United States Patent 6,028,222: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
The United States Patent 6,028,222, titled "Stable Liquid Paracetamol Compositions, and Method for Preparing Same," is a crucial patent in the pharmaceutical industry, particularly in the formulation and stabilization of acetaminophen (also known as paracetamol) solutions. This patent, held by Pharmatop and exclusively licensed to Cadence Pharmaceuticals, Inc., has been at the center of significant litigation and has played a key role in the market for injectable acetaminophen products.
Background of the Invention
Acetaminophen is a widely used analgesic and antipyretic drug, commonly found in various over-the-counter and prescription medications. However, in aqueous solutions, acetaminophen is prone to decomposition into potentially toxic products, which necessitates the development of stable formulations[2][4].
Patent Overview
Issuance and Expiration
The '222 patent was issued on February 22, 2000, and it expired on August 5, 2017. It originated from U.S. Patent Application No. 09/051,246, which claimed priority to French Application No. 96/09858 filed on August 5, 1996[1][2].
Inventors and Assignees
The named inventors of the '222 patent are Francois Dietlin and Daniele Fredj. The patent is owned by Pharmatop, with Cadence Pharmaceuticals holding an exclusive license[1][2].
Claims of the Patent
Independent Claim
The '222 patent contains a single independent claim, which is Claim 1:
- "A stable, liquid formulation consisting essentially of acetaminophen dispersed in an aqueous medium containing a buffering agent and at least one member of the group consisting of a free radical scavenger and a radical antagonist."[1][2].
Dependent Claims
The patent includes several dependent claims that further specify the conditions and components of the formulation. For example:
- Claim 3: The formulation of Claim 1 wherein the aqueous medium is buffered at a pH of 4 to 8.
- Claim 4: The formulation of Claim 3 wherein the aqueous medium is buffered at a pH of 5.5 to 6.
- Claim 5: The formulation of Claim 1 containing a free radical antagonist selected from the group consisting of ascorbic acid, ascorbic acid derivatives, organic compounds having at least one thiol, and alkyl polyhydroxylated and cycloalkyl polyhydroxylated compounds[1][2].
Stabilization Mechanism
The patent addresses the stability issue of acetaminophen in aqueous solutions by introducing two key components:
- Buffering Agent: To maintain a stable pH, which helps in preventing the decomposition of acetaminophen.
- Free Radical Scavenger/Radical Antagonist: To capture free radicals and prevent the oxidation of acetaminophen, thereby maintaining its stability[1][2][4].
Manufacturing Process
The patent also describes a process for preparing these stable formulations, which includes bubbling the aqueous solvent with an inert gas to remove oxygen and maintain the stability of acetaminophen[4].
Litigation and Infringement
The '222 patent has been central to litigation involving Cadence Pharmaceuticals and Exela PharmSci, Inc. Exela filed an Abbreviated New Drug Application (ANDA) with the FDA for a generic version of Cadence's injectable acetaminophen product, Ofirmev®, which led to a patent infringement lawsuit. The district court found that Exela infringed claims 1, 3, 4, 5, 9, 10, 12, 16, 17, and 18 of the '222 patent and that these claims were valid[2].
Claim Construction and Appeal
Exela appealed the district court's construction of certain claim terms, but the Federal Circuit affirmed the district court's decisions on both infringement and validity. The appeal highlighted the importance of claim construction in patent litigation and the application of the doctrine of equivalents[2].
Reexamination by USPTO
In 2013, the USPTO initiated an ex parte reexamination of the '222 patent following a third-party request. Although the USPTO issued a non-final initial office action rejecting certain claims, Cadence Pharmaceuticals remained confident in the patent's validity and scope. The reexamination process is ongoing, but it does not affect the pending litigation[5].
Patent Landscape
The '222 patent is part of a broader patent landscape related to acetaminophen formulations. Another key patent in this landscape is U.S. Patent No. 6,992,218, which covers the process for deoxygenating aqueous formulations to stabilize acetaminophen. This patent also involves bubbling with an inert gas or placing under vacuum to reduce oxygen content below 2 ppm[2][4].
Market Impact
The '222 patent has significant market implications, particularly in the context of injectable acetaminophen products. Cadence Pharmaceuticals' product, Ofirmev®, is protected by this patent, and any generic versions would need to navigate the claims and validity of this patent. The litigation and reexamination processes have underscored the importance of this patent in maintaining market exclusivity[2][5].
Key Takeaways
- The '222 patent addresses the stability of acetaminophen in aqueous solutions through the use of buffering agents and free radical scavengers/antagonists.
- The patent includes a single independent claim and several dependent claims that specify the formulation conditions.
- The patent has been central to litigation involving Cadence Pharmaceuticals and Exela PharmSci, Inc.
- The USPTO has initiated a reexamination of the patent, but the claims remain valid until a final action is taken.
- The patent is crucial for maintaining market exclusivity for injectable acetaminophen products like Ofirmev®.
FAQs
What is the main innovation of the '222 patent?
The main innovation of the '222 patent is the development of stable aqueous formulations of acetaminophen by using a buffering agent and a free radical scavenger or radical antagonist to prevent decomposition.
Who are the inventors of the '222 patent?
The inventors of the '222 patent are Francois Dietlin and Daniele Fredj.
What is the current status of the '222 patent?
The '222 patent expired on August 5, 2017, but its validity and scope were subject to litigation and reexamination processes during its term.
How does the '222 patent relate to Ofirmev®?
The '222 patent covers the formulation of Ofirmev®, an injectable acetaminophen product marketed by Cadence Pharmaceuticals.
What was the outcome of the litigation between Cadence and Exela?
The district court found that Exela infringed the '222 patent and that the claims were valid. The Federal Circuit affirmed this decision on appeal.
Cited Sources:
- District of Delaware - Cadence Pharm., Inc. v. Exela PharmSci, Inc., 2013 U.S. Dist. LEXIS 166097 (D.Del. Nov. 14, 2013).
- Casetext - Cadence Pharms. Inc. v. Exela Pharmsci Inc.
- SSRN - Patent Claims and Patent Scope, September 2016.
- Google Patents - Aqueous formulations of acetaminophen for injection, WO2009047634A2.
- Mallinckrodt - Cadence Pharmaceuticals Comments on USPTO's Non-Final, Initial Office Action on Reexamination of Patent.
