DCT

1:16-cv-00917

Forest Laboratories LLC v. Amerigen Pharma Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:16-cv-00917, D. Del., 10/07/2016
  • Venue Allegations: Venue is alleged to be proper based on Defendants' incorporation in Delaware, presence and systematic contacts within the district, and conduct in prior litigation in the district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for generic versions of the drug Namzaric® constitutes an act of infringement of twelve patents related to pharmaceutical formulations and methods for treating Central Nervous System (CNS) conditions.
  • Technical Context: The patents relate to formulations of memantine, alone or in combination with donepezil, for treating CNS disorders such as Alzheimer's disease, focusing on modified-release properties to improve dosing schedules and patient tolerability.
  • Key Procedural History: The complaint notes that this action follows a prior, ongoing lawsuit (Civil Action No. 15-966-LPS) filed by the same Plaintiffs against the same Defendants concerning the original ANDA submission for generic Namzaric®. This new complaint was filed in response to Defendants' amendments to that ANDA seeking approval for additional dosage strengths. The existence of the prior litigation may streamline discovery and claim construction, and it is cited by Plaintiffs to support allegations of knowledge for potential enhanced damages or a finding of an exceptional case.

Case Timeline

Date Event
2004-06-17 Priority Date for ’009 Patent
2005-04-06 Priority Date for ’291, ’379, ’794, ’485, ’486, ’858 Patents
2005-11-22 Priority Date for ’209, ’708, ’752, ’085, ’233 Patents
2011-10-18 U.S. Patent No. 8,039,009 Issues
2011-11-15 U.S. Patent No. 8,058,291 Issues
2012-05-01 U.S. Patent No. 8,168,209 Issues
2012-05-08 U.S. Patent No. 8,173,708 Issues
2012-10-09 U.S. Patent No. 8,283,379 Issues
2012-10-23 U.S. Patent No. 8,293,794 Issues
2012-12-11 U.S. Patent No. 8,329,752 Issues
2012-12-25 U.S. Patent Nos. 8,338,485 and 8,338,486 Issue
2013-01-29 U.S. Patent No. 8,362,085 Issues
2013-11-12 U.S. Patent No. 8,580,858 Issues
2013-12-03 U.S. Patent No. 8,598,233 Issues
2015-09-10 Amerigen submits ANDA No. 208237 (on or before this date)
2015-10-23 Plaintiffs file initial patent infringement action (No. 15-966-LPS)
2016-09-23 Amerigen amends ANDA No. 208237 for 21 mg dosage (on or before this date)
2016-09-26 Amerigen amends ANDA No. 208237 for 7 mg dosage (on or before this date)
2016-10-07 Complaint Filed

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

U.S. Patent No. 8,039,009 - "Modified Release Formulations Of Memantine Oral Dosage Forms"

  • Issued: October 18, 2011

The Invention Explained

  • Problem Addressed: The patent describes that the then-current twice-daily dosing regimen for memantine (an Alzheimer's drug) may be undesirable due to decreased patient compliance and that immediate-release tablets can lead to adverse events from a fast rate of drug absorption (Compl. ¶13; ’009 Patent, col. 2:65-col. 3:9).
  • The Patented Solution: The invention is a once-a-day, solid oral dosage form of memantine that provides a modified-release profile. It employs a polymeric matrix, such as hydroxypropyl methylcellulose, to sustain the release of memantine over an extended period, aiming to improve patient compliance and tolerability (Compl. ¶13; ’009 Patent, Abstract; col. 3:10-22).
  • Technical Importance: This approach provided a method for potentially improving the safety and efficacy profile of memantine by creating a more stable drug concentration in the body over 24 hours, a significant goal for drugs treating chronic conditions in elderly populations (’009 Patent, col. 3:1-9).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 2 and 21-23 (Compl. ¶34).
  • Independent Claim 1 requires:
    • A method for treating Alzheimer's disease.
    • Comprising once daily administration of a modified release solid oral dosage form.
    • The dosage form comprises 28 mg ±5% of memantine or a pharmaceutically acceptable salt thereof.
    • The dosage form includes a pharmaceutically acceptable polymeric carrier that substantially contributes to modifying the release.
    • The dosage form sustains the release of memantine from about 4 to 24 hours after entering a use environment.
    • The dosage form has a single phase dissolution rate of less than about 80% after 6 hours.
  • The complaint does not explicitly reserve the right to assert additional dependent claims.

U.S. Patent No. 8,058,291 - "Methods And Compositions For The Treatment Of CNS-Related Conditions"

  • Issued: November 15, 2011

The Invention Explained

  • Problem Addressed: The patent identifies challenges in treating CNS disorders, noting that available dosage forms of NMDA receptor antagonists like memantine often require frequent administration and dose escalation to avoid side effects, which complicates therapy and harms patient compliance (Compl. ¶14; ’291 Patent, col. 1:56-col. 2:2).
  • The Patented Solution: The invention proposes a combination therapy that includes an NMDA receptor antagonist (e.g., memantine) and an acetylcholinesterase inhibitor (AChEI) (e.g., donepezil). A key aspect is that at least one of these agents is provided in an extended-release formulation to achieve a release profile characterized by a reduced rate of concentration change ("dC/dT") compared to an immediate-release form, aiming to improve tolerability and allow for once-daily dosing (Compl. ¶14; ’291 Patent, Abstract; col. 3:10-24).
  • Technical Importance: This combination approach aims to provide additive or synergistic therapeutic benefits for conditions like Alzheimer's disease while simultaneously using pharmacokinetic control to improve the safety profile and simplify the dosing regimen for patients (’291 Patent, col. 2:47-54).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 48 and numerous dependent claims (Compl. ¶34).
  • Independent Claim 1 requires:
    • A method of treating a CNS-related condition.
    • Comprising orally administering once a day to a human subject:
    • (a) 5-40 mg memantine (or a salt) in an extended release dosage form.
    • This extended release form provides a change in plasma concentration over time ("dC/dT") that is less than about 50% of the "dC/dT" of an equivalent immediate release form, measured from time 0 to Tmax.
    • (b) a therapeutically effective amount of donepezil (or a salt).
    • The CNS-related condition is selected from Alzheimer's disease and dementia.
  • The complaint does not explicitly reserve the right to assert additional dependent claims.

Multi-Patent Capsules

  • Patent Identification: U.S. Patent No. 8,168,209, "Method And Composition For Administering An NMDA Receptor Antagonist To A Subject," issued May 1, 2012 (Compl. ¶15).

  • Technology Synopsis: This patent describes solid pharmaceutical compositions for once-daily administration of an NMDA receptor antagonist like memantine. The invention focuses on achieving specific dissolution profiles and pharmacokinetic parameters (e.g., "dC/dT", "Cmax/Cmean") that are slower than immediate-release forms to improve tolerability (’209 Patent, col. 1:11-23; col. 2:10-23).

  • Asserted Claims: Claims 1 and 10-14 are asserted (Compl. ¶34). Independent claims are 1 and 10.

  • Accused Features: The accused features are Amerigen's proposed generic extended-release memantine capsules, which are alleged to meet the specific pharmacokinetic and formulation claims of the patent (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,173,708, "Method And Composition For Administering An NMDA Receptor Antagonist To A Subject," issued May 8, 2012 (Compl. ¶16).

  • Technology Synopsis: This patent is directed to methods of treating CNS-related conditions by administering a composition containing an NMDA receptor antagonist (e.g., memantine). The claims focus on achieving a specific pharmacokinetic profile where the initial rate of rise in plasma concentration is significantly lower than that of an immediate-release formulation, which may reduce adverse effects (’708 Patent, col. 2:1-23).

  • Asserted Claims: Claims 12 and 16 are asserted (Compl. ¶34). Claim 12 is an independent claim.

  • Accused Features: The accused features are Amerigen's generic extended-release memantine products, which are alleged to infringe the claimed methods of treatment by virtue of their formulation and intended use (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,283,379, "Method And Compositions For The Treatment Of CNS-Related Conditions," issued October 9, 2012 (Compl. ¶17).

  • Technology Synopsis: This patent covers methods of treating CNS-related conditions like Alzheimer's by administering a combination of memantine and an AChEI (e.g., donepezil). The claims specify that the memantine is in an extended-release form providing a controlled rate of concentration change ("dC/dT"), while the AChEI can be in immediate or extended release form (’379 Patent, Abstract; col. 2:45-54).

  • Asserted Claims: Claims 7, 9, 11, and 12 are asserted (Compl. ¶34). Claim 7 is an independent claim.

  • Accused Features: The accused features are Amerigen's combination capsules of extended-release memantine and donepezil, which are alleged to be used in a manner that infringes the claimed treatment methods (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,293,794, "Methods And Compositions For The Treatment Of CNS-Related Conditions," issued October 23, 2012 (Compl. ¶18).

  • Technology Synopsis: Similar to the ’291 and ’379 patents, this patent claims compositions and methods for treating CNS disorders using a combination of an NMDA receptor antagonist (memantine) and an AChEI (donepezil). The claims focus on specific release profiles and pharmacokinetic characteristics of the drug combination (’794 Patent, Abstract; col. 2:46-55).

  • Asserted Claims: Claims 1-3, 9, 10, 14-16, 23, 24, and 28 are asserted (Compl. ¶34). Independent claim 1 is asserted.

  • Accused Features: The accused instrumentality is Amerigen’s combination drug product containing extended-release memantine and donepezil (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,329,752, "Composition For Administering An NMDA Receptor Antagonist To A Subject," issued December 11, 2012 (Compl. ¶19).

  • Technology Synopsis: This patent covers solid oral dosage forms of memantine providing an extended-release profile. The claims are directed to the composition itself, defined by specific in vitro dissolution rates at multiple time points and pharmacokinetic parameters achieved upon administration (’752 Patent, Abstract; col. 2:10-23).

  • Asserted Claims: Claims 1 and 9 are asserted (Compl. ¶34). Claim 1 is an independent claim.

  • Accused Features: Amerigen’s extended-release memantine capsule product is alleged to be a composition that infringes the claims of the ’752 patent (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,338,485, "Compositions For The Treatment of CNS-Related Conditions," issued December 25, 2012 (Compl. ¶20).

  • Technology Synopsis: This patent claims pharmaceutical compositions containing a combination of extended-release memantine and immediate-release donepezil. The claims define the composition by the specific pharmacokinetic profile of memantine it produces in a patient, including limitations on the rate of concentration change ("dC/dT") (’485 Patent, Abstract; col. 2:45-54).

  • Asserted Claims: Claims 1, 3, 9, and 11 are asserted (Compl. ¶34). Independent claims are 1 and 9.

  • Accused Features: Amerigen's generic capsule containing extended-release memantine and donepezil is alleged to be an infringing composition (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,338,486, "Methods For The Treatment of CNS-Related Conditions," issued December 25, 2012 (Compl. ¶21).

  • Technology Synopsis: This patent is directed to methods of treating CNS conditions like Alzheimer's by administering a combination of memantine and donepezil. The claims define the method by the specific pharmacokinetic profile of memantine that results from the administration, including particular "dC/dT" values over defined time periods (’486 Patent, Abstract; col. 2:45-54).

  • Asserted Claims: Claims 1, 3, 7, and 9 are asserted (Compl. ¶34). Independent claims are 1 and 7.

  • Accused Features: The accused act is the filing of the ANDA for a product intended to be used in a manner that would infringe the claimed methods of treatment (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,362,085, "Method For Administering An NMDA Receptor Antagonist To A Subject," issued January 29, 2013 (Compl. ¶22).

  • Technology Synopsis: This patent claims methods for administering memantine in an extended-release formulation to a patient with a neurological condition. The claims focus on the resulting pharmacokinetic profile, specifically a "dC/dT" that is lower than an immediate-release formulation and achieves a specific maximum concentration (Cmax) (’085 Patent, Abstract; col. 2:10-23).

  • Asserted Claims: Claims 1 and 7 are asserted (Compl. ¶34). Claim 1 is an independent claim.

  • Accused Features: The accused infringement is based on Amerigen's ANDA, which seeks approval to market a drug product for use in a method that allegedly meets the claimed pharmacokinetic parameters (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,580,858, "Compositions For the Treatment Of CNS-Related Conditions," issued November 12, 2013 (Compl. ¶23).

  • Technology Synopsis: This patent claims pharmaceutical compositions comprising extended-release memantine and immediate-release donepezil. The invention is defined by the pharmacokinetic profile it produces, particularly the rate of change in memantine concentration ("dC/dT") over specific time intervals post-administration (’858 Patent, Abstract; col. 2:50-59).

  • Asserted Claims: Claims 1, 2, 4, and 10 are asserted (Compl. ¶34). Independent claims are 1 and 10.

  • Accused Features: Amerigen’s generic capsule product containing extended-release memantine and donepezil is alleged to be an infringing composition (Compl. ¶32, ¶34).

  • Patent Identification: U.S. Patent No. 8,598,233, "Method For Administering An NMDA Receptor Antagonist To A Subject," issued December 3, 2013 (Compl. ¶24).

  • Technology Synopsis: The patent claims methods of administering an extended-release formulation of memantine to a subject with a neurological condition. The method is defined by the resulting pharmacokinetic profile, which includes specific limits on the rate of change in plasma concentration ("dC/dT") over defined time periods after administration (’233 Patent, Abstract; col. 2:10-23).

  • Asserted Claims: Claims 1 and 4 are asserted (Compl. ¶34). Claim 1 is an independent claim.

  • Accused Features: The infringement allegation is based on the intended use of Amerigen’s generic product, which Plaintiffs allege will meet the pharmacokinetic parameters of the claimed method (Compl. ¶32, ¶34).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are Defendants' proposed generic capsule products containing extended-release memantine hydrochloride and donepezil hydrochloride, for which Defendants submitted ANDA No. 208237 to the FDA (Compl. ¶28). The complaint specifically identifies proposed dosage strengths of 7 mg, 14 mg, 21 mg, and 28 mg of extended-release memantine hydrochloride, each combined with 10 mg of donepezil hydrochloride (Compl. ¶28, ¶30, ¶31).

Functionality and Market Context

  • The products are generic versions of Plaintiffs' branded drug, Namzaric®, which is approved for the treatment of CNS conditions such as moderate to severe dementia of the Alzheimer's type (Compl. ¶25, ¶29). The complaint alleges that all twelve patents-in-suit are listed for Namzaric® in the FDA's "Orange Book" (Compl. ¶25). The filing of ANDA No. 208237 seeks FDA approval to market these generic products prior to the expiration of the patents-in-suit (Compl. ¶32).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that the submission of ANDA No. 208237, including its subsequent amendments, for approval to market the accused generic products before the expiration of the patents-in-suit constitutes an act of infringement under the Hatch-Waxman Act, 35 U.S.C. § 271(e)(2)(A) (Compl. ¶34). The complaint does not contain detailed infringement contentions or claim charts. The following charts summarize the infringement theory as can be inferred from the complaint's description of the accused products and the patent claims.

8,039,009 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating Alzheimer's disease comprising once daily administration of a modified release solid oral dosage form... The accused products are intended for once-daily use to treat conditions such as Alzheimer's dementia, and are formulated as capsules for oral administration. ¶28, ¶32 col. 23:9-11
...comprising 28 mg ±5% of memantine or a pharmaceutically acceptable salt thereof... Defendants' ANDA seeks approval for, among other strengths, a capsule product containing 28 mg of extended-release memantine hydrochloride. ¶28 col. 23:12-14
...and a pharmaceutically acceptable polymeric carrier substantially contributing to the modification of the release of the memantine... The accused products contain "extended-release memantine hydrochloride," which implies the use of a release-modifying carrier such as a polymer. ¶28, ¶32 col. 23:15-18
...said dosage form sustaining release of the memantine... from about 4 hours to about 24 hours following entry of said form into a use environment... The "extended-release" nature of the memantine in the accused products is alleged to result in a sustained release over an extended period consistent with once-daily dosing. ¶28, ¶32 col. 23:19-22
...wherein said dosage form has a single phase dissolution rate of less than about 80% after passage of about 6 hours... The formulation of the accused "extended-release" product is alleged to have dissolution characteristics that meet this limitation. ¶28, ¶32 col. 23:23-25

8,058,291 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a CNS-related condition... selected from the group consisting of Alzheimer's disease and dementia, comprising orally administering once a day to a human subject in need thereof: The accused products are generic versions of Namzaric®, intended for once-daily oral administration for treating Alzheimer's disease. ¶28, ¶32 col. 30:52-59
(a) 5-40 mg memantine or a pharmaceutically acceptable salt thereof provided in an extended release dosage form... The accused products contain 7, 14, 21, or 28 mg of memantine hydrochloride in an extended-release formulation. ¶28, ¶30, ¶31 col. 30:60-62
...wherein said extended release memantine... provides a change in plasma concentration as a function of time (dC/dT) that is less than about 50% of the dC/dT of the same quantity of an immediate release form of memantine... The "extended-release" formulation of memantine in the accused products is alleged to produce a slower rate of drug absorption and a correspondingly lower "dC/dT" compared to an immediate-release version. ¶28, ¶32 col. 30:62-col. 31:4
(b) a therapeutically effective amount of donepezil or a pharmaceutically acceptable salt thereof... The accused products contain 10 mg of donepezil hydrochloride. ¶28, ¶30, ¶31 col. 31:5-7

Identified Points of Contention

  • Scope Questions: A central point of contention for all asserted patents will likely be whether the specific pharmacokinetic (PK) and in vitro dissolution parameters recited in the claims (e.g., "dC/dT," "single phase dissolution rate," specific percentage releases at specific times) read on the actual performance of Defendants' proposed generic products. The dispute will question whether the formulation characteristics of the accused products fall within the scope of these functional limitations.
  • Technical Questions: An evidentiary question will be what proof Plaintiffs can adduce that the accused products, if marketed, would actually meet the claimed PK parameters in human subjects. This analysis often involves comparing the ANDA filing data against the claims and may require expert testimony on pharmaceutical formulation and bioequivalence. The complaint's lack of specific factual allegations mapping the accused product's characteristics to the claim limitations suggests these details will be a primary focus of discovery.

V. Key Claim Terms for Construction

  • The Term: "a single phase dissolution rate" (’009 Patent, Claim 1)

  • Context and Importance: This term appears in the main independent claim of the ’009 patent and defines a key performance characteristic of the invention. The infringement analysis will depend on whether the dissolution profile of the accused product can be characterized as "single phase" and whether it meets the subsequent rate limitation. Practitioners may focus on this term because its definition is not explicitly provided and could be interpreted based on the shape of the dissolution curve shown in the patent's figures.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes the invention in terms of providing sustained release from a matrix, which generally produces a smooth, continuous release curve without abrupt changes. The patent contrasts this with multiphase profiles that have distinct immediate-release and extended-release stages (’009 Patent, col. 2:56-64). This could support a construction covering any formulation that avoids a significant initial dose dump.
    • Evidence for a Narrower Interpretation: The figures in the patent (e.g., FIG. 1, FIG. 10) consistently show dissolution curves with a specific, continuous, and concave-down shape. A defendant may argue that "single phase" requires a profile that closely matches this illustrated shape, potentially excluding profiles with different curvatures or initial lag times.

  • The Term: "a change in plasma concentration as a function of time (dC/dT) that is less than about 50% of the dC/dT of the same quantity of an immediate release form of memantine" (’291 Patent, Claim 1)

  • Context and Importance: This limitation defines the invention's core functional improvement—a slower rate of drug absorption—by comparison to a reference standard ("an immediate release form"). The entire infringement case for the ’291 patent and many of the other asserted patents will turn on how this comparative pharmacokinetic parameter is measured and interpreted.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification broadly describes the goal of reducing the concentration ramp to "reduce or eliminate the need to dose escalate the drug" (’291 Patent, col. 4:12-14). This purpose could support a construction where any statistically significant reduction in the initial slope of the plasma concentration curve relative to an immediate-release version meets the limitation.
    • Evidence for a Narrower Interpretation: The patent provides detailed simulated pharmacokinetic graphs (e.g., FIG. 1B, FIG. 6A-E) and data tables (FIG. 8) that illustrate specific "dC/dT" values and Tmax shifts. A defendant could argue that the term requires not just any reduction, but a reduction of the magnitude shown in the patent's own examples and figures, and that the "immediate release form" used for comparison must be a specific, established reference product (e.g., commercially available Namenda® IR tablets).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce and contribute to the infringement of the asserted method claims (Compl. ¶34, ¶35). The basis for contributory infringement is the allegation that the accused products are not staple articles of commerce suitable for substantial non-infringing use and are especially adapted for an infringing use (Compl. ¶36). The basis for inducement is the allegation that Defendants will actively encourage direct infringement by medical professionals and patients, presumably through product labeling and marketing materials once the generic is launched (Compl. ¶35).
  • Willful Infringement: The complaint does not explicitly use the word "willful" but lays the groundwork for such a claim. It alleges that Defendants were aware of the patents-in-suit prior to filing the ANDA amendments that are the subject of this complaint, citing the prior, ongoing litigation between the parties on the same patents (Compl. ¶37, ¶38). Furthermore, the complaint seeks a finding that this is an "exceptional case" under 35 U.S.C. § 285, which is the statutory basis for awarding attorney's fees, often in cases of willful infringement or litigation misconduct (Compl. ¶39).

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

  • A core issue will be one of pharmacokinetic and dissolution scope: Do the specific quantitative parameters recited in the asserted claims—such as the rate of plasma concentration change ("dC/dT"), the ratio of maximum to mean concentration ("Cmax/Cmean"), and "single phase dissolution rate"—read on the actual performance characteristics of the accused generic products as disclosed in ANDA No. 208237? This will likely be a battle of competing expert analyses of the ANDA data.
  • A second central question will be one of claim construction and comparison: How should the reference standard "immediate release form," which is central to the limitations in the '291 patent family, be defined for the purpose of the "dC/dT" comparison, and does the evidence from the ANDA show that the accused products meet the claimed percentage reduction relative to that standard?
  • A key procedural and legal issue will be the impact of the prior litigation: How will the court and parties leverage the existence of the earlier-filed suit on the same patents (No. 15-966-LPS)? This raises questions about the potential for early claim construction rulings, issue preclusion, and the strength of Plaintiffs' assertion that Defendants' continued pursuit of FDA approval in the face of that litigation makes this an "exceptional case."