DCT
2:21-cv-12998
Takeda Pharma America Inc v. Apotex Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Takeda Pharmaceuticals America, Inc., Takeda Pharmaceuticals U.S.A., Inc., and ARIAD Pharmaceuticals, Inc. (Delaware)
- Defendant: Apotex, Inc. (Canada)
- Plaintiff’s Counsel: Quinn Emanuel Urquhart & Sullivan, LLP; Gibbons P.C.
- Case Identification: 2:21-cv-12998, D.N.J., 06/25/2021
- Venue Allegations: Venue is alleged to be proper because Defendant Apotex, Inc. is a Canadian corporation and may therefore be sued in any judicial district.
- Core Dispute: In this Hatch-Waxman action, Plaintiffs allege that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug ICLUSIG® constitutes an act of infringement of a patent covering a specific crystalline form of the active ingredient, ponatinib hydrochloride.
- Technical Context: The case centers on pharmaceutical polymorphs—different crystalline structures of the same chemical compound—which can have distinct physical properties affecting a drug's stability, manufacturability, and bioavailability.
- Key Procedural History: The litigation was initiated in response to a notice letter from Apotex, dated May 14, 2021, which included a Paragraph IV certification stating that U.S. Patent No. 9,493,470 is invalid and/or will not be infringed by Apotex's proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2012-12-13 | '470 Patent Priority Date |
| 2016-11-15 | '470 Patent Issue Date |
| 2021-05-14 | Apotex Letter notifying of ANDA submission |
| 2021-06-25 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,493,470 - "Crystalline forms of 3-(imidazo[1,2-B]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt"
The Invention Explained
- Problem Addressed: The patent addresses the challenge that an active pharmaceutical ingredient (API), such as ponatinib hydrochloride, can exist in various physical forms, including amorphous and different crystalline structures (polymorphs). These forms may have different physical properties, and for pharmaceutical development, it is critical to identify a specific, stable polymorph to ensure consistent performance, quality, and manufacturability of the final drug product (’470 Patent, col. 3:5-21).
- The Patented Solution: The invention is the discovery and characterization of several novel crystalline forms of ponatinib hydrochloride (’470 Patent, col. 3:52-55). The patent specifically identifies and defines these forms, including the anhydrate "Form A," by their unique physical characteristics, such as their X-ray powder diffraction (XRPD) patterns, which serve as a structural fingerprint (’470 Patent, col. 13:50-58; Fig. 4).
- Technical Importance: Identifying a stable, well-characterized crystalline form of an API is a critical step in drug development, as it allows for the creation of a reliable and consistent pharmaceutical composition suitable for administration to patients (’470 Patent, col. 3:12-21).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 8 (Compl. ¶33, ¶36).
- Independent Claim 1 (Composition Claim):
- Crystalline Form A of ponatinib hydrochloride
- characterized by an x-ray powder diffraction pattern comprising at least five 2θ values (±0.3) chosen from the list: 5.9, 7.1, 10.0, 12.5, 16.4, 19.3, 21.8, 23.8, and 26.1.
- Independent Claim 8 (Method Claim):
- A method for treating chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia in a subject in need thereof
- comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition
- which comprises Crystalline Form A ponatinib hydrochloride according to claim 1.
- The complaint alleges infringement of claims 1-17, thereby reserving the right to assert dependent claims (Compl. ¶32).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is the "Apotex ANDA Product," for which Apotex submitted ANDA No. 215893 to the FDA (Compl. ¶1). This product is intended to be a generic version of Plaintiffs' ICLUSIG® (ponatinib hydrochloride) 15 mg and 45 mg tablets (Compl. ¶1, ¶27).
Functionality and Market Context
The Apotex ANDA Product is a pharmaceutical composition designed for the treatment of adult patients with specific forms of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia (Compl. ¶7, ¶10-12). The central technical allegation is that this generic product will contain the specific "crystalline Form A of ponatinib hydrochloride" covered by the ’470 Patent (Compl. ¶34). The product is intended to compete directly with ICLUSIG® in the U.S. market upon receiving FDA approval (Compl. ¶26-27).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
Claim Chart Summary
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Crystalline Form A of ponatinib hydrochloride | The Apotex ANDA Product is alleged to contain "crystalline Form A of ponatinib hydrochloride." | ¶34 | col. 13:50-52 |
| characterized by an x-ray powder diffraction pattern comprising at least five 2θ values (±0.3) chosen from 5.9, 7.1, 10.0, 12.5, 16.4, 19.3, 21.8, 23.8, and 26.1. | The crystalline Form A in the Apotex ANDA Product is alleged to be characterized by an XRPD pattern comprising at least five of the specified 2θ values. | ¶35 | col. 13:52-58 |
Identified Points of Contention
- Scope Questions: A potential dispute may arise over the definition of "Crystalline Form A." Does the claim term require a substance to match the full analytical "fingerprint" of Form A as detailed in the patent's specification (e.g., Fig. 4), or is it sufficient for a substance to simply exhibit "at least five" of the enumerated XRPD peaks?
- Technical Questions: The primary technical question is one of fact: does the ponatinib hydrochloride API in Apotex's ANDA product actually possess the structural characteristics of "Crystalline Form A"? The complaint makes this allegation on "information and belief" (Compl. ¶34-35), raising the question of what evidence from Apotex's ANDA filing or subsequent discovery will show regarding the product's actual crystalline structure.
V. Key Claim Terms for Construction
- The Term: "Crystalline Form A of ponatinib hydrochloride"
- Context and Importance: This term is the subject of the asserted composition claim and the core of the patented invention. The entire infringement analysis for claim 1, and by extension the method claims that depend on it, will turn on whether the substance in Apotex's product falls within the scope of this term. Practitioners may focus on this term because its definition dictates whether a purely factual comparison of analytical data is sufficient or if a more nuanced interpretation based on the specification is required.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The plain language of claim 1 defines the form by "comprising at least five 2θ values (±0.3) chosen from" a list of nine peaks (’470 Patent, col. 75:62-65). This open-ended "comprising" language and "at least five" phrasing could support an interpretation that any crystalline form meeting this minimum criterion infringes, regardless of other properties.
- Evidence for a Narrower Interpretation: The specification provides an extensive and specific characterization of what the inventors identified as "Form A," including a representative XRPD pattern (Fig. 4), differential scanning calorimetry (DSC) data (Fig. 5), and thermogravimetric analysis (TGA) data (Fig. 6) (’470 Patent, col. 13:50-15:28). Apotex may argue that "Crystalline Form A" is a term of art defined by this complete set of characteristics, and that merely matching a subset of XRPD peaks is insufficient to meet the claim limitation.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Apotex will induce infringement by "intentionally encourag[ing] acts of direct infringement," presumably by marketing the generic product with a label that instructs physicians and patients to use it in a manner that directly infringes the patented method claims (Compl. ¶39). It also alleges contributory infringement, asserting that the Apotex product is "especially adapted for a use that infringes" and has "no substantial non-infringing use" (Compl. ¶40).
- Willful Infringement: The complaint alleges that Apotex has had "knowledge of the ’470 patent since at least the date it submitted the Apotex ANDA" (Compl. ¶41). This allegation of pre-suit knowledge, combined with the assertion that the case is "exceptional" (Compl. ¶43), forms the basis for a potential claim of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of structural identity: will discovery and expert analysis demonstrate, as a matter of scientific fact, that the crystalline form of ponatinib hydrochloride in Apotex's proposed generic product exhibits the specific X-ray powder diffraction pattern that defines "Crystalline Form A" as claimed in the '470 patent?
- A key legal and factual question will be one of claim scope: will the court construe "Crystalline Form A" as being defined solely by the presence of "at least five" of the listed XRPD peaks, or will it require a closer match to the more detailed polymorph "fingerprint" described throughout the patent's specification?
- A central question for the method claims will be one of inducement: assuming the composition is found to infringe, does the proposed product label for the Apotex ANDA Product provide sufficient evidence that Apotex will actively encourage or instruct medical professionals and patients to administer the drug in a manner that directly infringes the patented methods of treatment?