Pfizer Inc v. Zydus Pharma USA Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Pfizer Inc. (Delaware) and its related entities.
  • Defendant: Zydus Pharmaceuticals (USA) Inc. (New Jersey) and Cadila Healthcare Ltd. (India).
  • Plaintiff’s Counsel: Arnold & Porter Kaye Scholer LLP.
• Case Identification: 3:20-cv-02227, D.N.J., 02/28/2020.
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Zydus Pharmaceuticals (USA) Inc. is a New Jersey corporation.
• Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug Xeljanz® constitutes an act of infringement of three U.S. patents covering the drug's active ingredient.
• Technical Context: The technology involves tofacitinib citrate, a small molecule inhibitor of Janus kinases (JAKs) used for treating autoimmune conditions such as rheumatoid arthritis and ulcerative colitis.
• Key Procedural History: This is a Hatch-Waxman action triggered by Zydus’s filing of ANDA No. 209829 with a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed. The ’023 patent is subject to a terminal disclaimer, tying its expiration date to that of the RE’783 patent. The RE’783 patent is a reissue of U.S. Patent No. 6,627,754 and its expiration date was extended by the USPTO.

Case Timeline

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

U.S. Patent No. 6,965,027 - "Crystalline 3-{4-METHYL-3-[METHYL-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-AMINO]-PIPERIDIN-1-YL}-3-OXO-PROPIONITRILE CITRATE"

The Invention Explained

• Problem Addressed: The patent addresses the need for a physically stable form of the tofacitinib citrate salt suitable for pharmaceutical manufacturing (Compl. ¶15; ’027 Patent, col. 1:29-50). The background implies that without a defined, stable form, developing a consistent and effective drug product is difficult.
• The Patented Solution: The invention is a specific crystalline polymorph of tofacitinib citrate. This crystalline form is defined by its unique physical properties, including a characteristic X-ray powder diffraction (XRPD) pattern and a specific melting temperature range measured by differential scanning calorimetry (DSC) (’027 Patent, Abstract; col. 2:6-25). The patent asserts this form possesses "solid state properties which are acceptable to support tablet development" (’027 Patent, col. 1:53-56).
• Technical Importance: In pharmaceutical development, having a stable, well-defined crystalline form of an active pharmaceutical ingredient (API) is critical for ensuring consistent purity, solubility, bioavailability, and manufacturability of the final drug product (’027 Patent, col. 1:51-56).

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 1 (Compl. ¶47).
• Claim 1:
  • A crystalline form of 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt.
• The complaint does not explicitly reserve the right to assert dependent claims, but the phrasing "at least claim 1" leaves this possibility open.

U.S. Patent No. 7,301,023 - "Chiral Salt Resolution"

The Invention Explained

• Problem Addressed: The synthesis of complex organic molecules like tofacitinib often produces a racemic mixture, which contains equal amounts of two non-superimposable mirror-image molecules (enantiomers) (’023 Patent, col. 3:36-42). For pharmaceutical use, it is often necessary to isolate a single enantiomer, as different enantiomers can have different biological activities or side effects.
• The Patented Solution: A Certificate of Correction dated February 17, 2009, replaced the original method claims with a single composition claim. The patented invention, as corrected, is the specific (3R,4R) enantiomer of the tofacitinib compound itself, or its salt (’023 Patent, Certificate of Correction, p. 1). The original specification described methods of resolving enantiomers using chiral resolving agents to isolate the desired stereoisomer, which provides context for how the claimed composition is obtained (’023 Patent, col. 5:10-49).
• Technical Importance: Isolating the correct enantiomer is crucial for drug efficacy and safety, as regulatory agencies typically require the specific, therapeutically active stereoisomer to be marketed (’023 Patent, col. 3:40-42).

Key Claims at a Glance

• The complaint asserts infringement of claim 1 (Compl. ¶53).
• Claim 1 (as corrected):
  • The compound 3-{(3R,4R)-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.
• The complaint does not explicitly reserve the right to assert dependent claims for this patent.

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

• Technology Synopsis: This patent claims a broad genus of chemical compounds, known as pyrrolo[2,3-d]pyrimidines, that function as JAK3 inhibitors (RE’783 Patent, Abstract). It discloses that these compounds are useful as immunosuppressive agents for treating conditions like organ transplant rejection and autoimmune diseases. The patent’s claims encompass the specific compound tofacitinib (RE’783 Patent, col. 24:4-10).
• Asserted Claims: At least claims 3 and 4 (Compl. ¶61).
• Accused Features: The complaint alleges that Zydus's proposed generic product, by containing tofacitinib citrate as its active ingredient, will infringe the claims covering that compound (Compl. ¶39, 61).

III. The Accused Instrumentality

Product Identification

• Defendant’s proposed "Zydus 10 mg Generic Tablets," which are described as generic copies of Pfizer’s Xeljanz® tablets (tofacitinib citrate EQ 10 mg tablets) (Compl. ¶37). The product is the subject of ANDA No. 209829 filed with the FDA (Compl. ¶9).

Functionality and Market Context

• The accused product contains tofacitinib citrate as its active ingredient (Compl. ¶39). Tofacitinib citrate is a Janus kinase (JAK) inhibitor indicated for the treatment of several autoimmune diseases, including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis (Compl. ¶14). By filing an ANDA, Zydus is seeking to market a bioequivalent version of Pfizer’s branded Xeljanz® product, creating the commercial and legal conflict at the heart of this lawsuit (Compl. ¶9, 37).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’027 Patent Infringement Allegations

’023 Patent Infringement Allegations

Identified Points of Contention

• Evidentiary Questions: A central factual dispute for the ’027 Patent will be whether Zydus’s proposed product utilizes the specific crystalline polymorph claimed. The analysis will depend on scientific evidence, such as comparing the XRPD and DSC data of Zydus’s API with the data and figures disclosed in the ’027 Patent.
• Scope Questions: For the ’023 and RE’783 patents, infringement appears to be a direct consequence of Zydus’s intent to market a bioequivalent generic of Xeljanz®. The complaint notes that Zydus's Paragraph IV notice primarily argues for invalidity rather than non-infringement (Compl. ¶43). This suggests the primary legal battle may concern the validity of the patents (e.g., on grounds of obviousness or anticipation) rather than disputes over claim scope.

V. Key Claim Terms for Construction

The Term: "crystalline form" (’027 Patent, Claim 1)

• Context and Importance: The patentability of the invention in the ’027 Patent rests entirely on this term, distinguishing the claimed subject matter from prior art amorphous or other crystalline forms of the same chemical compound. Practitioners may focus on this term because its construction will determine whether infringement requires matching the exact XRPD peaks and DSC data in the specification, or merely showing a crystalline, non-amorphous structure.
• Intrinsic Evidence for a Broader Interpretation: The body of the patent describes the invention as "a novel crystalline form" generally, which a party could argue supports a meaning not strictly limited to a single set of characterization data (’027 Patent, col. 1:14-15).
• Intrinsic Evidence for a Narrower Interpretation: The patent defines the form with high specificity, stating it "exhibits an X-ray diffraction pattern with characteristic peaks expressed in degrees 2-theta (2θ) at 5.7, 16.1, 20.2 and 20.5" and providing a detailed table and figures (’027 Patent, col. 2:11-15; Fig. 1; Table 1). A party would argue this data is not merely illustrative but definitional, limiting the claim to a polymorph that exhibits these exact characteristics.

VI. Other Allegations

Indirect Infringement

• The complaint’s prayer for relief seeks to enjoin Zydus from "inducing or contributing to" infringement, which is standard in such pleadings (Prayer for Relief ¶C). However, the body of the complaint does not allege specific facts to support a separate theory of indirect infringement, focusing instead on the direct infringement arising from the ANDA filing under 35 U.S.C. § 271(e)(2).

Willful Infringement

• The complaint alleges that Zydus had knowledge of the patents-in-suit at the time it submitted its ANDA (Compl. ¶48, 54, 60). This allegation is supported by Zydus's own Notice Letter dated January 31, 2020, which explicitly references the patents (Compl. ¶37). These allegations of pre-suit knowledge may form the basis for a later claim of willful infringement and support the request for a finding that the case is "exceptional" under 35 U.S.C. § 285 (Prayer for Relief ¶D).

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

• A core issue will be one of polymorphic identity: Will discovery and expert analysis establish that the active ingredient in Zydus’s proposed generic product is, in fact, the specific "crystalline form" defined by the characteristic spectral and thermal data claimed in the ’027 patent, or does it utilize a different, non-infringing form?
• A key strategic question will be one of validity versus infringement: Given that Zydus’s product is designed to be a bioequivalent of Xeljanz®, which embodies the chemical compositions of the ’023 and RE’783 patents, will the case primarily hinge on Zydus's invalidity defenses (e.g., obviousness, anticipation) rather than on plausible arguments of non-infringement for those two patents?
• An underlying legal question will concern prosecution history: How might the reissue of the RE’783 patent, the subsequent correction of the ’023 patent’s claims, and the terminal disclaimer linking the two patents be leveraged by Zydus to construct arguments regarding claim scope or obviousness-type double patenting?