DCT

3:24-cv-10235

Intra Cellular Therapies Inc v. Aurobindo Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-10235, D.N.J., 11/01/2024
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Aurobindo Pharma USA, Inc. has a principal place of business in the state, and Defendant Aurobindo Pharma Ltd. is subject to personal jurisdiction there.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of CAPLYTA® (lumateperone) constitutes an act of infringement of three U.S. patents covering methods of use, pharmaceutical compositions, and specific formulations of the drug.
  • Technical Context: The technology lies in the field of antipsychotic pharmaceuticals, specifically concerning the compound lumateperone, which is used to treat neuropsychiatric conditions such as schizophrenia and bipolar depression.
  • Key Procedural History: This lawsuit was filed under the Hatch-Waxman Act following a notice letter from Aurobindo regarding its ANDA submission. The complaint notes that this action is related to prior, consolidated patent infringement lawsuits filed by the Plaintiff against the same Defendants concerning other patents also listed in the FDA's Orange Book for CAPLYTA®.

Case Timeline

Date Event
2018-08-31 U.S. Patent No. 12,128,043 Priority Date
2019-07-07 U.S. Patent No. 12,090,155 Priority Date
2019-12-11 U.S. Patent No. 12,122,792 Priority Date
2024-02-12 Aurobindo sends Notice Letter to Plaintiff
2024-03-27 Plaintiff files prior related lawsuit against Aurobindo
2024-08-29 Plaintiff files another prior related lawsuit against Aurobindo
2024-09-17 U.S. Patent No. 12,090,155 Issues
2024-10-22 U.S. Patent No. 12,122,792 Issues
2024-10-29 U.S. Patent No. 12,128,043 Issues
2024-11-01 Complaint Filing Date

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

U.S. Patent No. 12,090,155 - Methods

  • Issued: September 17, 2024

The Invention Explained

  • Problem Addressed: The patent addresses the need for safer and more effective treatments for Bipolar II Disorder. It notes that existing therapies are often associated with significant side effects, such as sedation, metabolic issues (e.g., weight gain, hyperglycemia), and an increased risk of suicidal thoughts, and that the sole previously approved antipsychotic for this indication, quetiapine, is reported to have these drawbacks (’155 Patent, col. 4:10-21).
  • The Patented Solution: The invention provides a method for treating depressive episodes associated with Bipolar II Disorder by administering a therapeutically effective amount of lumateperone, specifically in its mono-tosylate salt form (’155 Patent, Abstract). The patent’s detailed description presents clinical trial data suggesting that lumateperone is effective in this patient population without causing common adverse effects like akathisia, restlessness, or significant metabolic changes, and without triggering manic episodes (’155 Patent, col. 5:8-28).
  • Technical Importance: The patented method claims a therapeutic approach for Bipolar II Disorder that may offer a more favorable safety and tolerability profile compared to previously available treatments (’155 Patent, col. 4:34-46).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 22 (Compl. ¶¶ 38, 39).
  • Independent Claim 1:
    • A method for treating a major depressive episode associated with Bipolar II Disorder,
    • comprising administering a therapeutically effective amount of lumateperone in mono-tosylate salt form,
    • wherein the method comprises once daily administration of a tablet or capsule,
    • which comprises about 60 mg of lumateperone mono-tosylate with a pharmaceutically acceptable diluent or carrier.
  • Independent Claim 22:
    • A method for treating a depressive episode associated with Bipolar II Disorder,
    • comprising administering a therapeutically effective amount of lumateperone in mono-tosylate salt form,
    • wherein the method comprises once daily administration of a tablet or capsule,
    • which comprises about 60 mg of lumateperone monotosylate with a pharmaceutically acceptable diluent or carrier.

U.S. Patent No. 12,122,792 - Pharmaceutical Compositions Comprising 4-((6bR,10aS)-3-methyl...yl)phenyl)butan-1-one for Treating Conditions of the Central Nervous System and Cardiac Disorders

  • Issued: October 22, 2024

The Invention Explained

  • Problem Addressed: The patent does not explicitly state a problem in its background section but instead focuses on disclosing a novel compound and its uses. The implicit problem is the need for new pharmaceutical compositions for treating central nervous system disorders (’792 Patent, col. 1:21-26).
  • The Patented Solution: The invention is a pharmaceutical composition that combines two specific compounds: lumateperone (identified as "Formula II") and a structurally related compound ("Formula I"), which the patent specification identifies as a synthetic by-product of lumateperone (’792 Patent, Abstract; col. 3:3-11). The claims cover compositions containing these two compounds in admixture with a pharmaceutically acceptable carrier, with some claims specifying particular salt forms and weight ratios (’792 Patent, col. 27:1-28:2).
  • Technical Importance: This patent protects specific pharmaceutical formulations that contain not only the active ingredient lumateperone but also a particular related impurity or by-product, potentially covering real-world drug products resulting from certain manufacturing processes (’792 Patent, col. 3:3-11).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 29 (Compl. ¶¶ 65, 66).
  • Independent Claim 1:
    • A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier in admixture with:
    • (i) a compound of Formula I in free base or pharmaceutically acceptable salt form; and
    • (ii) a compound of Formula II in free base or pharmaceutically acceptable salt form.
  • Independent Claim 29:
    • A pharmaceutical composition comprising:
      1. a compound of Formula I in free base or pharmaceutically acceptable salt form; and
    • (ii) a compound of Formula II in toluenesulfonic acid addition salt form;
    • wherein the composition comprises the two compounds in a weight ratio in the range of from 1:200 to 1:2000.

U.S. Patent No. 12,128,043 - Pharmaceutical Capsules Comprising Lumateperone Mono-Tosylate

  • Issued: October 29, 2024

Technology Synopsis

This patent is directed to specific pharmaceutical capsule formulations containing lumateperone mono-tosylate in a solid crystal form (’043 Patent, col. 3:27-31). The claims recite specific quantitative parameters for the formulation, including the amount of active ingredient equivalent free base, the weight percentage of the active ingredient in the total blend, and a particular dissolution profile in an acidic medium (’043 Patent, col. 19:20-43).

Asserted Claims

Independent claim 1 (Compl. ¶92).

Accused Features

The complaint alleges that Aurobindo's ANDA Product is a pharmaceutical capsule comprising lumateperone mono-tosylate in a solid crystal form, blended with specific diluents or carriers, and that it meets the dissolution parameters recited in the asserted claim (Compl. ¶93).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Aurobindo's ANDA Product," a proposed generic version of Plaintiff's CAPLYTA® (lumateperone) 42 mg capsules, for which Aurobindo has filed ANDA No. 219085 seeking FDA approval (Compl. ¶¶ 1, 2).

Functionality and Market Context

The product is a pharmaceutical capsule containing lumateperone, intended for the same therapeutic uses as CAPLYTA®, which is approved for the treatment of schizophrenia and depressive episodes associated with bipolar disorder (Compl. ¶¶ 26, 27). The complaint alleges, based on information and belief, that the product is a generic equivalent that will be prescribed and used according to a proposed label that directs infringing uses of the ’155 Patent (Compl. ¶¶ 37, 40). It further alleges the product's formulation infringes the composition claims of the ’792 and ’043 Patents (Compl. ¶¶ 67, 93). The product represents a generic competitor seeking to enter the market prior to the expiration of the patents-in-suit (Compl. ¶1). The complaint includes a visual of the chemical structure of lumateperone mono-tosylate, the active ingredient in the accused product (Compl. ¶92).

IV. Analysis of Infringement Allegations

U.S. Patent No. 12,090,155 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for the treatment of a major depressive episode associated with Bipolar II Disorder... The complaint alleges, upon information and belief, that the use of Aurobindo's product as directed by its proposed label would involve treating this specific medical condition. ¶40 col. 5:8-13
comprising administering to a patient in need thereof, a therapeutically effective amount of lumateperone in mono-tosylate salt form... The ANDA product is alleged to contain lumateperone, and its proposed label will allegedly direct administration in a therapeutically effective amount for the claimed indication. ¶¶36, 40 col. 4:34-36
wherein the method comprises once daily administration of a tablet or capsule comprising about 60 mg of lumateperone mono-tosylate... The proposed label will allegedly direct once-daily administration of a capsule containing about 60 mg of lumateperone mono-tosylate. The accused product is a 42 mg capsule, which corresponds to 60 mg of the tosylate salt. ¶40 col. 9:58-62
  • Identified Points of Contention:
    • Scope Questions: A potential issue may be the construction of "about 60 mg." The complaint alleges Aurobindo's product is a 42 mg capsule, which refers to the free base equivalent of the active ingredient. The patent specification appears to directly equate "42 mg" of lumateperone free base with "60 mg" of the tosylate salt, which may support the Plaintiff's infringement theory (’155 Patent, col. 9:58-62).
    • Technical Questions: The infringement allegation for this method-of-use patent is contingent on the specific instructions in Aurobindo's proposed product label. A key evidentiary question will be whether the final, FDA-approved label will instruct administration specifically for "a major depressive episode associated with Bipolar II Disorder," as required by the claim.

U.S. Patent No. 12,122,792 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising... (i) a compound of Formula I... Upon information and belief, Aurobindo's ANDA Product is alleged to be a pharmaceutical composition that contains the compound of Formula I. The complaint provides a chemical structure diagram of Formula I (Compl. ¶65). ¶67 col. 25:52-64
...and (ii) a compound of Formula II... The ANDA Product is alleged to contain the compound of Formula II (lumateperone). The complaint provides a chemical structure diagram of Formula II (Compl. ¶65). ¶¶63, 67 col. 26:1-12
  • Identified Points of Contention:
    • Scope Questions: For claim 1, a question may arise as to whether the term "comprising a... compound of Formula I" is met by the presence of mere trace-level manufacturing impurities, or if a more substantial quantity is required.
    • Technical Questions: The infringement allegation is based "upon information and belief." The central technical question is factual: does Aurobindo's generic product actually contain the compound of Formula I, which is described in the patent as a synthetic by-product? This will likely require discovery and chemical analysis of the accused product to resolve.

V. Key Claim Terms for Construction

  • The Term: "a major depressive episode associated with Bipolar II Disorder" (’155 Patent, claim 1)
  • Context and Importance: The infringement case for the ’155 Patent hinges on whether Aurobindo’s product label will instruct treatment for this specific clinical condition. Practitioners may focus on this term because its definition will determine the scope of infringing activity; a defendant may argue for a narrow construction tied to specific clinical trial parameters to avoid infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a standard clinical definition: "Bipolar II Disorder-defined by a pattern of depressive episodes and hypomanic episodes, but not the full-blown manic episodes described above" (’155 Patent, col. 3:31-34).
    • Evidence for a Narrower Interpretation: The patent’s clinical trial example (Example 1) recruited patients based on specific diagnostic criteria, including scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) (’155 Patent, col. 12:10-18). A party could argue that the claim term should be interpreted in light of the specific patient population described as having been successfully treated in the patent.
  • The Term: "a weight ratio in the range of from 1:200 to 1:2000" (’792 Patent, claim 29)
  • Context and Importance: This term is critical for infringement of claim 29. Unlike claim 1, which only requires the presence of the Formula I by-product, this claim requires it to be present within a specific quantitative range relative to lumateperone. The dispute will be purely factual, turning on precise chemical analysis of the accused product.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent provides several examples of compositions falling within this ratio, but does not suggest the range is limited to those examples (’792 Patent, cols. 9-10). The language "in the range of" is generally given its plain and ordinary meaning.
    • Evidence for a Narrower Interpretation: The patent does not appear to offer intrinsic evidence that would narrow the plain meaning of this numerical range. The dispute over this term is more likely to be factual (i.e., does the accused product fall in the range) rather than a matter of claim construction.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Aurobindo will actively induce infringement of the method claims of the ’155 Patent by providing a product label that instructs physicians and patients to perform the claimed method of treatment. It further alleges contributory infringement for all three patents, stating that Aurobindo's ANDA Product is especially made or adapted for an infringing use and is not a staple article of commerce suitable for substantial noninfringing use (Compl. ¶¶ 47-48, 74-75, 99-100).
  • Willful Infringement: The complaint alleges that Aurobindo has acted with "full knowledge" of the patents-in-suit and "without a reasonable basis for believing that it would not be liable for infringement." This allegation is based on Aurobindo's participation in the Hatch-Waxman process, which requires notice of patents listed in the FDA's Orange Book (Compl. ¶¶ 51, 78, 103).

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

  • A core issue will be one of factual composition: does Aurobindo's generic lumateperone product, as manufactured, contain the specific "Formula I" by-product recited in the ’792 Patent, and if so, does it fall within the weight ratios required by claim 29? The case for this patent will turn entirely on the results of chemical analysis of the accused product.
  • A second central issue will be one of label-driven inducement: will the final FDA-approved product labeling for Aurobindo's generic explicitly instruct its use for treating "depressive episodes associated with Bipolar II Disorder," thereby creating liability for induced infringement of the ’155 Patent's method claims?
  • A key evidentiary question for the ’043 patent will be one of formulation equivalence: can Plaintiff prove through testing that Aurobindo's capsule formulation exhibits the specific blend percentages and dissolution profiles that are explicitly quantified in the patent's composition claims?