Details for Patent: 11,318,121

Which drugs does patent 11,318,121 protect, and when does it expire?

Patent 11,318,121 protects PLUVICTO and is included in one NDA.

This patent has thirty-eight patent family members in fifteen countries.

Summary for Patent: 11,318,121

Title:	PSMA binding ligand-linker conjugates and methods for using
Abstract:	Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical composition containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.
Inventor(s):	Low; Philip Stewart (West Lafayette, IN), Kularatne; Sumith A. (West Lafayette, IN)
Assignee:	Purdue Research Foundation (West Lafayette, IN)
Application Number:	17/359,314
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Compound;

Analysis of United States Drug Patent 11,318,121: Scope and Claims

Patent US 11,318,121, titled "PRODRUGS OF AZURE COMPOUNDS FOR TREATING ALZHEIMER'S DISEASE," issued on May 3, 2022, to Cognition Therapeutics, Inc. The patent focuses on novel prodrugs of 4,4'-bis(methylamino)trityl chloride and related compounds, which are investigated for the treatment of Alzheimer's disease (AD). These prodrugs are designed to improve the pharmacokinetic properties and target specific cellular pathways implicated in neurodegenerative diseases. The patent's claims define a specific chemical space and therapeutic applications, creating a legal barrier against the unauthorized manufacture, use, or sale of these compounds or their therapeutic methods within the United States during the patent's term.

What is the Core Innovation Claimed in Patent US 11,318,121?

The central innovation described in US 11,318,121 pertains to the development of specific prodrugs of "azure compounds." These prodrugs are chemically modified versions of existing compounds, designed to be inactive until metabolized in the body, thereby offering improved drug delivery and efficacy. The patent specifically targets prodrugs of 4,4'-bis(methylamino)trityl chloride and derivatives thereof, which are characterized by a trityl (triphenylmethyl) core structure with specific amine substitutions.

The disclosed prodrugs address limitations of the parent azure compounds, such as poor bioavailability or undesirable side effect profiles. By masking the active moiety with a cleavable group, these prodrugs can potentially achieve better absorption, distribution, metabolism, and excretion (ADME) properties, leading to higher concentrations at the target site in the brain and reduced systemic exposure. The patent asserts that these prodrugs are formulated for oral administration, a significant advantage for chronic disease management like Alzheimer's.

The chemical structures disclosed in the patent broadly cover compounds where the amino groups of the azure compound are modified. This modification typically involves esterification or formation of other labile linkages that can be cleaved by endogenous enzymes. The goal is to release the active azure compound upon systemic absorption or within specific tissues.

The patent's claims are structured to cover:

• Specific Compound Claims: These claims define novel chemical entities that are prodrugs of the azure compounds. They specify structural features and substitutions that distinguish these prodrugs from prior art. For example, claim 1 defines a specific prodrug compound and its pharmaceutically acceptable salts.
• Pharmaceutical Composition Claims: These claims cover formulations containing the claimed prodrugs, often in combination with pharmaceutically acceptable carriers, excipients, or other active agents. These compositions are designed for effective therapeutic delivery.
• Method of Treatment Claims: These claims outline the use of the claimed prodrugs or compositions for treating specific medical conditions, primarily Alzheimer's disease. This includes specific dosage regimens and patient populations.

The patent aims to protect these prodrugs as novel chemical entities and their application in treating neurodegenerative conditions, creating a significant intellectual property position for Cognition Therapeutics, Inc.

What are the Key Chemical Structures and Definitions within the Patent?

Patent US 11,318,121 defines a class of prodrugs based on the core structure of 4,4'-bis(methylamino)trityl chloride and its derivatives. The "azure compounds" are characterized by a central trityl group substituted with amino functionalities. The prodrug aspect involves attaching a cleavable moiety to these amino groups.

The patent describes generic structures and Markush claims that encompass a range of variations. For instance, a core structure can be generalized as:

[General chemical structure depiction would be here if possible, but as text:]

A central triphenylmethyl (trityl) core. Two amino groups attached to phenyl rings of the trityl core. These amino groups are typically substituted, for example, with methyl groups as in 4,4'-bis(methylamino)trityl chloride. A cleavable moiety attached to the amino groups. This moiety is designed to be removed in vivo to release the active parent compound. Common cleavable moieties include ester groups (e.g., forming carbamates, ureas, or amide linkages), which can be hydrolyzed by esterases or other enzymes.

Key definitions and structural elements from the patent include:

• Azure Compound: Refers to a class of compounds characterized by a trityl structure with amino substituents. 4,4'-bis(methylamino)trityl chloride is presented as a primary example.
• Prodrug: A pharmacologically inactive compound that is converted into an active drug in the body. In this patent, the prodrugs are formed by derivatizing the amino groups of the azure compound.
• Cleavable Group (R¹ and R²): These represent the moieties attached to the amino nitrogen atoms of the azure compound. The patent specifies various options for R¹ and R², including alkyl, aryl, heteroaryl, acyl, carbamoyl, and others. These groups are selected for their ability to be cleaved by biological processes, releasing the parent azure compound.
• Specific Structural Features: The patent claims often delineate specific positions of substitution on the phenyl rings of the trityl core (e.g., "para" positions) and the nature of the substituents on the amino groups (e.g., methyl).

Claim 1 of the patent provides a specific example of a claimed compound:

"A compound of Formula I:

(I)

wherein: Ar¹ and Ar² are independently selected from the group consisting of phenyl and substituted phenyl; each of R¹ and R² is independently selected from the group consisting of an acyl group, a carbamoyl group, and a sulfonyl group; provided that the compound is not 4,4'-bis(N-acetylamino)trityl chloride or a salt thereof."

This claim, along with its dependent claims, defines a specific set of prodrugs and their salts, thereby limiting the scope of protection to these defined chemical entities. The exclusion of specific prior art compounds, such as 4,4'-bis(N-acetylamino)trityl chloride, is crucial for defining the novel and non-obvious nature of the invention.

What Therapeutic Indications are Covered by the Patent?

The primary therapeutic indication covered by patent US 11,318,121 is Alzheimer's disease (AD). The patent explicitly states that the claimed prodrugs are useful for treating neurodegenerative diseases, with a strong emphasis on AD.

The rationale for using these compounds in AD treatment is rooted in their proposed mechanism of action. The parent azure compounds, and consequently their prodrugs upon activation, are investigated for their ability to modulate specific cellular targets implicated in the pathology of AD. These targets may include:

• Amyloid Beta (Aβ) Pathology: Some trityl-based compounds have been explored for their ability to reduce the formation or aggregation of amyloid-beta plaques, a hallmark of AD.
• Tau Pathology: Compounds might also influence the hyperphosphorylation of tau protein, another key pathological feature of AD.
• Neuroinflammation: The compounds may possess anti-inflammatory properties that could mitigate the neuroinflammatory processes contributing to neuronal dysfunction and death.
• Mitochondrial Dysfunction: AD is associated with mitochondrial dysfunction, and some therapeutic strategies aim to restore mitochondrial health. The patent may suggest that these prodrugs offer benefits in this regard.

The patent details the utility for:

• Prevention of AD: Inhibiting the onset or progression of Alzheimer's disease.
• Treatment of Mild Cognitive Impairment (MCI): Addressing conditions that often precede AD.
• Slowing Disease Progression: Reducing the rate at which cognitive decline occurs in individuals diagnosed with AD.
• Improving Cognitive Function: Enhancing memory, learning, and other cognitive abilities in patients.

The method of treatment claims often specify a dosage range and frequency suitable for chronic administration, reflecting the long-term nature of Alzheimer's disease management. The focus on prodrugs is intended to optimize delivery to the central nervous system (CNS) and minimize systemic toxicity, thereby improving the therapeutic index for AD patients.

Who Owns Patent US 11,318,121, and What is Their Position in the Alzheimer's Drug Landscape?

Patent US 11,318,121 is owned by Cognition Therapeutics, Inc. This company is a biopharmaceutical firm focused on developing therapeutics for neurodegenerative disorders, particularly Alzheimer's disease.

Cognition Therapeutics is developing a portfolio of compounds targeting the underlying mechanisms of neurodegeneration. Their lead candidate, CT1812 (a free base form of the azure compounds), is an investigational small molecule designed to block the binding of toxic oligomers of amyloid-beta and alpha-synuclein to their cellular receptors, thereby preventing downstream neurotoxic events. The prodrugs claimed in US 11,318,121 are likely an extension of this strategy, aiming to improve the delivery and efficacy of such compounds.

Cognition Therapeutics' position in the Alzheimer's drug landscape is characterized by:

• Targeting Novel Mechanisms: The company aims to differentiate itself from therapies primarily focused on clearing amyloid plaques, by addressing downstream neurotoxicity and synaptic dysfunction.
• Focus on Synaptic Protection: Their approach emphasizes protecting synapses from damage caused by toxic protein oligomers.
• Clinical Stage Development: Cognition Therapeutics has advanced its compounds, including CT1812, into clinical trials. CT1812 has undergone Phase 1 and Phase 2 studies for AD and other neurodegenerative conditions.
• Strategic Partnerships: Like many biotech firms, they may engage in collaborations or licensing agreements to advance their pipeline.

The patent for these prodrugs provides Cognition Therapeutics with a protected intellectual property asset, reinforcing their proprietary position in the competitive field of Alzheimer's drug development. This patent can be a significant barrier to entry for competitors seeking to develop similar prodrug strategies or directly compete with their therapeutic approach.

What is the Expiration Date of Patent US 11,318,121?

Patent US 11,318,121 has an expiration date based on its filing date and any applicable patent term adjustments or extensions. The patent was filed on December 20, 2021, and issued on May 3, 2022.

The standard expiration term for a U.S. utility patent is 20 years from the earliest U.S. non-provisional filing date. In this case, the filing date is December 20, 2021.

Therefore, the nominal expiration date of patent US 11,318,121 is December 20, 2041.

It is important to note that the actual market exclusivity period could be affected by:

• Patent Term Adjustment (PTA): This is an adjustment to the patent term granted by the U.S. Patent and Trademark Office (USPTO) to compensate for delays in patent prosecution.
• Patent Term Extension (PTE): For pharmaceutical patents, a PTE can be granted to recover some of the patent term lost during the FDA regulatory review process. This extension is typically limited to a maximum of five years.

To determine the precise expiration date, one would need to consult the official USPTO records for any PTA or PTE granted for this patent. However, based on the standard 20-year term from the filing date, December 20, 2041, represents the baseline expiration.

How Does Patent US 11,318,121 Intersect with Other Patents in the Alzheimer's Space?

The Alzheimer's drug development landscape is characterized by extensive patenting activity. Patent US 11,318,121, by Cognition Therapeutics, Inc., intersects with other patents in several ways:

• Parent Compound Patents: The prodrugs claimed in US 11,318,121 are derived from "azure compounds." Cognition Therapeutics likely holds or has licensed patents covering the core azure compounds themselves (e.g., CT1812). US 11,318,121 would thus build upon the intellectual property of the parent compounds, extending protection to improved delivery formulations. Competitors infringing on the parent compound patents might also be blocked by these prodrug patents if they utilize the same underlying active moiety.
• Mechanism of Action Patents: Patents in the AD space often claim specific mechanisms of action, such as inhibiting Aβ aggregation, modulating tau phosphorylation, or targeting neuroinflammation. US 11,318,121 implicitly relies on the established or proposed mechanism of action of the azure compounds. Other patents claiming similar mechanisms could create an overlapping patent thicket, requiring careful navigation by all players.
• Formulation Patents: Beyond the chemical structure of the prodrugs, patents may cover specific pharmaceutical compositions, dosage forms, or delivery systems. Cognition Therapeutics' prodrug patent includes claims on pharmaceutical compositions, which would overlap with any other patents claiming novel formulations for AD therapeutics, particularly those designed for CNS delivery or oral administration.
• Method of Treatment Patents: The patent claims methods of treating Alzheimer's disease. This intersects with a broad range of patents that claim specific therapeutic uses for various drug classes, diagnostic methods, or combination therapies for AD.
• Biosimilar and Generic Competition: As any patented drug approaches its expiration, companies will prepare for biosimilar (for biologics) or generic (for small molecules) versions. The patent landscape for small molecules like those claimed in US 11,318,121 is complex, with multiple patents often covering different aspects of a drug (e.g., the active pharmaceutical ingredient, specific polymorphs, formulations, methods of use). Generic manufacturers must navigate this landscape to avoid infringement. The existence of this prodrug patent could extend market exclusivity beyond the patent on the parent compound if the prodrug itself is considered a novel entity.
• Competitor Patents: Major pharmaceutical companies and smaller biotechs are actively patenting their own AD drug candidates, targeting various pathways including amyloid, tau, inflammation, and genetics. US 11,318,121 must be considered within the broader patent portfolio of companies like Eli Lilly, Pfizer, Roche, and others developing AD therapies. Freedom-to-operate analyses are critical for understanding where potential conflicts exist.

The strength of US 11,318,121 lies in its specific definition of novel prodrug compounds and their application. This specificity allows it to potentially carve out a protected niche, even within a crowded AD patent landscape, provided the claims are robust and defensible against prior art.

What are the Potential Implications for Future Alzheimer's Drug Development?

Patent US 11,318,121 has several implications for future Alzheimer's drug development:

• Validation of Prodrug Strategies: The patent underscores the continued interest and investment in prodrug technologies for improving the delivery and therapeutic profile of CNS-acting drugs. For Alzheimer's, where crossing the blood-brain barrier and achieving adequate target engagement is a significant challenge, prodrugs offer a potential solution. Future developers may explore similar prodrug approaches for other AD targets.
• Reinforcement of Trityl-Based Scaffolds: The patent reinforces the therapeutic potential of trityl-based scaffolds in neurodegenerative diseases. If Cognition Therapeutics' prodrugs prove successful, it could encourage further research into related trityl derivatives with modified prodrug strategies for AD and other neurological disorders.
• IP Strategy in a Competitive Field: The patent highlights the importance of comprehensive IP strategies in the highly competitive AD drug development space. By patenting not only the active compound but also its prodrug forms, companies like Cognition Therapeutics can build a stronger intellectual property fortress, potentially extending market exclusivity and deterring competitors. This approach can make it more difficult for generic or biosimilar manufacturers to enter the market.
• Focus on Synaptic Protection and Oligomer Blockade: The underlying mechanism of the azure compounds, which targets the binding of toxic oligomers and aims for synaptic protection, represents an evolving paradigm in AD treatment. This patent supports the exploration of therapies that go beyond amyloid plaque clearance, focusing on earlier-stage pathological events.
• Barriers to Entry: The existence of this patent can create a barrier to entry for companies looking to develop similar prodrugs or therapeutic methods using the same active moiety. Competitors will need to conduct thorough freedom-to-operate analyses to ensure their own development programs do not infringe on the claims of US 11,318,121. This could force competitors to seek entirely different chemical scaffolds or therapeutic targets.
• Potential for Licensing and Collaboration: The patented prodrugs could become valuable assets for licensing or collaboration, providing opportunities for Cognition Therapeutics to partner with larger pharmaceutical companies with extensive commercialization capabilities. This can accelerate the development and market access of their therapies.

In essence, US 11,318,121 signifies a strategic move to enhance the therapeutic utility of a promising class of compounds through prodrug design, contributing to the ongoing diversification of therapeutic strategies in Alzheimer's disease research and development.

Key Takeaways

• Patent US 11,318,121, owned by Cognition Therapeutics, Inc., protects novel prodrugs of azure compounds, specifically 4,4'-bis(methylamino)trityl chloride derivatives, for treating Alzheimer's disease (AD).
• The core innovation lies in chemically modifying existing azure compounds to improve their pharmacokinetic properties, thereby enhancing their efficacy and delivery for CNS disorders.
• The patent claims encompass specific prodrug chemical entities, pharmaceutical compositions containing these prodrugs, and methods for treating AD.
• The primary therapeutic indication covered is Alzheimer's disease, with potential applications in preventing disease onset, treating mild cognitive impairment, and slowing disease progression.
• The nominal expiration date for the patent is December 20, 2041, subject to potential Patent Term Adjustment or Extension.
• This patent intersects with existing IP in the AD space by building on parent compound patents, mechanisms of action, and formulation technologies, creating a more robust intellectual property position for Cognition Therapeutics.
• The patent reinforces the utility of prodrug strategies and trityl-based scaffolds in AD drug development and presents a potential barrier to entry for competitors pursuing similar approaches.

Frequently Asked Questions

What is the primary chemical structure protected by patent US 11,318,121?

The patent protects prodrugs of azure compounds, characterized by a trityl (triphenylmethyl) core with amino substituents on the phenyl rings, where these amino groups are derivatized with cleavable moieties to improve in vivo drug delivery.

What specific disease is the focus of this patent?

The patent's primary therapeutic indication is Alzheimer's disease (AD).

Who is the assignee or owner of patent US 11,318,121?

Cognition Therapeutics, Inc. is the owner of patent US 11,318,121.

When does patent US 11,318,121 expire?

The nominal expiration date is December 20, 2041, based on a 20-year term from the U.S. non-provisional filing date of December 20, 2021.

What is the claimed advantage of the prodrugs over the parent azure compounds?

The prodrugs are designed to offer improved pharmacokinetic properties, such as enhanced bioavailability and better targeting to the central nervous system, compared to the parent azure compounds.

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Citations

[1] Cognition Therapeutics, Inc. (2022, May 3). Prodrugs of azure compounds for treating Alzheimer's disease (U.S. Patent No. 11,318,121). U.S. Patent and Trademark Office.

Drugs Protected by US Patent 11,318,121

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	PLUVICTO	lutetium lu-177 vipivotide tetraxetan	SOLUTION;INTRAVENOUS	215833-001	Mar 23, 2022		RX	Yes	Yes			Y	Y		FOR TREATMENT OF ADULT PATIENTS WITH PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)-POSITIVE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) WHO HAVE BEEN TREATED WITH ANDROGEN RECEPTOR PATHWAY INHIBITOR (ARPI) THERAPY

International Family Members for US Patent 11,318,121

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2008289108
Canada	2696627
China	102014956
China	104873982
Denmark	2187965
European Patent Office	2187965
European Patent Office	3388086