Merck Sharp & Dohme BV v. Mylan Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Merck Sharp & Dohme B.V. (Netherlands) and Organon USA Inc. (New Jersey)
  • Defendant: Mylan Pharmaceuticals Inc. (West Virginia), Mylan Inc. (Pennsylvania), and Mylan API US LLC (Delaware)
  • Plaintiff’s Counsel: Goodwin & Goodwin, LLP
• Case Identification: 1:20-cv-00061, N.D. W. Va., 04/02/2020
• Venue Allegations: Venue is alleged to be proper as to Mylan Pharmaceuticals Inc. based on its having a regular and established place of business in West Virginia and having committed acts of infringement in the district. Venue over the other Mylan defendants is predicated on their business contacts and alleged agency relationships with Mylan Pharmaceuticals Inc.
• Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the anesthetic reversal agent Bridion® (sugammadex) constitutes an act of infringement of a patent covering the sugammadex compound.
• Technical Context: The technology involves modified cyclodextrins, a class of chemical compounds designed to act as chelating agents that encapsulate and neutralize specific drug molecules in the body, in this case, neuromuscular blocking agents used during surgery.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants’ submission of a Paragraph IV certification notice letter. The patent-in-suit, U.S. Reissue Patent No. RE44,733, is a reissue of an earlier patent and has received a determination from the USPTO for a five-year patent term extension, which would extend its expiration to 2026. The complaint notes that in their notice letter, Defendants did not contest infringement of claims 1-5 and 11-14.

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	U.S. Reissue Patent No. RE44,733 Issued
2015-12-15	FDA approved commercial marketing of Bridion®
2020-02-04	USPTO issued Notice of Final Determination for Patent Term Extension
2020-02-18	Mylan sent Paragraph IV Notice Letter to Merck
2020-04-02	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"

(Asserted in Complaint ¶¶34-35)

The Invention Explained

• Problem Addressed: The patent describes the problems associated with then-existing agents for reversing neuromuscular blockade after surgery ('733 Patent, col. 2:1-14). These agents, primarily acetylcholinesterase inhibitors, non-selectively increase acetylcholine levels throughout the body, causing significant side effects like bradycardia and hypotension that require co-administration of other drugs, which themselves have side effects ('733 Patent, col. 2:1-10). Furthermore, these agents were not reliably effective at reversing a "profound block" of neuromuscular function ('733 Patent, col. 2:15-27).
• The Patented Solution: The invention provides a new class of molecules—specifically, 6-mercapto-cyclodextrin derivatives—that act as "chemical chelators" or "sequestrants" ('733 Patent, col. 2:28-32). Instead of interacting with the body's neurotransmitter systems, these molecules are designed with a specific three-dimensional cavity to directly capture and encapsulate the neuromuscular blocking drug molecules, forming a stable "guest-host complex" ('733 Patent, col. 2:30-32). This direct encapsulation inactivates the blocking agent, allowing for rapid and safe reversal of muscle relaxation without the systemic side effects of prior art agents ('733 Patent, col. 2:35-43).
• Technical Importance: The complaint asserts that this direct encapsulation mechanism represented a "first-in-class drug" and a "significant advance in the field of anesthesiology" (Compl. ¶¶40-41).

Key Claims at a Glance

• The complaint asserts at least claim 1 of the '733 patent (Compl. ¶53).
• Independent Claim 1 recites:
  • A 6-mercapto-cyclodextrin derivative having a specific general chemical formula (Formula I).
  • The formula specifies a cyclodextrin ring structure (where m+n=7 or 8, indicating a β- or γ-cyclodextrin).
  • The structure includes a linker group "R" (defined as an alkylene or phenylene-containing group) connecting the cyclodextrin to a terminal group "X".
  • The terminal group "X" is defined as one of several specified chemical moieties, including COOH (a carboxylic acid).
  • The claim also includes a list of seven specific, previously known compounds that are explicitly excluded from the claim's scope.
• The complaint alleges that Defendants did not contest infringement of claims 1-5 and 11-14 in their Paragraph IV notice letter (Compl. ¶54).

III. The Accused Instrumentality

Product Identification

Defendants' Abbreviated New Drug Application (ANDA) No. 213915 seeks approval to market "Mylan ANDA Products" (Compl. ¶9). These are purported generic versions of Bridion® (sugammadex) Injection, in 200 mg/2 mL and 500 mg/5 mL strengths (Compl. ¶9).

Functionality and Market Context

The active ingredient in the accused products is identified as sugammadex (Compl. ¶49). The complaint defines sugammadex as 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin (Compl. ¶37). The function of the accused products is to reverse neuromuscular blockade induced by certain anesthetic agents during surgery (Compl. ¶46). The complaint characterizes the branded version, Bridion®, as a "first-in-class drug" and a "significant advance" in its field (Compl. ¶¶40-41).

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 |
|:----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 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|:----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |:-----------------------|:--------------------|
| 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; with the exclusion of [a list of 7 specific prior art compounds]. | The Mylan ANDA Products contain the active ingredient sugammadex, which the complaint identifies as 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin. The complaint alleges this specific compound is encompassed by the structure recited in Claim 1. | ¶37, ¶49, ¶53 | col. 4:51-53; col. 9:1-4 |
| Note: The complaint does not contain a detailed element-by-element infringement analysis. The allegation is based on the identity of the active ingredient in the accused product. | The complaint states that in their Paragraph IV notice letter, Defendants "did not contest infringement of claims 1-5 and 11-14 of the '733 patent." | ¶54 | N/A |

• Identified Points of Contention:
  • Scope Questions: The complaint’s allegation that Defendants did not contest infringement of claims 1-5 and 11-14 raises the question of whether infringement of the asserted claims is a central point of dispute in this litigation (Compl. ¶54). The case may instead focus primarily on Defendants' asserted defenses of invalidity and/or unenforceability (Compl. ¶48).
  • Technical Questions: A primary technical question for the court will be whether the specific compound identified as sugammadex, 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin, falls within the literal scope of Claim 1. The '733 patent discloses this exact compound as a preferred embodiment (Example 4), which may support the plaintiff's infringement position ('733 Patent, col. 9:1-4).

V. Key Claim Terms for Construction

• The Term: "6-mercapto-cyclodextrin derivative"
• Context and Importance: This term defines the genus of chemical compounds covered by the patent. Its construction is fundamental to determining the overall scope of the claims. Practitioners may focus on this term because the breadth of the "derivative" definition could be a point of attack for a validity challenge based on written description or enablement.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification defines cyclodextrins broadly as "a class of cyclic molecules containing six or more a-D-glucopyranose units" and notes that derivatives according to Formula I "are highly active in vivo" ('733 Patent, col. 2:61-64, col. 3:25-27). This language could support a construction covering a wide range of modified cyclodextrins.
  • Evidence for a Narrower Interpretation: The specification also lists a number of "particularly preferred" embodiments, including the specific compound that constitutes sugammadex ('733 Patent, col. 4:51-64). A party arguing for a narrower scope might point to the specific examples and the explicit exclusion of seven other derivatives from Claim 1 as evidence that the invention is limited to a smaller, more specific set of compounds.

VI. Other Allegations

• Indirect Infringement: The complaint alleges Defendants will induce infringement by marketing their ANDA products with a product label that includes instructions for administering the drug in a manner that will directly infringe the '733 patent (Compl. ¶60). It further alleges contributory infringement, stating the Mylan ANDA products are especially made for infringing use and are not staple articles suitable for substantial noninfringing use (Compl. ¶62).
• Willful Infringement: Willfulness is alleged based on Defendants having "full knowledge of the '733 patent" through the ANDA and Paragraph IV notice process (Compl. ¶65). The complaint asserts Defendants acted "without a reasonable basis for believing that they would not be liable for direct infringement" and filed their ANDA "without adequate justification" for their assertions of invalidity and non-infringement (Compl. ¶65).

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

• A central question appears to be one of patent validity. Given the complaint's allegation that Defendants did not contest infringement of several key claims, the litigation will likely focus on whether Defendants can prove by clear and convincing evidence that the asserted claims of the '733 patent are invalid, potentially on grounds of obviousness or lack of adequate written description for the claimed genus.
• Another key issue will be one of objective reasonableness. The court will likely need to evaluate the strength and basis of Defendants' invalidity and unenforceability defenses. The outcome of this analysis will be critical not only for the underlying infringement case but also for determining whether Defendants’ conduct was willful and whether the case is "exceptional" for the purpose of awarding attorneys' fees.