DCT
3:23-cv-21098
Bristol Myers Squibb Co v. Zydus Pharma USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bristol-Myers Squibb Company (Delaware)
- Defendant: Zydus Pharmaceuticals (USA) Inc. (New Jersey) and Zydus Lifesciences Limited (India)
- Plaintiff’s Counsel: Walsh Pizzi Oreilly Falanga LLP
- Case Identification: 3:23-cv-21098, D.N.J., 10/12/2023
- Venue Allegations: Venue for Zydus Pharmaceuticals (USA) Inc. is based on its incorporation and principal place of business in New Jersey. Venue for Zydus Lifesciences Limited, a foreign corporation, is alleged based on its not residing in any U.S. judicial district and its past litigation conduct within the District of New Jersey.
- Core Dispute: Plaintiff alleges that Defendants' Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's SPRYCEL® (dasatinib) tablets constitutes an act of infringement of patents covering crystalline forms of the drug and processes for its manufacture.
- Technical Context: The technology concerns pharmaceutical solid-state chemistry, specifically the crystalline structure of dasatinib, a kinase inhibitor used in cancer therapies, and methods for its synthesis.
- Key Procedural History: This Hatch-Waxman action was initiated after Plaintiff received a Paragraph IV certification letter from Zydus, dated on or about September 7, 2023, asserting that the patents-in-suit are invalid or will not be infringed by Defendants' proposed generic product.
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 |
| 2023-09-07 | Zydus Sends Paragraph IV Letter to BMS (approximate) |
| 2023-10-12 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,680,103
- Patent Identification: U.S. Patent No. 8,680,103, "Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors," issued March 25, 2014. (Compl. ¶27).
The Invention Explained
- Problem Addressed: The patent's prosecution history, which it shares with the '725 patent, notes that prior art methods for synthesizing the subject kinase inhibitors suffered from drawbacks including side-product formation, use of expensive reagents, and low yields. ('725 Patent, col. 3:5-10).
- The Patented Solution: The invention described in the '103 patent family provides efficient processes for preparing 2-aminothiazole-5-aromatic carboxamides. ('725 Patent, col. 3:33-54). The '103 patent specifically claims pharmaceutical compositions comprising a crystalline monohydrate form of the active compound (dasatinib), which is characterized by specific unit cell parameters and a distinct X-ray diffraction pattern, providing a stable and reproducible form of the drug for formulation. ('103 Patent, Abstract; col. 25:2-34).
- Technical Importance: Identifying and controlling a specific, stable crystalline form (polymorph) of a drug is critical for ensuring consistent purity, solubility, and bioavailability in a pharmaceutical product. ('103 Patent, col. 25:35-46).
Key Claims at a Glance
- The complaint alleges infringement of at least one claim. (Compl. ¶47).
- Independent Claim 1, selected as representative, contains the following essential elements:
- A pharmaceutical composition comprising,
- A therapeutically acceptable amount of crystalline monohydrate of the compound of formula (IV),
- Wherein the crystalline monohydrate is characterized by specific, enumerated unit cell parameters,
- And pharmaceutically acceptable carriers, including two or more from the group of a binder, a diluent, a disintegrant, and/or a lubricant. ('103 Patent, col. 50:15-32).
- The complaint does not explicitly reserve the right to assert dependent claims, but the general allegation of infringing "at least one claim" may encompass them. (Compl. ¶47).
Multi-Patent Capsule: U.S. Patent No. 7,491,725
- Patent Identification: U.S. Patent No. 7,491,725, "Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors," issued February 17, 2009. (Compl. ¶26).
- Technology Synopsis: This patent, a parent to the '103 patent, addresses the need for efficient synthesis of 2-aminothiazole-5-aromatic carboxamides, a class of kinase inhibitors. It discloses novel chemical processes that provide high yields while avoiding undesirable side-reactions. ('725 Patent, col. 3:5-10, 33-54). The patent also claims distinct crystalline forms of the final compound, including butanol and ethanol solvates. ('725 Patent, col. 26:1-10).
- Asserted Claims: The complaint alleges infringement of at least one claim. (Compl. ¶35).
- Accused Features: The complaint alleges that the future manufacture, use, offer for sale, or sale of the Zydus ANDA Products will infringe the '725 patent. (Compl. ¶¶37-42).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are "Zydus's 20 mg, 50, mg, 70 mg, 80 mg, 100 mg, and 140 mg dasatinib oral tablets" for which Zydus submitted ANDA No. 218719. (Compl. ¶¶9-10).
Functionality and Market Context
The Zydus ANDA Products are proposed generic versions of Bristol-Myers Squibb's SPRYCEL® (dasatinib), a kinase inhibitor used for treating certain types of cancer. (Compl. ¶¶1, 28). The act of infringement alleged is the submission of the ANDA to the FDA, which seeks approval to market these tablets prior to the expiration of the patents-in-suit. (Compl. ¶¶35, 47). The complaint alleges that Zydus's ANDA relies on the clinical data of SPRYCEL® and contains data intended to demonstrate bioequivalence. (Compl. ¶33). The '103 Patent, included as an exhibit to the complaint, provides a powder X-ray diffraction (PXRD) pattern for the claimed crystalline monohydrate form of dasatinib. (Compl. Ex. 2, '103 Patent, FIG. 1).
IV. Analysis of Infringement Allegations
The complaint does not provide specific factual allegations mapping claim elements to the accused product, instead relying on the statutory act of infringement created by the ANDA filing. The following chart is based on the implicit allegation that the Zydus ANDA product is a generic equivalent of SPRYCEL® and therefore embodies the patented invention.
'103 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising, | The Zydus ANDA Products are alleged to be pharmaceutical compositions in the form of oral tablets. | ¶10 | col. 32:3-33 |
| 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); | The complaint alleges that the '103 patent covers the SPRYCEL® product, and that the Zydus ANDA Products are a generic version, implying the tablets contain the claimed crystalline monohydrate of dasatinib. | ¶¶1, 30, 49 | col. 25:2-20 |
| and pharmaceutically acceptable carriers, including two or more of, a binder, a diluent, a disintegrant, and/or a lubricant. | The Zydus ANDA Products are described as "oral tablets," which by their nature contain pharmaceutically acceptable carriers and excipients. | ¶10 | col. 32:3-33 |
- Identified Points of Contention:
- Technical Question: A primary factual dispute will concern whether the crystalline form of dasatinib in Zydus's ANDA product is structurally identical to the monohydrate claimed in the '103 patent. This will likely be resolved through competing expert analysis of characterization data (e.g., PXRD, DSC) obtained during discovery.
- Scope Question: Should discovery reveal minor differences between Zydus's crystalline form and the patent's description, the case may turn on the construction of "approximately equal to." This raises the question of how much deviation from the recited unit cell parameters is permissible before a product is considered non-infringing.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for a full analysis of potential claim construction disputes. However, based on the technology, the following term will be critical.
- The Term: "crystalline monohydrate ... characterized by unit cell parameters approximately equal to the following..." ('103 Patent, cl. 1)
- Context and Importance: This term defines the scope of the patented polymorph. The interpretation of "approximately equal to" is central to the infringement analysis, as it dictates the degree of structural variation allowed between an accused product and the claimed invention. Practitioners may focus on this term because nearly all infringement disputes over patented crystalline forms involve arguments over whether the accused form is the same as, or different from, the claimed form.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent itself uses qualifying language, stating a form is characterized by a PXRD pattern "substantially in accordance with that shown in FIG. 1," which may support an interpretation that the claims are not limited to a mathematically exact match. ('103 Patent, col. 26:63-65). The plain meaning of "approximately" suggests some tolerance for deviation.
- Evidence for a Narrower Interpretation: The patent provides highly specific numerical values for the unit cell parameters, down to four or five significant figures. ('103 Patent, col. 25:13-20). A party could argue that this high degree of precision was intended to narrowly define the invention, limiting the scope of "approximately" to measurement error and not to encompass structurally distinct, albeit similar, crystalline forms.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement on the basis that Zydus's future "promotional activities and package inserts" for its ANDA products will instruct or encourage direct infringement by end-users. (Compl. ¶¶41, 53). Contributory infringement is alleged on the grounds that the Zydus ANDA products are "especially made or adapted for use in infringing" the patents and are not staple articles of commerce. (Compl. ¶¶39, 51).
- Willful Infringement: The complaint does not use the term "willful," but it alleges that Zydus had knowledge of the patents-in-suit, at the latest, upon sending its Paragraph IV certification letter. (Compl. ¶34). It further pleads that the case is "exceptional" under 35 U.S.C. § 285, which forms the basis for a request for attorneys' fees. (Compl. ¶¶44, 56).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of structural identity: does the dasatinib in Zydus’s proposed generic product exist in the specific crystalline monohydrate form claimed in the ’103 patent? The answer will depend on factual evidence developed through discovery and presented by technical experts.
- The case may also turn on a question of definitional scope: what is the permissible range of structural variation encompassed by the claim term "approximately equal to"? The court's construction of this term will be critical if Zydus's product is found to be similar, but not identical, to the patented crystalline form.