DCT

2:20-cv-02786

Merck Sharp & Dohme BV v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:20-cv-02786, D.N.J., 03/13/2020
  • Venue Allegations: Venue is alleged to be proper as to Defendant Lupin Limited because it is a foreign entity, and as to Defendants Lupin Pharmaceuticals, Inc. and Lupin Inc. because they allegedly maintain a regular and established place of business in New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the drug Bridion® (sugammadex) constitutes an act of infringement of a patent covering the sugammadex compound.
  • Technical Context: The technology concerns modified cyclodextrins, a class of chemical compounds used as reversal agents to inactivate and remove other drugs—in this case, neuromuscular blocking agents used during surgery.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' filing of ANDA No. 214338 with a Paragraph IV certification. The patent-in-suit, RE44,733, is a reissue of U.S. Patent No. 6,670,340. The complaint notes that the USPTO has determined the patent is eligible for a five-year patent term extension (PTE), which would extend its expiration date to January 27, 2026.

Case Timeline

Date Event
1999-11-29 Earliest Priority Date for RE44,733 Patent
2003-12-30 Issue Date of Original U.S. Patent No. 6,670,340
2014-01-28 Issue Date of Reissue RE44,733 Patent
2015-12-15 FDA Approval of Bridion® (sugammadex) Injection
2020-01-31 Date of Lupin's ANDA Notice Letter to Merck
2020-02-04 USPTO Issues Notice of Final Determination on Patent Term Extension
2020-03-13 Complaint Filing Date

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, Issued Jan. 28, 2014

The Invention Explained

  • Problem Addressed: The patent describes the limitations of then-existing agents used to reverse neuromuscular blockade in surgical patients. These agents, known as anticholinesterase inhibitors, work by increasing levels of the neurotransmitter acetylcholine. This mechanism can cause significant side effects, such as dangerous changes in heart rate and blood pressure, and is not reliably effective in cases of very deep neuromuscular blockade, known as a "profound block" (’733 Patent, col. 2:2-27).
  • The Patented Solution: The invention proposes a different approach using chemically modified cyclodextrins. Instead of affecting neurotransmitter levels, these molecules act as "chemical chelators" that directly capture and encapsulate the neuromuscular blocking drug, forming a stable "guest-host complex." This complex inactivates the drug, allowing for a rapid reversal of its effects without the side effects associated with anticholinesterase inhibitors (’733 Patent, Abstract; col. 2:28-44).
  • Technical Importance: This encapsulation mechanism represented a novel and potentially safer method for reversing drug-induced paralysis, offering a solution for cases of "profound block" where previous agents were inadequate (Compl. ¶¶ 43-44).

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 1 and notes that infringement of claims 1-5, 9, 11-14, 20, and 21 was not contested by the defendant in its pre-suit notice letter (Compl. ¶¶ 56-57). Independent Claim 1 recites:
    • A 6-mercapto-cyclodextrin derivative having a specified general chemical structure (Formula I);
    • Wherein variables m and n define the size of the cyclodextrin ring (either a β- or γ-cyclodextrin);
    • Wherein R is a specified alkylene or phenylene linker group;
    • Wherein X is one of several specified negatively charged or polar terminal chemical groups (e.g., COOH, SO₂OH);
    • The claim also includes a list of specific, structurally similar compounds that are explicitly excluded from the claim's scope.
  • The complaint reserves the right to assert other claims, including dependent claims.

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendants' proposed generic sugammadex injection products in 200 mg/2 mL and 500 mg/5 mL strengths, as described in ANDA No. 214338 ("Lupin ANDA Products") (Compl. ¶10).
  • Functionality and Market Context: The Lupin ANDA Products are identified as purported generic versions of Plaintiffs' Bridion® drug product (Compl. ¶¶ 1, 46). The active ingredient in the accused products is sugammadex (Compl. ¶52), which is identified as a modified cyclodextrin designed to reverse neuromuscular blockade by encapsulating and inactivating specific neuromuscular blocking agents (Compl. ¶¶ 40, 43). The filing of the ANDA is an act of infringement under 35 U.S.C. § 271(e)(2), which allows for litigation to resolve patent disputes before the generic product is commercially launched (Compl. ¶58).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

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 . . . wherein m is 0-7 and n is 1-8 and m+n=7 or 8; R is (C₁-₆)alkylene . . .; X is COOH . . . or pharmaceutically acceptable salts thereof The complaint alleges that the active ingredient in the Lupin ANDA Products is sugammadex, which is the sodium salt of 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin. This specific chemical structure is alleged to be encompassed by the formula and definitions recited in Claim 1. ¶¶ 40, 52, 56 col. 3:5-25
  • Identified Points of Contention:
    • Infringement vs. Validity: The complaint alleges that in its pre-suit notice letter, Lupin "did not contest infringement of claims 1-5, 9, 11-14, 20 and 21 of the '733 patent" (Compl. ¶57). This suggests that the central dispute in the case may not be over whether the accused product meets the claim limitations, but rather over Defendants’ assertion that the patent claims are invalid or unenforceable, as stated in their Paragraph IV certification (Compl. ¶51).
    • Technical Questions: A key question for the court will be to assess the merits of Defendants' unstated invalidity and unenforceability arguments. Such arguments in pharmaceutical cases often focus on whether the claimed invention was obvious in light of prior art publications describing similar chemical structures or whether there was any inequitable conduct during patent prosecution. The complaint itself does not provide the basis for Defendants' contentions.

V. Key Claim Terms for Construction

While the complaint suggests infringement of the compound claims is not the primary dispute, the construction of certain terms may still be relevant to the analysis of patent validity.

  • The Term: "(C1-6)alkylene"
  • Context and Importance: This term defines the chemical linker 'R' connecting the cyclodextrin core to the terminal functional group 'X'. The scope of this term could be critical for obviousness arguments, as the choice of linker length and structure can impact the efficacy of the final compound. Practitioners may focus on this term because prior art may disclose cyclodextrin derivatives with different linkers, raising the question of whether modifying a known linker to arrive at the claimed structure would have been obvious.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification provides a broad definition, stating the term "means a branched or straight chain bivalent carbon radical containing 1-6 carbon atoms" and provides a non-exhaustive list of examples like "methylene, ethylene . . . 1,6-hexanediyl" (’733 Patent, col. 4:20-27).
    • Evidence for a Narrower Interpretation: The patent’s preferred embodiments and working examples, including the compound that corresponds to sugammadex, primarily utilize short, two- or three-carbon linkers (e.g., "carboxyethyl," "carboxypropyl") (’733 Patent, col. 5:52-62). A party might argue that the invention’s success is tied to these specific short linkers, potentially supporting a narrower construction in the context of validity.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce infringement of the patent’s method claims. This allegation is based on the assertion that Defendants will market their ANDA products with a product label and instructions for use that are substantially similar to those for Bridion®. If followed by healthcare professionals, these instructions would allegedly result in direct infringement of the patented methods of reversing neuromuscular blockade (Compl. ¶63).
  • Willful Infringement: The complaint alleges that Defendants' infringement was and is willful. This claim is based on Defendants' alleged knowledge of the ’733 patent at the time of their ANDA submission and their filing of a Paragraph IV certification "without adequate justification for asserting that the '733 patent is invalid, unenforceable, and/or not infringed" (Compl. ¶68).

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

  • A central issue will be one of patent validity: Given that infringement of the product claims is allegedly uncontested, the case will likely turn on whether Defendants can prove by clear and convincing evidence that the asserted claims of the ’733 patent are invalid (e.g., for obviousness over prior art) or otherwise unenforceable. The patent's explicit exclusion of several related compounds in Claim 1 indicates a crowded prior art field, which may be a focus of litigation.
  • A key secondary issue will be one of induced infringement: Assuming the patent's method claims are found valid, the court will need to determine whether the proposed labeling for Defendants' generic product instructs users to perform the patented methods of administration, thereby making Defendants liable for inducing infringement by healthcare providers.