DCT

1:24-cv-04914

AbbVie Inc v. Fresenius Kabi USA LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-04914, N.D. Ill., 06/13/2024
  • Venue Allegations: Venue is alleged to be proper in the Northern District of Illinois based on Defendant Fresenius USA's principal place of business being located in Lake Zurich, Illinois, and its registration to do business in the state.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the antibacterial drug AVYCAZ® constitutes an act of infringement of five U.S. patents covering crystalline forms of the active ingredient avibactam, pharmaceutical compositions, and processes for preparing the compound.
  • Technical Context: The dispute concerns avibactam, a beta-lactamase inhibitor combined with the cephalosporin antibiotic ceftazidime to treat serious, and often drug-resistant, Gram-negative bacterial infections.
  • Key Procedural History: The complaint states this action is a "protective suit" intended to preserve Plaintiffs' rights under the Hatch-Waxman Act, noting a separate suit was filed against Fresenius and other parties in the District of New Jersey on June 6, 2024.

Case Timeline

Date Event
2009-11-23 Priority Date for ’025 and ’455 Patents
2012-06-15 Priority Date for ’566, ’314, and ’122 Patents
2013-06-25 ’025 Patent Issued
2014-09-16 ’455 Patent Issued
2015-02-25 FDA approved AVYCAZ® New Drug Application
2015-03-03 ’566 Patent Issued
2016-03-15 ’314 Patent Issued
2017-07-04 ’122 Patent Issued
2024-04-30 Plaintiffs received Defendants' Notice Letter regarding ANDA submission
2024-06-13 Complaint Filed

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

No probative visual evidence provided in complaint.

U.S. Patent No. 8,471,025, “Crystalline forms of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide sodium salt,” issued June 25, 2013 (’025 Patent)

The Invention Explained

  • Problem Addressed: The patent describes that the active pharmaceutical ingredient, avibactam sodium salt (referred to as NXL-104), is intrinsically sensitive to moisture and heat, particularly in its amorphous (non-crystalline) form. This instability can lead to degradation, which poses a challenge for creating a stable, manufacturable drug product. (’025 Patent, col. 4:36-52).
  • The Patented Solution: The invention provides novel crystalline forms, or polymorphs, of avibactam sodium salt. These crystalline forms arrange the molecules in a defined, repeating lattice structure, which is intended to improve physical properties such as stability and ease of handling compared to the amorphous form. The patent identifies and characterizes these new forms using techniques like X-Ray Powder Diffractometry (XRPD), which produces a unique pattern of peaks for each crystalline structure. (’025 Patent, Abstract; col. 4:28-32, FIG. 2).
  • Technical Importance: Discovering stable crystalline forms of a drug substance is a critical step in pharmaceutical development, enabling the creation of a product with a reliable and consistent shelf life and manufacturing process. (Compl. ¶58).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’025 Patent (Compl. ¶77). Claim 1 is the first independent claim.
  • Claim 1 Elements:
    • A crystalline form of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide or a pharmaceutically acceptable salt thereof,
    • wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peak at about 13.0 and about 17.3+/-0.5 degrees 20.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 8,835,455, “Crystalline forms of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide sodium salt,” issued September 16, 2014 (’455 Patent)

The Invention Explained

  • Problem Addressed: The patent addresses the need for pharmaceutical compositions containing avibactam sodium salt that have a high degree of purity and stability. A key challenge in drug formulation is minimizing the presence of degradation products and process impurities, which can affect the safety and efficacy of the final product. (’455 Patent, col. 17:1-20).
  • The Patented Solution: The invention is directed to a pharmaceutical composition containing the sodium salt of avibactam that is defined by a low level of a specific impurity, identified as a "decarbonyl compound." By claiming a composition with less than about 2% of this impurity, the patent seeks to protect a stable and pure formulation of the drug substance suitable for therapeutic use. (’455 Patent, col. 18:1-20, Claim 1).
  • Technical Importance: Controlling impurity levels is a fundamental requirement of pharmaceutical manufacturing regulated by health authorities like the FDA; patents on low-impurity compositions can provide protection for the final, commercially viable drug product.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’455 Patent (Compl. ¶97). Claim 1 is the first independent claim.
  • Claim 1 Elements:
    • A pharmaceutical composition comprising a sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3,2,1]octane-2-carboxamide
    • and a compound of Formula (I) [the decarbonyl compound],
    • wherein the composition comprises about 0.05% to about 1.5% of the compound of Formula (I).
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 8,969,566, “Processes for preparing heterocyclic compounds including trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof,” issued March 3, 2015 (’566 Patent)

  • Technology Synopsis: This patent claims processes for making avibactam and related compounds. The invention provides specific chemical synthesis routes and methods for preparing these heterocyclic compounds, which are useful as beta-lactamase inhibitors. (’566 Patent, Abstract).
  • Asserted Claims: One or more claims are asserted (Compl. ¶117). Claim 1 is the first independent claim.
  • Accused Features: The process by which Defendants manufacture or intend to manufacture the avibactam sodium salt for their proposed generic product is alleged to infringe. (Compl. ¶119, ¶131).

U.S. Patent No. 9,284,314, “Processes for preparing heterocyclic compounds including trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof,” issued March 15, 2016 (’314 Patent)

  • Technology Synopsis: As a continuation in the same family as the ’566 Patent, this patent also claims processes for preparing avibactam and related compounds. It describes specific chemical synthesis pathways for producing the drug substance. (’314 Patent, Abstract).
  • Asserted Claims: One or more claims are asserted (Compl. ¶138). Claim 1 is the first independent claim.
  • Accused Features: The manufacturing process for the avibactam sodium salt active ingredient in Defendants' proposed generic product is the accused instrumentality. (Compl. ¶140, ¶152).

U.S. Patent No. 9,695,122, “Processes for preparing heterocyclic compounds including trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof,” issued July 4, 2017 (’122 Patent)

  • Technology Synopsis: This patent is also in the same family as the ’566 and ’314 patents and is directed to processes for making avibactam and its salts. The claims cover methods of chemical synthesis for the active pharmaceutical ingredient. (’122 Patent, Abstract).
  • Asserted Claims: One or more claims are asserted (Compl. ¶159). Claim 1 is the first independent claim.
  • Accused Features: The infringement allegation targets the process Defendants use to synthesize the avibactam sodium salt for their ANDA product. (Compl. ¶161).

III. The Accused Instrumentality

Product Identification

Defendants’ proposed generic version of AVYCAZ®, identified as "Ceftazidime and Avibactam for Injection, 2 g/0.5 g per vial, Sterile Powder," which is the subject of ANDA No. 219325 (Compl. ¶2, ¶68).

Functionality and Market Context

The accused product is an antibacterial combination drug intended for injection (Compl. ¶64, ¶68). As a generic, it is represented to the FDA as having the same active ingredients (ceftazidime and avibactam), dosage form, strength, and route of administration as Plaintiffs' brand-name AVYCAZ® product (Compl. ¶72). AVYCAZ® is used to treat serious bacterial infections, including complicated intra-abdominal infections and complicated urinary tract infections (Compl. ¶65). The complaint alleges that Defendants' submission of the ANDA seeking FDA approval to market this generic product before the expiration of the patents-in-suit is an act of infringement (Compl. ¶4, ¶68-69).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed claim chart or specific factual allegations mapping claim elements to the accused product. The infringement theory for the product patents (’025 and ’455) appears to be based on the regulatory requirement that Fresenius's proposed generic product contains the same active ingredients and is bioequivalent to Plaintiffs' AVYCAZ® product, which Plaintiffs allege embodies the patented inventions (Compl. ¶72). The infringement theory for the process patents is based on information and belief that the process used to make the generic product will infringe the patented methods (Compl. ¶131, ¶152).

’025 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide or a pharmaceutically acceptable salt thereof... The avibactam sodium salt active pharmaceutical ingredient contained in Defendants' proposed generic product is alleged to be this patented crystalline form. ¶68, ¶72, ¶77 col. 4:28-32
...wherein the crystalline form has an X-Ray powder diffraction pattern comprising a characteristic peak at about 13.0 and about 17.3+/-0.5 degrees 20. Based on the requirement for bioequivalence with AVYCAZ®, the complaint infers that the avibactam sodium salt in the proposed generic product will exhibit these claimed XRPD peaks. ¶72, ¶77 col. 5:1-4
  • Identified Points of Contention:
    • Evidentiary Question: The complaint does not present direct evidence (such as analytical data from the accused product) that the avibactam in Fresenius's ANDA product is the specific crystalline form claimed in the ’025 Patent. A central dispute will be the actual polymorphic form of avibactam used by Fresenius, which may be a different, non-infringing polymorph or an amorphous form. Plaintiffs note they have not yet received access to the confidential ANDA (Compl. ¶74).
    • Scope Question: The claim uses the term "about" to describe the location of the XRPD peaks. The interpretation of this term will be critical in determining whether minor variations in the measured peaks of the accused product would still fall within the scope of the claim.

’455 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising a sodium salt of (1R,2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide... The finished drug product described in ANDA No. 219325 is alleged to be this pharmaceutical composition. ¶68, ¶97, ¶99 col. 45:12-19
...and a compound of Formula (I), wherein the composition comprises about 0.05% to about 1.5% of the compound of Formula (I). The complaint alleges on information and belief that Defendants' proposed product will meet this purity limitation, as it is intended for commercial sale and must meet regulatory standards for stability and purity. ¶97, ¶99 col. 45:15-19
  • Identified Points of Contention:
    • Evidentiary Question: The infringement allegation depends on the actual impurity profile of the accused generic product. The complaint lacks specific data on the level of the "decarbonyl compound" in Fresenius's product. The dispute will turn on analytical testing of the accused product to determine if it meets the claimed purity profile.

V. Key Claim Terms for Construction

  • The Term: "a characteristic peak at about [X] degrees 20" (’025 Patent, Claim 1)
  • Context and Importance: This term defines the scope of the claim to the crystalline form. The word "about" creates a potential ambiguity regarding how close a measured XRPD peak from an accused product must be to the recited value to infringe. Practitioners may focus on this term because the entire infringement analysis for the ’025 Patent could depend on whether Fresenius's product, if it has a similar but not identical XRPD pattern, falls within the range implied by "about."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The repeated use of "about" throughout the claims suggests the patentee did not intend the values to be exact and anticipated some experimental variability.
    • Evidence for a Narrower Interpretation: The specification provides an explicit range in some descriptions, stating "at about 13.0+/-0.5 degrees 20" (’025 Patent, col. 4:55-57). A party could argue this text defines the precise scope of "about 13.0," limiting it to the 12.5-13.5 range. The patent also provides tables with peak values measured to two decimal places (e.g., "12.97"), which a party could argue suggests a higher degree of precision is intended. (’025 Patent, col. 5:22-24).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that should FDA approval be granted, Defendants will induce infringement by marketing their generic product and encouraging doctors and patients to use it for its intended, patented purpose (Compl. ¶79-81, ¶99-101). Contributory infringement is also alleged on the basis that the product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶82, ¶102).
  • Willful Infringement: The complaint does not use the word "willful" but alleges that Defendants have had knowledge of the patents-in-suit since at least the time they sent their Notice Letter (Compl. ¶83, ¶103). The prayer for relief requests a declaration that the case is "exceptional" and an award of attorneys' fees, which is the statutory remedy for conduct such as willful infringement (Compl. ¶185).

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

This case appears to be a standard Hatch-Waxman action where the initial complaint is based on the statutory act of infringement (the ANDA filing) rather than on technical analysis of the actual generic product. The central issues will likely be factual and evidentiary, emerging only after Plaintiffs gain access to the confidential portion of the ANDA and product samples.

  • A core issue will be one of polymorphic identity: What is the actual solid-state form of the avibactam sodium active ingredient in Fresenius's proposed generic product? The outcome of the infringement analysis for the ’025 Patent will depend entirely on whether that form is the specific crystalline polymorph claimed by Plaintiffs.
  • A second key question will be one of process identity: Does the confidential manufacturing process described in Fresenius's ANDA for synthesizing avibactam fall within the scope of the steps claimed in the ’566, ’314, and ’122 patents? This will require a direct comparison of the ANDA process against the claim language.
  • A final evidentiary question will be one of compositional purity: Does the final drug product specified in the ANDA meet the impurity limitations claimed in the ’455 Patent? This will depend on the stability and analytical data contained within the ANDA submission.