DCT

2:20-cv-02892

Merck Sharp & Dohme BV v. Fresenius Kabi USA LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:20-cv-02892, D.N.J., 03/16/2020
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey based on Defendant Fresenius USA’s business activities in the state, including the marketing and sale of generic drugs. The complaint notes that Fresenius USA has informed Plaintiff it will not contest personal jurisdiction or venue.
  • Core Dispute: This is a patent infringement action under the Hatch-Waxman Act, where Plaintiff alleges that Defendant's Abbreviated New Drug Application (ANDA) for a generic version of the drug Bridion® (sugammadex) infringes a patent covering the sugammadex molecule.
  • Technical Context: The technology concerns modified cyclodextrins, which are large, ring-shaped molecules designed to encapsulate and inactivate other drugs, specifically agents used to induce neuromuscular blockade during surgery.
  • Key Procedural History: The asserted patent is a reissue of an earlier patent and has been granted a five-year patent term extension (PTE), extending its expiration to 2026. The lawsuit was filed within the 45-day window following receipt of Defendant's Paragraph IV notice letter, triggering an automatic 30-month stay on FDA approval of the generic product.

Case Timeline

Date Event
1999-11-29 '733 Patent Priority Date
2003-12-30 Original U.S. Patent No. 6,670,340 Issued
2014-01-28 Reissue U.S. Patent No. RE44,733 Issued
2015-12-15 FDA approval for Bridion® (NDA No. 022225)
2020-02-03 Fresenius sends Paragraph IV Notice Letter
2020-02-04 USPTO issues Notice of Final Determination on Patent Term Extension
2020-03-16 Complaint Filed

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

U.S. Reissue Patent No. RE44,733 - "6-Mercapto-Cyclodextrin Derivatives: Reversal Agents For Drug-Induced Neuromuscular Block"

  • Patent Identification: U.S. Reissue Patent No. RE44,733, "6-Mercapto-Cyclodextrin Derivatives: Reversal Agents For Drug-Induced Neuromuscular Block," issued January 28, 2014.

The Invention Explained

  • Problem Addressed: The patent describes the problem that traditional agents used to reverse surgically-induced paralysis (neuromuscular blockade) work by broadly increasing levels of the neurotransmitter acetylcholine. This non-selective action causes significant side effects like heart rate changes and increased salivation, requiring co-administration of other drugs to manage them. Furthermore, these agents are not reliably effective at reversing a "profound block" of neuromuscular function (ʼ733 Patent, col. 4:1-27).
  • The Patented Solution: The invention proposes a different approach using chemically modified cyclodextrins. These are large, sugar-based ring molecules with a hollow core. The patent teaches modifying the cyclodextrin with specific side chains (Formula I) that allow it to act as a "chemical chelator." Instead of affecting neurotransmitter levels, this molecule directly encapsulates and binds to the neuromuscular blocking drug in the patient's bloodstream, inactivating it and allowing muscle function to return (ʼ733 Patent, Abstract; col. 4:28-40).
  • Technical Importance: This encapsulation mechanism represented a significant advance, offering the potential for faster reversal from any depth of blockade and avoiding the systemic, "cholinergic" side effects associated with older reversal agents (Compl. ¶¶34-35).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶47).
  • Independent Claim 1 recites:
    • A 6-mercapto-cyclodextrin derivative defined by a general chemical structure (Formula I).
    • The cyclodextrin ring size is defined as having 7 or 8 units (m+n=7 or 8).
    • A linker group R is defined as (C1-6)alkylene or a phenylene-containing group.
    • A terminal functional group X is selected from a list including COOH (a carboxylic acid group).
    • The claim includes the option for "pharmaceutically acceptable salts thereof."
    • The claim concludes with a negative limitation, excluding a specific list of nine previously known cyclodextrin derivatives.
  • The complaint notes that Defendant's notice letter did not contest infringement of claims 1-5 and 11-14 (Compl. ¶48).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the "Fresenius ANDA Products," which are purported generic versions of Bridion® (sugammadex) Injection in 200 mg/2 mL and 500 mg/5 mL strengths (Compl. ¶7).

Functionality and Market Context

  • The complaint alleges that the Fresenius ANDA Products contain sugammadex as the active ingredient (Compl. ¶43).
  • Sugammadex, the active ingredient in Bridion®, is a modified cyclodextrin that reverses neuromuscular blockade by directly encapsulating neuromuscular blocking agents like rocuronium and vecuronium, thereby reducing the amount of the agent available to act at the neuromuscular junction (Compl. ¶34).
  • The complaint positions Bridion® as a "first-in-class drug" and a "significant advance in the field of anesthesiology" due to its unique mechanism and clinical benefits, such as rapid recovery and the ability to reverse profound blockade (Compl. ¶¶34-35).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint alleges that the active ingredient in the Fresenius ANDA Products, sugammadex, is encompassed by at least claim 1 of the ’733 patent (Compl. ¶47). Sugammadex is the common name for 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin (Compl. ¶31).

RE44,733 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A 6-mercapto-cyclodextrin derivative having the general formula I The Fresenius ANDA Products contain sugammadex, which is 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin, a specific 6-mercapto-cyclodextrin derivative. ¶¶31, 43, 47 col. 5:51-53
wherein m is 0-7 and n is 1-8 and m+n=7 or 8; Sugammadex is a derivative of γ-cyclodextrin, which is composed of 8 glucose units (m+n=8). As a "per" substituted compound, n=8 and m=0. ¶31 col. 5:42-44
R is (C1-6)alkylene... The "ethyl" portion of the sugammadex side chain, (2-carboxyethyl)thio, is a C2 alkylene, falling within the scope of (C1-6)alkylene. ¶31 col. 5:20-27
X is COOH... The "carboxy" portion of the sugammadex side chain, (2-carboxyethyl)thio, is a COOH group. ¶31 col. 5:16-19
or pharmaceutically acceptable salts thereof; The Fresenius ANDA Products are injectable formulations of sugammadex, which are pharmaceutically acceptable salts. ¶¶7, 43 col. 6:46-52
with the exclusion of [list of 9 compounds] The specific chemical structure of sugammadex is not among the nine compounds explicitly excluded from the claim's scope. ¶¶31, 47 col. 19:29-43

Identified Points of Contention

  • Scope Questions: The complaint's infringement theory appears straightforward, as sugammadex is listed as a preferred embodiment in the patent (ʼ733 Patent, col. 5:51-53). A dispute could theoretically arise if the Defendant's invalidity argument hinges on showing that the asserted claims are invalid if read broadly enough to cover sugammadex, but are not infringed under a narrower, valid construction.
  • Technical Questions: As this is a Hatch-Waxman case initiated after a Paragraph IV certification, the primary technical dispute will likely concern validity. The complaint states Defendant certified the '733 Patent is "invalid, unenforceable, and/or will not be infringed" (Compl. ¶42). The key question will be what evidence Defendant presents to support its assertion that the claims covering sugammadex are invalid, likely on grounds of obviousness over the prior art, including the compounds listed in the claim's negative limitation.

V. Key Claim Terms for Construction

  • The Term: "with the exclusion of..." (the negative limitation in Claim 1)
  • Context and Importance: Practitioners may focus on this term because negative limitations are often added during prosecution to distinguish the invention from prior art. The scope of this exclusion and the relationship between the claimed compounds and the excluded compounds will be central to any obviousness analysis. Defendant will likely argue that the differences between the claimed invention and the excluded prior art are minor and would have been obvious to a skilled artisan.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue for a broad interpretation of the claimed space by emphasizing that the excluded compounds are a very specific and finite list, implying that anything not on the list, including compounds structurally similar to those on the list, is covered. The patent describes the excluded compounds as specific prior art examples (ʼ733 Patent, col. 5:28-55).
    • Evidence for a Narrower Interpretation: A party might argue that the exclusion of compounds like "6-per-deoxy-6-per-(2-hydroxyethylthio)-γ-cyclodextrin" suggests that the "inventive step" is narrow. They may argue the claims should not be construed to cover compounds that are merely obvious modifications of these excluded structures.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement based on the assertion that Defendant will provide a product label with instructions for use that will cause healthcare professionals to directly infringe. The complaint alleges this will be done with knowledge of the patent and intent to cause infringement (Compl. ¶¶54-55). It also alleges contributory infringement, stating the accused product is not a staple article of commerce and is especially adapted for an infringing use (Compl. ¶56).
  • Willful Infringement: Willfulness is alleged based on Defendant having "full knowledge of the '733 patent and without a reasonable basis for believing that they would not be liable," stemming from the filing of the ANDA with an allegedly unjustified Paragraph IV certification (Compl. ¶59).

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

  • A core issue will be one of patent validity: Can Defendant prove by clear and convincing evidence that the asserted claims covering sugammadex are invalid as obvious? This will likely involve a detailed comparison between the claimed invention and the prior art compounds explicitly excluded by the claim's negative limitation, focusing on whether the chemical modifications would have been obvious to a person of ordinary skill in the art.
  • A related question will be the scope of the negative limitation: How does the explicit exclusion of specific prior art compounds affect the obviousness analysis for structurally similar compounds like sugammadex? The court will need to determine if the differences are sufficient to support patentability.
  • Finally, a key question for damages and potential enhancement will be one of objective reasonableness: Was Defendant's Paragraph IV certification, which asserted invalidity and/or non-infringement, supported by a reasonable, good-faith basis at the time it was made, or was it objectively baseless, potentially supporting a finding of willful infringement?