Intra Cellular Therapies Inc v. Sandoz Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Intra-Cellular Therapies, Inc. (Delaware / New York)
  • Defendant: Sandoz Inc. (Delaware / New Jersey)
  • Plaintiff’s Counsel: Walsh Pizzi O'Reilly Falanga LLP; Williams & Connolly LLP
• Case Identification: 3:24-cv-08855, D.N.J., 08/29/2024
• Venue Allegations: Venue is alleged to be proper as Defendant Sandoz has a principal place of business in New Jersey, has committed acts of infringement in the district by preparing and submitting its ANDA there, and will market and sell the accused product in the district.
• Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of the drug CAPLYTA® (lumateperone) constitutes an act of infringement of two recently issued patents covering methods of use and specific pharmaceutical compositions.
• Technical Context: The technology relates to pharmaceutical treatments for neuropsychiatric disorders, specifically the compound lumateperone, which is used to treat conditions like schizophrenia and bipolar depression.
• Key Procedural History: The complaint notes this action is related to a prior, pending lawsuit filed by Plaintiff against Sandoz on March 28, 2024 (Civil Action No. 3:24-cv-04327), which asserts infringement of a different set of patents by the same accused ANDA product. This new complaint asserts two patents that issued after the original suit was filed.

Case Timeline

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

U.S. Patent No. 11,980,617, "Methods of Treating Acute Depression and/or Acute Anxiety," Issued May 14, 2024

The Invention Explained

• Problem Addressed: The patent describes a significant drawback of conventional antidepressants (e.g., SSRIs), which is their delayed onset of action, often taking weeks or months to become fully effective. This delay is particularly problematic for patients with acute depression, where a rapid therapeutic response is needed. It also notes that existing rapid-acting alternatives like ketamine have significant dissociative side effects and a high risk of abuse. (’617 Patent, col. 3:7-44).
• The Patented Solution: The invention claims a method for the acute treatment of depression or anxiety by administering lumateperone. The patent suggests that lumateperone, a 5-HT2A/D2 receptor ligand, provides a rapid, orally-available antidepressant effect by modulating the glutamatergic system, a different mechanism from traditional SSRIs, thereby avoiding their delayed onset and the adverse side effects of ketamine. (’617 Patent, Abstract; col. 4:46-65).
• Technical Importance: The invention purports to provide a much-needed therapeutic option: an orally-available, rapid-acting antidepressant suitable for acute depressive episodes that lacks the significant side effects associated with ketamine. (’617 Patent, col. 4:50-65).

Key Claims at a Glance

• The complaint asserts independent claim 1.
• The essential elements of claim 1 are:
  • A method of treating acute depression and/or acute anxiety,
  • comprising administering to a patient in need thereof,
  • a therapeutically effective amount of a Compound of Formula I,
  • in free, or pharmaceutically acceptable salt form.
• The complaint does not explicitly reserve the right to assert dependent claims but alleges infringement of "one or more claims" (Compl. ¶38).

U.S. Patent No. 12,070,459, "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate," Issued August 27, 2024

The Invention Explained

• Problem Addressed: The development of a commercially viable oral drug product requires a formulation that is stable, manufacturable, and provides a predictable and effective pharmacokinetic (PK) profile (i.e., how the drug is absorbed, distributed, metabolized, and excreted by the body). The patent background describes the therapeutic profile of lumateperone for treating various central nervous system disorders. (’459 Patent, col. 1:36 - col. 2:65).
• The Patented Solution: The invention is a specific pharmaceutical capsule containing lumateperone as a mono-tosylate salt in a solid crystal form. The claims precisely define the drug concentration within the capsule (10-30% by weight), the total amount of the drug salt (about 60 mg), the types of other ingredients (excipients) used, and, critically, the specific PK profile (Cmax, Tmax, and AUC) that results from administering a single capsule under fasting conditions. (’459 Patent, Abstract; col. 13:4-14:5).
• Technical Importance: This patent defines a specific, tangible oral dosage form that delivers a consistent and therapeutically effective amount of lumateperone with a known, predictable absorption profile, which is a fundamental requirement for regulatory approval and safe clinical use. (’459 Patent, col. 14:1-5).

Key Claims at a Glance

• The complaint asserts independent claim 1.
• The essential elements of claim 1 are:
  • A pharmaceutical capsule for oral administration,
  • comprising lumateperone in mono-tosylate salt form,
  • wherein the lumateperone mono-tosylate is in solid crystal form,
  • wherein the capsule comprises the lumateperone mono-tosylate in an amount of about 60 mg,
  • wherein the capsule comprises a blend of 10 to 30% by weight of the lumateperone mono-tosylate,
  • and one or more pharmaceutically acceptable diluents or carriers (e.g., diluent/filler, binder, disintegrant, lubricant, glidant),
  • wherein administration of an oral dose of a single capsule under fasting conditions provides specific pharmacokinetic outcomes for Cmax (15-55 ng/mL), Tmax (0.7-1.5 hours), and/or AUC (51-135 hours-ng/mL).
• The complaint alleges infringement of "one or more claims" (Compl. ¶66).

III. The Accused Instrumentality

• Product Identification: The accused instrumentality is Sandoz's ANDA No. 218938 Product, a generic version of CAPLYTA® (lumateperone) capsules intended for commercial sale in 10.5 mg, 21 mg, and 42 mg dosage strengths (Compl. ¶¶1-2, 28).
• Functionality and Market Context: The branded drug, CAPLYTA®, is approved for treating schizophrenia and depressive episodes associated with bipolar I or II disorder (Compl. ¶27). The complaint alleges that Sandoz’s product is a generic version of CAPLYTA® and that Sandoz submitted its ANDA with studies intended to demonstrate its bioavailability and/or bioequivalence to the branded product (Compl. ¶28). The act of filing the ANDA to seek approval for marketing this generic drug prior to the expiration of the patents-in-suit is the basis for this Hatch-Waxman litigation (Compl. ¶1).

IV. Analysis of Infringement Allegations

U.S. Patent No. 11,980,617 Infringement Allegations

• Identified Points of Contention:
  • Scope Questions: A principal question will be whether Sandoz’s proposed label instructs or encourages the specific method of "treating acute depression and/or acute anxiety." The infringement theory rests on the contents of this label, which are not detailed in the complaint. The construction of the term "acute" will be central to this inquiry.
  • Technical Questions: What evidence does the complaint provide that the proposed use is for acute conditions, as opposed to the general treatment of depressive episodes associated with bipolar disorder? The court will examine the specific language of Sandoz's proposed label to determine if it induces infringement of this specific method claim.

U.S. Patent No. 12,070,459 Infringement Allegations

• Identified Points of Contention:
  • Scope Questions: What is the scope of "about 60 mg"? The parties may dispute whether Sandoz’s product, which contains an amount of tosylate salt equivalent to 42 mg of free base, falls within the range of this term.
  • Technical Questions: The infringement analysis will turn on the specific details of Sandoz's ANDA. Key factual questions include: (1) Does Sandoz’s product use the exact "mono-tosylate" salt in the specific "solid crystal form" required by the patent? (2) Is the concentration of the active ingredient between 10-30% by weight? (3) Do Sandoz's own bioequivalence studies demonstrate that its product meets the specific pharmacokinetic parameters recited in the claim when administered under fasting conditions?

V. Key Claim Terms for Construction

• The Term: "acute depression and/or acute anxiety" (’617 Patent, Claim 1)

• Context and Importance: This term defines the entire scope of the patented method. The infringement case for the ’617 Patent hinges on whether Sandoz's proposed label will instruct for treatment of this specific condition. Practitioners may focus on this term because its boundaries will determine whether the label for a general bipolar depression treatment can be read to induce infringement of a method for an acute condition.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent states that "acute depression" refers to the "initial period of what may be a brief or a chronic episode of depression" (’617 Patent, col. 35:36-39), which could be argued to cover the onset of any depressive episode.
  • Evidence for a Narrower Interpretation: The specification explicitly references specific DSM-5 definitions, such as "short-duration depressive episode" (4-14 days) and "recurrent brief depression" (2-13 days), which could support a narrower construction limited to these clinically defined short-term conditions. (’617 Patent, col. 35:1-10).

• The Term: "solid crystal form" (’459 Patent, Claim 1)

• Context and Importance: This term is critical because different crystal forms (polymorphs) of a drug are chemically distinct and can have different properties. Infringement requires Sandoz's product to use the same crystal form as claimed. Practitioners may focus on this term because a finding that Sandoz uses a different polymorph or an amorphous form would likely lead to a finding of non-infringement.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The claim language itself is general. A party might argue that without more specific limitations in the claim itself, the term should not be unduly restricted.
  • Evidence for a Narrower Interpretation: The ’459 patent specification explicitly incorporates by reference U.S. Patent No. 8,648,077, which discloses the physical properties, including the X-ray powder diffraction (XRPD) data, of a specific tosylate salt crystal form (’459 Patent, col. 4:10-14). A party will argue that "solid crystal form" is implicitly limited to the specific form detailed in the incorporated reference.

VI. Other Allegations

• Indirect Infringement: For the ’617 method patent, the complaint alleges Sandoz will actively induce infringement because its proposed product labeling will instruct physicians and patients to perform the claimed method of treating acute depression/anxiety (Compl. ¶46). For both patents, it alleges contributory infringement on the basis that the Sandoz product is not a staple article of commerce and is not suitable for substantial non-infringing use for the patented methods/compositions (Compl. ¶¶47, 72).
• Willful Infringement: The complaint alleges willful infringement based on Sandoz’s knowledge of the patents-in-suit, evidenced by its filing of a Paragraph IV certification, and its continued intent to market the generic product notwithstanding this knowledge (Compl. ¶¶50, 75).

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

• A core issue will be one of definitional scope and label interpretation: For the ’617 patent, can the term "acute depression," which the patent links to specific, short-duration clinical definitions, be construed to read on the instructions in Sandoz's proposed product label for the general treatment of depressive episodes in bipolar disorder?
• A second central issue will be one of factual and technical correspondence: For the ’459 patent, does the specific formulation detailed in Sandoz's confidential ANDA—including the polymorphic form of the lumateperone salt, the drug load percentage, and the resulting pharmacokinetic data from its bioequivalence studies—fall within the precise boundaries of the composition and performance parameters recited in Claim 1?