DCT
1:18-cv-00664
AstraZeneca Ab v. Zydus Pharma USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AstraZeneca AB (Sweden)
- Defendant: Zydus Pharmaceuticals (USA) Inc. (New Jersey)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 1:18-cv-00664, D. Del., 03/13/2019
- Venue Allegations: Plaintiff alleges venue is proper in Delaware based on Defendant's business activities, marketing and sales within the state, and Defendant’s prior litigation conduct in the district, which Plaintiff asserts constitutes a concession to venue.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for generic dapagliflozin tablets constitutes an act of infringement of three patents related to the compound and its methods of use for treating diabetes.
- Technical Context: The technology at issue involves C-aryl glucoside compounds that function as SGLT2 inhibitors, a class of drugs that treat type 2 diabetes by increasing the urinary excretion of glucose.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 211582 and a corresponding Notice Letter to Plaintiff dated March 20, 2018, which certified that its proposed generic product would not infringe Plaintiff's patents or that the patents are invalid.
Case Timeline
| Date | Event |
|---|---|
| 1999-10-12 | ’126 and ’117 Patents Priority Date |
| 2002-07-02 | ’126 Patent Issue Date |
| 2003-02-04 | ’117 Patent Issue Date |
| 2009-05-27 | ’934 Patent Priority Date |
| 2014-01-08 | FDA Approval of FARXIGA® (dapagliflozin) |
| 2014-04-01 | ’934 Patent Issue Date |
| 2018-03-20 | Defendant Zydus sends Notice Letter regarding ANDA filing |
| 2019-03-13 | First Amended Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,414,126 - C-Aryl Glucoside SGLT2 Inhibitors and Method
- Issued: July 2, 2002
The Invention Explained
- Problem Addressed: The patent’s background section identifies a need for new, safe, and orally active anti-diabetic agents to treat type II diabetes (NIDDM), which is characterized by hyperglycemia due to excessive hepatic glucose production and peripheral insulin resistance (’126 Patent, col. 1:21-27). It notes that existing therapies have potential side effects and that hyperglycemia is a major risk factor for diabetic complications (’126 Patent, col. 1:35-42).
- The Patented Solution: The invention provides a class of compounds, C-aryl glucosides, that inhibit the sodium-dependent glucose transporter SGLT2 found in the kidney (’126 Patent, col. 2:10-14). By inhibiting SGLT2, the major transporter responsible for glucose reuptake, the compounds promote the excretion of glucose in urine, which in turn helps normalize plasma glucose levels in diabetic patients (’126 Patent, Abstract; col. 2:19-24). This mechanism operates independently of insulin action.
- Technical Importance: The invention provided a novel, insulin-independent therapeutic pathway for managing hyperglycemia, offering a potential treatment for patients with significant insulin resistance and a way to avoid side effects associated with other anti-diabetic agents, such as hypoglycemia (’126 Patent, col. 2:41-57).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 and method claim 26 (Compl. ¶¶30, 31).
- Independent Claim 1 claims a compound having a specific chemical structure defined by a Markush formula, with the following essential elements:
- A C-aryl glucoside core structure.
- A linker group "A" between the aryl and a second phenyl ring, where A can be O, S, NH, or (CH2)n.
- Substituents R¹, R², and R²ª on the first phenyl ring, selected from a group including hydrogen, OH, OR⁵, lower alkyl, and halogen.
- Substituents R³ and R⁴ on the second phenyl ring, selected from a large group of chemical moieties including hydrogen, OH, OR⁵ª, lower alkyl, and halogen.
- The complaint explicitly asserts dependent and independent claims, including method of treatment claim 26 (Compl. ¶31).
U.S. Patent No. 6,515,117 - C-Aryl Glucoside SGLT2 Inhibitors and Method
- Issued: February 4, 2003
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the ’126 patent: the need for new therapeutic agents to treat type II diabetes and its associated hyperglycemia (’117 Patent, col. 2:1-10).
- The Patented Solution: The ’117 patent discloses and claims specific C-aryl glucoside compounds that are SGLT2 inhibitors, including the specific compound dapagliflozin (’117 Patent, claim 17). Like the parent ’126 patent, the invention works by inhibiting renal glucose reabsorption to lower blood glucose levels (’117 Patent, col. 2:11-25).
- Technical Importance: This patent claims the specific chemical entity, dapagliflozin, that became the active ingredient in Plaintiff's FARXIGA® product, representing a specific and commercially significant embodiment of the broader C-aryl glucoside technology.
Key Claims at a Glance
- The complaint asserts at least independent claim 1 and dependent claim 14 (Compl. ¶¶47, 48).
- Independent Claim 1 claims a method for treating diabetes, with the following elements:
- A method for treating diabetes or related diseases.
- Comprising administering to a mammalian species in need of treatment.
- A therapeutically effective amount of a compound of a specific structure (Formula I) or a pharmaceutically acceptable salt thereof.
- The complaint explicitly reserves the right to assert other claims (Compl. ¶48).
U.S. Patent No. 8,685,934 - Methods for Treating Extreme Insulin Resistance in Patients Resistant to Previous Treatment with Other Anti-Diabetic Drugs Employing an SGLT2 Inhibitor and Compositions Thereof
- Issued: April 1, 2014
The Invention Explained
- This patent addresses the treatment of a specific, difficult-to-treat patient population: type 2 diabetes patients with extreme insulin resistance who have failed previous treatments with other anti-diabetic drugs (’934 Patent, Abstract). The patented solution is a method of administering a therapeutically effective amount of an SGLT2 inhibitor, such as dapagliflozin, to this patient population (’934 Patent, Abstract).
Key Claims at a Glance
- Asserted Claims: The complaint asserts at least independent claim 8 (Compl. ¶61).
- Accused Features: The accused feature is the proposed use of Defendant's generic dapagliflozin product to treat type 2 diabetes, which Plaintiff alleges will be encouraged by the product's label, thereby inducing infringement of this patented method of use (Compl. ¶¶63-64).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are Defendant Zydus’s "ANDA Products": 5 mg and 10 mg dapagliflozin tablets for which Zydus seeks FDA approval via ANDA No. 211582 (Compl. ¶1).
Functionality and Market Context
The complaint alleges that the ANDA Products are generic versions of AstraZeneca’s FARXIGA® drug product (Compl. ¶1). Functionally, they contain the active ingredient dapagliflozin, an SGLT2 inhibitor intended to treat type 2 diabetes (Compl. ¶¶4, 26). The complaint alleges that Zydus has represented to the FDA that its products have the same active ingredient, dosage form, strength, and are bioequivalent to FARXIGA® (Compl. ¶26). In the market, the ANDA Products are intended to be substitutable generic competitors to FARXIGA® (Compl. ¶6).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’126 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compound having the structure [of Formula I] | The complaint alleges that Zydus's ANDA Products contain dapagliflozin as the active ingredient, which is a C-aryl glucoside compound alleged to fall within the chemical genus defined by Formula I. | ¶¶26, 30 | col. 6:25-59; col. 65:66-68:20 |
| wherein R¹, R², R²ª...R³, R⁴... and A are selected from specified chemical groups | The specific structure of dapagliflozin allegedly satisfies the definitions for each of the R-group and A-linker substituents as recited in the claim. | ¶30 | col. 6:25-59; col. 65:66-68:20 |
- Identified Points of Contention: The primary technical question for direct infringement will be one of chemical scope: does the specific molecular structure of dapagliflozin, as specified in Zydus's ANDA, meet every limitation of the Markush group claim defining the genus of compounds in Claim 1? A court may need to construe terms such as "lower alkyl" to determine if dapagliflozin's ethyl and chloro substituents are covered.
’117 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating diabetes or related diseases in a mammalian species in need of treatment... | Zydus is seeking approval to market its ANDA Products for the same indications as FARXIGA®, including the treatment of type 2 diabetes. Its product label will allegedly instruct this use. | ¶¶27, 50 | col. 4:54-58 |
| ...comprising administering...a therapeutically effective amount of a compound of structure I... | The ANDA Products contain dapagliflozin, which Plaintiff alleges is the compound of structure I. The 5 mg and 10 mg dosage forms are alleged to be therapeutically effective amounts. | ¶¶1, 26, 47 | col. 3:48-67; col. 65:42-66:23 |
- Identified Points of Contention: The analysis for this method claim will likely focus on indirect infringement. A key legal question will be whether Zydus’s proposed product labeling, by copying the indications of FARXIGA®, demonstrates the specific intent required to induce physicians to prescribe and patients to use the generic drug in a manner that infringes the patented method.
V. Key Claim Terms for Construction
For the ’126 Patent
- The Term: "lower alkyl"
- Context and Importance: This term is used to define the scope of several substituent groups (R¹, R², R²ª, R³, R⁴, R⁵) in the Markush structure of independent claim 1. The precise definition of "lower alkyl" is critical for determining whether the genus claimed by the ’126 patent is broad enough to encompass the specific dapagliflozin molecule, which contains an ethyl group.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides an explicit definition: "'lower alkyl' as employed herein alone or as part of another group includes both straight and branched chain hydrocarbons containing 1 to 8 carbons" (’126 Patent, col. 22:46-49). This broad definition may support an expansive reading of the claim.
- Evidence for a Narrower Interpretation: A defendant might argue that the scope should be limited by the examples provided in the patent. The specification lists exemplary alkyl groups such as "methyl, ethyl, propyl, isopropyl, butyl, t-butyl, isobutyl," and others, which could be used to argue that the term should be understood in light of these specific embodiments (’126 Patent, col. 22:52-56).
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for the method claims of all three patents-in-suit. The allegations of inducement are based on Zydus's intent for its ANDA Products to be used by physicians and patients in an infringing manner, with this intent evidenced by the proposed product labeling, which is required by regulation to copy the FARXIGA® label (Compl. ¶¶34, 50, 63). The contributory infringement allegations are based on Zydus selling a product that is a material part of the invention and not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶35, 51, 64).
- Willful Infringement: While the complaint does not contain a formal count for willful infringement, it alleges that Zydus has "actual knowledge" of each of the patents-in-suit as a result of receiving the Notice Letter dated March 20, 2018 (Compl. ¶¶29, 46, 60). These allegations could form the factual basis for a subsequent claim of willful infringement for any post-suit infringing activities.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue for the ’126 patent will be one of chemical scope: does dapagliflozin, the specific compound in the ANDA product, fall within the metes and bounds of the genus of C-aryl glucoside compounds defined by the Markush group structure in claim 1?
- A central question for the asserted method-of-use claims (’117 and ’934 patents) will be induced infringement: will Zydus's act of seeking approval to market a generic product with a label that mirrors the FARXIGA® label be found to constitute specific intent to encourage physicians and patients to perform the patented methods of treatment?
- A key question for the litigation will be the validity of the asserted claims: will the patents-in-suit withstand Zydus's anticipated challenges on grounds such as obviousness or lack of enablement, which are common defenses in ANDA litigation?