Pfizer Inc v. Sun Pharmaceutical Industries Ltd

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: Sun Pharmaceutical Industries Limited (India) and Sun Pharmaceutical Industries, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:23-cv-00718, D. Del., 06/30/2023
• Venue Allegations: Venue is asserted based on Defendant Sun Pharmaceutical Industries, Inc. being a Delaware corporation and the parent company's alleged intent to market and sell the accused generic drug in Delaware upon FDA approval.
• Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) for a generic version of the drug Xeljanz® (tofacitinib) constitutes an act of infringement of a patent covering the tofacitinib compound itself.
• Technical Context: The technology involves a specific class of chemical compounds, pyrrolo[2,3-d]pyrimidines, which function as Janus Kinase (JAK) inhibitors for the treatment of autoimmune diseases such as rheumatoid arthritis.
• Key Procedural History: The patent-in-suit, U.S. Patent No. RE41,783, is a reissue of an earlier patent and is listed in the FDA's "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book") for Pfizer's Xeljanz®. The lawsuit was triggered by Defendant's submission of a Paragraph IV certification with its ANDA, asserting the patent is invalid, unenforceable, or will not be infringed by its proposed generic product.

Case Timeline

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

U.S. Reissue Patent No. RE41,783 - “Pyrrolo[2,3-d]pyrimidine Compounds,” issued September 28, 2010

The Invention Explained

• Problem Addressed: The patent addresses the need for therapeutic agents that can suppress the immune system to treat a range of conditions, including organ transplant rejection and autoimmune diseases like rheumatoid arthritis (RE’783 Patent, col. 5:12-16, 39-42).
• The Patented Solution: The invention provides a class of chemical compounds, specifically pyrrolo[2,3-d]pyrimidines, designed to inhibit the Janus Kinase 3 (JAK3) enzyme (RE’783 Patent, Abstract). The patent explains that JAK3 plays an essential role in signaling pathways for immune cells, and by blocking this enzyme, the claimed compounds can modulate immune activity (RE’783 Patent, col. 5:26-39).
• Technical Importance: The selective targeting of JAK3, which has an expression pattern largely limited to hematopoietic (blood and immune) cells, represented a novel mechanism for immunosuppression that could potentially offer a more targeted therapeutic effect compared to broader-acting agents (RE’783 Patent, col. 5:26-28).

Key Claims at a Glance

• The complaint asserts infringement of "at least claim 4" (Compl. ¶40). Claim 4 is dependent on claim 3, which in turn depends on claims 1 and 2. The relevant independent claim is Claim 1.
• Independent Claim 1 defines a genus of chemical compounds with the core structure of a pyrrolo[2,3-d]pyrimidine, defined by the following essential elements:
  • A compound of a specified core chemical formula (Formula I) or its pharmaceutically acceptable salt.
  • Wherein substituent R¹ is a group of a specified formula containing a piperidinyl ring (R⁵).
  • Wherein R² and R³ are hydrogen.
  • Wherein the piperidinyl ring (R⁵) is substituted with one or more specified chemical groups.
• The complaint does not explicitly reserve the right to assert other claims but notes the action is for infringement of "at least claim 4."

III. The Accused Instrumentality

Product Identification

• Sun Generic Tofacitinib Tablets (Compl. ¶2).

Functionality and Market Context

• The accused instrumentality is a proposed generic drug product for which Defendant Sun has filed ANDA No. 214351 seeking FDA approval (Compl. ¶2). The product is described as "tofacitinib immediate-release tablets, for oral use," containing a 5 mg or 10 mg equivalent of tofacitinib in the form of tofacitinib citrate (Compl. ¶32).
• As a JAK inhibitor, the product is intended for the same indications as Pfizer's Xeljanz®, including the treatment of rheumatoid arthritis (Compl. ¶20-21). The complaint alleges that upon approval, these generic tablets will be marketed and sold as a lower-cost alternative to Xeljanz® before the expiration of the RE'783 patent (Compl. ¶2, ¶33).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint alleges that the filing of ANDA No. 214351 is a statutory act of infringement under 35 U.S.C. § 271(e)(2) with respect to claim 4 (Compl. ¶40). The core of this allegation is that the product described in the ANDA contains the specific chemical compound claimed in the patent.

RE'783 Patent Infringement Allegations

• Identified Points of Contention:
  • Technical Questions: In this ANDA context, the infringement analysis raises a direct factual question: does the active pharmaceutical ingredient described in Sun's ANDA No. 214351 meet the structural limitations of claim 4? The complaint alleges that the proposed product's active ingredient, tofacitinib citrate (Compl. ¶19, ¶32), is a pharmaceutically acceptable salt of the compound recited in claim 4 of the 'RE'783 patent.
  • Scope Questions: A potential point of contention could be the scope of the term "pharmaceutically acceptable salt thereof." However, the complaint alleges that Sun's pre-suit notice letter did not include a non-infringement argument with respect to claim 4, which suggests that the primary legal battle may not be over infringement of this claim but rather over its validity or enforceability (Compl. ¶36).

V. Key Claim Terms for Construction

• The Term: "pharmaceutically acceptable salt thereof"
• Context and Importance: This term's construction is central to confirming that Sun's product, which contains the citrate salt of tofacitinib (Compl. ¶32), falls within the scope of claim 4. Since both the branded and proposed generic products are formulated as salts, the precise definition of what constitutes a "pharmaceutically acceptable salt" is fundamental to the infringement analysis.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent specification provides an explicit and broad definition, stating that these are salts which form "non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions" (RE’783 Patent, col. 6:1-5). It proceeds to provide a non-exhaustive list of examples that includes "citrate" (RE’783 Patent, col. 6:6-8). This language may support an interpretation that the term is well-understood in the art and expressly covers the salt form used in the accused product.
  • Evidence for a Narrower Interpretation: The complaint does not provide sufficient detail for analysis of potential narrowing interpretations. A party could theoretically argue that specific unlisted salts or salt-formation processes fall outside the scope, but the express inclusion of "citrate" in the specification's examples presents a significant hurdle to such an argument in this case.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that the U.S. subsidiary, Sun Pharmaceutical Industries, Inc., induced infringement by the parent company, Sun Pharmaceutical Industries Limited (Compl. Count II). This is based on the allegation that the U.S. entity "actively and knowingly caused to be submitted and/or assisted with, participated in, contributed to, and/or directed the submission" of the ANDA, knowing it would constitute an act of infringement (Compl. ¶47).
• Willful Infringement: While not pleaded as a separate count, the complaint alleges pre-suit knowledge as the basis for willfulness. It states, "Sun had knowledge of the RE’783 patent when it submitted ANDA No. 214351 to the FDA" (Compl. ¶41).

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

• A foundational issue in the case will be one of statutory infringement: does Sun’s filing of an ANDA for a product that is required by law to be the bioequivalent of Xeljanz®, and which is described as containing tofacitinib citrate (Compl. ¶32), constitute infringement of claim 4, which specifically claims the tofacitinib molecule or its pharmaceutically acceptable salts?
• Given the complaint’s allegation that Sun’s pre-suit notice did not contest infringement of claim 4 (Compl. ¶36), a critical question for the litigation will be whether Sun's challenges to the validity and enforceability of the RE'783 patent, asserted in its Paragraph IV certification (Compl. ¶34), can overcome the patent's statutory presumption of validity and thereby allow for lawful market entry.