Xeris Pharma Inc v. Sandoz Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Xeris Pharmaceuticals, Inc. (Delaware) and Strongbridge Dublin Limited (Ireland)
  • Defendant: Sandoz Inc. (Delaware), Sandoz Private Limited (India), Sandoz GmbH (Austria), Sandoz International GmbH (Germany); Zydus Lifesciences Global FZE (UAE), Zydus Pharmaceuticals (USA) Inc. (New Jersey), and Zydus Lifesciences Limited (India)
  • Plaintiff's Counsel: FBT Gibbons LLP (with Latham & Watkins LLP of counsel)
• Case Identification: 2:26-cv-02929, D.N.J., 03/20/2026
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Sandoz Inc. has its principal place of business in Princeton, New Jersey, from which it allegedly submitted its ANDA, and Defendant Zydus USA has its principal place of business in Pennington, New Jersey. Plaintiffs also allege the defendants regularly conduct business in the district and intend to sell the accused products there.
• Core Dispute: Plaintiff alleges that Defendants' proposed generic versions of the drug RECORLEV® (levoketoconazole), for which they seek FDA approval via Abbreviated New Drug Applications (ANDAs), will infringe four patents covering methods of treating Cushing's syndrome.
• Technical Context: The technology concerns specific methods for administering levoketoconazole, a cortisol synthesis inhibitor, particularly for patients with comorbidities like type 2 diabetes or those taking other medications, requiring careful dose titration and monitoring to manage drug interactions and side effects.
• Key Procedural History: This lawsuit was filed under the Hatch-Waxman Act following Plaintiffs' receipt of "Notice Letters" from Sandoz and Zydus. These letters notified Plaintiffs that the Defendants had filed ANDAs with Paragraph IV certifications, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by their proposed generic products. The filing of this suit within 45 days of receiving the notice letters triggers an automatic 30-month stay of FDA approval for the Defendants' ANDAs.

Case Timeline

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

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

The Invention Explained

• Problem Addressed: The patent addresses the treatment of Cushing's syndrome, a disease caused by excessive cortisol, particularly in patients who also have type 2 diabetes and are taking metformin U.S. Patent 11,020,393, col. 1:9-22 U.S. Patent 11,020,393, col. 7:10-14 Co-administration of levoketoconazole can increase a patient's systemic exposure to metformin, creating a risk of adverse events U.S. Patent 11,020,393, col. 12:41-57
• The Patented Solution: The invention provides a specific method for safely co-administering levoketoconazole and metformin. The method involves administering levoketoconazole using a "titration scheme" to find the effective dose, monitoring the patient for specific "dose limiting events" (such as abnormal kidney function or low Vitamin B-12 levels), and adjusting the levoketoconazole dose based on a specific formula if the patient cannot tolerate an increase U.S. Patent 11,020,393, abstract U.S. Patent 11,020,393, col. 11:1-12
• Technical Importance: This claimed method provides a protocol for managing the known drug-drug interaction between levoketoconazole and metformin, aiming to allow patients with both Cushing's syndrome and diabetes to benefit from both therapies while mitigating safety risks U.S. Patent 11,020,393, col. 12:58-64

Key Claims at a Glance

• The complaint asserts at least independent claim 1 Compl. ¶87
• Essential elements of claim 1 include:
  • A method of treating persistent or recurrent Cushing's syndrome in a subject who also has type 2 diabetes 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" (defined as 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 be the difference between the further increased dose and the incremental value from the last cycle.
• The complaint does not explicitly reserve the right to assert dependent claims but makes broad allegations covering "one or more claims" Compl. ¶88

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

The Invention Explained

• Problem Addressed: Similar to the '393 Patent, this patent addresses the treatment of Cushing's syndrome in patients with type 2 diabetes taking metformin U.S. Patent 11,278,547, col. 1:9-22 This patent specifically targets the sub-population of patients who have had "previous surgery or radiation" to treat their Cushing's syndrome, suggesting a focus on patients with persistent or recurrent disease post-intervention U.S. Patent 11,278,547, claim 1
• The Patented Solution: The invention claims a method for this specific patient population that involves administering levoketoconazole via a titration scheme, monitoring for dose-limiting events, and, critically, "reducing the amount of metformin" if such an event occurs U.S. Patent 11,278,547, abstract U.S. Patent 11,278,547, claim 1 This differs from the dose-adjustment step in the '393 Patent's claim 1.
• Technical Importance: The claimed method provides a specific safety protocol-adjusting the co-administered drug (metformin) rather than the primary therapeutic (levoketoconazole)-for a defined sub-population of Cushing's patients who have already undergone major interventions U.S. Patent 11,278,547, col. 12:41-57

Key Claims at a Glance

• The complaint asserts at least independent claim 1 Compl. ¶105
• Essential elements of claim 1 include:
  • A method of treating Cushing's syndrome in a subject who has had previous surgery or radiation for the condition, also has type 2 diabetes, 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" (defined as decreased fasting glucose, abnormal kidney function, and/or low Vitamin B-12).
  • If the subject experiences a dose limiting event, "reducing the amount of metformin" administered to the subject.
• The complaint does not explicitly reserve the right to assert dependent claims but makes broad allegations covering "one or more claims" Compl. ¶106

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

Technology Synopsis

The '940 Patent addresses drug-drug interactions by focusing on the biological mechanism. It claims a method of treating Cushing's syndrome in patients who are being co-administered a substrate for the organic cation transporter 2 (OCT2), a protein involved in drug clearance U.S. Patent 11,903,940, abstract The method involves administering levoketoconazole via titration, monitoring for a dose-limiting event caused by increased exposure to the OCT2 substrate, and then reducing the dose of the OCT2 substrate U.S. Patent 11,903,940, claim 1

Asserted Claims

At least independent claim 1 Compl. ¶123

Accused Features

The complaint alleges that Defendants' proposed product labels will instruct co-administration with metformin (an OCT2 substrate), thereby directing healthcare providers to perform the patented method Compl. ¶124 Compl. ¶125

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

Technology Synopsis

The '096 Patent is similar to the '940 Patent but focuses on a different drug transporter: multidrug and toxin extrusion transporter 1 (MATE1) U.S. Patent 12,377,096, abstract It claims a method of treating Cushing's syndrome in patients taking a MATE1 substrate, using a titration and monitoring scheme, and reducing the MATE1 substrate dose if a dose-limiting event occurs U.S. Patent 12,377,096, claim 1 Metformin is also a substrate for MATE1.

Asserted Claims

At least independent claim 1 Compl. ¶141

Accused Features

The complaint alleges that the proposed generic product labels will instruct co-administration with metformin (a MATE1 substrate), which will lead healthcare providers to perform the claimed method Compl. ¶142 Compl. ¶143

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the Defendants' "Sandoz ANDA Product" and "Zydus ANDA Product," which are proposed generic versions of RECORLEV® (levoketoconazole) in 150 mg oral tablets Compl. ¶66 Compl. ¶73 Compl. ¶76 Compl. ¶83 The infringement allegations are based on the submission of ANDA No. 220804 (Sandoz) and ANDA No. 220935 (Zydus) to the FDA Compl. ¶17 Compl. ¶25

Functionality and Market Context

• The products are oral tablets containing 150 mg of levoketoconazole, the same active ingredient and strength as Plaintiffs' branded drug, RECORLEV® Compl. ¶73 Compl. ¶83
• The infringement allegations center not on the composition of the tablets themselves, but on the proposed use as directed by the product labeling that will accompany the generic products upon FDA approval Compl. ¶88 Compl. ¶106
• The complaint alleges that the Defendants seek approval to market their products as bioequivalent generic versions of RECORLEV®, intending to sell them in the United States, including New Jersey, upon approval Compl. ¶19 Compl. ¶27 Compl. ¶74 No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'393 Patent Infringement Allegations

'547 Patent Infringement Allegations

Identified Points of Contention

• Evidentiary Questions: The core of the dispute will depend on the specific instructions contained in the Defendants' proposed product labels, which are not included in the complaint. The central question will be whether those labels instruct, encourage, or require physicians to perform each and every step of the asserted claims.
• Scope Questions: The case may raise questions about the scope of the claim term "titration scheme." The court will need to determine if the titration methods described in the proposed generic labels fall within the definition of the scheme as claimed in the patents.
• Technical Questions: A potential point of contention regarding the '393 Patent is the mismatch between the final step of claim 1 and the corresponding infringement allegation. Claim 1 requires a specific dose calculation if a patient does not tolerate a dose increase Compl. ¶87, whereas the complaint's narrative allegation describes "reducing the amount of metformin" Compl. ¶88 This raises the question of whether the factual basis alleged in the complaint for infringement of the '393 patent aligns with the actual language of its asserted claim.

V. Key Claim Terms for Construction

• The Term: "titration scheme"

• Context and Importance: This term appears in the independent claims of all four asserted patents and is central to the claimed methods. The infringement analysis will turn on whether the dosing instructions in the Defendants' proposed labels describe a method that meets the definition of the claimed "titration scheme." Practitioners may focus on whether the specific steps, dose increments, and decision points described in the patent specifications limit the scope of this term.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The claim language itself does not specify the exact starting dose, incremental value, or duration of each step, which may support a construction that covers various methods of incremental dose adjustment.
  • Evidence for a Narrower Interpretation: The patent specifications describe specific, multi-step titration cycles, including an initial dose of "150 mg twice daily" and an "incremental value of 150 mg daily" U.S. Patent 11,020,393, col. 11:1-12 This detailed embodiment could be used to argue for a narrower construction limited to schemes with these specific parameters.

• The Term: "dose limiting event"

• Context and Importance: This term defines the trigger for the key safety-related actions in the claims (e.g., reducing a metformin dose). The dispute will hinge on whether the adverse events for which the Defendants' labels recommend action are the same as the "dose limiting events" defined in the claims.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The use of "and/or" in the claim ("decreased fasting glucose level, abnormal kidney function, and/or a low Vitamin B-12 level") suggests the event can be any one of these conditions, potentially broadening the term's scope U.S. Patent 11,020,393, claim 1
  • Evidence for a Narrower Interpretation: The specification provides more detailed definitions for these conditions, such as defining abnormal kidney function by a specific eGFR value U.S. Patent 11,020,393, col. 13:40-44 A defendant may argue that the term is limited to these specific clinical parameters.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Defendants will induce infringement by selling their ANDA products with labels that instruct healthcare providers to perform the patented methods Compl. ¶99 Compl. ¶117 Compl. ¶161 The complaint further alleges contributory infringement, stating that the ANDA products are not staple articles of commerce and are especially made for use in an infringing manner Compl. ¶100 Compl. ¶118
• Willful Infringement: Willfulness is not explicitly pleaded as a separate count, but the complaint alleges that Defendants had actual and constructive knowledge of the asserted patents prior to and during the ANDA submission process, at least because the patents are listed in the FDA's Orange Book for RECORLEV® Compl. ¶97 Compl. ¶98 Compl. ¶115 Compl. ¶116 The complaint also requests a declaration that the case is "exceptional" under 35 U.S.C. § 285, which could entitle Plaintiffs to attorneys' fees Compl. ¶102

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

1. A primary evidentiary question will be one of label interpretation: Do the specific instructions for dosing, monitoring, and managing adverse events in the Defendants' proposed product labels direct, recommend, or inevitably lead healthcare providers to perform every step of the asserted method claims, or do the labels describe a clinically distinct, non-infringing method of use?
2. A central issue will be one of claim construction: Will the term "titration scheme" be construed broadly to cover any incremental dose-adjustment protocol, or will it be limited to the specific dosing regimens and incremental values described as embodiments in the patent specifications?
3. A key legal and factual question will be one of divided infringement: The complaint alleges that prescribing healthcare providers will "direct or control" the performance of steps carried out by the patient. A key issue for the court will be whether the alleged facts are sufficient to establish that a single actor (the healthcare provider) is responsible for the performance of all steps of the claimed methods, as required to prove direct infringement.