DCT

1:25-cv-00530

Aurinia Pharma Inc v. Difgen Pharma LLC

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00530, D. Del., 05/01/2025
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because the defendant, DifGen Pharmaceuticals LLC, is incorporated in Delaware.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the drug LUPKYNIS® (voclosporin) constitutes an act of infringement of two patents covering therapeutic protocols for treating lupus nephritis.
  • Technical Context: The technology concerns a pharmacodynamic dosing method for voclosporin, a calcineurin inhibitor, used to treat lupus nephritis, a serious kidney inflammation caused by the autoimmune disease systemic lupus erythematosus (SLE).
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of an ANDA with a Paragraph IV certification, asserting that Plaintiff's patents are invalid, unenforceable, or will not be infringed. The patents-in-suit are listed in the FDA's "Orange Book" for LUPKYNIS®. The '991 patent is a continuation of the application that resulted in the '036 patent.

Case Timeline

Date Event
2017-05-12 Earliest Priority Date for '036 and '991 Patents
2019-05-14 '036 Patent Issue Date
2021-01-22 FDA Approval of LUPKYNIS® New Drug Application
2023-04-11 '991 Patent Issue Date
2025-03-17 Date of Defendant's ANDA Notice Letter to Plaintiff
2025-05-01 Complaint Filing Date

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

U.S. Patent No. 10,286,036 - "Protocol for the Treatment of Lupus Nephritis"

  • Patent Identification: U.S. Patent No. 10,286,036, titled “Protocol for the Treatment of Lupus Nephritis,” issued on May 14, 2019 (Compl. ¶16).

The Invention Explained

  • Problem Addressed: The patent’s background section states that the standard of care for lupus nephritis (LN) has had limited success, with complete remission rates below 10% and partial remission in only about 50% of patients (’036 Patent, col. 1:37-43).
  • The Patented Solution: The invention is a "pharmacodynamic method" for treating proteinuric kidney diseases like LN by administering voclosporin in combination with other drugs. The core of the method is a feedback loop: a physician assesses a patient's estimated Glomerular Filtration Rate (eGFR) at different time points and adjusts the voclosporin dosage—either reducing it or continuing it—based on whether the eGFR has decreased by a specified target percentage to below a predetermined value (’036 Patent, Abstract; col. 3:1-19). This protocol aims to optimize treatment efficacy while managing a key side effect, nephrotoxicity, which manifests as a drop in eGFR (’036 Patent, col. 2:61-66).
  • Technical Importance: This personalized dosing strategy sought to improve clinical outcomes for a severe autoimmune condition where standardized treatments were often failing (’036 Patent, col. 1:41-43).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim (Compl. ¶30). Independent claim 1 is representative and includes the following essential elements:
    • A pharmacodynamic method to treat a proteinuric kidney disease which method comprises administering to a subject diagnosed with said disease a predetermined daily dosage of effective amounts of voclosporin over a projected treatment period of at least 24 weeks.
    • The method further comprises assessing the subject's estimated Glomerular Filtration Rate (eGFR) at a first and second time point.
    • If the eGFR decreases by more than a target percentage (between 20-45%) to below a predetermined value (between 50-90 ml/min/1.73 m²), the daily dosage is reduced or stopped.
    • If the eGFR decreases by less than the target percentage, the same daily dosage is continued.
  • The complaint reserves the right to assert additional claims (Compl. ¶30).

U.S. Patent No. 11,622,991 - "Protocol for Treatment of Lupus Nephritis"

  • Patent Identification: U.S. Patent No. 11,622,991, titled “Protocol for Treatment of Lupus Nephritis,” issued on April 11, 2023 (Compl. ¶17).

The Invention Explained

  • Problem Addressed: Like its parent patent, the ’991 Patent addresses the need for more effective LN treatments and mitigation of side effects from calcineurin inhibitors like voclosporin (’991 Patent, col. 1:31-48).
  • The Patented Solution: This patent refines the treatment protocol by claiming a method that begins with a specific starting dose of voclosporin (23.7 mg twice daily) alongside mycophenolate mofetil (MMF) and corticosteroids. The dose adjustment logic is more specific: the voclosporin dose is reduced (to 15.8 mg or 7.9 mg twice daily) if the patient's eGFR decreases within a narrower range of >20% to <30% (’991 Patent, Claim 1). The patent also introduces the use of early-response biomarkers, such as a reduction in urinary protein/creatinine ratio (UPCR) at 8 weeks, to predict long-term success and determine whether to terminate an apparently ineffective treatment early (’991 Patent, col. 8:1-10).
  • Technical Importance: The invention provides a more structured and data-driven treatment algorithm, aiming to enhance safety and efficacy by specifying a starting dose, a more precise dose-reduction window, and criteria for early discontinuation of therapy (’991 Patent, col. 3:30-38).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim (Compl. ¶43). Independent claim 1 is representative and includes the following essential elements:
    • A method of treating LN by selecting a subject and determining their baseline eGFR.
    • Administering voclosporin at a starting dose of 23.7 mg twice daily, along with MMF and corticosteroids.
    • Assessing the subject's eGFR at a second time point.
    • Administering a reduced dose of 15.8 mg or 7.9 mg twice daily if the eGFR decreases by >20% to <30% to below 60 ml/min/1.73 m².
  • The complaint reserves the right to assert additional claims (Compl. ¶43).

III. The Accused Instrumentality

Product Identification

  • Defendant DifGen’s generic voclosporin drug products, for which it filed Abbreviated New Drug Application (ANDA) No. 220332 with the FDA (Compl. ¶1).

Functionality and Market Context

  • The complaint alleges that DifGen's ANDA seeks approval to market a generic version of Aurinia's LUPKYNIS® drug product for the treatment of lupus nephritis (Compl. ¶1, ¶18). The filing of the ANDA itself is the statutory act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶27, ¶40). The infringement theory is based on the allegation that the proposed labeling for DifGen’s generic product will instruct physicians and patients to use it in a manner that practices the methods claimed in the '036 and '991 patents (Compl. ¶33, ¶46). The complaint alleges DifGen's product is "the same, or substantially the same, as Aurinia's LUPKYNIS®" (Compl. ¶21).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not include a claim chart or the specific text of the accused product label. The infringement theory is therefore based on future, intended use as directed by that label.

The complaint alleges that DifGen's submission of its Voclosporin ANDA constitutes an act of infringement of both the '036 and '991 patents under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶27, ¶40). The central theory is that DifGen's proposed package insert for its generic voclosporin product will necessarily instruct healthcare professionals and patients to perform the steps of the patented methods (Compl. ¶33, ¶46). This includes administering voclosporin for lupus nephritis and performing the claimed eGFR-based monitoring and dose adjustments. Upon FDA approval, this instructed use would allegedly constitute direct infringement by end-users, for which DifGen would be liable for inducing infringement (Compl. ¶32, ¶45). The specifics of this theory, however, depend on the precise language of the proposed label, which is not detailed in the complaint.

  • Identified Points of Contention:
    • Evidentiary Question: A central issue for the court will be whether the instructions in DifGen’s proposed product label, once produced in discovery, map to all elements of the asserted claims. For instance, does the label mandate the specific eGFR monitoring frequencies and the exact percentage-based dose reduction thresholds required by Claim 1 of the '036 Patent and Claim 1 of the '991 Patent?
    • Technical Question: A key question is whether a general instruction on a drug label to monitor kidney function and adjust dosage as clinically indicated is sufficient to meet the specific, multi-step algorithmic limitations of the asserted claims. For example, does the label for the generic product instruct administering a specific reduced dose (e.g., 15.8 mg BID) in response to a specific range of eGFR decline (e.g., >20% to <30%), as required by Claim 1 of the '991 Patent?

V. Key Claim Terms for Construction

  • Term ('036 Patent): "pharmacodynamic method"

    • Context and Importance: This preamble term frames the entire claim. Its construction is critical because it could be interpreted as either a mere label for the subsequent steps or as a substantive limitation requiring the achievement of a particular biological effect. Practitioners may focus on this term to argue whether infringement requires only performing the steps or also achieving a measurable pharmacodynamic outcome.
    • Intrinsic Evidence for a Broader Interpretation: The body of claim 1 recites a set of concrete, objective steps (assessing eGFR, reducing/continuing dose) without reference to a required clinical result, which may support an interpretation that performing these steps is sufficient to infringe (’036 Patent, col. 9:60-col. 10:11).
    • Intrinsic Evidence for a Narrower Interpretation: The specification repeatedly states the goal is to adjust dosage "in accordance with the response of the subject" to maximize effectiveness, which could support a narrower construction requiring that the claimed steps be performed for the purpose of, and in response to, the patient's individual pharmacodynamic reaction (’036 Patent, col. 2:64-col. 3:2).

  • Term ('991 Patent): "selecting for treatment a subject having LN"

    • Context and Importance: This is the first step of the claimed method. Its construction will determine what actions by a physician satisfy the limitation. The dispute may center on whether a routine diagnosis of LN is sufficient, or if the "selecting" step requires consideration of the specific clinical parameters that defined the patient population in the studies underlying the patent.
    • Intrinsic Evidence for a Broader Interpretation: The plain language of Claim 1 does not add further qualifications to the "selecting" step beyond the subject "having LN," which could support a construction where a standard clinical diagnosis suffices (’991 Patent, col. 28:58-59).
    • Intrinsic Evidence for a Narrower Interpretation: The specification describes the clinical study's entry criteria in detail, such as a UPCR ≥1.0 or 1.5 mg/mg and an eGFR ≥45 ml/min/1.73 m² (’991 Patent, col. 2:1-7). A party could argue that "selecting" should be construed to require that a patient meet these or similar specific criteria, thereby narrowing the pool of infringing acts.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement for both patents. The factual basis is that DifGen, with alleged knowledge of the patents, will commercialize its generic product with a package insert that will "recommend, suggest, encourage, and/or instruct others" to use the product in a manner that directly infringes the patented methods (Compl. ¶33, ¶46).
  • Willful Infringement: The complaint alleges that DifGen had actual knowledge of the '036 and '991 patents at least as of the date it sent its Paragraph IV Notice Letter on March 17, 2025 (Compl. ¶29, ¶42). While these allegations could support a later claim for willfulness, the complaint does not explicitly plead willful infringement or seek enhanced damages under 35 U.S.C. § 284 in its prayer for relief. It does, however, request relief under 35 U.S.C. § 285 for attorney's fees (Prayer for Relief ¶E).

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

  • A core evidentiary question will be one of label-directed infringement: Will the precise language of DifGen's proposed product label, once it becomes available, be found to instruct, encourage, or require physicians to perform every step of the asserted method claims, including the specific starting doses and eGFR-based dose-adjustment logic?
  • A key legal question will be one of claim scope: Can the patented methods—which claim specific, quantitative, and conditional steps for adjusting a drug's dosage based on a standard clinical marker (eGFR)—be distinguished from what a skilled clinician would have considered standard, albeit unwritten, medical practice? This will be central to the obviousness analysis of DifGen's asserted invalidity defense.
  • The case may also turn on a question of divided infringement: As the claimed methods involve actions by a physician over a period of weeks or months, a key issue may be whether all steps of any single asserted claim are attributable to a single actor, or if direction or control must be proven to establish infringement.