DCT

1:15-cv-00760

Janssen Pharmaceutica NV v. Mylan Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:15-cv-00760, D. Del., 01/26/2016
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Delaware based on Defendants' purposeful availment of Delaware's laws, persistent and continuous contacts with the district, substantial revenue derived from the district, and registration to do business in the state.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the HIV treatment drug "COMPLERA®" constitutes infringement of five U.S. patents covering the drug's active ingredients, combination, salt form, and manufacturing processes.
  • Technical Context: The technology relates to antiretroviral drugs for treating Human Immunodeficiency Virus (HIV), a market where effective combination therapies are critical for managing the virus and combating drug resistance.
  • Key Procedural History: The litigation was triggered by Defendants' submission of ANDA No. 208452 to the U.S. Food and Drug Administration. This submission included a "Paragraph IV certification," a formal assertion by the generic applicant that Plaintiffs' patents listed in the FDA's "Orange Book" are invalid or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2001-08-13 U.S. Patent No. 7,125,879 Priority Date
2002-08-09 U.S. Patent No. 7,399,856 Priority Date
2002-08-09 U.S. Patent No. 7,563,922 Priority Date
2004-09-03 U.S. Patent No. 8,101,629 Priority Date
2006-10-24 U.S. Patent No. 7,125,879 Issued
2008-07-15 U.S. Patent No. 7,399,856 Issued
2008-10-08 U.S. Patent No. 8,841,310 Priority Date
2009-07-21 U.S. Patent No. 7,563,922 Issued
2012-01-24 U.S. Patent No. 8,101,629 Issued
2014-09-23 U.S. Patent No. 8,841,310 Issued
2015-07-24 Mylan sends Paragraph IV Letter to Plaintiffs
2016-01-26 Complaint Filed

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

U.S. Patent No. 8,841,310 - "Combinations of a Pyrimidine Containing NNRTI with RT Inhibitors"

The Invention Explained

  • Problem Addressed: The patent describes the challenge of treating HIV infection, which often requires a combination of different antiretroviral agents to suppress the virus effectively and prevent the emergence of drug-resistant strains (’310 Patent, col. 1:15-32).
  • The Patented Solution: The invention claims a specific combination therapy product containing three active ingredients: "Compound A" (rilpivirine), emtricitabine, and tenofovir disoproxil fumarate. This combination of a non-nucleoside reverse transcriptase inhibitor (NNRTI) with other reverse transcriptase (RT) inhibitors is designed to provide a comprehensive treatment for HIV infection (’310 Patent, Abstract).
  • Technical Importance: The claimed three-drug combination provides a complete antiretroviral regimen in a single product, which may simplify treatment and improve patient adherence compared to regimens requiring multiple, separate medications.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims (Compl. ¶67). Independent claim 1 is representative:
    • A product containing (a) Compound A [4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile], or a pharmaceutically acceptable salt thereof;
    • (b) emtricitabine, or a pharmaceutically acceptable salt thereof; and
    • (c) tenofovir disoproxil fumarate, or a pharmaceutically acceptable salt thereof,
    • as a combined preparation for simultaneous, separate or sequential use in the treatment of HIV infection.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 7,125,879 - "HIV Inhibiting Pyrimidines Derivatives"

The Invention Explained

  • Problem Addressed: The patent addresses the need for new compounds to combat HIV, particularly strains that have developed resistance to existing antiretroviral drugs (’879 Patent, col. 1:40-47).
  • The Patented Solution: The invention discloses a class of pyrimidine derivative compounds that function as HIV replication inhibitors. The core chemical structure defined in the claims was found to have an improved ability to inhibit the replication of drug-resistant HIV strains (’879 Patent, col. 1:40-47, Abstract). The patent specifically identifies the compound later known as rilpivirine (’879 Patent, col. 67:47-68:10, Cmpd. 1).
  • Technical Importance: The development of these compounds provided a new chemical entity for use in HIV therapy, offering a new tool against both wild-type and mutated virus strains.

Key Claims at a Glance

  • The complaint alleges Mylan's generic product would infringe claims 1-3, 5-8, and 11-19 (Compl. ¶52, ¶74). Independent claim 18 is representative of the asserted compound claims:
    • A compound which is 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile, or a stereoisomeric form thereof.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,101,629 - "Salt of 4-[[4-[[4-(2-Cyanoethenyl)-2,6-Dimethylphenyl]amino]-2-Pyrimidinyl]Amino]Benzonitrile"

  • Technology Synopsis: This patent claims a specific salt form of the rilpivirine compound, the hydrochloride salt. The patent suggests that particular salt forms of a drug can offer advantages in properties such as stability, solubility, and bioavailability, which are critical for effective pharmaceutical formulations (’629 Patent, Abstract, col. 1:36-42).
  • Asserted Claims: One or more claims (Compl. ¶81).
  • Accused Features: The complaint alleges that Mylan's generic tablets will contain the claimed hydrochloride salt of rilpivirine (Compl. ¶81).

U.S. Patent No. 7,399,856 - "Processes for the Preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-2pyrimidinyl]amino] benzonitrile"

  • Technology Synopsis: This patent claims specific chemical processes for manufacturing the rilpivirine active pharmaceutical ingredient (API). Such process patents protect the methods used to create a compound, not the compound itself (’856 Patent, Abstract).
  • Asserted Claims: Claims 1 and 3-12 (Compl. ¶90).
  • Accused Features: The complaint alleges, under 35 U.S.C. § 271(g), that Mylan will import, sell, or use a product (its generic tablets) that is made by a process covered by the ’856 Patent claims (Compl. ¶57, ¶90).

U.S. Patent No. 7,563,922 - "Processes for the Preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-2pyrimidinyl]amino] benzonitrile"

  • Technology Synopsis: This patent claims processes for preparing 3-(4-Amino-3,5-dimethylphenyl)acrylonitrile, which the complaint identifies as an essential component used in the synthesis of the rilpivirine API (’922 Patent, Abstract; Compl. ¶44).
  • Asserted Claims: Claims 1-6 (Compl. ¶100).
  • Accused Features: The complaint alleges infringement under 35 U.S.C. § 271(g), stating that Mylan uses the patented process to prepare a key intermediate for its rilpivirine API, and that this intermediate is incorporated into the final imported product (Compl. ¶58, ¶59, ¶100).

III. The Accused Instrumentality

  • Product Identification: The accused products are Mylan's generic tablets intended as copies of Plaintiffs' "COMPLERA®" tablets (Compl. ¶1, ¶45).
  • Functionality and Market Context: The accused generic tablets are a fixed-dose combination drug product containing three active pharmaceutical ingredients: emtricitabine, rilpivirine, and tenofovir disoproxil fumarate (Compl. ¶1). This product is designed for the treatment of HIV infection. The complaint characterizes the branded version, "COMPLERA®", as "highly successful," suggesting significant commercial importance in the antiretroviral market (Compl. ¶1). Mylan seeks FDA approval to manufacture and sell these generic tablets in the U.S. prior to the expiration of the patents-in-suit (Compl. ¶1, ¶45). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’310 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A product containing (a) Compound A ... or a pharmaceutically acceptable salt thereof Mylan's proposed generic product is a tablet containing rilpivirine, one of the active ingredients in COMPLERA®. ¶1, ¶43 col. 2:1-12
(b) emtricitabine, or a pharmaceutically acceptable salt thereof Mylan's proposed generic product is a tablet containing emtricitabine, one of the active ingredients in COMPLERA®. ¶1 col. 2:1-12
and (c) tenofovir disoproxil fumarate, or a pharmaceutically acceptable salt thereof Mylan's proposed generic product is a tablet containing tenofovir disoproxil fumarate, one of the active ingredients in COMPLERA®. ¶1 col. 2:1-12
as a combined preparation for simultaneous ... use in the treatment of HIV infection Mylan's proposed product is a fixed-dose combination tablet intended for the treatment of HIV. ¶1, ¶45 col. 2:13-16

’879 Patent Infringement Allegations

Claim Element (from Independent Claim 18) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound which is 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile Mylan's proposed generic product contains rilpivirine, which is the specific chemical compound recited in the claim. ¶1, ¶43 col. 67:47-68:10
or a stereoisomeric form thereof. The complaint alleges that Mylan’s generic product contains the claimed compound. ¶52, ¶74 col. 7:6-10

Identified Points of Contention

  • Scope Questions: The primary dispute articulated in the complaint is not infringement but validity, as Mylan's Paragraph IV letter certified that the product patents ('310, '879, '629) are invalid (Compl. ¶51). The complaint alleges Mylan did not dispute that its generic tablets would infringe the asserted claims (Compl. ¶52, ¶68, ¶82). However, future disputes may raise questions about whether the specific salt form or stereoisomer used by Mylan falls within the scope of the claims as construed by the court.
  • Technical Questions: For the process patents (’856 and ’922), a central evidentiary question will be whether Plaintiffs can prove that the specific manufacturing process used by Mylan for its rilpivirine API, or a key intermediate, is the same as, or equivalent to, the processes claimed in those patents (Compl. ¶57, ¶58).

V. Key Claim Terms for Construction

  • The Term: "pharmaceutically acceptable salt thereof" (from '310 Patent, Claim 1)

  • Context and Importance: This term is critical because pharmaceutical compounds are often formulated as salts to improve properties like stability and solubility. Practitioners may focus on this term because Mylan could argue that its chosen salt form, if different from the one used in the branded product or described in the patent, is not "pharmaceutically acceptable" in the context of the invention or is otherwise outside the claim's scope.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides a non-exhaustive list of suitable inorganic and organic acids that can form such salts, including hydrochloric, sulfuric, acetic, and malic acids, suggesting the term covers a wide range of possibilities (’310 Patent, col. 4:32-47).
    • Evidence for a Narrower Interpretation: The specification later describes the active ingredients "in their free base form or as a pharmaceutically acceptable salt thereof, in particular, as a pharmaceutically acceptable acid addition salt," which might be used to argue that only acid addition salts are contemplated (’310 Patent, col. 5:2-5).

  • The Term: "stereoisomeric form thereof" (from '879 Patent, Claim 18)

  • Context and Importance: The cyanoethenyl group in rilpivirine can exist as an E- or Z-isomer. The definition of "stereoisomeric form" will determine whether the claim covers only the preferred E-isomer, the Z-isomer, or mixtures thereof. This is critical as the infringement and validity analyses could depend on which specific isomer(s) Mylan's product contains and which are enabled and described by the patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent defines "stereochemically isomeric forms" broadly to include "all possible stereoisomeric forms," encompassing mixtures of diastereomers and enantiomers as well as individual isomers "substantially free ... of the other isomers" (’879 Patent, col. 7:51-64).
    • Evidence for a Narrower Interpretation: The detailed examples exclusively synthesize and characterize the E-isomer of the final compound (e.g., Compound 1, Example B1), which a defendant might argue limits the effective scope of the claim to what was actually made and described, despite the broader definitional language (’879 Patent, col. 67:47-68:10).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Mylan's commercial manufacture, use, sale, and offer for sale of its generic tablets would contribute to and/or induce the infringement of the patents-in-suit (Compl. ¶67, ¶74, ¶81, ¶90, ¶100). The basis for this allegation appears to be that Mylan's actions would enable and encourage direct infringement by end-users and healthcare providers.
  • Willful Infringement: Willfulness is specifically alleged for infringement of the '856 and '922 process patents (Compl. ¶92, ¶102). The complaint asserts this is based on Mylan's alleged actual and constructive notice of these patents prior to its filing of ANDA No. 208452 (Compl. ¶91, ¶101).

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

  • A core issue will be one of validity: Mylan's Paragraph IV certification explicitly challenges the validity of the product patents ('310, '879, '629). The case will likely turn on whether Mylan can present clear and convincing evidence that the asserted claims are invalid, potentially based on prior art that renders them anticipated or obvious.
  • A key evidentiary question will be one of process infringement: For the '856 and '922 patents, the dispute will center on evidence governed by 35 U.S.C. § 271(g). The central question is whether Plaintiffs can demonstrate that Mylan’s actual, and likely confidential, manufacturing process for its rilpivirine API falls within the scope of the claimed processes.
  • A potential secondary issue will be one of definitional scope: Should the validity challenges fail, the litigation may focus on claim construction, particularly whether the terms "pharmaceutically acceptable salt" and "stereoisomeric form" are broad enough to cover the specific chemical composition of Mylan's proposed generic product.