DCT

1:18-cv-01465

Bayer Healthcare LLC v. Apotex Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01465, D. Del., 09/21/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Apotex Corp. is a Delaware corporation, and Defendant Apotex Inc. is alleged to have purposefully availed itself of the district and consented to jurisdiction in prior litigation.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug STIVARGA® constitutes an act of infringement of a patent claiming a specific crystalline monohydrate form of the active ingredient, regorafenib.
  • Technical Context: The technology concerns a specific solid-state form (polymorph) of a pharmaceutical compound, which can have significant implications for a drug’s stability, manufacturability, and clinical performance.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following a notice letter, dated August 10, 2018, in which Apotex notified Bayer of its ANDA filing and its certification that the patent-in-suit is invalid, unenforceable, or will not be infringed by Apotex’s proposed generic product (a "Paragraph IV certification").

Case Timeline

Date Event
2006-10-11 ’232 Patent Priority Date
2018-05-01 ’232 Patent Issue Date
2018-08-10 Apotex sends Paragraph IV Notice Letter
2018-09-21 Complaint Filing Date

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

U.S. Patent No. 9,957,232 - "4-[4-({[4-Chloro-3-(Trifluoromethyl)Phenyl]Carbamoyl}Amino)-3-Fluorophenoxy]-N-Methylpyridine-2-Carboxamide Monohydrate"

The Invention Explained

  • Problem Addressed: The patent addresses the need for new solid-state forms of the known anti-cancer compound regorafenib. Different crystalline forms of a drug can possess different physical properties, and the patent background implies that the previously known form, "polymorph I," could be improved upon for pharmaceutical use (Compl. ¶27; ’971 Patent, col. 1:31-38).
  • The Patented Solution: The invention is a specific crystalline monohydrate form of regorafenib, designated as the compound of formula (II), which incorporates one molecule of water into its crystal structure (’971 Patent, col. 1:40-52). This monohydrate form is described as having a "high stability in the manufacture of pharmaceutical compositions" and is distinguished from the prior art polymorph I by a unique set of physical characteristics, including a distinct X-ray powder diffraction (XRPD) pattern (’971 Patent, col. 1:55-63, Fig. 2).
  • Technical Importance: Identifying and characterizing a stable crystalline form of an active pharmaceutical ingredient is critical for ensuring lot-to-lot consistency, predictable dissolution, and reliable shelf-life for a commercial drug product (’971 Patent, col. 1:63-65).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 19 (’971 Patent, Compl. ¶42).
  • The essential elements of independent claim 19 are:
    • The compound of the formula (II) [regorafenib monohydrate]
    • which shows in the X-ray diffractometry a peak maximum of the 2 Theta angle of 21.2
  • The complaint does not explicitly reserve the right to assert dependent claims but alleges infringement of "one or more claims."

III. The Accused Instrumentality

Product Identification

Apotex’s proposed generic "Regorafenib oral tablets, 40 mg," as described in Abbreviated New Drug Application (ANDA) No. 209765 (the "Apotex ANDA Product") (Compl. ¶2).

Functionality and Market Context

  • The Apotex ANDA Product is a generic version of Bayer’s branded kinase inhibitor, STIVARGA®, and contains the active ingredient regorafenib (Compl. ¶2, ¶34). It is indicated for the treatment of certain types of cancer, including colorectal cancer (Compl. ¶1, ¶23).
  • The complaint alleges on information and belief that the Apotex ANDA Product "contains regorafenib monohydrate as claimed in the '232 patent" (Compl. ¶41).
  • The product is a generic drug intended to enter the market and compete with STIVARGA® upon receiving FDA approval (Compl. ¶1, ¶9).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

Claim Chart Summary

Claim Element (from Independent Claim 19) Alleged Infringing Functionality Complaint Citation Patent Citation
The compound of the formula (II) The complaint alleges that Apotex's ANDA Product contains regorafenib (¶34). On information and belief, it is alleged to contain the specific "regorafenib monohydrate as claimed in the '232 patent" (¶41). ¶34, ¶41 col. 1:40-52
which shows in the X-ray diffractometry a peak maximum of the 2 Theta angle of 21.2. The complaint alleges that the claims of the '232 patent cover regorafenib monohydrate that exhibits this specific X-ray diffraction peak (¶27). It further alleges that Apotex's ANDA Product will infringe one or more claims of the patent, including at least claim 19 (¶42). ¶27, ¶42 col. 21:14-17

Identified Points of Contention

  • Technical Question: The primary factual dispute will concern the physical properties of the drug substance specified in Apotex's confidential ANDA. What evidence does the ANDA contain to demonstrate that Apotex's regorafenib product is, or is not, the specific monohydrate crystalline form defined by the characteristic XRPD peak at a 2 Theta angle of 21.2?
  • Scope Questions: The case raises the question of how to interpret the numerical limitation "21.2." Does this term require the peak to be centered at exactly 21.2 degrees 2-Theta, or does it encompass a range of values reflecting normal experimental variation in XRPD analysis?

V. Key Claim Terms for Construction

The Term

"a peak maximum of the 2 Theta angle of 21.2"

Context and Importance

This term is the "fingerprint" that distinguishes the claimed monohydrate from other potential solid-state forms. The infringement analysis for claim 19 will turn entirely on whether Apotex's product, as defined in its ANDA, possesses this specific, measurable physical property. Practitioners may focus on this term because its construction—whether it is read as an exact value or allows for some variance—could be dispositive of infringement.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification describes multiple laboratory-scale methods for preparing the monohydrate, for example by using different solvent systems such as acetone/water or ethanol (’232 Patent, col. 14:1-29). A party could argue that such variations in preparation could lead to minor, instrument-dependent shifts in peak position, suggesting the term should not be construed with absolute mathematical rigidity.
  • Evidence for a Narrower Interpretation: The patent claims and specification consistently use the precise value "21.2" without any qualifying language such as "about" or "approximately" (’232 Patent, col. 21:14-17). Table 2, which lists the characteristic peaks, presents "21.2" as a distinct value to differentiate the monohydrate from the prior art "polymorph I," suggesting the patentee intended to define the invention by this precise measurement.

VI. Other Allegations

Indirect Infringement

The complaint alleges that Apotex "plans and intends to, and will, actively induce infringement" upon ANDA approval (Compl. ¶44). This allegation is based on the future sale of the product with proposed labeling that would direct medical professionals and patients to use the product in an infringing manner (Compl. ¶54).

Willful Infringement

While the complaint does not use the term "willful," it alleges that "Apotex had knowledge of the claims of the '232 patent before it filed its Paragraph IV Certification" (Compl. ¶31, ¶43). This allegation of pre-suit knowledge provides a potential factual basis for a later claim of willful infringement or a request for enhanced damages.

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

  • A core issue will be one of evidentiary proof: What do the confidential specifications within Apotex’s ANDA reveal about the crystalline form of its regorafenib drug substance? The case will likely depend on a technical comparison of the physical characterization data for Apotex’s product against the requirements of the patent’s claims.
  • A key legal question will be one of definitional precision: Will the court construe the claim term "a peak maximum of the 2 Theta angle of 21.2" to require an exact match, or will it be interpreted to include a margin of error inherent in crystallographic measurements? The outcome of this claim construction battle could determine the scope of the patent and the viability of the infringement case.