1:18-cv-00278
Osmotica Pharmaceutical US LLC v. Adamas Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Osmotica Pharmaceutical US LLC, and Vertical Pharmaceuticals, LLC (Delaware)
- Defendant: Adamas Pharmaceuticals, Inc., and Adamas Pharma, LLC (Delaware)
- Plaintiff’s Counsel: Young Conaway Stargatt & Taylor, LLP
- Case Identification: 1:18-cv-00278, D. Del., 02/16/2018
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because both Defendant entities are incorporated in the State of Delaware.
- Core Dispute: Plaintiff seeks a declaratory judgment that its Osmolex ER™ amantadine tablets, for the treatment of Parkinson's disease, do not infringe eleven patents owned by Defendant related to amantadine formulations and methods of use.
- Technical Context: The technology concerns pharmaceutical formulations of amantadine, particularly extended-release compositions designed to manage symptoms of neurological disorders while mitigating side effects.
- Key Procedural History: The complaint alleges that this declaratory judgment action was precipitated by a June 1, 2015 letter from Defendant Adamas threatening patent enforcement upon the commercialization of Plaintiff's Osmolex ER™ product.
Case Timeline
| Date | Event |
|---|---|
| 2004-11-24 | Earliest Priority Date for '578, '337, '740, '614, '615, '616, '617, '618, '333, '697 Patents |
| 2009-12-02 | Earliest Priority Date for '343 Patent |
| 2013-03-05 | U.S. Patent No. 8,389,578 Issues |
| 2014-06-03 | U.S. Patent No. 8,741,343 Issues |
| 2014-08-05 | U.S. Patent No. 8,796,337 Issues |
| 2014-11-18 | U.S. Patent No. 8,889,740 Issues |
| 2014-11-25 | U.S. Patent Nos. 8,895,614, 8,895,615, 8,895,616, 8,895,617, and 8,895,618 Issue |
| 2015-03-24 | U.S. Patent No. 8,987,333 Issues |
| 2015-06-01 | Adamas sends letter to Osmotica regarding alleged future infringement |
| 2015-07-07 | U.S. Patent No. 9,072,697 Issues |
| 2017-01-18 | Osmotica submits 505(b)(2) application to FDA for Osmolex ER™ |
| 2017-08-24 | Adamas receives FDA approval for its Gocovri™ product |
| 2018-02-16 | Osmotica receives FDA approval for its Osmolex ER™ product |
| 2018-02-16 | Complaint for Declaratory Judgment of Noninfringement filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,389,578 - Composition and Method for Treating Neurological Disease, Issued March 5, 2013
The Invention Explained
- Problem Addressed: The patent's background describes that while levodopa is a widely prescribed therapy for Parkinson's disease (PD), its chronic use is associated with debilitating side effects, such as dyskinesia (involuntary movements) (’578 Patent, col. 1:35-41).
- The Patented Solution: The invention proposes combining levodopa/carbidopa in an immediate-release (IR) form with an N-Methyl-D-Aspartate receptor (NMDAr) antagonist, such as amantadine, in an extended-release (ER) form (’578 Patent, col. 2:1-7). By extending the release of amantadine, the invention seeks to maintain a more stable and effective plasma concentration, which is postulated to enhance the efficacy of levodopa while significantly reducing dyskinesia side effects (’578 Patent, col. 2:10-16).
- Technical Importance: This approach attempts to decouple the therapeutic benefits of levodopa from its long-term motor complications, a central challenge in the management of advanced Parkinson's disease.
Key Claims at a Glance
- The complaint identifies independent claim 1 as representative (Compl. ¶126).
- Essential elements of Claim 1:
- A method of treating a patient with PD comprising orally administering a first agent and a second agent.
- The first agent comprises a therapeutically effective amount of levodopa/carbidopa in an immediate-release form.
- The second agent consists essentially of a therapeutically effective amount of amantadine (200 mg to 500 mg) in an extended-release form.
- The extended-release amantadine provides a change in plasma concentration over time (dC/dT) that is less than about 40% of the dC/dT provided by an immediate-release form of amantadine.
U.S. Patent No. 8,741,343 - Method of Administering Amantadine Prior to a Sleep Period, Issued June 3, 2014
The Invention Explained
- Problem Addressed: The patent describes that immediate-release amantadine can act as a stimulant, causing insomnia and sleep disturbance. To minimize this side effect, the last daily dose is typically administered no later than 4 p.m., resulting in low plasma concentrations of the drug in the morning (’343 Patent, col. 1:21-34).
- The Patented Solution: The invention claims a method of administering an extended-release amantadine composition at bedtime (less than three or four hours before sleep) (’343 Patent, col. 2:13-18). The extended-release profile is designed to delay the absorption of amantadine, thereby avoiding the initial stimulant effects at bedtime while providing a therapeutically effective plasma concentration when the patient wakes up in the morning (’343 Patent, col. 2:5-12).
- Technical Importance: This method seeks to enable a novel dosing paradigm for amantadine that addresses morning symptoms of PD without compromising the patient's sleep.
Key Claims at a Glance
- The complaint identifies independent claim 1 as representative (Compl. ¶133).
- Essential elements of Claim 1:
- A method of administering a composition comprising amantadine to a human subject.
- The composition is an extended release oral dosage form comprising a capsule containing a plurality of pellets.
- The composition is administered orally once daily 0 to 4 hours before bedtime.
U.S. Patent No. 8,796,337 - Composition and Method for Treating Neurological Disease, Issued August 5, 2014
Technology Synopsis
This patent, related to the ’578 patent, claims a method of administering amantadine in a modified-release composition that provides a mean change in amantadine plasma concentration (dC/dT) of less than 40% of that provided by an immediate-release form during the first 0 to 4 hours after administration (Compl. ¶140-141; ’337 Patent, col. 22:39-56). The goal is to achieve therapeutic effects while reducing side effects associated with rapid increases in plasma concentration.
Asserted Claims
Claim 1 is asserted as representative (Compl. ¶140).
Accused Features
The complaint alleges Osmolex ER™ does not infringe because its immediate-release component results in a dC/dT profile greater than 40% of an immediate-release form in the initial 0 to 4 hour period (Compl. ¶141).
U.S. Patent No. 8,889,740 - Composition and Method for Treating Neurological Disease, Issued November 18, 2014
Technology Synopsis
This patent claims a dosage form of amantadine where at least 50% of the drug is in an extended-release form. The formulation is defined by a specific pharmacokinetic profile: its mean change in plasma concentration (dC/dT) between 2 and 4 hours post-administration is less than 30% of the dC/dT provided by an IR form between 0 and 2 hours post-administration (Compl. ¶147; ’740 Patent, col. 23:9-22).
Asserted Claims
Claim 1 is asserted as representative (Compl. ¶147).
Accused Features
The complaint argues that Osmolex ER™ contains an immediate-release component and therefore does not meet the claimed pharmacokinetic profile, which it contends is properly limited to dosage forms without an IR component (Compl. ¶147-148).
U.S. Patent No. 8,895,614 - Composition and Method for Treating Neurological Disease, Issued November 25, 2014
Technology Synopsis
This patent claims an amantadine dosage form where at least 50% is extended-release. The form provides a mean change in plasma concentration (dC/dT) that is less than 40% of that provided by an immediate-release form, as measured over the time period between 0 and 4 hours after administration (Compl. ¶154; ’614 Patent, col. 23:17-32).
Asserted Claims
Claim 1 is asserted as representative (Compl. ¶154).
Accused Features
The complaint alleges Osmolex ER™ does not infringe because its immediate-release component results in a dC/dT profile that is greater than 40% of an immediate-release form in the specified time period (Compl. ¶154).
U.S. Patent No. 8,895,615 - Composition and Method for Treating Neurological Disease, Issued November 25, 2014
Technology Synopsis
This patent claims a method of administering a once-daily dose of amantadine that provides a mean change in plasma concentration (dC/dT) of less than 40% of that provided by an immediate-release form, measured between 0 and 4 hours after administration (Compl. ¶162, ¶165; ’615 Patent, col. 22:55-23:2).
Asserted Claims
Claim 1 is asserted as representative (Compl. ¶162).
Accused Features
The complaint contends Osmolex ER™ does not infringe because it contains an immediate-release component and its resulting dC/dT profile is greater than the claimed 40% threshold (Compl. ¶163, ¶165).
U.S. Patent No. 8,895,616 - Composition and Method for Treating Neurological Disease, Issued November 25, 2014
Technology Synopsis
This patent is directed to a method of administering a once-daily dose of amantadine. It claims a dosage form "consisting of" amantadine and an excipient, with context suggesting it does not comprise an immediate-release component (Compl. ¶172; ’616 Patent, col. 22:56-59).
Asserted Claims
Claim 1 is asserted as representative (Compl. ¶171).
Accused Features
The complaint argues that Osmolex ER™, which consists of an extended-release core surrounded by an immediate-release outer layer, does not meet the "consisting of" limitation and is not properly limited to ER-only forms (Compl. ¶172-173).
U.S. Patent No. 8,895,617 - Composition and Method for Treating Neurological Disease, Issued November 25, 2014
Technology Synopsis
This patent is substantially similar to the '616 patent, directed to a method of administering a once-daily dose of amantadine "consisting of" amantadine and an excipient (Compl. ¶180; ’617 Patent, col. 22:56-58).
Asserted Claims
Claim 1 is asserted as representative (Compl. ¶179).
Accused Features
The complaint repeats its argument that Osmolex ER™ contains an immediate-release component and therefore does not meet the "consisting of" limitation that it alleges is properly limited to ER-only forms (Compl. ¶180-181).
U.S. Patent No. 8,895,618 - Composition and Method for Treating Neurological Disease, Issued November 25, 2014
Technology Synopsis
This patent claims a dosage form of amantadine comprising an extended-release form that provides a mean change in plasma concentration (dC/dT) less than 40% of that from an immediate-release form, measured between 0 and 4 hours after administration (Compl. ¶187; ’618 Patent, col. 23:35-47).
Asserted Claims
Claim 1 is asserted as representative (Compl. ¶187).
Accused Features
The complaint argues Osmolex ER™ contains an immediate-release component and thus does not meet the claimed pharmacokinetic profile, which it alleges is properly limited to ER-only forms (Compl. ¶187-188).
U.S. Patent No. 8,987,333 - Composition and Method for Treating Neurological Disease, Issued March 24, 2015
Technology Synopsis
This patent claims an osmotic device for amantadine delivery, comprising a core and an immediate-release overcoat. It requires that the device provide a mean change in plasma concentration (dC/dT) that is less than 40% of that provided by an immediate-release form, measured between 0 and 4 hours after administration (Compl. ¶194; ’333 Patent, col. 23:21-40).
Asserted Claims
Claim 1 is asserted as representative (Compl. ¶194).
Accused Features
The complaint alleges the dC/dT profile of Osmolex ER™ is greater than the claimed 40% threshold due to its immediate-release component (Compl. ¶195).
U.S. Patent No. 9,072,697 - Composition and Method for Treating Neurological Disease, Issued July 7, 2015
Technology Synopsis
This patent claims a method of administering a once-daily dose of amantadine wherein at least 90% of the drug in the composition is in an extended-release form (Compl. ¶202; ’697 Patent, col. 24:20-23).
Asserted Claims
Claim 6 is asserted as representative (Compl. ¶201).
Accused Features
The complaint alleges that in the Osmolex ER™ product, the amount of amantadine HCl in the extended-release core is less than 90% of the total dose, and thus it does not meet this limitation (Compl. ¶203).
III. The Accused Instrumentality
Product Identification
Osmolex ER™ tablets (Compl. ¶1).
Functionality and Market Context
Osmolex ER™ is a pharmaceutical product approved by the FDA for the treatment of Parkinson's disease and drug-induced extrapyramidal reactions in adults (Compl. ¶4, ¶86). The product is formulated as a single tablet containing a combination of both immediate-release and extended-release amantadine HCl as its active ingredient (Compl. ¶8, ¶84). The approved label recommends an initial dosage of 129 mg administered orally once daily in the morning (Compl. ¶87). The complaint alleges that Osmolex ER™ is an innovative therapeutic option that is unique among existing amantadine products and positions it as a competitor to Adamas's Gocovri™ product (Compl. ¶8, ¶10). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
U.S. Patent No. 8,389,578 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Non-Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a first agent comprising a therapeutically effective amount of levodopa/carbidopa in an immediate-release form | The Osmolex ER™ product consists solely of amantadine HCl as the active agent and does not contain levodopa/carbidopa. | ¶127 | col. 23:42-45 |
| a second agent consisting essentially of a therapeutically effective amount of amantadine...in an amount ranging from 200 mg to 500 mg in extended release form | Osmolex ER™ product is a combination of immediate-release and extended-release amantadine, not a formulation consisting essentially of an extended-release form. | ¶127 | col. 23:45-48 |
| the amantadine...provides change in plasma concentration as a function of time (dC/dT)...that is less than about 40% of the dC/dT provided by...an immediate release form... | Due to its immediate-release component, the dC/dT profile of Osmolex ER™ in the initial 0-4 hour period is alleged to be greater than 40% of the dC/dT of a comparable immediate-release form. | ¶141, ¶154 | col. 23:50-24:3 |
Identified Points of Contention
- Scope Questions: A primary question for the court will be whether a method claim requiring two distinct agents (levodopa/carbidopa and amantadine) can be read on the use of a product containing only one of those agents (amantadine). Further, the use of "consisting essentially of" in relation to the amantadine agent raises the question of whether Osmolex ER's combined IR/ER formulation falls outside the scope of a claim directed to an "extended release form."
- Technical Questions: A key factual question will be whether the pharmacokinetic profile of Osmolex ER™ meets the functionally defined dC/dT limitation of the claim. The complaint's assertion that its IR component leads to a faster initial rise in plasma concentration than required by the claim suggests this will be a central point of technical dispute.
U.S. Patent No. 8,741,343 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Non-Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| orally administering said composition once daily 0 to 4 hours before bedtime to a human subject | The FDA-approved product label for Osmolex ER™ explicitly recommends dosing "in the morning." | ¶134 | col. 55:66-67 |
Identified Points of Contention
- Scope Questions: The dispute raises the question of how to interpret "before bedtime" in the context of a product label that specifies "in the morning." The analysis will likely focus on the ordinary meaning of these terms and whether any ambiguity exists that would permit a broader construction.
- Technical Questions: The central technical question is one of induced infringement: does Osmotica, by marketing a product with instructions for morning use, instruct or encourage users to perform the claimed method step of administering the drug at bedtime? The complaint's position is that the product label directly contradicts the claimed method.
V. Key Claim Terms for Construction
For the ’578 Patent
- The Term: "second agent consisting essentially of...amantadine...in an extended release form"
- Context and Importance: This term is critical because Osmolex ER™ is formulated with both immediate-release and extended-release amantadine (Compl. ¶84). Practitioners may focus on whether the restrictive term "consisting essentially of" an "extended release form" excludes a product that also contains a pharmacologically active immediate-release component of the same drug.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that if the "essential" character of the formulation is its extended-release profile, an additional IR component that does not materially affect that character could be permitted.
- Evidence for a Narrower Interpretation: The specification consistently distinguishes between "immediate release" and "extended release" as distinct formulation types (’578 Patent, col. 2:1-7). The use of "consisting essentially of" suggests an intent to exclude other forms of the active ingredient that would materially alter the basic and novel properties, such as the claimed pharmacokinetic (dC/dT) profile.
For the ’343 Patent
- The Term: "before bedtime"
- Context and Importance: The infringement analysis for this patent hinges entirely on this temporal limitation, as the accused product is labeled for morning administration (Compl. ¶134). Practitioners will recognize this as a potentially dispositive issue.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party could argue that for individuals with atypical sleep schedules (e.g., night-shift workers), "morning" could be "before bedtime," suggesting the term is relative to the individual's sleep period.
- Evidence for a Narrower Interpretation: The patent's background explicitly frames the invention as a solution to the problem of insomnia caused by evening doses of amantadine, stating the last dose is typically given "no later than 4 pm" (’343 Patent, col. 1:28-30). This context strongly suggests "bedtime" refers to the conventional end-of-day sleep period for a typical patient.
VI. Other Allegations
Indirect Infringement
This is a declaratory judgment action for non-infringement. Osmotica's allegations are framed to preempt claims of both direct and indirect infringement. The complaint repeatedly asserts that any use of Osmolex ER™ by third parties (e.g., physicians and patients) in accordance with its approved product label will not satisfy the limitations of the asserted claims (Compl. ¶127, ¶134). This directly addresses the "intent" element of induced infringement, arguing that Osmotica's instructions actively teach away from, rather than encourage, any infringing use.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of formulation mismatch: Across numerous asserted patents, the central question will be whether Osmolex ER's combined immediate-release/extended-release (IR/ER) tablet can be found to infringe claims directed to purely "extended-release" compositions, particularly those using restrictive language such as "consisting essentially of."
- A key evidentiary question will be one of pharmacokinetic functionality: For the majority of the patents that define the invention by a specific, slow initial rate of drug release (a dC/dT less than a certain threshold), the case will likely turn on clinical data showing whether the immediate-release component of Osmolex ER™ causes its pharmacokinetic profile to fall outside these claimed functional limits.
- A dispositive issue for the '343 patent will be one of temporal contradiction: Can a product expressly labeled for administration "in the morning" be found to infringe a method claim that explicitly requires administration "0 to 4 hours before bedtime"?