DCT
2:24-cv-03206
Merck Sharp & Dohme BV v. Hikma Pharma USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme B.V. (Netherlands) and Merck Sharp & Dohme LLC (New Jersey)
- Defendant: Hikma Pharmaceuticals USA Inc. (Delaware)
- Plaintiff’s Counsel: GIBBONS P.C.
- Case Identification: 2:24-cv-03206, D.N.J., 03/15/2024
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant maintains a regular and established place of business in the state, specifically its U.S. headquarters, and has committed acts related to the alleged infringement within the district.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for a generic version of the anesthetic reversal agent Bridion® constitutes an act of patent infringement under the Hatch-Waxman Act.
- Technical Context: The technology concerns chemically modified cyclodextrins designed to encapsulate and neutralize neuromuscular blocking agents, thereby reversing their effects in patients after surgery.
- Key Procedural History: The complaint notes that the patent-in-suit, RE44,733, is a reissue of U.S. Patent No. 6,670,340. The patent's term was extended via a Patent Term Extension (PTE) to January 27, 2026. The validity of a portion of this extension was challenged in prior litigation, IN RE SUGAMMADEX, where the court upheld the full extension. An appeal of that judgment is currently pending before the Federal Circuit.
Case Timeline
| Date | Event |
|---|---|
| 1999-11-29 | RE'733 Patent Priority Date |
| 2003-12-30 | Original U.S. Patent No. 6,670,340 Issued |
| 2014-01-28 | RE'733 Patent Reissued |
| 2015-12-15 | Plaintiff's Bridion® (sugammadex) NDA Approved |
| 2020-02-04 | PTO Issues Final Determination on Patent Term Extension |
| 2024-02-02 | Defendant Sends Paragraph IV Notice Letter to Plaintiff |
| 2024-03-15 | 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"
The Invention Explained
- Problem Addressed: The patent's background describes the shortcomings of traditional agents used to reverse surgically-induced paralysis (neuromuscular block) (RE’733 Patent, col. 1:53-61). These agents, primarily acetylcholinesterase inhibitors, non-selectively increase acetylcholine levels throughout the body, leading to significant side effects like bradycardia and nausea that require co-administration of other drugs (RE’733 Patent, col. 2:1-12). They are also often ineffective at reversing a "profound block" of neuromuscular function (RE’733 Patent, col. 2:13-28).
- The Patented Solution: The invention proposes a different mechanism using specific modified cyclodextrins as "chemical chelators" (RE’733 Patent, col. 2:29-32). These molecules have a cage-like structure that is designed to directly capture and encapsulate the neuromuscular blocking drug, forming a stable complex that inactivates the drug and is then cleared from the body (RE’733 Patent, col. 2:32-35; Abstract). This targeted sequestration avoids the systemic side effects of older reversal agents.
- Technical Importance: This "guest-host" complexing approach represented a new paradigm for reversing neuromuscular blockade, offering the potential for faster, more predictable reversal without the side-effect profile of earlier agents (Compl. ¶23).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶36).
- The essential elements of independent claim 1 are:
- A 6-mercapto-cyclodextrin derivative having a specific chemical structure defined by general formula I
- The core cyclodextrin ring size is defined by m+n=7 or 8
- A linker group R, which is a (C1-6)alkylene or a phenylene-containing group
- A terminal functional group X, selected from a Markush group including COOH (a carboxylic acid)
- Or pharmaceutically acceptable salts thereof
- The claim explicitly excludes a list of eight specific, known cyclodextrin derivatives.
- The complaint’s general allegations of infringing "one or more claims" suggest it reserves the right to assert other independent or dependent claims (Compl. ¶39).
III. The Accused Instrumentality
Product Identification
- Defendant’s Abbreviated New Drug Application No. 218727 is for a "purported generic version of sugammadex sodium EQ 200 mg base/2 ml solution" (Compl. ¶5). This product is referred to as the "HUSA ANDA Product."
Functionality and Market Context
- The HUSA ANDA Product contains the active ingredient sugammadex (Compl. ¶29). Sugammadex is the active ingredient in Plaintiff's commercial product, Bridion®, which is used for the reversal of neuromuscular blockade induced by rocuronium and vecuronium in adults undergoing surgery (Compl. ¶21). The complaint characterizes Bridion® as a "first-in-class drug" and a "significant advance in the field of anesthesiology" because its mechanism of encapsulating neuromuscular blocking agents avoids many side effects of prior reversal agents (Compl. ¶22-23).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
- Claim Chart Summary: The complaint’s infringement theory is based on the chemical identity of the active ingredient in Defendant's ANDA product. It alleges that sugammadex, the active ingredient, is a compound that falls within the scope of the asserted claims. The complaint states that Defendant, in its Paragraph IV notice letter, "did not contest infringement of the claims of the the RE’733 patent" (Compl. ¶37). The following chart summarizes the infringement allegations for claim 1 against sugammadex, which the patent identifies as 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin (Compl. ¶18; RE'733 Patent, col. 4:52-53).
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A 6-mercapto-cyclodextrin derivative having the general formula I | The active ingredient of the HUSA ANDA Product, sugammadex, is alleged to be a 6-mercapto-cyclodextrin derivative. | ¶18, ¶29, ¶36 | col. 3:5-19 |
| wherein m is 0-7 and n is 1-8 and m+n=7 or 8 | Sugammadex is a γ-cyclodextrin derivative, for which m=0 and n=8, satisfying the m+n=8 requirement. | ¶18 | col. 4:42-44 |
| R is (C1-6)alkylene ... | In sugammadex, the linker group between the sulfur atom and the terminal functional group is an ethyl group (-CH₂-CH₂-), which is a (C1-6)alkylene. | ¶18 | col. 4:20-27 |
| X is COOH ... or tetrazol-5-yl | In sugammadex, the terminal functional group is a carboxylic acid (COOH), which is an enumerated option for X in the claim. | ¶18 | col. 3:13-14 |
| or pharmaceutically acceptable salts thereof | The HUSA ANDA Product is a sugammadex sodium salt, which is alleged to be a pharmaceutically acceptable salt. | ¶5 | col. 3:18-19 |
| with the exclusion of [list of 8 compounds] | Sugammadex is not one of the eight specific compounds listed in the claim's exclusion clause. | ¶36 | col. 3:21-49 |
- Identified Points of Contention:
- Infringement Scope: The complaint alleges that Defendant did not contest infringement in its notice letter (Compl. ¶37). This suggests the primary dispute may not be over whether the chemical structure of sugammadex literally reads on the claims, but rather on other issues such as patent validity or the enforceability of the patent term.
- Patent Term: The complaint highlights Defendant's acknowledgment of the In re Sugammadex litigation and its assertion that the district court "erred" in upholding the patent term extension (Compl. ¶30). This indicates a central point of contention will be the legal status and duration of the patent term itself, which is currently under appeal.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail to identify specific claim construction disputes, particularly given the allegation that infringement was not contested by the Defendant. However, based on the technology, certain terms are fundamental to defining the scope of the claims.
- The Term: "6-mercapto-cyclodextrin derivative"
- Context and Importance: This term defines the core chemical scaffold of the invention. Its construction is critical for determining the boundaries of the claimed class of compounds. Practitioners may focus on this term to ascertain whether any potential impurities or variants in an accused product fall outside the claimed genus.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification introduces cyclodextrins as a general class of "cyclic molecules containing six or more α-D-glucopyranose units" (RE’733 Patent, col. 2:60-63), which could support a construction encompassing a range of related structures.
- Evidence for a Narrower Interpretation: The claim itself provides a precise chemical structure in "general formula I" (RE’733 Patent, col. 3:5-19), and the specification provides specific synthesis examples (e.g., Examples 1-19). This may support a construction limited to compounds that strictly conform to that formula and can be made by the disclosed methods.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). The factual basis is that Defendant will knowingly and intentionally sell its ANDA product with a product label that instructs healthcare professionals to administer it in a manner that infringes the patent claims (Compl. ¶43).
- Willful Infringement: The complaint alleges willful infringement based on Defendant's knowledge of the RE’733 patent, allegedly evidenced by its Paragraph IV certification and notice letter, and its continued intent to market the accused product prior to patent expiration (Compl. ¶46).
VII. Analyst’s Conclusion: Key Questions for the Case
Given that literal infringement appears to be a secondary issue, the case will likely center on the following questions:
A core issue will be one of patent enforceability and term: Can the Defendant succeed in its challenge to the validity of the Patent Term Extension for the RE’733 patent, which is currently on appeal from a separate litigation? The resolution of this issue will determine whether the patent is enforceable until its extended expiration date of January 27, 2026.
A second key question will be one of patent validity: As this case arises from a Paragraph IV certification, Defendant has necessarily asserted that the RE’733 patent is invalid and/or unenforceable. The case will therefore turn on the patent’s ability to withstand challenges under 35 U.S.C. §§ 102, 103, and/or 112, the specific grounds for which will emerge in subsequent pleadings.