DCT

2:19-cv-14737

AstraZeneca LP v. HEC Pharm Co Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:19-cv-14737, D.N.J., 07/03/2019
  • Venue Allegations: Venue is alleged to be proper for HEC Pharm Co., Ltd. as it is a foreign corporation and for HEC Pharm USA as it is incorporated in New Jersey.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the drug Brilinta® (ticagrelor) constitutes an act of infringement of patents covering the ticagrelor compound and a specific crystalline form of it.
  • Technical Context: The technology concerns small-molecule pharmaceutical compounds used as P2T receptor antagonists to prevent platelet aggregation and treat cardiovascular diseases.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's May 2019 Notice Letter, which contained a Paragraph IV certification against the asserted patents. A prior lawsuit between the parties concerning ticagrelor was filed in 2015 and subsequently dismissed without prejudice in 2016.

Case Timeline

Date Event
1998-12-04 Priority Date for U.S. Patent No. RE46,276
2000-06-02 Priority Date for U.S. Patent No. 7,265,124
2003-02-25 Issue Date for original U.S. Patent No. 6,525,060
2007-09-04 Issue Date for U.S. Patent No. 7,265,124
2016-02-04 Prior litigation (No. 15-8082) closed via dismissal
2017-01-17 Issue Date for U.S. Reissue Patent No. RE46,276
2019-05-23 Date of Defendant's Paragraph IV Notice Letter
2019-07-03 Complaint Filing Date

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

U.S. Reissue Patent No. RE46,276 - "Triazolo(4,5-d)pyrimidine compounds", issued January 17, 2017

The Invention Explained

  • Problem Addressed: The patent describes the central role of platelet aggregation in arterial thrombosis, which can lead to myocardial infarction and unstable angina. It notes that existing anti-thrombotic agents like aspirin have limited efficacy because they only block one pathway to platelet activation ('276 Patent, col. 1:31-2:9). The patent identifies the P2T receptor on platelets as a key mediator of aggregation and thus a critical target for more effective antithrombotic drugs (Compl. ¶1; '276 Patent, col. 2:10-21).
  • The Patented Solution: The invention provides a class of triazolo[4,5-d]pyrimidine compounds that act as potent antagonists of the P2T receptor, thereby inhibiting platelet aggregation. The patent provides methods for synthesizing these compounds, with the claimed invention specifically covering the compound known as ticagrelor and oral pharmaceutical formulations containing it ('276 Patent, col. 2:32-3:4; col. 27:14-28:28).
  • Technical Importance: The invention provided a novel, potent, and metabolically stable compound for use in antiplatelet therapy, a cornerstone treatment for patients with acute coronary syndromes ('276 Patent, col. 2:21-31).

Key Claims at a Glance

  • The complaint asserts independent claims 18 and 19 (Compl. ¶48).
  • Claim 18 is a composition of matter claim directed to a specific chemical compound, identified in the complaint as ticagrelor, or one other specified compound (Compl. ¶¶ 49, 51; '276 Patent, col. 28:10-18).
  • Claim 19 is a formulation claim directed to an oral pharmaceutical composition comprising ticagrelor in a form such as a tablet, pill, capsule, liquid, powder, or granule (Compl. ¶50; '276 Patent, col. 28:19-28).
  • The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶61).

U.S. Patent No. 7,265,124 - "Cristalline and amorphous form of a triazolo (4,5-D) pyridimine compound", issued September 4, 2007

The Invention Explained

  • Problem Addressed: The patent explains that for a drug substance to be commercially viable, it must be in a form that is stable, pure, and can be reliably manufactured and formulated. Amorphous (non-crystalline) materials can present significant problems, including chemical instability and unpredictable solubility, which can affect a drug's performance and shelf life (’124 Patent, col. 1:15-34).
  • The Patented Solution: The invention solves this problem by identifying and characterizing several distinct solid-state forms of the ticagrelor compound, including four different crystalline forms (Polymorphs I, II, III, and IV) and an amorphous form. Each crystalline form is defined by unique physical properties, particularly its X-ray powder diffraction (XRPD) pattern, which provides a structural fingerprint (’124 Patent, col. 2:36-43; Figs. 1.1-1.4). These stable, well-defined forms allow for consistent and reliable manufacturing of the final drug product.
  • Technical Importance: Discovering and controlling polymorphism is a critical aspect of pharmaceutical development, as the specific crystalline form of an active ingredient can have profound effects on the drug's safety, efficacy, and manufacturability (’124 Patent, col. 1:45-49).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 21 (Compl. ¶48).
  • Claim 1 is a composition of matter claim directed to the compound ticagrelor (Formula I), where the compound is selected from a group of different polymorphs, each "characterised by an X-ray powder diffraction pattern containing specific peaks of high intensity" at specific angles (’124 Patent, col. 15:12-50).
  • Claim 21 is a formulation claim directed to a pharmaceutical composition comprising a compound as claimed in claim 1 in admixture with a pharmaceutically acceptable diluent, adjuvant, or carrier (’124 Patent, col. 17:32-34).
  • The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶69).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is HEC’s generic ticagrelor tablets, for which HEC seeks FDA approval via ANDA No. 208508 (Compl. ¶1).

Functionality and Market Context

  • The complaint alleges that HEC's ANDA product contains the same active ingredient (ticagrelor), has the same dosage form and strength, and is intended for the same medical indications as AstraZeneca’s Brilinta® product (Compl. ¶¶ 57-58). Specifically, the complaint alleges that HEC's Notice Letter admits that its proposed product will contain ticagrelor in a specific crystalline form known as "polymorph II" (Compl. ¶48). The complaint alleges HEC will market this generic product throughout the United States, including in New Jersey, upon receiving FDA approval (Compl. ¶11).

IV. Analysis of Infringement Allegations

RE46,276 Patent Infringement Allegations

Claim Element (from Independent Claim 19) Alleged Infringing Functionality Complaint Citation Patent Citation
An oral pharmaceutical composition comprising [1S-[1α,2α,3β(1S*,2R*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol Defendant's proposed ANDA product contains the active ingredient ticagrelor, which Defendant allegedly admits is the chemical compound recited in the claim. ¶¶ 51, 57 col. 28:20-24
in combination with a pharmaceutically acceptable diluent, adjuvant, and/or carrier suitable for oral administration, Defendant's ANDA product is formulated as a tablet for oral use and therefore contains pharmaceutically acceptable excipients. ¶51 col. 28:24-26
wherein said oral pharmaceutical composition is in the form of a tablet, pill, capsule, liquid, powder, or granule. Defendant's Notice Letter allegedly admits that its proposed ticagrelor ANDA product will be a tablet for oral use. ¶51 col. 28:26-28

7,265,124 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound of formula (I) Defendant's proposed ANDA product contains the active ingredient ticagrelor, which is the compound of formula (I). The complaint includes a diagram of this chemical structure. (Compl. ¶52). ¶¶ 51, 52 col. 15:1-12
characterised by an X-ray powder diffraction pattern containing specific peaks of high intensity at 5.5° (±0.1°), 13.5° (±0.1°), 18.3° (±0.1°), 22.7° (±0.1°) and 24.3° (±0.1°) 2θ Defendant's Notice Letter allegedly admits its product contains "Polymorph II" of ticagrelor, which is the crystalline form recited in claim 1 and defined by these specific XRPD peaks. ¶¶ 48, 54 col. 15:20-25

Identified Points of Contention

  • Scope Questions: The complaint's allegations rely heavily on admissions purportedly made in HEC’s Notice Letter (Compl. ¶¶ 48, 51, 54). A central question will be the precise scope and legal effect of these admissions. It remains to be seen whether HEC will be precluded from arguing non-infringement on the facts, or if it will contend that its product does not meet every limitation despite the statements in its letter. The case, as framed by the complaint, suggests the primary dispute will be over the validity of the patents rather than the factual particulars of infringement (Compl. ¶48).
  • Technical Questions: For the ’124 patent, a technical question is whether HEC’s product, as specified in its ANDA, in fact exhibits the XRPD pattern of "Polymorph II" as claimed. This will be a matter of comparing the ANDA's characterization data against the claim limitations. For the ’276 patent, the question is whether the active ingredient in HEC's product is chemically identical to the structure recited in claim 18, an issue fundamental to the ANDA process itself.

V. Key Claim Terms for Construction

  • The Term: "characterised by an X-ray powder diffraction pattern containing specific peaks of high intensity at..." (’124 Patent, Claim 1)
  • Context and Importance: This term is the central limitation defining the patented polymorph. Its construction will determine what evidence is required to prove infringement. Practitioners may focus on this term because disputes often arise over whether "containing" means the listed peaks are necessary but not sufficient, and what the threshold for "high intensity" is, especially if the accused product contains excipients that generate other peaks or background noise.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue that the plain language "containing" only requires the presence of the five recited peaks, regardless of other peaks that may be present. The specification provides a more extensive list of peaks for Polymorph II, but the claim only recites a subset, suggesting the claim is intentionally broader than the specific example in the detailed description (’124 Patent, col. 3:61-67).
    • Evidence for a Narrower Interpretation: A party could argue that "characterised by" implies that the recited peaks are the defining fingerprint of the polymorph. This may suggest that the overall diffraction pattern of the accused substance must substantially match the pattern for Polymorph II shown in the patent's Figure 1.2, not merely contain five isolated peaks that could potentially appear in a different form or a mixture.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that HEC will indirectly infringe by inducing and contributing to infringement by others (Compl. ¶62). The basis for this allegation is that HEC is seeking approval to market its generic product for the same indications as Brilinta®, and its product label will instruct physicians and patients to use the drug in an infringing manner (Compl. ¶58).
  • Willful Infringement: The complaint does not contain a separate count for willful infringement. However, it lays the factual predicate for a potential willfulness claim for any post-approval infringement by alleging that HEC received a Notice Letter and therefore has "actual knowledge" of the patents-in-suit (Compl. ¶¶ 60, 68).

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

  • A core issue will be one of validity: As the complaint heavily relies on alleged admissions of infringement from the Defendant's Notice Letter, the central legal battle will likely concern whether the asserted claims of the compound patent (’276) and the polymorph patent (’124) are valid and enforceable in light of the prior art.
  • A key evidentiary question will be one of structural identity: Notwithstanding any admissions, the case will depend on technical evidence from HEC's ANDA. Does the data conclusively show that the proposed generic product contains the exact chemical compound ticagrelor and, specifically, the crystalline "Polymorph II" defined by the XRPD peak limitations of the ’124 patent?
  • A procedural question will be the legal scope of admission: To what extent do the statements made by HEC in its Paragraph IV Notice Letter, as required by the Hatch-Waxman Act, legally bar HEC from contesting the factual elements of infringement, thereby focusing the court's inquiry almost exclusively on patent validity?