DCT

1:23-cv-00866

Par Pharmaceutical Inc v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00866, D. Del., 12/11/2023
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendant Zydus USA is subject to personal jurisdiction in the district and has previously consented to venue there in other patent litigations. Venue is alleged to be proper for Zydus Lifesciences as a foreign corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s generic varenicline tablets infringe patents related to novel manufacturing processes and compositions for purified varenicline with reduced levels of carcinogenic nitrosamine impurities.
  • Technical Context: The technology addresses the critical need for a safe supply of the smoking cessation drug varenicline after the branded version, CHANTIX®, was withdrawn from the market due to unacceptable levels of nitrosamine impurities.
  • Key Procedural History: The complaint states that after Pfizer withdrew CHANTIX® from the market, Plaintiff developed and received FDA approval for the first generic varenicline tablets meeting the FDA’s stringent nitrosamine impurity limits. Plaintiff alleges it sent multiple letters notifying Defendant of its patented technology, including after the application for the ’524 Patent received a Notice of Allowance. Defendant allegedly launched its accused generic product after receiving these notices but before the patent formally issued.

Case Timeline

Date Event
2022-03-11 ’524 and ’587 Patents Priority Date
2023-06-12 FDA approves Defendant's ANDA for generic varenicline tablets
2023-06-13 Defendant issues press release announcing imminent launch of accused tablets
2023-08-08 U.S. Patent No. 11,717,524 issues
2023-10-10 U.S. Patent No. 11,779,587 issues
2023-12-11 First Amended Complaint filed

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

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The patent’s background section describes that the smoking cessation drug varenicline (marketed as CHANTIX®) was withdrawn from the market due to an "unacceptable level of nitrosamine impurities" (’524 Patent, col. 1:52-57).
  • The Patented Solution: The invention is a process for purifying varenicline to remove these impurities. The process employs an "acid-base treatment" where crude varenicline free base, contaminated with nitrosamines, is mixed with an acid in an aqueous solution to form a varenicline salt. Because the nitrosamine impurities are not basic, they do not form salts and can be separated by extraction into an organic solvent. The purified varenicline is then recovered from the aqueous salt solution (’524 Patent, Fig. 1; col. 2:30-34).
  • Technical Importance: This purification technology enabled the creation of varenicline tablets with nitrosamine levels low enough to meet FDA safety standards, addressing a significant public health need after the market withdrawal of the branded drug (Compl. ¶¶ 26-28).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶33).
  • Essential elements of claim 1 include:
    • 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) means for reducing the nitrosamine impurities to less than 50 ppm per tablet.
    • The "means" is defined as comprising an "acid-base treatment."

U.S. Patent No. 11,779,587 - “Varenicline Compound and Process of Manufacture Thereof,” issued October 10, 2023

The Invention Explained

  • Problem Addressed: Similar to the ’524 Patent, the background addresses the problem of "unacceptable level of nitrosamine impurities in CHANTIX®" and the corresponding need for a varenicline active pharmaceutical ingredient ("API") that meets safety standards (’587 Patent, col. 1:52-57).
  • The Patented Solution: Rather than claiming the method, this patent claims the purified product itself. The invention is a pharmaceutical composition in tablet form containing varenicline tartrate, characterized by having very low levels of specific impurities: less than 50 parts per million (ppm) of N-nitroso-varenicline and less than 0.15% by weight of a "diamide" impurity (’587 Patent, Abstract; col. 69:37-47). The specification indicates these purity levels are achieved through the manufacturing processes also described in the ’524 Patent (’587 Patent, Fig. 1).
  • Technical Importance: This patent provides protection for the low-impurity varenicline composition, creating a potential barrier to competitors who develop a product with the same purity profile (Compl. ¶¶ 34-35).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶35).
  • Essential elements of claim 1 include:
    • A pharmaceutical composition in the form of a tablet, comprising varenicline tartrate.
    • The tablet comprises less than 50 ppm of N-nitroso-varenicline impurity.
    • The tablet also comprises less than 0.15% (w/w) of diamide impurity.

III. The Accused Instrumentality

  • Product Identification: The accused products are Defendant’s generic Varenicline Tartrate Tablets in 0.5 mg and 1 mg dosage strengths (the "Accused Tablets") (Compl. ¶37).
  • Functionality and Market Context: The Accused Tablets are generic versions of the prescription drug used for smoking cessation (Compl. ¶37). The complaint alleges that to be sold in the U.S., these tablets must meet the FDA's acceptable daily intake limit for nitrosamine impurities, which translates to 18.5 ppm (Compl. ¶¶ 19, 46). The complaint presents a table of FDA laboratory analysis showing Plaintiff's product having nitrosamine levels of 3 ppm, whereas the withdrawn CHANTIX® product had levels up to 474 ppm (Compl. p. 9). Plaintiff alleges that the only commercially viable methods to achieve such low levels are its patented ones (Compl. ¶46).

IV. Analysis of 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... Third-party laboratory testing of the Accused Tablets allegedly showed nitrosamine levels below 2 ppm, which is less than the claimed 50 ppm limit. ¶54.B col. 69:17-19
(a) mixing varenicline free base with tartaric acid to form varenicline tartrate The Accused Tablets' approved labeling allegedly confirms that the active pharmaceutical ingredient is varenicline tartrate. ¶54.A col. 69:20-21
(b) means for reducing the nitrosamine impurities... wherein the means comprises an acid-base treatment. Plaintiff alleges on information and belief that Defendant uses its patented method because it is the only commercially viable way to achieve the required low impurity levels. ¶¶46, 53, 55 col. 69:22-26

  • Identified Points of Contention (’524 Patent):

    • Scope Questions: This claim includes a means-plus-function limitation ("means for reducing..."). A central legal question will be whether the specific steps in Defendant’s manufacturing process perform the claimed function and are structurally the same as or equivalent to the "acid-base treatment" described in the patent’s specification (’524 Patent, col. 69:40-50).
    • Technical Questions: A key evidentiary question is what manufacturing process Defendant actually uses. The complaint relies on inference, alleging that the low impurity levels in the Accused Tablets can only be achieved by using Plaintiff's patented method (Compl. ¶46). The case will likely depend on what is revealed in discovery regarding Defendant's actual purification techniques.

  • 11779587 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition in the form of a tablet, comprising varenicline tartrate... The approved prescribing information for the Accused Tablets confirms that the active ingredient is varenicline tartrate. ¶54.A col. 69:38-39
...wherein the tablet comprises less than 50 ppm of N-nitroso-varenicline... impurity... Third-party testing of the Accused Tablets allegedly showed nitrosamine levels below 2 ppm. ¶54.B col. 69:40-44
...and less than 0.15% (w/w) of diamide... impurity... The complaint alleges on information and belief that the Accused Tablets have levels of nitrosamines and "other impurities that fall within the limitations" of the patent. ¶62 col. 69:44-47
  • Identified Points of Contention (’587 Patent):
    • Technical Questions: The complaint provides specific test results for the N-nitroso-varenicline impurity but not for the diamide impurity. A primary factual question for the court will be whether the Accused Tablets meet the "less than 0.15% (w/w) of diamide" limitation. This will require chemical analysis of the accused product through discovery.

V. Key Claim Terms for Construction

  • The Term: "acid-base treatment" (’524 Patent, Claim 1)
    • Context and Importance: This term defines the patented purification process. The scope of this term is central to the infringement analysis for the ’524 Patent, as the complaint lacks direct evidence of the process Defendant uses. Practitioners may focus on this term because its construction will determine what types of purification processes fall within the claim's scope.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification describes the underlying principle as converting the varenicline free base into a salt to separate it from non-basic nitrosamine impurities, a general chemical concept (’524 Patent, col. 2:30-34). Claim 6 further describes the treatment broadly as "(a) converting the varenicline free base into a varenicline salt...; (b) extracting the nitrosamine impurities...; and (c) isolating purified varenicline free base..." (’524 Patent, col. 69:40-50).
      • Evidence for a Narrower Interpretation: The patent’s specific examples and Figure 1 illustrate the process using L-(+)-Tartaric acid and methylene dichloride as the organic solvent (’524 Patent, Fig. 1; col. 15:61-col. 16:15). A defendant may argue that the term should be limited to the specific embodiments disclosed.

VI. Other Allegations

  • Indirect Infringement: For the ’524 process patent, the complaint alleges infringement under 35 U.S.C. § 271(g), which prohibits the importation into the U.S. of a product made abroad by a process patented in the U.S. (Compl. ¶¶ 52, 53, 56). The complaint also alleges induced infringement under § 271(b) for both patents (Compl. ¶¶ 52, 61).
  • Willful Infringement: The complaint alleges willful infringement for both patents (Compl. ¶¶ 59, 66). The basis for this allegation is Defendant's alleged pre-suit knowledge. The complaint details that Plaintiff sent Defendant multiple notice letters, including a "Second Notice Letter" on June 9, 2023, advising that the PTO had issued a Notice of Allowance for the application that became the ’524 Patent. Defendant allegedly launched its product after receiving these notices (Compl. ¶¶ 39, 49).

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

  • A core issue will be one of evidentiary proof for the manufacturing process: For the ’524 Patent, can Plaintiff produce direct evidence from discovery to show that Defendant’s process in India uses an "acid-base treatment" as claimed, or will the analysis turn on circumstantial evidence and the burden-shifting framework of 35 U.S.C. § 295, which the complaint invokes?
  • A key technical question will be one of compositional analysis: For the ’587 Patent, does Defendant’s product as sold in the U.S. meet the claimed limitation of containing "less than 0.15% (w/w) of diamide... impurity"? The resolution of this issue will likely depend on the results of third-party laboratory testing conducted during discovery.
  • A central question for damages will be one of intent and willfulness: Did Defendant's decision to launch its product after receiving explicit notice that the claims of the pending ’524 patent had been allowed by the PTO constitute objective recklessness, potentially justifying an award of enhanced damages for willful infringement?