DCT
1:19-cv-01854
Belcher Pharma LLC v. Hospira Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Belcher Pharmaceuticals, LLC (Florida)
- Defendant: Hospira, Inc. (Delaware)
- Plaintiff’s Counsel: Bayard, P.A.
- Case Identification: 1:19-cv-01854, D. Del., 10/02/2019
- Venue Allegations: Venue is alleged to be proper based on Defendant's incorporation in Delaware, its regular business activities within the state, and its maintenance of a registered agent for service of process in the district.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for an epinephrine injection product constitutes an act of infringement of patents related to more stable, low-impurity formulations of l-epinephrine.
- Technical Context: The technology concerns pharmaceutical formulations of epinephrine engineered to minimize chemical degradation (racemization and oxidation), thereby increasing potency and safety, particularly for emergency treatments.
- Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendant's Paragraph IV certification filed with the FDA, challenging patents listed in the FDA's Orange Book. The complaint notes that both patents-in-suit are the subject of reissue applications filed on December 28, 2018, which could potentially alter the scope of the asserted claims during the litigation. The complaint also references a prior litigation between the parties.
Case Timeline
| Date | Event |
|---|---|
| 2014-08-15 | Earliest Priority Date for ’728 Patent |
| 2017-05-16 | Priority Date for ’700 Patent |
| 2017-10-04 | Date related to Defendant's package insert from prior litigation |
| 2018-06-26 | U.S. Patent No. 10,004,700 Issues |
| 2018-08-07 | U.S. Patent No. 10,039,728 Issues |
| 2018-12-28 | Reissue Applications Filed for ’700 and ’728 Patents |
| 2019-08-19 | Plaintiff receives Defendant's Paragraph IV Notice Letter |
| 2019-10-02 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,004,700
- Patent Identification: U.S. Patent No. 10,004,700, titled “More Potent And Less Toxic Formulations Of Epinephrine And Methods Of Medical Use,” issued June 26, 2018. (Compl. ¶14).
The Invention Explained
- Problem Addressed: The patent’s background section states that existing liquid epinephrine formulations suffer from two major problems: racemization, the conversion of potent l-epinephrine into its less active d-epinephrine isoform, and oxidation. (’700 Patent, col. 2:57-63). It further notes that antioxidant additives like sulfites, used to prevent oxidation, can themselves trigger severe allergic reactions in susceptible patients. (’700 Patent, col. 2:25-34).
- The Patented Solution: The invention is a sulfite-free and preservative-free liquid formulation of l-epinephrine that achieves stability by controlling the pH to a narrow range of 2.8 to 3.3. (’700 Patent, col. 5:5-6). The patent asserts this pH range was a non-obvious discovery that unexpectedly minimized racemization, which the inventors identified as a more significant stability problem than oxidation. (’700 Patent, col. 3:55-63).
- Technical Importance: The invention claims to provide a safer and more reliably potent epinephrine formulation for emergency use, especially for patients with sulfite sensitivities. (’700 Patent, col. 7:41-48).
Key Claims at a Glance
- The complaint asserts independent claim 1. (Compl. ¶24).
- The essential elements of independent claim 1 include:
- A method of treating allergic reaction, anaphylaxis, or shock by injecting a liquid pharmaceutical formulation of l-epinephrine from a prefilled syringe.
- The formulation is compounded in an aqueous solution and includes a tonicity agent.
- The formulation has a pH between 2.8 and 3.3.
- The formulation has no more than about 6% d-epinephrine and 0.5% adrenalone at release.
- The formulation has no more than about 12% d-epinephrine and 0.5% adrenalone over a shelf-life of at least 12 months.
- The complaint does not explicitly reserve the right to assert dependent claims but does not limit its allegations to independent claim 1.
U.S. Patent No. 10,039,728
- Patent Identification: U.S. Patent No. 10,039,728, titled “More Potent And Less Toxic Formulations Of Epinephrine And Methods Of Medical Use,” issued August 7, 2018. (Compl. ¶17).
The Invention Explained
- Problem Addressed: The patent addresses the same problems of chemical instability (racemization, oxidation) and additive toxicity (sulfites) in epinephrine formulations as the ’700 Patent. (’728 Patent, col. 2:5-13, 41-51). It also identifies a need for safer methods of continuous intravenous administration for patients requiring hemodynamic support. (’728 Patent, col. 3:28-40).
- The Patented Solution: The invention describes a method of treating a patient by injecting a prefilled syringe containing a stable, high-purity l-epinephrine formulation (as described in the ’700 Patent) into an intravenous (IV) fluid bag for continuous infusion. (’728 Patent, col. 10:55-66). The patent suggests that using an IV bag containing dextrose helps prevent oxidation and racemization of the diluted epinephrine. (’728 Patent, col. 11:14-17).
- Technical Importance: This method provides a way to administer epinephrine via continuous IV infusion in a critical care setting while minimizing degradation of the drug, ensuring the patient receives a more potent and pure dose. (’728 Patent, col. 10:48-56).
Key Claims at a Glance
- The complaint asserts independent claims 1, 2, and 3. (Compl. ¶24).
- The essential elements of independent claim 1 include:
- A method of treating a patient for septic or anaphylactic shock via a continuous intravenous infusion of l-epinephrine.
- The method involves injecting a prefilled syringe of a 1 mg l-epinephrine formulation into an IV bag containing a saline or dextrose solution.
- The prefilled syringe formulation includes a tonicity agent and has no more than 12.5% total impurities or 12% d-epinephrine.
- The method includes diluting the l-epinephrine to a concentration of about 1 microgram per mL in the IV bag.
- The complaint does not explicitly reserve the right to assert dependent claims.
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is "Hospira's Epinephrine Injection USP, Abboject™ Syringe 1 mg/10 mL," for which Defendant Hospira submitted Abbreviated New Drug Application (ANDA) No. 209359 to the FDA for approval. (Compl. ¶8, ¶20).
- Functionality and Market Context: The complaint alleges that Hospira’s ANDA product is a generic version of Belcher’s approved epinephrine product. (Compl. ¶12, ¶14, ¶17, ¶22). The infringement alleged is statutory infringement under 35 U.S.C. § 271(e)(2), which makes the submission of an ANDA for a patented drug an act of infringement for jurisdictional purposes. (Compl. ¶30, ¶37). The complaint alleges that upon approval, the product would be manufactured, marketed, and sold for the same medical indications as Belcher's product, including the treatment of allergic reactions and shock. (Compl. ¶33, ¶40). The complaint does not provide specific details regarding the formulation of Hospira's product.
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’700 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating allergic reaction, anaphylaxis, anaphylactic shock, or a combination thereof by an injection of at least one dosage of an injectable liquid pharmaceutical formulation of l-epinephrine sterile solution administered by a prefilled syringe... | The complaint alleges that Hospira's product labeling will instruct medical personnel to administer the ANDA product to patients for these indications, constituting induced infringement of the method. | ¶33 | col. 9:56-65 |
| said injectable liquid pharmaceutical formulation compounded in an aqueous solution and further including a tonicity agent; | The complaint makes a general allegation that the manufacture and use of the ANDA Product is covered by the claims of the ’700 Patent. | ¶24 | col. 5:1-6 |
| said injectable liquid pharmaceutical formulation containing up to 1.1 mg of l-epinephrine per prefilled syringe and having a pH between 2.8 and 3.3; | It is alleged on information and belief that Hospira’s ANDA product, for which it seeks approval, will possess the formulation characteristics required by the claim. | ¶24, ¶30 | col. 5:5-6 |
| said liquid pharmaceutical formulation including no more than about 6% d-epinephrine and no more than about 0.5% adrenalone at release, and no more than about 12% d-epinephrine and no more than about 0.5% adrenalone over a shelf-life of at least 12 months. | It is alleged on information and belief that Hospira’s ANDA product will meet the claimed impurity profile both at the time of release and throughout its shelf-life. The complaint provides no specific data from Hospira's ANDA to support this allegation. | ¶24, ¶30 | col. 5:21-30 |
’728 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a patient having, developing, or recovering from septic shock or anaphylactic shock with a continuous intravenous infusion of l-epinephrine delivered via an at least one intravenous fluid bag... | The complaint alleges Hospira's product labeling will instruct medical personnel to administer the ANDA product to treat shock, thereby inducing infringement of the claimed method. | ¶40 | col. 14:1-13 |
| said method comprising the step of injecting an at least one prefilled syringe of a 1 mg injectable liquid pharmaceutical formulation of l-epinephrine into each said at least one intravenous fluid bag... | The accused product is identified as a prefilled syringe, and the complaint alleges its use will involve injection into an IV bag as part of the induced method of treatment. | ¶8, ¶40 | col. 11:1-4 |
| said at least one prefilled syringe injectable liquid pharmaceutical formulation of l-epinephrine including a tonicity agent and having no more than 12.5% total impurities or no more than 12% d-epinephrine: | It is alleged on information and belief that Hospira's ANDA product meets the claimed impurity limitations. | ¶24, ¶37 | col. 14:10-12 |
| said method further comprising the diluting of l-epinephrine to a concentration of about 1 microgram per mL in each said at least one intravenous fluid bag during said continuous intravenous infusion of l-epinephrine... | The complaint alleges that the instructions for use accompanying Hospira's product will direct medical personnel to perform the claimed dilution step as part of the continuous infusion method. | ¶40 | col. 11:1-14 |
Identified Points of Contention
- Technical Questions: The central factual dispute will be whether Hospira's ANDA product actually possesses the specific chemical properties recited in the claims. Specifically, what is the pH of Hospira's formulation, and what are its d-epinephrine and total impurity levels at release and over its proposed shelf-life? The complaint does not provide this information, which will be a primary focus of discovery.
- Scope Questions: A key legal question will concern inducement. What specific instructions, warnings, and indications will be included in Hospira's final, FDA-approved product label? The court will need to determine if that language actively encourages or instructs medical professionals to perform every step of the claimed methods, such as administering for specific types of shock or performing the continuous IV infusion as claimed in the ’728 Patent.
V. Key Claim Terms for Construction
The Term: "pH between 2.8 and 3.3" (from ’700 Patent, Claim 1)
Context and Importance: This pH range is presented as the central feature of the invention, responsible for the unexpected reduction in racemization. Infringement will likely depend on whether Hospira’s product formulation falls squarely within this range. Practitioners may focus on this term because its boundaries define the core of the patented solution.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The plain meaning of "between" is typically inclusive of the endpoints. The patent consistently refers to this range as the inventive step.
- Evidence for a Narrower Interpretation: The specification states this pH range was a "discovery" that led to a "nonobvious solution to the problem of racemization." (’700 Patent, col. 3:60-64). A defendant could argue that the term should be narrowly construed as being functionally tied to achieving the specific results disclosed, potentially limiting the scope of equivalents for pH values outside but near the range.
The Term: "no more than about 6% d-epinephrine" (from ’700 Patent, Claim 1)
Context and Importance: This limitation defines the required purity of the formulation. The word "about" introduces a degree of ambiguity. The construction of "about" will be critical if Hospira's product has d-epinephrine levels at or very near the 6% threshold.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patentee's use of "about" signals an intent not to be strictly bound to the numerical value, allowing for minor variations or measurement tolerances.
- Evidence for a Narrower Interpretation: The patent repeatedly emphasizes the achievement of "new limits" for impurities. (’700 Patent, col. 5:35-40). A defendant may argue that "about" should be interpreted narrowly in light of the specification's emphasis on achieving specific, improved purity levels that distinguish it from the prior art.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced infringement under 35 U.S.C. § 271(b) and contributory infringement under § 271(c). (Compl. ¶¶ 31, 38). The inducement theory is based on allegations that Hospira's product package insert will direct medical professionals to use the product in an infringing manner. (Compl. ¶¶ 33, 40). The contributory infringement theory is supported by the allegation that Hospira’s product has no substantial noninfringing uses for the claimed indications. (Compl. ¶¶ 34, 41).
- Willful Infringement: The complaint alleges that Hospira was aware of the patents-in-suit at the time it submitted its Paragraph IV certification to the FDA. (Compl. ¶¶ 23, 32, 39). While the term "willful" is not used, this allegation of pre-suit knowledge could form the basis for a later claim of willful infringement. The prayer for relief also seeks a determination that the case is "exceptional" under 35 U.S.C. § 285, which could lead to an award of attorneys' fees. (Compl. p. 9).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core evidentiary question will be one of chemical composition: Does Hospira’s ANDA product, as it is actually formulated, possess the specific chemical properties required by the asserted claims—namely, a pH within the 2.8 to 3.3 range and d-epinephrine impurity levels below the claimed thresholds? The outcome of this factual inquiry, which will depend on discovery, is central to the dispute.
- A key legal question will be one of induced infringement: Will the language of Hospira’s proposed product label be found to actively encourage medical professionals to perform all steps of the patented methods, including administration for specific conditions and the method of continuous IV infusion detailed in the ’728 patent?
- A dispositive issue of claim construction will likely be the interpretation of "about" as it modifies the numerical impurity limits. The breadth the court affords this term will directly impact the analysis of whether Hospira's product literally infringes if its impurity levels are close to the claimed values.