Merck Sharp & Dohme BV v. Gland Pharma Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Merck Sharp & Dohme B.V. (Netherlands) and Organon USA Inc. (New Jersey)
  • Defendant: Gland Pharma Limited (India)
  • Plaintiff’s Counsel: GIBBONS P.C.
• Case Identification: 2:20-cv-02750, D.N.J., 03/12/2020
• Venue Allegations: Venue is asserted on the basis that the defendant, Gland Pharma Limited, is a foreign entity that may be sued in any judicial district.
• Core Dispute: Plaintiffs allege that Defendant's 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 molecule and its use.
• Technical Context: The technology concerns modified cyclodextrin derivatives used as reversal agents for neuromuscular blocking agents, which are administered during surgical anesthesia to induce muscle relaxation.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's notification to Plaintiffs of its ANDA filing, which included a Paragraph IV certification asserting the patent-in-suit is invalid, unenforceable, or not infringed. The patent-in-suit, RE44,733, is a reissue of U.S. Patent No. 6,670,340 and has received a five-year patent term extension (PTE) from the USPTO. The complaint was filed within the 45-day statutory window, triggering an automatic 30-month stay of FDA approval for the defendant's generic product.

Case Timeline

Date	Event
1999-11-29	Priority Date for U.S. Patent No. RE44,733
2003-12-30	Issue Date for original U.S. Patent No. 6,670,340
2014-01-28	Issue Date for U.S. Reissue Patent No. RE44,733
2015-12-15	FDA approves New Drug Application for Plaintiffs' Bridion®
2020-01-31	Date of Defendant's notice letter regarding its ANDA filing
2020-02-04	USPTO issues Notice of Final Determination for 5-year PTE
2020-03-12	Complaint Filing Date
2026-01-27	Alleged expiration date of the '733 patent with PTE

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 describes the challenge of reversing drug-induced neuromuscular blockade after surgery (Compl. ¶25). Traditional reversal agents, known as anticholinesterases, can cause significant side effects like bradycardia and hypotension by non-selectively increasing levels of the neurotransmitter acetylcholine throughout the body (’733 Patent, col. 2:2-10). These agents are also unable to reliably reverse a "profound block," where neuromuscular function is completely suppressed (’733 Patent, col. 2:15-21).
• The Patented Solution: The patent discloses a class of 6-mercapto-cyclodextrin derivatives that act as "chemical chelators" (’733 Patent, col. 2:28-34). Instead of affecting neurotransmitter levels, these large, ring-like molecules are designed to directly capture and encapsulate neuromuscular blocking agent (NMBA) molecules in the bloodstream, forming a stable "guest-host complex" that inactivates the NMBA (’733 Patent, col. 2:30-34). This novel mechanism is described as avoiding the side effects of prior art agents (’733 Patent, col. 2:37-44). The general chemical structure of these derivatives is depicted in Formula I (’733 Patent, col. 3:5-15).
• Technical Importance: This approach represented a new paradigm for reversing neuromuscular blockade, offering the potential for faster, more reliable recovery, especially from deep blockade, without the adverse effects associated with anticholinesterase drugs (Compl. ¶¶25-26).

Key Claims at a Glance

• The complaint asserts infringement of one or more claims, with a specific focus on at least claim 1 (Compl. ¶38).
• Independent Claim 1 recites the core elements of the invention:
  • A 6-mercapto-cyclodextrin derivative defined by a specific chemical structure (Formula I)
  • The cyclodextrin ring size is defined as γ-cyclodextrin (m+n=8) or β-cyclodextrin (m+n=7)
  • A linker group "R" (an alkylene or phenylene chain) connects the cyclodextrin to a functional group "X"
  • The functional group "X" is selected from a list of chemical moieties including carboxyl (COOH) and sulfonyl (SO₂OH) groups
  • The claim includes pharmaceutically acceptable salts of the derivative
  • The claim explicitly excludes a list of eight specific cyclodextrin derivatives known from the prior art (’733 Patent, col. 19:1-44).
• The complaint notes that the defendant did not contest infringement of claims 1-3, 5, and 11-14 in its notice letter (Compl. ¶39).

III. The Accused Instrumentality

Product Identification

• Defendant Gland Pharma's proposed generic versions of Bridion® (sugammadex) Injection, in 200 mg/2 mL and 500 mg/5 mL strengths, for which it submitted ANDA No. 214364 to the FDA (Compl. ¶5).

Functionality and Market Context

• The complaint alleges that Gland's ANDA products contain sugammadex as the active ingredient (Compl. ¶34). Sugammadex is the common name for the chemical compound 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin (Compl. ¶22).
• The Gland ANDA Products are intended for the same use as the reference drug Bridion®: the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults undergoing surgery (Compl. ¶31). As a generic, the product is intended to be a lower-cost, bioequivalent substitute for Bridion® (Compl. ¶28).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

Claim Chart Summary

The complaint alleges that the active ingredient in the Gland ANDA Products, sugammadex, is encompassed by at least claim 1 of the ’733 patent (Compl. ¶38). The following chart maps the chemical structure of sugammadex to the elements of claim 1.

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A 6-mercapto-cyclodextrin derivative having the general formula I	The accused product's active ingredient is sugammadex, identified as 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin, which is a 6-mercapto-cyclodextrin derivative.	¶¶22, 34, 38	col. 3:5-15
wherein m is 0-7 and n is 1-8 and m+n=7 or 8	Sugammadex is a derivative of γ-cyclodextrin, which has 8 glucose units (m+n=8). The "per" designation in its chemical name indicates all 8 primary hydroxyl groups are substituted (n=8, m=0).	¶22	col. 4:42-44
R is (C₁-₆)alkylene...	The chemical name "(2-carboxyethyl)thio" indicates the linker "R" is an ethyl group, which is a C₂ alkylene and falls within the definition of (C₁-₆)alkylene.	¶22	col. 4:20-27
X is COOH...	The chemical name "(2-carboxyethyl)thio" indicates the functional group "X" is a carboxyl group (COOH).	¶22	col. 19:22-24
or pharmaceutically acceptable salts thereof	The accused product is an injectable formulation, which is typically prepared as a pharmaceutically acceptable salt to ensure solubility and stability.	¶5	col. 6:46-52
with the exclusion of [list of 8 compounds]	The accused compound, a γ-cyclodextrin with a (2-carboxyethyl)thio side chain, is not among the eight specifically excluded compounds, which include β-cyclodextrin derivatives and a γ-cyclodextrin derivative with a different side chain (2-hydroxyethylthio).	¶¶22, 38	col. 19:30-44

Identified Points of Contention

• Scope Questions: Based on the complaint, the infringement allegation appears to rely on a direct mapping of the chemical structure of sugammadex onto the language of claim 1. The central dispute is therefore unlikely to be over the scope of the claim terms as they apply to the accused product.
• Technical Questions: The primary question for the court will not be whether sugammadex infringes, but whether the claims covering it are valid. The defendant's Paragraph IV certification asserts that the ’733 Patent is invalid and/or unenforceable (Compl. ¶33). The case will likely focus on Gland's arguments, presumably based on prior art, that the invention would have been obvious or lacked adequate written description at the time of filing.

V. Key Claim Terms for Construction

The Term: "(C₁-₆)alkylene"

• Context and Importance: This term defines the chemical linker (R) between the cyclodextrin core and the terminal functional group (X). The accused product's "ethyl" linker must fall within this definition for literal infringement. Practitioners may focus on this term to determine if any ambiguity in the specification or prosecution history could limit its scope, although for a simple structure like ethyl, this is a standard analysis.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification provides a clear and broad definition: "a branched or straight chain bivalent carbon radical containing 1-6 carbon atoms, such as methylene, ethylene (1,2-ethandiyl), propylene..." (’733 Patent, col. 4:20-27). This language supports a standard, inclusive definition.
  • Evidence for a Narrower Interpretation: The complaint and patent do not present obvious evidence for a narrower interpretation that would exclude a simple ethyl group. A defendant would need to develop an argument based on extrinsic evidence or a nuanced reading of the prosecution history, which is not detailed in the complaint.

The Term: "with the exclusion of"

• Context and Importance: Claim 1 is a composition claim with a negative limitation, carving out eight specific compounds. Infringement requires proving that the accused product, sugammadex, is not one of these excluded compounds.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation (of the claimed scope): The list of excluded compounds is precise and finite. The principle of expressio unius est exclusio alterius suggests that any compound not explicitly listed is intended to be covered if it meets the other claim limitations. The accused sugammadex is chemically distinct from the listed "6-per-deoxy-6-per-(2-hydroxyethylthio)-γ-cyclodextrin" (’733 Patent, col. 19:33-34), as "carboxyethyl" (in sugammadex) is not "hydroxyethyl."
  • Evidence for a Narrower Interpretation (of the claimed scope): A party could argue that the excluded compounds are merely exemplary of a broader, implicitly excluded class of compounds. However, such an argument faces a high bar, as negative limitations are typically interpreted as written. The complaint provides no basis for such an argument.

VI. Other Allegations

Indirect Infringement

• The complaint alleges active inducement of infringement under 35 U.S.C. § 271(b). The factual basis is the allegation that Gland will knowingly and intentionally encourage infringement by marketing its ANDA product with a product label and instructions that direct healthcare professionals to use it in a manner that infringes the patent's claims (Compl. ¶45). Gland's knowledge and intent are alleged to be established by its filing of a Paragraph IV certification, which demonstrates awareness of the patent (Compl. ¶46).

Willful Infringement

• The complaint alleges that Gland's infringement is willful. This allegation is based on Gland's purported "full knowledge of the '733 patent" and its decision to seek FDA approval "without a reasonable basis for believing that it would not be liable for direct infringement" (Compl. ¶50). Plaintiffs also seek a declaration that the case is "exceptional" under 35 U.S.C. § 285, which would permit an award of attorneys' fees (Compl. ¶50).

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

• A core issue will be one of patent validity: given that the infringement allegation rests on a straightforward chemical structure match, the case will almost certainly pivot to whether the Defendant can prove, by clear and convincing evidence, that the asserted claims of the ’733 patent are invalid over the prior art, likely on grounds of obviousness.
• A key question for damages and fees will be one of objective reasonableness: did the Defendant's Paragraph IV certification, which asserts invalidity and non-infringement, rely on an objectively reasonable and good-faith basis? The answer to this question will determine its exposure to claims of willful infringement and a finding that the case is exceptional.