DCT

1:18-cv-01671

Cipla Ltd v. ICOS Corp

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01671, S.D. Ind., 07/27/2018
  • Venue Allegations: Venue is alleged to be proper in the Southern District of Indiana because Defendants reside in the district, maintain their principal places of business there, and have committed acts giving rise to the declaratory judgment action within the district.
  • Core Dispute: Plaintiff seeks a declaratory judgment that Defendants' patents covering pharmaceutical formulations of tadalafil are invalid, primarily based on prior administrative proceedings, in an effort to clear a path for market entry of its generic drug product.
  • Technical Context: The technology concerns pharmaceutical formulations of tadalafil, a beta-carboline compound and PDE5 inhibitor, which is used to treat conditions such as erectile dysfunction and pulmonary arterial hypertension.
  • Key Procedural History: The complaint alleges that the patents-in-suit are listed in the FDA's Orange Book for tadalafil. Plaintiff Cipla filed an Abbreviated New Drug Application (ANDA) with a Paragraph IV certification challenging the patents. After the patent holders did not file suit within the statutory 45-day window, Cipla initiated this declaratory judgment action. The complaint's central argument rests on prior inter partes review (IPR) proceedings where the Patent Trial and Appeal Board (PTAB) found all claims of both patents unpatentable, a decision later affirmed by the U.S. Court of Appeals for the Federal Circuit. Cipla seeks a district court judgment of invalidity, which it contends is necessary to trigger the forfeiture of a 180-day marketing exclusivity period held by a first-to-file generic competitor, Mylan/Synthon.

Case Timeline

Date Event
1999-08-03 Priority Date for '975 and '958 Patents
2004-11-23 U.S. Patent No. 6,821,975 Issued
2007-02-27 U.S. Patent No. 7,182,958 Issued
2009-10-15 First Paragraph IV certification for tadalafil tablets filed (Synthon)
2012-04-13 Mylan/Synthon ANDA receives tentative FDA approval
2015-01-13 Actelion Pharmaceuticals files IPR petitions against both patents
2015-08-04 PTAB institutes IPR proceedings for both patents
2016-08-03 PTAB issues Final Written Decisions finding all claims unpatentable
2017-12-06 Cipla sends Paragraph IV notice letter to Defendants
2018-04-18 Federal Circuit affirms PTAB decisions of unpatentability
2018-05-25 Federal Circuit issues mandate, closing the IPR appeal
2018-07-27 Complaint for Declaratory Judgment of Invalidity Filed

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

U.S. Patent No. 6,821,975 - "Beta-Carboline Drug Products," issued November 23, 2004

The Invention Explained

  • Problem Addressed: The patent's background section describes that beta-carboline compounds, useful as PDE5 inhibitors, have poor solubility. Previous attempts to address this using "coprecipitate" formulations led to manufacturing difficulties in creating "precisely reproducible lots" and resulted in a slow onset of therapeutic action, with maximum blood concentrations achieved in 3 to 4 hours (’975 Patent, col. 1:46-60). The patent identifies a need for an oral formulation with a more rapid therapeutic effect (’975 Patent, col. 1:60-68).
  • The Patented Solution: The invention is a particulate form of the beta-carboline drug (tadalafil) that is not embedded in a polymer coprecipitate (i.e., it is a "free drug"). The key feature is the control of the drug's particle size, with the patent claiming preparations where at least 90% of the particles are smaller than approximately 40 microns (’975 Patent, Abstract; col. 2:30-38). This reduction in particle size is intended to increase the dissolution rate, leading to a "rapid achievement of maximum blood concentration" and a quicker onset of the drug's therapeutic effects (’975 Patent, col. 2:9-12).
  • Technical Importance: For poorly water-soluble drugs like tadalafil, controlling particle size is a key formulation technique to enhance bioavailability and modify the pharmacokinetic profile, which can be critical for drugs intended for on-demand use (’975 Patent, col. 1:60-65).

Key Claims at a Glance

  • The complaint seeks a declaration that all claims of the patent are invalid (Compl. ¶92). Independent claim 1 is representative.
  • Independent Claim 1:
    • A free drug particulate form of a compound having the chemical structure of tadalafil, or its pharmaceutically acceptable salts and solvates.
    • Wherein the formulation comprises particles of the compound.
    • And wherein at least 90% of the particles have a particle size of less than about 40 microns.

U.S. Patent No. 7,182,958 - "β-Carboline Pharmaceutical Compositions," issued February 27, 2007

The Invention Explained

  • Problem Addressed: Like the ’975 patent, the ’958 patent addresses the challenges of formulating poorly soluble beta-carboline compounds. It notes that prior coprecipitate formulations suffered from reproducibility problems and slow onset of action, creating a "continuing need in the art for oral dosage forms of β-carbolines" with improved characteristics (’958 Patent, col. 1:47-68).
  • The Patented Solution: The invention is not just the small-particle drug substance, but a complete pharmaceutical composition that combines it with a specific set of excipients. The patent claims a formulation comprising the small-particle tadalafil active ingredient in combination with a water-soluble diluent, a lubricant, a specific type of hydrophilic binder (e.g., a cellulose derivative), and a specific type of disintegrant (e.g., croscarmellose sodium) (’958 Patent, Abstract; col. 2:31-41). This claimed combination is designed to yield a final drug product with "uniform potency, and desirable stability and bioavailability characteristics" (’958 Patent, col. 1:19-21).
  • Technical Importance: The invention provides a specific recipe for a solid oral dosage form, addressing not only the bioavailability of the active ingredient but also the practical requirements for manufacturing a stable and effective tablet (’958 Patent, col. 2:42-54).

Key Claims at a Glance

  • The complaint seeks a declaration that all claims of the patent are invalid (Compl. ¶100). Independent claim 1 is representative.
  • Independent Claim 1:
    • A pharmaceutical formulation comprising tadalafil as a free drug with at least 90% of particles having a size less than about 40 microns.
    • Combined with about 50% to 85% by weight of a water-soluble diluent.
    • A lubricant.
    • A hydrophilic binder selected from a group consisting of a cellulose derivative, povidone, and mixtures thereof.
    • A disintegrant selected from a group consisting of croscarmellose sodium, crospovidone, and mixtures thereof.

III. The Accused Instrumentality

Product Identification

The subject of the declaratory judgment action is Cipla's Abbreviated New Drug Application (ANDA) No. 210255, which seeks FDA approval for the commercial manufacture, use, and sale of "tadalafil tablets in the 20 mg dosage strength" (Compl. ¶23).

Functionality and Market Context

Cipla's ANDA product is a generic version of the tadalafil drug product marketed by Defendants (Compl. ¶¶ 22-23). The complaint states that Cipla filed its ANDA with a "Paragraph IV" certification, asserting that the '975 and '958 patents listed in the Orange Book are "unenforceable, invalid and/or will not be infringed" by its generic product (Compl. ¶24). The lawsuit is framed as a necessary step for Cipla to enter the market, which it claims is currently blocked by the 180-day generic marketing exclusivity period held by Mylan, the first ANDA filer. Cipla alleges that a court judgment of invalidity could trigger a forfeiture of that exclusivity, allowing for earlier generic competition (Compl. ¶¶ 57-60, 74).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not allege infringement but rather seeks a declaratory judgment of invalidity. The core invalidity allegations are summarized as follows:

The complaint’s primary, and sole detailed, basis for invalidity is the preclusive effect of prior administrative patent challenges (Compl. ¶¶ 76-86). Cipla alleges that a third party, Actelion Pharmaceuticals Ltd., filed inter partes review (IPR) petitions against both the ’975 and ’958 patents (Compl. ¶76). The complaint states that the Patent Trial and Appeal Board (PTAB) instituted reviews and, on August 3, 2016, issued Final Written Decisions finding all claims of both patents to be unpatentable on the grounds of obviousness under 35 U.S.C. § 103 (Compl. ¶80).

For the ’975 Patent, the PTAB's alleged finding of unpatentability was based on a combination of four prior art references (Compl. ¶81). For the ’958 Patent, the finding was based on a combination of three prior art references in view of common pharmaceutical knowledge (Compl. ¶82).

The complaint further alleges that the patent owner, ICOS, appealed these decisions to the U.S. Court of Appeals for the Federal Circuit, which subsequently affirmed the PTAB's judgments of unpatentability on April 18, 2018 (Compl. ¶¶ 83-84). Cipla argues that because these IPR decisions are final and binding, it is entitled to a judicial declaration from the district court that the claims of the ’975 and ’958 patents are invalid (Compl. ¶¶ 96-97, 104-105).

  • Identified Points of Contention:
    • Legal Question (Statutory Interpretation): A central legal question is whether an affirmed IPR decision invalidating a patent constitutes a "final decision" from "a declaratory judgment action" under the Hatch-Waxman Act, 21 U.S.C. § 355(j)(5)(D)(i)(I)(bb)(AA). The complaint raises this issue by noting that the FDA has not yet determined that an IPR proceeding can trigger the forfeiture of a first-filer's 180-day exclusivity period, which is the ultimate relief Cipla appears to seek (Compl. ¶¶ 87-89, 74).
    • Legal Question (Issue Preclusion): The case raises the question of whether the doctrine of collateral estoppel (issue preclusion) prevents the Defendants from re-litigating the validity of patents that have already been held unpatentable in a final, non-appealable administrative proceeding that was affirmed by the Federal Circuit.

V. Key Claim Terms for Construction

The complaint's invalidity arguments are not grounded in claim construction disputes but rather on the outcome of prior IPR proceedings. The complaint does not identify any specific claim terms as being central to the dispute between Cipla and the Defendants.

VI. Other Allegations

  • Exceptional Case Allegation: In its prayer for relief, Cipla requests that the court declare the case "exceptional" and award expenses, costs, and attorneys' fees under 35 U.S.C. § 285 (Compl., Prayer for Relief ¶C). The complaint does not provide an explicit factual basis for this request. However, such an allegation may be based on an argument that Defendants' continued assertion of the patents via the Orange Book listing is unreasonable in light of the final, affirmed PTAB decisions holding all claims unpatentable (Compl. ¶¶ 22, 84, 86).

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

This case appears to turn less on technical patent disputes and more on the complex interplay between patent law, administrative agency decisions, and pharmaceutical regulations. The key questions for the court are likely to be:

  • A core issue will be one of issue preclusion: are the Defendants collaterally estopped from contesting the invalidity of the '975 and '958 patents in this district court action, given that the PTAB's finding of unpatentability was fully litigated and affirmed on appeal by the Federal Circuit?
  • A central question of statutory interpretation will be whether a district court's declaratory judgment of invalidity, if based entirely on a prior IPR decision, qualifies as a triggering event for the forfeiture of a first-filer's 180-day marketing exclusivity under the Hatch-Waxman Act.
  • A secondary question will be one of exceptionality: does a patent holder's conduct in maintaining an Orange Book listing for patents that have been definitively invalidated through the IPR and appeal process rise to the level of unreasonable conduct sufficient to justify an award of attorneys' fees under 35 U.S.C. § 285?