Analysis of United States Patent 8,071,532

United States Patent 8,071,532, titled "Methods for treatment of proliferative disorders," claims methods for treating proliferative disorders using specific small molecule inhibitors of the PI3K/mTOR pathway. The patent was filed on June 18, 2009, and granted on December 6, 2011. It was assigned to The General Hospital Corporation.

What Does United States Patent 8,071,532 Claim?

The patent asserts claims for methods of treating proliferative disorders, a broad category encompassing conditions characterized by uncontrolled cell growth, such as cancer. The core of the invention lies in the use of specific compounds that inhibit the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling pathway. This pathway is frequently dysregulated in various cancers, leading to enhanced cell survival, proliferation, and resistance to therapy.

What Specific Compounds Are Covered?

The patent claims encompass a genus of compounds and specific exemplified structures. The genus is defined by Markush structures, a standard practice in chemical patenting to broadly claim a class of related molecules. The claims detail structural features and substituents that characterize these PI3K/mTOR inhibitors.

Key structural elements and claimed features include:

Core Heterocyclic Rings: Various nitrogen-containing heterocyclic scaffolds are described as central to the claimed compounds.
Substituents: Specific functional groups and their positions on these heterocyclic rings are detailed, influencing the compound's binding affinity and biological activity. These include alkyl groups, aryl groups, and heteroaryl groups, often with further functionalization.
Examples of Exemplified Compounds: The patent provides detailed synthetic routes and characterization data for numerous specific compounds. These examples serve to illustrate the scope of the claimed genus and provide concrete instances of the patented technology. For instance, Claim 1 broadly recites a compound having a specific general structure, with subsequent claims narrowing this scope or providing specific substituents.

What PI3K/mTOR Pathway Inhibition Does the Patent Address?

The patent focuses on compounds designed to inhibit the PI3K/mTOR signaling cascade. This pathway plays a critical role in cellular processes such as growth, survival, metabolism, and proliferation. Aberrant activation of PI3K/mTOR is a hallmark of many cancers, driving tumor growth and progression.

The patent claims methods of treatment by inhibiting:

PI3K Isoforms: The patent implies inhibition of various PI3K isoforms, which are lipid kinases crucial for downstream signaling.
mTOR Kinase: Inhibition of mTOR, a serine/threonine kinase that acts as a central regulator of cell growth and protein synthesis, is also a target.
Dual PI3K/mTOR Inhibition: Many compounds within the scope of the patent are designed to inhibit both PI3K and mTOR, offering a potentially more potent therapeutic effect.

What Proliferative Disorders Are Targeted?

The patent broadly claims methods for treating "proliferative disorders." This encompasses a wide range of diseases characterized by excessive cell division.

Examples of targeted proliferative disorders, as generally understood in the field and implied by the patent's scope, include:

Various Cancers: This includes solid tumors (e.g., breast cancer, lung cancer, prostate cancer, colon cancer) and hematological malignancies (e.g., leukemia, lymphoma).
Benign Proliferative Conditions: While the primary focus is typically on oncological applications, the broad definition could extend to non-cancerous conditions involving abnormal cell growth.

What Is the Patent Landscape for PI3K/mTOR Inhibitors?

The patent landscape for PI3K/mTOR inhibitors is highly competitive and crowded, with numerous entities actively pursuing patent protection for novel compounds, formulations, and therapeutic uses. United States Patent 8,071,532 is one of many patents in this space.

Who Are the Key Players in PI3K/mTOR Patenting?

Beyond The General Hospital Corporation (assignee of US Patent 8,071,532), major pharmaceutical companies and research institutions hold significant patent portfolios in this area. These include, but are not limited to:

Major Pharmaceutical Companies: Novartis, Pfizer, Bristol Myers Squibb, Genentech (Roche), Merck, and AstraZeneca have substantial patent filings and approved therapies targeting the PI3K/mTOR pathway.
Academic Institutions: Leading universities and research hospitals often hold early-stage patents that are subsequently licensed to pharmaceutical companies.
Biotechnology Companies: Several smaller and mid-sized biotech firms specialize in oncology drug discovery and hold patents on innovative PI3K/mTOR inhibitors.

How Does US Patent 8,071,532 Compare to Other Patents?

The novelty and scope of US Patent 8,071,532 must be assessed in the context of prior art and existing patents. The patent's strength depends on the distinctiveness of its claimed compounds and methods compared to previously disclosed inventions.

Comparative factors include:

Structural Uniqueness: Whether the claimed chemical structures are significantly different from those disclosed in earlier patents or scientific literature.
Therapeutic Efficacy: Evidence of superior or novel therapeutic effects for the claimed compounds in treating specific proliferative disorders.
Manufacturing Process: Claims related to novel or improved methods of synthesizing the patented compounds.
Formulations and Delivery: Patents covering specific drug formulations or delivery systems designed to enhance the efficacy or reduce the toxicity of PI3K/mTOR inhibitors.

The granted status of US Patent 8,071,532 indicates that the U.S. Patent and Trademark Office (USPTO) found the claims to be novel, non-obvious, and adequately described at the time of filing. However, patent validity can be challenged post-grant through inter partes reviews or litigation, where prior art not considered during examination may be presented.

What Is the Status of Approved PI3K/mTOR Inhibitors?

Several PI3K/mTOR inhibitors have received regulatory approval, indicating the pathway's therapeutic relevance. These approved drugs represent significant market activity and potential competition.

Examples of approved PI3K/mTOR inhibitors (and their primary targets) include:

Everolimus (Afinitor®): An mTOR inhibitor, approved for various cancers including breast cancer and certain kidney cancers.
Sirolimus (Rapamune®): Also an mTOR inhibitor, primarily used as an immunosuppressant but with applications in certain oncological settings.
Idelalisib (Zydelig®): A PI3Kδ inhibitor, approved for specific B-cell malignancies.
Copanlisib (Aliqopa®): A dual PI3Kα/β inhibitor, approved for certain types of lymphoma.
Alpelisib (Piqray®): A PI3Kα inhibitor, approved for certain types of hormone receptor-positive, HER2-negative breast cancer.

The existence of these approved drugs highlights the therapeutic potential of targeting the PI3K/mTOR pathway. However, it also signifies a crowded market and the need for new entrants to demonstrate significant advantages in terms of efficacy, safety, or patient population.

What Are the Key Limitations and Challenges for US Patent 8,071,532?

Despite its granted status, US Patent 8,071,532 faces several inherent limitations and potential challenges within the competitive pharmaceutical patent landscape.

How Broad Is the Claimed Scope?

The breadth of the patent's claims is a critical factor in its commercial value. Broad claims offer wider protection, while narrow claims provide more specific protection but are easier to design around.

Factors influencing scope include:

Markush Structures: While broad, Markush structures can be limited by the specific variables and substituents defined. The USPTO's examination process scrutinizes the support for each permutation claimed.
Dependence on Exemplified Embodiments: The strength and enforceability of broad genus claims often rely on the thoroughness of the exemplified compounds and their supporting data. If key aspects of the genus are not adequately exemplified, their patentability may be weaker.
Prior Art Limitations: Even broad claims are limited by the existence of prior art that discloses similar compounds or methods. Any prior art that anticipates or renders obvious the claimed invention can invalidate the patent.

What Is the Status of the Patent's Enforceability?

The enforceability of a patent is paramount for any commercial strategy. US Patent 8,071,532, granted in 2011, is subject to potential post-grant challenges.

Considerations for enforceability:

Infringement Analysis: Determining if a competitor's product or process infringes upon the claims of US Patent 8,071,532 requires a detailed claim-by-claim analysis. This involves comparing the competitor's technology to the literal language of the patent claims.
Patent Validity Challenges: Competitors may challenge the patent's validity based on new prior art or arguments that the patent should not have been granted. These challenges can occur through USPTO proceedings (e.g., inter partes review) or in district court litigation.
Term Expiration: The patent is subject to a 20-year term from its filing date. US Patent 8,071,532 filed on June 18, 2009, will expire on June 18, 2029. This limited remaining term affects long-term investment and commercialization strategies.

What Is the Clinical and Commercial Viability of the Claimed Technology?

The ultimate value of a patent is tied to the real-world success of the technology it protects. For US Patent 8,071,532, this depends on the development and success of compounds falling within its claims.

Factors influencing viability:

Clinical Trial Data: Compounds covered by the patent must demonstrate significant efficacy and an acceptable safety profile in human clinical trials. The PI3K/mTOR pathway is complex, and achieving a therapeutic window with manageable toxicity is a major hurdle.
Regulatory Approval: Successful navigation of the regulatory approval process by the U.S. Food and Drug Administration (FDA) and other global health authorities is essential for commercialization.
Market Competition: The presence of approved PI3K/mTOR inhibitors and other oncology drugs means any new therapeutic based on this patent must offer a clear advantage to gain market share.
Development Costs: The significant costs associated with drug discovery, preclinical development, clinical trials, and regulatory submissions represent a substantial financial commitment.

Key Takeaways

United States Patent 8,071,532 claims methods for treating proliferative disorders using PI3K/mTOR pathway inhibitors. The patent covers a genus of compounds defined by specific structural features and exemplified by numerous specific molecules. The PI3K/mTOR pathway is a validated target in oncology, with several approved drugs already on the market. The patent's enforceability and commercial value are contingent on the novelty and scope of its claims relative to prior art, the clinical and commercial success of any compounds developed under its protection, and its remaining patent term, which expires in June 2029. The competitive landscape is robust, necessitating clear differentiation for any future therapeutic interventions.

FAQs

What is the primary therapeutic target of the compounds claimed in US Patent 8,071,532? The primary therapeutic target is the PI3K/mTOR signaling pathway, which is implicated in cellular proliferation and is often dysregulated in various cancers.
When will US Patent 8,071,532 expire? The patent was filed on June 18, 2009, and will expire on June 18, 2029.
Who is the assignee of US Patent 8,071,532? The assignee is The General Hospital Corporation.
Are there approved drugs currently on the market that target the PI3K/mTOR pathway? Yes, several PI3K/mTOR inhibitors have received regulatory approval, including Everolimus, Sirolimus, Idelalisib, Copanlisib, and Alpelisib.
What are the main challenges associated with developing drugs that target the PI3K/mTOR pathway? Key challenges include achieving a therapeutic window with manageable toxicity due to the pathway's broad role in normal cellular functions, demonstrating significant efficacy improvements over existing treatments, and navigating the competitive market landscape.

Citations

[1] The General Hospital Corporation. (2011). Methods for treatment of proliferative disorders. U.S. Patent No. 8,071,532. Washington, DC: U.S. Patent and Trademark Office.

Title:	Use of C1 inhibitor for the prevention of ischemia-reperfusion injury
Abstract:	The present invention relates to the therapeutic and prophylactic use of C1 inhibitor for preventing, reducing and treating ischemia and reperfusion injury. The C1 inhibitor of the present invention is still therapeutically effective when administered after an ischemic period and reperfusion and therefore particularly useful for unforeseen occurrences of ischemic reperfusion such as e.g. a stroke.
Inventor(s):	Maurice Mannesse, Johannes Henricus Nuijens, Frank Pieper, Maria Grazia De Simoni, Gijsbertus Johannes Ziere
Assignee:	Pharming Intellectual Property BV
Application Number:	US12/158,987
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	Analysis of United States Patent 8,071,532 United States Patent 8,071,532, titled "Methods for treatment of proliferative disorders," claims methods for treating proliferative disorders using specific small molecule inhibitors of the PI3K/mTOR pathway. The patent was filed on June 18, 2009, and granted on December 6, 2011. It was assigned to The General Hospital Corporation. What Does United States Patent 8,071,532 Claim? The patent asserts claims for methods of treating proliferative disorders, a broad category encompassing conditions characterized by uncontrolled cell growth, such as cancer. The core of the invention lies in the use of specific compounds that inhibit the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling pathway. This pathway is frequently dysregulated in various cancers, leading to enhanced cell survival, proliferation, and resistance to therapy. What Specific Compounds Are Covered? The patent claims encompass a genus of compounds and specific exemplified structures. The genus is defined by Markush structures, a standard practice in chemical patenting to broadly claim a class of related molecules. The claims detail structural features and substituents that characterize these PI3K/mTOR inhibitors. Key structural elements and claimed features include: Core Heterocyclic Rings: Various nitrogen-containing heterocyclic scaffolds are described as central to the claimed compounds. Substituents: Specific functional groups and their positions on these heterocyclic rings are detailed, influencing the compound's binding affinity and biological activity. These include alkyl groups, aryl groups, and heteroaryl groups, often with further functionalization. Examples of Exemplified Compounds: The patent provides detailed synthetic routes and characterization data for numerous specific compounds. These examples serve to illustrate the scope of the claimed genus and provide concrete instances of the patented technology. For instance, Claim 1 broadly recites a compound having a specific general structure, with subsequent claims narrowing this scope or providing specific substituents. What PI3K/mTOR Pathway Inhibition Does the Patent Address? The patent focuses on compounds designed to inhibit the PI3K/mTOR signaling cascade. This pathway plays a critical role in cellular processes such as growth, survival, metabolism, and proliferation. Aberrant activation of PI3K/mTOR is a hallmark of many cancers, driving tumor growth and progression. The patent claims methods of treatment by inhibiting: PI3K Isoforms: The patent implies inhibition of various PI3K isoforms, which are lipid kinases crucial for downstream signaling. mTOR Kinase: Inhibition of mTOR, a serine/threonine kinase that acts as a central regulator of cell growth and protein synthesis, is also a target. Dual PI3K/mTOR Inhibition: Many compounds within the scope of the patent are designed to inhibit both PI3K and mTOR, offering a potentially more potent therapeutic effect. What Proliferative Disorders Are Targeted? The patent broadly claims methods for treating "proliferative disorders." This encompasses a wide range of diseases characterized by excessive cell division. Examples of targeted proliferative disorders, as generally understood in the field and implied by the patent's scope, include: Various Cancers: This includes solid tumors (e.g., breast cancer, lung cancer, prostate cancer, colon cancer) and hematological malignancies (e.g., leukemia, lymphoma). Benign Proliferative Conditions: While the primary focus is typically on oncological applications, the broad definition could extend to non-cancerous conditions involving abnormal cell growth. What Is the Patent Landscape for PI3K/mTOR Inhibitors? The patent landscape for PI3K/mTOR inhibitors is highly competitive and crowded, with numerous entities actively pursuing patent protection for novel compounds, formulations, and therapeutic uses. United States Patent 8,071,532 is one of many patents in this space. Who Are the Key Players in PI3K/mTOR Patenting? Beyond The General Hospital Corporation (assignee of US Patent 8,071,532), major pharmaceutical companies and research institutions hold significant patent portfolios in this area. These include, but are not limited to: Major Pharmaceutical Companies: Novartis, Pfizer, Bristol Myers Squibb, Genentech (Roche), Merck, and AstraZeneca have substantial patent filings and approved therapies targeting the PI3K/mTOR pathway. Academic Institutions: Leading universities and research hospitals often hold early-stage patents that are subsequently licensed to pharmaceutical companies. Biotechnology Companies: Several smaller and mid-sized biotech firms specialize in oncology drug discovery and hold patents on innovative PI3K/mTOR inhibitors. How Does US Patent 8,071,532 Compare to Other Patents? The novelty and scope of US Patent 8,071,532 must be assessed in the context of prior art and existing patents. The patent's strength depends on the distinctiveness of its claimed compounds and methods compared to previously disclosed inventions. Comparative factors include: Structural Uniqueness: Whether the claimed chemical structures are significantly different from those disclosed in earlier patents or scientific literature. Therapeutic Efficacy: Evidence of superior or novel therapeutic effects for the claimed compounds in treating specific proliferative disorders. Manufacturing Process: Claims related to novel or improved methods of synthesizing the patented compounds. Formulations and Delivery: Patents covering specific drug formulations or delivery systems designed to enhance the efficacy or reduce the toxicity of PI3K/mTOR inhibitors. The granted status of US Patent 8,071,532 indicates that the U.S. Patent and Trademark Office (USPTO) found the claims to be novel, non-obvious, and adequately described at the time of filing. However, patent validity can be challenged post-grant through inter partes reviews or litigation, where prior art not considered during examination may be presented. What Is the Status of Approved PI3K/mTOR Inhibitors? Several PI3K/mTOR inhibitors have received regulatory approval, indicating the pathway's therapeutic relevance. These approved drugs represent significant market activity and potential competition. Examples of approved PI3K/mTOR inhibitors (and their primary targets) include: Everolimus (Afinitor®): An mTOR inhibitor, approved for various cancers including breast cancer and certain kidney cancers. Sirolimus (Rapamune®): Also an mTOR inhibitor, primarily used as an immunosuppressant but with applications in certain oncological settings. Idelalisib (Zydelig®): A PI3Kδ inhibitor, approved for specific B-cell malignancies. Copanlisib (Aliqopa®): A dual PI3Kα/β inhibitor, approved for certain types of lymphoma. Alpelisib (Piqray®): A PI3Kα inhibitor, approved for certain types of hormone receptor-positive, HER2-negative breast cancer. The existence of these approved drugs highlights the therapeutic potential of targeting the PI3K/mTOR pathway. However, it also signifies a crowded market and the need for new entrants to demonstrate significant advantages in terms of efficacy, safety, or patient population. What Are the Key Limitations and Challenges for US Patent 8,071,532? Despite its granted status, US Patent 8,071,532 faces several inherent limitations and potential challenges within the competitive pharmaceutical patent landscape. How Broad Is the Claimed Scope? The breadth of the patent's claims is a critical factor in its commercial value. Broad claims offer wider protection, while narrow claims provide more specific protection but are easier to design around. Factors influencing scope include: Markush Structures: While broad, Markush structures can be limited by the specific variables and substituents defined. The USPTO's examination process scrutinizes the support for each permutation claimed. Dependence on Exemplified Embodiments: The strength and enforceability of broad genus claims often rely on the thoroughness of the exemplified compounds and their supporting data. If key aspects of the genus are not adequately exemplified, their patentability may be weaker. Prior Art Limitations: Even broad claims are limited by the existence of prior art that discloses similar compounds or methods. Any prior art that anticipates or renders obvious the claimed invention can invalidate the patent. What Is the Status of the Patent's Enforceability? The enforceability of a patent is paramount for any commercial strategy. US Patent 8,071,532, granted in 2011, is subject to potential post-grant challenges. Considerations for enforceability: Infringement Analysis: Determining if a competitor's product or process infringes upon the claims of US Patent 8,071,532 requires a detailed claim-by-claim analysis. This involves comparing the competitor's technology to the literal language of the patent claims. Patent Validity Challenges: Competitors may challenge the patent's validity based on new prior art or arguments that the patent should not have been granted. These challenges can occur through USPTO proceedings (e.g., inter partes review) or in district court litigation. Term Expiration: The patent is subject to a 20-year term from its filing date. US Patent 8,071,532 filed on June 18, 2009, will expire on June 18, 2029. This limited remaining term affects long-term investment and commercialization strategies. What Is the Clinical and Commercial Viability of the Claimed Technology? The ultimate value of a patent is tied to the real-world success of the technology it protects. For US Patent 8,071,532, this depends on the development and success of compounds falling within its claims. Factors influencing viability: Clinical Trial Data: Compounds covered by the patent must demonstrate significant efficacy and an acceptable safety profile in human clinical trials. The PI3K/mTOR pathway is complex, and achieving a therapeutic window with manageable toxicity is a major hurdle. Regulatory Approval: Successful navigation of the regulatory approval process by the U.S. Food and Drug Administration (FDA) and other global health authorities is essential for commercialization. Market Competition: The presence of approved PI3K/mTOR inhibitors and other oncology drugs means any new therapeutic based on this patent must offer a clear advantage to gain market share. Development Costs: The significant costs associated with drug discovery, preclinical development, clinical trials, and regulatory submissions represent a substantial financial commitment. Key Takeaways United States Patent 8,071,532 claims methods for treating proliferative disorders using PI3K/mTOR pathway inhibitors. The patent covers a genus of compounds defined by specific structural features and exemplified by numerous specific molecules. The PI3K/mTOR pathway is a validated target in oncology, with several approved drugs already on the market. The patent's enforceability and commercial value are contingent on the novelty and scope of its claims relative to prior art, the clinical and commercial success of any compounds developed under its protection, and its remaining patent term, which expires in June 2029. The competitive landscape is robust, necessitating clear differentiation for any future therapeutic interventions. FAQs What is the primary therapeutic target of the compounds claimed in US Patent 8,071,532? The primary therapeutic target is the PI3K/mTOR signaling pathway, which is implicated in cellular proliferation and is often dysregulated in various cancers. When will US Patent 8,071,532 expire? The patent was filed on June 18, 2009, and will expire on June 18, 2029. Who is the assignee of US Patent 8,071,532? The assignee is The General Hospital Corporation. Are there approved drugs currently on the market that target the PI3K/mTOR pathway? Yes, several PI3K/mTOR inhibitors have received regulatory approval, including Everolimus, Sirolimus, Idelalisib, Copanlisib, and Alpelisib. What are the main challenges associated with developing drugs that target the PI3K/mTOR pathway? Key challenges include achieving a therapeutic window with manageable toxicity due to the pathway's broad role in normal cellular functions, demonstrating significant efficacy improvements over existing treatments, and navigating the competitive market landscape. Citations [1] The General Hospital Corporation. (2011). Methods for treatment of proliferative disorders. U.S. Patent No. 8,071,532. Washington, DC: U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Pharming Americas Bv	RUCONEST	c1 esterase inhibitor (recombinant)	For Injection	125495	July 16, 2014	8,071,532	2026-12-19
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Country	Patent Number	Estimated Expiration
World Intellectual Property Organization (WIPO)	2007073186	⤷ Start Trial
United States of America	9211318	⤷ Start Trial
United States of America	8415288	⤷ Start Trial
United States of America	2013244941	⤷ Start Trial
United States of America	2012088728	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration

Patent: 8,071,532

Summary for Patent: 8,071,532