DCT
1:16-cv-00879
Hospira Inc v. Par Sterile Products LLC
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Hospira, Inc. (Delaware)
- Defendant: Par Sterile Products, LLC (Delaware)
- Plaintiff’s Counsel: Connolly Gallagher LLP; Jenner & Block LLP
- Case Identification: 1:16-cv-00879, D. Del., 09/29/2016
- Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Defendant’s incorporation in the state and its conduct of business within the district.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for generic dexmedetomidine hydrochloride products constitutes an act of infringement of four patents covering ready-to-use, premixed formulations of the sedative.
- Technical Context: The technology concerns pharmaceutical formulations of the sedative dexmedetomidine that are sold in a premixed, patient-ready format, which is intended to increase safety and convenience in clinical settings by eliminating the need for dilution from a concentrate.
- Key Procedural History: The action arises under the Hatch-Waxman Act. Defendant filed ANDA No. 208266 seeking FDA approval to market a generic version of Plaintiff's PRECEDEX™ product. The ANDA included a Paragraph IV certification alleging that Plaintiff’s Orange Book-listed patents are invalid. Plaintiff received Defendant's notice letter on August 16, 2016, and filed this complaint within the statutory 45-day window.
Case Timeline
| Date | Event |
|---|---|
| 1999-12-17 | Original FDA approval of Hospira's NDA for PRECEDEX™ |
| 2012-01-04 | Priority Date for ’158, ’470, ’527, and ’106 Patents |
| 2012-08-14 | ’158 Patent Issue Date |
| 2012-12-25 | ’470 Patent Issue Date |
| 2013-03-13 | FDA approval of amendment to Hospira's NDA for premix formulation |
| 2013-06-04 | ’527 Patent Issue Date |
| 2014-02-11 | ’106 Patent Issue Date |
| 2014-11-14 | FDA approval of amendment to Hospira's NDA for premix formulation |
| 2016-08-15 | Date of Defendant's Paragraph IV Notice Letter |
| 2016-08-16 | Plaintiff receives Defendant's Notice Letter |
| 2016-09-29 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,242,158 - "Dexmedetomidine Premix Formulation"
- Patent Identification: U.S. Patent No. 8,242,158, "Dexmedetomidine Premix Formulation," issued August 14, 2012. (Compl. ¶10).
The Invention Explained
- Problem Addressed: The patent describes that, prior to the invention, dexmedetomidine was supplied as a concentrate that required a dilution step before being administered to a patient. This process was associated with "additional costs and inconvenience, as well as the risk of possible contamination or overdose due to human error." (’158 Patent, col. 1:50-54).
- The Patented Solution: The invention is a "patient-ready, premixed" liquid pharmaceutical formulation of dexmedetomidine that does not require reconstitution or dilution prior to administration. (’158 Patent, col. 1:7-12; col. 2:60-64). The patent discloses the discovery that such a premixed formulation could be created that "remains stable and active after prolonged storage." (’158 Patent, col. 2:65-col. 3:1).
- Technical Importance: By providing a ready-to-use formulation, the invention aimed to reduce the risk of medication errors and contamination while improving efficiency in clinical environments. (’158 Patent, col. 1:55-59).
Key Claims at a Glance
- The complaint asserts infringement of at least one claim. Independent claim 1 is the broadest composition claim. (Compl. ¶24).
- Independent Claim 1:
- A ready to use liquid pharmaceutical composition for parenteral administration to a subject,
- comprising dexmedetomidine or a pharmaceutically acceptable salt thereof at a concentration of about 4 µg/mL
- disposed within a sealed glass container.
- The complaint reserves the right to assert other claims.
U.S. Patent No. 8,338,470 - "Dexmedetomidine Premix Formulation"
- Patent Identification: U.S. Patent No. 8,338,470, "Dexmedetomidine Premix Formulation," issued December 25, 2012. (Compl. ¶11).
The Invention Explained
- Problem Addressed: The patent addresses the identical problem as the ’158 Patent: the costs, risks, and inconvenience associated with diluting concentrated drug formulations before patient administration. (’470 Patent, col. 2:51-59).
- The Patented Solution: The invention is a premixed, ready-to-use liquid formulation of dexmedetomidine. The claims of the ’470 patent are directed to a broader range of concentrations compared to the ’158 Patent. (’470 Patent, Abstract; col. 2:1-5).
- Technical Importance: The invention provides the same clinical benefits of safety and convenience as the '158 Patent by providing a formulation that avoids the need for dilution. (’470 Patent, col. 2:56-62).
Key Claims at a Glance
- The complaint asserts infringement of at least one claim. Independent claim 1 is the broadest composition claim. (Compl. ¶30).
- Independent Claim 1:
- A ready to use liquid pharmaceutical composition for parenteral administration to a subject,
- comprising dexmedetomidine or a pharmaceutically acceptable salt thereof at a concentration of about 0.005 to about 50 µg/mL
- disposed within a sealed glass container.
- The complaint reserves the right to assert other claims.
U.S. Patent No. 8,455,527 - "Methods of Treatment Using a Dexmedetomidine Premix Formulation"
- Patent Identification: U.S. Patent No. 8,455,527, "Methods of Treatment Using a Dexmedetomidine Premix Formulation," issued June 4, 2013. (Compl. ¶12).
- Technology Synopsis: This patent addresses the same clinical problem as the parent patents but claims methods of treatment rather than compositions. The invention is a method for providing sedation to a patient by administering an effective amount of a ready-to-use, premixed liquid dexmedetomidine formulation from a sealed glass container. (’527 Patent, Claim 1).
- Asserted Claims: The complaint generally asserts infringement of at least one claim; independent claim 1 is the broadest method claim. (Compl. ¶36).
- Accused Features: The complaint alleges that the future use of Defendant's proposed products, as instructed by the proposed package insert, will directly infringe the method claims. (Compl. ¶36-37).
U.S. Patent No. 8,648,106 - "Dexmedetomidine Premix Formulation"
- Patent Identification: U.S. Patent No. 8,648,106, "Dexmedetomidine Premix Formulation," issued February 11, 2014. (Compl. ¶13).
- Technology Synopsis: This patent claims a composition similar to those in the '158 and '470 patents but adds a specific stability requirement. The claimed invention is a ready-to-use liquid dexmedetomidine formulation that, when stored in a sealed glass container for at least five months, exhibits "no more than about 2% decrease in the concentration of dexmedetomidine." (’106 Patent, Claim 1).
- Asserted Claims: The complaint generally asserts infringement of at least one claim; independent claim 1 is the broadest composition claim. (Compl. ¶42).
- Accused Features: The complaint alleges that Defendant's proposed products themselves will infringe, which implies they possess the claimed stability profile. (Compl. ¶42).
III. The Accused Instrumentality
Product Identification
- The "Proposed Par Dexmedetomidine Products" are the subject of Defendant's ANDA No. 208266. (Compl. ¶5, 16).
Functionality and Market Context
- The accused products are described as generic "Dexmedetomidine Hydrochloride, 200 mcg/50mL and 400mcg/100mL, for injection." (Compl. ¶19). Both of these formulations have a concentration of 4 µg/mL.
- The products are intended for market entry prior to the expiration of the patents-in-suit as a generic equivalent to Plaintiff's PRECEDEX™ premixed product. (Compl. ¶5). The filing of the ANDA is the statutory act of infringement giving rise to the lawsuit. (Compl. ¶5, 23).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that Defendant's Paragraph IV certification is based solely on invalidity, and that the "Notice Letter does not allege non-infringement of any claim" of the patents-in-suit. (Compl. ¶18, 24, 30, 36, 42). This suggests the central dispute may concern patent validity rather than infringement.
’158 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A ready to use liquid pharmaceutical composition for parenteral administration to a subject, | The Proposed Par Dexmedetomidine Products are liquid formulations intended for injection. | ¶19 | col. 1:7-9 |
| comprising dexmedetomidine or a pharmaceutically acceptable salt thereof at a concentration of about 4 µg/mL | The products are formulated as dexmedetomidine hydrochloride at 200 mcg/50mL and 400mcg/100mL, which corresponds to a concentration of 4 µg/mL. | ¶19 | col. 2:6-8 |
| disposed within a sealed glass container. | The complaint alleges this limitation is met but provides no specific facts regarding the container material of the proposed generic product. | ¶24 | col. 2:13-14 |
’470 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A ready to use liquid pharmaceutical composition for parenteral administration to a subject, | The Proposed Par Dexmedetomidine Products are liquid formulations intended for injection. | ¶19 | col. 1:12-14 |
| comprising dexmedetomidine or a pharmaceutically acceptable salt thereof at a concentration of about 0.005 to about 50 µg/mL | The 4 µg/mL concentration of the accused products falls within the claimed range. | ¶19 | col. 8:45-48 |
| disposed within a sealed glass container. | The complaint alleges this limitation is met but provides no specific facts regarding the container material of the proposed generic product. | ¶30 | col. 2:19-20 |
Identified Points of Contention
- Factual Questions: The complaint does not provide factual support for several key elements. A primary question for discovery will be the composition of the container for Defendant's proposed product and whether it is a "sealed glass container" as required by the claims of the '158, '470, and '527 patents. Another factual question relates to the '106 patent: does the accused product meet the specific stability limitation of losing no more than about 2% concentration over five months?
- Scope Questions: The term "about 4 µg/mL" in the '158 patent appears to be met literally by the accused products' 4 µg/mL concentration. However, the scope of "about" is a frequent subject of claim construction and could become a point of dispute.
V. Key Claim Terms for Construction
- The Term: "ready to use"
- Context and Importance: This term is central to the patents' novelty, distinguishing the claimed invention from prior art concentrates that required dilution. The definition of this term is critical because it underpins the core inventive concept. Practitioners may focus on this term to determine if any preparatory step whatsoever, however minor, could take an accused product outside the claim scope.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification defines "premix" and "premixture" as a formulation that "does not require reconstitution or dilution prior to administration to a patient." (’158 Patent, col. 3:48-51). The patent uses "ready to use" to refer to such premixed compositions, suggesting the term's primary meaning is the absence of a dilution step. (’158 Patent, col. 3:56-59).
- Evidence for a Narrower Interpretation: A party could argue that the term implies a state of absolute readiness for administration, and that any required user action (e.g., connecting a bag to an IV line) constitutes a preparatory step not contemplated by the claims. The specification, however, appears to equate "ready to use" with "premixed," which may limit the viability of a narrower construction. (’158 Patent, col. 2:60-64).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendant will induce infringement of the method claims of the '527 patent. This allegation is based on the claim that Defendant will provide a package insert with instructions that encourage and direct medical professionals to administer the product in an infringing manner. (Compl. ¶25, 31, 37, 43).
- Willful Infringement: Willfulness is alleged based on Defendant’s knowledge of the patents-in-suit prior to filing its ANDA. The complaint asserts that this knowledge is evidenced by the act of filing a Paragraph IV certification against these specific patents, which are listed in the FDA's Orange Book. (Compl. ¶26, 32, 38, 44).
VII. Analyst’s Conclusion: Key Questions for the Case
- Validity vs. Infringement: The complaint states that the Defendant’s Paragraph IV letter alleged only invalidity and not non-infringement. A primary question for the case is therefore one of patent validity: are the claims covering a ready-to-use, 4 µg/mL dexmedetomidine formulation in a glass container valid over the prior art? The Defendant's decision to challenge validity rather than infringement suggests the core of the dispute may lie here.
- Evidentiary Proof: Should the patents be found valid, a key evidentiary question will be one of factual correspondence: can the plaintiff produce evidence that the accused generic product meets every claim limitation? This will turn on discovering the specific characteristics of the defendant's proposed product, including its container material (is it glass?) and its long-term stability profile (does it meet the requirements of the '106 patent?).