Fresenius Kabi USA LLC v. Amneal Pharma LLC

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Fresenius Kabi USA, LLC (Delaware)
  • Defendant: Amneal Pharmaceuticals LLC, Amneal Pharmaceuticals of New York, LLC, and Amneal EU, Limited (collectively "Amneal")
  • Plaintiff’s Counsel: Hill Wallack LLP
• Case Identification: 2:23-cv-04343, D.N.J., 08/11/2023
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendants having a principal place of business in the district, engaging in systematic business contacts, and having previously not contested venue in the district in other litigation.
• Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the anesthetic Diprivan® constitutes an act of infringement of a patent related to stable propofol formulations.
• Technical Context: The lawsuit concerns pharmaceutical formulations of propofol, a widely used intravenous sedative and anesthetic, and specifically addresses the chemical stability of the drug when stored in containers with certain types of closures.
• Key Procedural History: The complaint notes that after an inter partes review (IPR) proceeding, the U.S. Patent and Trademark Office cancelled several claims of the patent-in-suit, including independent claim 1. The complaint’s primary infringement allegations are based on dependent claim 21, which depends from the now-cancelled claim 1, raising a threshold question about the viability of the infringement claim.

Case Timeline

Date	Event
2003-07-10	'010 Patent Priority Date (Filing)
2013-07-02	'010 Patent Issue Date
2020-01-16	USPTO cancels claims 1, 13-15, 17, 18, 20, and 24-28 of the '010 Patent post-IPR
2023-06-28	Defendant sends Notice Letter regarding ANDA filing
2023-08-11	Complaint Filing Date

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

No probative visual evidence provided in complaint.

U.S. Patent No. 8,476,010 - "Propofol Formulations with Non-Reactive Container Closures"

• Patent Identification: U.S. Patent No. 8,476,010, “Propofol Formulations with Non-Reactive Container Closures,” issued July 2, 2013.

The Invention Explained

• Problem Addressed: The patent describes challenges with formulating the anesthetic propofol. While reducing the oil content in propofol emulsions can mitigate the risk of hyperlipidemia in patients, the patent asserts that these low-oil formulations are susceptible to degradation when stored in containers sealed with common closures, such as rubber stoppers ('010 Patent, col. 4:43-65). This degradation can lead to a loss of potency and the formation of impurities ('010 Patent, col. 4:50-56).
• The Patented Solution: The invention claims a sterile propofol composition stored in a container having a closure that is "inert or non-reactive," thereby preventing significant degradation of the propofol ('010 Patent, Abstract). The patent teaches that certain closures, such as those made of metal or coated with fluoropolymers, maintain propofol stability, while specific rubber closures cause substantial potency loss ('010 Patent, col. 24:22-35). The claims define this stability with a functional requirement: the composition must maintain at least 93% of its initial propofol concentration after being agitated for 16 hours under specific conditions.
• Technical Importance: The patented solution purports to enable the creation of low-oil propofol formulations that remain stable over time, combining the clinical benefit of reduced lipid load with the shelf-life required for a commercial pharmaceutical product ('010 Patent, col. 4:36-42).

Key Claims at a Glance

• The complaint asserts infringement of at least claim 21 of the ’010 Patent (Compl. ¶47).
• Claim 21 is a dependent claim that incorporates all limitations of claim 1, which the complaint acknowledges was cancelled by the USPTO (Compl. ¶36, ¶48). The essential elements of asserted claim 21 are:
  • A sterile pharmaceutical composition of propofol in a container, which includes a closure and the composition.
  • The composition comprises from 0.5% to 10% by weight propofol and from about 0 to about 10% by weight solvent for propofol.
  • When agitated at a frequency of 300-400 cycles/minute for 16 hours at room temperature, the composition maintains a propofol concentration that is at least 93% of the starting concentration.
  • The closure is selected from the group consisting of siliconized bromobutyl rubber, metal, and siliconized chlorobutyl rubber.
  • The closure also comprises metal.
• The complaint does not explicitly reserve the right to assert other dependent claims.

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are Defendants' generic Diprivan® products, specifically identified as "Propofol Injectable Emulsion USP, 10 mg/mL, in 20 mL, 50 mL and 100 mL single-dose vials," for which Defendants filed ANDA No. 217525 with the FDA (Compl. ¶40).

Functionality and Market Context

• The accused product is a generic version of an injectable emulsion containing propofol, a drug used for the induction and maintenance of general anesthesia and sedation (Compl. ¶38). The complaint alleges that Defendants seek FDA approval to manufacture, use, offer for sale, and sell this product in the United States prior to the expiration of the ’010 Patent (Compl. ¶40).

IV. Analysis of Infringement Allegations

’010 Patent Infringement Allegations

Claim Element (from Independent Claim 1, as incorporated into asserted Claim 21)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a sterile pharmaceutical composition of propofol in a container; a container which includes a closure and a composition in the container;	The complaint alleges on information and belief that Defendants' generic products comprise this element.	¶49	col. 4:6-9
a composition in the container comprising from 0.5% to 10% by weight propofol and from about 0 to about 10% by weight solvent for propofol,	The complaint alleges on information and belief that the accused products' composition contains propofol and solvent within these specified weight percentages.	¶49	col. 5:30-33
where when the composition in the container sealed with the closure is agitated at a frequency of 300-400 cycles/minute for 16 hours at room temperature, the composition maintains a propofol concentration (w/v) measured by HPLC that is at least 93% of the starting concentration (w/v) of the propofol;	The complaint alleges on information and belief that the accused products meet this functional stability requirement.	¶49	col. 23:22-38
where the closure is selected from the group consisting of siliconized bromobutyl rubber, metal, and siliconized chlorobutyl rubber;	The complaint alleges on information and belief that the accused products use a closure selected from this group.	¶49	col. 28:1-3
and wherein the closure also comprises metal.	The complaint alleges on information and belief that the accused products' closure comprises metal, thus meeting the additional limitation of claim 21.	¶49	col. 29:10-11

• Identified Points of Contention:
  • Legal Question: A threshold legal issue is presented by Plaintiff's assertion of dependent claim 21, as the complaint acknowledges that its parent, independent claim 1, was cancelled during inter partes review (Compl. ¶36). This raises the question of whether an infringement action can be maintained on a dependent claim whose base claim is no longer part of the patent.
  • Technical Question: The complaint's infringement allegations are made "upon information and belief" (Compl. ¶49). A central factual dispute will likely concern whether the accused generic product actually meets the quantitative functional limitation of the claim—specifically, whether it maintains at least 93% propofol concentration under the rigorous agitation test described in the patent. The complaint does not present any test data to support this allegation.

V. Key Claim Terms for Construction

• The Term: "closure"

• Context and Importance: The concept of an "inert" or "non-reactive" closure is the central inventive concept. The definition of "closure" and whether a specific component of the accused product qualifies will be fundamental to the infringement analysis. Practitioners may focus on this term because the asserted claim limits it to a specific Markush group, and the dispute will likely involve mapping the accused product's components onto that group.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification describes a closure in general terms as potentially being a "rubber stopper, plunger, lid, top or the like" (ʼ010 Patent, col. 9:38-39).
  • Evidence for a Narrower Interpretation: The asserted claim itself narrows the term to a Markush group of "siliconized bromobutyl rubber, metal, and siliconized chlorobutyl rubber" (ʼ010 Patent, col. 28:1-3). A party could argue that the term should be further limited by the patent's teaching that the closure must be "inert or non-reactive" such that it does not cause "significant degradation or loss in potency" ('010 Patent, col. 6:40-49).

• The Term: "solvent for propofol"

• Context and Importance: The patent's premise is that degradation is a particular problem in low-solvent formulations. The claim limitation of "from about 0 to about 10% by weight solvent" makes the definition of "solvent" critical for determining whether the accused formulation falls within the scope of the claim.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification provides a wide-ranging list of potential solvents, including vegetable oils, marine oils, esters of fatty acids, and other organic solvents (ʼ010 Patent, col. 5:50-67).
  • Evidence for a Narrower Interpretation: A party could argue that the term should be interpreted in the context of the patent's examples, which focus on soybean oil as the solvent whose presence or absence affects propofol stability when in contact with certain closures (ʼ010 Patent, col. 25, Example 34).

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Defendants will induce infringement by directing others (e.g., healthcare providers) to use the generic product upon its approval and sale (Compl. ¶52). The factual basis for this allegation is the anticipated commercial launch following FDA approval.
• Willful Infringement: The complaint does not use the term "willful," but it does allege pre-suit knowledge of the patent, stating that "Defendants were aware of the '010 patent prior to the submission of Defendants' ANDA" (Compl. ¶51). This knowledge is also evidenced by the filing of a Paragraph IV certification, which is a required element of the ANDA process when challenging a listed patent.

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

This case appears to present two primary questions for the court, one legal and one factual.

• A dispositive threshold issue will be one of legal viability: can Plaintiff maintain an infringement action based on dependent claim 21 when the independent claim from which it depends, claim 1, was previously cancelled by the U.S. Patent and Trademark Office?
• Should the case proceed past the initial pleadings, a central evidentiary question will be one of functional performance: does discovery and testing reveal that the accused generic product's formulation and closure system meets the specific, quantitative stability requirement of maintaining at least 93% propofol concentration after 16 hours of prescribed agitation, as mandated by the asserted claim?