Indivior Inc v. Lupin Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Indivior Inc. (Delaware)
  • Defendant: Lupin Inc., Lupin Limited, and Lupin Pharmaceuticals, Inc. (Delaware & India)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:25-cv-00757, D. Del., 06/20/2025
• Venue Allegations: Venue is alleged to be proper in Delaware as two Defendant entities are incorporated in the state, and the foreign Defendant, Lupin Limited, is subject to personal jurisdiction in the district.
• Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) seeking to market a generic version of OPVEE® (nalmefene) nasal spray infringes patents covering compositions and methods for treating opioid overdose.
• Technical Context: The technology relates to intranasal formulations of nalmefene, an opioid receptor antagonist, designed for the emergency treatment of opioid overdose, a significant public health issue exacerbated by the prevalence of synthetic opioids.
• Key Procedural History: The action arises under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 219264 with a Paragraph IV certification challenging the asserted patents. The patents-in-suit are listed in the U.S. Food and Drug Administration's "Orange Book" for Plaintiff's OPVEE® product, which was granted Fast Track designation and Priority Review by the FDA.

Case Timeline

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

U.S. Patent No. 11,458,091 - "Compositions and Methods for the Treatment of Opioid Overdose"

• Patent Identification: U.S. Patent No. 11,458,091, "Compositions and Methods for the Treatment of Opioid Overdose," issued October 4, 2022 (Compl. ¶31).

The Invention Explained

• Problem Addressed: The patent describes a need for an opioid overdose treatment that is effective against powerful synthetic opioids, long-lasting to prevent re-emergence of symptoms, and easy enough for untrained individuals to administer without the risks associated with needles (’091 Patent, col. 1:16-20, 1:45-54, 2:5-8). Existing treatments like injectable naloxone have a short duration of action and require trained personnel, which are significant limitations in community or emergency settings (’091 Patent, col. 1:45-54, 2:5-8).
• The Patented Solution: The patent discloses intranasal formulations of the opioid antagonist nalmefene, which has a longer half-life than naloxone (’091 Patent, Abstract; col. 1:55-64). The nasal spray format allows for rapid, needle-free administration by first responders or laypersons (’091 Patent, col. 2:8-11). The formulation includes specific excipients, such as an absorption enhancer (e.g., dodecyl maltoside), to promote rapid uptake and achieve a therapeutically effective plasma concentration quickly (’091 Patent, col. 3:20-24; Fig. 1).
• Technical Importance: This approach provides a rapid-acting, long-lasting, and user-friendly emergency intervention that is critical for combatting the opioid overdose crisis, particularly for overdoses occurring outside of traditional medical settings (’091 Patent, col. 2:21-30).

Key Claims at a Glance

• The complaint asserts infringement of one or more claims without specification (Compl. ¶45). Independent claim 1 is a representative composition claim:
  • A pharmaceutical formulation for intranasal administration, comprising: about 3% (w/v) nalmefene hydrochloride;
  • between about 0.1% (w/v) and about 0.5% (w/v) dodecyl maltoside;
  • between about 0.2% (w/v) and about 1.2% (w/v) NaCl;
  • between about 0.13% (w/v) and about 0.67% (w/v) disodium edetate;
  • between about 0.001% (w/v) and about 0.1% (w/v) benzalkonium chloride;
  • an amount of an acid or base sufficient to achieve a pH of between 3.5 and 5.5; and
  • water in an amount sufficient to achieve a final volume of about 50 µL to about 200 µL.
• The complaint implicitly reserves the right to assert additional claims, including dependent claims.

U.S. Patent No. 12,290,596 - "Compositions and Methods for the Treatment of Opioid Overdose"

• Patent Identification: U.S. Patent No. 12,290,596, "Compositions and Methods for the Treatment of Opioid Overdose," issued May 6, 2025 (Compl. ¶33).

The Invention Explained

• Problem Addressed: The ’596 Patent addresses the same technical problem as the ’091 Patent: the need for a rapid, sustained, and easy-to-use treatment for opioid overdose suitable for layperson administration (’596 Patent, col. 1:18-22, 2:25-34).
• The Patented Solution: This patent claims methods of treating opioid overdose by administering a specific intranasal nalmefene formulation that achieves a defined pharmacokinetic (PK) and pharmacodynamic (PD) profile (’596 Patent, Abstract). The claims require not just the administration of the drug, but that the administration results in specific outcomes, such as a time to maximum plasma concentration (Tmax) of between 12 and 18 minutes and a time to onset of respiratory reversal of between 2.5 and 5 minutes, as measured in a remifentanil challenge model (’596 Patent, col. 159:45-67; Fig. 24A).
• Technical Importance: By claiming a method that yields a specific, rapid, and effective clinical outcome, the patent seeks to protect the functional advantages of its particular formulation beyond just its list of ingredients (’596 Patent, col. 4:1-9).

Key Claims at a Glance

• The complaint asserts infringement of one or more claims without specification (Compl. ¶52). Independent claim 1 is a representative method of treatment claim, requiring:
  • Nasally administering an aqueous solution of about 100 µL containing specific amounts of nalmefene hydrochloride, NaCl, dodecyl maltoside, benzalkonium chloride, and disodium edetate, at a pH of 4.1 to 4.9.
  • Wherein the administration results in a median Tmax that is less and a Cmax geometric mean that is higher than for a 1 mg intramuscular injection of nalmefene hydrochloride.
  • Wherein the time to onset of reversal of remifentanil-induced respiratory depression is 2.5 to 5 minutes.
  • Wherein the time to full reversal of remifentanil-induced depression is 5 to 15 minutes.
  • Wherein the resulting plasma concentration curve has a Tmax of between 12 and 18 minutes.
  • Wherein the Cmax geometric mean is between 8 ng/mL and 12 ng/mL.
• The complaint implicitly reserves the right to assert additional claims, including dependent claims.

III. The Accused Instrumentality

Product Identification

• Defendant's proposed generic nalmefene nasal spray, identified as "Lupin's ANDA Product," for which it seeks FDA approval via ANDA No. 219264 (Compl. ¶1, 8).

Functionality and Market Context

• The complaint alleges that Lupin's ANDA Product contains nalmefene hydrochloride as its active ingredient and is designed to be a generic equivalent to Indivior's OPVEE® nasal spray (Compl. ¶1, 39). It is alleged to have a strength equivalent to 2.7 milligrams of nalmefene per spray and to be bioequivalent to OPVEE® (Compl. ¶40). Upon approval, the product is intended for commercial manufacture, marketing, and sale throughout the United States, where it would compete directly with and displace sales of OPVEE® (Compl. ¶10, 18).

Visual Evidence

• No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that Defendant's ANDA submission constitutes an act of infringement and that the future commercialization of the ANDA product would directly and indirectly infringe the patents-in-suit (Compl. ¶45, 47, 52, 54). As is typical in ANDA litigation at the pleading stage, the complaint does not contain a detailed claim chart. The infringement theory is based on the allegation that the product described in the ANDA is a bioequivalent generic version of the brand-name product, for which the patents-in-suit are listed in the FDA's Orange Book (Compl. ¶36, 40).

'091 Patent Infringement Allegations

The central allegation is that the composition of Lupin's ANDA Product will meet the limitations of the '091 Patent's composition claims.

• Identified Points of Contention:
  • Scope Questions: A likely point of dispute will be the construction of "about 3% (w/v)." The analysis will turn on whether the concentration of nalmefene hydrochloride in Defendant's product, specified in its ANDA, falls within the scope of this term.
  • Technical Questions: The primary question is factual and will depend on the contents of the confidential ANDA. Does the accused formulation contain dodecyl maltoside, NaCl, disodium edetate, and benzalkonium chloride within the specific ranges required by the claim?

'596 Patent Infringement Allegations

The central allegation is that the use of Lupin's ANDA Product as directed by its proposed label will result in the specific PK/PD outcomes recited in the '596 Patent's method claims.

• Identified Points of Contention:
  • Scope Questions: A central issue may be whether the term "time to onset of reversal," which is defined in the patent specification via a specific clinical model (the remifentanil challenge), can be proven by the bioequivalence data contained in an ANDA.
  • Technical Questions: Does the data within Defendant's confidential ANDA demonstrate that its product, when administered, will meet every PK and PD limitation of the asserted claims? Defendant may argue that being "bioequivalent" for regulatory purposes does not equate to meeting the specific functional limitations of the patent claims.

V. Key Claim Terms for Construction

• Term from '091 Patent: "about 3% (w/v)"

  • Context and Importance: The infringement analysis for the '091 Patent will likely hinge on whether the concentration of the active ingredient in Defendant's product falls within the scope of this term. Given that ANDA products often formulate to the exact specification of the reference drug, the breadth of "about" is a critical question.
  • Evidence for a Broader Interpretation: The specification uses "about" extensively when describing dosages and concentrations, such as "a therapeutically effective amount is equivalent to about 1 mg to about 10 mg of nalmefene hydrochloride" (’091 Patent, col. 2:40-42). This may suggest that the patentee intended the term to convey a degree of numerical flexibility.
  • Evidence for a Narrower Interpretation: The specification includes detailed tables with example formulations, one of which specifies a nalmefene concentration of exactly 30 mg/mL, or 3% w/v (’091 Patent, Table 4, Ex. 5). A party could argue that this specific disclosure limits the scope of "about" to values very close to 3.0%.

• Term from '596 Patent: "time to onset of reversal...of a remifentanil-induced respiratory depression"

  • Context and Importance: This is a key pharmacodynamic limitation that defines the claimed method's efficacy. The infringement case depends on proving that use of the accused product achieves this clinical outcome. Practitioners may focus on this term because its definition is tied to a specific experimental model described in the patent, raising questions of how infringement can be proven outside of that exact context.
  • Evidence for a Broader Interpretation: A party could argue this term should be construed to mean a clinically significant improvement in respiration within the claimed timeframe, consistent with the patent's overall goal of providing a rapid-acting treatment, rather than being strictly limited to the precise methodology of the patent's examples (’596 Patent, col. 2:25-30).
  • Evidence for a Narrower Interpretation: The patent specification explicitly ties this functional language to data from a specific clinical study model, describing "the non-inferiority study comparing nasal nalmefene and nasal naloxone in reversing the respiratory depression produced by remifentanil" (’596 Patent, Fig. 23; col. 8:14-22). A party could argue that the term must be interpreted as being defined by and limited to the results obtained under that specific experimental protocol.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Defendant will induce infringement by "instruct[ing] healthcare providers to use Lupin's ANDA Product in accordance with the proposed product labeling" (Compl. ¶46, 60). For the '596 Patent, the complaint also alleges contributory infringement, stating the accused product is especially made for an infringing use and has no substantial non-infringing use (Compl. ¶62).
• Willful Infringement: The complaint alleges that Defendant had knowledge of the '091 Patent when it submitted its ANDA and that its infringement is "deliberate" (Compl. ¶48). It further alleges that Defendant had knowledge of the '596 Patent no later than the filing of the complaint and is acting with specific intent to infringe (Compl. ¶55, 64).

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

• A central factual question will be one of compositional identity: does the formulation detailed in Defendant's confidential ANDA contain each excipient within the specific concentration ranges required by Claim 1 of the '091 patent, and will the term "about 3% (w/v)" be construed to read on the accused product's specified strength?
• A key legal and evidentiary question will be one of pharmacodynamic mapping: does the bioequivalence data supporting Defendant's ANDA prove, for infringement purposes, that administration of the generic product will necessarily result in the specific clinical outcomes and plasma concentration profiles (e.g., "time to onset of reversal", "Tmax", "Cmax") recited in the method claims of the '596 patent?