DCT
2:20-cv-02787
Merck Sharp & Dohme BV v. Mankind Pharma Ltd
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme B.V. (Netherlands) and Organon USA Inc. (New Jersey)
- Defendant: Mankind Pharma Limited (India) and LifeStar Pharma LLC (Delaware)
- Plaintiff’s Counsel: Gibbons P.C.
- Case Identification: 2:20-cv-02787, D.N.J., 03/13/2020
- Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey because Defendant LifeStar has its principal place of business in the district. Venue is alleged to be proper for Defendant Mankind Pharma Limited, a foreign entity, in any judicial district. Personal jurisdiction over Mankind is alleged based on its U.S. subsidiary's activities in New Jersey and purposeful availment of the jurisdiction.
- Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the anesthetic reversal agent Bridion® (sugammadex) constitutes an act of infringement of two U.S. patents.
- Technical Context: The technology concerns modified cyclodextrin molecules designed to act as encapsulating agents to reverse the effects of neuromuscular blocking drugs used during surgical procedures.
- Key Procedural History: This is a Hatch-Waxman action triggered by Defendants' ANDA filing and Paragraph IV certification. The complaint notes that U.S. Patent No. RE44,733 is a reissue of U.S. Patent No. 6,670,340. It also states that on February 4, 2020, the U.S. Patent and Trademark Office determined that the '733 patent is eligible for a five-year Patent Term Extension (PTE), which would extend its expiration to January 27, 2026.
Case Timeline
| Date | Event |
|---|---|
| 1999-11-29 | Earliest Priority Date for '733 and '527 Patents |
| 2003-12-30 | Issue Date of U.S. Patent No. 6,670,340 (original of '733 Patent) |
| 2005-09-27 | Issue Date of '527 Patent |
| 2014-01-28 | Issue Date of '733 Reissue Patent |
| 2015-12-15 | FDA Approval of Bridion® New Drug Application (NDA) |
| 2020-01-31 | Date of Mankind's Notice Letter regarding ANDA filing |
| 2020-02-04 | PTO Final Determination on Patent Term Extension for '733 Patent |
| 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 January 28, 2014)
The Invention Explained
- Problem Addressed: The patent describes the limitations of conventional agents used to reverse drug-induced neuromuscular blockade in surgical patients. These agents, acetylcholinesterase (AChE) inhibitors, can cause significant side effects like bradycardia and are often ineffective at reversing a very deep ("profound") level of blockade (RE44,733 Patent, col. 2:1-24).
- The Patented Solution: The invention is a class of modified cyclodextrin derivatives that act as "chemical chelators" or "sequestrants" ('733 Patent, col. 2:26-30). Instead of affecting the nervous system, these molecules are designed with a three-dimensional cavity that physically encapsulates and binds to neuromuscular blocking agents in the bloodstream. This direct complexation inactivates the blocking agents, allowing for a rapid and complete reversal of muscle relaxation without the side effects associated with AChE inhibitors ('733 Patent, col. 2:30-43).
- Technical Importance: This technology represents a distinct mechanism of action for reversing neuromuscular blockade, offering the potential for faster, more predictable recovery from anesthesia and the ability to reverse even profound blockade, which was previously difficult to manage (Compl. ¶40).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶52).
- The essential elements of claim 1 are:
- A 6-mercapto-cyclodextrin derivative having a specified general formula
- wherein the cyclodextrin ring size is defined by m+n=7 or 8
- wherein side chains (R) are attached via a sulfur atom and are defined as (C₁-₆)alkylene, optionally substituted with OH groups, or a phenylene-containing group
- wherein the side chains are terminated by an ionic group (X), such as COOH
- The complaint notes that in their Paragraph IV notice letter, Defendants did not contest infringement of claims 1-5, 9, 11-14, 20, and 21 (Compl. ¶53).
U.S. Patent No. 6,949,527 - "6-Mercapto-Cyclodextrin Derivatives: Reversal Agents For Drug-Induced Neuromuscular Block" (issued September 27, 2005)
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the '733 Patent: the side effects and limited efficacy of existing agents for reversing surgical muscle relaxation ('527 Patent, col. 2:1-24).
- The Patented Solution: The invention, as described in the specification, is identical to that of the '733 Patent. It discloses the use of modified cyclodextrins as sequestering agents that form guest-host complexes with neuromuscular blocking drugs, thereby neutralizing their effects ('527 Patent, col. 2:26-40).
- Technical Importance: As part of the same patent family as the '733 patent, this invention contributed to the same advance in anesthesiology by providing a novel, targeted mechanism for reversing neuromuscular blockade (Compl. ¶40).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 4 (Compl. ¶67).
- The essential elements of claim 4 are:
- A method of treatment of a patient with a neuromuscular blocking agent
- comprising the step of reversing the drug-induced neuromuscular block
- by administering an effective amount of a reversal agent
- wherein the reversal agent is selected from a group of specific modified cyclodextrins, including 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin
- The complaint states that Defendants did not contest infringement of claims 4 and 5 in their notice letter (Compl. ¶68).
III. The Accused Instrumentality
Product Identification
- Defendants’ proposed generic versions of Bridion® (sugammadex) Injection, 200 mg/2 mL and 500 mg/5 mL, as described in ANDA No. 214230 ("Mankind ANDA Products") (Compl. ¶7).
Functionality and Market Context
- The active pharmaceutical ingredient in the accused products is sugammadex (Compl. ¶48). The complaint identifies sugammadex as 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin (Compl. ¶32).
- The product is intended to be used for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults undergoing surgery (Compl. ¶45).
- The complaint describes the mechanism of sugammadex as directly encapsulating, binding, and inactivating neuromuscular blocking agents, thereby reducing the amount available to bind to receptors and reversing the muscle blockade (Compl. ¶39).
- Plaintiffs position the branded version of the drug, Bridion®, as a "first-in-class drug" and a "significant advance" in anesthesiology (Compl. ¶39, ¶40). The accused generic product would compete with this branded product.
IV. Analysis of Infringement Allegations
The complaint references Exhibit C, the prescribing information for Bridion®, which serves as a basis for the allegations of induced infringement (Compl. ¶59, ¶74).
RE44,733 Patent 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 and n is 8... R is (C₂)-alkylene... X is COOH... | The Mankind ANDA Products contain sugammadex as the active ingredient. Sugammadex is the specific molecule 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin. | ¶48, ¶52 | col. 8:46-48 |
Identified Points of Contention
- Scope Questions: The complaint alleges that Defendants did not contest infringement of the asserted composition claims (Compl. ¶53). This suggests the primary dispute may concern patent validity rather than infringement. However, a potential issue could arise regarding whether any impurities or different salt forms in the Defendants' product place it outside the literal scope of the asserted claims.
- Technical Questions: The central factual question for direct infringement is whether the chemical compound in Defendants' ANDA product is, in fact, the claimed 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin. The complaint's allegation that infringement is uncontested suggests this may not be a point of dispute.
6,949,527 Patent Infringement Allegations
| Claim Element (from Independent Claim 4) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treatment... comprising the step... of reversing the drug-induced neuromuscular block by administration of an effective amount of... a reversal agent... | The proposed product labeling for the Mankind ANDA Products will instruct healthcare professionals to administer the product for the purpose of reversing neuromuscular blockade. | ¶59, ¶73, ¶74 | col. 2:26-30 |
| ... the reversal agent selected from the group consisting of... 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin... | The active ingredient in the Mankind ANDA Products to be administered is sugammadex, which is 6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin. | ¶48, ¶67 | col. 8:46-48 |
Identified Points of Contention
- Scope Questions: This is a method claim, and infringement is based on inducement. The key question will be whether the language in Defendants' proposed product labeling instructs users to perform all steps of the claimed method. The complaint alleges the proposed label is "substantially similar" to the Bridion® label (Compl. ¶74; Exhibit C).
- Technical Questions: The primary evidentiary question for induced infringement will be the content of Defendants' proposed product label. The court will need to compare the instructions on that label with the limitations of the asserted method claims.
V. Key Claim Terms for Construction
The Term: "6-per-deoxy-6-per-(2-carboxyethyl)thio-γ-cyclodextrin" ('733 Patent, Claim 1; '527 Patent, Claim 4)
- Context and Importance: This term defines the chemical structure of the active ingredient. While the complaint alleges infringement is not contested, the precise scope of this term could become relevant if Defendants argue their product contains a different salt, isomer, or purity profile that falls outside a proper construction of the claim.
- Evidence for a Broader Interpretation: The claim itself does not specify a particular salt form (e.g., sodium salt) or purity level, which may support a construction covering the molecule regardless of its associated counter-ion or the presence of impurities.
- Evidence for a Narrower Interpretation: Defendants could point to the specific embodiment in the patent, "Example 4," which describes the synthesis of the "sodium salt" of the compound, to argue the claims should be interpreted more narrowly ('733 Patent, col. 8:46-48).
The Term: "reversing the drug-induced neuromuscular block" ('527 Patent, Claim 4)
- Context and Importance: This term defines the purpose and outcome of the claimed method. Its construction is critical for determining what actions the accused product's label must instruct users to perform to induce infringement.
- Evidence for a Broader Interpretation: The patent specification describes the invention broadly as providing "reversal of drug-induced neuromuscular block" without quantifying the required degree of reversal ('527 Patent, Abstract). This may support a construction covering any clinically significant reversal.
- Evidence for a Narrower Interpretation: The specification emphasizes the invention's ability to reverse "profound block" as a key advantage over the prior art ('527 Patent, col. 2:16-20). A party could argue that "reversing" should be construed to require this higher level of efficacy, potentially limiting the claim's scope.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. The inducement allegation is based on the assertion that Defendants' proposed product labeling will instruct healthcare providers to administer the product in a manner that directly infringes the method claims and uses the claimed composition (Compl. ¶59, ¶74). The contributory infringement allegation is based on the assertion that the Mankind ANDA Products are not staple articles of commerce and are especially made for use in an infringing manner (Compl. ¶61, ¶76).
- Willful Infringement: Willfulness is alleged for both the '733 and '527 patents. The complaint bases this on Defendants having filed their ANDA with full knowledge of the patents-in-suit and without a reasonable basis for believing they would not be liable for infringement (Compl. ¶64, ¶79).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central question will be one of patent validity. As the complaint alleges that Defendants did not contest infringement of the asserted claims in their Paragraph IV notice letter, the litigation will likely focus on Defendants' ability to prove, by clear and convincing evidence, that the asserted claims of the '733 and '527 patents are invalid on grounds such as obviousness or lack of adequate written description.
- A key procedural issue will be the statutory remedy under the Hatch-Waxman Act. A primary goal for the Plaintiffs is to secure a court order preventing the FDA from granting final approval to Defendants' ANDA until after the expiration of the '733 patent, inclusive of its anticipated five-year patent term extension.
- A secondary question will be one of induced infringement scope. For the '527 method patent, the court will need to determine if the instructions in Defendants' final, FDA-approved product labeling direct medical professionals to perform the specific steps recited in the asserted method claims, thereby giving rise to induced infringement.