DCT
2:24-cv-08624
Axsome Malta LTD. v. Aurobindo Pharma USA, INC.
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Axsome Malta Ltd. (Republic of Malta) and Axsome Therapeutics, Inc. (Delaware)
- Defendant: Aurobindo Pharma USA, Inc. (Delaware) and Aurobindo Pharma Limited (India)
- Plaintiff’s Counsel: Saul Ewing LLP
- Case Identification: 2:24-cv-08624, D.N.J., 08/21/2024
- Venue Allegations: Venue is alleged based on Defendant Aurobindo Pharma USA, Inc.’s principal place of business in the District of New Jersey, its systematic and continuous business conduct in the district, and its prior consent to personal jurisdiction in the district. Venue over foreign Defendant Aurobindo Pharma Limited is alleged based on its purposeful availment of the U.S. market through its U.S. subsidiary.
- Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) seeking to market a generic version of the drug Sunosi® (solriamfetol) constitutes an act of infringement of four U.S. patents covering specific formulations and methods of administering the drug.
- Technical Context: The technology relates to solriamfetol, a dopamine and norepinephrine reuptake inhibitor (DNRI) approved for improving wakefulness in adults with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.
- Key Procedural History: This Hatch-Waxman litigation was triggered by Defendant Aurobindo's submission of ANDA No. 218725 and its subsequent sending of Paragraph IV certification notice letters to Plaintiff Axsome between August 2023 and July 2024, asserting that the patents-in-suit are invalid and/or will not be infringed by its proposed generic product. The complaint also notes related, consolidated litigation involving the same plaintiffs and defendants concerning the same pharmaceutical product.
Case Timeline
| Date | Event |
|---|---|
| 2016-09-06 | Earliest Priority Date for ’639 Patent |
| 2017-06-01 | Earliest Priority Date for ’454 and ’455 Patents |
| 2022-03-03 | Earliest Priority Date for ’036 Patent |
| 2023-08-10 | Aurobindo sends first Paragraph IV Notice Letter to Axsome (no earlier than) |
| 2023-12-08 | Aurobindo sends second Paragraph IV Notice Letter to Axsome (no earlier than) |
| 2024-02-13 | Aurobindo sends third Paragraph IV Notice Letter to Axsome (no earlier than) |
| 2024-02-27 | Aurobindo sends fourth Paragraph IV Notice Letter to Axsome (no earlier than) |
| 2024-05-21 | U.S. Patent No. 11,986,454 Issues |
| 2024-05-21 | U.S. Patent No. 11,986,455 Issues |
| 2024-05-21 | Aurobindo sends fifth Paragraph IV Notice Letter to Axsome (no earlier than) |
| 2024-06-04 | U.S. Patent No. 11,998,639 Issues |
| 2024-06-11 | U.S. Patent No. 12,005,036 Issues |
| 2024-07-09 | Aurobindo sends sixth Paragraph IV Notice Letter to Axsome (no earlier than) |
| 2024-08-21 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,986,454 - “Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function” (Issued May 21, 2024)
The Invention Explained
- Problem Addressed: The patent’s background section explains that solriamfetol (APC-HCl) is eliminated from the body primarily through renal excretion, meaning patients with impaired kidney function would be expected to have higher, potentially unsafe, exposure to the drug (ʼ454 Patent, col. 2:40-50). Prior to the invention, it was reportedly unknown what dosage, if any, would be safe and effective for this patient population given the drug's specific pharmacological profile (ʼ454 Patent, col. 2:50-54).
- The Patented Solution: The invention provides specific, adjusted dosing regimens for administering solriamfetol to subjects based on their level of renal impairment, as measured by their estimated glomerular filtration rate (eGFR) (ʼ454 Patent, Abstract). For patients with moderate renal impairment, the patent discloses a dose-escalation scheme starting with a lower initial dose (37.5 mg) and increasing to a lower maximum dose (75 mg) only after at least five days to allow for tolerance development (ʼ454 Patent, col. 3:1-12). For patients with severe renal impairment, a lower maximum daily dose (37.5 mg) is specified (ʼ454 Patent, col. 3:12-15).
- Technical Importance: This patented method provides a way to safely administer a therapeutic agent to a specific patient subpopulation who might otherwise be at risk for dose-dependent adverse effects or be excluded from treatment (ʼ454 Patent, col. 2:55-65).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶37).
- Claim 1 recites essential elements for a method of treating excessive daytime sleepiness, including:
- Selecting a subject who does not have end-stage renal disease.
- Determining the subject's eGFR.
- For a subject with an eGFR of about 30-59 mL/min/1.73 m² (moderate impairment), administering a first oral daily dose equivalent to 37.5 mg of the active pharmaceutical ingredient (APC) for a period of five or more days, followed by a second oral daily dose equivalent to 75 mg APC.
- For a subject with an eGFR of about 15-29 mL/min/1.73 m² (severe impairment), administering an oral daily dose equivalent to 37.5 mg APC.
U.S. Patent No. 11,986,455 - “Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function” (Issued May 21, 2024)
The Invention Explained
- Problem Addressed: The ʼ455 Patent, which shares a specification with the ʼ454 Patent, addresses the same technical problem: the lack of a known safe and effective dosing regimen for the renally-cleared drug solriamfetol in patients with impaired kidney function (ʼ455 Patent, col. 2:40-54).
- The Patented Solution: The invention provides optimized and adjusted dosing methods for solriamfetol based on a patient's degree of renal impairment (ʼ455 Patent, Abstract). The solution involves specific dose-escalation schemes and maximum daily dosages tailored to patients with moderate and severe renal impairment, respectively, to minimize adverse effects while maintaining therapeutic benefit (ʼ455 Patent, col. 3:1-18).
- Technical Importance: The claimed methods enable the safe administration of solriamfetol to renally impaired patients, a population that requires specific dosing considerations due to altered drug clearance (ʼ455 Patent, col. 2:55-65).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶46).
- Claim 1 recites essential elements for a method of treating excessive daytime sleepiness in a subject with moderate or severe renal impairment, including:
- For a subject with moderate renal impairment, administering a first oral daily dose equivalent to 37.5 mg APC for a period of five or more days, followed by a second oral daily dose equivalent to 75 mg APC.
- For a subject with severe renal impairment, administering an oral daily dose equivalent to 37.5 mg APC.
U.S. Patent No. 11,998,639 - “Formulations of (R)-2-Amino-3-Phenylpropyl Carbamate” (Issued June 4, 2024)
- Patent Identification: U.S. Patent No. 11,998,639, "Formulations of (R)-2-Amino-3-Phenylpropyl Carbamate," issued June 4, 2024 (Compl. ¶10).
- Technology Synopsis: The patent addresses the need for an immediate-release oral tablet of solriamfetol that has a high drug load but still dissolves quickly and consistently across the different pH environments of the gastrointestinal tract (ʼ639 Patent, col. 4:50-58). The invention is a specific formulation comprising 90-98% active pharmaceutical ingredient, 1-5% of a binder such as hydroxypropyl cellulose, and 0.1-2% of a lubricant, which achieves rapid dissolution without requiring a traditional disintegrant excipient (ʼ639 Patent, Abstract).
- Asserted Claims: At least independent claim 1 (Compl. ¶55).
- Accused Features: The complaint alleges that Aurobindo's proposed generic solriamfetol oral tablets are formulations that will infringe the ’639 Patent (Compl. ¶55).
U.S. Patent No. 12,005,036 - “Methods of Administering Solriamfetol to Lactating Women” (Issued June 11, 2024)
- Patent Identification: U.S. Patent No. 12,005,036, "Methods of Administering Solriamfetol to Lactating Women," issued June 11, 2024 (Compl. ¶11).
- Technology Synopsis: The patent addresses the technical problem of how to safely administer solriamfetol to a lactating mother while minimizing the drug's transfer to her breastfed infant ('036 Patent, col. 1:16-21). The patented solution is a method wherein the mother waits a specific period of time after taking the drug before feeding the infant (e.g., at least 5 hours), thereby avoiding feeding during the period of peak drug concentration in the breast milk and reducing the infant's overall exposure ('036 Patent, Abstract).
- Asserted Claims: At least independent claim 1 (Compl. ¶64).
- Accused Features: The complaint alleges that the product labeling for Aurobindo's proposed generic product will instruct lactating women on methods of administration that will induce infringement of the ’036 Patent (Compl. ¶67).
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is Aurobindo’s proposed generic solriamfetol oral tablets, for which it filed Abbreviated New Drug Application No. 218725 with the U.S. Food and Drug Administration (Compl. ¶1, ¶18).
- Functionality and Market Context: The proposed product is a generic version of Axsome's Sunosi® drug product, which is a dopamine and norepinephrine reuptake inhibitor (DNRI) (Compl. ¶1, ¶2). It is indicated to improve wakefulness in adult patients suffering from excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (Compl. ¶2). The complaint alleges that Aurobindo seeks approval to commercially manufacture and sell this generic product in the United States prior to the expiration of the patents-in-suit (Compl. ¶1).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint. The complaint does not provide sufficient detail, such as Aurobindo's proposed product label or formulation specifications, for a granular claim-by-claim analysis. The infringement allegations are based on the act of filing the ANDA for uses and formulations covered by the patents-in-suit. The following tables summarize the core theory of infringement for the lead patents.
'454 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating excessive daytime sleepiness in a subject in need thereof... comprising: | Aurobindo's ANDA seeks approval for its product to be used for treating excessive daytime sleepiness. | ¶37 | col. 47:40-42 |
| selecting a subject for not having end stage renal disease; | The proposed product label will allegedly instruct physicians to select patients according to their renal status, consistent with the claimed method. | ¶37 | col. 48:26-28 |
| determining the estimated glomerular filtration rate (eGFR) of the subject; | The proposed product label will allegedly instruct physicians to determine a patient's eGFR to guide dosing. | ¶37 | col. 48:29-31 |
| (a) providing to the subject having... an eGFR of about 30 mL/min/1.73 m² to about 59 mL/min/1.73 m²: a first oral daily dose equivalent to 37.5 mg... for... five or more days, and a second oral daily dose equivalent to 75 mg... | The proposed product label will allegedly instruct the specific dose escalation regimen for patients with moderate renal impairment as claimed. | ¶37 | col. 48:32-42 |
| (b) providing to the subject having... an eGFR of about 15 mL/min/1.73 m² to about 29 mL/min/1.73 m²: an oral daily dose equivalent to 37.5 mg APC... | The proposed product label will allegedly instruct the specific maximum dose for patients with severe renal impairment as claimed. | ¶37 | col. 48:43-49 |
'455 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating excessive daytime sleepiness in a subject in need thereof having moderate or severe renal impairment... comprising: | Aurobindo's ANDA seeks approval for its product to be used for treating excessive daytime sleepiness in the specific patient populations claimed. | ¶46 | col. 47:40-43 |
| (a) providing to the subject having moderate renal impairment... a first oral daily dose equivalent to 37.5 mg APC... for... five or more days... and a second oral daily dose equivalent to 75 mg APC... | The proposed product label will allegedly instruct the specific dose escalation regimen for patients with moderate renal impairment as recited in the claim. | ¶46 | col. 47:44-54 |
| (b) providing to the subject having severe renal impairment... an oral daily dose equivalent to 37.5 mg APC... | The proposed product label will allegedly instruct the specific maximum dose for patients with severe renal impairment as recited in the claim. | ¶46 | col. 47:55-61 |
- Identified Points of Contention:
- Scope Questions: A primary issue for the method patents ('454, '455, and '036) will be whether the specific instructions, warnings, and dosage recommendations in Aurobindo's proposed product labeling will be found by the court to "encourage, recommend, or promote" the exact steps recited in the asserted claims. Minor differences in wording, recommended timing, or dosage values between the label and the claims may form the basis of a non-infringement defense.
- Technical Questions: For the formulation patent ('639), the dispute will likely center on the precise composition of Aurobindo's tablet. The analysis will raise the factual question of whether an excipient in Aurobindo's product, even if not primarily labeled as such, functions as a "disintegrant," which would place the product outside the literal scope of claims containing that negative limitation.
V. Key Claim Terms for Construction
- The Term: 'wherein n₁ is an integer equal to or greater than 5' ('454 Patent, cl. 1; '455 Patent, cl. 1)
- Context and Importance: This term defines the minimum duration for the initial, lower dose in the claimed dose-escalation regimen for moderately renally impaired patients. Practitioners may focus on this term because Aurobindo's non-infringement defense could argue its proposed label instructs a different, shorter, or more flexible titration period, thereby designing around the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The complaint does not provide sufficient detail for analysis of evidence supporting a broader interpretation.
- Evidence for a Narrower Interpretation: The patent specification explains that this specific, multi-day titration schedule was developed to "account for tolerance development in the patient" and is based on pharmacokinetic and safety profile analyses ('454 Patent, col. 3:8-12). This suggests the "greater than 5" day period is a critical safety feature tied to the invention's technical contribution, which may support a narrow, literal interpretation of the term.
- The Term: 'wherein the formulation does not comprise a disintegrant' ('639 Patent, cl. 1)
- Context and Importance: This negative limitation is a defining feature of the claimed formulation. The infringement analysis will likely depend on whether any of the excipients in Aurobindo's generic tablet fall within the scope of the term "disintegrant." Practitioners may focus on this term because many pharmaceutical excipients can have multiple functions.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation (of what is NOT a disintegrant): The patent states that the claimed tablets "dissolve rather than disintegrate" and that the presence of a disintegrant "may actually slow down release" ('639 Patent, col. 7:10-15). This suggests a functional definition, where an excipient is only a "disintegrant" if it primarily functions to break the tablet apart, as opposed to merely facilitating dissolution.
- Evidence for a Narrower Interpretation (of what IS a disintegrant): The patent does not provide an explicit definition of the term, which may lead the court to rely on its plain and ordinary meaning in the pharmaceutical arts. An accused infringer could argue that an excipient (e.g., a type of starch or cellulose derivative) commonly known in the art as a disintegrant, even if it also serves as a binder or filler, would satisfy this limitation.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all four asserted patents. The basis for inducement is the allegation that Aurobindo's product labeling will intentionally encourage and instruct physicians and patients to perform the patented methods of use (Compl. ¶¶40, 49, 58, 67). The basis for contributory infringement is the allegation that Aurobindo's product is especially designed for an infringing use and lacks a substantial non-infringing use (Compl. ¶¶41, 50, 59, 68).
- Willful Infringement: The complaint does not explicitly plead willful infringement. However, it alleges that Aurobindo has knowledge of the patents-in-suit via the Paragraph IV notice letters and will intentionally encourage infringement (e.g., Compl. ¶40). Furthermore, the prayer for relief requests a judgment that this is an "exceptional case" pursuant to 35 U.S.C. § 285, which could entitle the plaintiff to an award of attorneys' fees (Compl., Prayer for Relief ¶J).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of instructional equivalence: will the specific directions for use in Aurobindo's proposed drug label be interpreted as instructing physicians and patients to perform the patented methods, particularly the precise dose-escalation timeline for moderately renally impaired patients and the feeding schedule for lactating mothers?
- A key factual question will be one of compositional analysis: does the chemical makeup of Aurobindo's proposed generic tablet, including its excipients and their respective functions, fall within the literal boundaries of the formulation claims of the '639 patent, especially the negative requirement that it "not comprise a disintegrant"?
- A central legal question will be the validity of the asserted claims, which Aurobindo has challenged in its Paragraph IV certifications. While the complaint asserts the patents are valid and enforceable, the ultimate resolution of the case will depend on whether Aurobindo can prove by clear and convincing evidence that the claims are invalid, for instance, on grounds of obviousness in light of prior art knowledge regarding pharmaceutical formulating or dose-adjusting for renally-cleared drugs.