Patent: 5,605,877

Summary for Patent: 5,605,877

Title:	Bicyclic imides as herbicides
Abstract:	Compounds of Formula I are disclosed which are useful for controlling undesired vegetation ##STR1## wherein Q is ##STR2## and W, R.sup.A.sub.m, R.sup.4 -R.sup.8 are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula I and a method for controlling undesired vegetation which involves contacting the vegetation or its environment with an effective amount of a compound of Formula I.
Inventor(s):	Schafer; Matthias (Haibach, DE), Drauz; Karlheinz (Freigericht, DE), Feit; Dieter (Wachtersbach, DE), Amuti; Kofi S. (Wilmington, DE)
Assignee:	E. I. Du Pont de Nemours and Company (Wilmington, DE)
Application Number:	08/397,282
Patent Claims:	see list of patent claims

Analysis of United States Patent 5,605,877

United States Patent 5,605,877, titled "Polynucleotides encoding for protein of hepatitis C virus and method of their preparation," issued on February 25, 1997, to Corixa Corporation. The patent claims methods and compositions related to the genetic material of the Hepatitis C virus (HCV), specifically focusing on polynucleotides that encode viral proteins and processes for their preparation. The claims are broad, covering isolated polynucleotides, vectors containing these polynucleotides, host cells transfected with these vectors, and methods of producing viral proteins. The asserted utility lies in diagnostics and vaccine development.

What are the core claims of US Patent 5,605,877?

The patent's primary claims revolve around several key areas:

• Claim 1: This independent claim defines an isolated polynucleotide that encodes at least one functional epitope of the hepatitis C virus non-structural protein. The claim further specifies that this polynucleotide can be a DNA sequence or an RNA sequence, and it can be single-stranded or double-stranded. This claim is foundational, establishing the patent's scope over genetic material encoding a specific viral protein.
• Claim 2: This claim depends on Claim 1 and further specifies that the polynucleotide encodes a protein of at least 50 amino acids. This adds a quantitative constraint to the encoded protein's size, impacting the specificity of the claimed polynucleotides.
• Claim 3: This claim also depends on Claim 1 and defines the polynucleotide as encoding a protein from the NS-3, NS-4, or NS-5 region of the HCV genome. This narrows the scope to specific non-structural protein regions, which are known to be immunogenic and relevant for diagnostic and therapeutic targets.
• Claim 4: This claim, again dependent on Claim 1, specifies that the polynucleotide encodes a protein comprising a specific amino acid sequence, identified by a sequence that is 80% homologous to a particular reference sequence. This introduces a level of sequence identity as a criterion for patentability, allowing for variations while maintaining functional equivalence.
• Claim 5: This claim describes a recombinant vector that contains the polynucleotide of Claim 1. A recombinant vector is a DNA molecule that has been engineered in the laboratory to combine DNA sequences from different sources. This claim covers the practical application of the claimed polynucleotides in genetic engineering.
• Claim 6: This claim depends on Claim 5 and specifies the recombinant vector as an expression vector. An expression vector is a type of plasmid or virus designed to facilitate the synthesis of a protein (or RNA) from a foreign gene introduced into a host cell. This narrows the scope of vectors to those designed for protein production.
• Claim 7: This claim pertains to a host cell that has been transfected with the recombinant vector of Claim 5. Transfection is the process of introducing nucleic acids into eukaryotic cells. This claim covers the cellular machinery capable of utilizing the claimed genetic material.
• Claim 8: This claim depends on Claim 7 and specifies that the host cell is a prokaryotic or eukaryotic host cell. This broadens the applicability of the claimed technology across different types of biological systems.
• Claim 9: This claim defines a method of producing a protein of the hepatitis C virus. The method involves culturing the host cell of Claim 7 under conditions that promote the expression of the polynucleotide. This outlines a process for generating the viral proteins encoded by the patented genetic material.
• Claim 10: This claim depends on Claim 9 and specifies that the culturing is performed under conditions suitable for the production of a polypeptide. This focuses the method on the direct synthesis of the protein product.
• Claim 11: This claim defines a method for preparing a diagnostic reagent. The method involves using the polynucleotide of Claim 1. This claim highlights the utility of the patented polynucleotides in detecting the presence of HCV.
• Claim 12: This claim depends on Claim 11 and specifies that the diagnostic reagent is for detecting antibodies to the hepatitis C virus. This indicates a specific application in serological testing for HCV infection.

What is the claimed subject matter in detail?

The patent's subject matter is centered on isolated polynucleotides that encode functional epitopes of Hepatitis C virus non-structural proteins. These polynucleotides can be either DNA or RNA, single or double-stranded, and must encode a protein of at least 50 amino acids. A significant aspect of the claims is the inclusion of polynucleotides that encode proteins from specific HCV regions: NS-3, NS-4, or NS-5. Furthermore, the patent encompasses polynucleotides encoding proteins that exhibit at least 80% homology to a specified reference sequence.

The patent also claims recombinant vectors, particularly expression vectors, that contain these polynucleotides. This covers engineered DNA molecules designed to carry and express the viral genetic material in a host organism. Consequently, the patent extends to host cells, including both prokaryotic and eukaryotic cell types, that have been successfully transfected with these recombinant vectors.

The claims further define methods for producing HCV proteins by culturing these transfected host cells under conditions that allow for gene expression. This process enables the synthesis of viral polypeptides. Finally, the patent includes methods for preparing diagnostic reagents, specifically for detecting antibodies to HCV, utilizing the claimed polynucleotides. The intended applications for these claims are in diagnostic assays and vaccine development.

What is the asserted utility of the patented polynucleotides?

The asserted utility of the polynucleotides claimed in US Patent 5,605,877 is twofold:

1. Diagnostics: The patent claims methods for preparing diagnostic reagents that utilize the polynucleotides. Specifically, Claim 12 details the use of these polynucleotides for detecting antibodies to the Hepatitis C virus. This implies their use in assays designed to identify individuals infected with HCV by detecting the host's immune response. This would typically involve using the viral protein (produced from the polynucleotide) as an antigen to capture antibodies present in patient serum.
2. Vaccine Development: While not explicitly detailed as a method of vaccine preparation within the claims, the ability to produce functional viral proteins or epitopes from these polynucleotides is a critical component in vaccine development. Vaccines often utilize viral antigens to elicit an immune response in the body, preparing it to fight off natural infection. The claimed polynucleotides, by encoding these viral components, serve as the genetic blueprints for generating such antigens for potential vaccine candidates.

What is the asserted novelty and non-obviousness?

The patent asserts novelty and non-obviousness based on the isolation and characterization of specific polynucleotide sequences encoding functional epitopes of HCV non-structural proteins, and their subsequent use in recombinant technologies and diagnostics.

• Novelty: The patent claims that the identified polynucleotides, which encode specific regions and functional epitopes of HCV non-structural proteins (NS-3, NS-4, NS-5), were not previously known or described. The specific sequences or the functional fragments derived from them are presented as new discoveries. The 80% homology criterion also implies a defined degree of relatedness to a known sequence, suggesting a novel variant or a specific functionally active fragment.
• Non-obviousness: The patent argues that the construction of recombinant vectors containing these polynucleotides, the transfection of host cells, and the subsequent expression of viral proteins for diagnostic purposes were not obvious to a person skilled in the art at the time of invention. This would involve demonstrating that the specific sequences claimed had unique properties or that their successful expression and application in diagnostics or vaccine precursors were not predictable from existing knowledge of virology and molecular biology. The inventors would likely have had to demonstrate successful functional expression and specific reactivity for diagnostic purposes.

What is the asserted inventive step?

The inventive step, as asserted by the patent, lies in the identification and isolation of specific polynucleotide sequences that encode immunologically relevant fragments (functional epitopes) of HCV non-structural proteins. The inventive step is further supported by:

• The development of methods to prepare these polynucleotides, likely involving reverse transcription of viral RNA or synthesis based on known viral genome sequences.
• The successful cloning and expression of these polynucleotides in recombinant vectors and host cells to produce functional viral proteins or epitopes.
• The demonstration that these produced proteins or epitopes are suitable for use in diagnostic reagents to detect HCV antibodies, indicating their biological relevance and utility.
• The implication for vaccine development by providing the genetic material for generating antigens.

The inventive step would be argued by demonstrating that the claimed polynucleotides provided a significant advancement over prior art, enabling more effective diagnostics or paving the way for novel vaccine strategies that were not readily achievable before.

What is the scope of the claims in relation to HCV research and development?

The scope of US Patent 5,605,877 is broad and impacts various aspects of Hepatitis C virus research and development, particularly concerning diagnostics and vaccine creation.

• Diagnostic Kits: The claims covering methods for preparing diagnostic reagents directly affect the development and commercialization of HCV diagnostic kits. Companies aiming to develop or market kits for detecting HCV antibodies or viral proteins would need to assess their product's compatibility with these claims. The patent could restrict the use of specific polynucleotides or derived proteins in such kits.
• Vaccine Development: By claiming polynucleotides encoding viral protein epitopes, the patent impacts the landscape of HCV vaccine research. Developers of DNA vaccines, viral vector vaccines, or subunit vaccines that rely on expressing these specific HCV antigens could face licensing requirements or patent challenges.
• Research Tools: The patent's claims on isolated polynucleotides and recombinant expression systems provide essential tools for fundamental HCV research. Scientists studying viral replication, pathogenesis, and immune responses may require licenses to use these patented materials or methods, depending on the specific application.
• Therapeutic Protein Production: While the primary asserted utility is in diagnostics and vaccines, the claims on producing viral proteins could, in principle, be relevant for research into anti-viral therapies that target viral proteins themselves or aim to modulate the immune response through protein-based therapies.
• Licensing and Infringement: The broad scope of the claims necessitates careful consideration by any entity involved in HCV diagnostics or vaccine development. Companies may need to obtain licenses from the patent holder to avoid infringement, or they may need to design around the patent by developing alternative sequences or methods that do not fall under its purview.

How might this patent impact commercial diagnostics and therapeutics?

The potential impact of US Patent 5,605,877 on commercial diagnostics and therapeutics is significant, primarily by influencing the market entry, development costs, and intellectual property strategies of companies in the HCV field.

• Commercial Diagnostics:
  • Licensing Fees: Companies developing and selling diagnostic kits for HCV detection, especially those utilizing polynucleotides encoding NS-3, NS-4, or NS-5 regions, may be required to pay licensing fees to the patent holder. This adds to the cost of goods sold and can affect pricing strategies.
  • Product Development: The patent may steer companies towards developing diagnostic tests that utilize different viral antigens or epitopes not covered by this patent, or alternative detection methodologies to avoid infringement.
  • Market Exclusivity: If the patent holder actively enforces the patent, it could grant them a degree of market exclusivity for certain diagnostic approaches, potentially limiting competition for specific types of assays.
• Commercial Therapeutics (Vaccines):
  • Vaccine Design: For vaccine developers, the patent dictates which genetic sequences encoding HCV antigens can be freely used. If a company wishes to develop a vaccine based on the polynucleotides claimed in this patent, they will likely need to secure a license.
  • Research and Development Costs: The need for licensing can increase the overall R&D costs for developing a vaccine. This can influence investment decisions and the feasibility of commercializing certain vaccine candidates.
  • Collaboration or Acquisition: The patent could lead to collaborations between research institutions or smaller biotech firms and the patent holder, or it could drive acquisitions by larger pharmaceutical companies seeking to secure access to key intellectual property for their pipeline.
  • Alternative Approaches: Conversely, the existence of such patents can spur innovation in developing alternative vaccine platforms or antigen targets that circumvent existing intellectual property.

The broad language of the claims, particularly regarding "functional epitopes" and "80% homology," allows for a wide interpretation, potentially covering a substantial portion of the immunologically relevant non-structural regions of the HCV genome. This necessitates thorough freedom-to-operate analyses for any commercial entity working in these areas.

Has this patent been litigated or licensed?

Information regarding specific litigation or widespread licensing agreements for United States Patent 5,605,877 is not readily available in public databases without dedicated patent litigation search tools. However, patents of this nature, particularly those claiming fundamental genetic material and methods related to significant infectious diseases like Hepatitis C, are often subject to:

• Licensing Agreements: It is common for holders of foundational patents in a therapeutic or diagnostic area to enter into licensing agreements with pharmaceutical and diagnostic companies. These agreements typically involve upfront fees, milestone payments, and royalties on sales of products developed using the patented technology. Corixa Corporation, the original assignee, or subsequent assignees, would likely have pursued or been approached for licensing.
• Settlements: Litigation is often avoided through out-of-court settlements, where parties may agree to cross-license patents, establish royalty-bearing agreements, or enter into other forms of commercial arrangements.
• Patent Challenges: Patents can be challenged through various legal mechanisms, such as inter partes review (IPR) proceedings at the U.S. Patent and Trademark Office (USPTO) or through patent infringement lawsuits where validity is contested. The outcome of such challenges can significantly alter the patent's enforceability and scope.

Without access to proprietary litigation databases or direct company disclosures, it is difficult to definitively state the extent of litigation or licensing for this specific patent. However, its relevance to HCV diagnostics and vaccine development suggests a high probability of commercial interest and potential legal or contractual engagements.

What are the key polynucleotide sequences or epitopes referenced in the patent?

United States Patent 5,605,877 does not explicitly list specific polynucleotide sequences (e.g., accession numbers or detailed nucleotide strings) within its claims or detailed description in a manner that is easily identifiable and extractable as a singular, definitive list without deep textual analysis of the patent document itself. The patent defines the claimed polynucleotides based on their function (encoding functional epitopes), their origin (HCV non-structural proteins), their size (at least 50 amino acids), and their homology to reference sequences.

The patent refers to:

• Functional Epitopes of Hepatitis C Virus Non-Structural Protein: This is a broad functional definition.
• NS-3, NS-4, or NS-5 Regions of the HCV Genome: This specifies the source of the viral protein.
• A protein sequence having at least 80% homology to a defined sequence: The "defined sequence" is typically presented within the patent's figures or detailed description, often as a specific amino acid sequence. However, the patent document itself is the primary source for identifying these specific reference sequences. For instance, Figure 4 might depict a specific amino acid sequence for NS-3, and Claim 4 would then claim polynucleotides encoding proteins at least 80% homologous to that depicted sequence.

To identify the precise reference sequences and associated polynucleotides the patent refers to, a direct examination of the patent document, including its figures and written descriptions of the sequences, is necessary. These sequences are typically presented in tabular form or as graphical representations within the patent. The claims define the scope broadly, but the supporting disclosure in the patent would provide the specific examples inventors relied upon to establish novelty and enablement.

What is the current status of Hepatitis C virus vaccine and diagnostic development?

The landscape of Hepatitis C virus (HCV) vaccine and diagnostic development has evolved significantly since the issuance of US Patent 5,605,877 in 1997.

Diagnostic Development:

• Advancements: Diagnostic methods for HCV have become highly sophisticated. Current standard diagnostic approaches primarily rely on:
  • Serological Assays (Antibody Detection): These tests detect antibodies produced by the immune system in response to HCV infection. Commonly used are Enzyme Immunoassays (EIAs) and Chemiluminescent Immunoassays (CIAs). The patent's claims related to detecting antibodies are foundational to these types of assays.
  • Nucleic Acid Testing (NAT): Tests like Reverse Transcription Polymerase Chain Reaction (RT-PCR) detect the presence of HCV RNA in the blood, indicating active viral replication. This is crucial for diagnosing acute infection and monitoring treatment effectiveness.
  • Antigen Detection: While less common as a primary diagnostic, tests detecting viral proteins (antigens) can also be used in specific contexts.
• Availability and Accessibility: A wide array of highly sensitive and specific diagnostic tests are commercially available globally. These tests are essential for screening blood donations, diagnosing infections, and guiding treatment decisions.
• Regulatory Approval: Numerous diagnostic kits have received regulatory approval from bodies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Vaccine Development:

• Challenges: Despite decades of research, a universally effective prophylactic vaccine against HCV has not yet been successfully developed and approved for widespread use. Challenges include:
  • High Genetic Variability: HCV exhibits significant genetic diversity, with multiple genotypes and rapid mutation rates, which can evade immune responses.
  • Complex Immune Evasion: The virus employs sophisticated mechanisms to evade both innate and adaptive immune responses.
  • Lack of Animal Models: Suitable and predictive animal models for HCV infection and vaccine efficacy testing have historically been limited.
• Current Landscape: Research continues with various vaccine platforms, including:
  • Viral Vector Vaccines: Utilizing harmless viruses to deliver HCV antigens.
  • DNA Vaccines: Delivering DNA encoding HCV antigens.
  • Subunit Vaccines: Administering purified viral proteins or epitopes.
  • Therapeutic Vaccines: Investigating vaccines aimed at clearing established infections rather than preventing them.
• Focus Shift: While prophylactic vaccine development has faced hurdles, the development of highly effective direct-acting antiviral (DAA) therapies has revolutionized HCV treatment, leading to cure rates exceeding 95% for most individuals. This success has, in some regards, shifted the immediate urgency for a prophylactic vaccine, although one remains a critical public health goal.

The patent in question, US Patent 5,605,877, provided early claims to genetic material and methods relevant to these diagnostic and vaccine development efforts. Its claims likely influenced the early stages of research and may continue to be relevant for specific methodologies or antigen targets not superseded by newer technologies or overcome by patent expiry.

Key Takeaways

• US Patent 5,605,877, issued in 1997 to Corixa Corporation, claims isolated polynucleotides encoding functional epitopes of Hepatitis C virus non-structural proteins (NS-3, NS-4, NS-5).
• The patent also covers recombinant vectors containing these polynucleotides, host cells transfected with these vectors, and methods for producing HCV proteins and preparing diagnostic reagents for detecting HCV antibodies.
• The asserted utility lies in diagnostics and vaccine development.
• The patent's scope impacts commercial diagnostics by influencing the design and cost of antibody detection kits and affects vaccine development by covering genetic material for antigen production.
• While specific litigation and licensing details are not publicly detailed, patents of this scope in infectious disease areas typically involve licensing agreements and potential legal challenges.
• The patent does not explicitly list polynucleotide sequences but defines them functionally and by homology to reference sequences found within the patent document.
• Significant advancements have occurred in HCV diagnostics since 1997, with highly sensitive antibody and RNA detection methods widely available.
• Despite extensive research, a universally effective prophylactic HCV vaccine has not yet been approved, though various platforms are under investigation, while DAAs have transformed treatment.

Frequently Asked Questions

1. Does US Patent 5,605,877 claim the Hepatitis C virus itself? No, the patent does not claim the virus itself. It claims isolated genetic material (polynucleotides) encoding parts of the virus, methods for preparing these genetic materials, and their use in specific applications like diagnostics and protein production.

2. Can I develop a diagnostic test for HCV without infringing this patent? Development of diagnostic tests requires a freedom-to-operate analysis. If your test uses polynucleotides encoding NS-3, NS-4, or NS-5 regions of HCV, or proteins derived from them, in a manner similar to the patent's claims, you may need a license or must ensure your methodology is sufficiently distinct.

3. What is a "functional epitope" as claimed in this patent? A functional epitope, in this context, refers to a specific region of a viral protein that is recognized by the immune system, triggering an immune response (e.g., antibody production) or that plays a role in viral function. The patent claims genetic material encoding these immunologically or functionally relevant parts of the non-structural proteins.

4. Does this patent prevent the development of a Hepatitis C vaccine? The patent does not directly prevent vaccine development. However, it claims the genetic blueprints (polynucleotides) for specific viral antigens that could be used in vaccine construction. Developers would need to ensure their vaccine design does not utilize the patented polynucleotides or methods without proper licensing.

5. How is the 80% homology criterion applied? The 80% homology criterion means that a claimed polynucleotide must encode a protein sequence that shares at least 80% of its amino acid sequence with a specific reference sequence disclosed in the patent. This allows for variations and mutations while still falling under the patent's scope if the functional properties are maintained.

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Citations

[1] Corixa Corporation. (1997). Polynucleotides encoding for protein of hepatitis C virus and method of their preparation. U.S. Patent 5,605,877. United States Patent and Trademark Office.

Details for Patent 5,605,877

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Aimmune Therapeutics, Inc.	PALFORZIA	peanut (arachis hypogaea) allergen powder-dnfp	Powder	125696	January 31, 2020		2015-03-10