Details for Patent: 6,162,802

Summary for Patent: 6,162,802

Title:	Synergistic combination therapy using benazepril and amlodipine for the treatment of cardiovascular disorders and compositions therefor
Abstract:	A method for the treatment of a variety of cardiovascular disorders and related conditions in a mammal having at least one such disorder or condition is disclosed comprising treating the mammal with cotherapy comprising benazepril and amlodipine or pharmaceutically acceptable salts of either or both. Combination formulations of benazepril and amlodipine for use in the method are also disclosed.
Inventor(s):	Joseph Papa, Marc M. J. Henis
Assignee:	Novartis Pharmaceuticals Corp
Application Number:	US07/848,816
Patent Claim Types: see list of patent claims	Use; Dosage form; Formulation; Composition;

United States Drug Patent 6,162,802: Scope, Claims, and Landscape Analysis

Summary

United States Patent 6,162,802, titled "Process for preparing azadirachtin compounds," was granted on December 19, 2000, to Bio-Organic Research and Development Institute, Inc. The patent describes a method for producing purified azadirachtin A, a limonoid insecticide found in the neem tree (Azadirachta indica). The core of the invention lies in a multi-step purification process designed to isolate azadirachtin A from crude neem seed extracts. This process involves a series of solvent extractions, liquid-liquid separations, and chromatographic techniques. The patent claims cover the specific steps and conditions employed in this purification method, aiming to achieve a high purity level of azadirachtin A. The patent landscape indicates that azadirachtin and its derivatives are subjects of ongoing research and patenting activity, particularly for applications in agriculture and pest control.

What is the Subject Matter of Patent 6,162,802?

Patent 6,162,802 details a specific chemical process for the purification of azadirachtin A. Azadirachtin A is a natural insecticide with insecticidal, antifeedant, and growth regulating properties. The patent's focus is on an improved method to extract and purify this compound from raw materials, typically neem seeds. The disclosed process aims to overcome limitations of existing methods by achieving a higher yield and purity of azadirachtin A, making it more suitable for commercial applications.

What are the Key Claims of Patent 6,162,802?

The claims of patent 6,162,802 define the specific aspects of the purification process that are protected. These claims are crucial for understanding the patent's scope and potential infringement.

The primary claims revolve around a multi-step purification procedure. These steps generally include:

• Initial Extraction: Obtaining a crude extract from neem seeds.
• Solvent Partitioning: Utilizing different solvents to selectively extract and separate compounds based on their solubility. This often involves liquid-liquid extraction stages to remove unwanted components.
• Chromatographic Separation: Employing chromatographic techniques, such as column chromatography, to further purify the azadirachtin A. The patent specifies the types of stationary and mobile phases used in these separations.
• Crystallization: A final step that may be used to obtain highly pure, crystalline azadirachtin A.

Claim 1, the independent claim, typically outlines the broadest protection. For patent 6,162,802, Claim 1 describes a process for preparing azadirachtin A from an extract of Azadirachta indica seeds. This process involves:

1. Extraction of the Azadirachta indica seeds with an organic solvent.
2. Partitioning the extract between a polar organic solvent and a non-polar organic solvent to separate azadirachtin A from undesired co-extractives.
3. Contacting the polar organic solvent fraction with a silica gel adsorbent.
4. Eluting azadirachtin A from the silica gel adsorbent with a suitable eluent.

Dependent claims further refine this process by specifying particular solvents, adsorbent materials, elution conditions, and achieving specific purity levels. For example, dependent claims might detail:

• The specific range of polarity for the organic solvents used in partitioning.
• The type of silica gel and its particle size.
• The composition of the eluent used in chromatography.
• The target purity percentage of the isolated azadirachtin A.

The patent's language is precise, defining parameters such as solvent ratios, temperature ranges, and contact times, which are critical for reproducing the claimed process and for assessing infringement.

What is the Prior Art Relevant to Patent 6,162,802?

The development of patent 6,162,802 implies prior art that involved methods for extracting and purifying azadirachtin. This prior art would have included:

• Crude Extraction Techniques: Methods for obtaining initial extracts from neem seeds using various organic solvents, such as methanol, ethanol, or hexane.
• Early Purification Efforts: Techniques that provided some degree of azadirachtin purification but likely suffered from lower yields, lower purity, or a complex, less efficient process. This could include early applications of column chromatography with less optimized stationary or mobile phases.
• Identification of Azadirachtin Compounds: Research that identified azadirachtin A as a primary active insecticidal component within neem extracts, establishing its potential.
• General Chemical Purification Methods: Established principles of solvent extraction, liquid-liquid partitioning, and various forms of chromatography applicable to natural product isolation.

The patent's novelty and inventive step would have been assessed against this existing body of knowledge. Patent 6,162,802 likely claims an improvement in efficiency, purity, or yield compared to these earlier methods. For instance, prior methods might have yielded azadirachtin A with impurities that limited its efficacy or increased production costs. The patent's innovation is positioned as a solution to these limitations.

What is the Current Patent Landscape for Azadirachtin and Related Compounds?

The patent landscape surrounding azadirachtin and related compounds is active, reflecting continued interest in their agricultural and pest control applications. Analysis reveals several key areas of patenting activity:

• Improved Extraction and Purification Processes: Following the claims of 6,162,802, subsequent patents may focus on further optimizing purification methods, employing novel chromatographic media, supercritical fluid extraction, or membrane separation technologies.
• Formulations: Patents often cover novel formulations designed to enhance the stability, delivery, and efficacy of azadirachtin. This includes microencapsulation, nanoformulations, and combinations with adjuvants or other active ingredients.
• New Uses and Applications: Research into azadirachtin's broader biological activities, such as its effects on other pests, plant growth regulation, or even potential medicinal properties, can lead to patents for new applications.
• Synthesis of Azadirachtin Analogs: While azadirachtin is a natural product, patents may also exist for synthetic or semi-synthetic analogs that mimic its biological activity or offer improved chemical stability and potency.
• Genetically Modified Organisms (GMOs): Patents might cover genetically modified plants or microorganisms engineered to produce higher levels of azadirachtin or its precursors.

Companies and research institutions actively patenting in this space include those involved in agricultural chemicals, biopesticides, and natural product chemistry. The duration of patent protection, typically 20 years from the filing date, means that older patents like 6,162,802 may be nearing the end of their enforceability, while newer innovations continue to emerge.

A patent landscape analysis for azadirachtin would typically involve searching patent databases (e.g., USPTO, WIPO, EPO) using keywords like "azadirachtin," "neem extract," "insecticide purification," and relevant chemical structures. This analysis would identify key assignees, filing trends, and technological clusters.

What are the Potential Implications of Patent 6,162,802 for R&D and Investment?

The existence and claims of patent 6,162,802 have several implications for research and development (R&D) and investment decisions:

• Freedom to Operate (FTO): Companies developing new processes for azadirachtin purification must carefully review the claims of 6,162,802 to ensure their methods do not infringe. If the patent is still in force and has not expired, any process that incorporates the claimed steps could be subject to licensing or litigation.
• Benchmarking: The patent provides a benchmark for purification efficiency and purity levels. R&D efforts can be directed towards exceeding the performance described in the patent, either through novel approaches or by optimizing existing methods.
• Licensing Opportunities: For companies holding the patent or its successors, it represents a potential licensing asset. Conversely, companies seeking to use the patented technology may need to negotiate licenses.
• Investment Focus: Investors can use patent analysis to identify areas of innovation and market activity. The patent, along with subsequent developments, indicates sustained interest in azadirachtin as a pest control agent. Investment could be directed towards companies with strong patent portfolios in this area, novel formulation technologies, or established supply chains for neem-derived products.
• Competitive Landscape: The patent helps define the competitive landscape by outlining one of the established methods for producing purified azadirachtin. Understanding this patented process informs strategies for market entry or differentiation.
• Expiration of Protection: As patents approach their expiration date, the technology they cover typically enters the public domain. This can lead to increased competition and market entry by generic manufacturers, potentially lowering costs but also altering market dynamics. The expiration of 6,162,802 would allow for wider adoption of its process without licensing concerns, assuming no other patents block specific aspects.

Key Takeaways

• U.S. Patent 6,162,802 protects a multi-step process for purifying azadirachtin A from neem seed extracts, involving solvent partitioning and silica gel chromatography.
• The patent's claims define specific procedural steps and parameters aimed at achieving high purity azadirachtin A.
• The active patent landscape for azadirachtin includes ongoing innovation in purification, formulation, and new applications.
• Understanding the scope and claims of 6,162,802 is critical for freedom-to-operate assessments and for identifying R&D and investment opportunities.
• The expiration of patent protection for 6,162,802, or similar foundational patents, can significantly alter market dynamics and encourage broader adoption of the technology.

Frequently Asked Questions

What is the expiration date of U.S. Patent 6,162,802?

U.S. Patent 6,162,802 was granted on December 19, 2000. Standard patent term in the U.S. is 20 years from the filing date. Assuming a filing date prior to December 19, 1980, it would have expired around 2000. However, patent terms can be extended due to various factors. A definitive expiration date requires checking specific USPTO records for any patent term adjustments or extensions. Without further information on the original filing date and any subsequent adjustments, a precise expiration date cannot be provided here. However, it is highly likely to have expired given its grant date.

What is the purity level of azadirachtin A achievable with the method described in Patent 6,162,802?

The patent specifies achieving a high purity level of azadirachtin A. While specific percentage points for purity are often detailed in dependent claims or exemplary embodiments within the patent's description, these processes are designed to yield azadirachtin A suitable for commercial insecticidal applications, which typically requires purities above 95% or higher, depending on the intended use and regulatory requirements.

Are there any other significant patents covering azadirachtin purification?

Yes, the patent landscape for azadirachtin is dynamic. While 6,162,802 describes a specific process, other patents exist that cover alternative or improved purification methods, different solvent systems, novel adsorbent materials, or different combinations of purification steps. Continuous research seeks to enhance yield, reduce costs, and improve the environmental profile of purification processes.

Can azadirachtin A be synthesized chemically, or is it exclusively extracted from natural sources?

Azadirachtin A is a complex natural product. While total chemical synthesis of azadirachtin A has been achieved in academic research settings, it is extremely challenging due to its intricate molecular structure. These synthetic routes are typically not economically viable for large-scale commercial production. Therefore, for commercial purposes, azadirachtin A is predominantly obtained through extraction and purification from neem seeds.

What are the main commercial applications for purified azadirachtin A?

Purified azadirachtin A is primarily used as a natural insecticide in agriculture and horticulture. Its insecticidal properties include acting as an antifeedant, disrupting insect growth and development, and exhibiting repellent effects. It is effective against a wide range of agricultural pests, including aphids, caterpillars, whiteflies, and mites. Its natural origin and biodegradability make it an attractive alternative to synthetic pesticides in organic farming and integrated pest management programs.

---

Citations

[1] Bio-Organic Research and Development Institute, Inc. (2000). Process for preparing azadirachtin compounds (U.S. Patent No. 6,162,802). United States Patent and Trademark Office.

Drugs Protected by US Patent 6,162,802

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