DCT
3:24-cv-10239
Intra Cellular Therapies Inc v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Intra-Cellular Therapies, Inc. (Delaware)
- Defendant: Sandoz Inc. (Delaware)
- Plaintiff’s Counsel: Walsh Pizzi Oreilly Falanga LLP; Williams & Connolly LLP
- Case Identification: 3:24-cv-10239, D.N.J., 11/01/2024
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Sandoz has a principal place of business in the district and has allegedly committed acts of infringement in New Jersey, including preparing and submitting its Abbreviated New Drug Application (ANDA).
- Core Dispute: Plaintiff alleges that Defendant’s submission of an ANDA to the FDA for a generic version of Plaintiff's CAPLYTA® (lumateperone) product constitutes an act of infringement of three U.S. patents related to methods of treatment, pharmaceutical compositions, and capsule formulations for lumateperone.
- Technical Context: The technology relates to pharmaceutical treatments for neuropsychiatric disorders, specifically concerning the compound lumateperone, which is approved for treating schizophrenia and depressive episodes associated with bipolar disorder.
- Key Procedural History: This lawsuit arises under the Hatch-Waxman Act, triggered by Defendant’s submission of an ANDA containing a Paragraph IV certification, challenging the validity or infringement of Plaintiff's patents. The complaint notes that this action is related to prior, consolidated litigation between the same parties concerning other patents listed in the FDA's Orange Book for CAPLYTA®, indicating an ongoing, multi-patent dispute over the same generic product.
Case Timeline
| Date | Event |
|---|---|
| 2018-08-31 | '043 Patent Priority Date |
| 2019-07-07 | '155 Patent Priority Date |
| 2019-12-11 | '792 Patent Priority Date |
| 2024-02-15 | Sandoz notifies Plaintiff of its ANDA filing |
| 2024-03-28 | Plaintiff files first related lawsuit against Sandoz |
| 2024-08-29 | Plaintiff files second related lawsuit against Sandoz |
| 2024-09-17 | '155 Patent Issues |
| 2024-10-22 | '792 Patent Issues |
| 2024-10-29 | '043 Patent Issues |
| 2024-11-01 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 12,090,155 - "Methods," issued September 17, 2024 (’155 Patent)
The Invention Explained
- Problem Addressed: The patent’s background section describes an unmet need for safer and more effective treatments for Bipolar II Disorder, noting that existing antipsychotic agents are often misdiagnosed, improperly treated, or cause significant side effects such as sedation, metabolic issues, movement disorders (extrapyramidal symptoms), and suicidal thoughts (’155 Patent, col. 3:25-33; col. 4:10-24).
- The Patented Solution: The invention provides a specific method for treating major or depressive episodes associated with Bipolar II Disorder by administering a therapeutically effective amount of lumateperone in its mono-tosylate salt form (’155 Patent, Abstract). The specification describes clinical trial results where lumateperone demonstrated efficacy without causing common adverse effects like akathisia (a movement disorder linked to suicide), restlessness, or significant weight gain, which are associated with other antipsychotics (’155 Patent, col. 5:8-28).
- Technical Importance: The claimed method provides a therapeutic approach for Bipolar II Disorder that may offer a more favorable safety profile compared to other treatments available at the time of the invention (’155 Patent, col. 4:25-33).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 22 (Compl. ¶¶40-41).
- Essential elements of independent claim 1 include:
- A method for the treatment of a major depressive episode associated with Bipolar II Disorder.
- Comprising administering to a patient a therapeutically effective amount of lumateperone in mono-tosylate salt form.
- Wherein the method comprises once daily administration of a tablet or capsule.
- Comprising "about 60 mg" of lumateperone mono-tosylate.
- In combination or association with a pharmaceutically acceptable diluent or carrier.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 12,122,792 - "Pharmaceutical Compositions Comprising 4-((6bR,10aS)-3-methyl2,3,6b,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin8(7H)-yl)-1-(4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)phenyl)butan-1-one for Treating Conditions of the Central Nervous System and Cardiac Disorders," issued October 22, 2024 (’792 Patent)
The Invention Explained
- Problem Addressed: The patent background discloses that a particular compound, a dimer of lumateperone (referred to as Formula I), was identified as a synthetic by-product in the synthesis of lumateperone (referred to as Formula II) (’792 Patent, col. 3:1-9). While typically considered an impurity, the inventors discovered this by-product possesses its own potent biological activity at key neurological receptors (’792 Patent, col. 3:1-9).
- The Patented Solution: The invention is a pharmaceutical composition that comprises both the lumateperone dimer (Formula I) and lumateperone itself (Formula II) in admixture with a pharmaceutically acceptable carrier (’792 Patent, Abstract; col. 5:3-13). This transforms a potential manufacturing impurity into a defined component of a new pharmaceutical composition.
- Technical Importance: The invention claims a novel composition containing what was previously considered a by-product, which the patent asserts has its own therapeutic potential, suggesting the possibility of a different or synergistic effect compared to lumateperone alone (’792 Patent, col. 3:1-9).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 29 (Compl. ¶¶67-68).
- Essential elements of independent claim 1 include:
- A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier in admixture with:
- (i) a compound of Formula I (the lumateperone dimer) in free base or salt form; and
- (ii) a compound of Formula II (lumateperone) in free base or salt form.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 12,128,043 - "Pharmaceutical Capsules Comprising Lumateperone Mono-Tosylate," issued October 29, 2024 (’043 Patent)
Technology Synopsis
This patent is directed to a specific pharmaceutical capsule formulation containing lumateperone mono-tosylate. The invention addresses the technical challenge of creating a stable, effective oral dosage form by defining the active ingredient's physical state (solid crystal form), its concentration within the capsule (10% to 30% by weight), the types of required excipients (e.g., diluent/filler, binder), and a specific functional characteristic related to its performance (a defined dissolution profile in aqueous hydrochloric acid) (’043 Patent, Abstract; col. 3:27-36).
Asserted Claims
Independent claim 1 is asserted (Compl. ¶94).
Accused Features
Plaintiff alleges that Sandoz's ANDA Product is a pharmaceutical capsule that meets each element of claim 1, including comprising lumateperone mono-tosylate in solid crystal form, blended with specific types of carriers in the claimed amounts, and exhibiting the claimed dissolution properties (Compl. ¶95).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Sandoz’s ANDA Product," a generic version of Plaintiff’s CAPLYTA® (lumateperone) capsules, for which Sandoz has filed ANDA No. 218938 seeking FDA approval (Compl. ¶¶1-2). The product is formulated in 10.5 mg, 21 mg, and 42 mg capsules (Compl. ¶2).
Functionality and Market Context
Sandoz's ANDA Product is a pharmaceutical intended for treating schizophrenia and depressive episodes associated with bipolar I or II disorder (Compl. ¶28). As a generic drug, it is designed to be bioequivalent to the branded CAPLYTA® product (Compl. ¶29). The act of infringement alleged under 35 U.S.C. § 271(e)(2) is the submission of the ANDA itself, which seeks approval to manufacture and sell the generic product before the expiration of the patents-in-suit (Compl. ¶45). Plaintiff alleges that upon approval, Sandoz intends to commercially manufacture, market, and sell the product throughout the United States (Compl. ¶8).
IV. Analysis of Infringement Allegations
’155 Patent 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... | Sandoz's proposed product labeling would allegedly direct and instruct physicians and patients to use the ANDA product to treat this condition. | ¶42 | col. 4:35-51 |
| ...comprising administering to a patient in need thereof, a therapeutically effective amount of lumateperone in mono-tosylate salt form... | Sandoz’s ANDA product contains lumateperone, and its proposed label would instruct administration of a therapeutically effective amount. | ¶38, ¶42 | col. 5:29-37 |
| ...wherein the method comprises once daily administration of a tablet or capsule... | The proposed labeling for Sandoz's capsule product would direct once daily administration. | ¶42 | col. 7:5-12 |
| ...comprising about 60 mg of lumateperone mono-tosylate... | The proposed labeling would instruct administration of a capsule comprising an amount equivalent to this dosage. | ¶42 | col. 7:5-12 |
| ...in combination or association with a pharmaceutically acceptable diluent or carrier. | Sandoz's ANDA product is a capsule formulation that contains pharmaceutically acceptable diluents and carriers. | ¶42 | col. 7:10-12 |
Identified Points of Contention:
- Scope Questions: A potential issue is the scope of "about 60 mg." Sandoz's product is allegedly dosed at 42 mg of lumateperone free base, which is the chemical equivalent of 60 mg of the mono-tosylate salt. The analysis may focus on whether this equivalence constitutes literal infringement of the "about 60 mg" limitation.
- Technical Questions: Since this is a method claim, the central question for infringement is one of inducement. The dispute will likely focus on the specific language in Sandoz's proposed product label. The key question for the court will be whether the label's instructions and indications for use would lead a physician or patient to directly infringe the steps of the patented method.
’792 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier in admixture with: | Sandoz's ANDA Product is alleged to be a pharmaceutical composition containing a diluent or carrier. | ¶69 | col. 5:3-5 |
| (i) a compound of Formula I... in free base or pharmaceutically acceptable salt form... | On information and belief, Sandoz’s ANDA Product is alleged to contain the compound of Formula I, which is a dimer of lumateperone. The complaint provides the chemical structure of Formula I (Compl. p. 15). | ¶69 | col. 1:45-60 |
| and (ii) a compound of Formula II... in free base or pharmaceutically acceptable salt form. | Sandoz's ANDA Product contains lumateperone, which is the compound of Formula II. | ¶65, ¶69 | col. 2:20-33 |
Identified Points of Contention:
- Scope Questions: A question may arise as to whether the presence of the Formula I dimer as a potential trace impurity, rather than an intentionally formulated ingredient, satisfies the claim requirement of a "pharmaceutical composition comprising" it "in admixture with" a carrier and Formula II.
- Technical Questions: The primary technical question is evidentiary: what proof exists that Sandoz's ANDA Product actually contains the compound of Formula I? The complaint makes this allegation "upon information and belief," suggesting that its presence is not explicitly disclosed by Sandoz. The resolution of this issue may depend on analytical chemistry testing of the accused product.
V. Key Claim Terms for Construction
For the ’155 Patent:
- The Term: "about 60 mg"
- Context and Importance: This term is critical because Sandoz's highest dosage strength is 42 mg of lumateperone free base, which Plaintiff will argue is the stoichiometric equivalent of 60 mg of the claimed mono-tosylate salt. The construction of "about" will determine whether this equivalence falls within the literal scope of the claim or if the doctrine of equivalents is required.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the word "about" itself suggests the patentee did not intend to be limited to a precise numerical value. The specification does not provide an explicit numerical range for "about," which may support giving the term its ordinary meaning of "approximately."
- Evidence for a Narrower Interpretation: The specification repeatedly and specifically references the clinical trial dose as "42 mg daily (administered orally as 60 mg of the tosylate salt)" (’155 Patent, col. 5:59-61). A party could argue this ties the claimed "about 60 mg" directly to the 42 mg free base equivalent, limiting the scope of "about" to that specific amount.
For the ’792 Patent:
- The Term: "pharmaceutical composition comprising"
- Context and Importance: This phrase is central to the infringement analysis for the ’792 Patent. Practitioners may focus on this term because the accused infringing element (the Formula I dimer) is alleged to be present on "information and belief," suggesting it could be an unintended manufacturing by-product. The definition of what it means for a "composition" to "comprise" a substance will be key to determining if the presence of a trace impurity meets this limitation.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term "comprising" is well-established in patent law as open-ended, meaning "including but not limited to." This could support an argument that the mere presence of Formula I, regardless of its amount or origin, is sufficient for the composition to "comprise" it.
- Evidence for a Narrower Interpretation: The patent describes the invention as a "pharmaceutical composition" (’792 Patent, Abstract). A party might argue that this implies a formulation where ingredients are intentionally included for a therapeutic purpose. Dependent claim 29, which specifies a weight ratio between Formula I and Formula II, could be cited as evidence that the inventors contemplated an intentional, formulated combination, not the incidental presence of an impurity.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement of infringement for all patents-in-suit. For the method claims of the ’155 Patent, this is the primary theory of infringement, based on the allegation that Sandoz’s proposed product label will instruct and encourage medical professionals and patients to perform the patented method (Compl. ¶49). The complaint alleges Sandoz has knowledge of the patents and specific intent to cause infringement (Compl. ¶49, ¶76, ¶101). Contributory infringement is also alleged on the basis that the accused product is not a staple article of commerce and is not suitable for substantial noninfringing use (Compl. ¶50, ¶77, ¶102).
- Willful Infringement: The complaint alleges that Sandoz has acted with "full knowledge" of the patents-in-suit, citing Sandoz's notice letter and Paragraph IV certification as evidence of pre-suit knowledge (Compl. ¶53, ¶80, ¶105). This forms the basis for a claim of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary question will be one of chemical presence: does Sandoz's ANDA Product contain the lumateperone dimer (Formula I) as required by the claims of the '792 patent? Resolution of this issue will likely rely on discovery into Sandoz’s manufacturing processes and the results of analytical testing on the accused product.
- A key legal and factual question for the '155 patent will be one of inducement: does the language of Sandoz's proposed product label provide sufficient instruction and encouragement to physicians to prescribe, and patients to use, the accused product in a manner that performs every step of the claimed method, thereby establishing the requisite intent for induced infringement?
- A core issue for the '043 patent will be one of functional performance: can Plaintiff demonstrate through testing that Sandoz’s capsule formulation meets the specific, multi-part dissolution profile recited in claim 1? This will likely involve a technical dispute over testing methodologies and results to determine if the accused product dissolves at the claimed rates under the specified conditions.