DCT
3:24-cv-08845
Intra Cellular Therapies Inc v. Alkem Laboratories Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Intra-Cellular Therapies, Inc. (Delaware)
- Defendant: Alkem Laboratories Ltd. (Republic of India)
- Plaintiff’s Counsel: Walsh Pizzi O'Reilly Falanga LLP; Williams & Connolly LLP
- Case Identification: 3:24-cv-08845, D.N.J., 08/29/2024
- Venue Allegations: Venue is alleged to be proper because the defendant is a company organized under the laws of the Republic of India and is subject to personal jurisdiction in the District of New Jersey.
- Core Dispute: Plaintiff alleges that Defendant's Abbreviated New Drug Application (ANDA) to market a generic version of CAPLYTA® (lumateperone) constitutes an act of infringement of two recently issued patents covering methods of use and specific pharmaceutical formulations of the drug.
- Technical Context: The technology relates to pharmaceutical treatments for central nervous system disorders, specifically methods and formulations for treating depression and anxiety.
- Key Procedural History: The complaint notes that Plaintiff previously sued Defendant on March 28, 2024, for infringement of other patents related to CAPLYTA®, and that case has been consolidated with another action. This current lawsuit addresses two patents that issued after the filing of the prior litigation.
Case Timeline
| Date | Event |
|---|---|
| 2018-03-16 | '617 Patent Priority Date |
| 2018-08-31 | '459 Patent Priority Date |
| 2024-02-16 | Alkem sends First Notice Letter regarding its ANDA filing |
| 2024-03-28 | Plaintiff files prior infringement suit against Alkem |
| 2024-05-14 | U.S. Patent No. 11,980,617 issues |
| 2024-08-02 | Alkem sends Second Notice Letter regarding the '617 Patent |
| 2024-08-27 | U.S. Patent No. 12,070,459 issues |
| 2024-08-29 | Complaint Filing Date |
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 need for new, fast-acting methods for the acute treatment of depression and anxiety, noting that conventional antidepressants like SSRIs often take weeks or months to achieve their full effect, while existing rapid-acting treatments like ketamine have significant adverse side effects and a high risk of abuse (ʼ617 Patent, col. 3:8-48).
- The Patented Solution: The invention is a method for the acute treatment of depression or anxiety by administering lumateperone. The patent asserts the surprising discovery that lumateperone provides a fast-acting antidepressant effect through a distinct mechanism involving the enhancement of NMDA and AMPA currents and activation of the mTOR signaling pathway, which is distinct from traditional antidepressants and lacks the side effects of ketamine (ʼ617 Patent, col. 4:46-6:1; Abstract).
- Technical Importance: The invention provides a method for an orally-available, rapid-acting treatment for acute depressive and anxiety episodes, which could fill a significant gap between slow-acting conventional therapies and rapid but problematic alternatives (ʼ617 Patent, col. 4:51-6:1).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims, with a focus on independent claim 1 (Compl. ¶¶38-39).
- Essential elements of independent claim 1 include:
- 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 (lumateperone),
- in free, or pharmaceutically acceptable salt form.
U.S. Patent No. 12,070,459 - Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate
Issued August 27, 2024
The Invention Explained
- Problem Addressed: The patent’s background discusses lumateperone's therapeutic potential for various central nervous system disorders (ʼ459 Patent, col. 1:34-2:4). The claims suggest the technical problem is the creation of a specific, reliable oral dosage form that achieves a predictable pharmacokinetic (PK) profile.
- The Patented Solution: The patent claims a specific pharmaceutical capsule for oral administration containing lumateperone mono-tosylate in a solid crystal form. The invention is defined by the amount of the drug (about 60 mg), a specific blend percentage of the drug relative to excipients (10-30% by weight), and, critically, the achievement of a specific PK profile (Cmax, Tmax, and/or AUC) upon administration under fasting conditions (ʼ459 Patent, col. 18:1-43; Abstract).
- Technical Importance: This technology defines a specific oral formulation that provides predictable bioavailability of lumateperone, a key factor for ensuring consistent and effective treatment (ʼ459 Patent, col. 8:30-49).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims, with a focus on independent claim 1 (Compl. ¶¶63-64).
- Essential elements of independent claim 1 include:
- 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 about 60 mg of the lumateperone mono-tosylate,
- wherein the capsule comprises a blend of 10 to 30% by weight of the lumateperone mono-tosylate and specific excipients, and
- wherein administration under fasting conditions provides a maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), and/or area under the plasma concentration curve (AUC) within specified ranges.
III. The Accused Instrumentality
- Product Identification: Defendant Alkem's Abbreviated New Drug Application (ANDA) No. 219200, which seeks FDA approval to market a generic version of Plaintiff's CAPLYTA® product. The accused product consists of lumateperone capsules in 10.5 mg, 21 mg, and 42 mg dosages (Compl. ¶¶1-2, 26).
- Functionality and Market Context: The accused product contains lumateperone and is alleged to be a generic version of CAPLYTA®, which is approved for treating schizophrenia and depressive episodes associated with bipolar I or II disorder (Compl. ¶¶25-26). The complaint alleges that upon approval, Alkem will market its product for these indications, in direct competition with Plaintiff's branded drug (Compl. ¶¶8, 15). Infringement allegations for the '617 patent are based on the product's proposed labeled use, while allegations for the '459 patent are based on the product's physical composition and resulting pharmacokinetic profile (Compl. ¶¶40, 65). The complaint includes a chemical diagram of the compound of Formula I, identified as lumateperone (Compl. ¶39).
IV. Analysis of Infringement Allegations
'617 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating acute depression and/or acute anxiety, | The proposed labeling for Alkem's ANDA Product will direct its use for treating acute depression and/or acute anxiety. | ¶40 | col. 45:7-9 |
| comprising administering to a patient in need thereof, | The proposed labeling will instruct administration to a patient in need of such treatment. | ¶40 | col. 45:9-10 |
| a therapeutically effective amount of a Compound of Formula I: [structure] | Alkem's ANDA Product contains lumateperone (Compound of Formula I), which will be administered in therapeutically effective doses according to the label. The complaint includes a chemical diagram of lumateperone as recited in claim 1 of the '617 patent (Compl. ¶39). | ¶¶37, 39-40 | col. 45:10-14 |
| in free, or pharmaceutically acceptable salt form. | Alkem's ANDA Product contains lumateperone in a free or pharmaceutically acceptable salt form. | ¶40 | col. 45:15 |
- Identified Points of Contention:
- Scope Questions: A central question for the court will be whether the intended indications on Alkem's proposed product label (e.g., "depressive episodes associated with bipolar I or II disorder") fall within the scope of the claim term "acute depression and/or acute anxiety" as defined and used in the patent.
- Technical Questions: The infringement theory is contingent on the specific instructions and indications that will be included in Alkem's FDA-approved label. The factual evidence of what that label directs will be paramount to the infringement analysis.
'459 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical capsule for oral administration, comprising lumateperone... in mono-tosylate salt form, | Alkem's ANDA Product is a pharmaceutical capsule for oral administration that contains lumateperone mono-tosylate. | ¶65 | col. 18:1-19 |
| wherein the lumateperone mono-tosylate is in solid crystal form, | The lumateperone mono-tosylate in Alkem's product is alleged to be in a solid crystal form. | ¶65 | col. 18:20-21 |
| wherein the capsule comprises the lumateperone mono-tosylate in an amount of about 60 mg... | The complaint alleges Alkem's ANDA Product is a capsule comprising lumateperone mono-tosylate in the "specific amounts recited in claim 1." | ¶65 | col. 18:22-25 |
| wherein the capsule comprises a blend of 10 to 30% by weight of lumateperone mono-tosylate... and one or more pharmaceutically acceptable diluents or carriers... | Alkem's ANDA Product is alleged to comprise a blend of lumateperone mono-tosylate and excipients in the specific amounts recited in the claim. | ¶65 | col. 18:26-34 |
| and wherein administration... provides a maximal plasma concentration of lumateperone of 15-55 ng/mL, and/or a time to maximal plasma concentration... of 0.7 to 1.5 hours, and/or an area under the plasma concentration curve... of 51 to 135 hours-ng/mL. | The administration of Alkem's ANDA Product under fasting conditions is alleged to provide a pharmacokinetic profile that falls within the specific ranges recited in the claim. | ¶65 | col. 18:35-43 |
- Identified Points of Contention:
- Scope Questions: The claim requires "about 60 mg" of the mono-tosylate salt. Alkem's highest dosage is 42 mg of the lumateperone free base, which is the stoichiometric equivalent of 60 mg of the tosylate salt. A key legal question is whether the term "about 60 mg" will be construed to cover a product containing this equivalent amount.
- Technical Questions: The infringement allegation rests on the assertion that Alkem's product not only has the claimed physical composition (e.g., solid crystal form, blend percentage) but also achieves the specific pharmacokinetic profile claimed. This raises a significant evidentiary question that will likely depend on bioequivalence studies and expert testimony.
V. Key Claim Terms for Construction
Term from the '617 Patent: "acute depression"
- Context and Importance: This term is central to the method claim, and its definition will determine whether the use of Alkem's product for its labeled indications constitutes infringement. Practitioners may focus on this term because its interpretation dictates the breadth of the method claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification defines "acute depression" as "the initial period of what may be a brief or a chronic episode of depression" and further discusses its applicability to major depressive episodes, which are a component of bipolar disorder (ʼ617 Patent, col. 35:36-40, 35:10-15). This could support an interpretation that covers the initial phase of any depressive episode, regardless of the underlying chronic condition.
- Evidence for a Narrower Interpretation: The patent contrasts its "acute" treatment with conventional, long-term therapies for chronic conditions. A defendant could argue this context limits the term to a specific, self-contained event rather than an episodic manifestation of a chronic illness like bipolar disorder (ʼ617 Patent, col. 3:8-18).
Term from the '459 Patent: "about 60 mg"
- Context and Importance: The construction of this term is critical because Alkem's product dosages are specified in milligrams of the free base (10.5, 21, and 42 mg), not the claimed tosylate salt. The infringement allegation for the highest dose relies on the 42 mg free base being equivalent to 60 mg of the salt.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the word "about" inherently introduces a degree of numerical flexibility. Plaintiff may argue that in the context of pharmaceutical formulation, this term is intended to cover stoichiometrically equivalent amounts, making the 42 mg free base product (equivalent to 60 mg of the salt) fall squarely within the claim's scope.
- Evidence for a Narrower Interpretation: A defendant may argue that the claim is specific to the salt form and its weight, and that a product dosed and marketed by its free base weight (42 mg) is distinct from one claimed as "about 60 mg" of a salt. The precision of other claim limitations, such as the pharmacokinetic parameters, could be used to argue for a less flexible interpretation of "about" (ʼ459 Patent, col. 18:35-43).
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. Inducement is based on the allegation that Alkem's proposed product labeling will actively instruct and encourage physicians and patients to use the product in an infringing manner. Contributory infringement is based on the allegation that Alkem's product is especially made for an infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶46-47, 71-72).
- Willful Infringement: Willfulness is alleged based on Alkem's "full knowledge" of the patents-in-suit, evidenced by its Paragraph IV certifications submitted to the FDA and its notice letters sent to the Plaintiff. The complaint alleges that Alkem acted "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶¶50, 75).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: can the term "acute depression," as claimed in the '617 patent, be construed to cover the treatment of depressive episodes associated with bipolar disorder, an indication for which the accused generic product will likely be labeled?
- A key evidentiary question will be one of pharmacokinetic and compositional identity: does Alkem's 42 mg lumateperone capsule, on a factual basis, contain the specific solid crystal form and blend percentages and, most importantly, exhibit the specific Cmax, Tmax, and AUC profile required by claim 1 of the '459 patent?
- A central claim construction question will be the interpretation of numerical scope: can the limitation "about 60 mg" of the lumateperone mono-tosylate salt in the '459 patent be interpreted to read on a product that contains 42 mg of the lumateperone free base, which is the exact stoichiometric equivalent?