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: Xeris Pharmaceuticals, Inc. v. Novitium Pharma, LLC, 2:26-cv-08641, D.N.J., 07/13/2026
• Venue Allegations: Venue is based on Defendants having principal places of business in New Jersey, being registered to do business in the state, and having committed acts of infringement in the District, including the submission of the subject Abbreviated New Drug Application (ANDA) from an established place of business in East Windsor, New Jersey.
• Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA seeking to market a generic version of Plaintiffs' RECORLEV® (levoketoconazole) product constitutes an act of infringement of two patents covering methods of treating Cushing's syndrome.
• Technical Context: The technology relates to pharmaceutical methods for treating Cushing's syndrome, a rare endocrine disorder, with the drug levoketoconazole, particularly focusing on managing drug-drug interactions when co-administered with metformin, a common treatment for 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' submission of ANDA No. 221336. The Asserted Patents are listed in the FDA's Orange Book for RECORLEV®. Plaintiffs' RECORLEV® was granted orphan drug exclusivity until December 30, 2028. The complaint notes this action was filed within 45 days of a "Second Notice Letter," triggering a statutory stay of FDA approval for the ANDA until June 30, 2029. The complaint also references a prior, related litigation between the same parties concerning the same patents.

Case Timeline

Date	Event
2019-03-04	Priority Date for '393 and '547 Patents
2021-06-01	'393 Patent Issued
2021-12-30	FDA Approved New Drug Application for RECORLEV®
2022-03-22	'547 Patent Issued
2026-04-24	Defendants Sent "First Notice Letter"
2026-06-12	Defendants Sent "Second Notice Letter"
2026-06-22	Prior Litigation Filed by Plaintiffs
2026-07-13	Complaint Filing Date
2028-12-30	RECORLEV® Orphan Drug Exclusivity Ends
2029-06-30	Statutory Stay of FDA Approval of ANDA Ends

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

U.S. Patent No. 11,020,393: "Methods of Treating Disease With Levoketoconazole" (Issued June 1, 2021)

The Invention Explained

• Problem Addressed: The patent background describes how ketoconazole, a drug used off-label to treat Cushing's syndrome, carries significant risks including liver damage (hepatotoxicity) and dangerous drug-drug interactions (DDIs) with other medications '393 Patent, col. 1:40-45 This created an "unmet need for a safe, FDA-approved therapy" '393 Patent, col. 1:49-51 The complaint further states that studies during the development of RECORLEV® revealed previously unknown interactions, including that levoketoconazole can nearly double a patient's exposure to metformin Compl. ¶43
• The Patented Solution: The invention uses levoketoconazole, the 2S,4R enantiomer of ketoconazole, which is described as more potently inhibiting cortisol synthesis '393 Patent, col. 1:51-59 The patent claims a specific method for treating Cushing's syndrome in patients who are also taking metformin for type 2 diabetes. The method involves administering levoketoconazole according to a titration scheme while monitoring for specific "dose limiting events" (e.g., related to glucose levels, kidney function, or Vitamin B-12) and adjusting the treatment in response '393 Patent, claim 1 This provides a protocol to manage the newly discovered DDI between the two drugs.
• Technical Importance: The claimed method provides a framework for safely co-administering levoketoconazole and metformin, a clinically relevant combination since patients with Cushing's syndrome often also have type 2 diabetes Compl. ¶51

Key Claims at a Glance

• The complaint asserts at least independent claim 1 Compl. ¶67
• Essential elements of claim 1, as recited in the complaint Compl. ¶66:
  • 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 to improve glycemic control.
  • Administering a therapeutically effective amount of levoketoconazole, determined via a titration scheme.
  • During the titration, monitoring the subject for a dose limiting event, defined as a decreased fasting glucose level, abnormal kidney function, and/or a low Vitamin B-12 level.
  • If the subject does not tolerate an increased dose, setting the patient's dose to the difference between the further increased dose and the incremental value from the last cycle.

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 underlying technical problem as the '393 Patent: the need for a safer, more effective treatment for Cushing's syndrome, particularly when managing DDIs with co-administered drugs like metformin '547 Patent, col. 1:40-51
• The Patented Solution: The '547 Patent claims a method of treatment specifically for a sub-population of Cushing's syndrome patients: those who have had "previous surgery or radiation" '547 Patent, claim 1 The claimed method involves administering levoketoconazole via a titration scheme, monitoring for the same dose-limiting events related to metformin interaction (decreased glucose, abnormal kidney function, low B-12), and explicitly "reducing the amount of metformin" if such an event occurs '547 Patent, claim 1
• Technical Importance: This patent provides a targeted treatment regimen for a potentially more refractory patient population (post-surgical or post-radiation) who are also on metformin, creating a protocol to manage DDI risk in this specific clinical context.

Key Claims at a Glance

• The complaint asserts at least independent claim 1 Compl. ¶88
• Essential elements of claim 1 Compl. ¶87:
  • A method of treating Cushing's syndrome in a subject who has type 2 diabetes, is co-administered metformin, and has had previous surgery or radiation to treat the Cushing's syndrome.
  • 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 low Vitamin B-12).
  • If a dose limiting event is experienced, reducing the amount of metformin administered to the subject.

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is the "Novitium ANDA Product," a proposed generic version of RECORLEV® (levoketoconazole) in 150 mg oral tablets, which is the subject of ANDA No. 221336 filed by Defendants Compl. ¶¶1 Compl. ¶52 Compl. ¶58

Functionality and Market Context

• The complaint alleges that the Novitium ANDA Product is intended to be a bioequivalent generic substitute for Plaintiffs' RECORLEV® Compl. ¶59 Compl. ¶71 The infringement theory is not based on the product's direct operation, but on the instructions for its use. The complaint alleges that to gain FDA approval, the proposed label for the Novitium ANDA Product must contain the same Drug Interaction instructions as the RECORLEV® label Compl. ¶59 These instructions allegedly direct healthcare providers to use the product in a manner that infringes the asserted method claims, particularly regarding co-administration with metformin and monitoring for adverse events Compl. ¶¶61 Compl. ¶67 The complaint includes a visual reproduction of the RECORLEV® label's "DRUG INTERACTIONS" section, which it alleges the defendants' label will copy Compl. p. 14 This visual highlights the specific interaction with metformin, instructing physicians to "Monitor glycemia, kidney function, and vitamin B12 and adjust metformin dosage as needed" Compl. p. 14

IV. Analysis of Infringement Allegations

The complaint's infringement theory is based on induced infringement, alleging that the label for Defendants' proposed ANDA product will instruct medical professionals to perform the steps of the patented methods (Compl. ¶72; Compl. ¶73).

'393 Patent Infringement Allegations

Claim Element (from Independent Claim 1 as recited in Compl. ¶66)	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... to improve glycemic control...	The proposed ANDA label will instruct the use of levoketoconazole for treating Cushing's syndrome, a population where co-morbidity with type 2 diabetes and co-administration of metformin is common.	¶67; ¶72	col. 1:4-10
administering a therapeutically effective amount of levoketoconazole... determined via a titration scheme...	The proposed label will allegedly instruct clinicians to administer the drug using a titration scheme to determine the effective dose.	¶67; ¶72	col. 2:10-17
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 will instruct monitoring for dose-limiting events, including those related to glycemia, kidney function, and Vitamin B-12, when co-administered with metformin.	¶72	col. 24:62-65
wherein if the subject does not tolerate the increased dose, the dose for the patient is equal to the difference between the further increased dose and the incremental value for the last cycle repetition.	The complaint alleges the proposed label, by directing treatment in accordance with the patented regimen, will induce this specific dose-adjustment step.	¶75	col. 11:5-10

'547 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of treating Cushing's syndrome... wherein the subject has had previous surgery or radiation to treat the subject's Cushing syndrome...	The proposed ANDA label's indication for Cushing's syndrome will allegedly lead to its use in patients who have previously undergone surgery or radiation.	¶88	col. 24:5-8
administering a therapeutically effective amount of levoketoconazole... determined via a titration scheme...	The proposed label will allegedly instruct clinicians to administer the drug using a titration scheme to determine the effective dose.	¶88	col. 24:14-17
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 will instruct monitoring for dose-limiting events, including those related to glycemia, kidney function, and Vitamin B-12, when co-administered with metformin.	¶88	col. 25:1-4
if the subject experiences a dose limiting event, reducing the amount of metformin... administered to the subject.	The proposed label's instruction to "adjust metformin dosage as needed" in response to interactions is alleged to instruct the claimed step of reducing the metformin dose.	¶88; ¶93	col. 25:5-8

• Identified Points of Contention:
  • Pleading Question: The complaint's recitation of claim 1 of the '393 Patent Compl. ¶66 does not appear to match claim 1 as issued in the patent document '393 Patent, col. 24:51-col. 25:4 This discrepancy raises a threshold question about the basis of the infringement allegation for this patent.
  • Scope Questions: A primary point of contention may be whether the proposed label's instruction to "adjust metformin dosage as needed" Compl. p. 14 is specific enough to induce infringement of the claims. This raises the question of whether "adjust" necessarily meets the limitation of "reducing the amount of metformin" ('547 Patent) or the more complex dose-calculation formula recited for the '393 Patent Compl. ¶66
  • Technical Questions: For the '547 Patent, a question may arise as to whether a general label for treating Cushing's syndrome is sufficient to induce infringement of a claim specifically limited to patients who have had "previous surgery or radiation," especially if a substantial non-infringing use exists for patients who have not had such prior treatments.

V. Key Claim Terms for Construction

• The Term: "a titration scheme"

• Context and Importance: This term is foundational to the claimed methods in both patents. The infringement allegation hinges on the defendants' label instructing a "titration scheme" Compl. ¶67 Compl. ¶88 Practitioners may focus on this term because its definition will determine whether the general dosage and administration instructions on a drug label can be considered equivalent to the specific, structured process claimed in the patents.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The claim language itself broadly links the "titration scheme" to the goal of determining a "therapeutically effective amount" '393 Patent, claim 1 '547 Patent, claim 1, which could support an interpretation covering any systematic dose-adjustment process.
  • Evidence for a Narrower Interpretation: The specifications describe a detailed, multi-step process of up-titration involving an "initial dose," an "incremental value," repeated "cycles," and specific actions based on patient tolerance '393 Patent, col. 11:1-10 Claim 8 of the '393 Patent explicitly recites these steps, suggesting the patentee knew how to claim this specific scheme when intended.

• The Term: "reducing the amount of metformin" '547 Patent, claim 1

• Context and Importance: This is the key responsive action in the '547 Patent's method. Its construction is critical because the accused label instructs to "adjust metformin dosage as needed" Compl. p. 14, and the court will have to determine if "adjust" is coterminous with "reducing."

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent explains that levoketoconazole increases exposure to metformin '393 Patent, abstract In that context, a skilled artisan might understand that the primary, if not only, safe "adjustment" in response to a dose-limiting event would be a reduction.
  • Evidence for a Narrower Interpretation: The term "reducing" is specific and does not facially encompass other possible "adjustments" a physician might make, such as temporarily discontinuing the drug or maintaining the dose while managing side effects. The patentee chose the specific word "reducing," which could support a narrower definition that excludes other discretionary actions.

VI. Other Allegations

• Indirect Infringement: The core of the complaint is indirect infringement. Induced infringement is alleged based on the assertion that the defendants' proposed product label will instruct and encourage medical professionals to perform the patented methods, with defendants possessing knowledge of the patents via their Orange Book listing and specific intent to cause infringement Compl. ¶¶64 Compl. ¶72 Compl. ¶80 Compl. ¶93 The complaint also pleads contributory infringement, alleging the ANDA product is not a staple article suitable for substantial non-infringing use and is especially made for infringing the patents Compl. ¶¶82 Compl. ¶¶105
• Willful Infringement: While the complaint does not use the term "willful infringement," it alleges that the case is "exceptional" under 35 U.S.C. § 285 and seeks attorneys' fees Compl. ¶¶84 Compl. ¶¶107 The basis for this allegation is that the defendants filed their ANDA "without adequate justification for asserting that the... Patent is invalid, unenforceable, and/or not infringed" (Compl. ¶84). Knowledge of the patents is alleged to have existed prior to the filing of the ANDA Compl. ¶81

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

• A core issue will be one of definitional scope: Can the generic instruction on the accused product's label to "adjust metformin dosage as needed" be construed to meet the specific claim requirements of either "reducing the amount of metformin" or performing a multi-step dose calculation, or does the label's language provide sufficient physician discretion to avoid inducement?
• A key evidentiary question will be one of intent for inducement: Assuming a gap between the label's instructions and the claim language, can Plaintiffs produce sufficient evidence to demonstrate that Defendants possessed the specific intent to encourage medical professionals to bridge that gap and perform the claimed methods, particularly for the '547 patent's limitation to patients with prior surgery or radiation?
• A threshold procedural question for the '393 patent will be the effect of the pleading: How will the court address the apparent discrepancy between the language of claim 1 as quoted in the complaint and the language of claim 1 as it appears in the issued patent, and can the plaintiff amend or proceed on the current pleading?