DCT

1:21-cv-01764

InfoRLife SA v. Hikma Pharma USA Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-01764, D. Del., 12/16/2021
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because the defendant, Hikma, is a corporation organized and existing under the laws of Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic midazolam intravenous solution constitutes an act of infringement of a patent covering a stable, ready-to-use formulation of the drug in a flexible bag.
  • Technical Context: The technology concerns ready-to-use intravenous formulations of the sedative midazolam, designed to improve safety and efficiency in clinical settings by eliminating the need for manual dilution of the drug from vials.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter from Hikma, dated November 3, 2021, which informed the Plaintiffs of its ANDA filing containing a Paragraph IV certification against the patent-in-suit. The complaint states it was filed within the 45-day statutory window, triggering a potential 30-month stay of FDA approval for Hikma's generic product.

Case Timeline

Date Event
2018-06-20 ’990 Patent Priority Date
2021-04-06 ’990 Patent Issue Date
2021-11-03 Hikma sends Paragraph IV Notice Letter
2021-12-16 Complaint Filing Date

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

  • Patent Identification: U.S. Patent No. 10,966,990, “MIDAZOLAM IN FLEXIBLE BAGS,” issued April 6, 2021.

The Invention Explained

  • Problem Addressed: The patent’s background section describes how the sedative midazolam is typically supplied in vials, requiring hospital personnel to manually transfer and dilute it into an IV bag before administration. This process introduces risks of medication errors, microbial contamination, and logistical challenges, as diluted solutions have a very short shelf-life, sometimes only four hours. (’990 Patent, col. 1:10-21, 1:45-54).
  • The Patented Solution: The invention is a pre-packaged, "ready-to-use" midazolam solution that is terminally sterilized and stable for long-term storage. The solution is specifically formulated with midazolam, water, a tonicity adjusting agent (like sodium chloride) to achieve a specific osmolality, and an acid (hydrochloric acid) to maintain a low pH (2.5 to 3.5), which is critical for midazolam's solubility and stability. This specific formulation is packaged in a multi-layer flexible plastic bag designed to be compatible with the drug and withstand sterilization. (’990 Patent, Abstract; col. 2:45-62).
  • Technical Importance: By providing a pre-mixed, stable formulation with a long shelf-life, the invention aims to offer "convenience and value to the medical profession because they do not require dilution," thereby reducing admixture errors and improving patient safety. (’990 Patent, col. 1:46-49).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1-4, 6-9, and 11-13, with claim 1 identified as an exemplary independent claim (Compl. ¶27, ¶28).
  • The essential elements of independent claim 1 are:
    • A ready-to-use terminally sterilized, preservative-free aqueous midazolam solution in an intravenous laminated flexible plastic bag.
    • The solution comprises 0.25 to 1.5 mg/ml of midazolam.
    • It contains a sufficient tonicity adjusting agent (selected from sodium chloride, potassium chloride, and calcium chloride) to yield an osmolality of 260 to 320 mosm/kg.
    • It contains sufficient acid (hydrochloric acid) and optionally a base (sodium hydroxide) to provide a pH of about 2.5 to 3.5.
    • The midazolam content remains greater than 97% after accelerated storage at 40° C. for six months.
    • The bag comprises from 3 to 7 layers and has an innermost layer comprising an ethylene-vinyl acetate copolymer.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Hikma’s ANDA Product," a generic version of "midazolam in 0.9% sodium chloride (50 mg/50 ml and 100 mg/100 ml) solution, for intravenous use" (Compl. ¶1).

Functionality and Market Context

  • The product is described as a ready-to-use solution for continuous intravenous infusion for sedation of patients in critical care settings (Compl. ¶14, ¶16). It is intended to be a generic equivalent to Plaintiff InfoRLife’s FDA-approved midazolam product (Compl. ¶1). The complaint alleges the product is contained in a "flexible plastic IV bag" (Compl. ¶26).

IV. Analysis of Infringement Allegations

The complaint alleges that Hikma's ANDA product infringes at least claim 1 of the ’990 Patent "under the doctrine of equivalents" (Compl. ¶29). The allegations are based on Plaintiffs' review of confidential information from Hikma's ANDA submission (Compl. ¶15).

No probative visual evidence provided in complaint.

’990 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A ready-to-use terminally sterilized, preservative-free aqueous midazolam solution in an intravenous laminated flexible plastic bag... The accused product is a ready-to-use midazolam solution for intravenous use in a "flexible plastic IV bag." ¶1, ¶16, ¶26 col. 2:63-65
comprising 0.25 to 1.5 mg/ml of midazolam... The product is formulated at 50 mg/50 ml and 100 mg/100 ml, both equivalent to 1 mg/ml, which is within the claimed range. ¶1 col. 2:35-37
sufficient tonicity adjusting agent to provide an osmolality of from 260 and 320 mosm/kg... wherein: the tonicity adjusting agent comprises... sodium chloride... The product is described as "midazolam in 0.9% sodium chloride." Sodium chloride is a claimed tonicity agent. ¶1, ¶26 col. 2:45-52
sufficient acid... to provide a pH of from about 2.5 to 3.5... wherein: the acid comprises hydrochloric acid... The complaint does not provide sufficient detail for analysis of the specific acid or pH. col. 3:4-10
the midazolam content after accelerated storage at 40° C. for six months is greater than 97% The complaint alleges infringement based on review of Hikma's confidential ANDA, implying the product meets this stability requirement. ¶15, ¶29 col. 6:28-40
the intravenous laminated flexible plastic bag comprises from 3 to 7 layers and has an innermost layer comprises an ethylene-vinyl acetate coplymer [sic]. The complaint alleges the product is in a "flexible plastic IV bag" but provides no further detail on its construction. ¶26 col. 3:27-32
  • Identified Points of Contention:
    • Doctrine of Equivalents: The complaint's explicit allegation of infringement of claim 1 "under the doctrine of equivalents" (Compl. ¶29) raises the question of which claim limitations are not literally met by the accused product. This suggests that Plaintiffs anticipate a dispute over whether certain features of Hikma's product are different from, but legally equivalent to, the claimed elements.
    • Bag Construction: A central question will be whether Hikma’s "flexible plastic IV bag" (Compl. ¶26) has the specific structure required by claim 1: "from 3 to 7 layers" with an "innermost layer" of "ethylene-vinyl acetate coplymer." The reliance on the doctrine of equivalents may indicate that Hikma's bag is constructed from different materials or has a different number of layers.
    • Formulation Specifics: The court will need to examine the confidential ANDA materials to determine if the accused product uses "hydrochloric acid" as the acid and meets the specific stability requirement of the claim.

V. Key Claim Terms for Construction

  • The Term: "intravenous laminated flexible plastic bag"
    • Context and Importance: The definition of this term is critical, as the claim further constrains it with specific requirements for the number of layers and the material of the innermost layer. Practitioners may focus on this term because the plaintiff's reliance on the doctrine of equivalents suggests the defendant's bag may differ from the literal claim language, making the scope of this term a central point of dispute.
    • Evidence for a Broader Interpretation: A party could argue the term should be interpreted broadly to cover various suitable containers, pointing to specification language that lists several types of commercially available bags and materials for pharmaceutical use. (’990 Patent, col. 3:15-24, col. 4:12-21).
    • Evidence for a Narrower Interpretation: A party could argue the term is narrowed by the explicit wherein clause of claim 1 itself, which requires "from 3 to 7 layers" and an "innermost layer comprises an ethylene-vinyl acetate coplymer." The specification’s reference to Nexcel® bags as a preferred and tested embodiment could be used to support this narrower construction. (’990 Patent, col. 3:31-32, col. 6:35-40).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Hikma will actively induce infringement upon ANDA approval. This allegation is based on the assertion that Hikma’s proposed product labeling will instruct healthcare professionals to administer the product in a manner that infringes the ’990 Patent. (Compl. ¶33, ¶34).
  • Willful Infringement: The complaint alleges that Hikma was aware of the ’990 Patent before it submitted its ANDA and therefore acted with knowledge of the patent. (Compl. ¶34). It further alleges that Hikma proceeded "without a reasonable basis for believing that it would not be liable for infringement," which forms the basis for a claim of willfulness and a request for enhanced damages and attorneys' fees. (Compl. ¶37; Prayer for Relief ¶E).

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

  • A core issue will be one of technical equivalence: Given the complaint’s reliance on the doctrine of equivalents, a central question is whether features of Hikma’s product—particularly the construction of its flexible IV bag—perform substantially the same function in substantially the same way to achieve the same result as the specific limitations recited in the patent claims, even if they are not identical.
  • A key evidentiary question will be one of ANDA disclosure: The infringement analysis will depend heavily on the confidential details within Hikma’s ANDA submission. The determination of infringement will turn on what this evidence reveals about the accused product’s precise chemical formulation, stability data, and packaging materials.