DCT
2:24-cv-10938
Axsome Therap Inc v. Teva Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Axsome Therapeutics, Inc. (Delaware) and Antecip Bioventures II LLC (Delaware)
- Defendant: Teva Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Saul Ewing LLP
- Case Identification: 2:24-cv-10938, D.N.J., 12/05/2024
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Teva Pharmaceuticals, Inc. maintains its U.S. Headquarters and a principal place of business in Parsippany, New Jersey, and conducts continuous business in the state.
- Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application for a generic version of Auvelity® constitutes an act of infringement of a patent covering methods of treating major depressive disorder with a combination of dextromethorphan and bupropion.
- Technical Context: The case involves a combination drug therapy for major depressive disorder, where one component (bupropion) modifies the metabolism of the other (dextromethorphan), requiring specific dosing regimens and patient management to ensure safety and efficacy in various patient populations.
- Key Procedural History: The complaint notes that this lawsuit is part of a larger, ongoing dispute between the parties over Teva's attempt to market a generic version of Auvelity®. The complaint references multiple prior Paragraph IV notice letters from Teva concerning other patents and identifies two existing, consolidated lawsuits in the same district (23-cv-1695 and 24-6489) involving the same parties and drug product but different patents. This action was triggered by the recent issuance of the patent-in-suit.
Case Timeline
| Date | Event |
|---|---|
| 2022-07-07 | '889 Patent Priority Date |
| 2023-02-09 | Teva's First Paragraph IV Notice Letter to Axsome (re: other patents) |
| 2023-11-02 | Teva's Second Paragraph IV Notice Letter to Axsome (re: other patents) |
| 2024-04-10 | Teva's Third Paragraph IV Notice Letter to Axsome (re: other patents) |
| 2024-05-01 | Teva's Fourth Paragraph IV Notice Letter to Axsome (re: other patents) |
| 2024-08-30 | Teva's Fifth Paragraph IV Notice Letter to Axsome (re: other patents) |
| 2024-11-19 | U.S. Patent No. 12,146,889 ('889 Patent) Issued |
| 2024-12-05 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
- Patent Identification: U.S. Patent No. 12,146,889, "Compounds and Combinations Thereof for Treating Neurological and Psychiatric Conditions," issued November 19, 2024.
- The Invention Explained:
- Problem Addressed: The patent addresses the challenge of safely administering a combination of dextromethorphan and bupropion for major depressive disorder (MDD) ('889 Patent, col. 25:1-4). Dextromethorphan is metabolized by the CYP2D6 enzyme, and bupropion inhibits this enzyme, which significantly increases dextromethorphan levels in the body ('889 Patent, col. 10:23-28). This interaction can lead to overexposure and adverse reactions, particularly in patients who have certain risk factors, such as concomitant use of other drugs containing the same active ingredients ('889 Patent, col. 25:1-26:10). The patent also notes that other advanced depression therapies, such as esketamine, carry significant risks of dissociation and require extensive patient monitoring, which the patented method seeks to avoid ('889 Patent, col. 11:1-12:6).
- The Patented Solution: The patent claims specific methods for managing patients being treated with the dextromethorphan/bupropion combination. The invention is not merely the drug itself, but a multi-step therapeutic method that includes screening patients for concomitant medications, administering the drug on a specific dosing schedule, monitoring for adverse reactions, and actively informing patients of specific risks like seizures or serotonin syndrome ('889 Patent, col. 25:1-26:21). These patient management steps are designed to mitigate the risks associated with drug interactions and ensure the therapy's safe use.
- Technical Importance: This approach provides a protocol to tailor a known drug combination to patients with complex medical profiles, potentially expanding its safe use while avoiding the burdensome monitoring and significant side effects associated with other treatments for MDD ('889 Patent, col. 12:1-6).
- Key Claims at a Glance:
- The complaint asserts independent claims 1, 6, and 11 (Compl. ¶25).
- Independent Claim 1 recites a method of treating MDD comprising:
- Screening a patient to determine if they are receiving other medications containing bupropion.
- If concomitant use is warranted, administering a tablet (45 mg dextromethorphan / 105 mg bupropion) once daily for 3 days, then twice daily thereafter.
- Instructing the patient not to crush, divide, or chew the tablet.
- Monitoring the patient for a neuropsychiatric reaction.
- Informing the patient of a dose-related seizure risk and discontinuing administration if a seizure occurs.
- Independent Claim 6 recites a similar method, but focuses on screening for concomitant use of dextromethorphan and informing the patient about the risk of serotonin syndrome.
- Independent Claim 11 recites a similar method, but focuses on screening for concomitant use of any serotonergic drug and informing the patient about the risk of serotonin syndrome.
- The complaint reserves the right to assert additional claims.
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is "Teva's Proposed Product," which is the generic version of Plaintiffs' Auvelity® described in Teva's Abbreviated New Drug Application (ANDA) No. 218147 (Compl. ¶1, 17).
- Functionality and Market Context:
- Teva's Proposed Product is a generic dextromethorphan hydrobromide and bupropion hydrochloride extended-release tablet (Compl. ¶1).
- It is intended for the treatment of major depressive disorder in adults (Compl. ¶7). The act of infringement alleged in the complaint is the submission of the ANDA itself, which seeks FDA approval to market this generic drug prior to the expiration of the '889 Patent (Compl. ¶1, 25). The infringement theory is prospective, based on the allegation that the use of Teva's product, as will be instructed by its FDA-approved label, would infringe the method claims of the '889 Patent (Compl. ¶27-28).
IV. Analysis of Infringement Allegations
The complaint alleges that the use of Teva's Proposed Product in accordance with its proposed label will directly and indirectly infringe the asserted claims (Compl. ¶27-29). The following chart summarizes the infringement theory for representative claim 1, based on the statutory framework of ANDA litigation where the proposed product label is the primary evidence of infringement.
No probative visual evidence provided in complaint.
'889 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating major depressive disorder, comprising screening a human patient who is experiencing major depressive disorder to determine if the human patient is receiving any other medications that contain bupropion; | The proposed label for Teva's product will allegedly instruct healthcare providers to take a patient history, which includes screening for concomitant medications such as other bupropion-containing products. | ¶25, 27-28 | col. 25:1-9 |
| and if the human patient is receiving a medication containing bupropion, and concomitant use...is clinically warranted, then: administering the tablet to the human patient once daily...for 3 days, and after 3 days, administering the tablet to the human patient twice daily... | The proposed label will allegedly instruct physicians to administer Teva's product according to the claimed dosing schedule for treating MDD. | ¶25, 27-28 | col. 25:10-18 |
| and instructing the patient to not crush, divide or chew the tablet... | The proposed label will allegedly contain instructions for patients to swallow the tablet whole and not to crush, divide, or chew it, consistent with its extended-release formulation. | ¶25, 27-28 | col. 25:17-19 |
| monitoring the human patient for a neuropsychiatric reaction, and instructing the human patient to contact a healthcare provider if a neuropsychiatric reaction occurs; | The proposed label will allegedly instruct healthcare providers to monitor patients for adverse neuropsychiatric events, a known consideration for this class of drugs. | ¶25, 27-28 | col. 25:20-24 |
| and informing the patient of a dose-related risk of seizure associated with bupropion-containing products and immediately discontinuing administration of the tablet if the human patient experiences a seizure. | The proposed label will allegedly instruct healthcare providers to inform patients about the risk of seizure associated with bupropion and to discontinue the drug if a seizure occurs. | ¶25, 27-28 | col. 25:25-31 |
- Identified Points of Contention:
- Scope Questions: A central issue may be whether the instructions and warnings in Teva's proposed product label will be specific enough to induce infringement of the affirmative "screening," "monitoring," and "informing" steps required by the claims. The court may need to decide if a general warning in a package insert satisfies a claim limitation requiring a healthcare provider to actively "inform" or "monitor" a patient in a particular way.
- Technical Questions: The dispute will likely focus on the precise language of Teva's proposed label. For infringement to be induced, the label must encourage, recommend, or promote the performance of all steps of the claimed method. A key question of fact will be whether the label's guidance on managing side effects and drug interactions maps directly onto the specific sequence of actions recited in claims 1, 6, and 11.
V. Key Claim Terms for Construction
The Term:
"screening a human patient ... to determine if"(Claim 1)Context and Importance: This term appears at the beginning of each independent claim and requires an active, pre-treatment step. The construction of "screening" is critical because it sets the bar for what a healthcare provider must do to directly infringe. Whether this requires a formal diagnostic or is met by a routine patient interview will be a key point of dispute.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not provide a specific definition for "screening," which may suggest the term should be given its plain and ordinary meaning, potentially encompassing any inquiry (e.g., verbal questioning) that determines the patient's concomitant medications.
- Evidence for a Narrower Interpretation: A defendant may argue that in the context of a detailed, multi-step method, "screening" implies a more formalized process than a casual question, though the specification does not appear to provide explicit support for a narrower definition.
The Term:
"monitoring the human patient for a neuropsychiatric reaction"(Claim 1)Context and Importance: This term defines an ongoing obligation for the healthcare provider. Practitioners may focus on this term because its definition will determine whether infringement requires specific, scheduled follow-up actions or if it is met by passive observation during routine appointments.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discusses monitoring in the context of neuropsychiatric reactions but does not define a specific protocol ('889 Patent, col. 19:8-15), potentially allowing the term to cover standard clinical vigilance.
- Evidence for a Narrower Interpretation: Plaintiffs may argue that the term, when read in light of the patent's focus on managing specific risks, requires more than routine care and implies an active, focused assessment for the particular reactions mentioned.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b), stating that Teva, with knowledge of the '889 Patent, will intentionally encourage infringement by physicians and patients through the instructions on its FDA-approved product label (Compl. ¶28). The complaint also alleges contributory infringement under § 271(c), asserting that Teva's product is specifically designed for an infringing use and lacks a substantial non-infringing use (Compl. ¶29).
- Willful Infringement: While the complaint does not contain a separate count for "willful infringement," it alleges that Teva will induce infringement "with knowledge of the '889 patent" (Compl. ¶28). This allegation of knowing infringement, combined with the request for a finding that the case is "exceptional" and thus merits an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶32), forms the factual basis for a potential enhancement of damages if infringement is found.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of label-based inducement: Will the final, FDA-approved label for Teva's generic product contain instructions and warnings that are specific enough to encourage medical professionals to perform each and every affirmative step of the asserted method claims, including the distinct
"screening","monitoring", and"informing"actions? - A key legal question will be one of claim scope: How will the court construe the active patient-management verbs in the claims? Whether terms like
"screening"and"monitoring"are interpreted to cover routine clinical practice and standard label warnings, or are found to require more specific, directed actions, will likely be determinative of the infringement analysis.