Grunenthal GmbH v. Teva PHARMACEUTICALS, INC.

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Grünenthal GmbH (Germany)
  • Defendant: Teva Pharmaceuticals, Inc. (Delaware) and Teva Pharmaceutical Industries Limited (Israel)
  • Plaintiff’s Counsel: Gibbons P.C.
• Case Identification: 2:24-cv-06104, D.N.J., 05/13/2024
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Teva Inc. is a resident of the state, and Defendant Teva Ltd. is a foreign corporation that may be sued in any judicial district.
• Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking approval to market generic versions of the pain medication NUCYNTA® ER, constitutes an act of infringement of a patent covering a specific method for titrating the drug.
• Technical Context: The technology concerns a specific dosing regimen for tapentadol, an opioid analgesic, designed to improve tolerability by reducing side effects like somnolence while maintaining effective pain management.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants’ submission of ANDA No. 204972 with a "Paragraph IV" certification. The certification alleges that U.S. Patent No. 11,344,512, which is listed in the FDA's Orange Book for NUCYNTA® ER, is invalid, unenforceable, or will not be infringed by the proposed generic product. Plaintiff filed this suit within the 45-day statutory window after receiving Defendants' notice letter, triggering a potential 30-month stay of FDA approval for the ANDA.

Case Timeline

Date	Event
2007-04-23	’512 Patent Priority Date
2022-05-31	’512 Patent Issue Date
2024-03-28	Plaintiff receives Defendants' Paragraph IV Notice Letter
2024-05-13	Complaint Filing Date

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

U.S. Patent No. 11,344,512 - "Titration of Tapentadol"

• Patent Identification: U.S. Patent No. 11,344,512, "Titration of Tapentadol," issued May 31, 2022. (Compl. ¶23).

The Invention Explained

• Problem Addressed: The patent describes that while the opioid analgesic tapentadol is well-tolerated, adverse events such as somnolence (drowsiness) can occur, particularly when initiating treatment, potentially causing patients to discontinue therapy. (’512 Patent, col. 2:7-12).
• The Patented Solution: The invention is a specific method of administering tapentadol that involves a "titration regimen," where treatment begins at a comparatively low dose and is successively increased over defined time intervals. (’512 Patent, col. 2:58-62). This graduated dosing schedule is designed to improve the drug's tolerability by minimizing side effects like somnolence, thereby enhancing patient compliance without sacrificing the analgesic effect. (’512 Patent, col. 2:36-44).
• Technical Importance: The claimed method provides a structured approach to balance the therapeutic benefit of a potent opioid with its potential side effects, a central challenge in the clinical management of chronic pain. (’512 Patent, col. 2:16-22).

Key Claims at a Glance

• The complaint asserts infringement of one or more claims, including at least independent claim 1. (Compl. ¶37).
• Independent Claim 1 recites:
  • A method of treating pain with a lower incidence of somnolence in a subject in need thereof, said method comprising orally administering to said subject:
  • (i) a first dose of tapentadol of 50 mg±5% or 100 mg±5% twice daily (bid) during a first administration interval of at least 1-3 days;
  • (ii) a second dose of tapentadol calculated by increasing said first dose by 50 mg to 100 mg±5% or 150 mg±5% twice daily (bid), respectively, during a second administration interval of at least 3-11 days following said first administration interval; and
  • (iii) a third dose of tapentadol calculated by increasing said second dose by 50 mg to 150 mg±5% or 200 mg±5% twice daily (bid), respectively, during a third administration interval of at least 3-14 days following said second administration interval.
• The complaint notes that various dependent claims are also infringed. (Compl. ¶37).

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are Defendants’ proposed generic tapentadol hydrochloride extended-release tablets in dosage strengths of 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg, as described in ANDA No. 204972. (Compl. ¶26).

Functionality and Market Context

• The proposed products are generic versions of the brand-name drug NUCYNTA® ER, an extended-release opioid analgesic. (Compl. ¶2). The complaint alleges that the proposed products are pharmaceutically and therapeutically equivalent to NUCYNTA® ER. (Compl. ¶34).
• The infringement allegation centers on the future use of these tablets. The complaint alleges that if the ANDA is approved, Defendants will market the products for managing severe pain and that the proposed product label will instruct healthcare providers and patients to use the various dosage strengths in a manner that practices the patented method. (Compl. ¶¶ 39, 45).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint alleges that the use of Defendants' proposed generic products, in accordance with their proposed product labeling, will infringe the '512 patent. (Compl. ¶¶ 41, 45). The act of infringement giving rise to this suit is the filing of the ANDA itself under 35 U.S.C. § 271(e)(2). (Compl. ¶36).

'512 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a method of treating pain with a lower incidence of somnolence in a subject in need thereof,	Use of Teva's proposed generic products for the management of severe and persistent pain, as will be instructed by the proposed product label.	¶39, ¶45	col. 34:6-8
said method comprising orally administering to said subject: (i) a first dose of tapentadol of 50 mg±5% or 100 mg±5% twice daily (bid) during a first administration interval of at least 1-3 days;	The administration of Teva's 50 mg or 100 mg tablets twice daily for a period of at least 1-3 days, as will allegedly be directed by the proposed product label to initiate therapy.	¶37, ¶45	col. 34:9-12
(ii) a second dose of tapentadol calculated by increasing said first dose by 50 mg to 100 mg±5% or 150 mg±5% twice daily (bid), respectively, during a second administration interval of at least 3-11 days following said first administration interval;	The subsequent administration of Teva's 100 mg or 150 mg tablets twice daily for a period of at least 3-11 days, as will allegedly be directed by the proposed product label as a second step in titration.	¶37, ¶45	col. 34:13-18
and (iii) a third dose of tapentadol calculated by increasing said second dose by 50 mg to 150 mg±5% or 200 mg±5% twice daily (bid), respectively, during a third administration interval of at least 3-14 days following said second administration interval.	The further administration of Teva's 150 mg or 200 mg tablets twice daily for a period of at least 3-14 days, as will allegedly be directed by the proposed product label as a third step in titration.	¶37, ¶45	col. 34:19-24

Identified Points of Contention

• Scope Questions: A central dispute will likely be whether the instructions in Teva's proposed (and ultimately approved) product label direct or encourage the specific three-step dosing regimen recited in Claim 1. The infringement case depends on the content of a document (the proposed label) not included with the complaint.
• Technical Questions: The claim preamble recites "with a lower incidence of somnolence." A key legal and factual question is whether this is a limiting claim element. If the court construes it as limiting, Grünenthal may have to prove not only that the accused method follows the claimed steps but also that it achieves this specific clinical outcome.

V. Key Claim Terms for Construction

The Term: "with a lower incidence of somnolence"

• Context and Importance: This phrase appears in the preamble of the independent claim. Its construction is critical because if it is deemed to be a limitation, it imposes an additional requirement for infringement. Plaintiff would need to prove that the administration of Teva's product according to its label actually results in this clinical benefit. Practitioners may focus on this term because preambles that state the purpose or intended result of an invention can be, but are not always, treated as limiting.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation (Non-Limiting): Plaintiff may argue that the body of the claim, which recites a complete set of specific dosing and timing steps, fully defines the invention. In this view, the preamble merely states an intended advantage or field of use without adding to the operative steps of the method.
  • Evidence for a Narrower Interpretation (Limiting): Defendant may argue the phrase is essential for patentability and distinguishes the invention from prior art dosing regimens. The patent's "Summary of the Invention" explicitly states an object of the invention is to "improve the tolerability of tapentadol... particularly to reduce the frequency of somnolence." (’512 Patent, col. 2:36-39). This suggests the reduction of somnolence is a fundamental aspect of the invention, not merely an incidental benefit.

The Term: "calculated by increasing"

• Context and Importance: This term describes how the second and third doses relate to the preceding doses. The dispute may turn on whether this requires the product label to explicitly instruct a "calculation" (e.g., "add 50 mg to the previous dose") or if it is sufficient that the label offers a series of dosage strengths that correspond to the claimed titration steps.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: Plaintiff may argue that the term simply defines a mathematical relationship between the doses (e.g., dose B = dose A + 50 mg) and does not require an explicit instruction to perform an arithmetic operation.
  • Evidence for a Narrower Interpretation: Defendant may argue that the active word "calculated" implies a process or instruction that must be present in the accused method (i.e., in the product label). The claim's structure—"a second dose of tapentadol calculated by increasing said first dose by 50 mg to [a resulting value]"—may suggest that the method of arriving at the dose is part of the claimed step itself. (’512 Patent, col. 34:13-15).

VI. Other Allegations

Indirect Infringement

• The complaint alleges that upon FDA approval, Teva will induce infringement by actively encouraging and instructing healthcare providers and patients to use its generic products in a manner that directly infringes the ’512 patent. (Compl. ¶46). The basis for this allegation is the content of Teva's proposed product label. (Compl. ¶45). Knowledge is alleged based on Teva's actual knowledge of the patent, as evidenced by its Paragraph IV notice letter. (Compl. ¶35).

Willful Infringement

• The complaint alleges that Teva has acted with knowledge of the ’512 patent, or at least with willful blindness, since at least the date it sent the notice letter. (Compl. ¶46). This forms the basis for the willfulness allegation should infringement be found after a potential commercial launch.

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

• A core issue will be one of label-driven infringement: will the specific text of Teva's proposed product label be found to actively instruct or encourage physicians to prescribe the multi-step dosing and timing regimen of Claim 1, or does it merely make available a range of doses that could be used in various ways?
• A key question of claim scope will be whether the preamble "with a lower incidence of somnolence" is a legally binding limitation. If it is, the case will expand beyond the text of the product label to include a factual dispute over clinical outcomes, adding a significant layer of evidentiary complexity.
• The ultimate outcome will also depend on validity. While not detailed in the complaint, Teva's Paragraph IV certification asserts that the patent is invalid. A central question for the court will be whether the specific dose amounts and administration intervals of the claimed titration method were obvious to a person of ordinary skill in the art at the time of the invention.