DCT
1:24-cv-00818
Bristol-Myers Squibb Company v. Apotex Inc.
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bristol-Myers Squibb Company (Delaware) and Receptos LLC (Delaware)
- Defendant: Apotex Inc. (Canada)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:24-cv-00818, D. Del., 07/15/2024
- Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign corporation subject to personal jurisdiction in the district, has systemic contacts with the jurisdiction, derives substantial revenue from sales in Delaware, and has previously availed itself of the court by filing other lawsuits in the district.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs’ Zeposia® drug product constitutes an act of infringement of a patent covering a specific crystalline form of the active ingredient, ozanimod hydrochloride.
- Technical Context: The case involves pharmaceutical formulation, where the specific crystalline structure (polymorph) of an active ingredient is critical for ensuring the drug's stability, dissolution profile, and manufacturing consistency.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a Notice Letter from the Defendant. In the letter, Defendant provided a certification under 21 U.S.C. § 355(j)(2)(A)(vii)(IV) (a "Paragraph IV certification") asserting that the patent-in-suit is invalid, which triggered the current litigation.
Case Timeline
| Date | Event |
|---|---|
| 2016-06-14 | ’050 Patent Priority Date |
| 2023-06-20 | ’050 Patent Issue Date |
| 2024-06-03 | Date of Defendant's Notice Letter |
| 2024-07-15 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,680,050 - "Crystalline Forms of Ozanimod and Ozanimod Hydrochloride, and Processes for Preparation Thereof"
- Patent Identification: U.S. Patent No. 11,680,050, “Crystalline Forms of Ozanimod and Ozanimod Hydrochloride, and Processes for Preparation Thereof,” issued June 20, 2023.
The Invention Explained
- Problem Addressed: The patent's background section describes the challenge that a pharmaceutically active substance must possess consistent and stable physicochemical properties to be suitable for commercial drug production. It notes that different solid-state forms of a compound can vary significantly in critical attributes like solubility, stability, and hygroscopicity (tendency to absorb moisture), which can impact a drug's efficacy and shelf-life. The patent states that prior art had not disclosed or suggested any specific crystalline forms of ozanimod. (’050 Patent, col. 2:20-49).
- The Patented Solution: The invention discloses novel, stable crystalline forms of the compound ozanimod and its hydrochloride salt. The patent describes a specific crystalline form of ozanimod hydrochloride, designated "Form CS1," which is identified by a unique signature in its X-ray powder diffraction (XRPD) pattern. This specific form is presented as providing a stable and reliable substance for use in pharmaceutical compositions. (’050 Patent, Abstract; col. 7:13-19).
- Technical Importance: Developing a stable, non-hygroscopic, and well-characterized crystalline form of a drug substance is a critical step in pharmaceutical development, as it allows for predictable manufacturing, consistent dosing, and reliable long-term storage of the final drug product. (’050 Patent, col. 2:20-38).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2-3, 5, and 7. (Compl. ¶23).
- Independent Claim 1 requires:
- A crystalline Form CS1 of ozanimod hydrochloride,
- wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 26.1°±0.20°, 24.4°±0.20° and 20.1°±0.20°
- using CuKα radiation.
- The complaint reserves the right to assert additional claims. (Compl. ¶27).
III. The Accused Instrumentality
Product Identification
- The "Apotex ANDA Product," which is the subject of Abbreviated New Drug Application No. 219450 submitted to the FDA. (Compl. ¶1).
Functionality and Market Context
- The accused product is a generic version of Plaintiffs' Zeposia® drug, intended for the same medical indications. (Compl. ¶¶2, 22).
- It is formulated as capsules containing 0.23 mg, 0.46 mg, or 0.92 mg of the active ingredient ozanimod. (Compl. ¶2).
- The complaint alleges that by filing its ANDA, Apotex has represented to the FDA that its product has the same active ingredient, dosage form, and is bioequivalent to Zeposia®. (Compl. ¶21).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
Claim Chart Summary
- The complaint alleges that Apotex's ANDA product, if approved and marketed, will infringe at least Claim 1 of the ’050 patent. The core allegations are summarized below.
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A crystalline Form CS1 of ozanimod hydrochloride, | The complaint alleges that the Apotex ANDA Product contains a crystalline Form CS1 of ozanimod hydrochloride. | ¶32 | col. 7:13-14 |
| wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 26.1°±0.20°, 24.4°±0.20° and 20.1°±0.20° | The complaint alleges that the X-ray powder diffraction pattern of the crystalline form in the accused product shows these characteristic peaks at the specified 2theta values. | ¶32 | col. 7:15-19 |
| using CuKα radiation. | The complaint alleges that the diffraction pattern is measured using CuKα radiation. | ¶31-32 | col. 7:15-19 |
Identified Points of Contention
- Infringement vs. Validity: The primary point of contention appears to be validity, not infringement. The complaint alleges that Apotex’s Notice Letter "does not contest that the commercial manufacture, use, offer to sell, sale, and/or importation of the Apotex ANDA Product will infringe" the asserted claims, but instead asserts that the claims are invalid under 35 U.S.C. §§ 102 and 103. (Compl. ¶23).
- Technical Questions: A central technical question will be evidentiary: does the analytical data for the Apotex ANDA Product, submitted to the FDA, show an XRPD pattern that meets the specific peak requirements of Claim 1? The complaint's allegation that infringement is uncontested suggests the data will likely confirm the presence of these peaks.
V. Key Claim Terms for Construction
- The Term: "crystalline Form CS1 of ozanimod hydrochloride"
- Context and Importance: This term defines the entire scope of Claim 1. The dispute will turn on whether the accused product is, in fact, this specific patented crystalline form. Practitioners may focus on this term because infringement in polymorph cases is a question of identity, determined by comparing the physical characteristics of the accused product with those defined in the patent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Plaintiffs may argue that the claim language itself provides the complete definition. Claim 1 defines "Form CS1" by the presence of three specific XRPD peaks within a given tolerance (±0.20°). An argument could be made that any crystalline form of ozanimod hydrochloride exhibiting these three peaks infringes, regardless of what other peaks may or may not be present in its full diffraction pattern.
- Evidence for a Narrower Interpretation: A defendant could argue that "Form CS1" is a holistic term that must be construed in light of the entire specification, including the examples and figures. The patent discloses a full XRPD pattern for Form CS1 (e.g., in FIG. 20 and Table 9) that contains many more peaks than the three recited in Claim 1. An argument could be made that the term is limited to the specific polymorph disclosed in the embodiments, which must substantially match the full pattern, not just a subset of three peaks.
VI. Other Allegations
Indirect Infringement
- The complaint alleges that upon FDA approval, Apotex would induce infringement by "encouraging the use of the Apotex ANDA Product in accordance with its proposed label" (Compl. ¶34) and would contributorily infringe because the product is a material part of the invention and not a staple article of commerce (Compl. ¶37).
Willful Infringement
- Willfulness is alleged based on pre-suit knowledge of the ’050 patent. The complaint states the patent is listed in the FDA's Orange Book for Zeposia® and that Apotex cited the patent in its Notice Letter, establishing knowledge prior to the infringing act of filing the ANDA. (Compl. ¶35). It further alleges Apotex is "willfully blind" to the fact that use of its product will infringe. (Compl. ¶36).
VII. Analyst’s Conclusion: Key Questions for the Case
Given that the complaint alleges infringement is not contested by the Defendant, the litigation will likely focus on the affirmative defense of invalidity. The key questions for the court appear to be:
A central issue will be one of validity: Are the claims to "crystalline Form CS1" valid over the prior art? The case will likely depend on whether Apotex can prove, by clear and convincing evidence, that this specific crystalline form was anticipated (§ 102) or rendered obvious (§ 103) by earlier disclosures.
A secondary question, which may influence the validity analysis, is one of definitional scope: Does the claim to "Form CS1," which is defined by only three characteristic XRPD peaks, properly distinguish the patented polymorph from other potential forms or the prior art? The court’s construction of this term will be critical in determining the breadth of the claim and its vulnerability to invalidity challenges.