DCT

3:20-cv-18334

Par Pharmaceutical Inc v. Aurobindo Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:20-cv-18334, D.N.J., 12/07/2020
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Aurobindo Pharma U.S.A., Inc. maintains a regular and established place of business in the district, and Defendant Aurobindo Pharma Limited is a foreign entity.
  • Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) for a generic vasopressin injection product will, upon approval, induce infringement of a patent covering a method of treating hypotension in patients with specific genetic markers.
  • Technical Context: The lawsuit concerns the field of pharmacogenomics, where treatment protocols are tailored to a patient's genetic profile to enhance safety and efficacy, specifically for administering vasopressin to treat life-threatening septic shock.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendant's submission of an ANDA to the FDA seeking to market a generic version of Plaintiff's drug, VASOSTRICT®. Plaintiff has a pending request with the FDA to amend the VASOSTRICT® label to include the patented genotype-based dosing regimen. Plaintiff has filed contemporaneous lawsuits against other ANDA filers over the same patent.

Case Timeline

Date Event
2012-09-25 JHP Pharmaceuticals submits original NDA for VASOSTRICT®
2014-04-17 FDA approves original NDA for VASOSTRICT®
2016-03-18 FDA approves supplemental NDA for reformulated VASOSTRICT®
2016-12-17 FDA approves supplemental NDA for multi-dose VASOSTRICT® vials
2020-03-24 Aurobindo submits ANDA No. 214314 (on or before this date)
2020-07-17 ’435 Patent Priority Date
2020-11-24 U.S. Patent No. 10,844,435 issues
2020-12-07 Complaint Filing Date

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

U.S. Patent No. 10,844,435 - "Method to Treat Hypotension Using Vasopressin in Certain Genotypes"

  • Patent Identification: U.S. Patent No. 10,844,435, "Method to Treat Hypotension Using Vasopressin in Certain Genotypes," issued November 24, 2020.

The Invention Explained

  • Problem Addressed: Vasopressin is a "lifesaving drug" used to treat dangerously low blood pressure (vasodilatory shock), but dosing is critical, as overdosage can lead to severe adverse events (Compl. ¶¶20, 26). The rate at which patients clear vasopressin from their system can vary, in part due to genetic variations (single nucleotide polymorphisms, or SNPs) in the gene for LNPEP, the enzyme that degrades vasopressin (’435 Patent, col. 1:38-49; Compl. ¶27). This creates a "need to better understand the dosing, efficacy and safety" for patients with different genotypes to avoid under- or over-dosing (Compl. ¶31; ’435 Patent, col. 2:11-15).
  • The Patented Solution: The patent claims a method of personalized medicine. The inventors state they "surprisingly found" that patients with the AA or AT genotype for a specific LNPEP SNP (rs4869317) clear vasopressin faster than patients with the TT genotype (Compl. ¶31; ’435 Patent, col. 2:25-30). The invention, therefore, is a method of administering vasopressin according to a specific dosing regimen tailored to the patient's genotype, which involves giving a higher overall dose to AA or AT patients to achieve a target blood pressure safely (’435 Patent, col. 2:31-35, Fig. 1). This genotype-specific approach is asserted to result in "improved survival rates and reduced adverse events" (Compl. ¶31).
  • Technical Importance: The claimed invention provides a method for moving beyond one-size-fits-all dosing for a critical care drug, using a patient's genetic information to optimize treatment for life-threatening conditions (Compl. ¶34).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶46).
  • The essential elements of independent claim 1 are:
    • A method of increasing blood pressure in a human patient with septic shock;
    • The patient is identified as having an LNPEP AA or AT rs4869317 genotype;
    • The method involves intravenously administering a vasopressin formulation;
    • The administration follows a specific protocol: a starting dose of 0.01 units/minute, titrated up by 0.005 units/minute at 10-15 minute intervals;
    • The administration protocol specifies a maximum dose of 0.085 units/minute.
  • The complaint does not explicitly reserve the right to assert other claims, but this remains a possibility.

III. The Accused Instrumentality

Product Identification

Aurobindo's "Proposed ANDA Product," identified as a generic Vasopressin Injection USP, 20 units/1 mL in multiple-dose vials, submitted to the FDA under ANDA No. 214314 (Compl. ¶37).

Functionality and Market Context

The product is a generic drug intended as a substitute for Par's branded VASOSTRICT®, which is used to increase blood pressure in adults with vasodilatory shock (Compl. ¶¶37, 41). The complaint alleges that Aurobindo's product will be sold to hospitals and other distributors to be administered in the same manner as VASOSTRICT® (Compl. ¶41). The infringement allegation is anticipatory; it is based on the future marketing and use of Aurobindo's product upon FDA approval (Compl. ¶¶51, 57).

IV. Analysis of Infringement Allegations

The complaint alleges that Aurobindo's commercialization of its Proposed ANDA Product would induce physicians to infringe the ’435 patent. The primary theory is that Aurobindo’s product label will be required by FDA regulation to conform to Par's VASOSTRICT® label, which Par is in the process of amending to include instructions that recite the patented method (Compl. ¶¶35, 39). The complaint includes a table from Par’s proposed label amendment, which specifies the starting, titrating, and maximum doses for patients with the AA/AT genotype (Compl. p. 12, ¶35). An alternative theory alleges inducement even without an explicit infringing label, based on the knowledge that physicians will follow the new standard of care established by the patent (Compl. ¶43).

’435 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of increasing blood pressure...in a human patient with septic shock wherein the patient has an LNPEP AA or AT rs4869317 genotype Aurobindo’s product label is expected to instruct physicians to treat septic shock patients identified by their AA or AT genotype, thereby causing physicians to perform this step. ¶¶40, 42 col. 5:50-54
the method comprising: intravenously administering to the patient a pharmaceutical formulation comprising vasopressin... The Proposed ANDA Product is a vasopressin formulation for intravenous administration, which physicians will be induced to use. ¶37 col. 2:24-25
at a starting dose of 0.01 units/minute The product label is alleged to instruct physicians to begin treatment for this patient group at the claimed starting dose. ¶40 col. 14:20-22
and titrating the dose up by 0.005 units/minute at 10 to 15 minute intervals to maintain the target blood pressure... The product label is alleged to instruct physicians to follow the claimed titration schedule. ¶40 col. 14:15-18
wherein the maximum dose is 0.085 units/minute. The product label is alleged to instruct physicians to adhere to the claimed maximum dose. Figure 1 from the patent application, included in the complaint, provides a flowchart that visually depicts the genotype-differentiated treatment pathways for both post-cardiotomy and septic shock (Compl. p. 11, ¶32). ¶40 col. 14:23-25
  • Identified Points of Contention:
    • Scope Questions: A central question is whether infringement can be established based on a future, anticipated label change. The dispute may turn on whether the regulatory requirement for a generic label to conform to the branded drug's label is sufficient to establish an affirmative act of inducement at the time of the ANDA filing.
    • Technical Questions: A key evidentiary question is one of intent. If Aurobindo's final approved label does not contain explicit instructions matching claim 1, the court will have to consider whether marketing a bioequivalent generic drug, with the alleged knowledge that it will be used by physicians in an infringing manner, is sufficient to prove the specific intent to encourage infringement required by law (Compl. ¶43).

V. Key Claim Terms for Construction

  • The Term: "wherein the patient has an LNPEP AA or AT rs4869317 genotype"

    • Context and Importance: This limitation defines the specific patient population for the claimed method. Its construction is critical because it determines what a physician must know or do to directly infringe, which is the predicate for the inducement claim. Practitioners may focus on this term because it raises the question of whether direct infringement requires a physician's subjective knowledge of a patient's genotype, or if it is met by the objective fact that the patient has the genotype.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent describes various methods for determining a patient's genotype, such as PCR and DNA sequencing, but does not explicitly include the act of "determining the genotype" as a step in the treatment method itself (’435 Patent, col. 9:28-43). This could support an interpretation that the limitation is satisfied so long as the patient factually possesses the genotype, regardless of whether a test was performed or its result was known by the physician at the time of treatment.
      • Evidence for a Narrower Interpretation: The patent's abstract and summary frame the invention as "administering a therapeutically effective amount of vasopressin based on genotype" (’435 Patent, Abstract). This language, along with the logic of personalized medicine, may support an interpretation that the physician must be aware of the patient's genotype to consciously choose and perform the claimed specific dosing regimen.

  • The Term: "maximum dose is 0.085 units/minute"

    • Context and Importance: This term sets a precise numerical boundary for the claimed method. Its construction will determine whether any deviation from this exact value avoids infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification frequently uses the word "about" when discussing dosage ranges, such as "about 0.075 to 0.085 units/minute" (’435 Patent, col. 14:54-55). This may suggest that the claimed value is not intended to be an absolute, rigid limit but rather the endpoint of a target range.
      • Evidence for a Narrower Interpretation: The claim language itself recites "is 0.085 units/minute" without any qualifying language like "about." Further, Table 3 in the specification, which outlines the dosing for septic shock, lists this value under a "Maximum Dose" heading, reinforcing its role as a specific, defined limit (’435 Patent, col. 14, Table 3).

VI. Other Allegations

  • Indirect Infringement: The complaint's central cause of action is for induced infringement under 35 U.S.C. § 271(b) (Compl., Count II). The complaint alleges Aurobindo knows of the ’435 patent and will intentionally induce infringement by physicians through at least two mechanisms: (1) its product label, which is expected to contain instructions for the patented method, and (2) its marketing of the product as a generic substitute for VASOSTRICT® with the knowledge that it will be used to practice the patented method (Compl. ¶¶57-58).
  • Willful Infringement: The complaint alleges that Aurobindo's infringement will be willful (Compl. ¶¶54, 61). This allegation is based on Aurobindo's alleged knowledge of the ’435 patent, which it allegedly gained either by monitoring PTO issuances or, at the latest, upon being served with the complaint, followed by its continued intent to commercialize the accused product (Compl. ¶47).

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

  • A core issue will be one of ripeness and contingent inducement: can Plaintiff establish an act of inducement based on the submission of an ANDA when the alleged infringing instructions are not yet on any FDA-approved label? The analysis will likely focus on whether the regulatory pathway mandating label conformity creates a controversy sufficiently definite to support a declaratory judgment of future inducement.
  • A key evidentiary question will be one of specific intent: if Aurobindo’s final label does not explicitly recite the claimed method, can Plaintiff prove that marketing a bioequivalent generic drug is sufficient to establish specific intent to encourage infringement, based on the theory that physicians will inevitably adopt the patented method as the new standard of care?
  • A central issue of claim scope will be the construction of the patient genotype limitation ("wherein the patient has..."). The outcome will define the universe of direct infringement that Plaintiff must prove Aurobindo will induce, turning on whether a physician must have contemporaneous, subjective knowledge of the patient's genetic status to perform the claimed method.