agent such as mRNA. The claimed particle includes specific molar percentages of a protonatable lipid compound, DSPC, cholesterol, and a PEG-modified lipid, with the protonatable lipid defined by specific structural characteristics. (Compl. ¶¶37-38).
Asserted Claims & Accused Features
- Asserted Claims: Independent claim 1 and dependent claims 2-4 and 11. (Compl. ¶¶97-98).
- Accused Features: The complete lipid particle formulation used in Defendants' COVID-19 Vaccine, which is alleged to contain the claimed components in the claimed ratios. (Compl. ¶¶2, 79).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is the Pfizer-BioNTech COVID-19 Vaccine, which is approved and marketed under the tradename COMIRNATY® (Compl. ¶¶3, 49).
Functionality and Market Context
- The COMIRNATY® vaccine is an mRNA-based vaccine designed to protect against COVID-19 (Compl. ¶2). It functions by using a lipid nanoparticle (LNP) delivery system to encapsulate and deliver nucleoside-modified messenger RNA (mRNA) that encodes the viral spike (S) glycoprotein of SARS-CoV-2 into human cells (Compl. ¶62). The complaint alleges this LNP technology is "essential to the efficacy and safety" of the vaccine, as it protects the "incredibly delicate" mRNA from degradation and facilitates its entry into cells (Compl. ¶¶58-59). The vaccine has achieved significant commercial success, with the complaint citing worldwide revenues of $37.8 billion for 2022 and forecasted revenues of $13.5 billion for 2023 (Compl. ¶54).
IV. Analysis of Infringement Allegations
’229 Patent Infringement Allegations
| Claim Element (from Independent Claim 27) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A vaccine comprising a lipid particle and a pharmaceutically acceptable diluent, excipient, or carrier | Defendants' COVID-19 Vaccine (COMIRNATY®) is a vaccine that comprises lipid particles and is formulated with diluents, excipients, or carriers. | ¶¶49, 61, 66 | col. 497:18-20 |
| wherein the lipid particle comprises: (i) a nucleic acid, wherein the nucleic acid comprises RNA | Each dose of the vaccine contains "30 mcg of a nucleoside-modified messenger RNA (mRNA)." | ¶62 | col. 497:21-22 |
| (ii) 35-65 mol% of a protonatable lipid compound | Upon information and belief, the infringing lipid particles contain 35-65 mol% of the protonatable lipid compound ALC-0315. | ¶61 | col. 497:23-24 |
| (iii) 3-12 mol% distearoylphosphatidylcholine (DSPC), (iv) 15-45 mol% cholesterol, and (v) 0.5-10 mol% of the PEG-modified lipid | Upon information and belief, the infringing lipid particles contain molar percentages of DSPC, cholesterol, and a PEG-modified lipid that fall within the claimed ranges. | ¶61 | col. 497:25-27 |
| wherein the protonatable lipid compound comprises a head group, hydrophobic tails, and a central moiety to which the head group and the hydrophobic tails are directly bonded, wherein: the central moiety is a nitrogen atom | The accused lipid ALC-0315, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)), has a central nitrogen atom to which the head group and hydrophobic tails are bonded. The chemical structure of ALC-0315 is depicted in the complaint. | ¶¶61, 63 | col. 497:32-38 |
| each of the two hydrophobic tails has the formula -R¹²-M¹-R¹³, wherein: R¹² is a C₁-C₁₄ alkyl group, M¹ is -OC(O)-, and R¹³ is a C₁₀-C₂₀ branched alkyl, wherein R¹³ is branched at the alpha position relative to the -OC(O)- group | The hydrophobic tails of ALC-0315 allegedly meet this structural formula, with the R¹³ alkyl group being branched at the alpha position relative to the ester group. | ¶63 | col. 497:39-46 |
| the chain length of formula -R¹²-M¹-R¹³ is 17 atoms; and the total carbon atom content of each hydrophobic tail is 21 to 26 carbon atoms | The hydrophobic tails of ALC-0315 allegedly have a chain length and total carbon atom content meeting these specific numerical limitations. | ¶63 | col. 497:47-50 |
Identified Points of Contention
- Scope Questions: A central question will be whether the specific chemical structure of the accused lipid, ALC-0315, falls within the scope of the structural limitations of claim 27. This may involve a detailed analysis of whether ALC-0315's "2-hexyldecanoate" portion satisfies the claim's requirement for a "C₁₀-C₂₀ branched alkyl, wherein R¹³ is branched at the alpha position."
- Technical Questions: What evidence does the complaint provide to support its "information and belief" allegations regarding the precise molar percentages of the four lipid components in the final, commercially sold vaccine? The actual composition of the manufactured product could become a key factual dispute.
’657 Patent Infringement Allegations
| Claim Element (from Independent Claim 15) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising a lipid particle and a pharmaceutically acceptable diluent | COMIRNATY® is a pharmaceutical composition containing lipid particles and formulated with diluents. | ¶¶49, 69, 71 | col. 499:1-3 |
| wherein the lipid particle comprises: (i) a nucleic acid; ... wherein the nucleic acid comprises an RNA | Each dose of the vaccine contains nucleoside-modified messenger RNA (mRNA). | ¶70 | col. 499:4, 11 |
| (ii) about 45-65 mol % of a protonatable lipid compound | Upon information and belief, the lipid particles in the vaccine contain 45-65 mol% of the protonatable lipid compound ALC-0315. | ¶69 | col. 499:5-6 |
| (iii) about 5-10 mol % distearoylphosphatidylcholine (DSPC), (iv) about 25-40 mol % of cholesterol, (v) 0.5-5 mol % of a PEG-modified lipid | Upon information and belief, the vaccine contains molar percentages of DSPC, cholesterol, and a PEG-modified lipid that fall within the claimed ranges. | ¶69 | col. 499:7-10 |
| wherein the protonatable lipid compound comprises a head group, hydrophobic tails, and a central moiety ... wherein: the central moiety is a nitrogen atom; the hydrophobic tails consist of two identical hydrophobic tails | The accused lipid ALC-0315 has a central nitrogen atom and two identical hydrophobic tails. The chemical structure of ALC-0315 is depicted in the complaint. | ¶¶63, 69 | col. 499:12-20 |
| each hydrophobic tail has the formula —R¹²-M¹-R¹³, wherein: R¹² is a C₄-C₁₄ alkyl group; M¹ is —OC(O)—; R¹³ is a C₁₀-C₂₀ alkyl group that is branched at the α-position relative to M¹ | The hydrophobic tails of ALC-0315 allegedly meet this specific structural formula. | ¶63 | col. 499:21-26 |
| the chain length of formula —R¹²-M¹-R¹³ is from 17 to 24 atoms; and the total carbon atom content of each hydrophobic tail is 21 to 26 carbon atoms | The hydrophobic tails of ALC-0315 allegedly have a chain length and total carbon atom content meeting these specific numerical limitations. | ¶63 | col. 499:27-30 |
Identified Points of Contention
- Scope Questions: As with the ’229 Patent, the analysis may focus on whether ALC-0315's chemical structure strictly conforms to the definition of the "protonatable lipid compound," particularly the branching position, chain length, and carbon counts. The use of the word "about" for the molar percentages may also be a point of contention regarding the scope of those ranges.
- Technical Questions: Does the complaint provide sufficient evidence that the molar percentages of the lipids in COMIRNATY® fall within the specific ranges of claim 15, which differ from those in claim 27 of the ’229 Patent?
V. Key Claim Terms for Construction
The Term: "protonatable lipid compound" (’229 Patent, cl. 27; ’657 Patent, cl. 15)
Context and Importance: This term defines the allegedly novel and essential active lipid component (ALC-0315) of the accused delivery system. The entire infringement case rests on whether ALC-0315 is properly classified as a "protonatable lipid compound" as defined by the very specific structural and chemical limitations that follow this term in the claims. Practitioners may focus on this term because the patents provide a highly detailed, multi-part definition that ALC-0315 must satisfy in its entirety.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims define the term through a structural formula (Markush group) with variables (e.g., R¹², M¹, R¹³), which could be argued to cover any compound fitting the generic formula, not just the specific examples shown in the specification (’229 Patent, col. 497:39-46).
- Evidence for a Narrower Interpretation: The specification provides numerous specific examples of cationic lipids and describes preferred embodiments with certain properties, such as a pKa "from about 4 to about 13" or a specific in vivo half-life (’229 Patent, col. 17:4-5; col. 24:3-9). A defendant may argue that the term should be limited by these disclosed properties or confined to structures closely resembling the preferred embodiments depicted, such as those in Table 1C (’229 Patent, col. 43-56).
The Term: "branched at the alpha position" (’229 Patent, cl. 27) / "branched at the α-position" (’657 Patent, cl. 15)
Context and Importance: This is a precise locational requirement for the chemical structure of the lipid's hydrophobic tail. A literal infringement finding requires that the branching in the accused ALC-0315 molecule occurs at this exact position relative to the ester group. This highly specific limitation makes it a likely focal point for non-infringement arguments.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term "alpha position" has a well-understood meaning in organic chemistry as the first carbon atom attached to a functional group. A party may argue for this plain and ordinary meaning without further limitation from the specification (’229 Patent, col. 497:45-46).
- Evidence for a Narrower Interpretation: The specification includes numerous figures illustrating exemplary hydrophobic tails (’229 Patent, Table 1C, col. 43-56). A party could argue that these examples define the universe of what the inventor considered to be the invention, potentially limiting the scope of the "branched alkyl" group to the specific structures or types of branching depicted.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement of infringement for all four patents pursuant to 35 U.S.C. § 271(b) (Compl. ¶¶ 86, 90, 94, 98). The allegations are based on Defendants manufacturing and selling the COVID-19 Vaccine with knowledge of the patents and with the specific intent that others (e.g., end users, distributors, healthcare providers) will directly infringe by using, selling, or importing the vaccine (Compl. ¶86).
- Willful Infringement: The complaint does not explicitly use the word "willful" or demand enhanced damages. However, it alleges that Defendants have known of each patent since at least its issue date and were notified of the underlying published patent applications months prior to issuance (Compl. ¶¶ 65, 67, 78, 83). These allegations of pre-suit knowledge could form the basis for a later claim of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of structural mapping: does the accused lipid, ALC-0315, meet every precise structural and numerical limitation recited in the claims for the "protonatable lipid compound," including the specific branching position, chain length, and total carbon atom counts of its hydrophobic tails?
- A key evidentiary question will be one of compositional proof: can Alnylam demonstrate that the molar percentages of the four distinct lipid types in Pfizer's final, commercially distributed vaccine formulation fall within the specific ranges claimed in the '229, '657, and '480 patents, moving beyond the complaint's "information and belief" pleading?
- A central dispute is likely to concern damages and apportionment: given the nature of the vaccine, where value is derived from both the mRNA active ingredient and the LNP delivery vehicle, what is the appropriate reasonable royalty for the patented LNP technology, and how should the value contributed by the patented components be apportioned from the overall value of the vaccine?