DCT
1:17-cv-00158
Pfizer Inc v. Zydus Pharma USA Inc
Key Events
Amended Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Pfizer Inc. (and related entities) (Delaware/Netherlands)
- Defendant: Micro Labs USA Inc. and Micro Labs, Ltd. (New Jersey/India)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:17-cv-00158, D. Del., 06/27/2018
- Venue Allegations: Venue is asserted in the District of Delaware based on Defendant's submission of an Abbreviated New Drug Application (ANDA), which constitutes a tortious act of patent infringement causing foreseeable harm in Delaware, and on Defendant's prior consent to jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendant’s proposed generic version of the rheumatoid arthritis drug Xeljanz® infringes three patents related to the drug's active ingredient, tofacitinib.
- Technical Context: The technology concerns specific chemical compositions and crystalline forms of tofacitinib, a Janus kinase (JAK) inhibitor used for treating autoimmune diseases.
- Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendant's filing of an ANDA containing a "Paragraph IV" certification, which asserts that Plaintiff's patents are invalid and/or will not be infringed. The RE'783 patent is a reissue of an earlier patent, and its expiration date has been extended by the USPTO. The '023 Patent has been subject to a Certificate of Correction that substantially altered its lead claim from a method claim to a composition claim.
Case Timeline
| Date | Event |
|---|---|
| 1999-12-10 | RE'783 Patent Priority Date |
| 2001-05-31 | '023 Patent Priority Date |
| 2001-12-06 | '027 Patent Priority Date |
| 2003-09-30 | Original patent for RE'783 (No. 6,627,754) Issues |
| 2005-11-15 | '027 Patent Issues |
| 2007-11-27 | '023 Patent Issues |
| 2010-09-28 | RE'783 Patent Reissues |
| 2016-12-14 | USPTO extends expiration date of RE'783 Patent |
| 2017-01-03 | Micro Labs sends Notice Letter regarding ANDA filing |
| 2018-06-27 | Amended Complaint Filed |
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," issued November 15, 2005
The Invention Explained
- Problem Addressed: The patent addresses the need for a version of the tofacitinib citrate compound with "solid state properties which are acceptable to support tablet development" (’027 Patent, col. 3:52-56). In pharmaceutical development, amorphous (non-crystalline) compounds or unstable crystalline forms can present significant challenges for manufacturing, stability, and bioavailability, making the discovery of a stable, manufacturable crystalline form a critical step.
- The Patented Solution: The patent discloses a specific, novel crystalline form (a polymorph) of the tofacitinib citrate salt (’027 Patent, Abstract). The invention is defined by its unique physical characteristics, including a specific X-ray powder diffraction (XRPD) pattern with characteristic peaks and a distinct melting temperature as measured by differential scanning calorimetry (DSC) (’027 Patent, col. 3:9-24, Fig. 1-2).
- Technical Importance: Identifying a stable crystalline polymorph is often essential for creating a reliable and effective solid oral dosage form, such as a tablet, ensuring consistent quality and therapeutic effect (’027 Patent, col. 3:52-56).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶53).
- 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.
U.S. Patent No. 7,301,023 - "Chiral Salt Resolution," issued November 27, 2007
The Invention Explained
- Problem Addressed: The patent's background explains that when synthesizing complex organic molecules like the precursors to tofacitinib, "Racemic mixtures... are initially obtained whereas the individual enantiomers in substantially isolated pure form are preferred and at times required for drug use" (’023 Patent, col. 3:39-43). The technical problem is separating these mirror-image molecules (enantiomers) to isolate only the one with the desired biological activity.
- The Patented Solution: As originally filed and prosecuted, the patent described a method for separating enantiomers using a resolving agent to precipitate one specific enantiomer from a mixture (’023 Patent, col. 5:7-21). However, a Certificate of Correction fundamentally altered the patent, deleting the method claims and replacing them with a single composition claim directed to the (3R,4R) tofacitinib compound itself or its salt (’023 Patent, p. 17).
- Technical Importance: The ability to isolate a single, specific stereoisomer of a drug is critical, as different enantiomers can have vastly different efficacy or toxicity profiles.
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶59).
- 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.
U.S. Reissue Patent No. RE41,783 - "Pyrrolo[2,3-D]pyrimidine Compounds," issued September 28, 2010
Technology Synopsis
This patent, a reissue of the original composition of matter patent for this drug class, discloses and claims a broad genus of chemical compounds, known as pyrrolo[2,3-d]pyrimidines, which inhibit the Janus Kinase 3 (JAK3) enzyme. The patent teaches that these compounds are useful as immunosuppressive agents for treating conditions like rheumatoid arthritis and organ transplant rejection (RE’783 Patent, Abstract; Background of the Invention).
Asserted Claims
The complaint asserts infringement of at least independent claim 1 (Compl. ¶65).
Accused Features
The accused feature is the active pharmaceutical ingredient (API) in the Micro Labs Generic Tablets, tofacitinib citrate (Compl. ¶42).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is the "Micro Labs Generic Tablets," a generic drug product containing tofacitinib citrate, which is the subject of Defendant's ANDA No. 209738 submitted to the FDA (Compl. ¶¶2, 13).
Functionality and Market Context
The ANDA seeks approval for 5 mg tablets of tofacitinib citrate (Compl. ¶13). This product is designed to be a generic equivalent of Pfizer's Xeljanz®, an inhibitor of Janus kinases indicated for the treatment of moderately to severely active rheumatoid arthritis (Compl. ¶¶2, 20). The filing of the ANDA signifies a commercial intent to market a lower-cost generic version of the branded drug upon receiving FDA approval (Compl. ¶44).
IV. Analysis of Infringement Allegations
The complaint does not provide specific, element-by-element infringement contentions or claim charts. The analysis below is based on the general allegations that the product described in the ANDA will infringe the asserted claims upon commercialization. No probative visual evidence provided in complaint.
- ’027 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A crystalline form of ... 3-oxo-propionitrile mono citrate salt. | The Micro Labs Generic Tablets are alleged to contain tofacitinib citrate as the active ingredient and are intended for commercial manufacture, use, and sale. | ¶42, ¶52 | col. 3:63-65 |
- ’023 Patent Infringement Allegations
| Claim Element (from Independent Claim 1, as corrected) | 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 accused generic tablets contain tofacitinib citrate, which the complaint identifies as the citrate salt of the (3R,4R) stereoisomer of the claimed compound. | ¶22, ¶42, ¶58 | col. 27:1-4 |
- Identified Points of Contention:
- Factual Question (’027 Patent): A central question for the ’027 Patent is whether the proposed generic product, as described in ANDA No. 209738, possesses the specific crystalline form defined by the patent’s claims. The complaint does not provide evidence, such as comparative XRPD data, to support this allegation, raising the question of what discovery will reveal about the physical form of the Defendant's API.
- Legal Question (’023 Patent): For the ’023 Patent, the infringement analysis appears straightforward, as the corrected claim reads directly on the known (3R,4R) stereoisomer of the tofacitinib API. The primary dispute will therefore likely concern the claim's validity. This raises the question of whether a composition claim, added via a Certificate of Correction to a patent originally directed to a resolution method, is valid in light of prior art disclosing the compound itself, including patents within the same family.
V. Key Claim Terms for Construction
Term (’027 Patent): "crystalline form"
- Context and Importance: The scope of this term is dispositive for the ’027 patent. The infringement analysis depends entirely on whether the defendant's product embodies the specific polymorph claimed. Practitioners may focus on this term because polymorphism is a common area of dispute in pharmaceutical patent law, and the definition will determine whether infringement requires an exact match of the patent's characterization data.
- Intrinsic Evidence for a Broader Interpretation: The plain language "crystalline form" could be argued to encompass any crystalline structure of the salt, not just one with identical properties to the example provided.
- Intrinsic Evidence for a Narrower Interpretation: The specification provides highly specific data to identify the invention, stating the crystalline form "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" (’027 Patent, col. 3:9-12). This explicit definition, along with the data in Figure 1 and Table 1, strongly suggests the term is limited to the specific polymorph characterized in the patent.
Term (’023 Patent): "The compound...or a pharmaceutically acceptable salt thereof"
- Context and Importance: This term, defining the subject matter of the corrected claim, is critical. While the chemical structure itself is unambiguous, practitioners may focus on the legal effect of its introduction via a Certificate of Correction. The dispute may not be over the term's meaning, but rather whether a claim to the compound is permissible in a patent whose specification is overwhelmingly directed to a method of resolution.
- Intrinsic Evidence for Interpretation: The patent's chemical name for tofacitinib citrate specifies the (3R,4R) stereoisomer, providing a clear definition of "the compound" (Compl. ¶22). The specification provides standard definitions for terms like "pharmaceutically acceptable salt" (’023 Patent, col. 4:10-22). The primary evidence for interpretation will be the Certificate of Correction itself, which unequivocally replaced the original method claims with this composition claim.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Micro Labs USA Inc. induced the infringement of Micro Labs, Ltd. (Compl. ¶69). The alleged inducing acts include actively causing, assisting with, and directing the submission of the ANDA to the FDA with knowledge of the patents-in-suit and with the knowledge that such a submission constituted direct infringement (Compl. ¶¶68-69).
- Willful Infringement: The complaint does not contain a formal count for willful infringement. However, it alleges that Defendant had pre-suit knowledge of the patents at the time it submitted its ANDA (Compl. ¶¶51, 57, 63) and requests a judgment that the case is "exceptional" under 35 U.S.C. § 285, which is the statutory basis for awarding attorneys' fees and can be predicated on willful conduct (Compl. p. 13, ¶E).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central legal issue will be one of validity: can the ’023 Patent’s composition claim, added via a Certificate of Correction to a patent whose specification describes a method of chiral resolution, survive challenges of anticipation or obviousness, particularly in view of prior patents in the same family that disclose the tofacitinib compound?
- A key factual question will be one of evidentiary proof: does the crystalline form of tofacitinib citrate in Micro Labs’ proposed generic product, as revealed in its ANDA and through discovery, fall within the scope of the specific polymorph claimed in the ’027 Patent?
- The case strategy may be shaped by the scope of the invalidity defense: the complaint alleges that Defendant’s Paragraph IV notice challenges the patents only on grounds of invalidity, not non-infringement (Compl. ¶46). If accurate, this would focus the litigation almost exclusively on the strength and validity of Pfizer’s patent portfolio rather than on technical comparisons of the accused product to the claims.