DCT
1:23-cv-00597
Janssen Pharma Inc v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Janssen Pharmaceuticals, Inc. (Pennsylvania) and Janssen Pharmaceutica NV (Belgium)
- Defendant: Sandoz Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Patterson Belknap Webb & Tyler LLP
- Case Identification: 1:23-cv-00597, D. Del., 05/31/2023
- Venue Allegations: Venue is based on Defendant Sandoz Inc. being a Delaware corporation.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's Spravato® (esketamine) nasal spray infringes four patents related to methods of use for treating depression and specific pharmaceutical compositions.
- Technical Context: The technology concerns pharmaceutical formulations and treatment protocols for esketamine, a rapid-acting antidepressant used for treating major depressive disorders, particularly in patients who have not responded to other treatments.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a Notice Letter, dated April 17, 2023, in which Sandoz informed Janssen of its ANDA submission containing a Paragraph IV certification of non-infringement, invalidity, or unenforceability for the patents-in-suit. The asserted patents are listed in the FDA's "Orange Book" as covering the Spravato® product. The complaint notes that as of the filing date, Sandoz has not provided Janssen with substantive technical details from its ANDA.
Case Timeline
| Date | Event |
|---|---|
| 2013-03-15 | ’260 Patent Priority Date |
| 2014-09-15 | ’844, ’134, and ’500 Patents Priority Date |
| 2020-12-22 | U.S. Patent No. 10,869,844 Issued |
| 2021-11-16 | U.S. Patent No. 11,173,134 Issued |
| 2022-04-26 | U.S. Patent No. 11,311,500 Issued |
| 2022-09-20 | U.S. Patent No. 11,446,260 Issued |
| 2023-04-17 | Sandoz sends Paragraph IV Notice Letter to Janssen |
| 2023-05-31 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,869,844 - "Methods for the Treatment of Depression"
- Issued: December 22, 2020
The Invention Explained
- Problem Addressed: The patent describes the clinical challenge of treating patients with depression, particularly treatment-resistant depression (TRD), and notes that many existing antidepressant therapies have a delayed onset of action, leaving patients symptomatic for extended periods ('844 Patent, col. 1:20-29).
- The Patented Solution: The invention provides specific methods for treating depression using intranasal esketamine (the S-enantiomer of ketamine) according to defined dosing regimens ('844 Patent, col. 2:20-33). The patent discloses an "induction phase" where the drug is administered frequently (e.g., twice weekly) for a set period to achieve a rapid antidepressant effect, and links treatment response to a patient's genetic profile related to the BDNF gene ('844 Patent, col. 26:1-20, Fig. 1).
- Technical Importance: This technology represents an approach to personalized medicine in psychiatry, using a genetic biomarker to potentially predict and optimize a patient's response to a rapid-acting antidepressant therapy ('844 Patent, Abstract).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 19, among others (Compl. ¶30).
- Claim 1 requires essential elements including:
- A method of treating major depressive disorder.
- Intranasally administering esketamine in an induction dosage.
- The dosage is in an amount of about 56 mg to about 84 mg.
- The induction phase is about four weeks.
- The dosage is administered at a frequency of twice per week during the induction phase.
- Claim 19 requires essential elements including:
- Genetically testing a patient to determine their Val66Met rs6265 polymorphism in the BDNF gene.
- Administering an esketamine dosing regimen matched to the patient's genotype.
- The complaint states that Plaintiffs reserve the right to assert additional claims, including dependent claims (Compl. ¶¶30, 36).
U.S. Patent No. 11,173,134 - "Methods for the Treatment of Depression"
- Issued: November 16, 2021
The Invention Explained
- Problem Addressed: The patent addresses the same problem as the ’844 Patent: the need for effective treatment regimens for major depressive disorder, including TRD ('134 Patent, col. 1:21-30).
- The Patented Solution: This patent builds on the '844 Patent by claiming a full treatment protocol comprising both an "induction phase" and a subsequent "maintenance phase" ('134 Patent, Abstract). The claims detail specific dosage amounts and reduced administration frequencies for the maintenance phase (e.g., once per week or once every two weeks) designed to sustain the antidepressant effect achieved during induction ('134 Patent, col. 2:48-58).
- Technical Importance: The invention provides a structured, long-term dosing strategy for intranasal esketamine, aiming to maintain treatment efficacy while potentially reducing the dosing burden on patients after the initial treatment period.
Key Claims at a Glance
- The complaint asserts claims 1-30, which include independent claims 1 and 21 (Compl. ¶45).
- Claim 1 requires essential elements including:
- A method of treating major depressive disorder during a maintenance phase.
- The patient has optionally been treated in an induction phase of about four weeks.
- Intranasally administering an aqueous formulation of esketamine.
- The maintenance dosage provides an effective amount of about 56 mg or about 84 mg.
- The dosage is administered at a frequency of once per week or once every two weeks.
- The complaint reserves the right to assert additional claims (Compl. ¶¶45, 52).
U.S. Patent No. 11,311,500 - "Methods for the Treatment of Depression"
- Issued: April 26, 2022
- Technology Synopsis: This patent, part of the same family as the ’844 and ’134 patents, also claims methods of treating depression with esketamine. It focuses on the complete treatment regimen involving an induction phase of specified duration and frequency (e.g., twice weekly for four weeks) followed by a maintenance phase with a different, less frequent dosing schedule ('500 Patent, Abstract).
- Asserted Claims: Claims 1-22 are asserted (Compl. ¶61).
- Accused Features: Sandoz's ANDA for generic esketamine nasal spray is accused of infringing by seeking approval for a product to be used according to these methods (Compl. ¶62).
U.S. Patent No. 11,446,260 - "Pharmaceutical Composition of S-Ketamine Hydrochloride"
- Issued: September 20, 2022
- Technology Synopsis: This patent is directed to the pharmaceutical formulation itself, not the method of treatment. It claims an aqueous formulation of S-ketamine hydrochloride for nasal administration that does not contain an antimicrobial preservative, based on the discovery that S-ketamine hydrochloride itself provides sufficient antimicrobial properties at certain concentrations ('260 Patent, Abstract, col. 2:16-24).
- Asserted Claims: Claims 1-3, 6-19, 22, 25-26, 31-43, 46-58, 61, 64-65, and 70-75 are asserted (Compl. ¶77).
- Accused Features: The composition of Sandoz's proposed generic esketamine nasal spray product is accused of infringing these formulation claims (Compl. ¶78).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are the proposed generic esketamine nasal spray products described in Sandoz's ANDA No. 215418 (Compl. ¶2).
Functionality and Market Context
- The complaint does not provide specific technical details of Sandoz's proposed product, stating that Sandoz has not yet provided access to its ANDA (Compl. ¶27). The infringement allegations are based on the statutory act of filing the ANDA and the legal requirement that a generic drug's labeling must generally be identical to the approved labeling for the reference listed drug, Janssen's Spravato® (Compl. ¶¶37, 39). The complaint alleges, upon information and belief, that Sandoz's ANDA seeks approval to market its generic products in one or more doses for the treatment of depression prior to the expiration of the patents-in-suit (Compl. ¶¶31, 46, 62, 78).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not contain a claim chart. The infringement allegations are based on the theory that Sandoz’s submission of ANDA No. 215418 constitutes an act of infringement under 35 U.S.C. § 271(e)(2) and that the future commercial product will infringe under § 271(a), (b), and (c). The narrative theory for the method patents ('844, '134, and '500) rests on the allegation that Sandoz's proposed product labeling will instruct users to perform the patented methods (Compl. ¶39).
'844 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating major depressive disorder in a human patient in need thereof | Sandoz’s ANDA allegedly seeks approval to market a generic esketamine nasal spray for the treatment of depression. | ¶31 | col. 1:20-22 |
| comprising intranasally administering (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone | Sandoz's proposed product is an esketamine nasal spray. | ¶31 | col. 2:20-25 |
| in an induction dosage... in an amount in the range of from about 56 mg to about 84 mg | The proposed product labeling, by copying the Spravato® label, will allegedly instruct administration of dosages within this range. | ¶39 | col. 27:50-55 |
| in an induction phase, wherein the induction phase comprises a treatment period of about four weeks, and the induction dosage is administered at a frequency of twice per week during the induction phase | The proposed product labeling will allegedly instruct users to follow this specific induction phase protocol. | ¶39 | col. 27:40-45 |
'134 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating major depressive disorder in a human patient in need thereof during a maintenance phase | Sandoz's ANDA allegedly seeks approval to market a product whose labeling will instruct use for long-term treatment of depression. | ¶46 | col. 1:21-23 |
| wherein, optionally, the patient has already been treated with... [esketamine] in an induction phase of about four weeks | The proposed product labeling will allegedly instruct a maintenance phase following an induction phase consistent with the patent. | ¶55 | col. 2:48-51 |
| in a maintenance dosage to provide a therapeutically effective amount of about 56 mg or about 84 mg | The proposed product labeling will allegedly instruct administration of dosages within this range during the maintenance phase. | ¶55 | col. 2:54-56 |
| wherein the maintenance dosage is administered at a frequency of once per week or once every two weeks during the maintenance phase | The proposed product labeling will allegedly instruct this reduced frequency of administration during the maintenance phase. | ¶55 | col. 2:57-58 |
Identified Points of Contention
- Scope Questions: A central question for claim 19 of the ’844 Patent will be whether Sandoz’s proposed label instructs or encourages "genetically testing" a patient for the BDNF polymorphism. If it does not, this may provide a basis for a non-infringement argument as to that claim.
- Technical Questions: For the ’260 Patent, the primary technical question will be whether Sandoz's formulation, as detailed in its confidential ANDA, literally meets the claim limitation of "does not contain an antimicrobial preservative." This will depend on the chemical identity and function of all excipients in the generic product. For the method patents, the key question is whether Sandoz's proposed labeling will instruct every step of the claimed methods.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for analysis of specific disputed claim terms. However, based on the technology and the nature of ANDA litigation, certain terms may become central to the dispute.
The Term: "antimicrobial preservative" (from the ’260 Patent)
- Context and Importance: This is a negative limitation, and its construction will be critical for determining infringement of the formulation patent. The dispute may focus on whether an excipient included for a primary purpose (e.g., as a solubilizer or buffer) that also possesses secondary antimicrobial properties falls within the scope of the term. Practitioners may focus on this term because Sandoz could argue its formulation contains an ingredient with some antimicrobial effect that Janssen will contend is not an "antimicrobial preservative" as the term is used in the patent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party could argue that any ingredient that has a material antimicrobial effect in the final formulation functions as a preservative, regardless of its primary purpose.
- Evidence for a Narrower Interpretation: The specification provides a list of conventional preservatives, such as "benzalkonium chloride, ... methyl paraben, ethyl paraben, propyl paraben," etc. ('260 Patent, col. 2:36-46). A party could argue that the term should be construed as limited to substances of these classes or those added for the primary purpose of preservation, especially in light of the patent's teaching that S-ketamine itself provides the necessary preservative effect ('260 Patent, col. 3:45-51).
The Term: "about" (used with dosage amounts and time periods in the method patents)
- Context and Importance: The scope of the numerical ranges in the method claims will depend on the construction of "about." Sandoz could potentially design its product or label to recommend a dosage or duration just outside the specified ranges, raising the question of whether "about" expands the range to cover that recommendation.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term "about" is used consistently, suggesting the patentee intended some flexibility around the stated numerical values.
- Evidence for a Narrower Interpretation: The specification provides specific dosages used in clinical trials, such as "esketamine 0.40 mg/kg, esketamine 0.20 mg/kg" ('844 Patent, col. 33:23-24). A party could argue these examples limit the scope of "about" to values very close to those explicitly disclosed.
VI. Other Allegations
Indirect Infringement
- The complaint alleges both induced and contributory infringement for all four patents. Inducement is primarily based on the allegation that Sandoz's proposed product labeling will actively encourage and instruct physicians and patients to perform the patented methods of treatment, thereby infringing the method claims (Compl. ¶¶39, 55, 71, 87). Contributory infringement is based on the allegation that Sandoz's product is specifically designed for an infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶40, 56, 72, 88).
Willful Infringement
- The complaint does not use the term "willful infringement," but alleges that Sandoz has "actual knowledge" of the patents-in-suit as demonstrated by its submission of the Paragraph IV certification letter (Compl. ¶¶35, 51, 67, 83). It also pleads that the case is "exceptional" and requests attorneys' fees under 35 U.S.C. § 285, which can be associated with findings of egregious infringement (Compl. ¶¶43, 59, 75, 91).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of induced infringement: does Sandoz's proposed product label, once disclosed, contain instructions that will lead physicians and patients to practice every limitation of the asserted method claims, particularly the specific dosage and frequency requirements for the induction and maintenance phases?
- A key technical question will be one of formulation identity: does the chemical composition of Sandoz's generic product, as specified in its ANDA, fall within the scope of the ’260 Patent’s claims, particularly the negative limitation requiring the absence of an "antimicrobial preservative"?
- A central claim construction question will be the definitional scope of "genetically testing" in claim 19 of the ’844 Patent, and whether any language in Sandoz's proposed label meets that limitation, which appears to be a key element distinguishing that claim from others in the family.