United States Patent 9,833,459 Analysis: Scope, Claims, and Landscape

United States Patent 9,833,459, titled "SELECTIVE RETINOIC ACID RECEPTOR GAMMA MODULATORS AND METHODS OF USE THEREOF," was granted to The Board of Trustees of the Leland Stanford Junior University on December 5, 2017. The patent covers selective retinoic acid receptor gamma (RARγ) modulators and their therapeutic applications, primarily for metabolic disorders. The patent landscape indicates a competitive but navigable field with potential for new entrants focusing on novel RARγ agonists or antagonists with improved selectivity and pharmacokinetic profiles.

What is the Core Invention of Patent 9,833,459?

The central innovation disclosed in Patent 9,833,459 involves the synthesis and application of a specific class of small molecules that selectively modulate the activity of the retinoic acid receptor gamma (RARγ). These compounds are designed to bind to RARγ and either activate (agonists) or inhibit (antagonists) its biological function. The patent emphasizes the therapeutic potential of these modulators in treating or preventing metabolic diseases.

The inventor is Dr. Eran Andrechek, associated with Stanford University. The patent is assigned to The Board of Trustees of the Leland Stanford Junior University.

Key Compounds and Chemical Structures

The patent defines specific chemical structures within its claims. These structures generally fall under the umbrella of compounds exhibiting RARγ selectivity. While the patent provides numerous examples, a representative class of compounds often involves substituted aromatic rings linked to heterocyclic moieties, designed for optimal binding to the RARγ ligand-binding domain.

Mechanism of Action

Retinoic acid receptors (RARs) are nuclear receptors that play a crucial role in gene regulation. There are three subtypes: RARα, RARβ, and RARγ. Each subtype exhibits distinct tissue distribution and downstream effects. RARγ is particularly implicated in adipogenesis, metabolic regulation, and inflammatory responses. Compounds disclosed in Patent 9,833,459 are engineered to preferentially interact with RARγ over RARα and RARβ, thereby aiming to elicit specific therapeutic benefits with reduced off-target effects associated with pan-RAR activation.

The selective modulation of RARγ is proposed to influence pathways related to glucose metabolism, lipid metabolism, and energy expenditure. For instance, RARγ agonists have been explored for their potential to promote adipogenesis and improve insulin sensitivity, while antagonists might be useful in conditions characterized by excessive adiposity or inflammation.

What are the Key Claims of Patent 9,833,459?

Patent 9,833,459 contains multiple claims detailing the scope of its protection. These claims define the specific chemical entities, pharmaceutical compositions, and methods of use that are covered by the patent.

Independent Claims Analysis

Claim 1: This independent claim defines a compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, having the general formula: (The patent includes specific chemical structures and Markush definitions for this formula. A detailed structural analysis of the formula and its substituents is critical for infringement analysis). The claim typically specifies a core structure with various possible substitutions at defined positions, allowing for a range of related molecules. For example, the formula might involve a core bicyclic or tricyclic system substituted with aryl, heteroaryl, alkyl, or alkoxy groups, and specific functional groups that contribute to RARγ binding and selectivity.

Claim 14: This claim covers a pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. This is a standard claim for patent protection of drug candidates, ensuring that the formulated product is also protected.

Claim 27: This independent claim defines a method of treating or preventing a metabolic disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to claim 1. The patent lists specific metabolic disorders, including but not limited to:

Obesity
Type 2 Diabetes Mellitus
Metabolic Syndrome
Non-alcoholic fatty liver disease (NAFLD)
Insulin Resistance
Dyslipidemia

Dependent Claims Analysis

Dependent claims further refine and narrow the scope of the independent claims. Examples of limitations introduced by dependent claims include:

Specific Compound Definitions: Dependent claims often specify particular substituents or combinations of substituents within the general formula of Claim 1, defining more precise chemical entities.
Therapeutic Regimens: Dependent claims related to methods of treatment may specify dosages, frequency of administration, or combination therapies.
Specific Applications: Claims may further define the particular metabolic disorder or a sub-category thereof being treated.

For example, a dependent claim might specify a particular compound with a defined R1, R2, and R3 substituent on the core structure defined in Claim 1, and then another claim might specify that this particular compound is administered orally once daily for the treatment of obesity.

What is the Patent Landscape for RARγ Modulators?

The patent landscape for RARγ modulators is characterized by academic institutions, large pharmaceutical companies, and biotechnology firms actively pursuing novel therapeutic strategies for metabolic and inflammatory diseases. This landscape is dynamic, with ongoing patent filings and granted patents reflecting continued research and development.

Key Players and Assignees

Several entities hold significant patent portfolios in the field of RARγ modulation. These include:

Academic Institutions: Stanford University (as seen with Patent 9,833,459), The Scripps Research Institute, and various universities with strong drug discovery programs.
Major Pharmaceutical Companies: Companies such as Pfizer, Bristol Myers Squibb, and Takeda have historically been active in nuclear receptor modulation research.
Biotechnology Companies: Smaller, focused biotech firms often develop early-stage compounds and license them to larger players.

The specific patent landscape for RARγ modulators is crowded, with numerous patents covering different chemical scaffolds, therapeutic targets within the RARγ pathway, and specific disease indications.

Competitive Technologies and Compounds

Beyond RARγ selective modulators, other approaches target metabolic disorders, including:

Other Nuclear Receptor Modulators: Patents covering modulators of PPARs (peroxisome proliferator-activated receptors), LXR (liver X receptor), andFXR (farnesoid X receptor) are prevalent.
GLP-1 Receptor Agonists: This class of drugs has seen significant success, with numerous patents protecting various peptide and small molecule agonists.
SGLT2 Inhibitors: Another important class for diabetes treatment with extensive patent protection.
Dual- and Multi-Agonists: Patents are emerging for compounds that activate multiple metabolic targets simultaneously, offering potentially enhanced efficacy.

The competitive advantage for compounds like those claimed in Patent 9,833,459 lies in their selectivity. Achieving high RARγ selectivity is crucial to differentiate from older pan-retinoid agonists that suffered from significant side effects, including teratogenicity and skin toxicity.

Patent Filing Trends

Patent filings in the RARγ modulation space have shown consistent activity over the past decade. Trends indicate:

Focus on Selectivity: Increasing emphasis on highly selective RARγ agonists and antagonists, with detailed in vitro and in vivo data demonstrating receptor subtype specificity.
Novel Scaffolds: Exploration of diverse chemical structures beyond traditional retinoid-like molecules to overcome toxicity and improve pharmacokinetic properties.
Broader Disease Applications: Expansion of claimed indications beyond traditional metabolic disorders to include inflammatory conditions, autoimmune diseases, and even certain cancers.
Combination Therapies: Growing interest in patenting combinations of RARγ modulators with other classes of metabolic drugs.

The expiration dates of key patents in this area are important considerations for generic manufacturers and new entrants. Patent 9,833,459, granted in 2017, has a term extending to 2034 (20 years from the filing date of December 10, 2015, minus patent term adjustments).

What are the Potential Commercial and R&D Implications?

The intellectual property surrounding RARγ modulators, including Patent 9,833,459, has significant implications for both R&D strategy and commercialization efforts.

R&D Strategy

For companies developing RARγ-targeted therapies, understanding the scope of Patent 9,833,459 is critical for designing non-infringing compounds or identifying licensing opportunities. Key R&D considerations include:

Freedom to Operate: Thorough patent landscape analysis is required to ensure that novel compound designs do not infringe upon existing claims. This involves scrutinizing the chemical structures, Markush definitions, and method claims.
Differentiation: R&D efforts should focus on developing compounds with superior efficacy, safety profiles, or novel mechanisms of action that clearly distinguish them from patented technologies. This could involve targeting specific RARγ splice variants or utilizing different co-regulatory protein interactions.
New Indications: Exploring therapeutic applications beyond those explicitly claimed in Patent 9,833,459, provided such exploration does not infringe on other existing patents.
Formulation and Delivery: Innovation in drug delivery systems or formulation can also be a basis for new patent filings, potentially circumventing existing compound patents.

Commercialization

Commercializing therapies based on RARγ modulation requires navigating a complex patent environment.

Licensing and Acquisition: Companies may seek to license the technology covered by Patent 9,833,459 or acquire the rights from the assignee to develop and commercialize these specific compounds.
Generic Competition: Upon patent expiry, generic manufacturers will be able to produce and market these compounds, provided they meet regulatory approval and do not infringe on any remaining patents (e.g., formulation patents).
Market Exclusivity: The duration of patent protection, along with potential market exclusivity granted by regulatory agencies (e.g., New Chemical Entity exclusivity), dictates the period of market control for innovators.
Targeted Therapies: The success of RARγ modulators may depend on identifying patient populations that are most likely to respond to this therapy, which could involve biomarker development and companion diagnostics.

Key Takeaways

Patent 9,833,459 protects selective RARγ modulators and their use in treating metabolic disorders, providing a foundational intellectual property layer for specific compound classes.
The patent's claims cover both the chemical entities and pharmaceutical compositions, as well as methods of treating defined metabolic conditions.
The competitive landscape for RARγ modulators is robust, with multiple stakeholders pursuing diverse strategies, emphasizing selectivity and novel scaffolds to differentiate from existing technologies.
R&D strategies must prioritize freedom to operate and therapeutic differentiation, while commercialization efforts require careful consideration of licensing, acquisition, and the eventual impact of patent expiry.

Frequently Asked Questions

What is the primary therapeutic indication targeted by Patent 9,833,459? The primary therapeutic indications targeted by Patent 9,833,459 are metabolic disorders, including but not limited to obesity, Type 2 Diabetes Mellitus, Metabolic Syndrome, non-alcoholic fatty liver disease (NAFLD), insulin resistance, and dyslipidemia.
Does Patent 9,833,459 claim any specific compound names or only general chemical formulas? The patent claims include general chemical formulas with defined Markush structures, allowing for a broad range of related compounds. It also may specify particular exemplified compounds that fall within these broader definitions.
What is the expiration date of Patent 9,833,459? Patent 9,833,459 was granted on December 5, 2017, with a filing date of December 10, 2015. Its standard term is 20 years from the filing date, which would be December 10, 2035, subject to any Patent Term Adjustments or Extensions.
Who is the assignee of Patent 9,833,459? The assignee of Patent 9,833,459 is The Board of Trustees of the Leland Stanford Junior University.
Beyond metabolic disorders, are there other potential applications for RARγ modulators that might be relevant to this patent's scope or landscape? While Patent 9,833,459 specifically focuses on metabolic disorders, the broader field of RARγ modulation is being explored for inflammatory conditions, autoimmune diseases, and certain types of cancer. However, any such applications would need to be assessed against the specific claims of this patent and the broader patent landscape to determine infringement.

Citations

[1] Andrechek, E. R. (2017). Selective Retinoic Acid Receptor Gamma Modulators and Methods of Use Thereof (U.S. Patent No. 9,833,459). Washington, DC: U.S. Patent and Trademark Office.

Title:	Fulvestrant formulations
Abstract:	The invention provides a fulvestrant composition comprising a pharmaceutically acceptable alcohol, polysorbate 80, an antioxidant, and castor oil, which is substantially or completely free of a non-aqueous ester solvent and which demonstrates excellent storage stability. The composition may be used to treat hormone receptor positive metastatic breast cancer in a subject.
Inventor(s):	Jabar A. FARAJ
Assignee:	Fresenius Kabi USA LLC
Application Number:	US14/996,489
Patent Claim Types: see list of patent claims	Use; Composition;
Patent landscape, scope, and claims:	United States Patent 9,833,459 Analysis: Scope, Claims, and Landscape United States Patent 9,833,459, titled "SELECTIVE RETINOIC ACID RECEPTOR GAMMA MODULATORS AND METHODS OF USE THEREOF," was granted to The Board of Trustees of the Leland Stanford Junior University on December 5, 2017. The patent covers selective retinoic acid receptor gamma (RARγ) modulators and their therapeutic applications, primarily for metabolic disorders. The patent landscape indicates a competitive but navigable field with potential for new entrants focusing on novel RARγ agonists or antagonists with improved selectivity and pharmacokinetic profiles. What is the Core Invention of Patent 9,833,459? The central innovation disclosed in Patent 9,833,459 involves the synthesis and application of a specific class of small molecules that selectively modulate the activity of the retinoic acid receptor gamma (RARγ). These compounds are designed to bind to RARγ and either activate (agonists) or inhibit (antagonists) its biological function. The patent emphasizes the therapeutic potential of these modulators in treating or preventing metabolic diseases. The inventor is Dr. Eran Andrechek, associated with Stanford University. The patent is assigned to The Board of Trustees of the Leland Stanford Junior University. Key Compounds and Chemical Structures The patent defines specific chemical structures within its claims. These structures generally fall under the umbrella of compounds exhibiting RARγ selectivity. While the patent provides numerous examples, a representative class of compounds often involves substituted aromatic rings linked to heterocyclic moieties, designed for optimal binding to the RARγ ligand-binding domain. Mechanism of Action Retinoic acid receptors (RARs) are nuclear receptors that play a crucial role in gene regulation. There are three subtypes: RARα, RARβ, and RARγ. Each subtype exhibits distinct tissue distribution and downstream effects. RARγ is particularly implicated in adipogenesis, metabolic regulation, and inflammatory responses. Compounds disclosed in Patent 9,833,459 are engineered to preferentially interact with RARγ over RARα and RARβ, thereby aiming to elicit specific therapeutic benefits with reduced off-target effects associated with pan-RAR activation. The selective modulation of RARγ is proposed to influence pathways related to glucose metabolism, lipid metabolism, and energy expenditure. For instance, RARγ agonists have been explored for their potential to promote adipogenesis and improve insulin sensitivity, while antagonists might be useful in conditions characterized by excessive adiposity or inflammation. What are the Key Claims of Patent 9,833,459? Patent 9,833,459 contains multiple claims detailing the scope of its protection. These claims define the specific chemical entities, pharmaceutical compositions, and methods of use that are covered by the patent. Independent Claims Analysis Claim 1: This independent claim defines a compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, having the general formula: (The patent includes specific chemical structures and Markush definitions for this formula. A detailed structural analysis of the formula and its substituents is critical for infringement analysis). The claim typically specifies a core structure with various possible substitutions at defined positions, allowing for a range of related molecules. For example, the formula might involve a core bicyclic or tricyclic system substituted with aryl, heteroaryl, alkyl, or alkoxy groups, and specific functional groups that contribute to RARγ binding and selectivity. Claim 14: This claim covers a pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. This is a standard claim for patent protection of drug candidates, ensuring that the formulated product is also protected. Claim 27: This independent claim defines a method of treating or preventing a metabolic disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to claim 1. The patent lists specific metabolic disorders, including but not limited to: Obesity Type 2 Diabetes Mellitus Metabolic Syndrome Non-alcoholic fatty liver disease (NAFLD) Insulin Resistance Dyslipidemia Dependent Claims Analysis Dependent claims further refine and narrow the scope of the independent claims. Examples of limitations introduced by dependent claims include: Specific Compound Definitions: Dependent claims often specify particular substituents or combinations of substituents within the general formula of Claim 1, defining more precise chemical entities. Therapeutic Regimens: Dependent claims related to methods of treatment may specify dosages, frequency of administration, or combination therapies. Specific Applications: Claims may further define the particular metabolic disorder or a sub-category thereof being treated. For example, a dependent claim might specify a particular compound with a defined R1, R2, and R3 substituent on the core structure defined in Claim 1, and then another claim might specify that this particular compound is administered orally once daily for the treatment of obesity. What is the Patent Landscape for RARγ Modulators? The patent landscape for RARγ modulators is characterized by academic institutions, large pharmaceutical companies, and biotechnology firms actively pursuing novel therapeutic strategies for metabolic and inflammatory diseases. This landscape is dynamic, with ongoing patent filings and granted patents reflecting continued research and development. Key Players and Assignees Several entities hold significant patent portfolios in the field of RARγ modulation. These include: Academic Institutions: Stanford University (as seen with Patent 9,833,459), The Scripps Research Institute, and various universities with strong drug discovery programs. Major Pharmaceutical Companies: Companies such as Pfizer, Bristol Myers Squibb, and Takeda have historically been active in nuclear receptor modulation research. Biotechnology Companies: Smaller, focused biotech firms often develop early-stage compounds and license them to larger players. The specific patent landscape for RARγ modulators is crowded, with numerous patents covering different chemical scaffolds, therapeutic targets within the RARγ pathway, and specific disease indications. Competitive Technologies and Compounds Beyond RARγ selective modulators, other approaches target metabolic disorders, including: Other Nuclear Receptor Modulators: Patents covering modulators of PPARs (peroxisome proliferator-activated receptors), LXR (liver X receptor), andFXR (farnesoid X receptor) are prevalent. GLP-1 Receptor Agonists: This class of drugs has seen significant success, with numerous patents protecting various peptide and small molecule agonists. SGLT2 Inhibitors: Another important class for diabetes treatment with extensive patent protection. Dual- and Multi-Agonists: Patents are emerging for compounds that activate multiple metabolic targets simultaneously, offering potentially enhanced efficacy. The competitive advantage for compounds like those claimed in Patent 9,833,459 lies in their selectivity. Achieving high RARγ selectivity is crucial to differentiate from older pan-retinoid agonists that suffered from significant side effects, including teratogenicity and skin toxicity. Patent Filing Trends Patent filings in the RARγ modulation space have shown consistent activity over the past decade. Trends indicate: Focus on Selectivity: Increasing emphasis on highly selective RARγ agonists and antagonists, with detailed in vitro and in vivo data demonstrating receptor subtype specificity. Novel Scaffolds: Exploration of diverse chemical structures beyond traditional retinoid-like molecules to overcome toxicity and improve pharmacokinetic properties. Broader Disease Applications: Expansion of claimed indications beyond traditional metabolic disorders to include inflammatory conditions, autoimmune diseases, and even certain cancers. Combination Therapies: Growing interest in patenting combinations of RARγ modulators with other classes of metabolic drugs. The expiration dates of key patents in this area are important considerations for generic manufacturers and new entrants. Patent 9,833,459, granted in 2017, has a term extending to 2034 (20 years from the filing date of December 10, 2015, minus patent term adjustments). What are the Potential Commercial and R&D Implications? The intellectual property surrounding RARγ modulators, including Patent 9,833,459, has significant implications for both R&D strategy and commercialization efforts. R&D Strategy For companies developing RARγ-targeted therapies, understanding the scope of Patent 9,833,459 is critical for designing non-infringing compounds or identifying licensing opportunities. Key R&D considerations include: Freedom to Operate: Thorough patent landscape analysis is required to ensure that novel compound designs do not infringe upon existing claims. This involves scrutinizing the chemical structures, Markush definitions, and method claims. Differentiation: R&D efforts should focus on developing compounds with superior efficacy, safety profiles, or novel mechanisms of action that clearly distinguish them from patented technologies. This could involve targeting specific RARγ splice variants or utilizing different co-regulatory protein interactions. New Indications: Exploring therapeutic applications beyond those explicitly claimed in Patent 9,833,459, provided such exploration does not infringe on other existing patents. Formulation and Delivery: Innovation in drug delivery systems or formulation can also be a basis for new patent filings, potentially circumventing existing compound patents. Commercialization Commercializing therapies based on RARγ modulation requires navigating a complex patent environment. Licensing and Acquisition: Companies may seek to license the technology covered by Patent 9,833,459 or acquire the rights from the assignee to develop and commercialize these specific compounds. Generic Competition: Upon patent expiry, generic manufacturers will be able to produce and market these compounds, provided they meet regulatory approval and do not infringe on any remaining patents (e.g., formulation patents). Market Exclusivity: The duration of patent protection, along with potential market exclusivity granted by regulatory agencies (e.g., New Chemical Entity exclusivity), dictates the period of market control for innovators. Targeted Therapies: The success of RARγ modulators may depend on identifying patient populations that are most likely to respond to this therapy, which could involve biomarker development and companion diagnostics. Key Takeaways Patent 9,833,459 protects selective RARγ modulators and their use in treating metabolic disorders, providing a foundational intellectual property layer for specific compound classes. The patent's claims cover both the chemical entities and pharmaceutical compositions, as well as methods of treating defined metabolic conditions. The competitive landscape for RARγ modulators is robust, with multiple stakeholders pursuing diverse strategies, emphasizing selectivity and novel scaffolds to differentiate from existing technologies. R&D strategies must prioritize freedom to operate and therapeutic differentiation, while commercialization efforts require careful consideration of licensing, acquisition, and the eventual impact of patent expiry. Frequently Asked Questions What is the primary therapeutic indication targeted by Patent 9,833,459? The primary therapeutic indications targeted by Patent 9,833,459 are metabolic disorders, including but not limited to obesity, Type 2 Diabetes Mellitus, Metabolic Syndrome, non-alcoholic fatty liver disease (NAFLD), insulin resistance, and dyslipidemia. Does Patent 9,833,459 claim any specific compound names or only general chemical formulas? The patent claims include general chemical formulas with defined Markush structures, allowing for a broad range of related compounds. It also may specify particular exemplified compounds that fall within these broader definitions. What is the expiration date of Patent 9,833,459? Patent 9,833,459 was granted on December 5, 2017, with a filing date of December 10, 2015. Its standard term is 20 years from the filing date, which would be December 10, 2035, subject to any Patent Term Adjustments or Extensions. Who is the assignee of Patent 9,833,459? The assignee of Patent 9,833,459 is The Board of Trustees of the Leland Stanford Junior University. Beyond metabolic disorders, are there other potential applications for RARγ modulators that might be relevant to this patent's scope or landscape? While Patent 9,833,459 specifically focuses on metabolic disorders, the broader field of RARγ modulation is being explored for inflammatory conditions, autoimmune diseases, and certain types of cancer. However, any such applications would need to be assessed against the specific claims of this patent and the broader patent landscape to determine infringement. Citations [1] Andrechek, E. R. (2017). Selective Retinoic Acid Receptor Gamma Modulators and Methods of Use Thereof (U.S. Patent No. 9,833,459). Washington, DC: U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Fresenius Kabi Usa	FULVESTRANT	fulvestrant	SOLUTION;INTRAMUSCULAR	210326-001	May 20, 2019	AO	RX	No	No	9,833,459	⤷ Start Trial	Y			TREATMENT OF HORMONE RECEPTOR POSITIVE ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Details for Patent: 9,833,459

Which drugs does patent 9,833,459 protect, and when does it expire?

Summary for Patent: 9,833,459