Xeris Pharma Inc v. Novitium Pharma LLC

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Xeris Pharmaceuticals, Inc. (Delaware) and Strongbridge Dublin Limited (Ireland)
  • Defendant: Novitium Pharma, LLC (Delaware) and ANI Pharmaceuticals, Inc. (Delaware)
  • Plaintiff's Counsel: FBT Gibbons LLP
• Case Identification: 2:26-cv-06568, D.N.J., 06/04/2026
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendants maintain a regular and established place of business in the district and because the filing of their Abbreviated New Drug Application (ANDA) from their New Jersey place of business constitutes an act of infringement within the district.
• Core Dispute: Plaintiffs allege that Defendants' submission of an ANDA to the FDA seeking approval to market a generic version of Plaintiffs' drug RECORLEV® (levoketoconazole) constitutes an act of infringement of four U.S. patents related to methods of treating Cushing's syndrome.
• Technical Context: The dispute is in the pharmaceutical space and concerns methods of safely administering levoketoconazole, a cortisol synthesis inhibitor, particularly by managing drug-drug interactions with co-administered medications like metformin for patients who also have type 2 diabetes.
• Key Procedural History: This is a Hatch-Waxman action filed under 35 U.S.C. § 271(e)(2) in response to Defendants' ANDA No. 221336 and Paragraph IV certification. Plaintiffs' drug, RECORLEV®, was approved by the FDA on December 30, 2021, and has orphan drug exclusivity until December 30, 2028. The asserted patents are listed in the FDA's Orange Book for RECORLEV®. The complaint was filed within 45 days of Plaintiffs' receipt of Defendants' notice letter, triggering a statutory stay of FDA approval for the generic product for up to 30 months.

Case Timeline

Date	Event
2019-03-04	Earliest Priority Date for '393, '547, '940, and '096 Patents
2021-06-01	'393 Patent Issued
2021-12-30	FDA Approved New Drug Application for RECORLEV®
2022-03-22	'547 Patent Issued
2024-02-20	'940 Patent Issued
2025-08-05	'096 Patent Issued
2026-04-24	Novitium Pharma, LLC Sent Paragraph IV Notice Letter
2026-04-27	Plaintiffs Received Paragraph IV Notice Letter
2026-06-04	Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 11,020,393 - Methods of Treating Disease With Levoketoconazole

• Patent Identification: U.S. Patent No. 11,020,393, "Methods of Treating Disease With Levoketoconazole," issued June 1, 2021.

The Invention Explained

• Problem Addressed: The patent describes that while ketoconazole has been used to treat Cushing's syndrome, it carries risks including liver damage (hepatoxicity) and significant drug-drug interactions, creating an unmet need for a safer, approved therapy Compl. ¶43 '393 Patent, col. 1:40-51
• The Patented Solution: The invention uses levoketoconazole, the 2S,4R enantiomer of ketoconazole, which is described as more potently inhibiting cortisol biosynthesis Compl. ¶44 '393 Patent, col. 1:52-59 The patent specifically discloses a method for managing the drug-drug interaction between levoketoconazole and metformin (a common diabetes drug) by monitoring the patient for specific "dose limiting events" and adjusting the metformin dose accordingly, based on clinical study findings that levoketoconazole increases metformin exposure '393 Patent, col. 2:52-62 '393 Patent, col. 23:20-25
• Technical Importance: The invention provides a specific, structured treatment protocol to safely manage co-administration of levoketoconazole and metformin, addressing a clinically significant drug-drug interaction discovered during development Compl. ¶45

Key Claims at a Glance

• The complaint asserts at least Claim 1 Compl. ¶68
• Independent Claim 1 requires:
  • A method of treating persistent or recurrent Cushing's syndrome in a subject who also has type 2 diabetes mellitus and is being co-administered metformin.
  • Administering a therapeutically effective amount of levoketoconazole determined via a titration scheme.
  • During the titration, monitoring the subject for a dose limiting event, specified as a decreased fasting glucose level, abnormal kidney function, and/or a low Vitamin B-12 level.
  • If the subject experiences a dose limiting event, reducing the amount of metformin administered.
• The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 11,278,547 - Methods of Treating Disease With Levoketoconazole

• Patent Identification: U.S. Patent No. 11,278,547, "Methods of Treating Disease With Levoketoconazole," issued March 22, 2022.

The Invention Explained

• Problem Addressed: The '547 patent addresses the same general problem as the '393 patent: the need for a safer, more effective treatment for Cushing's syndrome than ketoconazole, particularly concerning the management of drug-drug interactions '547 Patent, col. 1:41-51
• The Patented Solution: The '547 patent claims a similar method of treatment as the '393 patent, involving the administration of levoketoconazole with co-administered metformin, but narrows the patient population to those who have already undergone surgery or radiation for their Cushing's syndrome '547 Patent, claim 1 This method also requires monitoring for specific dose-limiting events and reducing the metformin dose if one occurs, addressing the interaction where levoketoconazole increases metformin exposure '547 Patent, col. 2:52-62 '547 Patent, col. 23:20-25
• Technical Importance: This patent provides a tailored treatment protocol for a specific sub-population of Cushing's syndrome patients (post-surgery/radiation), who may have persistent or recurrent disease and require medical therapy.

Key Claims at a Glance

• The complaint asserts at least Claim 1 Compl. ¶89
• Independent Claim 1 requires:
  • A method of treating Cushing's syndrome in a subject who has had previous surgery or radiation to treat the subject's Cushing syndrome, who also has type 2 diabetes mellitus, and is being co-administered metformin.
  • Administering a therapeutically effective amount of levoketoconazole determined via a titration scheme.
  • During the titration, monitoring for a dose limiting event (decreased fasting glucose, abnormal kidney function, and/or a low Vitamin B-12 level).
  • If a dose limiting event is experienced, reducing the amount of metformin administered.
• The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 11,903,940 - Methods of Treating Disease With Levoketoconazole

• Patent Identification: U.S. Patent No. 11,903,940, "Methods of Treating Disease With Levoketoconazole," issued February 20, 2024.
• Technology Synopsis: This patent focuses on the specific biochemical mechanism behind the drug-drug interaction between levoketoconazole and other drugs. It claims a method of treating Cushing's syndrome in a patient who is also taking an organic cation transporter 2 (OCT2) substrate. The method involves monitoring for and reacting to dose-limiting events caused by levoketoconazole's inhibition of OCT2, which increases the patient's exposure to the co-administered OCT2 substrate '940 Patent, abstract '940 Patent, claim 1
• Asserted Claims: At least Claim 1 Compl. ¶110
• Accused Features: The proposed label for the Novitium ANDA Product is alleged to instruct co-administration with metformin (an OCT2 substrate) and direct monitoring for dose-limiting events and adjusting dosage, thereby inducing infringement Compl. ¶111

U.S. Patent No. 12,377,096 - Methods of Treating Disease With Levoketoconazole

• Patent Identification: U.S. Patent No. 12,377,096, "Methods of Treating Disease With Levoketoconazole," issued August 5, 2025.
• Technology Synopsis: This patent is similar to the '940 patent but focuses on a different transporter mechanism. It claims a method of treating Cushing's syndrome in a patient also taking a multidrug and toxin extrusion transporter 1 (MATE1) substrate. The method requires monitoring for dose-limiting events caused by increased exposure to the MATE1 substrate (due to levoketoconazole's inhibitory effect) and reducing the MATE1 substrate dose if such an event occurs '096 Patent, abstract '096 Patent, claim 1
• Asserted Claims: At least Claim 1 Compl. ¶128
• Accused Features: The proposed label for the Novitium ANDA Product is alleged to instruct co-administration with metformin (a MATE1 substrate) and direct monitoring for dose-limiting events and adjusting dosage, thereby inducing infringement Compl. ¶129

III. The Accused Instrumentality

• Product Identification: The accused instrumentality is the "Novitium ANDA Product," which is a proposed generic version of RECORLEV® (levoketoconazole) in the form of 150 mg oral tablets Compl. ¶54 Compl. ¶59
• Functionality and Market Context: As a generic drug, the Novitium ANDA Product is intended to be bioequivalent to RECORLEV® and used for the same indications Compl. ¶60 The infringement allegations center not on the composition of the drug itself, but on the use that will be induced by its FDA-approved label Compl. ¶61 The complaint alleges that to obtain FDA approval, the generic label must contain the same drug interaction warnings as the RECORLEV® label Compl. ¶60 The complaint includes a visual reproduction of the RECORLEV® label's "DRUG INTERACTIONS" section, which instructs physicians to, among other things, "Monitor glycemia, kidney function, and vitamin B12 and adjust metformin dosage as needed" when co-administered Compl. p. 14 The complaint alleges this instruction, when copied onto the generic label, will induce physicians to perform the patented methods Compl. ¶73

IV. Analysis of Infringement Allegations

'393 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of treating persistent or recurrent Cushing's syndrome in a subject in need thereof, wherein the subject also has type 2 diabetes mellitus and is being co-administered metformin...	The proposed label for the Novitium ANDA product allegedly will instruct its use in Cushing's syndrome patients, including those with type 2 diabetes who are co-administered metformin.	¶68	col. 2:50-54
administering a therapeutically effective amount of levoketoconazole... determined via a titration scheme,	The proposed label allegedly instructs administering a therapeutically effective amount determined via a titration scheme, mirroring the RECORLEV® label.	¶68	col. 9:60-11:13
during the levoketoconazole titration scheme, monitoring the subject for a dose limiting event wherein the dose limiting event is a decreased fasting glucose level, abnormal kidney function, and/or a low Vitamin B-12 level;	The proposed label allegedly directs healthcare providers to monitor for these specific dose-limiting events during titration.	¶73	col. 13:47-51
if the subject experiences a dose limiting event, reducing the amount of metformin... administered to the subject.	The proposed label allegedly instructs providers to reduce the metformin dosage if the patient experiences a dose-limiting event.	¶73	col. 2:14-19

'547 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of treating Cushing's syndrome in a subject... wherein the subject has had previous surgery or radiation to treat the subject's Cushing syndrome, [and] also has type 2 diabetes mellitus and is being co-administered metformin...	The Novitium ANDA Product's proposed label will allegedly induce practice of the claimed method in this specific patient sub-population (post-surgery/radiation with co-morbid diabetes).	¶89	col. 25:1-3
administering a therapeutically effective amount of levoketoconazole... determined via a titration scheme,	The proposed label allegedly instructs administering a therapeutically effective amount determined via a titration scheme.	¶89	col. 9:60-11:13
during the levoketoconazole titration scheme, monitoring the subject for a dose limiting event wherein the dose limiting event is a decreased fasting glucose level, abnormal kidney function, and/or a low Vitamin B-12 level;	The proposed label allegedly directs providers to monitor patients for these specified dose-limiting events during titration.	¶94	col. 13:47-51
if the subject experiences a dose limiting event, reducing the amount of metformin... administered to the subject.	The proposed label allegedly instructs providers to reduce the dosage of metformin if a dose-limiting event occurs.	¶94	col. 2:14-19

• Identified Points of Contention:
  • Scope Questions: The core of the dispute will likely be whether the instructions on the proposed generic label are specific enough to induce infringement of every limitation of the method claims. A question for the court may be whether an instruction to "adjust metformin dosage as needed" Compl. p. 14 necessarily directs the claimed step of "reducing the amount of metformin" Compl. ¶67 The defense may argue that "adjust" could mean increase, decrease, or maintain, and thus does not mandate the claimed reduction.
  • Technical Questions: A key technical question is whether the label's general instruction to "Monitor glycemia, kidney function, and vitamin B12" Compl. p. 14 constitutes monitoring for a "dose limiting event" as that term is used and defined in the patents. The claims link the monitoring to the titration scheme for the purpose of identifying a "dose limiting event," which is a term of art that may require specific interpretation. The complaint alleges that the label's instructions are sufficient to induce monitoring for events like "decreased fasting glucose level, abnormal kidney function, and/or low Vitamin B-12 levels" Compl. ¶73, which directly map to the claim language.

V. Key Claim Terms for Construction

Term 1: "dose limiting event"

• Context and Importance: This term is central to the monitoring and dose-reduction steps of the asserted claims. The infringement case hinges on the allegation that the defendants' product label will instruct physicians to monitor for and react to events that qualify as a "dose limiting event." Practitioners may focus on this term because its scope will determine whether the general safety monitoring described on the product label meets this specific claim requirement.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification lists numerous potential dose limiting events, suggesting the term is not exhaustive. For instance, it mentions QTc prolongation, elevated liver function tests, and adverse reactions like diarrhea and nausea in the context of increased metformin exposure '393 Patent, col. 12:22-13:61 This could support an interpretation covering a wide range of adverse events that would prompt a physician to alter a dose.
  • Evidence for a Narrower Interpretation: Independent Claim 1 of the '393 and '547 patents explicitly defines the relevant events with a "wherein" clause: "wherein the dose limiting event is a decreased fasting glucose level, abnormal kidney function, and/or a low Vitamin B-12 level" '393 Patent, claim 1 This language could be interpreted as defining and limiting the scope of the term for the purpose of that claim, restricting it to only those three specified events.

Term 2: "reducing the amount of metformin"

• Context and Importance: This is the final active step in the asserted method claims of the '393 and '547 patents. For inducement to be found, the defendants' label must be shown to encourage or instruct this specific action. The alleged instruction is to "adjust metformin dosage as needed" Compl. p. 14 The dispute will turn on whether "adjust" is equivalent to "reduce."
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: A defendant might argue that in the context of clinical practice, "adjust" is a broad term and that the patent does not provide a special definition to narrow it.
  • Evidence for a Narrower Interpretation: The specification consistently frames the interaction as levoketoconazole increasing exposure to metformin, necessitating a dose adjustment to mitigate side effects '393 Patent, abstract '393 Patent, col. 2:11-19 For example, the '393 patent states "the therapeutically effective amount of the MATE1 substrate or OCT2 substrate, is reduced relative to a subject who is not being administered levoketoconazole" '393 Patent, col. 2:14-19 This context suggests that the only logical and safe "adjustment" in response to a dose-limiting event caused by increased exposure would be a reduction.

VI. Other Allegations

• Indirect Infringement: The complaint is founded on a theory of induced infringement. It alleges that Defendants, by filing an ANDA for a generic version of RECORLEV®, intend for their product to be prescribed and used in the same manner as the brand-name drug Compl. ¶72 The complaint alleges that Defendants know and intend that the proposed product label, by copying the drug interaction warnings of the RECORLEV® label, will instruct and encourage physicians and patients to perform the steps of the patented methods Compl. ¶¶73-74
• Willful Infringement: The complaint alleges willful infringement based on Defendants' pre-suit knowledge of the asserted patents. This knowledge is alleged to come from the patents' listing in the FDA's Orange Book and from the formal notice letter sent by Plaintiffs Compl. ¶81 Compl. ¶82 The complaint asserts that Defendants' decision to proceed with the ANDA filing and Paragraph IV certification despite this knowledge constitutes objective recklessness and renders the infringement willful Compl. ¶82

VII. Analyst's Conclusion: Key Questions for the Case

This case appears to be a classic Hatch-Waxman dispute centered on induced infringement of method-of-use patents. The outcome will likely depend on the resolution of two main issues:

1. Label-Directed Infringement: A central question for the court will be one of inducement: does the anticipated language on the Defendants' generic drug label, which is expected to mirror the RECORLEV® label, provide instructions that are sufficiently specific to lead a fact-finder to conclude that it will inevitably direct physicians to perform each and every step of the asserted claims? This will involve a close comparison of the label's text with the specific limitations of the patent claims.

2. Definitional Scope: The case may turn on a key question of claim construction: can the term "dose limiting event", as used in the claims, be met by the general safety monitoring instructions on the product label? Furthermore, does the label's instruction to "adjust metformin dosage as needed" satisfy the claim requirement to "reduc[e] the amount of metformin," or does this create a non-infringing alternative for physicians?