DCT
1:23-cv-00625
Array Biopharma Inc v. Teva Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Array BioPharma Inc. (Delaware)
- Defendant: Teva Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Arnold & Porter Kaye Scholer LLP
- Case Identification: 1:23-cv-00625, D. Del., 06/08/2023
- Venue Allegations: Venue is asserted based on Defendant being a Delaware corporation and its alleged intent to market, distribute, and sell the accused product in Delaware.
- Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s MEKTOVI® (binimetinib) product constitutes an act of infringement of three patents covering crystallized binimetinib and methods of its use.
- Technical Context: The technology resides in pharmaceutical chemistry and oncology, specifically concerning a crystalline form of a MEK inhibitor compound used to treat certain BRAF-mutated melanomas.
- Key Procedural History: The action was triggered by Defendant’s submission of ANDA No. 217509 with a Paragraph IV certification, alleging that Plaintiff’s patents are invalid, unenforceable, and/or will not be infringed by its generic product. The patents-in-suit are listed in the FDA’s Orange Book for MEKTOVI®. The complaint notes Defendant’s notice letter is dated August 8, 2022, and that Defendant's detailed statement asserts invalidity of the patents based on obviousness.
Case Timeline
| Date | Event |
|---|---|
| 2012-10-19 | Priority Date for ’016, ’376, and ’944 Patents |
| 2017-02-07 | U.S. Patent No. 9,562,016 Issues |
| 2017-03-21 | U.S. Patent No. 9,598,376 Issues |
| 2018-05-29 | U.S. Patent No. 9,980,944 Issues |
| 2022-08-08 | Date of Teva’s Notice Letter Regarding ANDA Submission |
| 2023-06-08 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,562,016 - “Preparation of and Formulation Comprising a MEK Inhibitor,” issued February 7, 2017
The Invention Explained
- Problem Addressed: The patent’s background section states that prior manufacturing processes for the MEK inhibitor binimetinib (referred to as "Compound A") were "disadvantageous for commercial production" and that there was a need for improved manufacturing methods that are more "scalable, safer, simpler, higher yielding and more economical" (’016 Patent, col. 2:35-49). It also identifies a need for "new solid forms for the treatment of cancer" (’016 Patent, col. 2:51-52).
- The Patented Solution: The invention provides processes for creating a crystallized form of binimetinib, as well as pharmaceutical compositions containing this crystallized form (’016 Patent, Abstract). The specification asserts that this crystallized compound possesses an "improved purity profile and an improved physical morphology which is advantageous in pharmaceutical drug development and manufacture" (’016 Patent, col. 2:57-62).
- Technical Importance: Binimetinib is a potent inhibitor of the MEK1 and MEK2 proteins, which are key components of the RAS/RAF/MEK signaling pathway that is frequently deregulated in human cancers (’016 Patent, col. 1:54-65). Developing a stable, pure, and consistently manufacturable solid form of an active pharmaceutical ingredient is a critical step in creating a viable drug product.
Key Claims at a Glance
- The complaint asserts infringement of at least claim 11 (Compl. ¶34, ¶35) and notes Defendant’s invalidity contentions are directed to claims 11-15 (Compl. ¶29). Independent claim 11 is representative of the asserted composition claims.
- The essential elements of independent claim 11 are:
- A pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide
- and a pharmaceutically acceptable carrier or excipient.
- The complaint does not explicitly reserve the right to assert dependent claims but alleges infringement of "at least" claim 11 (Compl. ¶35).
U.S. Patent No. 9,598,376 - “Preparation of and Formulation Comprising a MEK Inhibitor,” issued March 21, 2017
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’016 patent, the ’376 patent addresses the same technical problem: the need for improved, commercially viable forms and manufacturing processes for the MEK inhibitor binimetinib for use in cancer therapy (’376 Patent, col. 2:39-49).
- The Patented Solution: While the ’016 patent focuses on the compound and compositions, this patent claims methods of using those compositions. Specifically, it claims a method of treating certain cancers, including melanoma, by administering a pharmaceutical composition that contains the crystallized form of binimetinib (’376 Patent, claim 1).
- Technical Importance: This patent protects the specific therapeutic application of the crystallized form of binimetinib, shifting the focus from the substance itself to its method of use for treating specific diseases outlined in the claims.
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶43, ¶44).
- The essential elements of independent claim 1 are:
- A method of treating a cancer selected from a list including melanoma in a patient in need thereof,
- comprising administering to the patient a pharmaceutical composition,
- wherein the composition comprises crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide,
- and a pharmaceutically acceptable carrier or excipient.
- The complaint reserves the right to assert additional claims by alleging infringement of "at least claim 1" (Compl. ¶43).
U.S. Patent No. 9,980,944 - “Preparation of and Formulation Comprising a MEK Inhibitor,” issued May 29, 2018
Technology Synopsis
This patent is in the same family as the ’016 and ’376 patents and is also directed to cancer treatment. It claims methods of treating specific types of melanoma, namely BRAF-mutant melanoma, by administering a pharmaceutical composition containing crystallized binimetinib (’944 Patent, Abstract; claim 1). This claim scope is more specific regarding the genetic subtype of the cancer than the asserted claim of the ’376 patent.
Asserted Claims
The complaint asserts infringement of at least independent claim 1 (Compl. ¶55, ¶56).
Accused Features
The accused feature is Teva’s proposed product labeling, which allegedly instructs for the treatment of patients with unresectable or metastatic melanoma having a BRAF V600E or V600K mutation, thereby inducing infringement of the patented method (Compl. ¶51, ¶55).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Teva’s ANDA Product," identified as 15 mg binimetinib tablets submitted for FDA approval under ANDA No. 217509 (Compl. ¶7, ¶26).
Functionality and Market Context
- The product is a generic version of Array’s MEKTOVI® tablets (Compl. ¶2). The active ingredient is binimetinib, a reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 (Compl. ¶11). The complaint provides the chemical structure for the active ingredient, binimetinib (Compl. p. 3). The complaint alleges that Teva’s ANDA Product contains "at least some 'crystallized' binimetinib" (Compl. ¶33, ¶41, ¶53).
- The product is intended for the treatment of patients with specific forms of melanoma, as indicated by its proposed labeling, which allegedly copies the FDA-approved indication for MEKTOVI® (Compl. ¶39, ¶51). The action is filed under the Hatch-Waxman Act, which provides a framework for resolving patent disputes before a generic drug is marketed (Compl. ¶2, ¶31).
IV. Analysis of Infringement Allegations
’016 Patent Infringement Allegations
| Claim Element (from Independent Claim 11) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising | Teva's ANDA Product is a pharmaceutical composition in tablet form. | ¶26 | col. 38:55-60 |
| crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide | The complaint alleges that "Teva's ANDA Product contains at least some 'crystallized' binimetinib." | ¶33 | col. 37:1-8 |
| and a pharmaceutically acceptable carrier or excipient. | As a tablet formulation intended for oral use, the product necessarily contains pharmaceutically acceptable carriers and excipients. | ¶13, ¶26 | col. 38:59-60 |
’376 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a cancer is selected from melanoma...in a patient in need thereof, | Teva's proposed product label allegedly copies the indication for treating patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. | ¶39 | col. 37:28-30 |
| comprising administering to said mammal a pharmaceutical composition | The proposed label allegedly provides instructions to administer Teva's ANDA Product to patients. | ¶39, ¶43 | col. 37:30-33 |
| comprising crystallized 6-(4-bromo-2-fluorophenylamino)...amide | The complaint alleges that Teva's ANDA Product contains "crystallized" binimetinib. | ¶41 | col. 37:33-37 |
| and a pharmaceutically acceptable carrier or excipient. | The product is a tablet formulation, which contains such carriers and excipients. | ¶26 | col. 37:37-38 |
Identified Points of Contention
- Technical Question: A primary point of contention will be factual: whether the binimetinib in Teva’s ANDA product is in a "crystallized" form as that term is construed. The complaint’s allegation is stated "on information and belief" or as a bare assertion (Compl. ¶33, ¶41, ¶53), and the case will require technical evidence, such as X-ray powder diffraction (XRPD) analysis, to establish the solid-state form of Teva's active ingredient.
- Scope Questions: The dispute may involve whether Teva's product contains a different polymorph (a different crystalline structure) of binimetinib that falls outside the scope of the claims. The construction of "crystallized" will be central to resolving this question. For the method claims in the ’376 and ’944 patents, the analysis will focus on whether Teva's proposed label is sufficient to prove inducement of infringement by medical professionals and patients.
V. Key Claim Terms for Construction
- The Term: "crystallized"
- Context and Importance: This term appears in every asserted independent claim and forms the technical basis of the invention over prior art binimetinib. The patent distinguishes between the compound itself and the "crystallized" form, suggesting the crystalline nature is a key innovation (’016 Patent, col. 2:57-62). The outcome of the infringement analysis for all three patents hinges on whether Teva’s product contains binimetinib that meets the definition of this term.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification does not provide an explicit definition for "crystallized," which may support an argument for its plain and ordinary meaning: a solid material whose constituents are arranged in a highly ordered microscopic structure. The patent contrasts its "crystallized" compound with prior art materials from processes that were "disadvantageous for commercial production" (’016 Patent, col. 2:39-42), which a plaintiff might argue supports a broad construction covering any commercially viable crystalline form.
- Evidence for a Narrower Interpretation: A defendant may argue that "crystallized" is implicitly limited to the specific crystalline form or forms (polymorphs) that result from the detailed processes disclosed in the patent's examples (e.g., ’016 Patent, Example 4, col. 36). The patent includes microscopy images in Figure 2 that depict the "crystalline Compound A" produced by the new process, which could be used to argue the term is limited to a specific crystal habit or morphology (’016 Patent, Fig. 2; col. 8:55-58).
VI. Other Allegations
Indirect Infringement
For the method claims of the ’376 and ’944 patents, the complaint alleges active inducement and contributory infringement. The inducement allegation is based on the claim that Teva's proposed product labeling instructs medical professionals and patients to administer the drug for the treatment of melanoma, thereby directing them to perform the patented methods (Compl. ¶44, ¶56). The contributory infringement allegation is based on the assertion that Teva's product and its label are especially made for an infringing use and are not suitable for substantial non-infringing use (Compl. ¶46, ¶58).
Willful Infringement
The complaint does not use the term "willful," but for each patent, it pleads that "Defendant had knowledge of the...patent when it submitted ANDA No. 217509 to the FDA" (Compl. ¶32, ¶40, ¶52). This allegation of pre-suit knowledge, required by the Paragraph IV certification process, could form the basis for a later claim of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of physical characterization: does the active ingredient in Teva’s ANDA product possess the "crystallized" structure required by the asserted claims? The resolution will depend on expert testimony and scientific evidence comparing the solid-state form of Teva's product to the claimed invention.
- A key question for the method patents ('376 and '944) will be one of induced infringement: does Teva’s proposed product label, by replicating the indications of the innovator drug, provide sufficient evidence of an affirmative intent to encourage medical providers to perform the patented methods of treatment?
- An overarching question will be one of validity: as noted in the complaint, Teva has asserted that the patents are invalid for obviousness (Compl. ¶29). The court will have to determine whether the claimed crystallized form of binimetinib and the methods of its use would have been an obvious development to a person of ordinary skill in the art at the time of the invention.