Par Pharmaceutical, Inc. v. Alkem Laboratories Ltd.

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Par Pharmaceutical, Inc. (New York) and Endo Par Innovation Co, LLC (Delaware)
  • Defendant: Alkem Laboratories Ltd. (India)
  • Plaintiff’s Counsel: Dechert LLP
• Case Identification: 2:23-cv-00400, E.D. Tex., 09/01/2023
• Venue Allegations: Venue is alleged to be proper because Defendant is a foreign corporation and is subject to personal jurisdiction in the district based on its Abbreviated New Drug Application (ANDA) filing seeking to market products throughout the United States, including Texas.
• Core Dispute: Plaintiff alleges that Defendant's method for manufacturing generic varenicline tartrate tablets, a smoking cessation drug, infringes a patent covering a novel process for removing potentially carcinogenic impurities.
• Technical Context: The technology addresses the critical need to purify varenicline tartrate by removing N-nitroso-varenicline impurities to levels that meet stringent FDA safety standards, a problem that led to the recall of the original brand-name drug, CHANTIX®.
• Key Procedural History: The original brand-name drug was withdrawn from the market in 2021 due to high impurity levels. Plaintiff subsequently developed a purification technology, obtained FDA approval for its own varenicline product, and secured the patent-in-suit. The complaint alleges that Defendant, after receiving multiple notice letters, is launching a generic product that must meet the same FDA impurity standards, allegedly by using the patented method.

Case Timeline

Date	Event
2020-09-01	FDA establishes acceptable daily intake limit for nitrosamine impurities in varenicline
2021-07-01	Pfizer withdraws CHANTIX® from the market due to high impurity levels
2021-08-11	FDA approves Plaintiff's ANDA for varenicline tartrate tablets
2022-03-11	Priority date for U.S. Patent No. 11,717,524
2023-05-17	Plaintiff sends first notice letter to Defendant regarding related patent
2023-06-07	USPTO issues Notice of Allowance for the '524 Patent application
2023-08-08	U.S. Patent No. 11,717,524 issues
2023-08-23	FDA approves Defendant's ANDA for generic varenicline tartrate tablets
2023-08-23	Plaintiff sends second notice letter to Defendant regarding the newly-issued '524 Patent
2023-09-01	Complaint filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 11,717,524 - Varenicline Compound and Process of Manufacture Thereof

• Patent Identification: U.S. Patent No. 11,717,524, "Varenicline Compound and Process of Manufacture Thereof," issued August 8, 2023.

The Invention Explained

• Problem Addressed: The patent's background section notes that the smoking cessation drug varenicline tartrate (marketed as CHANTIX®) was withdrawn from the market due to an "unacceptable level of nitrosamine impurities," creating a need for a version of the active pharmaceutical ingredient (API) with acceptably low impurity levels (’524 Patent, col. 1:50-57).
• The Patented Solution: The invention is a purification process, specifically an "acid-base treatment," to remove these nitrosamine impurities from the varenicline free base (’524 Patent, col. 13:15-19). The process functions by converting the basic varenicline into a salt using an acid, causing it to dissolve in an aqueous solution. The non-basic nitrosamine impurities do not form a salt and remain in a separate organic solvent layer, allowing for their removal through physical separation (’524 Patent, col. 21:20-31; Fig. 1).
• Technical Importance: This purification method was technically significant because it provided a viable pathway to produce varenicline that meets the FDA's stringent safety standards for carcinogenic impurities, enabling the drug to be reintroduced to the market (Compl. ¶¶17, 27, 31).

Key Claims at a Glance

• The complaint asserts representative independent claim 1 and reserves the right to assert other claims (Compl. ¶¶54, 56).
• The essential elements of independent claim 1 are:
  • A method of making a varenicline tartrate tablet comprising less than 50 ppm of nitrosamine impurities.
  • The method comprises: (a) mixing varenicline free base with tartaric acid to form varenicline tartrate.
  • The method further comprises: (b) a means for reducing the nitrosamine impurities to less than 50 ppm per tablet.
  • The means is defined as comprising an "acid-base treatment."

III. The Accused Instrumentality

Product Identification

• Defendant Alkem's generic varenicline tartrate tablets in 0.5 mg and 1 mg dosage strengths, and the process by which they are manufactured (Compl. ¶41).

Functionality and Market Context

• The complaint alleges that for Alkem to obtain FDA approval, its generic varenicline tablets must contain N-nitroso-varenicline impurities below the FDA's acceptable daily intake limit, which translates to 18.5 parts per million (ppm) (Compl. ¶¶20, 43).
• The complaint asserts that the difficulty of achieving this low impurity level is substantial, noting that the original manufacturer, Pfizer, was unable to reformulate its billion-dollar product to meet the new standard (Compl. ¶31). Plaintiff alleges that its patented method is one of the "only commercially-viable methods" to achieve the required purity (Compl. ¶43). The complaint includes a table from an FDA analysis to illustrate the dramatic difference in impurity levels between the withdrawn Pfizer product (155-474 ppm) and Plaintiff's own product (3 ppm), which uses the patented technology (Compl. p. 10).

IV. Analysis of Infringement Allegations

'524 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of making a varenicline tartrate tablet comprising less than 50 ppm of nitrosamine impurities...	The complaint alleges that to secure FDA approval, Defendant's product must have impurity levels below the FDA's 18.5 ppm limit, which is less than the claimed 50 ppm threshold.	¶43	col. 21:1-9
(a) mixing varenicline free base with tartaric acid to form varenicline tartrate	The complaint cites the FDA's public database as confirmation that the active pharmaceutical ingredient in Defendant's tablets is varenicline tartrate, which is formed by this process.	¶55.A	col. 2:33-39
(b) means for reducing the nitrosamine impurities to less than 50 ppm per tablet as measured by LC-ESI-HRMS Method; wherein the means comprises an acid-base treatment.	The complaint alleges on information and belief that Defendant must be using the patented acid-base treatment method, or an equivalent, because it is among the only commercially viable ways to achieve the required low impurity levels.	¶¶43, 53	col. 21:20-31

• Identified Points of Contention:
  • Scope Questions: A central issue will be the scope of the means-plus-function element in Claim 1(b), "means for reducing the nitrosamine impurities." The infringement analysis will depend on how the court defines the corresponding "acts" described in the patent specification for performing this function.
  • Technical Questions: The primary technical question is what manufacturing process Defendant actually uses. The complaint is based on inference, alleging that because Defendant's product meets the FDA's strict impurity standard, it must use Plaintiff's patented method (Compl. ¶53). The case will likely depend on evidence obtained during discovery regarding the specific steps of Defendant's confidential manufacturing process.

V. Key Claim Terms for Construction

• The Term: "means for reducing the nitrosamine impurities... wherein the means comprises an acid-base treatment" (Claim 1)
• Context and Importance: This term is a means-plus-function limitation governed by 35 U.S.C. § 112(f). Its construction is critical because it will define the specific steps an accused process must perform to infringe. Practitioners may focus on this term because the outcome of the infringement analysis will depend entirely on whether the acts disclosed in the patent are the same as, or equivalent to, the acts performed by the defendant's manufacturing process.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: A party could argue the term should not be limited to a single embodiment, pointing to general statements that the invention is an "acid-base treatment to remove nitrosamine impurities" (’524 Patent, col. 13:15-19).
  • Evidence for a Narrower Interpretation: The patent discloses a specific set of corresponding acts for this means. Claim 6, for example, defines the "acid-base treatment" as a three-step process: (a) converting the varenicline into a salt in an aqueous solution, (b) extracting the impurities with an organic solvent, and (c) isolating the purified varenicline by adding a base (’524 Patent, Claim 6). This multi-step, liquid-liquid extraction process, also illustrated in Figure 1, may be construed as the definitive "acts" corresponding to the claimed "means."

VI. Other Allegations

• Indirect Infringement: The complaint makes a general allegation of induced infringement, stating Defendant has acted "with full knowledge of the '524 patent" to "induce and encourage others to do so" (Compl. ¶58). Because the patent claims a method of manufacture, direct infringement liability under 35 U.S.C. § 271(g) would arise from the importation of a product made by the patented process, with the direct infringer being the importer (potentially Alkem itself).
• Willful Infringement: The complaint alleges that Defendant had pre-suit knowledge of the '524 Patent and its relevance. It cites multiple notice letters sent to Defendant, including one on August 23, 2023, advising of the newly-issued patent, and alleges that Defendant ignored these communications (Compl. ¶¶39, 46, 57).

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

• A central issue will be one of evidence and discovery: What are the precise steps of Defendant's confidential manufacturing process? The complaint is filed on information and belief, making the discovery of Defendant's ANDA and related manufacturing documents the pivotal next step in the litigation.
• The case will also turn on a question of claim scope and infringement: What are the specific "acts" corresponding to the "means for reducing... impurities" as claimed in the patent? The court's construction of this means-plus-function limitation will set the stage for a technical comparison to determine if Defendant's process performs the identical function in the same or an equivalent way.