Pfizer Inc v. Apotex Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Pfizer Inc. (Delaware); C.P. Pharmaceuticals International C.V. (Netherlands); PF Prism CV. (Netherlands); PBG Puerto Rico LLC (Puerto Rico); and PF Prism Imb BV. (Netherlands)
  • Defendant: Apotex Inc. (Canada) and Apotex Corp. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Arnold & Porter Kaye Scholer LLP; DLA Piper LLP (US)
• Case Identification: 1:23-cv-00445, D. Del., 04/21/2023
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Apotex Corp. is a Delaware corporation and because the Defendants' proposed generic products will, upon approval, be marketed and distributed in Delaware.
• Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) seeking to market generic versions of Plaintiff's Xeljanz® (tofacitinib) tablets constitutes an act of infringement of a patent covering the tofacitinib compound itself.
• Technical Context: The technology at issue involves a small molecule compound, tofacitinib, which functions as a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases such as rheumatoid arthritis.
• Key Procedural History: The patent-in-suit is a reissue of an earlier patent and its expiration date was extended by the USPTO to December 8, 2025. The lawsuit was triggered by Apotex’s Paragraph IV certification, filed with its ANDA, asserting that the patent is invalid and/or unenforceable. The complaint notes that Apotex's notification letter did not include an argument for non-infringement.

Case Timeline

II. Technology and Patent(s)-in-Suit Analysis

U.S. Reissue Patent No. RE41,783 - Pyrrolo[2,3-d]pyrimidine Compounds

The Invention Explained

• Problem Addressed: The patent identifies a need for new immunosuppressive agents to treat a range of conditions, including organ transplant rejection and autoimmune diseases like rheumatoid arthritis and psoriasis (RE’783 Patent, col. 5:11-24).
• The Patented Solution: The invention discloses a class of compounds built on a pyrrolo[2,3-d]pyrimidine chemical scaffold that inhibit protein kinases, particularly Janus Kinase 3 (JAK3) (RE’783 Patent, Abstract). Because JAK3 expression is primarily limited to immune cells, inhibiting it provides a targeted way to modulate immune system activity, which is useful in treating T-cell proliferative disorders (RE’783 Patent, col. 5:26-42).
• Technical Importance: The invention provided a novel therapeutic strategy by selectively targeting the JAK3 signaling pathway, which is essential for the function and maturation of specific lymphocytes involved in the immune response (RE’783 Patent, col. 5:37-42).

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 4 (Compl. ¶39).
• Claim 4 consists of the following elements:
  • A compound with the chemical name "3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile"
  • or a pharmaceutically acceptable salt thereof

III. The Accused Instrumentality

Product Identification

Apotex's 5 mg and 10 mg generic tablets, which are proposed generic versions of Pfizer's Xeljanz® product (Compl. ¶2). The active ingredient is identified as tofacitinib citrate (Compl. ¶19).

Functionality and Market Context

The accused instrumentalities are generic drugs intended to be therapeutically equivalent to Pfizer's branded Xeljanz® tablets (Compl. ¶31). The act of infringement alleged in the complaint is the submission of ANDA No. 281096 to the FDA, which seeks approval to market these generic tablets prior to the expiration of the RE’783 patent (Compl. ¶39). The complaint states that the FDA-approved chemical name for tofacitinib citrate is "(3R,4R)-4-methyl-3-(methyl-7H-pyrrolo [2,3-d] pyrimidin-4-ylamino)-ß-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-propanetricarboxylate (1:1)", which corresponds to a citrate salt of the compound claimed in the RE’783 patent (Compl. ¶20). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

RE41,783 Infringement Allegations

Identified Points of Contention

• Validity vs. Infringement: The complaint alleges that Apotex's Paragraph IV notification letter asserts that all claims of the RE’783 patent are invalid but "does not contain a noninfringement argument" (Compl. ¶¶33, 35). This suggests the primary dispute in the case may concern the patent's validity, rather than whether Apotex's product infringes.
• Technical Questions: The central technical question for infringement is one of direct identity: does the active pharmaceutical ingredient in Apotex's ANDA product, tofacitinib citrate, meet the definition of the specific compound recited in claim 4 or a "pharmaceutically acceptable salt thereof"? The complaint alleges that it does (Compl. ¶¶19-20).

V. Key Claim Terms for Construction

• The Term: "pharmaceutically acceptable salt thereof"
• Context and Importance: The infringement analysis depends on whether tofacitinib citrate, the active ingredient in Apotex's proposed product, is considered a "pharmaceutically acceptable salt" of the base compound recited in claim 4. Practitioners may focus on this term as it directly links the accused product to the claim language.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent specification provides a non-exhaustive list of acids that can be used to form such salts, explicitly including "citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate," among many others (RE’783 Patent, col. 6:5-11). This explicit inclusion of citrate may support an interpretation that covers Apotex's product.
  • Evidence for a Narrower Interpretation: The complaint and the patent's intrinsic record do not present obvious evidence for a narrow construction of this term. An argument for a narrower scope would likely need to rely on extrinsic evidence or a specific disclaimer during patent prosecution, which is not referenced in the complaint.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Apotex Corp. induced the infringement of Apotex Inc. (Compl. ¶¶51-52). This claim focuses on the inter-company actions leading to the filing of the ANDA itself, alleging Apotex Corp. knowingly caused or directed the submission of the ANDA by Apotex Inc., which constitutes the statutory act of infringement under 35 U.S.C. § 271(e)(2)(A).
• Willful Infringement: The complaint alleges that Apotex had pre-suit knowledge of the RE’783 patent at the time it submitted its ANDA (Compl. ¶¶40, 46). This allegation is based on Apotex's filing of a Paragraph IV certification, which is a required part of the ANDA process when a listed patent exists.

VII. Analyst’s Conclusion: Key Questions for the Case

• A core issue will be one of validity: Given the complaint's assertion that Apotex's challenge focuses on invalidity without a corresponding non-infringement argument, the case will likely center on whether claim 4 of the RE’783 patent is valid over the prior art and meets other statutory requirements.
• A secondary question is one of infringement by identity: Although infringement appears to be factually straightforward based on the complaint, the court will still need to resolve whether Apotex's tofacitinib citrate product is, in fact and law, the compound claimed in claim 4 or a "pharmaceutically acceptable salt thereof."
• Finally, a key question for remedies will be exceptionality: Will Apotex's conduct in challenging the patent, particularly its decision to proceed despite its apparent concession on infringement, be deemed to make the case "exceptional" under 35 U.S.C. § 285, potentially exposing it to an award of Pfizer's attorneys' fees?