DCT
1:24-cv-05299
Impax Laboratories LLC v. Ascent Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Impax Laboratories, LLC (Delaware)
- Defendant: Ascent Pharmaceuticals Inc. (New York)
- Plaintiff’s Counsel: Troutman Pepper Hamilton Sanders LLP
- Case Identification: 1:24-cv-05299, D.N.J., 04/18/2024
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant conducts substantial business in the state, including developing, marketing, and selling generic pharmaceutical products. The complaint further alleges that Defendant has a regular and established place of business in New Jersey through an affiliated company and has consented to venue in prior actions.
- Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's RYTARY® (carbidopa/levodopa) extended-release capsules constitutes an act of infringement of eight U.S. patents.
- Technical Context: The technology concerns controlled-release oral pharmaceutical formulations for treating Parkinson's disease, designed to provide steadier plasma concentrations of the drug levodopa to reduce motor fluctuations.
- Key Procedural History: The lawsuit was triggered by Defendant's submission of an ANDA with a Paragraph IV certification, alleging that the patents-in-suit are invalid, unenforceable, and/or not infringed by its proposed generic product. The complaint notes prior litigation involving several of the patents-in-suit against other generic drug manufacturers, including Actavis Laboratories, Zydus Pharmaceuticals, and Sandoz Inc.
Case Timeline
| Date | Event |
|---|---|
| 2007-12-28 | Earliest Priority Date for all Patents-in-Suit |
| 2013-02-19 | U.S. Patent No. 8,377,474 Issued |
| 2013-06-04 | U.S. Patent No. 8,454,998 Issued |
| 2013-10-15 | U.S. Patent No. 8,557,283 Issued |
| 2015-07-28 | U.S. Patent No. 9,089,607 Issued |
| 2015-07-28 | U.S. Patent No. 9,089,608 Issued |
| 2016-10-11 | U.S. Patent No. 9,463,246 Issued |
| 2017-01-03 | U.S. Patent No. 9,533,046 Issued |
| 2018-02-27 | U.S. Patent No. 9,901,640 Issued |
| 2024-03-08 | Plaintiff received Defendant’s ANDA Notice Letter |
| 2024-04-18 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,377,474 - “Controlled Release Formulations of Levodopa and Uses Thereof”
The Invention Explained
- Problem Addressed: The patent describes that conventional treatments for Parkinson's disease using levodopa (LD) and a decarboxylase inhibitor like carbidopa (CD) result in fluctuating plasma concentrations of LD. These fluctuations can lead to debilitating "on-off" periods where patients unpredictably lose mobility as the drug's effect wears off between doses (’474 Patent, col. 1:24-2:11). Existing controlled-release formulations were an attempt to solve this but were problematic, often having a slow onset of action that left patients immobile in the morning (’474 Patent, col. 2:11-2:22).
- The Patented Solution: The invention is a multiparticulate oral formulation that combines immediate-release and controlled-release components to achieve a more stable, infusion-like plasma profile of levodopa. The formulation comprises three distinct parts: (i) an immediate-release component of CD/LD for rapid onset, (ii) a controlled-release component of CD/LD for sustained effect, and (iii) a carboxylic acid component (such as tartaric acid), which the inventors discovered helps control the absorption of LD to yield steadier plasma concentrations (’474 Patent, Abstract; col. 2:50-2:62).
- Technical Importance: This multi-component approach was designed to provide patients with faster relief ("time to 'on'") while also extending the duration of efficacy ("on time") and reducing motor fluctuations throughout the day (’474 Patent, col. 2:40-2:49).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶49).
- Essential elements of claim 1 include:
- A multiparticulate, controlled release oral solid formulation of levodopa comprising:
- i) a controlled release component comprising a mixture of levodopa, a decarboxylase inhibitor and a rate controlling excipient;
- ii) a carboxylic acid component; and
- iii) an immediate release component comprising a mixture of levodopa and a decarboxylase inhibitor.
- The complaint reserves the right to assert additional claims (Compl. ¶49).
U.S. Patent No. 8,454,998 - “Controlled Release Formulations of Levodopa and Uses Thereof”
The Invention Explained
- Problem Addressed: This patent, from the same family as the ’474 Patent, addresses the same technical problem of motor fluctuations in Parkinson's patients due to unstable levodopa plasma levels from existing oral therapies (’998 Patent, col. 1:24-2:11).
- The Patented Solution: The ’998 Patent claims methods of using the formulation technology described in the ’474 Patent. It focuses on the therapeutic outcome of administering such a formulation—specifically, a method for treating a movement disorder by administering a formulation that achieves a particular levodopa plasma concentration profile over time (’998 Patent, Abstract). This profile is characterized by a rapid initial rise in concentration followed by a sustained, steadier level, which reduces "off" times and motor fluctuations (’998 Patent, col. 2:40-2:49).
- Technical Importance: By claiming the method of treatment that results in a specific pharmacokinetic profile, the patent seeks to protect the therapeutic regimen and clinical benefits derived from the novel formulation, not just the composition itself.
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶60).
- Essential elements of claim 1 include:
- A method for treating a movement disorder in a patient suffering therefrom,
- comprising administering to the patient an effective amount of a multiparticulate, controlled release oral solid formulation of levodopa,
- the formulation comprising: i) a controlled release component comprising levodopa, carbidopa and one or more rate controlling excipients, ii) an immediate release component comprising levodopa and carbidopa, and iii) a carboxylic acid component,
- wherein the molar ratio of carboxylic acid to levodopa is greater than 1:4 and less than 3:2.
- The complaint reserves the right to assert additional claims (Compl. ¶60).
U.S. Patent No. 8,557,283 - “Controlled Release Formulations of Levodopa and Uses Thereof”
- Patent Identification: U.S. Patent No. 8,557,283, issued October 15, 2013 (Compl. ¶22).
- Technology Synopsis: A continuation of the same technology, this patent claims a method of reducing motor fluctuations in a Parkinson's patient by administering the multiparticulate formulation containing immediate-release, controlled-release, and carboxylic acid components to achieve a specific pharmacokinetic profile (’283 Patent, col. 3:10-4:24).
- Asserted Claims: At least independent claim 1 is asserted (Compl. ¶77).
- Accused Features: The Defendant's ANDA product and its proposed use to treat Parkinson's disease are accused of infringement (Compl. ¶78).
U.S. Patent No. 9,089,607 - “Controlled Release Formulations of Levodopa and Uses Thereof”
- Patent Identification: U.S. Patent No. 9,089,607, issued July 28, 2015 (Compl. ¶23).
- Technology Synopsis: This patent claims methods for treating Parkinson's disease by administering the multiparticulate formulation, specifying particular pharmacokinetic outcomes, such as achieving a levodopa plasma concentration that remains at or above 50% of the peak concentration for a defined duration (’607 Patent, col. 46:11-28).
- Asserted Claims: At least independent claim 1 is asserted (Compl. ¶92).
- Accused Features: The Defendant's ANDA product and its intended use for treating Parkinson's disease, which is alleged to result in the claimed pharmacokinetic profile (Compl. ¶¶ 92-93).
U.S. Patent No. 9,089,608 - “Controlled Release Formulations of Levodopa and Uses Thereof”
- Patent Identification: U.S. Patent No. 9,089,608, issued July 28, 2015 (Compl. ¶24).
- Technology Synopsis: This patent claims a method for providing a therapeutic concentration of levodopa over a 4-hour period by administering the multiparticulate formulation. It specifies a pharmacokinetic profile with a rapid onset and a sustained therapeutic level, defined by two distinct concentration peaks (’608 Patent, col. 46:12-42).
- Asserted Claims: At least independent claim 1 is asserted (Compl. ¶103).
- Accused Features: The Defendant's ANDA product, which is alleged to produce the claimed dual-peak pharmacokinetic profile when administered (Compl. ¶103).
U.S. Patent No. 9,463,246 - “Controlled Release Formulations of Levodopa and Uses Thereof”
- Patent Identification: U.S. Patent No. 9,463,246, issued October 11, 2016 (Compl. ¶25).
- Technology Synopsis: This patent claims an oral dosage form that contains a combination of immediate-release and controlled-release beads of carbidopa and levodopa. It specifies the in vitro dissolution profiles of the controlled-release beads, requiring a slower dissolution rate compared to the immediate-release beads (’246 Patent, col. 49:50-50:2).
- Asserted Claims: At least independent claim 26 is asserted (Compl. ¶114).
- Accused Features: The specific formulation of Defendant's ANDA product, which allegedly contains beads with the claimed dissolution characteristics (Compl. ¶115).
U.S. Patent No. 9,533,046 - “Controlled Release Formulations of Levodopa and Uses Thereof”
- Patent Identification: U.S. Patent No. 9,533,046, issued January 3, 2017 (Compl. ¶26).
- Technology Synopsis: This patent claims a method for treating Parkinson's disease by administering a multiparticulate formulation with specific populations of controlled-release beads that exhibit different dissolution profiles. This combination of bead populations is designed to achieve the desired overall pharmacokinetic profile (’046 Patent, col. 45:60-46:30).
- Asserted Claims: At least independent claim 1 is asserted (Compl. ¶130).
- Accused Features: The Defendant's ANDA product, which is alleged to be formulated with multiple bead populations that infringe the claimed method (Compl. ¶¶ 131-132).
U.S. Patent No. 9,901,640 - “Controlled Release Formulations of Levodopa and Uses Thereof”
- Patent Identification: U.S. Patent No. 9,901,640, issued February 27, 2018 (Compl. ¶27).
- Technology Synopsis: This patent claims an oral modified-release dosage form comprising carbidopa, levodopa, a carboxylic acid, and a modified-release excipient. The claims specify a particular molar ratio of carboxylic acid to levodopa and a peak-to-trough plasma level of about 1 to 3 after administration every six hours (’640 Patent, col. 49:55-50:4).
- Asserted Claims: At least independent claim 15 is asserted (Compl. ¶146).
- Accused Features: The Defendant's ANDA product, which is alleged to have the claimed molar ratio and to produce the claimed peak-to-trough levodopa plasma level when administered as directed (Compl. ¶146).
III. The Accused Instrumentality
Product Identification
Defendant’s carbidopa/levodopa extended-release capsules for oral use, which are the subject of ANDA No. 219307 (the "Ascent ANDA Products") (Compl. ¶31).
Functionality and Market Context
The Ascent ANDA Products are a generic version of Plaintiff’s RYTARY® product, intended for the treatment of Parkinson's disease (Compl. ¶1, ¶35). The complaint alleges that by filing its ANDA, Defendant represented to the FDA that its product has the same active ingredients, method of administration, dosage forms, and strengths as RYTARY®, and is bioequivalent to RYTARY® (Compl. ¶35). The product is intended to be sold under a label that is substantively the same as the RYTARY® label, positioning it to compete directly with Plaintiff’s branded product upon FDA approval (Compl. ¶35).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges infringement based on Defendant's filing of ANDA No. 219307, an act of infringement under 35 U.S.C. § 271(e)(2). Due to the confidential nature of the ANDA submission, the complaint does not provide specific factual allegations mapping elements of the accused product to the claim limitations (Compl. ¶40). The infringement theory is that because the Ascent ANDA Product is a bioequivalent copy of RYTARY®, it will necessarily practice the claims that cover the RYTARY® formulation and its method of use (Compl. ¶35, ¶49).
’474 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A multiparticulate, controlled release oral solid formulation of levodopa | The complaint alleges the Ascent ANDA Product is a multiparticulate, controlled release oral solid formulation of levodopa, as it is a generic version of RYTARY®. | ¶49 | col. 6:24-26 |
| i) a controlled release component comprising a mixture of levodopa, a decarboxylase inhibitor and a rate controlling excipient; | The complaint alleges, based on a review of confidential ANDA documents, that the Ascent ANDA Product contains this controlled release component. | ¶49 | col. 6:27-30 |
| ii) a carboxylic acid component; and | The complaint alleges, based on a review of confidential ANDA documents, that the Ascent ANDA Product contains this carboxylic acid component. | ¶49 | col. 6:31-31 |
| iii) an immediate release component comprising a mixture of levodopa and a decarboxylase inhibitor. | The complaint alleges, based on a review of confidential ANDA documents, that the Ascent ANDA Product contains this immediate release component. | ¶49 | col. 6:32-34 |
’998 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating a movement disorder...comprising administering...a multiparticulate, controlled release oral solid formulation of levodopa | The complaint alleges Ascent will induce infringement by marketing the ANDA product with a label instructing its use for treating Parkinson's disease, a movement disorder. | ¶62, ¶65 | col. 29:32-37 |
| the formulation comprising: i) a controlled release component..., ii) an immediate release component..., and iii) a carboxylic acid component... | The complaint alleges the Ascent ANDA Product contains these formulation components. | ¶61 | col. 29:38-44 |
| wherein the molar ratio of carboxylic acid to levodopa is greater than 1:4 and less than 3:2. | The complaint alleges, based on a review of confidential ANDA documents, that the Ascent ANDA Product has the claimed molar ratio. | ¶61 | col. 29:45-47 |
- Identified Points of Contention:
- Technical Questions: A primary technical question for the case, resolvable only through discovery, is whether the specific "rate controlling excipient(s)" and formulation architecture used in the Ascent ANDA Product meet the definitions of the claimed components. The analysis will depend on the precise materials used, their quantities, and their physical arrangement within the capsule.
- Scope Questions: The dispute may raise questions about the scope of the term "component." For instance, if Ascent's formulation integrates the carboxylic acid with one of the other components rather than providing it as a physically distinct element, it would raise the question of whether this arrangement meets the claim limitation requiring three separate "components."
V. Key Claim Terms for Construction
The Term: "carboxylic acid component" (’474 Patent, cl. 1)
Context and Importance: This term is central because the novel inclusion of a carboxylic acid is a key feature of the invention. The definition of what constitutes a distinct "component" will be critical. Practitioners may focus on this term because if Ascent's formulation combines the carboxylic acid with another element, the question of whether it is a separate "component" as claimed will be a primary non-infringement argument.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes that all components "are coformulated into a single component" in one embodiment, which may support an argument that the components need not be physically separate beads to meet the definition (’474 Patent, col. 6:50-53).
- Evidence for a Narrower Interpretation: The specification also describes an embodiment where the "controlled release component, the immediate release component and the carboxylic acid component are each manufactured as distinct, separable beads," which may support a narrower construction requiring physical separation (’474 Patent, col. 6:45-49).
The Term: "a levodopa plasma or serum concentration profile" (’998 Patent, cl. 15)
Context and Importance: This term is foundational to the asserted method claims. The infringement analysis for these claims will require a comparison between the pharmacokinetic (PK) profile generated by Ascent's ANDA product and the profile defined in the claims. Practitioners may focus on this term because disputes in ANDA cases often center on whether the generic product, despite being "bioequivalent" for FDA purposes, actually produces a PK profile that meets all the specific numerical limitations of a patent claim.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent defines the profile in terms of relative values (e.g., a second concentration being "equal to about fifty percent of said second concentration"), which provides some flexibility and could be read broadly to cover profiles that are substantially similar (’998 Patent, col. 30:52-65).
- Evidence for a Narrower Interpretation: The claim recites a series of specific relationships between concentrations at different time points. A defendant may argue that these create a precise, multi-part definition that must be met exactly, and that any deviation in its product's PK profile, even if minor, avoids infringement.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents. Inducement is based on the allegation that Ascent's product label and promotional materials will instruct healthcare professionals and patients to administer the drug in a manner that directly infringes the method claims (e.g., Compl. ¶50, ¶65). Contributory infringement is based on the allegation that the Ascent ANDA Products are not suitable for substantial non-infringing use and are especially made for an infringing use (e.g., Compl. ¶51, ¶67).
- Willful Infringement: The complaint alleges that Defendant has had knowledge of the patents-in-suit since at least the date it submitted its ANDA and Paragraph IV certifications (Compl. ¶53, ¶69). It is alleged that Defendant was aware that the submission of the ANDA constituted an act of infringement. Based on this alleged knowledge, the complaint asserts that any subsequent commercial activity would constitute willful infringement and requests a finding that the case is "exceptional" under 35 U.S.C. § 285, which would entitle Plaintiff to attorneys' fees (Compl. ¶54, ¶70).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of factual correspondence: Does the specific formulation detailed in Ascent’s confidential ANDA—including its particular excipients, manufacturing methods, and component structure—fall within the scope of the patent claims? This question can only be resolved after discovery into the contents of the ANDA.
- A key evidentiary question will be one of pharmacokinetic identity: Will Ascent's generic product, upon administration, produce a levodopa plasma concentration profile that meets the specific numerical and relational limitations recited in the asserted method claims? This will involve a technical comparison of clinical data and may be a central point of contention, even if the product is deemed bioequivalent by the FDA.
- Finally, a central legal issue will be one of validity: While not detailed in the complaint, Ascent’s Paragraph IV certification asserts that the patents are invalid. The viability of Ascent’s defenses will likely depend on its ability to present prior art that anticipates or renders obvious the claimed combination of immediate-release, controlled-release, and carboxylic acid components for levodopa delivery.