United States Patent 5,824,784: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
United States Patent 5,824,784, titled "N-terminally chemically modified protein compositions and methods," is a significant patent in the field of biotechnology, particularly in the modification of proteins. This patent, issued to various inventors, has been central in several high-profile litigations involving biosimilar products.
Background and Invention
The patent describes methods and compositions related to the attachment of water-soluble polymers to proteins, specifically focusing on N-terminal modifications. This technology is crucial for enhancing the stability, solubility, and half-life of therapeutic proteins. For instance, the patent discusses the pegylation of proteins, a process where polyethylene glycol (PEG) molecules are covalently attached to the protein, often at the N-terminus[1].
Key Claims
The patent includes several key claims that define its scope:
- Claim 1: This claim describes a method for preparing a protein composition by attaching a water-soluble polymer to the N-terminus of a protein.
- Claim 2: This claim specifies the type of water-soluble polymer, such as polyethylene glycol (PEG), and the conditions under which the attachment is performed.
- Claim 3: This claim details the resulting protein composition and its characteristics, including improved stability and solubility.
These claims are foundational in understanding the patent's scope and its application in biotechnology[1].
Patent Landscape
The patent landscape surrounding U.S. Patent 5,824,784 is complex and has been shaped by several factors, including litigation and regulatory interpretations.
Litigation Involvement
This patent has been a focal point in several significant litigations, particularly in the context of biosimilar products. For example, in the case of Amgen v. Apotex, Amgen asserted this patent against Apotex's biosimilar versions of Neulasta® (pegfilgrastim) and Neupogen® (filgrastim). The litigation centered on whether Apotex's biosimilar products infringed the claims of this patent, among others[2][4][5].
Regulatory Interpretations
The litigation also involved interpretations of the Biologics Price Competition and Innovation Act (BPCIA), specifically the requirement for a 180-day notice before commercial marketing of a biosimilar product. The Federal Circuit's decision in Amgen v. Apotex emphasized that this notice is mandatory, even for biosimilar applicants who participate in the patent dance process[2][4].
Technical Details
Protein Modification
The patent delves into the technical aspects of modifying proteins at the N-terminus. This involves the use of reactive groups to attach water-soluble polymers, such as PEG, to the protein. The modification can enhance the therapeutic properties of the protein by reducing immunogenicity and increasing its half-life in the bloodstream[1].
Examples of Modified Proteins
The patent provides examples of proteins that can be modified using this method, including granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6). These modifications are critical for developing therapeutic agents with improved efficacy and safety profiles[1].
Impact on Biotechnology
The technology described in U.S. Patent 5,824,784 has had a significant impact on the biotechnology industry.
Therapeutic Applications
The ability to modify proteins at the N-terminus has led to the development of several therapeutic products. For instance, pegfilgrastim (Neulasta®), a pegylated form of G-CSF, is used to stimulate the production of white blood cells in patients undergoing chemotherapy[4].
Patent Strategy
The patent has been part of a comprehensive patent strategy by biologics manufacturers to protect their intellectual property. The litigation involving this patent highlights the complexities and challenges faced by biosimilar applicants in navigating the patent landscape[2][5].
Expiration and Current Status
The patent has expired, which is a common outcome for patents that were issued in the mid-1990s. Despite its expiration, the patent remains relevant in understanding the historical and ongoing developments in protein modification technologies[2][4].
Conclusion
U.S. Patent 5,824,784 is a pivotal patent in the field of biotechnology, particularly in the area of protein modification. Its claims and technical details have been central in various litigations and have shaped the patent landscape for biosimilar products. Understanding this patent is essential for appreciating the complexities of biotechnology innovation and the legal frameworks that govern it.
Key Takeaways
- N-terminal Modification: The patent describes methods for attaching water-soluble polymers to the N-terminus of proteins.
- Pegylation: The process of attaching PEG molecules to proteins is a key aspect of the patent.
- Litigation: The patent has been involved in significant litigations, including Amgen v. Apotex.
- Regulatory Impact: The patent has influenced interpretations of the BPCIA, particularly regarding the 180-day notice requirement.
- Therapeutic Applications: The technology has led to the development of therapeutic products like pegfilgrastim.
- Patent Strategy: The patent is part of a broader strategy to protect intellectual property in biotechnology.
FAQs
What is the main focus of U.S. Patent 5,824,784?
The main focus of U.S. Patent 5,824,784 is on methods and compositions for attaching water-soluble polymers to the N-terminus of proteins.
Which biologic products have been involved in litigations related to this patent?
The biologic products involved include pegfilgrastim (Neulasta®) and filgrastim (Neupogen®), which are biosimilar versions developed by Apotex.
What is the significance of the 180-day notice requirement in BPCIA litigations?
The 180-day notice requirement is mandatory for biosimilar applicants before commercial marketing, allowing the reference product sponsor time to assess infringement positions and adjudicate patent disputes.
How has the expiration of U.S. Patent 5,824,784 affected its relevance?
Despite its expiration, the patent remains relevant for understanding historical and ongoing developments in protein modification technologies and the patent landscape for biosimilar products.
What are some examples of proteins modified using the methods described in this patent?
Examples include granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), which are modified to enhance their therapeutic properties.
Sources
- US5824784A - N-terminally chemically modified protein compositions and methods - Google Patents
- Litigation Spotlight: The Apotex Filgrastim (Neupogen®) and Pegfilgrastim (Neulasta®) Biosimilar Litigation - Biosimilars IP
- Patent Claims and Patent Scope - Hoover Institution
- Federal Circuit Requires 180 Day Notice For All Biosimilars, Even If Patent Dance Is Completed - JD Supra
- Amgen Pursues Third BPCIA Lawsuit on Newly Issued Patent - Paul Hastings
