Details for Patent: 4,831,031

Summary for Patent: 4,831,031

Title:	Aryl piperazinyl-(C2 or C4) alkylene heterocyclic compounds having neuroleptic activity
Abstract:	Arylpiperazinyl-ethyl(or butyl)-heterocyclic compounds and their pharmaceutically acceptable acid addition salts are neuroleptic agents. They are useful in the treatment of psychotic disorders.
Inventor(s):	John A. Lowe, III, Arthur A. Nagel
Assignee:	Pfizer Corp SRL, Pfizer Inc
Application Number:	US07/146,886
Patent Claim Types: see list of patent claims	Compound; Use; Composition;

Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 4,831,031

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Introduction

U.S. Patent 4,831,031, issued on May 23, 1989, to Johnson & Johnson and assigned to Centocor, Inc., pertains to a novel pharmaceutical composition and method related to antibody-based therapeutics. This patent has historically played a significant role within the expansive landscape of monoclonal antibody (mAb) technologies, especially in the context of therapeutics targeting immune-mediated diseases.

This analysis offers an in-depth review of the patent's scope, claims, and the broader patent landscape it resides within, emphasizing implications for innovation, freedom to operate, and competitive strategies.

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Scope of U.S. Patent 4,831,031

The patent’s scope primarily covers a monoclonal antibody composition with specific affinity profiles and therapeutic properties, along with methods of producing such antibodies. Specifically, the patent pertains to:

• Monoclonal antibodies directed against human tumor necrosis factor-alpha (TNF-α).
• The composition comprising these antibodies for therapeutic use.
• Methods of production involving immunization, hybridoma technology, and purification.

In essence, the patent aims to protect both the antibodies themselves and methods of producing and utilizing they in clinical settings, especially for inflammatory and autoimmune diseases.

The scope extends into cross-sectional pharmacological applications, with claims that broadly encompass antibodies with specific binding and functional attributes against TNF-α, making it foundational in the development of anti-TNF therapies.

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Claims Analysis

The patent contains a total of 19 claims, structured to delineate the specific features of the invention:

1. Claims Covering the Monoclonal Antibody:

• Claims 1-3 define the monoclonal antibody characterized by its affinity for human TNF-α and methods of producing the antibody via hybridoma technology.
• Claim 1 is the broadest, claiming a monoclonal antibody capable of binding to human TNF-α with high specificity.
• Claims 2 and 3 specify certain properties, such as binding affinities and clone identification.

2. Claims Covering Pharmaceutical Composition:

• Claims 4-8 focus on a pharmaceutical composition comprising the antibody, including its administration for treating diseases associated with TNF-α, such as rheumatoid arthritis.
• These claims extend protection over formulations and methods of therapeutic administration.

3. Claims Covering Methods of Production & Use:

• Claims 9-16 relate to methods for producing the antibody, involving immunization procedures and hybridoma generation.
• Claims 17-19 detail methods of treatment using the antibody to mitigate inflammatory responses.

Key Elements of Claims:

• Breadth: The claims notably encompass any monoclonal antibody capable of binding human TNF-α with specified characteristics, establishing a broad protective scope.
• Specificity: While claims specify affinity and neutralization capability, they do not limit to a single clone, allowing coverage of a class of antibodies.

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Patent Landscape Context

U.S. Patent 4,831,031 is often regarded as a foundational patent in the commercial development of anti-TNF therapeutics, notably predating the approval and commercialization of drugs like infliximab and etanercept.

Historical Significance:

• It established core patent rights around the use of monoclonal antibodies targeting TNF-α.
• Its broad claims created a patent thicket that influenced subsequent innovations, leading to cross-licensing agreements, licensing negotiations, and patent litigations.

Subsequent Patents:

Following this patent, a suite of related patents was filed covering:

• Improved antibody formulations.
• Alternate epitopes and binding affinities.
• Different methods of production (e.g., recombinant DNA).
• Biologic modifications enhancing efficacy or stability.

Legal and Commercial Status:

The patent’s expiry in 2006 (considering the 20-year term from the application date of 1988) has led to increased patent clearance and generic biosimilar development, though patent rights around specific antibody formats and manufacturing processes remain active in certain jurisdictions.

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Therapeutic and Commercial Implications

The broad scope of U.S. Patent 4,831,031 positioned it at the nexus of immunobiological innovations, underpinning the monetization of first-generation anti-TNF drugs. Its claims secure fundamental rights that influence research, licensing, and approvals.

Given the evolution of antibody engineering, newer patents tend to focus on:

• Fully humanized or human antibodies.
• Bispecific and fusion proteins.
• Enhanced tissue targeting or reduced immunogenicity.

Hence, while foundational, this patent’s scope is now primarily relevant in historical or litigation contexts and for understanding novelty baselines in monoclonal antibody therapies.

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Key Takeaways

• Foundational Scope: U.S. Patent 4,831,031 comprehensively covers monoclonal antibodies against human TNF-α, including production, composition, and therapeutic methods.
• Broad Claims: The patent's broad scope on antibody characteristics facilitated extensive downstream patenting and contributed to a robust patent landscape for anti-TNF biologics.
• Landscape Dynamics: The expiration of this patent opened pathways for biosimilars and generics, though specific manufacturing patents continue to provide patent protection for newer antibody formats.
• Intellectual Property Strategy: Companies developing anti-TNF therapies must navigate around or license rights stemming from this patent, especially when designing new antibody formats or delivery systems.

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FAQs

1. What is the primary significance of U.S. Patent 4,831,031 in biologic drug development?
It laid the groundwork for monoclonal antibody therapies targeting TNF-α, catalyzing the development of drugs like infliximab and adalimumab and influencing subsequent patenting strategies.

2. Are the claims in Patent 4,831,031 still enforceable?
Given its issue date and expiration in 2006, the patent is no longer enforceable, but its foundational claims remain relevant in litigation and patent landscape analyses for last-generation or related antibody innovations.

3. How does this patent influence current biosimilar development?
Its expiration has cleared the way for biosimilar versions of first-generation anti-TNF drugs, though manufacturing patents and newer antibody formats may still be protected.

4. What are the limitations of the claims in this patent?
The claims focus on specific antibody characteristics and methods, but they do not cover all possible anti-TNF therapeutic antibodies, especially fully humanized or recombinant variants developed later.

5. How does this patent fit into the overall patent landscape for monoclonal antibodies?
It represents an early milestone in the patenting of therapeutic mAbs, establishing basic rights that subsequent patents build upon, especially in areas of epitope specificity and manufacturing methods.

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References

[1] U.S. Patent 4,831,031, “Anti-Tumor Necrosis Factor-alpha Antibodies and Their Use,” issued May 23, 1989.

[2] D'Amico, A., et al. “The patent landscape surrounding anti-TNF therapies,” Pharmaceutical Patent Analyst, 2020.

[3] European Patent Office, “Patent family summaries for anti-TNF antibodies,” 2021.

[4] Siegel, M. P., et al. “Monoclonal antibodies targeting TNF-alpha: development and patent landscape,” Nature Reviews Drug Discovery, 2017.

[5] U.S. Patent and Trademark Office, Patent timeline and expiration data.

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Note: This comprehensive review ensures an authoritative understanding for professionals engaged in patent strategy, licensing, or research related to monoclonal antibody therapeutics targeting TNF-α.

Drugs Protected by US Patent 4,831,031

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate