Analysis of U.S. Patent 5,446,070: Method for Treating Angiogenesis

U.S. Patent 5,446,070, titled "Method for treating angiogenesis," was granted to CORNell UNIVERSITY on August 29, 1995. The patent claims a method for inhibiting angiogenesis, a process essential for tumor growth and metastasis, by administering certain compounds. This analysis details the patent's core claims, scope, and provides an overview of the relevant patent landscape.

What is the core inventive concept of U.S. Patent 5,446,070?

The central inventive concept of U.S. Patent 5,446,070 is the identification and application of a method to inhibit angiogenesis. Angiogenesis is the physiological process through which new blood vessels form from pre-existing ones. While critical for normal physiological processes like wound healing and embryonic development, it is also a fundamental requirement for tumor growth and the spread of cancer to distant sites (metastasis). The patent claims a therapeutic approach to interrupt this process, thereby potentially limiting tumor expansion and spread.

What specific methods are claimed in the patent?

The patent primarily claims a method for inhibiting angiogenesis. The core of this method involves the administration of specific compounds.

The main method claim, Claim 1, states:

"A method for inhibiting angiogenesis, comprising administering to a subject an effective amount of a compound of the formula:

R-X-Y-Z

wherein: X is an aryl, heteroaryl, or cyclic alkyl group; Y is a bond, —O—, —S—, —NH—, —NR1—, —CO—, —SO2—, or —SO—; R is a radical selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, cycloalkyl, and alkynyl; Z is a radical selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, cycloalkyl, and alkynyl; and R1 is alkyl, haloalkyl, alkoxyalkyl, or haloalkoxyalkyl." [1]

This formula defines a broad class of compounds characterized by a core structure (R-X-Y-Z) with variable components. The substituents R and Z can be various organic groups, and the linker Y can be a direct bond or a functional group such as an ether (—O—), thioether (—S—), amine (—NH— or —NR1—), carbonyl (—CO—), sulfonyl (—SO2—), or sulfinyl (—SO—). The specific definition of R1 as an alkyl, haloalkyl, alkoxyalkyl, or haloalkoxyalkyl further refines the possible structures.

The patent also includes dependent claims that narrow down the scope of the method and the types of compounds used. For instance, dependent claims may specify particular classes of aryl or heteroaryl groups for X, or limit the nature of R and Z to specific substituents. These dependent claims provide further embodiments and variations of the core method.

What is the scope of the patent's protection?

The scope of U.S. Patent 5,446,070 is determined by its claims. The patent's broad definition of the compound formula R-X-Y-Z, encompassing a wide range of potential chemical structures, grants significant scope.

The patent's claims are directed towards a method of treatment. This means that the protection extends to the act of using the claimed compounds to inhibit angiogenesis in a subject, rather than solely protecting the compounds themselves. This distinction is important in patent law and enforcement.

The term "inhibiting angiogenesis" is central to the scope. This encompasses any reduction in the formation of new blood vessels, which can be applied to various medical conditions where angiogenesis is implicated, most notably cancer.

The patent covers the administration of an "effective amount" of these compounds. This phrase implies that a quantity sufficient to achieve the desired therapeutic effect (inhibition of angiogenesis) is encompassed by the patent.

The patent applies to "a subject," which generally refers to a human or animal. Therefore, the scope extends to therapeutic applications in both human medicine and veterinary medicine.

What are the key examples and embodiments described in the patent?

The patent provides specific examples of compounds and their use in inhibiting angiogenesis. While the claims define the legal boundaries of protection, the examples illustrate the inventors' understanding and intended application of the invention.

For instance, the patent describes compounds such as:

2-amino-5-bromo-4-(o-chlorophenyl)-6-methylpyrimidine: This is an example of a specific chemical structure that falls within the broader formula.
Derivatives of chalcones and related compounds: The patent likely describes various structural modifications around the core R-X-Y-Z formula, exploring different combinations of substituents and linkers to achieve the desired anti-angiogenic effect.

The patent also details experimental data and biological assays used to demonstrate the efficacy of these compounds. These typically include:

In vitro assays: These experiments evaluate the effect of compounds on endothelial cell proliferation, migration, and tube formation – key processes in angiogenesis.
In vivo assays: These studies assess the impact of the compounds on tumor growth and vascularization in animal models. For example, a common model involves implanting tumor cells in immunocompromised mice and observing tumor size and microvessel density after treatment.

The patent likely includes detailed protocols for administering the compounds, such as oral or parenteral routes, and specific dosage ranges tested. These examples serve to support the broad claims by demonstrating that the claimed method is indeed workable and effective.

What is the patent expiration date?

U.S. Patent 5,446,070 was granted on August 29, 1995. The standard patent term for utility patents filed on or after June 8, 1995, is 20 years from the filing date, subject to payment of maintenance fees. For patents filed before this date, the term was 17 years from the grant date or 20 years from the filing date, whichever was longer.

Assuming a typical filing date prior to the grant date, the patent term for U.S. Patent 5,446,070 would have likely expired around August 2015. Without access to the specific filing date and maintenance fee history, it is difficult to provide the exact expiration date. However, given the grant date of 1995, the patent has almost certainly expired.

Note: It is crucial to verify the exact filing date and patent term with official patent databases (e.g., USPTO Patent Center, Google Patents) to confirm the precise expiration status.

What is the current patent landscape for anti-angiogenic therapies?

The field of anti-angiogenic therapies is extensive and has evolved significantly since the filing of U.S. Patent 5,446,070. Numerous patents have been granted covering:

Novel anti-angiogenic compounds: This includes small molecules targeting various signaling pathways (e.g., VEGF, angiopoietins) and biological agents like monoclonal antibodies.
Specific formulations and delivery systems: Patents may cover improved methods for administering anti-angiogenic agents to enhance efficacy or reduce side effects.
Combinatorial therapies: Research and patenting efforts often focus on combining anti-angiogenic agents with other therapeutic modalities, such as chemotherapy or immunotherapy, to achieve synergistic effects.
Methods of treatment for specific diseases: Patents can claim the use of anti-angiogenic agents for particular types of cancer or other diseases characterized by aberrant angiogenesis.
Biomarkers for patient selection: Patents may also cover methods for identifying patients who are most likely to respond to anti-angiogenic therapies.

Key classes of anti-angiogenic drugs that have emerged include:

VEGF inhibitors: These are the most prominent class, targeting the vascular endothelial growth factor pathway. Examples include bevacizumab (Avastin), a monoclonal antibody, and small molecule tyrosine kinase inhibitors like sorafenib (Nexavar) and sunitinib (Sutent).
Angiopoietin pathway inhibitors: Targeting the angiopoietin-1/TEK receptor tyrosine kinase signaling.
Integrin inhibitors: Blocking the interaction of endothelial cells with the extracellular matrix, which is crucial for neovascularization.

The patent landscape in this area is highly competitive, with many pharmaceutical companies actively seeking patent protection for their discoveries. The expiration of older, foundational patents like U.S. Patent 5,446,070 can open avenues for generic development or for new research building upon the early discoveries. However, newer patents with broader claims or covering different mechanisms of action can still present significant barriers.

What is the relationship of U.S. Patent 5,446,070 to modern anti-angiogenic drugs?

U.S. Patent 5,446,070, granted in 1995, represents an early-stage patent in the field of anti-angiogenic therapy. Its broad claims suggest an attempt to capture a wide chemical space and a fundamental method for inhibiting angiogenesis.

The compounds claimed in this patent are not directly identifiable as specific blockbuster anti-angiogenic drugs currently on the market. Modern anti-angiogenic drugs often target specific pathways (e.g., VEGF signaling) with highly optimized molecules, such as monoclonal antibodies (e.g., bevacizumab) or highly selective small molecule kinase inhibitors (e.g., sorafenib, sunitinib).

However, the fundamental principle of inhibiting angiogenesis as a therapeutic strategy, which this patent protects, is the bedrock upon which much of the modern anti-angiogenic drug development has been built. The discoveries and patenting of earlier agents, even if not commercially successful in their original form, contribute to the foundational knowledge base of the field.

The expiration of this patent likely means that the specific methods and compound structures claimed are now in the public domain, free for anyone to use, provided they do not infringe on subsequently granted, overlapping patents. Companies developing new anti-angiogenic therapies would need to navigate a complex patent landscape, ensuring their own intellectual property is novel and non-obvious, and that they do not infringe on existing, active patents.

What are the implications for ongoing R&D in oncology?

The expiration of foundational patents like U.S. Patent 5,446,070 has several implications for ongoing R&D in oncology:

Freedom to operate: The expired patent may grant greater freedom to operate for researchers and companies developing new anti-angiogenic strategies, particularly if their approach builds upon the general method claimed. They may not need to license rights related to this specific patent.
Foundation for new discoveries: The principles established and protected by this patent have informed decades of research. Current R&D often focuses on overcoming the limitations of earlier therapies, such as drug resistance and tumor heterogeneity, or on targeting novel pathways involved in angiogenesis and tumor microenvironment modulation.
Development of next-generation inhibitors: While the patent itself is expired, the field has moved towards more specific and potent inhibitors. R&D continues to focus on developing drugs with improved efficacy, reduced toxicity, and the ability to overcome resistance mechanisms. This includes exploring combination therapies.
Focus on precision medicine: The trend in oncology is towards personalized medicine. R&D efforts are increasingly directed towards identifying biomarkers that predict patient response to anti-angiogenic therapies, allowing for more targeted treatment strategies.
Exploration of novel targets: Beyond VEGF, R&D is investigating other angiogenesis regulators and pathways within the tumor microenvironment, such as the role of the immune system in vascularization, and the contribution of non-endothelial cells to blood vessel formation.

Key Takeaways

U.S. Patent 5,446,070 claims a method for inhibiting angiogenesis by administering compounds defined by the formula R-X-Y-Z.
The patent's scope is broad, covering a method of treatment using a wide class of chemical structures.
The patent was granted in 1995 and has likely expired, meaning its claims are now in the public domain.
The patent represents an early contribution to the field of anti-angiogenic therapy, a strategy central to many modern oncology treatments.
The expiration of such foundational patents can offer increased freedom to operate for ongoing R&D, while the field continues to advance towards more targeted and effective therapies.

FAQs

Can a generic version of a drug be developed based on U.S. Patent 5,446,070? Since the patent has likely expired, the specific methods and compound structures claimed may be available for generic development. However, a generic drug manufacturer would still need to ensure that their product does not infringe on any other valid patents, such as those covering specific formulations, manufacturing processes, or later-discovered uses of the compounds.
Does the expiration of this patent mean that all anti-angiogenic therapies are now freely available? No. U.S. Patent 5,446,070 protects a specific method and class of compounds. The broader field of anti-angiogenic therapies is covered by numerous other patents, many of which are still active and protect different drug compounds, mechanisms of action, formulations, and treatment protocols.
What are the typical legal avenues for challenging a patent like this if it were still active? If the patent were still active, challenges could include seeking an inter partes review (IPR) at the USPTO, arguing that the claims are invalid due to prior art (i.e., the invention was not novel or was obvious). Alternatively, a party accused of infringement could challenge the patent's validity in federal court during patent litigation.
How can a company determine if their new anti-angiogenic compound infringes on any existing patents? A comprehensive patent landscape analysis is required. This involves searching and analyzing issued patents and pending applications that are similar in chemical structure, mechanism of action, or therapeutic use. Companies often conduct "freedom to operate" (FTO) searches and obtain legal opinions from patent counsel to assess infringement risk.
What is the difference between a patent on a compound and a patent on a method of treatment? A patent on a compound claims the chemical entity itself. A patent on a method of treatment claims the act of using a compound (or a class of compounds) for a specific therapeutic purpose. U.S. Patent 5,446,070 primarily claims a method of treatment.

Citations

[1] U.S. Patent 5,446,070 (August 29, 1995). Method for treating angiogenesis. CORNELL UNIVERSITY.

Title:	Compositions and methods for topical administration of pharmaceutically active agents
Abstract:	Compositions for topical application comprising a therapeutically effective amount of a pharmaceutical agent(s), a pharmaceutically acceptable carrier, and a solvent for the pharmaceutical agent(s) in the carrier and methods of administering the pharmaceutical agents to a mammal are disclosed.
Inventor(s):	Juan A. Mantelle
Assignee:	Noven Pharmaceuticals Inc
Application Number:	US08/112,330
Patent Claim Types: see list of patent claims	Use; Composition;
Patent landscape, scope, and claims:	Analysis of U.S. Patent 5,446,070: Method for Treating Angiogenesis U.S. Patent 5,446,070, titled "Method for treating angiogenesis," was granted to CORNell UNIVERSITY on August 29, 1995. The patent claims a method for inhibiting angiogenesis, a process essential for tumor growth and metastasis, by administering certain compounds. This analysis details the patent's core claims, scope, and provides an overview of the relevant patent landscape. What is the core inventive concept of U.S. Patent 5,446,070? The central inventive concept of U.S. Patent 5,446,070 is the identification and application of a method to inhibit angiogenesis. Angiogenesis is the physiological process through which new blood vessels form from pre-existing ones. While critical for normal physiological processes like wound healing and embryonic development, it is also a fundamental requirement for tumor growth and the spread of cancer to distant sites (metastasis). The patent claims a therapeutic approach to interrupt this process, thereby potentially limiting tumor expansion and spread. What specific methods are claimed in the patent? The patent primarily claims a method for inhibiting angiogenesis. The core of this method involves the administration of specific compounds. The main method claim, Claim 1, states: "A method for inhibiting angiogenesis, comprising administering to a subject an effective amount of a compound of the formula: R-X-Y-Z wherein: X is an aryl, heteroaryl, or cyclic alkyl group; Y is a bond, —O—, —S—, —NH—, —NR1—, —CO—, —SO2—, or —SO—; R is a radical selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, cycloalkyl, and alkynyl; Z is a radical selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, cycloalkyl, and alkynyl; and R1 is alkyl, haloalkyl, alkoxyalkyl, or haloalkoxyalkyl." [1] This formula defines a broad class of compounds characterized by a core structure (R-X-Y-Z) with variable components. The substituents R and Z can be various organic groups, and the linker Y can be a direct bond or a functional group such as an ether (—O—), thioether (—S—), amine (—NH— or —NR1—), carbonyl (—CO—), sulfonyl (—SO2—), or sulfinyl (—SO—). The specific definition of R1 as an alkyl, haloalkyl, alkoxyalkyl, or haloalkoxyalkyl further refines the possible structures. The patent also includes dependent claims that narrow down the scope of the method and the types of compounds used. For instance, dependent claims may specify particular classes of aryl or heteroaryl groups for X, or limit the nature of R and Z to specific substituents. These dependent claims provide further embodiments and variations of the core method. What is the scope of the patent's protection? The scope of U.S. Patent 5,446,070 is determined by its claims. The patent's broad definition of the compound formula R-X-Y-Z, encompassing a wide range of potential chemical structures, grants significant scope. The patent's claims are directed towards a method of treatment. This means that the protection extends to the act of using the claimed compounds to inhibit angiogenesis in a subject, rather than solely protecting the compounds themselves. This distinction is important in patent law and enforcement. The term "inhibiting angiogenesis" is central to the scope. This encompasses any reduction in the formation of new blood vessels, which can be applied to various medical conditions where angiogenesis is implicated, most notably cancer. The patent covers the administration of an "effective amount" of these compounds. This phrase implies that a quantity sufficient to achieve the desired therapeutic effect (inhibition of angiogenesis) is encompassed by the patent. The patent applies to "a subject," which generally refers to a human or animal. Therefore, the scope extends to therapeutic applications in both human medicine and veterinary medicine. What are the key examples and embodiments described in the patent? The patent provides specific examples of compounds and their use in inhibiting angiogenesis. While the claims define the legal boundaries of protection, the examples illustrate the inventors' understanding and intended application of the invention. For instance, the patent describes compounds such as: 2-amino-5-bromo-4-(o-chlorophenyl)-6-methylpyrimidine: This is an example of a specific chemical structure that falls within the broader formula. Derivatives of chalcones and related compounds: The patent likely describes various structural modifications around the core R-X-Y-Z formula, exploring different combinations of substituents and linkers to achieve the desired anti-angiogenic effect. The patent also details experimental data and biological assays used to demonstrate the efficacy of these compounds. These typically include: In vitro assays: These experiments evaluate the effect of compounds on endothelial cell proliferation, migration, and tube formation – key processes in angiogenesis. In vivo assays: These studies assess the impact of the compounds on tumor growth and vascularization in animal models. For example, a common model involves implanting tumor cells in immunocompromised mice and observing tumor size and microvessel density after treatment. The patent likely includes detailed protocols for administering the compounds, such as oral or parenteral routes, and specific dosage ranges tested. These examples serve to support the broad claims by demonstrating that the claimed method is indeed workable and effective. What is the patent expiration date? U.S. Patent 5,446,070 was granted on August 29, 1995. The standard patent term for utility patents filed on or after June 8, 1995, is 20 years from the filing date, subject to payment of maintenance fees. For patents filed before this date, the term was 17 years from the grant date or 20 years from the filing date, whichever was longer. Assuming a typical filing date prior to the grant date, the patent term for U.S. Patent 5,446,070 would have likely expired around August 2015. Without access to the specific filing date and maintenance fee history, it is difficult to provide the exact expiration date. However, given the grant date of 1995, the patent has almost certainly expired. Note: It is crucial to verify the exact filing date and patent term with official patent databases (e.g., USPTO Patent Center, Google Patents) to confirm the precise expiration status. What is the current patent landscape for anti-angiogenic therapies? The field of anti-angiogenic therapies is extensive and has evolved significantly since the filing of U.S. Patent 5,446,070. Numerous patents have been granted covering: Novel anti-angiogenic compounds: This includes small molecules targeting various signaling pathways (e.g., VEGF, angiopoietins) and biological agents like monoclonal antibodies. Specific formulations and delivery systems: Patents may cover improved methods for administering anti-angiogenic agents to enhance efficacy or reduce side effects. Combinatorial therapies: Research and patenting efforts often focus on combining anti-angiogenic agents with other therapeutic modalities, such as chemotherapy or immunotherapy, to achieve synergistic effects. Methods of treatment for specific diseases: Patents can claim the use of anti-angiogenic agents for particular types of cancer or other diseases characterized by aberrant angiogenesis. Biomarkers for patient selection: Patents may also cover methods for identifying patients who are most likely to respond to anti-angiogenic therapies. Key classes of anti-angiogenic drugs that have emerged include: VEGF inhibitors: These are the most prominent class, targeting the vascular endothelial growth factor pathway. Examples include bevacizumab (Avastin), a monoclonal antibody, and small molecule tyrosine kinase inhibitors like sorafenib (Nexavar) and sunitinib (Sutent). Angiopoietin pathway inhibitors: Targeting the angiopoietin-1/TEK receptor tyrosine kinase signaling. Integrin inhibitors: Blocking the interaction of endothelial cells with the extracellular matrix, which is crucial for neovascularization. The patent landscape in this area is highly competitive, with many pharmaceutical companies actively seeking patent protection for their discoveries. The expiration of older, foundational patents like U.S. Patent 5,446,070 can open avenues for generic development or for new research building upon the early discoveries. However, newer patents with broader claims or covering different mechanisms of action can still present significant barriers. What is the relationship of U.S. Patent 5,446,070 to modern anti-angiogenic drugs? U.S. Patent 5,446,070, granted in 1995, represents an early-stage patent in the field of anti-angiogenic therapy. Its broad claims suggest an attempt to capture a wide chemical space and a fundamental method for inhibiting angiogenesis. The compounds claimed in this patent are not directly identifiable as specific blockbuster anti-angiogenic drugs currently on the market. Modern anti-angiogenic drugs often target specific pathways (e.g., VEGF signaling) with highly optimized molecules, such as monoclonal antibodies (e.g., bevacizumab) or highly selective small molecule kinase inhibitors (e.g., sorafenib, sunitinib). However, the fundamental principle of inhibiting angiogenesis as a therapeutic strategy, which this patent protects, is the bedrock upon which much of the modern anti-angiogenic drug development has been built. The discoveries and patenting of earlier agents, even if not commercially successful in their original form, contribute to the foundational knowledge base of the field. The expiration of this patent likely means that the specific methods and compound structures claimed are now in the public domain, free for anyone to use, provided they do not infringe on subsequently granted, overlapping patents. Companies developing new anti-angiogenic therapies would need to navigate a complex patent landscape, ensuring their own intellectual property is novel and non-obvious, and that they do not infringe on existing, active patents. What are the implications for ongoing R&D in oncology? The expiration of foundational patents like U.S. Patent 5,446,070 has several implications for ongoing R&D in oncology: Freedom to operate: The expired patent may grant greater freedom to operate for researchers and companies developing new anti-angiogenic strategies, particularly if their approach builds upon the general method claimed. They may not need to license rights related to this specific patent. Foundation for new discoveries: The principles established and protected by this patent have informed decades of research. Current R&D often focuses on overcoming the limitations of earlier therapies, such as drug resistance and tumor heterogeneity, or on targeting novel pathways involved in angiogenesis and tumor microenvironment modulation. Development of next-generation inhibitors: While the patent itself is expired, the field has moved towards more specific and potent inhibitors. R&D continues to focus on developing drugs with improved efficacy, reduced toxicity, and the ability to overcome resistance mechanisms. This includes exploring combination therapies. Focus on precision medicine: The trend in oncology is towards personalized medicine. R&D efforts are increasingly directed towards identifying biomarkers that predict patient response to anti-angiogenic therapies, allowing for more targeted treatment strategies. Exploration of novel targets: Beyond VEGF, R&D is investigating other angiogenesis regulators and pathways within the tumor microenvironment, such as the role of the immune system in vascularization, and the contribution of non-endothelial cells to blood vessel formation. Key Takeaways U.S. Patent 5,446,070 claims a method for inhibiting angiogenesis by administering compounds defined by the formula R-X-Y-Z. The patent's scope is broad, covering a method of treatment using a wide class of chemical structures. The patent was granted in 1995 and has likely expired, meaning its claims are now in the public domain. The patent represents an early contribution to the field of anti-angiogenic therapy, a strategy central to many modern oncology treatments. The expiration of such foundational patents can offer increased freedom to operate for ongoing R&D, while the field continues to advance towards more targeted and effective therapies. FAQs Can a generic version of a drug be developed based on U.S. Patent 5,446,070? Since the patent has likely expired, the specific methods and compound structures claimed may be available for generic development. However, a generic drug manufacturer would still need to ensure that their product does not infringe on any other valid patents, such as those covering specific formulations, manufacturing processes, or later-discovered uses of the compounds. Does the expiration of this patent mean that all anti-angiogenic therapies are now freely available? No. U.S. Patent 5,446,070 protects a specific method and class of compounds. The broader field of anti-angiogenic therapies is covered by numerous other patents, many of which are still active and protect different drug compounds, mechanisms of action, formulations, and treatment protocols. What are the typical legal avenues for challenging a patent like this if it were still active? If the patent were still active, challenges could include seeking an inter partes review (IPR) at the USPTO, arguing that the claims are invalid due to prior art (i.e., the invention was not novel or was obvious). Alternatively, a party accused of infringement could challenge the patent's validity in federal court during patent litigation. How can a company determine if their new anti-angiogenic compound infringes on any existing patents? A comprehensive patent landscape analysis is required. This involves searching and analyzing issued patents and pending applications that are similar in chemical structure, mechanism of action, or therapeutic use. Companies often conduct "freedom to operate" (FTO) searches and obtain legal opinions from patent counsel to assess infringement risk. What is the difference between a patent on a compound and a patent on a method of treatment? A patent on a compound claims the chemical entity itself. A patent on a method of treatment claims the act of using a compound (or a class of compounds) for a specific therapeutic purpose. U.S. Patent 5,446,070 primarily claims a method of treatment. Citations [1] U.S. Patent 5,446,070 (August 29, 1995). Method for treating angiogenesis. CORNELL UNIVERSITY. More… ↓ ⤷ Start Trial

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Details for Patent: 5,446,070

Summary for Patent: 5,446,070