DCT

1:18-cv-00844

Astellas Pharma Inc v. Cipla Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00844, D. Del., 06/05/2018
  • Venue Allegations: Venue is asserted based on Defendant Cipla's business activities in Delaware and its act of sending a statutory notice letter concerning its Abbreviated New Drug Application (ANDA) to Plaintiff Astellas Pharma U.S., Inc., a Delaware corporation.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an ANDA to market a generic version of the drug VESIcare® (solifenacin succinate) constitutes an act of infringement of a patent covering the active pharmaceutical ingredient.
  • Technical Context: The technology involves a specific chemical compound, solifenacin, which functions as a selective muscarinic M3 receptor antagonist for the treatment of overactive bladder.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's notice to Plaintiff on April 25, 2018, of its ANDA filing. The complaint notes the patent-in-suit is listed in the FDA's "Orange Book" with an expiration date of November 19, 2018, and a period of pediatric exclusivity extending to May 19, 2019. The complaint also notes that a third party, Teva Pharmaceuticals, holds first-filer marketing exclusivity for solifenacin succinate.

Case Timeline

Date Event
1994-12-28 U.S. Patent No. 6,017,927 Priority Date
2000-01-25 U.S. Patent No. 6,017,927 Issue Date
2004-11-19 FDA Approval of VESIcare® New Drug Application
2018-04-25 Date of Cipla's ANDA Notice Letter to Plaintiffs
2018-06-05 Complaint Filing Date

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

U.S. Patent No. 6,017,927 - "Quinuclidine Derivatives and Medicinal Composition Thereof"

  • Patent Identification: U.S. Patent No. 6,017,927, "Quinuclidine Derivatives and Medicinal Composition Thereof", issued January 25, 2000.

The Invention Explained

  • Problem Addressed: The patent's background section describes a need for improved treatments for conditions involving the muscarinic M3 receptor, such as overactive bladder. It notes that existing non-selective antagonists like atropine block multiple receptor subtypes (M1, M2, and M3), which can lead to significant side effects, including adverse cardiac events associated with blocking the M2 receptor (’927 Patent, col. 1:26-41).
  • The Patented Solution: The invention claims to solve this problem by providing a novel class of quinuclidine derivatives that exhibit "excellent selective antagonistic activity against muscarinic M3 receptor" ('927 Patent, col. 2:22-24). This selectivity is intended to provide the desired therapeutic effect on the bladder's smooth muscle while minimizing side effects on other systems, particularly the heart ('927 Patent, col. 9:60-68). The core of the invention is a chemical structure combining a tetrahydroisoquinoline or similar skeleton with a quinuclidinyloxycarbonyl group ('927 Patent, col. 3:5-12).
  • Technical Importance: This approach represented a step toward more targeted pharmacotherapy for overactive bladder by isolating the therapeutic mechanism (M3 antagonism) from known side-effect pathways (M2 antagonism), potentially offering an improved safety profile over older, less selective drugs ('927 Patent, col. 9:50-68).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1-7, which includes independent claims 1 and 7 (Compl. ¶¶30-31).
  • Independent Claim 1 recites:
    • A quinuclidine derivative represented by a specific chemical formula (I).
    • The formula includes several variables defining substituent groups (Ring A, R) and structural features (X, l, m, n).
    • The claim also covers "a salt thereof, an N-oxide thereof, or a quaternary ammonium salt thereof."
  • Independent Claim 7 recites a pharmaceutical composition comprising the derivative of claim 1 and a "pharmaceutically acceptable carrier."
  • The complaint reserves the right to assert dependent claims 2-6, which further limit the chemical structure defined in claim 1 (Compl. ¶¶30-31).

III. The Accused Instrumentality

Product Identification

  • Defendant's proposed generic drug product containing solifenacin succinate in 5 mg and 10 mg oral tablet forms, as described in ANDA No. 209839 (the "ANDA Product") (Compl. ¶23).

Functionality and Market Context

  • The ANDA Product contains solifenacin succinate as its active pharmaceutical ingredient and is intended for the treatment of overactive bladder (Compl. ¶¶10, 23). The complaint provides a chemical structure diagram depicting solifenacin succinate, which is described as a salt of solifenacin and succinic acid (Compl. ¶19; p. 5). The complaint's visual evidence depicts the chemical structure of solifenacin succinate, showing the active solifenacin molecule bonded with succinic acid (Compl. p. 5). The ANDA filing itself represents a bid to market a generic equivalent of Plaintiff's branded drug, VESIcare®, prior to the expiration of the '927 Patent (Compl. ¶¶7, 18, 23).

IV. Analysis of Infringement Allegations

The complaint alleges that the act of filing the ANDA constitutes infringement under 35 U.S.C. § 271(e)(2) and that future commercialization would constitute infringement under § 271(a) (Compl. ¶¶30-31). The allegations are not presented in a formal claim chart exhibit but are based on the identity of the compound in the ANDA Product.

’927 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A quinuclidine derivative represented by the following formula (I): ... 3-quinuclidinyl 1-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate, ... a salt thereof The ANDA Product is a pharmaceutical composition containing solifenacin succinate, which is alleged to be a salt of the compound solifenacin, chemically named (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate. ¶19, ¶23, p. 5 col. 73:55-58

Identified Points of Contention

  • Scope Questions: As is common in ANDA litigation over compound patents, a central dispute may not be infringement but rather the validity of the asserted claims. Defendant's notice letter asserted that the claims are "invalid, unenforceable and/or not infringed" (Compl. ¶26). A potential infringement question could be whether the specific salt form (succinate) or stereoisomer in the ANDA Product falls within the scope of the asserted claims as properly construed.
  • Technical Questions: The primary technical question will be one of structural identity. The court will need to determine if the active pharmaceutical ingredient defined in Defendant's ANDA, including its specific salt form, stereochemistry, and any potential polymorphs, is a structure that meets all the limitations of the asserted patent claims.

V. Key Claim Terms for Construction

The Term: "a salt thereof"

  • Context and Importance: This term is critical because the accused ANDA Product is solifenacin succinate, a specific salt form (Compl. ¶19). The infringement analysis depends on whether this specific salt is encompassed by the claim language. Practitioners may focus on this term to dispute whether the patent provides adequate written description and enablement for the succinate salt specifically.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a non-exhaustive list of acids that can be used to form salts, explicitly including "succinic acid" among the enumerated organic acids ('927 Patent, col. 7:50-58). This language may support a construction that expressly includes the accused salt form.
    • Evidence for a Narrower Interpretation: A party seeking a narrower construction may note that while many acids are listed, the patent's working examples only describe the preparation of oxalate and hydrochloride salts ('927 Patent, col. 19:26-36; col. 21:42-22:10). This could form the basis of an argument that only the exemplified salt types were fully contemplated and enabled by the inventors.

The Term: "quinuclidine derivative represented by the following formula (I)"

  • Context and Importance: This term defines the core chemical structure of the invention. While the ANDA Product is identified as solifenacin, a dispute could arise over whether the specific stereoisomer in that product is covered by the claims.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent states that the invention "contains an asymmetric carbon atom so that there exist optical isomers" and that the invention "embraces diastereomers and enantiomers... as well as mixtures thereof" ('927 Patent, col. 7:41-47). This suggests the claims are intended to cover all stereoisomeric forms unless otherwise specified.
    • Evidence for a Narrower Interpretation: The patent provides examples for preparing specific stereoisomers, such as the (1R,3'R) isomer (Example 8) ('927 Patent, col. 21:42). A party could argue that the claims should be limited to the specific isomers that were actually prepared and tested and which demonstrate the selective M3 antagonism described as a key feature of the invention.

VI. Other Allegations

  • Indirect Infringement: The complaint does not provide sufficient detail for analysis of indirect infringement, as its focus is on the statutory act of infringement under 35 U.S.C. § 271(e)(2) and the prospective direct infringement from commercialization.
  • Willful Infringement: The complaint alleges that Defendant "was aware of the '927 patent and its infringement of that patent when it filed ANDA No. 209839," establishing a claim of pre-suit knowledge (Compl. ¶35). This allegation, combined with the assertion that the case is "exceptional," forms the basis for a potential willfulness claim and a request for enhanced damages and attorneys' fees (Compl. ¶36; Prayer for Relief G).

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

  • A primary issue will likely be the validity of the asserted claims. Given that the accused product is a generic version of a branded drug, the dispute will probably focus less on whether the chemical structures are identical and more on whether the patent claims covering that structure are valid in view of the prior art or subject to other invalidity challenges like lack of enablement or written description.
  • A second core issue will be one of definitional scope: can the term "a salt thereof" be construed to unambiguously cover the succinate salt of solifenacin, and does the patent provide adequate written description for this specific salt, even though it is expressly named in a list of potential salt-forming acids but not reduced to practice in an example?
  • A key evidentiary question will be one of structural scope: does the patent's disclosure provide sufficient support to claim all stereoisomers of the claimed compound, or could the claims be limited to the specific isomers shown to possess the advantageous properties touted by the inventors, potentially creating a non-infringement pathway for the Defendant?