DCT

1:23-cv-00161

Shionogi & Co Ltd v. Norwich Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00161, D. Del., 02/13/2023
  • Venue Allegations: Venue is asserted on the basis that both Defendants are corporations organized and existing under the laws of Delaware.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market generic versions of the influenza drug XOFLUZA® constitutes an act of infringement against eight U.S. patents covering the active compound baloxavir, its prodrug baloxavir marboxil, pharmaceutical compositions, and manufacturing processes.
  • Technical Context: The technology relates to antiviral compounds, specifically cap-dependent endonuclease inhibitors, designed to treat and prevent influenza by disrupting a key enzyme essential for viral proliferation.
  • Key Procedural History: The action arises from Defendants' submission of ANDA No. 217449 with a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by the proposed generic products. Plaintiffs initiated this lawsuit within the 45-day period following receipt of Defendants' December 29, 2022 notice letter, triggering a potential 30-month stay of FDA approval for the ANDA.

Case Timeline

Date Event
2009-06-15 Earliest Priority Date for ’710 and ’835 Patents
2010-09-30 Earliest Priority Date for ’441 Patent
2015-01-06 ’710 Patent Issued
2015-03-24 ’441 Patent Issued
2015-04-28 Earliest Priority Date for ’406 and ’397 Patents
2016-06-20 Earliest Priority Date for ’198 Patent
2016-08-10 Earliest Priority Date for ’814 and ’106 Patents
2017-11-14 ’835 Patent Issued
2019-08-27 ’406 Patent Issued
2020-04-28 ’397 Patent Issued
2020-09-01 ’814 Patent Issued
2022-03-01 ’198 Patent Issued
2022-04-19 ’106 Patent Issued
2022-12-29 Date of Defendants' ANDA Notice Letter
2023-02-13 Complaint Filing Date

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

U.S. Patent No. 8,927,710 - "Substituted Polycyclic Carbamoylpyridone Derivative"

Issued January 6, 2015 (’710 Patent)

The Invention Explained

  • Problem Addressed: The patent background describes a need for new anti-influenza drugs with novel mechanisms of action, prompted by the emergence of viral strains resistant to existing treatments and the side effects associated with them (’710 Patent, col. 1:24-32).
  • The Patented Solution: The invention provides a class of polycyclic carbamoylpyridone compounds that inhibit cap-dependent endonuclease, an enzyme specific to the influenza virus and essential for its proliferation (’710 Patent, col. 1:33-49). By targeting this enzyme, the compounds are intended to block the synthesis of viral proteins and thereby inhibit viral growth (’710 Patent, col. 1:45-56). The patent specification discloses a core chemical structure and various substituent groups that confer this inhibitory activity (’710 Patent, Abstract).
  • Technical Importance: This approach provided a new target for antiviral therapy distinct from the mechanisms of then-existing drugs like neuraminidase inhibitors (e.g., Tamiflu), offering a potential new tool against resistant influenza strains (’710 Patent, col. 1:15-32).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’710 Patent (Compl. ¶52). Independent claim 1 is representative.
  • Claim 1 recites:
    • A compound represented by a specific chemical formula (II), or a pharmaceutically acceptable salt or solvate thereof.
    • The formula defines a complex, multi-ring heterocyclic core structure.
    • The formula includes various substituent groups (e.g., R1a, R1b, R2c, R3a) whose definitions and positions are specified within the claim.

U.S. Patent No. 8,987,441 - "Substituted Polycyclic Carbamoyl Pyridone Derivative Prodrug"

Issued March 24, 2015 (’441 Patent)

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of delivering therapeutically effective amounts of the active antiviral compounds, a common issue in pharmaceutical development where an active ingredient may have suboptimal properties for in vivo administration, such as poor absorption (’441 Patent, col. 1:60-65).
  • The Patented Solution: The invention discloses prodrugs of the active antiviral compounds described in related patents. A prodrug is an inactive or less active precursor that, after administration, is converted in the body into the active drug (’441 Patent, col. 19:60-65). The patented solution involves modifying a hydroxyl group on the parent compound with a promoiety (designated Pd in the claims) designed to improve pharmacokinetic properties before being cleaved in vivo to release the active compound (’441 Patent, Abstract; col. 2:1-12).
  • Technical Importance: The development of a prodrug form was a critical step for the commercial viability of baloxavir, as it allowed for effective oral administration and bioavailability of the active compound (’441 Patent, col. 20:1-10).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’441 Patent (Compl. ¶62). Independent claim 1 is representative.
  • Claim 1 recites:
    • A compound represented by a specific chemical formula (I), or a pharmaceutically acceptable salt or solvate thereof.
    • The formula features a core structure similar to that in the ’710 patent but includes a promoiety Pd attached to an oxygen atom, designating it as a prodrug.
    • The claim defines Pd as being selected from a list of chemical groups suitable for forming a prodrug.

U.S. Patent No. 9,815,835 - "Substituted Polycyclic Carbamolypyridone Derivative"

Issued November 14, 2017 (’835 Patent)

  • Technology Synopsis: This patent, related to the ’710 Patent, claims a specific genus of polycyclic carbamoylpyridone compounds with antiviral activity against influenza via inhibition of cap-dependent endonuclease. It covers the active compound baloxavir (’835 Patent, Abstract; col. 1:33-49).
  • Asserted Claims: One or more claims, with Claim 1 being an independent claim defining a compound by a specific chemical formula (Compl. ¶70).
  • Accused Features: The presence of baloxavir in the Proposed ANDA Products after in vivo conversion from baloxavir marboxil (Compl. ¶70).

U.S. Patent No. 10,392,406 - "Substituted Polycyclic Pyridone Derivatives and Prodrugs Thereof"

Issued August 27, 2019 (’406 Patent)

  • Technology Synopsis: This patent claims compounds with anti-viral activity, including specific polycyclic pyridone derivatives (parent compounds) and their prodrugs, which are designed to be efficiently absorbed and exhibit high pharmacological effect after administration (’406 Patent, col. 4:35-44).
  • Asserted Claims: One or more claims, with Claim 1 being an independent claim defining a compound by a specific chemical formula covering both active compounds and prodrugs (Compl. ¶80).
  • Accused Features: The presence of baloxavir marboxil in the Proposed ANDA Products (Compl. ¶80).

U.S. Patent No. 10,633,397 - "Substituted Polycyclic Pyridone Derivatives and Prodrugs Thereof"

Issued April 28, 2020 (’397 Patent)

  • Technology Synopsis: This patent, related to the ’406 Patent, also claims substituted polycyclic pyridone derivatives and their prodrugs that possess anti-influenza activity by inhibiting cap-dependent endonuclease (’397 Patent, col. 4:35-44).
  • Asserted Claims: One or more claims, with Claim 1 being an independent claim defining a class of compounds by chemical formula (Compl. ¶88).
  • Accused Features: The presence of baloxavir marboxil in the Proposed ANDA Products (Compl. ¶88).

U.S. Patent No. 10,759,814 - "Pharmaceutical Compositions Containing Substituted Polycyclic Pyridone Derivatives and Prodrug Thereof"

Issued September 1, 2020 (’814 Patent)

  • Technology Synopsis: This patent claims pharmaceutical compositions comprising the antiviral compounds (including prodrugs like baloxavir marboxil) along with a pharmaceutically acceptable salt or carrier. The invention is directed to the final drug formulation rather than only the active ingredient (’814 Patent, Abstract).
  • Asserted Claims: One or more claims, with Claim 1 being an independent claim to a pharmaceutical composition comprising a compound of a specified formula (Compl. ¶96).
  • Accused Features: The formulated generic tablets, which are pharmaceutical compositions containing baloxavir marboxil (Compl. ¶96).

U.S. Patent No. 11,261,198 - "Process for Preparing Substituted Polycyclic Pyridone Derivative and Crystal Thereof"

Issued March 1, 2022 (’198 Patent)

  • Technology Synopsis: This patent claims a specific process for preparing the antiviral compounds and claims a specific crystal form of the resulting compound. Such claims are directed at the method of manufacture and the specific solid-state structure of the drug substance (’198 Patent, Abstract).
  • Asserted Claims: One or more claims, with independent claims directed to processes of manufacturing and crystal forms (Compl. ¶104).
  • Accused Features: The process by which the Proposed ANDA Products are manufactured and the resulting crystal form of the active ingredient (Compl. ¶¶45, 104).

U.S. Patent No. 11,306,106 - "Pharmaceutical Compositions Containing Substituted Polycyclic Pyridone Derivatives and Prodrug Thereof"

Issued April 19, 2022 (’106 Patent)

  • Technology Synopsis: This patent, related to the ’814 Patent, also claims pharmaceutical compositions containing the polycyclic pyridone derivatives and their prodrugs. It protects the formulated drug product comprising the active ingredient and other excipients (’106 Patent, Abstract).
  • Asserted Claims: One or more claims, with Claim 1 being an independent claim to a pharmaceutical composition (Compl. ¶113).
  • Accused Features: The proposed generic tablets as complete pharmaceutical compositions (Compl. ¶113).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the "Proposed ANDA Products," which are generic versions of 40 mg and 80 mg XOFLUZA® (baloxavir marboxil) tablets for oral use, for which Defendants seek FDA approval via ANDA No. 217449 (Compl. ¶1).

Functionality and Market Context

  • The Proposed ANDA Products contain baloxavir marboxil, a prodrug of the active antiviral compound baloxavir (Compl. ¶¶41, 42). The complaint alleges that upon oral administration to a patient, the baloxavir marboxil in the tablets will be converted into baloxavir, the active form that inhibits the influenza virus (Compl. ¶46). The ANDA filing asserts that the proposed generic products are bioequivalent to Plaintiffs' XOFLUZA® tablets (Compl. ¶47). The filing of the ANDA itself is the statutory act of infringement under 35 U.S.C. § 271(e)(2) for the purpose of obtaining regulatory approval prior to patent expiration (Compl. ¶53).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not provide a claim chart or detailed element-by-element infringement allegations. Instead, it presents a narrative theory of infringement based on the Defendants' submission of ANDA No. 217449.

  • Infringement Theory for the ’710 Patent and other active compound patents (e.g., ’835): The complaint alleges that infringement will occur upon patient use of the Proposed ANDA Products. It states that the baloxavir marboxil contained in the generic tablets is converted in vivo into baloxavir, the active compound claimed in the ’710 Patent (Compl. ¶¶ 46, 52). The complaint further notes that in their Notice Letter, Defendants do not dispute that this conversion will occur and will result in a compound that infringes one or more claims of the ’710 Patent (Compl. ¶59).

  • Infringement Theory for the ’441 Patent and other prodrug/composition patents (e.g., ’406, ’397, ’814, ’106): The complaint alleges that the Proposed ANDA Products directly infringe because they will contain baloxavir marboxil, the specific prodrug claimed in the ’441 Patent, in a formulated tablet as claimed in the composition patents (Compl. ¶¶ 62, 80, 88, 96, 113). The act of seeking approval to commercially manufacture, use, and sell these products before patent expiration constitutes infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶63). The complaint repeatedly states that Defendants do not dispute that their proposed products infringe claims of these patents (Compl. ¶¶ 67, 85, 93, 101, 118).

  • Identified Points of Contention:

    • Validity Questions: The complaint states that Defendants' Paragraph IV certification asserts the patents-in-suit are invalid and/or unenforceable (Compl. ¶39). As the complaint alleges that infringement itself is not disputed for many patents, the central legal battle may focus on the validity of the asserted claims, a common feature of ANDA litigation.
    • Infringement Scope Questions: While the complaint alleges non-dispute of infringement, discovery may reveal characteristics of the Proposed ANDA Products (e.g., specific crystalline forms, impurity profiles, or manufacturing processes) that Defendants will argue fall outside the scope of certain claims, particularly for process- and crystal-form-focused patents like the ’198 Patent.

V. Key Claim Terms for Construction

  • For the ’710 Patent (active compound):

    • The Term: The compound of formula (II) as defined in Claim 1.
    • Context and Importance: The precise structural definition of the claimed compound is the foundation of the patent. Any non-infringement argument would have to contend that baloxavir, as formed in vivo, does not meet a limitation of this structural definition. Practitioners may focus on the scope of the substituent groups (e.g., R1a, R1b) to determine if any variation could exist that falls outside the claim language.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: Claim 1 defines several substituent groups with language such as "lower alkyl optionally substituted by substituent group A," which itself includes a list of possible substituents, suggesting a range of possible structures fall within the claim's scope (’710 Patent, col. 23:55-67).
      • Evidence for a Narrower Interpretation: The specification provides numerous specific examples ("Example 1," "Example 2," etc.) of synthesized compounds (’710 Patent, col. 147:1-onward). A defendant may argue that the claims should be limited to structures more closely resembling these specific embodiments.

  • For the ’441 Patent (prodrug):

    • The Term: "a group to form a prodrug" (as embodied by the Pd moiety in Claim 1).
    • Context and Importance: This term is critical because it defines the feature that distinguishes the claimed invention from the underlying active compound. The central infringement question for this patent is whether the baloxavir marboxil in the generic product is a prodrug as defined by this claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: Claim 1 provides a list of over 20 different chemical structures that can serve as the Pd promoiety, indicating that the term is intended to cover a wide variety of chemical groups that can be attached to create a prodrug (’441 Patent, col. 28:1-col. 29:67).
      • Evidence for a Narrower Interpretation: The detailed description explains that the purpose of the prodrug is to be "converted into a compound (I) (parent compound) having an inhibitory activity on cap-dependent endonuclease in vivo after administration" (’441 Patent, col. 20:1-5). A defendant could potentially argue that if their specific formulation or moiety did not function in precisely this way, it would not meet the functional definition of a prodrug as described.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that if the Proposed ANDA Products are approved, Defendants will actively induce infringement by others under 35 U.S.C. § 271(b) (Compl. ¶¶ 55, 65). The basis for this allegation is that the proposed product labels will instruct healthcare providers and patients to administer the tablets, which will lead to the in vivo formation of the claimed active compound (baloxavir), thereby causing direct infringement (Compl. ¶¶ 48, 54).
  • Willful Infringement: While the complaint does not use the word "willful," it lays the groundwork for such a claim by alleging that Defendants had knowledge of the patents-in-suit when they submitted their ANDA and Paragraph IV certification (Compl. ¶¶ 40, 56, 66, 74, 84, 92, 100, 108, 117). The prayer for relief requests a declaration that the case is "exceptional within the meaning of 35 U.S.C. § 285," which can be a basis for awarding attorneys' fees, often in cases of willful or egregious conduct (Compl. p. 22).

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

  • A central issue will be one of patent validity: Given that the complaint alleges infringement is largely undisputed, the case will likely turn on whether Defendants can prove by clear and convincing evidence that the asserted claims of the eight patents are invalid, potentially on grounds of obviousness over prior antiviral research or lack of adequate written description for the claimed chemical space.
  • A secondary issue may be one of infringement scope for specific claims: While infringement of core compound claims appears straightforward, a key evidentiary question will be whether the specific crystalline form of baloxavir marboxil in Defendants' product, or the precise process used to manufacture it, falls within the scope of the narrower claims of patents like the ’198 Patent.
  • A final question will be one of remedy and timing: Should the patents be found valid and infringed, the court will need to determine the effective date of any FDA approval for ANDA No. 217449, which Plaintiffs request be no earlier than the expiration of all asserted patents and any applicable extensions (Compl. p. 21).