DCT
1:15-cv-00004
Pfizer Inc v. Mylan Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Pfizer Inc. (Delaware) and related entities
- Defendant: Mylan Inc. (Pennsylvania) and related entities
- Plaintiff’s Counsel: Schrader Byrd & Companion, PLLC; Williams & Connolly LLP
- Case Identification: [Pfizer Inc.](https://ai-lab.exparte.com/party/pfizer-inc) v. [Mylan Inc.](https://ai-lab.exparte.com/party/mylan-inc), 1:15-cv-00004, N.D. W. Va., 01/09/2015
- Venue Allegations: Venue is based on Defendants' alleged regular transaction of business, maintenance of a headquarters, and manufacturing operations within the Northern District of West Virginia.
- Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the antibiotic TYGACIL® constitutes an act of infringement of patents covering stable compositions and specific crystalline forms of the active ingredient, tigecycline.
- Technical Context: The technology concerns pharmaceutical formulations designed to improve the stability of tigecycline, a tetracycline-class antibiotic used for treating serious bacterial infections.
- Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following a notice letter dated November 26, 2014, in which Defendants informed Plaintiff of their ANDA submission containing a Paragraph IV certification, asserting that the patents-in-suit are either invalid or will not be infringed by the proposed generic product. The complaint also notes that an exclusive license to the patents-in-suit was granted to Plaintiff PF Prism CV., which subsequently contributed its rights to Plaintiff Pfizer Pharmaceuticals LLC.
Case Timeline
| Date | Event |
|---|---|
| 2005-03-14 | ’828 Patent Priority Date |
| 2005-05-27 | ’995 Patent Priority Date |
| 2011-02-01 | ’828 Patent Issue Date |
| 2013-02-12 | ’995 Patent Issue Date |
| 2014-11-26 | Defendant's ANDA Paragraph IV Notice Letter Sent |
| 2015-01-09 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,879,828 - "Tigecycline Compositions and Methods of Preparation" (Issued Feb. 1, 2011)
The Invention Explained
- Problem Addressed: The patent describes tigecycline, a potent antibiotic, as being unstable in solution, where it is prone to rapid degradation through two primary pathways: oxidation and epimerization (a structural rearrangement that inactivates the drug) ('828 Patent, col. 1:57 - col. 2:11). This instability creates challenges for manufacturing and requires hospital staff to prepare and administer the drug quickly, limiting practical flexibility ('828 Patent, col. 2:11-24).
- The Patented Solution: The invention claims to solve this problem with a formulation that combines tigecycline with a "suitable carbohydrate" (such as lactose) and an acid or buffer to create an acidic solution environment ('828 Patent, Abstract). The acidic pH is intended to minimize oxidative degradation, while the patent asserts that the carbohydrate stabilizes the tigecycline against epimerization, which would otherwise be the predominant degradation pathway at low pH ('828 Patent, col. 4:50-61). The resulting composition can be lyophilized (freeze-dried) into a more stable solid product.
- Technical Importance: This formulation aimed to provide a commercial version of tigecycline with improved stability in both its solid and reconstituted forms, thereby extending its shelf-life and the window for its preparation and administration in a clinical setting ('828 Patent, col. 4:60-65).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" of the patent (Compl. ¶35). Independent claims 1 and 12 are directed to compositions.
- Independent Claim 1 requires:
- A composition comprising tigecycline, lactose, and an acid
- The acid is selected from hydrochloric acid and gentisic acid
- The molar ratio of tigecycline to lactose is between about 1:0.2 and about 1:5
- The pH of the composition in a solution is between about 3.0 and about 7.0
U.S. Patent No. 8,372,995 - "Crystalline Solid Forms of Tigecycline and Methods of Preparing Same" (Issued Feb. 12, 2013)
The Invention Explained
- Problem Addressed: The patent explains that drug substances are often manufactured as amorphous (non-crystalline) solids, which are typically less stable than their crystalline counterparts ('995 Patent, col. 1:42-45). The background notes it would be "advantageous... if one were able to use and manufacture crystalline solid forms of tigecycline without the need for special handling systems" that amorphous powders might require ('995 Patent, col. 1:47-50).
- The Patented Solution: The invention discloses the discovery and characterization of several distinct crystalline solid forms (polymorphs) of tigecycline, including the one designated "Form I" ('995 Patent, Abstract). These forms are defined by unique physical properties, primarily their characteristic X-ray powder diffraction (XRPD) patterns and thermal melting points, which distinguish them from each other and from the amorphous state ('995 Patent, col. 3:56 - col. 4:1).
- Technical Importance: The identification of stable, crystalline polymorphs is a critical step in pharmaceutical development, as it can lead to a drug product with greater chemical stability, more consistent manufacturing processes, and predictable performance ('995 Patent, col. 2:20-29).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" of the patent (Compl. ¶46). Independent claims 1 and 2 are directed to products.
- Independent Claim 1 requires:
- A "Form I tigecycline"
- Having X-ray powder diffraction peaks at about 5.2°, 8.3°, 11.1°, and 24.8° 2θ
- Having a hot stage melting point onset temperature of about 170° C. to about 172° C.
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is "Defendants' ANDA Product," identified as ANDA No. 203309 for a generic version of Pfizer's TYGACIL® (Compl. ¶¶ 1, 28). It is described as a "tigecycline lyophilized product for IV infusion containing 50 mg tigecycline" (Compl. ¶28).
- Functionality and Market Context: The product is a generic antibiotic intended for intravenous administration for the treatment of complicated infections (Compl. ¶23). The complaint alleges that by filing its ANDA, Defendant seeks FDA approval to "engage in the commercial manufacture, use, offer for sale, sale, and/or importation" of this generic product prior to the expiration of the patents-in-suit (Compl. ¶29). The act of filing the ANDA for this purpose is the statutory act of infringement alleged in the complaint (Compl. ¶34). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint was filed before Plaintiffs reviewed the confidential details of the ANDA and thus alleges infringement "upon information and belief" (Compl. ¶¶ 31, 35). The theory is that to be a generic equivalent of TYGACIL®, the Defendants' product must necessarily adopt the patented features.
’828 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A composition comprising tigecycline... | The accused product is identified as a "tigecycline lyophilized product." | ¶28 | col. 14:40-41 |
| ...lactose... | The branded product, TYGACIL®, contains lactose. The complaint alleges upon information and belief that the generic ANDA product, to be equivalent, would also contain lactose. | ¶¶23, 35 | col. 14:40-41 |
| ...and an acid selected from hydrochloric acid and gentisic acid... | It is alleged upon information and belief that the ANDA product would infringe, suggesting the use of a claimed acid to create a stable, bioequivalent formulation. | ¶35 | col. 14:41-42 |
| ...the pH of the composition in a solution is between about 3.0 and about 7.0. | It is alleged upon information and belief that the ANDA product, when reconstituted, would have a pH within the claimed range to ensure stability and bioequivalence with the branded product. | ¶35 | col. 14:45-47 |
- Identified Points of Contention:
- Evidentiary Question: The central dispute will be factual: what are the actual excipients, molar ratios, and pH characteristics of the product specified in Defendants' confidential ANDA? Discovery will be required to determine if the proposed formulation reads on the elements of the asserted claims.
- Scope Question: A potential point of contention could be the scope of the term "about" as it applies to the claimed molar ratios and pH range, and whether Defendants' product falls within that scope.
’995 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A Form I tigecycline... | The complaint alleges upon information and belief that the ANDA product infringes, which suggests it contains or is manufactured from the claimed "Form I" polymorph. | ¶46 | col. 16:11-12 |
| ...having X-ray powder diffraction peaks at about 5.2° 2θ, about 8.3° 2θ, about 11.1° 2θ, and about 24.8° 2θ... | It is alleged upon information and belief that the tigecycline in the ANDA product possesses the specific crystalline structure defined by these XRPD peaks. | ¶46 | col. 16:12-14 |
| ...and having a hot stage melting point onset temperature of about 170° C. to about 172° C. | It is alleged upon information and belief that the tigecycline in the ANDA product exhibits the claimed thermal properties. | ¶46 | col. 16:14-16 |
- Identified Points of Contention:
- Technical Question: Does the tigecycline active pharmaceutical ingredient (API) in Defendants' ANDA product actually exist in the claimed "Form I" crystalline state, as defined by the specific XRPD peaks and melting point?
- Scope Question: The interpretation of "about" will be critical. The infringement analysis will depend on whether the measured XRPD peaks of Defendants' API fall within the range defined by "about" for each claimed peak.
V. Key Claim Terms for Construction
- Term: "about" (as applied to the XRPD peaks in claim 1 of the '995 Patent)
- Context and Importance: The determination of literal infringement will likely hinge on the precise numerical scope of "about." A narrow construction could allow the accused product to fall outside the claims, while a broader one could support infringement. Practitioners may focus on this term because the patent’s specification provides an explicit definition.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The complaint does not provide a basis for an interpretation broader than that in the specification. A party might argue for a wider range based on extrinsic evidence of industry custom, but this would conflict with the intrinsic record.
- Evidence for a Narrower Interpretation: The '995 Patent specification explicitly states: "A typical precision of the 2θ x-axis value of a peak in a powder pattern is on the order of plus or minus 0.2° 2θ" ('995 Patent, col. 3:29-32). This statement provides strong intrinsic evidence for construing "about" as a specific numerical range of ±0.2° 2θ.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement, stating that Defendants' proposed product labeling will instruct users to reconstitute and administer the generic drug in a way that infringes the claims (Compl. ¶¶ 37-38, 48-49). It further alleges contributory infringement on the basis that the ANDA product is "especially made or adapted for use in infringing" the patents and is not suitable for a "substantial noninfringing use" (Compl. ¶¶ 39, 50).
- Willful Infringement: The complaint alleges willful infringement based on Defendants having "acted with full knowledge" of the patents, for which the Defendants' Paragraph IV notice letter serves as evidence of pre-suit knowledge (Compl. ¶¶ 42, 53).
VII. Analyst’s Conclusion: Key Questions for the Case
- An Evidentiary Question of Composition: The primary issue is factual: What are the precise formulation and physical properties of the product detailed in Defendants' confidential ANDA? The outcome of the case will depend heavily on whether discovery reveals that the generic product's composition, pH, and crystalline structure fall within the boundaries of the asserted claims.
- A Question of Validity: As this is an ANDA case, Defendants have certified that the patents are invalid or not infringed. A central question for the court will therefore be whether Defendants can meet their burden of proving, by clear and convincing evidence, that the asserted claims of the '828 and '995 patents are invalid over the prior art.
- A Claim Construction Question of Scope: The dispute may turn on the construction of the term "about" in the '995 patent. A key question is whether the patent's explicit definition of the term as ±0.2° 2θ is dispositive, and whether the physical characteristics of Defendants' product will fall inside or outside of that narrowly defined range.