DCT
1:24-cv-01244
Pfizer Inc v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Pfizer Inc. (Delaware) and PF Prism Imb BV. (Netherlands)
- Defendant: Sandoz Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Williams & Connolly LLP
- Case Identification: 1:24-cv-01244, D. Del., 11/12/2024
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Sandoz Inc. is a Delaware corporation and is subject to personal jurisdiction in the district.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug Inlyta® (axitinib) constitutes an act of infringement of a patent covering specific crystalline forms of the active ingredient.
- Technical Context: The lawsuit concerns pharmaceutical polymorphism, a field where the specific crystalline structure of an active pharmaceutical ingredient can significantly impact its stability, manufacturability, and therapeutic performance.
- Key Procedural History: This action was filed under the Hatch-Waxman Act, triggered by Sandoz’s submission of ANDA No. 219705 with a Paragraph IV certification. This certification alleges that U.S. Patent No. 8,791,140 is invalid, unenforceable, or will not be infringed by Sandoz's proposed generic product. The complaint was filed within the 45-day window following receipt of Sandoz's notice letter, initiating the litigation.
Case Timeline
| Date | Event |
|---|---|
| 2007-04-05 | '140 Patent Priority Date |
| 2012-01-27 | FDA Approval of Inlyta® (axitinib) |
| 2014-07-29 | '140 Patent Issue Date |
| 2024-10-01 | Sandoz sends Paragraph IV Notice Letter to Pfizer |
| 2024-11-12 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,791,140 - "Crystalline Forms of 6-[2-(METHYLCARBAMOYL)PHENYLSULFANYL]-3-E-[2-(PYRIDIN-2-YL) ETHENYONDAZOLE SUITABLE FOR THE TREATMENT OF ABNORMAL CELL GROWTH IN MAMMALS"
The Invention Explained
- Problem Addressed: The patent addresses the challenge that different solid-state forms of the same chemical compound can have varying physical properties. For pharmaceutical development, it is desirable to identify and control the specific form of a drug substance to ensure reliable and consistent manufacturing, formulation, and stability ('140 Patent, col. 2:15-18, 2:31-39).
- The Patented Solution: The invention identifies and claims novel polymorphic (crystalline) forms of the compound axitinib. These specific forms are distinguished from each other and from amorphous forms by their unique crystal lattice structures, which result in characteristic and reproducible powder X-ray diffraction (PXRD) patterns ('140 Patent, Abstract; col. 2:56-64). For example, Figure 6 of the patent displays a PXRD graph with a unique pattern of peaks that corresponds to the claimed "Form XLI" polymorph ('140 Patent, Fig. 6).
- Technical Importance: Controlling the polymorphic form of a drug is critical because properties like solubility and stability can directly affect a drug's bioavailability and shelf life, making the identification of a stable, manufacturable form a key step in pharmaceutical development ('140 Patent, col. 2:39-46).
Key Claims at a Glance
- The complaint asserts claims 1-6, with a specific infringement example for independent claim 1 ('140 Patent, col. 35:14-24; Compl. ¶¶32, 34).
- Independent Claim 1 requires:
- A crystalline form of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole (axitinib);
- Wherein the crystalline form has a powder X-ray diffraction pattern comprising a peak at a diffraction angle (2θ) of 6.0±0.1; and
- Further comprising at least one peak at a diffraction angle (2θ) selected from the group consisting of 11.5±0.1, 21.0±0.1, and 26.9±0.1.
- The complaint alleges infringement of dependent claims 2-6, which add further limitations defining the specific crystalline form by requiring additional PXRD peaks or by defining the form through solid-state NMR chemical shifts ('140 Patent, col. 35:25-50; Compl. ¶34).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Sandoz's generic axitinib tablets, 1 mg and 5 mg, as described in Abbreviated New Drug Application (ANDA) No. 219705 ("Sandoz's ANDA Product") (Compl. ¶¶1-2).
Functionality and Market Context
The Sandoz product is a proposed generic equivalent to Pfizer's branded drug Inlyta®, which is approved for the treatment of advanced renal cell carcinoma (Compl. ¶17). The technical functionality central to the dispute is the solid-state crystalline structure of the axitinib active pharmaceutical ingredient contained within the proposed generic tablets (Compl. ¶33). By filing an ANDA, Sandoz seeks FDA approval to market its generic product prior to the expiration of the '140 Patent, which is listed in the FDA's Orange Book in connection with Inlyta® (Compl. ¶¶18, 20).
IV. Analysis of Infringement Allegations
'140 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| [a] crystalline form of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl] indazole | Sandoz's ANDA Product is alleged to contain this specific crystalline compound. | ¶33 | col. 35:15-18 |
| wherein said crystalline form has a powder X-ray diffraction pattern comprising a peak at diffraction angle (20) of 6.0±0.1 | The complaint alleges that the Sandoz ANDA Product has a PXRD pattern that includes this specific peak. | ¶33 | col. 4:50-61 |
| and further comprising at least one peak at diffraction angle (20) selected from 11.5±0.1, 21.0±0.1 and 26.9±0.1. | The complaint alleges the Sandoz ANDA Product's PXRD pattern further includes at least one peak from this specified group. | ¶33 | col. 4:50-61 |
Identified Points of Contention
- Technical Questions: The core of the infringement dispute will be a highly technical and factual question: does the crystalline form of axitinib in Sandoz's ANDA Product actually exhibit the specific combination of PXRD peaks required by the asserted claims? The complaint makes a direct allegation but does not provide the underlying analytical data from Sandoz's ANDA to support this conclusion (Compl. ¶¶33, 27). The case will likely depend on expert analysis of competing PXRD data for the accused product. No probative visual evidence provided in complaint.
- Scope Questions: The open-ended transition term "comprising" in Claim 1 raises a potential scope question. If Sandoz's product exhibits the required peaks but also contains additional, prominent peaks not characteristic of the polymorph described in the patent, a question may arise as to whether the product is in fact a different, non-infringing polymorph that happens to share some spectral features.
V. Key Claim Terms for Construction
Term: "crystalline form"
Context and Importance: This term is foundational to all asserted claims. Its construction is critical because pharmaceutical compounds can exist in various states, including fully crystalline, fully amorphous (non-crystalline), or as mixtures. Practitioners may focus on this term because Sandoz could argue its product contains sufficient amorphous content or is a different polymorphic form, thereby falling outside the scope of the claimed "crystalline form."
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent defines "crystalline" as "any solid substance exhibiting three-dimensional order, which... gives a distinctive XRPD pattern with sharply defined peaks" ('140 Patent, col. 13:20-24). This functional definition could support an argument that any product meeting this test is a "crystalline form."
- Evidence for a Narrower Interpretation: The patent explicitly distinguishes crystalline forms from "amorphous" forms, which "lack[s] order in three dimensions" ('140 Patent, col. 13:4-5). This distinction could support an argument that the term requires a high degree of crystallinity and does not read on products that are partially amorphous or contain a mixture of forms.
Term: "a peak at diffraction angle (2θ) of 6.0±0.1"
Context and Importance: The numerical ranges with "±" tolerances are the specific technical limitations that define the patented invention. The construction of this tolerance (e.g., "±0.1") will be central to determining whether PXRD data from the Sandoz product literally meets the claim requirements.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification notes that with PXRD, "typical peak position and intensity variability are taken into account" and that peak positions can show variability of "as much as 0.1 to 0.2 degrees" depending on various factors ('140 Patent, col. 12:31-36). A party could argue this context supports a reading that the claimed "±0.1" is not an absolute, rigid boundary.
- Evidence for a Narrower Interpretation: A party could argue that the patentees deliberately chose the specific "±0.1" tolerance in the claim language itself, distinguishing it from the more general discussion of "0.1 to 0.2" degrees of variability in the specification. This would suggest the claim scope is strictly limited to the recited tolerance.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Sandoz will induce and contribute to infringement upon approval of its ANDA. The inducement allegation is based on Sandoz's alleged intent for its product to be used in an infringing manner, with knowledge of the '140 patent (Compl. ¶¶38-39). The contributory infringement allegation is based on the assertion that Sandoz's product is especially made for an infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶40).
- Willful Infringement: The complaint alleges that Sandoz acted with "full knowledge of the '140 patent" and without a reasonable basis for believing it would not be liable (Compl. ¶42). This allegation is based on Sandoz's act of sending a Paragraph IV notice letter, which demonstrates pre-suit knowledge of the patent being challenged (Compl. ¶¶2, 11).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: What will expert analysis of the Sandoz ANDA product's powder X-ray diffraction data reveal? The entire infringement case rests on whether this data confirms the complaint's allegation that the product's crystalline structure falls within the specific numerical boundaries defined by Claim 1.
- The case may also turn on a question of holistic versus elemental claim interpretation: Is the presence of the few PXRD peaks recited in Claim 1 sufficient for infringement under the "comprising" standard, or can Sandoz successfully argue that its product represents a different, non-infringing polymorph if its overall PXRD pattern differs from the Form XLI polymorph disclosed in the patent?
- Finally, an underlying issue inherent in any Hatch-Waxman case is validity: Can Sandoz prove by clear and convincing evidence that the '140 patent's claims to this specific polymorph are invalid, as it asserted in its Paragraph IV certification, potentially on grounds such as obviousness over prior art forms or lack of adequate written description?