DCT

1:17-cv-00775

Belcher Pharma LLC v. Hospira Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00775, D. Del., 06/16/2017
  • Venue Allegations: Venue is based on Defendant Hospira, Inc. being a Delaware corporation.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of a New Drug Application (NDA) for an epinephrine injection product constitutes an act of infringement under the Hatch-Waxman Act, as the proposed product would infringe a patent covering stable, low-impurity epinephrine formulations.
  • Technical Context: The technology concerns pharmaceutical chemistry, specifically creating stable, injectable epinephrine formulations that minimize degradation and impurities without relying on potentially allergenic sulfite-based preservatives.
  • Key Procedural History: This action was initiated under the Hatch-Waxman framework following Defendant's submission of NDA No. 209359 with a Paragraph IV certification, asserting that its proposed drug product does not infringe or that the patent-in-suit is invalid. The patent-in-suit is listed in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book") in connection with Plaintiff's own approved epinephrine product. The complaint was filed within the 45-day statutory window following receipt of Defendant's notice letter.

Case Timeline

Date Event
2014-08-15 ’197 Patent Priority Date
2016-03-15 ’197 Patent Issue Date
2017-05-03 Date of Hospira's Notice Letter and Paragraph IV Certification
2017-05-04 Approximate date Plaintiff received Hospira's Notice Letter
2017-06-16 Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,283,197 - "More Potent And Less Toxic Formulations Of Epinephrine And Methods Of Medical Use"

The Invention Explained

  • Problem Addressed: The patent's background section describes how existing liquid epinephrine formulations were plagued by chemical instability, specifically oxidation and racemization—the conversion of therapeutically active l-epinephrine into its less-active "d-epinephrine" isoform (’197 Patent, col. 2:56-59). Prior art solutions involved adding sulfite antioxidants, which can cause severe allergic reactions, and using "overages" of the active ingredient to compensate for degradation, leading to potentially hazardous and unpredictable dosing (’197 Patent, col. 2:15-28, 36-40).
  • The Patented Solution: The invention is a sulfite-free and preservative-free l-epinephrine formulation that achieves stability by controlling specific parameters. The specification describes the discovery that racemization was a more significant problem than oxidation, and that, contrary to expectations, raising the in-process pH to a narrow range of 2.8 to 3.3 "unexpectedly reduced the racemization of l-epinephrine" (’197 Patent, col. 4:49-55). This approach allows for a formulation with minimal overages and strictly controlled low levels of impurities like d-epinephrine and adrenalone over a long shelf-life.
  • Technical Importance: This technical approach allows for the creation of an epinephrine product that is potentially safer, by avoiding sulfite allergens, and more reliable, by ensuring a more consistent and predictable dosage of the active l-epinephrine isomer (’197 Patent, col. 2:52-55).

Key Claims at a Glance

  • The complaint explicitly identifies Claim 6 for infringement (Compl. ¶20). Claim 6 is an independent claim.
  • The essential elements of independent Claim 6 are:
    • An injectable liquid pharmaceutical formulation of l-epinephrine sterile solution;
    • said liquid pharmaceutical formulation having a pH between 2.8 and 3.3;
    • said injectable liquid pharmaceutical formulation compounded in an aqueous solution as 1.0 to 1.06 mg/mL l-epinephrine, and further including a tonicity agent;
    • 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.
  • The complaint reserves the right to assert other claims, stating the accused product is covered by "one or more claims" of the patent (Compl. ¶20, 24).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Hospira's Epinephrine Injection USP, Abboject™ Syringe 1mg/10mL (the “NDA Product”), which is the subject of New Drug Application (NDA) No. 209359 submitted to the U.S. Food and Drug Administration (FDA) (Compl. ¶8, 17).

Functionality and Market Context

As this is a Hatch-Waxman action, the infringement allegation is not based on a currently marketed product but on the technical specifications of the product for which Hospira seeks regulatory approval (Compl. ¶23). The complaint alleges that the manufacture of this proposed product will infringe the ’197 patent (Compl. ¶20). The technical details of the accused product's formulation, such as its pH and impurity profile, are contained within Hospira’s confidential NDA submission. No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-chart analysis. The infringement allegation is a conclusory statement that "The manufacture of Hospira's NDA Product is covered by one or more claims of the '197 patent, including but not limited to Claim 6" (Compl. ¶20). The factual basis for this allegation presumably resides in the contents of Hospira’s confidential NDA, which are not detailed in the complaint.

  • Identified Points of Contention: The dispute will likely center on a comparison of the technical data within Hospira's confidential NDA submission against the limitations of the asserted claims.
    • Technical Questions: The primary factual question is whether the formulation described in NDA No. 209359 possesses the characteristics required by the claims. Does Hospira’s stability and manufacturing data demonstrate a product with a pH between 2.8 and 3.3? Do the specifications for the product show levels of d-epinephrine and adrenalone, both at release and over a 12-month shelf-life, that fall within the claimed numerical limits?
    • Scope Questions: A likely point of dispute will be the interpretation of product-by-process language. Does the claim phrase "compounded in an aqueous solution as 1.0 to 1.06 mg/mL l-epinephrine" limit the claim to products made by a specific process, or does it merely describe a characteristic of the final product?

V. Key Claim Terms for Construction

  • The Term: "about" (e.g., "no more than about 6% d-epinephrine")

    • Context and Importance: This term of degree is critical, as infringement will depend on whether the impurity levels in Hospira's product, as specified in its NDA, fall within the range implied by "about." The difference between literal infringement and non-infringement could hinge on the scope afforded to this term.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of "about" itself suggests the patentee did not intend to be limited to the exact numerical values recited.
      • Evidence for a Narrower Interpretation: The specification contrasts the invention with prior art having specific, higher impurity levels (e.g., "approximately 14%...racemized" vs. the inventive method's reduction to "5%") (’197 Patent, col. 4:24-26, 51-52). This may suggest that the numerical values are technologically significant and the scope of "about" should be narrow.

  • The Term: "compounded in an aqueous solution as 1.0 to 1.06 mg/mL l-epinephrine"

    • Context and Importance: Practitioners may focus on this term because it raises the question of whether Claim 6 is a true "product-by-process" claim. If it is, Belcher might need to prove not only that Hospira’s final product has certain characteristics but also that its manufacturing process includes the recited "compounding" step.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation (as a product characteristic): A party could argue the phrase simply describes a property of the final solution (i.e., its concentration corresponds to having been made that way), rather than limiting the claim to the specific manufacturing act.
      • Evidence for a Narrower Interpretation (as a process limitation): The specification explicitly details a "compounding step" and a "batch formula per mL" (’197 Patent, col. 3:15, 28-35). A party could argue the term "compounded as" directly ties the claim to this described process, limiting its scope to products made in that manner.

VI. Other Allegations

  • Indirect Infringement: The complaint includes forward-looking allegations that the future commercial manufacture, use, or sale of the NDA Product will induce and contribute to infringement of the ’197 patent (Compl. ¶24).
  • Willful Infringement: The complaint alleges that Hospira was aware of the ’197 patent when it submitted its NDA, citing its required Paragraph IV certification as evidence of pre-suit knowledge (Compl. ¶19, 25). This allegation supports the request for a finding that the case is "exceptional" under 35 U.S.C. § 285 (Compl. ¶(F) at p. 6).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of evidentiary proof: does the technical data contained within Hospira's confidential NDA describe a product that meets every specific numerical limitation of the asserted claims, including pH, concentration, and impurity percentages at release and over time?
  • A key legal question will be one of claim scope: how broadly will the term "about" be construed in the context of the claimed impurity limits? The viability of the infringement claim may depend on whether this term encompasses the specific values found in Hospira's NDA data.
  • A central dispute may be one of claim type: will the "compounded as" language be interpreted as a product-by-process limitation, which would require Belcher to prove elements of Hospira's manufacturing method, or as a mere description of the final product's characteristics, which would focus the inquiry solely on the composition of the resulting formulation?