DCT
2:17-cv-05914
Sanofi Aventis US LLC v. Merck Sharp & Dohme Corp
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Sanofi-Aventis U.S. LLC (Delaware), Sanofi-Aventis Deutschland GmbH (Germany), and Sanofi Winthrop Industrie (France)
- Defendant: Merck Sharp & Dohme Corp. (New Jersey)
- Plaintiff’s Counsel: Walsh Pizzi O'Reilly Falanga LLP
- Case Identification: 2:17-cv-05914, D.N.J., 08/08/2017
- Venue Allegations: Venue is based on Defendant's incorporation and principal place of business being within the District of New Jersey.
- Core Dispute: Plaintiff alleges that Defendant’s submission of a New Drug Application to the FDA for a proposed insulin glargine vial product constitutes an act of infringement of two patents related to stable, acidic insulin formulations.
- Technical Context: The technology concerns pharmaceutical formulations designed to improve the chemical and physical stability of acidic, long-acting insulin analogs, such as insulin glargine, by using specific surfactants.
- Key Procedural History: This action was filed under the Hatch-Waxman Act following Defendant's notice of a Paragraph IV certification against the patents-in-suit, which are listed in the FDA's Orange Book for Plaintiff's Lantus® products. The complaint notes that on June 5, 2017, non-party Mylan Pharmaceuticals Inc. filed petitions for inter partes review (IPR) of both patents-in-suit, which had not yet been instituted at the time of filing. In subsequent proceedings (IPR2017-01526 and IPR2017-01528), the Patent Trial and Appeal Board ultimately cancelled all claims of both patents-in-suit.
Case Timeline
| Date | Event |
|---|---|
| 2002-06-18 | Earliest Priority Date for ’652 and ’930 Patents |
| 2009-01-13 | ’652 Patent Issue Date |
| 2010-05-11 | ’930 Patent Issue Date |
| 2017-06-05 | Mylan files IPR petitions against ’652 and ’930 Patents |
| 2017-06-27 | Merck sends Notice of Paragraph IV Certification to Sanofi |
| 2017-08-08 | Complaint Filing Date |
| 2021-01-05 | PTAB issues certificates cancelling all claims of the ’652 and ’930 Patents |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,476,652 - “Acidic Insulin Preparations Having Improved Stability,” Issued January 13, 2009
The Invention Explained
- Problem Addressed: The patent describes that while acidic solutions are necessary for certain insulin analogs like insulin glargine, these formulations exhibit decreased stability and an increased tendency to aggregate and form particles, particularly when subjected to thermal or physicomechanical stress (e.g., shaking) ('652 Patent, col. 3:1-7). This aggregation can be accelerated by contact with hydrophobic surfaces, such as the glass vials or stoppers used for storage ('652 Patent, col. 3:8-14).
- The Patented Solution: The invention addresses this stability problem by adding a specific surfactant to the acidic insulin formulation ('652 Patent, col. 3:40-42). The addition of small quantities of a surfactant, such as polysorbate 20 or polysorbate 80, is described as greatly increasing the stability of the preparation against the formation of aggregates and particles, even after months of storage or stress ('652 Patent, col. 3:52-56, 7:17-22).
- Technical Importance: For long-acting insulin therapies to be safe and effective, maintaining the product’s integrity and preventing particle formation over its shelf-life and during patient use is a critical requirement.
Key Claims at a Glance
- The complaint asserts infringement of one or more unspecified claims. Independent claim 1 is representative.
- Independent Claim 1: A pharmaceutical formulation comprising:
- Gly(A21), Arg(B31), Arg(B32)-human insulin;
- at least one chemical entity chosen from polysorbate 20 and polysorbate 80;
- at least one preservative; and
- water,
- wherein the pharmaceutical formulation has a pH in the acidic range from 1 to 6.8.
- The complaint reserves the right to assert additional claims (Compl. ¶ 30).
U.S. Patent No. 7,713,930 - “Acidic Insulin Preparations Having Improved Stability,” Issued May 11, 2010
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’652 Patent, this patent addresses the same technical problem of aggregation and instability in acidic insulin glargine formulations ('930 Patent, col. 3:5-11).
- The Patented Solution: The solution is identical in concept to that of the ’652 Patent: the use of a surfactant to stabilize the acidic formulation ('930 Patent, col. 3:45-48). However, the claims are directed to a broader class of surfactants than the specific polysorbates recited in the ’652 Patent.
- Technical Importance: The technical importance is identical to that of the parent ’652 Patent, focusing on ensuring the stability and safety of insulin glargine products.
Key Claims at a Glance
- The complaint asserts infringement of one or more unspecified claims. Independent claim 1 is representative.
- Independent Claim 1: A pharmaceutical formulation comprising:
- Gly(A21), Arg(B31), Arg(B32)-human insulin;
- at least one chemical entity chosen from esters and ethers of polyhydric alcohols;
- at least one preservative; and
- water,
- wherein the pharmaceutical formulation has a pH in the acidic range from 1 to 6.8.
- The complaint reserves the right to assert additional claims (Compl. ¶ 30).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Merck’s "Proposed Vial Product," identified as an insulin glargine formulation for subcutaneous injection (100 units/mL) that is the subject of New Drug Application ("NDA") No. 209-764 (Compl. ¶ 21).
Functionality and Market Context
- The Proposed Vial Product is a drug formulation submitted for FDA approval through the 505(b)(2) pathway, which relies in part on data from Sanofi's approved NDA for its Lantus® products (Compl. ¶ 21). The complaint alleges, on information and belief, that Merck intends to commercially manufacture and sell this product in the United States upon FDA approval, positioning it as a follow-on or generic competitor to Sanofi's established Lantus® brand (Compl. ¶ 12). The complaint does not contain specific details of the accused product's formulation, as Plaintiff notes it had not yet received the un-redacted NDA from Defendant at the time of filing (Compl. ¶ 27). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that the submission of NDA No. 209-764 is a technical act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶¶ 32, 36). The infringement theory is based on the information and belief that the product described in the NDA will contain all elements of the asserted claims.
- ’652 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical formulation comprising Gly(A21), Arg(B31), Arg(B32)-human insulin; | The complaint alleges Merck’s Proposed Vial Product is a formulation of insulin glargine. | ¶21 | col. 2:57-59 |
| at least one chemical entity chosen from polysorbate 20 and polysorbate 80; | Plaintiff alleges on information and belief that the accused formulation contains a surfactant recited by this limitation to achieve stability. | ¶30 | col. 3:52-56 |
| at least one preservative; and | Plaintiff alleges on information and belief that the accused formulation contains at least one preservative. | ¶30 | col. 3:58-60 |
| water, wherein the pharmaceutical formulation has a pH in the acidic range from 1 to 6.8. | Plaintiff alleges on information and belief that the accused formulation is an acidic, aqueous solution. | ¶30 | col. 3:1-4 |
- ’930 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical formulation comprising Gly(A21), Arg(B31), Arg(B32)-human insulin; | The complaint alleges Merck’s Proposed Vial Product is a formulation of insulin glargine. | ¶21 | col. 2:60-62 |
| at least one chemical entity chosen from esters and ethers of polyhydric alcohols; | Plaintiff alleges on information and belief that the accused formulation contains a surfactant from this broad chemical class. | ¶30 | col. 3:53-58 |
| at least one preservative; and | Plaintiff alleges on information and belief that the accused formulation contains at least one preservative. | ¶30 | col. 4:1-2 |
| water, wherein the pharmaceutical formulation has a pH in the acidic range from 1 to 6.8. | Plaintiff alleges on information and belief that the accused formulation is an acidic, aqueous solution. | ¶30 | col. 3:5-8 |
- Identified Points of Contention:
- Factual Question: The primary point of contention would be factual: what are the specific excipients contained in Merck's Proposed Vial Product? The complaint is based on "information and belief" (Compl. ¶ 30), and discovery would be required to determine if the formulation actually includes a claimed surfactant and preservative.
- Scope Question: A key issue for the ’930 Patent revolves around the scope of "esters and ethers of polyhydric alcohols." The case may raise the question of whether Merck's chosen surfactant, if any, falls within the technical and legal boundaries of this term.
V. Key Claim Terms for Construction
The Term: "at least one preservative" (’652 Patent, claim 1; ’930 Patent, claim 1)
- Context and Importance: The presence of a preservative is a required element in the broadest independent claims of both patents. The definition of this term is critical because if Merck’s formulation uses a stabilizing agent that is not classified as a "preservative" in the context of the patent, it may support a non-infringement argument.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a non-exhaustive list, stating the formulation can contain preservatives "(e.g. phenol, cresol, parabens)" ('652 Patent, col. 3:58-60). The use of "e.g." (for example) may support an interpretation that the term is not limited to the specific examples listed.
- Evidence for a Narrower Interpretation: A party could argue that the term should be construed in light of its function and the specific examples provided, potentially limiting its scope to substances primarily used for their antimicrobial properties in such pharmaceutical contexts.
The Term: "esters and ethers of polyhydric alcohols" (’930 Patent, claim 1)
- Context and Importance: This term defines the required surfactant in the ’930 Patent. Its construction is central to the infringement analysis for that patent, as it is broader than the "polysorbate 20 and polysorbate 80" limitation of the ’652 Patent. Practitioners may focus on this term because its breadth could capture a wide range of nonionic surfactants that a competitor might use.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification lists several examples that fall under this class, including Span®, Tween®, Myrj®, and Brij® ('930 Patent, col. 3:53-58), suggesting the term is intended to cover a variety of structurally related surfactant families.
- Evidence for a Narrower Interpretation: A party might argue that the term, when read in light of the full specification, should be limited to surfactants with properties analogous to those explicitly tested and shown to be effective in stabilizing insulin glargine in the patent's examples.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that if Merck's NDA is approved, its subsequent commercial manufacture, use, and sale of the Proposed Vial Product would constitute direct infringement under 35 U.S.C. § 271(a) and indirect infringement (inducement and/or contributory infringement) under §§ 271(b) and (c) (Compl. ¶¶ 33, 37). The factual basis for indirect infringement is not detailed beyond the planned marketing of the drug.
- Willful Infringement: Willfulness is implicitly alleged through the assertion that "Merck was aware of the '652 Patent prior to filing NDA No. 209-764" and likewise for the ’930 Patent (Compl. ¶¶ 33, 37). This alleged pre-filing knowledge forms the basis for a potential claim of willful infringement should the product be commercialized post-approval.
VII. Analyst’s Conclusion: Key Questions for the Case
- Procedural Finality: The most significant issue in this case is procedural: given that all claims of both patents-in-suit were subsequently cancelled in inter partes review proceedings, the core basis for the infringement action has been eliminated. The central question is what effect this has on the present litigation, which was filed before the IPRs were concluded.
- Factual Infringement: At the time of filing, a key question was one of evidentiary proof: does the specific formulation detailed in Merck’s confidential NDA No. 209-764 actually contain the elements required by the patent claims, specifically a claimed surfactant (e.g., a polysorbate or another ester/ether of a polyhydric alcohol) and a claimed preservative within the specified acidic pH range?
- Claim Scope: Had the case proceeded, a dispositive issue would have been one of definitional scope: how broadly would the court construe the term "esters and ethers of polyhydric alcohols" in the ’930 patent? The outcome of this construction would have determined whether a potentially wide array of modern, non-polysorbate surfactants would fall within the patent's reach.