DCT
3:22-cv-06968
Bristol Myers Squibb Co v. Handa Oncology LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bristol-Myers Squibb Company (Delaware)
- Defendant: Handa Oncology, LLC (California)
- Plaintiff’s Counsel: Kirkland & Ellis LLP
- Case Identification: 3:22-cv-06968, N.D. Cal., 11/07/2022
- Venue Allegations: Plaintiff alleges venue is proper in the Northern District of California because Defendant is a California entity that resides in, has committed acts of infringement in, and maintains a regular and established place of business in the district.
- Core Dispute: Plaintiff alleges that Defendant’s submission of a New Drug Application for a generic version of the cancer drug SPRYCEL® (dasatinib) constitutes an act of infringement of two patents covering a specific crystalline monohydrate form of the active pharmaceutical ingredient.
- Technical Context: The patents relate to specific, stable crystalline forms (polymorphs) of a kinase inhibitor, which is critical for ensuring consistent quality, bioavailability, and manufacturability in pharmaceutical products.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of a New Drug Application (NDA) to the FDA containing a Paragraph IV certification, asserting that Plaintiff’s patents are invalid or will not be infringed. Plaintiff received notice of this certification on or about September 26, 2022, prompting this lawsuit. The asserted patents are listed in the FDA’s Orange Book for SPRYCEL®.
Case Timeline
| Date | Event |
|---|---|
| 2004-02-06 | Earliest Priority Date for ’725 and ’103 Patents |
| 2009-02-17 | U.S. Patent No. 7,491,725 Issued |
| 2014-03-25 | U.S. Patent No. 8,680,103 Issued |
| 2022-09-26 | Plaintiff Received Defendant’s Paragraph IV Notice Letter |
| 2022-11-07 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,491,725 - Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors
- Patent Identification: U.S. Patent No. 7,491,725, issued February 17, 2009.
The Invention Explained
- Problem Addressed: The patent’s background section notes that prior methods for synthesizing the class of compounds to which dasatinib belongs presented significant drawbacks, including the production of side-products, the need for expensive reagents, and undesirable yields (’725 Patent, col. 3:5-10). In pharmaceutical development, having a well-defined and stable crystalline form of an active ingredient is crucial for consistent product performance.
- The Patented Solution: While the patent title and background focus on manufacturing processes, the asserted claims relate to a specific crystalline form of the dasatinib compound. The invention identifies and characterizes a stable crystalline monohydrate of the compound of formula (IV), which is dasatinib (Compl. p. 5). The patent provides detailed analytical data, such as X-ray powder diffraction (XRPD) patterns and thermal analysis, to uniquely define this specific solid-state form, distinguishing it from other potential forms like solvates or amorphous solids (’725 Patent, col. 25:1-34). The complaint provides a visual representation of the chemical structure of this compound (Compl. p. 5, fig. (IV)).
- Technical Importance: The discovery and characterization of a specific, stable polymorph like this monohydrate is a critical step in drug development, as it allows for reliable and repeatable manufacturing of a drug product with predictable properties such as solubility and stability (’725 Patent, col. 27:6-10).
Key Claims at a Glance
- The complaint asserts claims 3 and 12 as representative (Compl. ¶¶27, 28).
- Independent Claim 3:
- Crystalline monohydrate of the compound of formula (IV)
- which is characterized by an x-ray powder diffraction pattern (CuKα λ=1.5418 Å at a temperature of about 23° C.)
- comprising four or more 2θ values selected from the group consisting of: 18.0±0.2, 18.4±0.2, 19.2±0.2, 19.6±0.2, 21.2±0.2, 24.5±0.2, 25.9±0.2, and 28.0±0.2.
U.S. Patent No. 8,680,103 - Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors
- Patent Identification: U.S. Patent No. 8,680,103, issued March 25, 2014.
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’725 Patent, this patent addresses the same fundamental challenge: the need for a well-defined, stable, and manufacturable solid form of the dasatinib active pharmaceutical ingredient for use in a final drug product (’103 Patent, col. 2:1-14).
- The Patented Solution: This patent also claims the crystalline monohydrate of dasatinib, but defines it using a different set of highly specific physical parameters. Instead of relying on a list of XRPD peaks, the asserted claim uses crystallographic unit cell parameters derived from single-crystal X-ray analysis to define the precise three-dimensional lattice structure of the monohydrate crystal (’103 Patent, col. 6:23-28). The invention is thus the unique spatial arrangement of molecules in the solid state, which gives rise to its specific, measurable properties.
- Technical Importance: Defining a crystalline form by its unit cell parameters provides a fundamental and highly precise characterization, intended to unambiguously distinguish it from any other solid forms that might exist.
Key Claims at a Glance
- The complaint asserts claim 1 as representative (Compl. ¶29).
- Independent Claim 1:
- A pharmaceutical composition comprising a therapeutically acceptable amount of crystalline monohydrate of the compound of formula (IV)
- which is characterized by unit cell parameters approximately equal to the following: Cell dimensions: a(Å)=13.8632(7); b(Å)=9.3307(3); c(Å)=38.390(2); Volume=4965.9(4)ų
- and by Space group Pbca, Molecules/unit cell 8, and a calculated Density of 1.354 g/cm³;
- and pharmaceutically acceptable carriers, including two or more of a binder, a diluent, a disintegrant, and/or a lubricant.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Defendant Handa’s proposed generic dasatinib capsules in 20, 50, 70, 80, 100, and 140 mg dosages, for which Handa seeks FDA approval via NDA No. 217058 (the "Handa NDA Products") (Compl. ¶6).
Functionality and Market Context
- The Handa NDA Products are intended to be a generic version of Plaintiff's SPRYCEL® product, a kinase inhibitor used for treating certain types of cancer (Compl. ¶¶1, 8). The complaint alleges that upon FDA approval, Handa will manufacture and sell these products in the United States as a lower-cost alternative to the brand-name drug (Compl. ¶8). The complaint alleges that the Handa NDA Products will contain or be made using the specific crystalline monohydrate of dasatinib claimed in the patents-in-suit (Compl. ¶¶31, 35). Due to heavy redactions in the complaint, the specific factual basis for this allegation is not publicly available (Compl. ¶¶20-26).
IV. Analysis of Infringement Allegations
’725 Patent Infringement Allegations
| Claim Element (from Independent Claim 3) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Crystalline monohydrate of the compound of formula (IV) | The Handa NDA Products allegedly contain the crystalline monohydrate form of dasatinib as the active pharmaceutical ingredient. | ¶31 | col. 25:1-3 |
| which is characterized by an x-ray powder diffraction pattern ... comprising four or more 2θ values selected from the group consisting of: 18.0±0.2, 18.4±0.2, 19.2±0.2, 19.6±0.2, 21.2±0.2, 24.5±0.2, 25.9±0.2, and 28.0±0.2. | The complaint alleges that Handa seeks approval for its products which will include the crystalline monohydrate characterized by at least four of the recited XRPD peaks. | ¶30 | col. 25:11-22 |
’103 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising, a therapeutically acceptable amount of crystalline monohydrate of the compound of formula (IV) | The Handa NDA Products are alleged to be pharmaceutical compositions that comprise the claimed crystalline monohydrate of dasatinib. | ¶34 | col. 25:30-34 |
| which is characterized by unit cell parameters approximately equal to the following: Cell dimensions: a(Å)=13.8632(7); b(Å)=9.3307(3); c(Å)=38.390(2); Volume=4965.9(4)ų... | The complaint alleges that the crystalline monohydrate in the Handa NDA Products is characterized by these specific unit cell parameters. | ¶34 | col. 6:23-28 |
| and pharmaceutically acceptable carriers, including two or more of, a binder, a diluent, a disintegrant, and/or a lubricant. | The Handa NDA Products are formulated with pharmaceutically acceptable carriers. | ¶35 | col. 6:4-6 |
- Identified Points of Contention:
- Factual Question: The central dispute will likely be a factual one: does the dasatinib active ingredient in Handa’s proposed product actually exhibit the physical properties (the specific XRPD peaks of the ’725 patent and the unit cell dimensions of the ’103 patent) required by the claims? The heavily redacted sections of the complaint obscure the evidence Plaintiff possesses on this point, making discovery critical (Compl. ¶¶20-26).
- Scope Questions: The term "approximately equal to" in claim 1 of the ’103 patent introduces a question of claim scope. The parties may dispute how much deviation from the recited crystallographic values is permissible for a finding of infringement. Similarly, for the ’725 patent, the use of "about 23° C." for the temperature and "±0.2" for the 2θ values raises questions about the intended precision of these measurements.
V. Key Claim Terms for Construction
- The Term: "approximately equal to"
- Context and Importance: This term, appearing in claim 1 of the ’103 Patent, governs the standard for infringement of the unit cell parameter limitations. Its construction is critical because crystallographic measurements can have inherent variability. Practitioners may focus on this term because its interpretation will define the boundary between a non-infringing variant and an infringing equivalent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification of the related ’725 Patent, incorporated by reference, states that an "X-ray diffraction pattern may be obtained with a measurement error" and that patterns should be considered "substantially identical," not necessarily perfectly identical (’725 Patent, col. 42:1-14). This language may support a construction that allows for some reasonable measurement tolerance.
- Evidence for a Narrower Interpretation: The claim recites the unit cell parameters to four decimal places and provides a specific parenthetical error for each (e.g., "a(Å)=13.8632(7)"), which may suggest the patentee intended a very high degree of precision, limiting the scope of "approximately." The patent’s detailed description of multiple distinct crystalline forms (e.g., butanol solvate, ethanol solvate) could be used to argue that small structural differences matter and the claims should be read narrowly to capture only the specific form defined (’725 Patent, col. 25-26).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Handa will induce and contribute to infringement. The inducement allegations are based on the knowledge that Handa’s promotional materials and product package inserts will instruct medical professionals and patients to use the infringing products in a manner that directly infringes (Compl. ¶¶47, 59). Contributory infringement is alleged on the basis that Handa's products are especially made for an infringing use and are not staple articles of commerce suitable for substantial non-infringing use (Compl. ¶¶45, 57).
- Willful Infringement: The complaint does not explicitly allege "willful infringement" but does request a finding that this is an "exceptional case" under 35 U.S.C. § 285, which would entitle Plaintiff to an award of attorneys' fees (Compl. ¶¶50, 62). The basis for this allegation appears to be Handa's act of filing an NDA with a Paragraph IV certification, which demonstrates knowledge of the patents-in-suit prior to engaging in the commercial activities that would follow an FDA approval (Compl. ¶39).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary question will be one of physical identity: Will discovery reveal that the crystalline form of dasatinib in Defendant's proposed generic product possesses the specific X-ray diffraction peaks and unit cell dimensions recited in the asserted claims, or is it a different, non-infringing polymorph? The redacted infringement allegations suggest this factual determination will be the core of the dispute.
- A key legal question will be one of definitional scope: How will the court construe the term "approximately equal to" from the ’103 patent? The resolution of this claim construction issue will directly impact the infringement analysis by setting the legal standard for how closely Defendant’s product must match the patent’s crystallographic data to be found infringing.