DCT
1:21-cv-01338
Puma Biotechnology Inc v. AstraZeneca Pharma LP
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Puma Biotechnology, Inc. (Delaware) and Wyeth LLC (Delaware)
- Defendant: AstraZeneca Pharmaceuticals LP (Delaware), AstraZeneca AB (Sweden), and AstraZeneca PLC (United Kingdom)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:21-cv-01338, D. Del., 09/22/2021
- Venue Allegations: Venue is alleged to be proper for AstraZeneca Pharmaceuticals LP based on its residence and established place of business in Delaware. For foreign defendants AstraZeneca AB and AstraZeneca PLC, venue is alleged to be proper in any judicial district.
- Core Dispute: Plaintiffs allege that Defendants’ cancer therapeutic Tagrisso® (osimertinib) infringes patents claiming methods for treating specific types of non-small cell lung cancer that have developed resistance to earlier therapies.
- Technical Context: The technology relates to second-generation tyrosine kinase inhibitors (TKIs) designed to overcome acquired resistance to first-generation EGFR-targeted cancer drugs.
- Key Procedural History: The complaint alleges that Plaintiff Puma licensed the patent rights from Wyeth in 2011. It further alleges that Defendants were aware of a corresponding European patent issued in 2011 and an underlying international patent application, which may be relevant to the allegations of willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 2005-02-03 | Priority Date for ’314 and ’162 Patents |
| 2015-11-13 | FDA approves Defendant's accused product, Tagrisso® (osimertinib) |
| 2020-03-24 | U.S. Patent No. 10,596,162 issues |
| 2020-03-31 | U.S. Patent No. 10,603,314 issues |
| 2021-09-22 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
No probative visual evidence provided in complaint.
U.S. Patent No. 10,603,314 - Method For Treating Gefitinib Resistant Cancer
The Invention Explained
- Problem Addressed: The patent addresses the clinical problem where patients with Non-Small Cell Lung Cancer (NSCLC) initially responsive to first-generation epidermal growth factor receptor (EGFR) inhibitors, such as gefitinib and erlotinib, later develop resistance to those treatments, causing the cancer to progress (Compl. ¶32).
- The Patented Solution: The invention is a method for treating these resistant cancers. The solution involves administering a different class of drug: an irreversible EGFR inhibitor that forms a permanent, covalent bond with a specific amino acid (cysteine 773) in the EGFR protein’s catalytic domain. This distinct mechanism of action is purported to be effective against cancers that no longer respond to reversible inhibitors like gefitinib (Compl. ¶33, ¶40; ’162 Patent, Abstract).
- Technical Importance: This approach provided a therapeutic strategy for a specific, difficult-to-treat patient population whose cancers had acquired resistance to the then-standard EGFR-targeted therapies (Compl. ¶33).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶49).
- Essential elements of claim 1:
- A method of treating gefitinib and/or erlotinib resistant non-small cell lung cancer (NSCLC) in a patient,
- comprising administering daily to the patient an irreversible epidermal growth factor receptor (EGFR) inhibitor,
- that covalently binds to cysteine 773 of the catalytic domain within the EGFR,
- wherein the irreversible EGFR inhibitor is administered orally.
U.S. Patent No. 10,596,162 - Method For Treating Gefitinib Resistant Cancer
The Invention Explained
- Problem Addressed: This patent, from the same family as the ’314 patent, addresses the same general problem of acquired resistance to gefitinib and erlotinib but focuses on a specific molecular cause: the T790M mutation in the EGFR gene, which is known to confer resistance (Compl. ¶42; ’162 Patent, col. 4:36-41).
- The Patented Solution: The patented solution is a method for treating NSCLC patients whose cancer is not only resistant to gefitinib/erlotinib but also specifically harbors the T790M EGFR mutation. The method involves administering an irreversible EGFR inhibitor, which covalently binds to cysteine 773, within a specified daily dosage range of 2-500 mg (Compl. ¶42; ’162 Patent, Claim 1).
- Technical Importance: This invention refines the treatment approach by targeting a patient sub-population defined by a specific genetic biomarker (the T790M mutation), representing a step toward personalized medicine for resistant NSCLC (Compl. ¶42).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶61).
- Essential elements of claim 1:
- A method of treating gefitinib and/or erlotinib resistant NSCLC having a T790M mutation in a patient,
- comprising administering daily to the patient,
- a pharmaceutical composition comprising a unit dosage of 2-500 mg of an irreversible EGFR inhibitor,
- that covalently binds to cysteine 773 of the catalytic domain within the EGFR having the T790M mutation, and
- wherein the inhibitor is not the specific compound CL-387,785.
III. The Accused Instrumentality
Product Identification
The accused products are osimertinib and Tagrisso® (osimertinib) dosage forms (Compl. ¶2).
Functionality and Market Context
- Tagrisso® (osimertinib) is an irreversible EGFR inhibitor approved by the FDA (Compl. ¶43). Its approved indications include the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed on or after prior EGFR TKI therapy (Compl. ¶43). The product is distributed as oral tablets in 40 mg and 80 mg dosage strengths (Compl. ¶6).
- The complaint alleges Tagrisso® was AstraZeneca's largest-selling product in 2020, with U.S. sales accounting for $1.566 billion (Compl. ¶25).
IV. Analysis of Infringement Allegations
’314 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating gefitinib and/or erlotinib resistant non-small cell lung cancer (NSCLC) in a patient... | Use of Tagrisso® is alleged to treat NSCLC in patients who are resistant to gefitinib and/or erlotinib, as instructed by the product label for patients who have progressed on prior therapy (Compl. ¶49). | ¶49 | col. 1:57-60 |
| ...comprising administering daily to the patient an irreversible... inhibitor... | The accused product, Tagrisso® (osimertinib), is alleged to be an irreversible EGFR inhibitor, and its product label allegedly instructs daily administration (Compl. ¶42-43). | ¶42, ¶43 | col. 8:58-60 |
| ...that covalently binds to cysteine 773 of the catalytic domain within the EGFR... | The complaint alleges that the patents-in-suit claim methods using an irreversible EGFR inhibitor that works by this mechanism, and that Tagrisso® is such an inhibitor (Compl. ¶40, ¶43). | ¶40, ¶43 | col. 3:61-64 |
| ...wherein the irreversible EGFR inhibitor is administered orally. | Tagrisso® is commercially manufactured and sold as oral tablets (Compl. ¶6). | ¶6 | col. 9:25-28 |
- Identified Points of Contention:
- Scope Questions: A central question may be whether the patient population treated with Tagrisso® according to its label necessarily meets the claim definition of "gefitinib and/or erlotinib resistant." The analysis will depend on how resistance is defined—clinically (e.g., progression on prior therapy) or molecularly—and whether the evidence of Tagrisso®'s use aligns with that definition.
- Technical Questions: The complaint alleges Tagrisso® is an "irreversible EGFR inhibitor." The court may need to consider technical evidence confirming that osimertinib's mechanism of action satisfies the specific claim requirement of covalently binding to cysteine 773.
’162 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating gefitinib and/or erlotinib resistant non-small cell lung cancer having a T790M mutation... in a patient... | The Tagrisso® Product Label allegedly instructs its use for treating patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed on or after prior EGFR TKI therapy, which the complaint alleges meets this limitation (Compl. ¶43, ¶61). | ¶43, ¶61 | col. 4:36-41 |
| ...comprising administering daily... a pharmaceutical composition comprising a unit dosage of 2-500 mg... | Tagrisso® is allegedly administered daily and is sold in 40 mg and 80 mg tablets, which falls within the claimed dosage range (Compl. ¶6, ¶42, ¶62). | ¶6, ¶42, ¶62 | col. 8:61-62 |
| ...of an irreversible EGFR inhibitor that covalently binds to cysteine 773 of the catalytic domain within the... EGFR... | The complaint alleges that Tagrisso® (osimertinib) is an irreversible EGFR inhibitor and that the patent claims a method using an inhibitor with this mechanism (Compl. ¶42, ¶43). | ¶42, ¶43 | col. 3:61-64 |
| ...wherein the irreversible EGFR inhibitor is not CL-387,785. | The accused product is osimertinib, which is a distinct chemical entity from the excluded compound CL-387,785 (Compl. ¶2, ¶43). | ¶2, ¶43 | Claim 1 |
- Identified Points of Contention:
- Scope Questions: Similar to the ’314 Patent, the dispute may focus on whether the instructions on the Tagrisso® label induce infringement. Specifically, does following the label for its T790M indication necessarily result in the treatment of a patient who is "gefitinib and/or erlotinib resistant" as required by the claim?
- Technical Questions: The factual basis for Tagrisso® being an irreversible EGFR inhibitor that covalently binds to cysteine 773 will be a key technical point, although this may not be a primary area of dispute given the drug's known mechanism of action.
V. Key Claim Terms for Construction
The Term: "gefitinib and/or erlotinib resistant"
Context and Importance: This term defines the patient population to be treated and is the central limitation distinguishing the patented method from prior art treatments. The scope of what constitutes "resistant" will be critical to determining infringement, as it dictates whether the patients treated with Tagrisso® fall within the claims.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent abstract states that "Progression of the cancer is indicative that the cancer is resistant" ('162 Patent, Abstract), which may support a clinical definition based on disease progression after treatment, regardless of the underlying molecular mechanism.
- Evidence for a Narrower Interpretation: The specification's detailed discussion of specific molecular mechanisms of resistance, particularly the T790M mutation, could support a narrower construction requiring a specific genetic or biochemical basis for resistance beyond mere clinical observation ('162 Patent, col. 4:36-41).
The Term: "irreversible... inhibitor that covalently binds to cysteine 773"
Context and Importance: This term defines the required mechanism of action for the therapeutic agent. Infringement hinges on whether the accused product, osimertinib, functions in this specific manner. Practitioners may focus on this term because it involves a precise chemical interaction that must be proven.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification's description of the problem and solution in functional terms—overcoming resistance by using an "irreversible" inhibitor—may support a construction that focuses on the functional outcome of irreversible binding rather than a specific chemical bond type or kinetic profile.
- Evidence for a Narrower Interpretation: The specification identifies specific examples of such inhibitors (EKB-569, HKI-272, HKI-357) and describes the covalent bond formation, which could be used to argue that the term is limited to inhibitors that operate through the same or a very similar chemical mechanism ('162 Patent, Abstract).
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement. Inducement is based on allegations that Defendants knowingly and intentionally provide Tagrisso® with a product label and instructions that encourage and direct physicians and patients to use the drug in a manner that directly infringes the method claims (Compl. ¶52, ¶65). Contributory infringement is based on allegations that Tagrisso® is especially made and adapted for an infringing use and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶55, ¶67).
- Willful Infringement: The complaint alleges that Defendants' infringement has been deliberate and willful. This allegation is based on purported pre-suit knowledge of the technology through awareness of the corresponding European patent (issued April 6, 2011) and the underlying PCT application publication. The complaint further alleges that other patents listed in the FDA Orange Book for Tagrisso® cite the patents-in-suit's parent application as important prior art, suggesting knowledge of the claimed invention before the asserted patents issued (Compl. ¶54, ¶64).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of induced infringement: Does the evidence show that the Tagrisso® Product Label and Defendants' marketing activities instruct and encourage medical professionals to administer the drug in a manner that practices every step of the claimed methods, specifically by treating patients who are definitively "gefitinib and/or erlotinib resistant"?
- A key question for damages and potential enhancement will be one of pre-suit knowledge and intent: Can Plaintiffs demonstrate that Defendants' alleged awareness of the predecessor European patent and related applications provided the requisite knowledge of infringement from the moment the U.S. patents issued, thereby rendering their continued commercialization of Tagrisso® an act of willful infringement?