1:20-cv-00968
AbbVie Inc v. DR Reddys Laboratories Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AbbVie Inc. (Delaware) and Genentech, Inc. (Delaware)
- Defendant: Dr. Reddy's Laboratories, Ltd. (India) and Dr. Reddy's Laboratories, Inc. (New Jersey)
- Plaintiff’s Counsel: Saul Ewing Arnstein & Lehr LLP; Paul Hastings LLP
- Case Identification: 1:20-cv-00968, D. Del., 10/07/2022
- Venue Allegations: Plaintiffs allege venue is proper because Defendants intend to market and sell the accused generic product in Delaware, have previously litigated in the district without challenging venue, and Defendant DRLI is registered as a pharmacy wholesaler in Delaware.
- Core Dispute: Plaintiffs allege that Defendants' Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug VENCLEXTA® (venetoclax) constitutes an act of infringement of three U.S. patents covering methods of treatment and drug formulation.
- Technical Context: The technology relates to cancer therapies targeting the B-cell CLL/lymphoma 2 (BCL-2) protein, which is involved in regulating programmed cell death (apoptosis) and is often overexpressed in cancer cells.
- Key Procedural History: This filing is a Third Amended Complaint in a consolidated action. The dispute arises under the Hatch-Waxman Act, where the filing of an ANDA with a Paragraph IV certification is a statutory act of infringement. Post-issuance, U.S. Patent No. 10,993,942 survived a Post-Grant Review (PGR) proceeding in which certain claims were cancelled but asserted independent claim 1 was confirmed as patentable. U.S. Patent No. 11,110,087 similarly survived an Inter Partes Review (IPR) proceeding where asserted independent claim 1 was found patentable.
Case Timeline
| Date | Event |
|---|---|
| 2012-09-07 | Priority Date for ’942 and ’087 Patents |
| 2014-07-24 | Priority Date for ’599 Patent |
| 2020-06-08 | Defendant's First ANDA Notice Letter |
| 2020-09-04 | Defendant's Second ANDA Notice Letter |
| 2021-05-04 | U.S. Patent No. 10,993,942 Issues |
| 2021-09-07 | U.S. Patent No. 11,110,087 Issues |
| 2022-02-03 | Post-Grant Review Filed for ’942 Patent (PGR2022-00023) |
| 2022-06-28 | U.S. Patent No. 11,369,599 Issues |
| 2022-08-30 | Defendant's Third ANDA Notice Letter |
| 2022-10-07 | Third Amended Complaint Filing Date |
| 2022-10-14 | Inter Partes Review Filed for ’087 Patent (IPR2023-00052) |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,993,942 - "Combination Therapy of a Type II Anti-CD20 Antibody with a Selective BCL-2 Inhibitor"
- Patent Identification: U.S. Patent No. 10,993,942, titled "Combination Therapy of a Type II Anti-CD20 Antibody with a Selective BCL-2 Inhibitor," issued May 4, 2021 (the ’942 Patent). (Compl. ¶37).
The Invention Explained
- Problem Addressed: The patent’s background section describes the role of the Bcl-2 family of proteins in regulating programmed cell death (apoptosis) and notes that dysregulation of this process is a hallmark of cancer. (’942 Patent, col. 2:20-27). It implicitly identifies the need for more effective therapies for cancers that rely on Bcl-2 for survival, such as CD20-expressing cancers. (’942 Patent, col. 1:24-28).
- The Patented Solution: The invention provides a combination therapy that pairs a selective Bcl-2 inhibitor (venetoclax, also referred to as GDC-0199 or ABT-199) with a type II anti-CD20 antibody (obinutuzumab). (’942 Patent, Abstract). The specification asserts that this combination produces a greater-than-additive, or synergistic, anti-tumor effect, as demonstrated in experimental data presented in Figure 1. (’942 Patent, col. 26:1-5; FIG. 1).
- Technical Importance: The combination approach aims to overcome drug resistance and achieve deeper, more durable responses in patients with certain leukemias and lymphomas than could be achieved with either therapeutic agent used alone. (’942 Patent, col. 26:1-12).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims. (Compl. ¶64). Independent claims 1 and 6 survived a Post-Grant Review proceeding. Claim 1 is representative:
- Independent Claim 1:
- A method for treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in a patient,
- the method comprising orally administering GDC-0199 in escalating doses to the patient,
- wherein the escalating doses comprise a dose of 50 mg of GDC-0199 per day for one week
- followed by a dose of 100 mg of GDC-0199 per day for one week. (’942 Patent, col. 35:46-54).
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 11,110,087 - "Combination Therapy of a Type II Anti-CD-20 Antibody with a Selective BCL-2 Inhibitor"
- Patent Identification: U.S. Patent No. 11,110,087, titled "Combination Therapy of a Type II Anti-CD-20 Antibody with a Selective BCL-2 Inhibitor," issued September 7, 2021 (the ’087 Patent). (Compl. ¶39).
The Invention Explained
- Problem Addressed: Similar to its family member, the ’942 Patent, the ’087 Patent addresses the need for improved treatments for CD20-expressing cancers by targeting the Bcl-2 apoptosis pathway. (’087 Patent, col. 2:20-27).
- The Patented Solution: This patent also claims a combination therapy of a Bcl-2 inhibitor and a type II anti-CD20 antibody but focuses on different dosing regimens. The claims cover specific dose-escalation schedules, including methods where the anti-CD20 antibody is administered before the Bcl-2 inhibitor dose escalation begins, a sequence intended to manage potential infusion-related reactions. (’087 Patent, Abstract; FIG. 3).
- Technical Importance: The claimed methods represent specific, clinically tested dosing schedules designed to maximize therapeutic synergy while managing patient safety and side effects. (’087 Patent, col. 26:27-44).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims. (Compl. ¶72). Independent claim 1 survived an Inter Partes Review proceeding.
- Independent Claim 1:
- A method for treating lymphoma or leukemia in a human patient,
- the method comprising orally administering once daily GDC-0199 to the patient in dosing cycles comprising escalating doses,
- wherein the escalating doses comprise a dose of 100 mg of GDC-0199 per day,
- followed by orally administering to the patient a dose of 200 mg of GDC-0199 per day,
- followed by orally administering to the patient a dose of 400 mg of GDC-0199 per day. (’087 Patent, col. 35:13-24).
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 11,369,599 - "Melt-extruded Solid Dispersions Containing an Apoptosis-Inducing Agent"
- Patent Identification: U.S. Patent No. 11,369,599, titled "Melt-extruded Solid Dispersions Containing an Apoptosis-Inducing Agent," issued June 28, 2022 (the ’599 Patent). (Compl. ¶41).
Technology Synopsis
The patent addresses the technical challenge of poor oral bioavailability for apoptosis-inducing drugs like venetoclax, which have very low water solubility. (’599 Patent, col. 3:15-25). The patented solution is a "solid dispersion" formulation created via melt-extrusion, where the active drug is dispersed in an "essentially non-crystalline or amorphous form" within a polymer carrier and a surfactant, thereby improving its dissolution in the gastrointestinal tract. (’599 Patent, Abstract; col. 7:1-8).
Asserted Claims
The complaint alleges infringement of one or more claims, including independent claim 1. (Compl. ¶79).
Accused Features
DRL's proposed generic venetoclax tablets are accused of being solid dispersion formulations that meet the specific compositional and structural requirements of the ’599 Patent claims. (Compl. ¶46-48, 79).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendants’ proposed generic venetoclax tablets, for which Defendants filed ANDA No. 214733 seeking FDA approval. (Compl. ¶1, 20).
Functionality and Market Context
The accused product is an oral tablet containing venetoclax as the active pharmaceutical ingredient, offered in 10 mg, 50 mg, and 100 mg dosage strengths. (Compl. ¶48). The complaint alleges that DRL’s proposed labeling for its generic version will be the same as or similar to that for VENCLEXTA®, indicating its use for treating adult patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML). (Compl. ¶50, 52). The filing of the ANDA seeks approval to market this product prior to the expiration of the patents-in-suit. (Compl. ¶19).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide claim charts. The infringement allegations are based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2)(A), which seeks approval to market a generic drug for uses and in a form allegedly covered by the patents-in-suit.
’942 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in a patient | DRL’s ANDA seeks approval to market generic venetoclax for indications that include treatment of CLL and SLL, as will be described in its proposed product labeling. | ¶50, 52, 64 | col. 35:46-48 |
| the method comprising orally administering GDC-0199 in escalating doses to the patient | DRL’s proposed labeling will allegedly instruct physicians and patients to administer the generic venetoclax tablets in escalating doses, consistent with the VENCLEXTA® label. | ¶51-52, 64 | col. 35:49-50 |
| wherein the escalating doses comprise a dose of 50 mg of GDC-0199 per day for one week followed by a dose of 100 mg of GDC-0199 per day for one week | The complaint alleges DRL’s proposed labeling will include dosing schedules for a ramp-up phase that will meet the specific dosage and duration limitations of the claim. | ¶51-52, 64 | col. 35:51-54 |
’087 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating lymphoma or leukemia in a human patient | DRL’s ANDA seeks approval to market generic venetoclax for indications that include treatment of lymphoma and leukemia, as will be described in its proposed product labeling. | ¶50, 52, 72 | col. 35:13-15 |
| the method comprising orally administering once daily GDC-0199 to the patient in dosing cycles comprising escalating doses | DRL’s proposed labeling will allegedly instruct physicians and patients to administer the generic venetoclax tablets once daily in escalating doses. | ¶51-52, 72 | col. 35:15-18 |
| wherein the escalating doses comprise a dose of 100 mg...followed by...200 mg...followed by...400 mg of GDC-0199 per day | The complaint alleges DRL’s proposed labeling will include dosing schedules for a ramp-up phase that will meet the specific dosage escalation limitations of the claim. | ¶51-52, 72 | col. 35:18-24 |
Identified Points of Contention
- Scope Questions: For the ’942 Patent, the complaint notes that DRL submitted a "Section viii certification," which is a statement that it is not seeking approval for a patented method of use. (Compl. ¶65). This raises the question of whether this "carve-out" from the proposed label will be effective to avoid inducing infringement of the claimed methods, or whether the remaining approved uses would still lead to infringement in practice.
- Technical Questions: For the ’599 Patent, the dispute will center on the physical and chemical properties of DRL's generic product. A primary question will be whether DRL's formulation is, in fact, a "melt-extruded solid dispersion" containing venetoclax in an "essentially non-crystalline or amorphous form" as required by the claims. The complaint does not provide technical data on this point, stating only that the limited information provided by DRL does not demonstrate non-infringement. (Compl. ¶59, 61).
V. Key Claim Terms for Construction
The Term: "escalating doses" (’942 Patent, Claim 1; ’087 Patent, Claim 1)
Context and Importance
This term is central to the asserted method claims. The infringement analysis will depend on whether the dosing schedule in DRL's proposed product labeling falls within the scope of this term as defined by the patents. Practitioners may focus on this term because any difference between the label's instructions and the claim's specific schedule could form a basis for a non-infringement defense.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The specifications of the ’942 and ’087 Patents describe the general clinical rationale for dose escalation as a way to manage the risk of tumor lysis syndrome, suggesting the concept is not limited to one rigid schedule. (’942 Patent, col. 26:27-50).
- Evidence for a Narrower Interpretation: The claims themselves recite very specific dose amounts and durations (e.g., "50 mg...per day for one week followed by...100 mg...per day for one week"). (’942 Patent, col. 35:51-54). The patent figures also illustrate highly specific dosing schemas, which could be argued to define the metes and bounds of the claimed invention. (’942 Patent, FIG. 2, FIG. 3).
The Term: "solid dispersion" and "essentially non-crystalline or amorphous form" (’599 Patent, e.g., Claim 1)
Context and Importance
These terms define the core structure of the claimed formulation. Infringement of the ’599 Patent will hinge on whether DRL's generic tablet meets these structural limitations. Practitioners may focus on these terms because they are subject to technical measurement and expert interpretation, creating a potential battle of experts over analytical data from the accused product.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The patent's background explains the invention's goal is to solve the general problem of poor bioavailability for a class of drugs, suggesting the term "solid dispersion" should be read in light of this functional purpose. (’599 Patent, col. 3:15-25).
- Evidence for a Narrower Interpretation: The specification provides a specific definition for "essentially non-crystalline," stating it means the active ingredient has "no more than about 10% crystallinity as measured by X-ray powder diffraction analysis." (’599 Patent, col. 7:6-10). The patent also repeatedly describes melt-extrusion as the process for forming the solid dispersion, potentially linking the definition of the final product to the process used to make it. (’599 Patent, Abstract).
VI. Other Allegations
Indirect Infringement
The complaint alleges that DRL will induce and contribute to the infringement of the ’942 and ’087 Patents. (Compl. ¶67, 74). This allegation is based on the claim that DRL's proposed product labeling will instruct physicians and patients to administer the generic drug in a manner that practices the patented methods of treatment. (Compl. ¶52).
Willful Infringement
Willfulness is not explicitly pleaded as a separate count, but the complaint alleges that DRL had "actual and constructive notice" of each patent since its publication date and "nonetheless maintained DRL's ANDA," which may form the basis for a future willfulness claim. (Compl. ¶68, 75, 82).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of induced infringement versus statutory carve-out: Can DRL’s "Section viii" certification for the ’942 Patent effectively shield it from liability for induced infringement, or will Plaintiffs be able to demonstrate that the remaining indications on the proposed label will inevitably lead prescribers to practice the patented method of treatment?
- A second central question will be one of technical formulation: Does the physical composition of DRL’s proposed generic tablet meet the specific quantitative and structural limitations of the ’599 Patent claims, particularly the weight percentages of its components and the "essentially non-crystalline" nature of the venetoclax active ingredient? This will likely be resolved through expert analysis of the physical product.
- Finally, a key issue for the method patents (’942 and ’087) will be one of claim scope versus label language: How precisely must the dosing instructions on DRL’s final, FDA-approved label track the specific "escalating doses" recited in the claims to support a finding of induced infringement?