DCT

1:15-cv-00478

Shionogi & Co Ltd v. Aurobindo Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:15-cv-00478, N.D. Ill., 01/16/2015
  • Venue Allegations: Venue is based on Defendant Aurobindo Pharma Ltd. having designated an agent for service of process in the district for its drug application and both defendants allegedly transacting substantial business and deriving revenue from sales within the district.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's DORIBAX® antibacterial drug constitutes an act of infringement of a patent directed to a specific crystalline form of the active ingredient, doripenem.
  • Technical Context: The technology concerns a specific stable crystalline form (polymorph) of a carbapenem antibiotic, which is critical for the drug's formulation, stability, and shelf-life.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of a notice letter, dated December 4, 2014, informing it that Defendant had filed an ANDA with a Paragraph IV certification. The certification asserts that the patent-in-suit is invalid, unenforceable, and/or not infringed by the proposed generic product. The patent is listed in the U.S. Food and Drug Administration's "Orange Book."

Case Timeline

Date Event
2000-03-31 U.S. Patent No. 8,247,402 Priority Date
2012-08-21 U.S. Patent No. 8,247,402 Issue Date
2014-12-04 (on or before) Aurobindo submits ANDA No. 207666 to the FDA
2014-12-04 Aurobindo sends Paragraph IV notice letter to Shionogi
2015-01-16 Complaint Filing Date

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

  • Patent Identification: U.S. Patent No. 8,247,402, "Crystal Form of Pyrrolidylthiocarbapenem Derivative," issued August 21, 2012.

The Invention Explained

  • Problem Addressed: The patent's background section explains that the active compound, S-4661 (doripenem), was previously known in an amorphous solid form that "has insufficient stability in storage," which could lead to "discoloration and a reduction in purity" over time (’402 Patent, col. 1:47-51). This instability presents a significant challenge for developing the compound into a commercial pharmaceutical product, especially an injectable formulation.
  • The Patented Solution: The invention provides novel, stable crystalline forms of the doripenem compound. The patent specifically describes what it terms "type III" and "type IV" crystals, which are defined by their unique powder X-ray diffraction (PXRD) patterns (’402 Patent, Abstract; col. 4:40-54). The claimed crystal form (Type IV) is described as a monohydrate that exhibits significantly improved storage stability compared to previously known forms, thereby solving the problem of degradation and making it suitable for pharmaceutical use (’402 Patent, col. 4:6-12).
  • Technical Importance: Achieving a specific, stable crystalline polymorph is a critical step in drug development, as it ensures consistent product quality, predictable bioavailability, and commercially viable shelf-life for the final drug product (’402 Patent, col. 1:50-54).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’402 Patent (Compl. ¶22). The primary independent claim is Claim 1.
  • Independent Claim 1 recites:
    • A crystal of a monohydrate of the specific doripenem compound, (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid;
    • Wherein the crystal has a powder X-ray diffraction pattern with peaks at specific diffraction angles (2θ) of "about 13.04, 14.98, 15.88, 16.62, 20.62, 21.06, 22.18, 23.90, 26.08, 28.22 and 28.98 (degrees)"; and
    • Wherein the pattern is obtainable using specified X-ray diffraction measurement conditions.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant's proposed generic doripenem for injection product, which is the subject of Abbreviated New Drug Application (ANDA) No. 207666 (Compl. ¶¶ 1, 17).

Functionality and Market Context

  • The product is intended to be a generic equivalent of Plaintiff's DORIBAX®, an antibacterial prescription drug (Compl. ¶¶ 1, 8). The complaint alleges that Defendant's product will contain a copy of the active ingredient doripenem and will be sold with a product label that contains "substantially the same instructions for administration and use as the Doribax® product label" (Compl. ¶18). The act of infringement alleged is the filing of the ANDA seeking FDA approval to market this product before the expiration of the ’402 Patent (Compl. ¶22).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’402 Patent Infringement Allegations

| Claim Element (from Independent Claim 1) - | Alleged Infringing Functionality ... | Complaint Citation | Patent Citation |
|:-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-:---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-:-----------------------|:-------------------|
| A crystal of a monohydrate of (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid,... | Defendant's generic doripenem for injection product allegedly "will contain a copy of the active ingredient in Doribax®," which is the compound recited in the claim (doripenem). - | ¶18 | col. 1:17-30 |
| ...said crystal having a powder X-ray diffraction pattern comprising peaks at diffraction angles (2θ) of about 13.04, 14.98, 15.88, 16.62, 20.62, 21.06, 22.18, 23.90, 26.08, 28.22 and 28.98 (degrees)... | The complaint alleges that the active ingredient in Defendant's product is "covered by the '402 patent" and that the submission of the ANDA for this product constitutes infringement under 35 U.S.C. § 271(e)(2)(A). | ¶¶18, 22 | col. 4:51-54 |

  • Identified Points of Contention:
    • Technical Questions: The central factual dispute will be whether the active pharmaceutical ingredient (API) described in Defendant's ANDA is, in fact, the specific crystalline monohydrate form claimed in the ’402 Patent. What does the powder X-ray diffraction data and moisture analysis for Defendant's proposed product actually show? The complaint does not contain this information, which will be a primary focus of discovery.
    • Scope Questions: Does the term "about," which modifies each of the claimed PXRD peak values, encompass any variations present in the Defendant's crystal form? The interpretation of this term will be critical in determining the literal scope of the claim.

V. Key Claim Terms for Construction

  • The Term: "about"

    • Context and Importance: This term precedes every numerical value in the list of required PXRD peaks. The construction of "about" will define the permissible range of deviation for the accused product's crystal structure from the patent's specified values. Practitioners may focus on this term because its interpretation could be dispositive; a narrow construction would provide Defendant a clearer path to arguing non-infringement, while a broader one would favor the Plaintiff.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification explicitly contemplates measurement variability, stating that "a measurement error of about ±0.2 may occur in the value of 2θ" (’402 Patent, col. 4:60-61). Plaintiff may argue this passage defines the scope of "about."
      • Evidence for a Narrower Interpretation: Defendant may argue that the term must be construed more narrowly to preserve the validity of the claim by distinguishing it from other known crystal forms, including other polymorphs (Type I, II, and III) discussed in the patent's own specification (’402 Patent, col. 1:57-64, col. 4:44-50).

  • The Term: "A crystal of a monohydrate"

    • Context and Importance: This limitation requires the claimed substance to be both crystalline (not amorphous) and to contain one molecule of water per molecule of doripenem. Proving infringement will require showing that Defendant's product meets this specific hydration state.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party might argue the term does not require perfect stoichiometric composition throughout the bulk material, but rather that the material is substantially a monohydrate consistent with pharmaceutical standards.
      • Evidence for a Narrower Interpretation: The patent clearly distinguishes the claimed "type IV crystal" as a "monohydrate" from the "type III crystal," which is described as a "dihydrate" (’402 Patent, col. 4:47-49). This explicit distinction suggests the hydration state is a critical and deliberate limitation, supported by specific theoretical and measured moisture content values provided for each form (’402 Patent, col. 7:19-20; col. 8:12-13).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will induce infringement by providing a product label and other materials that instruct and encourage medical professionals and patients to use the generic drug in an infringing manner (Compl. ¶¶ 26, 31). It further alleges the doripenem product is not a staple article of commerce with substantial non-infringing uses and is especially adapted for infringement, which are allegations supporting contributory infringement (Compl. ¶31).
  • Willful Infringement: The complaint alleges that Defendant had actual notice of the ’402 Patent before submitting its ANDA and proceeded despite an "objectively high likelihood" of infringement (Compl. ¶23). This allegation forms the basis for a claim of willful infringement and a request for enhanced damages.

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

  • A core issue will be one of "polymorphic identity": does the specific crystalline form of doripenem in Defendant's ANDA product, as revealed through discovery, actually possess the powder X-ray diffraction pattern and monohydrate state required by Claim 1?
  • A second central issue will be the "definitional scope of 'about'": how much variance from the patent's specified PXRD peak values does the term "about" permit? The court's construction of this term will set the boundaries for the factual infringement analysis.
  • Finally, a key question for the defense will be "patent validity": as raised by the Paragraph IV certification, does the claimed crystal form represent a novel and non-obvious invention over any prior art, including other known polymorphs or crystallization techniques?