I. Executive Summary and Procedural Information
- Parties & Counsel:
- Case Identification: 1:17-cv-00214, D. Del., 03/02/2017
- Venue Allegations: Venue is asserted in the District of Delaware based on Defendant Zydus Pharmaceuticals (USA) Inc.'s filing of an Abbreviated New Drug Application (ANDA) seeking approval to market its generic product throughout the United States, including in Delaware, where Plaintiff Pfizer Inc. is incorporated.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an ANDA to market a generic version of the rheumatoid arthritis drug Xeljanz® constitutes an act of infringement of three patents covering the drug's active ingredient, its specific stereoisomer, and its specific crystalline salt form.
- Technical Context: The technology relates to tofacitinib citrate, a small-molecule inhibitor of Janus kinases (JAKs) used for treating autoimmune disorders such as rheumatoid arthritis.
- Key Procedural History: This action arises under the Hatch-Waxman Act following Defendant's submission of ANDA No. 209829 with a Paragraph IV certification, asserting that Plaintiff's patents are invalid and/or not infringed. Plaintiff was notified of the ANDA filing via a letter dated January 19, 2017. The complaint notes that the USPTO issued a determination on December 14, 2016, extending the expiration date of the RE'783 patent.
Case Timeline
| Date |
Event |
| 1999-12-10 |
’783 Patent Priority Date |
| 2001-05-31 |
’023 Patent Priority Date |
| 2001-12-06 |
’027 Patent Priority Date |
| 2005-11-15 |
'027 Patent Issue Date |
| 2007-11-27 |
'023 Patent Issue Date |
| 2010-09-28 |
RE'783 Patent Issue Date |
| 2016-12-14 |
USPTO extends expiration date of RE'783 Patent |
| 2017-01-19 |
Zydus Notice Letter sent to Pfizer |
| 2017-03-02 |
Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,965,027
- Patent Identification: 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," issued November 15, 2005. (Compl. ¶25).
The Invention Explained
- Problem Addressed: The patent addresses the need for a form of the tofacitinib citrate compound with physical properties suitable for pharmaceutical manufacturing. The background states that the invention "was determined to have solid state properties which are acceptable to support tablet development." (’027 Patent, col. 3:52-56).
- The Patented Solution: The patent discloses a specific, novel crystalline form of tofacitinib mono citrate salt. This crystalline structure, or polymorph, is defined by characteristic physical data, including a specific X-ray powder diffraction (XRPD) pattern and a distinct melting point, which differentiate it from other potential solid forms. (’027 Patent, Abstract; col. 3:7-14, FIG. 1).
- Technical Importance: Establishing a stable, reproducible crystalline form of an active pharmaceutical ingredient is critical for ensuring consistency in drug manufacturing, stability, and bioavailability. (’027 Patent, col. 3:52-56).
Key Claims at a Glance
- The complaint asserts at least independent claim 1. (Compl. ¶44).
- Independent Claim 1 requires:
- 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. (’027 Patent, col. 9:32-36).
- The complaint alleges infringement of "one or more claims," preserving the right to assert additional claims. (Compl. ¶42).
U.S. Patent No. 7,301,023
- Patent Identification: U.S. Patent No. 7,301,023, "Chiral Salt Resolution," issued November 27, 2007. (Compl. ¶27).
The Invention Explained
- Problem Addressed: The patent's background notes that pyrrolo[2,3-d]pyrimidine compounds are often first synthesized as "racemic mixtures," which contain equal amounts of two mirror-image molecular structures (enantiomers). For drug use, it is often preferable or necessary to use only one specific enantiomer, requiring a method for their separation. (’023 Patent, col. 3:39-49).
- The Patented Solution: The patent claims the specific, therapeutically active (3R,4R) enantiomer of the tofacitinib compound. The specification describes a method of "chiral salt resolution" where a resolving agent is used to selectively bind to and precipitate one enantiomer from a racemic mixture, allowing for its isolation in substantially pure form. (’023 Patent, col. 5:40-58).
- Technical Importance: Isolating a single enantiomer is a crucial step in pharmaceutical development, as different enantiomers of the same molecule can have vastly different biological activities, with one being therapeutic and the other being inactive or potentially harmful. (’023 Patent, col. 3:41-43).
Key Claims at a Glance
- The complaint asserts claim 1. (Compl. ¶50).
- Independent Claim 1, as set forth in the Certificate of Correction, requires:
- 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. (’023 Patent, Certificate of Correction; col. 27:14-18).
- The complaint alleges infringement of "one or more claims," preserving the right to assert additional claims. (Compl. ¶48).
U.S. Reissue Patent No. RE41,783
- Patent Identification: U.S. Reissue Patent No. RE41,783, "Pyrrolo[2,3-d]pyrimidine Compounds," issued September 28, 2010. (Compl. ¶29).
Technology Synopsis
- The patent addresses the need for effective immunosuppressive agents to treat organ transplant rejection and autoimmune diseases such as rheumatoid arthritis. (RE’783 Patent, col. 1:11-22). The solution provided is a class of compounds, known as pyrrolo[2,3-d]pyrimidines, that inhibit the Janus Kinase 3 (JAK3) enzyme, which plays an essential role in the function of immune cells. (RE’783 Patent, col. 1:25-36).
Asserted Claims & Accused Features
- Asserted Claims: The complaint asserts at least independent claim 1. (Compl. ¶56).
- Accused Features: The accused feature is the active pharmaceutical ingredient, tofacitinib, which the complaint alleges will be contained in the Zydus Generic Tablets. (Compl. ¶¶34, 56).
III. The Accused Instrumentality
- Product Identification: The accused instrumentalities are "Zydus Generic Tablets," described as 5 mg tofacitinib tablets for which Zydus filed ANDA No. 209829. (Compl. ¶11).
- Functionality and Market Context:
- The complaint alleges that the Zydus Generic Tablets will contain tofacitinib citrate as the active ingredient. (Compl. ¶34). Tofacitinib citrate is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis. (Compl. ¶18).
- The complaint alleges Zydus is "one of the top 10 U.S. generic companies in total prescriptions" and "one of the fastest growing pharmaceutical companies in the U.S." (Compl. ¶15).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint provides a high-level notice of infringement as is typical in ANDA litigation, without detailed element-by-element analysis. The infringement theory is based on the act of filing an ANDA for a product that, if marketed, would infringe the patents-in-suit. (Compl. ¶¶42, 48, 54).
'027 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) |
Alleged Infringing Functionality |
Complaint Citation |
Patent Citation |
| 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 alleges that Zydus's filing of ANDA No. 209829 for its generic tablets is an act of infringement, and that future manufacture and sale of the tablets will infringe, which suggests the tablets will contain the claimed crystalline form. |
¶42, ¶44 |
col. 9:32-36 |
'023 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) |
Alleged Infringing Functionality |
Complaint Citation |
Patent Citation |
| 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 alleges that Zydus Generic Tablets will contain tofacitinib citrate as the active ingredient, which is a salt of the claimed (3R,4R) enantiomer. |
¶34, ¶50 |
col. 27:14-18 |
Identified Points of Contention
- Factual Question ('027 Patent): The primary infringement question for the ’027 Patent will be factual: does the active ingredient in Zydus's proposed generic product exist in the specific crystalline form claimed in the patent? The complaint does not provide evidence on this point, which will be a subject of discovery and expert analysis.
- Legal Question (All Patents): Zydus's notice letter included a Paragraph IV certification, and its Detailed Statement asserts that all claims of the patents-in-suit are invalid. (Compl. ¶¶37-38). This suggests the central dispute for the ’023 Patent and RE’783 Patent, and a primary defense for the ’027 Patent, will be validity rather than non-infringement.
V. Key Claim Terms for Construction
- The Term: "crystalline form" (from '027 Patent, Claim 1)
- Context and Importance: The entirety of the ’027 Patent is directed to a specific crystalline polymorph of tofacitinib citrate, distinct from other solid forms. The definition of this term is therefore dispositive for the infringement analysis of this patent. Practitioners may focus on this term because the case may turn on whether Zydus's product meets the specific structural and physical characteristics that define this particular "crystalline form."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent repeatedly refers to the invention as "a novel crystalline form," which a party could argue distinguishes it broadly from the prior art amorphous material without being strictly limited to the exact data presented. (’027 Patent, col. 3:15-16, 62-63).
- Evidence for a Narrower Interpretation: The specification provides highly specific characterization data, including an X-ray diffraction pattern with characteristic peaks listed in Table 1 and depicted in Figure 1, as well as a specific melting temperature range shown in a calorimetry thermogram in Figure 2. (’027 Patent, col. 3:7-14; col. 3:20-28; col. 10:4-9). Dependent claim 2 further narrows the scope by explicitly reciting specific diffraction peaks, suggesting the independent claim may be construed in light of these specific embodiments.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendant Cadila Healthcare Ltd. induced infringement by "actively and knowingly" causing, assisting, or directing its subsidiary, Zydus Pharmaceuticals (USA) Inc., to submit the ANDA with knowledge of the asserted patents. (Compl. ¶¶60-61).
- Willful Infringement: The complaint does not use the word "willful," but it alleges that Zydus had "knowledge" of each patent-in-suit at the time it submitted its ANDA. (Compl. ¶¶43, 49, 55). This allegation of pre-suit knowledge, combined with the prayer for relief seeking attorneys' fees for an "exceptional case," lays the groundwork for a potential finding of willfulness. (Compl. Prayer for Relief E).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary question will be one of polymorphic identity: does the tofacitinib citrate in Zydus's ANDA product exhibit the specific crystalline structure defined by the claims and specification of the '027 patent, or does it utilize a different, non-infringing crystalline or amorphous form? The outcome will depend on expert analysis of Zydus's proposed product.
- A core legal question, foreshadowed by Zydus's Paragraph IV certification, will be the validity of the asserted patents: can Zydus present clear and convincing evidence that the claims covering the compound itself (RE'783), its specific enantiomer ('023), and its crystalline form ('027) are invalid as being anticipated or rendered obvious by prior art?