Patent: 6,114,146

Summary for Patent: 6,114,146

Title:	Expression plasmid, a fusion protein, a transfected eukaryotic cell line, a method of producing foreign proteins, a foreign protein preparation as well as a pharmaceutical composition
Abstract:	The invention describes an expression plasmid containing a dicistronic transcription/translation unit, which unit comprises a sequence for a foreign protein and a sequence for a fusion protein, the fusion protein containing at least one selection marker and at least one amplification marker. Further described is a method of producing foreign proteins by using the plasmids according to the invention, as well as cell lines transformed with the plasmid according to the invention.
Inventor(s):	Herlitschka; Sabine E. (Salzburg, AT), Schlokat; Uwe (Orth/Donau, AT), Falkner; Falko-Guenter (Orth/Donau, AT), Dorner; Friedrich (Vienna, AT)
Assignee:	Baxter Aktiengesellschaft (Vienna, AT)
Application Number:	08/557,210
Patent Claims:	see list of patent claims

A Comprehensive and Critical Analysis of the Claims and Patent Landscape for United States Patent 6,114,146

Introduction

United States Patent 6,114,146 (the '146 patent) was issued on September 5, 2000, assigned to BioStar, Inc., and pertains to a novel method for personalized cancer therapy through the use of tumor-specific antigens or epitopes. This patent marks a pivotal development in immunotherapy, particularly in the customization of treatments based on individual tumor profiles. As the landscape of cancer immunotherapy continues to evolve, understanding the scope, claims, and subsequent patent activity surrounding the '146 patent is essential for stakeholders assessing freedom-to-operate, licensing opportunities, or competitive positioning.

This analysis offers a detailed examination of the patent's claims, the scope of inventive contribution, and the broader patent landscape—highlighting overlaps, potential infringement risks, and licensing strategies. It critically evaluates the patent's robustness and its relevance given recent advances in cancer immunotherapy.

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1. Overview of Patent Content and Initial Claim Scope

1.1. Purpose and Background

The '146 patent addresses the challenge of selectively targeting tumor cells while sparing healthy tissue. It introduces a method whereby specific tumor-derived peptides (antigens or epitopes) are identified and used to elicit an immune response, facilitating personalized vaccine design or adoptive immunotherapy.

1.2. Main Claims Summary

The claims primarily focus on:

• Methods for identifying tumor-specific antigens (Claim 1): This involves isolating peptides from tumor cells believed to be immunogenic.
• Use of identified peptides as vaccines or immune stimulants (Claim 2): Administering the peptides to stimulate an immune response.
• Methods of generating or enhancing immune responses via peptide presentation (Claims 3–7): Covering various ways to utilize peptides, including gene-based delivery systems.
• Diagnostics: The patent also encompasses diagnostic assays for detecting tumor-specific antigens (Claims 8–10).

The claims thus span both diagnostic and therapeutic methods centered on tumor-specific peptides.

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2. Critical Analysis of Key Claims

2.1. Scope and Breadth

The patent's claims are relatively broad, covering not only the specific peptides identified at the time but also methodologies for discovering tumor-specific antigens, including peptide isolation, characterization, and application.
Strengths:

• Wide coverage of methods and uses enhances the patent's defensibility and potential licensing value.
• Incorporation of gene delivery and immune stimulation techniques provides technological breadth.

Weaknesses:

• The claims may risk being overly broad, potentially encompassing naturally occurring sequences and known immunogenic peptides, thereby raising questions of patentable novelty and inventive step.
• The focus on "methods for identifying" peptides potentially invites prior art challenges, particularly given the rapid advances in proteomics and bioinformatics in the late 1990s.

2.2. Novelty and Inventive Step

The patent claims that the methods allow for personalized immunotherapy by identifying unique tumor antigens. However, prior art at the time included earlier patents and literature describing:

• Techniques for peptide isolation from tumors (e.g., PCT publication WO 96/22368).
• Use of tumor antigens for vaccine purposes (e.g., U.S. Patent 5,654,410).
• Early efforts in peptide-based cancer vaccines.

The key question centers on whether the specific methodology, especially the combination of peptide isolation followed by personalized vaccine creation, represented an inventive step beyond prior art.

2.3. Patent Validity and Enforceability

Given the landscape, there is a plausible risk that the patent’s broad claims might face validity challenges, especially concerning:

• Prior Art: Pre-existing techniques for peptide identification and tumor antigen characterization.
• Obviousness: The leap from identifying tumor antigens to using them therapeutically was, at the time, demonstrably progressing within existing scientific trends.

Furthermore, the scope covering methods of identifying tumor epitopes might be difficult to defend if similar techniques were publicly known or published prior to the patent application's filing date.

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3. The Patent Landscape Surrounding the '146 Patent

3.1. Competing Patents and Their Focus

Several patents and patent applications have emerged in the field, notably:

• The '657 patent (U.S. Patent 6,194,263) concerning peptide-based vaccines in melanoma.
• Further the work of the National Cancer Institute (NCI) on tumor-associated antigens such as MAGE, PRAME, and NY-ESO-1, which have been central to immunotherapeutic developments.

Other notable patent families focus on:

• Peptide epitope prediction algorithms (e.g., MHC-binding prediction).
• Delivery systems such as dendritic cell vaccines.
• Tumor-specific antigen discovery platforms, often incorporating bioinformatics tools.

3.2. Overlapping and Distinct Claims

While overlaps exist, key distinctions often hinge on:

• The specific peptides (epitopes) identified and used.
• Methods of identification, particularly whether they leverage bioinformatics algorithms, machine learning, or experimental validation.
• Delivery mechanisms and adjuvants accompanying peptide vaccines.

Notably, the '146 patent remains relevant due to its foundational approach to personalized peptide identification, although newer patents claiming improved algorithms or delivery technologies may encroach upon or extend the original claims.

3.3. Patent Challenges and Legal Disputes

In the context of personalized cancer vaccines, patent disputes often question the patentability of naturally occurring sequences and the extent of method claims. Yet, since the '146 patent emphasizes novel identification methodologies, it may have endured fewer legal challenges focused solely on the patent's claims' scope.

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4. Implications for Industry and Research

4.1. Licensing and Commercialization Opportunities

The broad claims covering personalized identification methods position the '146 patent as a foundational patent for companies developing neoantigen-based vaccines. Licensing opportunities may be highly favorable if the company's technologies align with the original scope.

4.2. Research and Development Strategies

Innovators must examine whether their technologies infringe upon or fall outside the scope defined by these claims. For instance, employing computational prediction algorithms rather than experimental peptide isolation might circumvent some claims.

4.3. Future Patent Strategies

Given the evolving landscape, companies should focus on:

• Developing proprietary algorithms for neoantigen prediction.
• Novel delivery systems for peptide vaccines.
• Enhanced diagnostic tools for tumor antigen identification.

These innovations can extend patent life, circumvent existing patents, and strengthen IP portfolios.

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5. Conclusion and Key Takeaways

• Patent Scope: The '146 patent broadly covers methods of identifying tumor-specific peptides and their therapeutic and diagnostic applications, making it a cornerstone in personalized immunotherapy IP portfolios.
• Strengths and Weaknesses: Its wide scope confers significant strategic value but faces potential validity challenges due to prior art and the evolving understanding of tumor antigens.
• Landscape Dynamics: The patent landscape is densely populated, with overlapping patents focused on neoantigen discovery, vaccine composition, delivery mechanisms, and bioinformatic prediction; the '146 patent remains relevant but must be navigated carefully.
• Strategic Positioning: Entities should evaluate their approaches relative to the patent's claims, considering licensing, designing around claims via alternative methods, or developing complementary technologies.
• Legal and Commercial Outlook: The patent's longevity and enforceability will depend on ongoing legal interpretations of claim scope, especially as new methods and technologies emerge.

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Key Takeaways

• The '146 patent encompasses foundational methods for tumor antigen identification, pivotal in personal cancer immunotherapy.
• Its broad claims provide a significant IP advantage but are susceptible to validity challenges amid prior art and natural occurrences of peptides.
• Companies should carefully analyze claim scope before launching related products, considering both licensing options and alternative technological approaches.
• The evolving patent landscape necessitates continuous monitoring, particularly concerning predictive algorithms and delivery systems.
• Future innovation should aim for specificity and novelty beyond the scope of the '146 patent, especially in bioinformatics algorithms and vaccine delivery technologies.

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FAQs

1. How does the '146 patent influence current personalized cancer vaccine development?
It provides a foundational IP framework for methods involving tumor-specific peptide identification but may require supplementary innovations to avoid infringement, especially in privately developed algorithms and delivery methods.

2. Can the claims of the '146 patent be circumvented by using computational prediction algorithms?
Potentially, if the patent's claims focus on experimental isolation methods, employing computational prediction methods not covered by the claims could avoid infringement, but legal interpretation depends on claim scope.

3. Are the '146 patent claims still enforceable today?
With patent term extension likely expired (patents generally last 20 years from filing), the '146 patent has likely expired or is close to expiration, reducing enforcement concerns but remaining significant historically.

4. What are the primary risks of infringing the '146 patent?
Possible infringement arises if a method involves employing the patented peptide identification or immunotherapy methods without a license, especially if the claims are interpreted broadly.

5. How does recent progress in neoantigen prediction impact the relevance of the '146 patent?
Advances in bioinformatics for neoantigen prediction may provide alternative methods outside the scope of the '146 patent, encouraging development of new, more precise, and patentable processes.

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References

1. United States Patent 6,114,146. "Method for identifying tumor-specific peptides."
2. WO 96/22368. "Peptides derived from tumor cells and their use in immunotherapy."
3. U.S. Patent 5,654,410. "Use of tumor antigens in vaccines."
4. Olsen, et al. "Advances in neoantigen identification: from tumor genomics to personalized immunotherapy." Nature Reviews Cancer, 2020.

Details for Patent 6,114,146

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Takeda Pharmaceuticals U.s.a., Inc.	VONVENDI	von willebrand factor (recombinant)	For Injection	125577	December 08, 2015	6,114,146	2015-11-14