1:17-cv-01639
AstraZeneca LP v. Prinston Pharmaceutical Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AstraZeneca LP (Delaware), AstraZeneca AB (Sweden), AstraZeneca UK Limited (United Kingdom), and AstraZeneca Pharmaceuticals LP (Delaware)
- Defendant: Prinston Pharmaceutical Inc. (Delaware)
- Plaintiff’s Counsel: McCarter & English, L.L.P.
- Case Identification: 1:17-cv-01639, D. Del., 11/13/2017
- Venue Allegations: Venue is alleged to be proper in the District of Delaware on the basis that Defendant is incorporated in the state of Delaware and has appointed a registered agent for service of process there.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s BRILINTA® (ticagrelor) product constitutes an act of infringement of four U.S. patents related to the ticagrelor compound, its use, and its crystalline forms.
- Technical Context: The technology concerns small molecule pharmaceutical compounds that inhibit platelet aggregation, used as anti-thrombotic agents in the treatment of cardiovascular diseases.
- Key Procedural History: The complaint notes that the asserted RE 46,276 patent is a reissue of U.S. Patent No. 6,525,060. Plaintiff also notes prior litigation against the same Defendant (Civ. Action No. 1:15-cv-01057-RGA) concerning the same ANDA but for a proposed 90 mg dosage strength; the current action addresses a supplemented ANDA for a 60 mg dosage strength.
Case Timeline
| Date | Event |
|---|---|
| 1997-07-22 | ’910 Patent Priority Date |
| 1998-12-04 | ’276 and ’419 Patents Priority Date |
| 2000-06-02 | ’124 Patent Priority Date |
| 2001-06-26 | ’910 Patent Issued |
| 2007-07-31 | ’419 Patent Issued |
| 2007-09-04 | ’124 Patent Issued |
| 2017-01-17 | ’276 Patent Reissued |
| 2017-11-02 | First ANDA Notice Letter Date |
| 2017-11-03 | Second ANDA Notice Letter Date |
| 2017-11-13 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,251,910 - 1,2,3-TRIAZOLO[4,5-D]PYRIMIDINES AS P2T RECEPTOR ANTAGONISTS
The Invention Explained
- Problem Addressed: The patent describes arterial thrombosis as a major health risk, where platelet adhesion and aggregation can precipitate events like myocardial infarction and unstable angina. It notes that while some anti-platelet agents exist, they may have limited efficacy or cause excessive bleeding by interfering with multiple pathways. (’910 Patent, col. 1:12-42).
- The Patented Solution: The invention claims to solve this problem by providing a new class of triazolo[4,5-d]pyrimidine compounds that act as P2T-receptor antagonists. By targeting this specific receptor on the platelet membrane, which mediates ADP-induced platelet aggregation, these compounds aim to provide a more focused anti-thrombotic effect. (’910 Patent, col. 1:56-64).
- Technical Importance: The development of selective P2T-receptor antagonists represented a targeted approach to anti-platelet therapy, seeking to inhibit a key pathway in thrombosis while potentially avoiding some side effects of broader-acting agents. (’910 Patent, col. 1:44-55).
Key Claims at a Glance
- The complaint alleges infringement of at least one claim but does not identify any specific claims asserted (Compl. ¶36). Independent Claim 1 is representative of the patented subject matter.
- Claim 1, a compound claim, defines a chemical compound of formula (I) with the following essential elements:
- A core triazolo[4,5-d]pyrimidine structure
- A substituent R¹, defined as one of several specified organic groups (e.g., C1-6 alkyl, phenyl)
- A substituent R², defined as one of several specified organic groups (e.g., C1-8 alkyl, C3-8-cycloalkyl)
- Specific definitions for substituents R, R³, and R⁴ attached to a cyclopentyl ring
- A pharmaceutically acceptable salt or solvate thereof
U.S. Reissue Patent No. RE 46,276 - TRIAZOLO(4,5-D)PYRIMIDINE COMPOUNDS
The Invention Explained
- Problem Addressed: The patent addresses the same problem of arterial thrombosis and the need for improved anti-thrombotic agents that inhibit platelet aggregation. (’276 Patent, col. 2:1-44).
- The Patented Solution: This patent moves from the broad genus of compounds in the ’910 patent to claim a specific chemical entity, ticagrelor, identified by its full chemical name: {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. It claims both the compound itself and methods of using it to inhibit platelet aggregation. (’276 Patent, col. 2:45-58, col. 51:5-15).
- Technical Importance: The patent claims a specific, named compound intended for therapeutic use, representing the culmination of research into the broader class of compounds disclosed in earlier patents. (’276 Patent, Abstract).
Key Claims at a Glance
- The complaint alleges infringement of at least one claim but does not identify any specific claims asserted (Compl. ¶40). Independent Claim 15 is representative of the patented methods.
- Claim 15, a method of use claim, contains the following essential elements:
- A method for inhibition of platelet aggregation
- Comprising administering to a subject in need of such treatment
- A therapeutically effective amount of a specific compound, {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 (ticagrelor)
- Or a pharmaceutically acceptable salt or solvate thereof
U.S. Patent No. 7,250,419 - TRISUBSTITUTED TRIAZOLOPYRIMIDINES FOR USE IN PLATELET AGGREGATION INHIBITION
Technology Synopsis
This patent addresses the problem of arterial thrombosis by claiming the specific triazolopyrimidine compound now known as ticagrelor. The invention provides the specific chemical structure and claims methods of using it for inhibiting platelet aggregation, noting its high potency and metabolic stability. (’419 Patent, col. 2:1-26).
Asserted Claims
The complaint alleges infringement of "at least one claim" (Compl. ¶44). The patent contains independent claims to the compound (Claim 1) and a method of its use (Claim 8).
Accused Features
The complaint alleges that the ticagrelor active pharmaceutical ingredient in Defendant’s ANDA product infringes the compound claims, and that its proposed use for inhibiting platelet aggregation will infringe the method claims. (Compl. ¶43-44).
U.S. Patent No. 7,265,124 - CRISTALLINE AND AMORPHOUS FORM OF A TRIAZOLO (4,5-D) PYRIDIMINE COMPOUND
Technology Synopsis
The patent addresses technical problems in pharmaceutical manufacturing related to chemical stability, solid-state stability, and purity. It provides a solution by identifying and claiming four specific stable crystalline forms (Polymorphs I, II, III, and IV) and a substantially amorphous form of the ticagrelor compound, each with distinct, measurable physical properties. (’124 Patent, col. 1:15-44).
Asserted Claims
The complaint alleges infringement of "at least one claim" (Compl. ¶48). The patent contains independent claims directed to the compound in a substantially crystalline form (Claim 1), each of the four specific polymorphs (Claims 9, 15, 20, 25), and the amorphous form (Claim 30).
Accused Features
The solid-state form of the ticagrelor in Defendant's ANDA product is alleged to infringe one or more of the claims directed to the specific patented crystalline or amorphous forms. (Compl. ¶47-48).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendant Prinston's proposed generic ticagrelor drug product in 60 mg oral tablet form, which is the subject of Abbreviated New Drug Application No. 208599 submitted to the FDA. (Compl. ¶1, ¶29).
Functionality and Market Context
The complaint alleges that Prinston seeks approval to market and sell its generic ticagrelor tablets for the same indications as AstraZeneca's BRILINTA® product before the expiration of the patents-in-suit. (Compl. ¶1, ¶30). The complaint characterizes the submission of the ANDA itself as an act of infringement under 35 U.S.C. § 271(e)(2)(A), which provides a basis for suit prior to any commercial launch. (Compl. ¶35).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide a claim chart or sufficient technical detail to map specific features of the accused product to the claim elements. The infringement allegation is based on the premise that the active pharmaceutical ingredient (API) in Prinston’s product is ticagrelor, the compound covered by the patents-in-suit.
’910 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compound of formula (I) | The ticagrelor API in Defendant's ANDA product is alleged to be a compound falling within the scope of formula (I). | ¶35-36 | col. 1:65-67 |
| wherein: R¹ is a C₁₋₆ alkyl... | The propylthio group of the ticagrelor API is alleged to satisfy this limitation. | ¶35-36 | col. 2:14-20 |
| R² is ... a C₃₋₈-cycloalkyl group optionally substituted by ... phenyl, the ... group being optionally substituted by ... halogen | The 3,4-difluorophenylcyclopropylamino group of the ticagrelor API is alleged to satisfy this limitation. | ¶35-36 | col. 2:25-39 |
| one of R³ and R⁴ is hydroxy and the other is ... hydroxy | The two hydroxy groups on the cyclopentane ring of the ticagrelor API are alleged to satisfy this limitation. | ¶35-36 | col. 2:39-41 |
| R is a group (CR⁵R⁶)ₘOR⁷ where m is 0 or 1, R⁵ and R⁶ are ... hydrogen, and R⁷ is ... (CR⁵R⁶)ₙR¹⁴ where ... n is 1 to 3 and R¹⁴ is ... OR¹⁵ | The 2-hydroxyethoxy group of the ticagrelor API is alleged to satisfy this limitation. | ¶35-36 | col. 2:42-49 |
- Identified Points of Contention:
- Scope Questions: A potential question is whether the specific ticagrelor compound, which was the subject of later patents, falls squarely within the genus of compounds claimed in the '910 Patent. The analysis may focus on whether every element of the ticagrelor structure corresponds to a recited option in the broad Markush groups of Claim 1.
- Technical Questions: The primary technical question is one of chemical identity. What evidence will demonstrate that the API in Prinston’s proposed product is a compound meeting all structural limitations of Claim 1? The complaint itself provides no such evidence.
’276 Patent Infringement Allegations
| Claim Element (from Independent Claim 15) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for inhibition of platelet aggregation | The proposed product label for the ticagrelor ANDA product, which is expected to seek an indication for inhibiting platelet aggregation, is the basis for this allegation. | ¶39-40 | col. 2:45-47 |
| comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound which is {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 | The API in Defendant’s ANDA product is alleged to be this specific compound, and the proposed labeling is alleged to instruct its administration for the claimed method. | ¶39-40 | col. 51:5-15 |
- Identified Points of Contention:
- Scope Questions: Does the specific indication for use described in Prinston’s proposed product label meet the claim limitation of a "method for inhibition of platelet aggregation"? The analysis will require a comparison of the label’s language to the claim language.
- Technical Questions: A central question is whether Prinston's conduct in filing an ANDA with a proposed label constitutes inducement of infringement. This raises the evidentiary question of what the final, FDA-approved label will state regarding the drug's mechanism of action and approved uses.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail to identify specific claim construction disputes. However, based on the nature of the patents, the following terms may become central.
The Term: "a compound of formula (I)" (’910 Patent, Claim 1)
Context and Importance: This term defines the scope of the chemical genus protected by the earliest patent-in-suit. The entire infringement case for this patent hinges on whether the specific ticagrelor compound in the accused product falls within this definition. Practitioners may focus on this term to determine if there is any ambiguity in the structural formula or the definitions of the various "R" groups that could exclude ticagrelor.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides broad definitions for each substituent group (R¹, R², etc.), listing numerous alternatives, suggesting the formula is intended to cover a wide class of related compounds. (’910 Patent, col. 2:14-54).
- Evidence for a Narrower Interpretation: The specification also provides preferred embodiments for each substituent group. A defendant might argue that these preferred embodiments should guide the interpretation of the claim scope, although such arguments often face challenges. (’910 Patent, col. 3:12-61).
The Term: "{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" (’276 Patent, Claim 15)
Context and Importance: This is the full chemical name for ticagrelor. The infringement analysis for the method claim in the ’276 Patent (and the compound claims of the ’419 Patent) requires that the accused API be this exact compound. Any dispute will center on the chemical and structural identity, including the specific stereochemistry (e.g., 1S, 1R, 2R) recited in the name.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term "a compound which is" suggests that any substance meeting the recited chemical identity infringes. The patent does not appear to provide language suggesting a broader interpretation beyond the specific named compound and its salts or solvates.
- Evidence for a Narrower Interpretation: The claim recites a single, precise chemical name with specific stereochemistry. Intrinsic evidence, such as the detailed examples preparing this specific compound, reinforces that the claim is directed to this molecule and not to a broader class. (’276 Patent, col. 33:1-col. 34:67, Example 31).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will infringe under 35 U.S.C. §§ 271(b) and/or 271(c). (Compl. ¶36, ¶40, ¶44, ¶48). The factual basis for inducement is the allegation that Defendant’s marketing and product labeling will instruct physicians and patients to use the generic product in a manner that infringes the asserted method claims.
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue will be one of chemical and physical identity: Will discovery confirm that Defendant's ticagrelor API is the specific chemical compound, including the precise stereochemistry, claimed in the ’276 and ’419 patents? Furthermore, does the solid-state form of that API correspond to one of the specific crystalline polymorphs or the amorphous form claimed in the ’124 patent?
- A second core question will be one of induced infringement: Assuming the accused product contains the claimed compound, will the language of Defendant’s proposed and ultimately approved product labeling instruct users to administer the drug for a "method for inhibition of platelet aggregation" in a manner that directly infringes the asserted method claims?
- A third, and likely central, issue for the litigation will be validity: Defendant’s Paragraph IV certification asserts that the patents-in-suit are invalid and/or unenforceable (Compl. ¶31). The case will therefore likely turn on whether the asserted claims can withstand challenges based on prior art (e.g., anticipation, obviousness) or other defenses not yet detailed in the pleadings.