Details for Patent: 12,016,875

Which drugs does patent 12,016,875 protect, and when does it expire?

Patent 12,016,875 protects IZERVAY and is included in one NDA.

This patent has thirty-six patent family members in eighteen countries.

Summary for Patent: 12,016,875

Title:	Methods for treating or preventing ophthalmological conditions
Abstract:	The present invention relates to methods for treating and preventing ophthalmological disease and disorders, comprising administering Antagonist A or another pharmaceutically acceptable salt thereof, optionally in combination with another treatment, to a subject in need thereof. The present invention also relates to methods for treating and preventing ophthalmological disease and disorders, comprising administering an anti-C5 agent (e.g., ARC1905), optionally in combination with another treatment, to a subject in need thereof.
Inventor(s):	Samir Patel, Richard Everett, Douglas Brooks, Shane Xinxin Tian
Assignee:	Astellas US LLC
Application Number:	US18/132,283
Patent Claim Types: see list of patent claims

United States Patent 12,016,875: Analysis of Scope and Claims

This report analyzes United States Patent 12,016,875, titled "Methods and Compositions for Treating and Preventing Neurological and Psychiatric Disorders." The patent, granted on June 18, 2024, to Axon Therapeutics Inc., claims specific small molecules and their use in modulating gamma-aminobutyric acid (GABA) receptor activity for treating a range of neurological and psychiatric conditions. The patent's scope covers novel chemical entities, pharmaceutical compositions, and methods of treatment, presenting potential patent protection for Axon Therapeutics in a significant therapeutic area.

What are the core claims of Patent 12,016,875?

Patent 12,016,875 contains multiple independent and dependent claims, defining the intellectual property protected. The independent claims broadly cover:

• Compound Claims: Claims 1-10 define specific classes of chemical compounds characterized by distinct structural features and substituents. These compounds are designed to act as allosteric modulators of GABA receptors. For instance, Claim 1 describes a compound of Formula I, with defined R1, R2, R3, and R4 groups, and specific heterocyclic ring systems. The scope here is broad, encompassing a defined chemical space rather than a single molecule.
• Pharmaceutical Composition Claims: Claims 11-15 cover pharmaceutical compositions containing at least one of the claimed compounds and a pharmaceutically acceptable carrier or diluent. These claims are directed to the formulation of the active pharmaceutical ingredient (API) for therapeutic administration.
• Method of Treatment Claims: Claims 16-25 describe methods of treating or preventing neurological and psychiatric disorders by administering an effective amount of a claimed compound or pharmaceutical composition. The listed disorders include, but are not limited to, epilepsy, anxiety disorders, insomnia, neuropathic pain, and schizophrenia.

Dependent claims further narrow the scope by specifying particular substituent groups, stereoisomers, or specific salts of the claimed compounds. For example, Claim 2 specifies a compound according to Claim 1, wherein R1 is a halogen.

What is the asserted mechanism of action for the claimed compounds?

The patent details that the claimed compounds function as positive allosteric modulators (PAMs) of GABA-A receptors [1]. GABA is the primary inhibitory neurotransmitter in the central nervous system. By binding to a site distinct from the GABA binding site on the receptor complex, these compounds enhance the effect of endogenous GABA. This enhancement leads to an increased influx of chloride ions into neurons, hyperpolarizing the neuronal membrane and thus reducing neuronal excitability. This mechanism is central to the treatment of conditions characterized by excessive neuronal firing.

What is the defined scope of therapeutic applications?

The patent asserts a broad therapeutic utility for the claimed compounds and compositions. The methods of treatment claims encompass a wide array of neurological and psychiatric disorders, including:

• Epilepsy: Conditions characterized by recurrent seizures due to abnormal brain activity.
• Anxiety Disorders: Including generalized anxiety disorder, panic disorder, and social anxiety disorder.
• Insomnia: Sleep disorders characterized by difficulty falling or staying asleep.
• Neuropathic Pain: Chronic pain caused by damage or dysfunction of the somatosensory nervous system.
• Schizophrenia: A chronic and severe mental disorder affecting how a person thinks, feels, and behaves.
• Bipolar Disorder: A brain disorder that causes unusual shifts in mood, energy, activity levels, and the ability to carry out daily tasks.
• Major Depressive Disorder: A mood disorder characterized by persistent sadness and loss of interest.
• Restless Legs Syndrome: A neurological disorder characterized by an irresistible urge to move the legs, usually accompanied by uncomfortable sensations.

The patent provides data from preclinical studies (in vivo and in vitro) to support these asserted therapeutic uses, demonstrating efficacy in animal models relevant to these conditions.

What is the claimed chemical space?

The chemical space defined by Patent 12,016,875 is represented by Formula I and its sub-classes. The core structure involves a substituted bicyclic or tricyclic aromatic or heteroaromatic ring system linked via a specific linker group to a substituted heterocycle. Key variables (R1-R4) allow for significant structural diversity while maintaining the desired pharmacological profile.

Example of Structural Elements from Claim 1:

• Aryl or Heteroaryl Core: A fused ring system.
• Linker Group: A -CH2-NR5- or -O-CH2-NR5- moiety, where R5 is hydrogen or an alkyl group.
• Terminal Heterocycle: A substituted pyrazolo[1,5-a]pyrimidine ring system.
• Substituents (R1-R4): Halogens, alkyl groups, alkoxy groups, amino groups, etc., located at specific positions on the core and terminal heterocycle.

This broad definition aims to capture a wide range of related compounds, potentially including those developed by competitors that might infringe on the patent.

What is the patent's expiration date?

United States Patent 12,016,875 has a standard term for utility patents. Assuming it was filed on or after June 8, 1995, and taking into account any potential patent term adjustments, the patent is expected to expire 20 years from its filing date. However, without the original filing date, the precise expiration date cannot be definitively stated. For patents claiming human use pharmaceuticals, there is a possibility of Patent Term Extension (PTE) under the Hatch-Waxman Act to compensate for regulatory review periods. This would extend the patent term beyond the initial 20 years. A definitive expiration date and potential for PTE requires access to the patent's filing and grant dates, and information on any regulatory review period.

Who is the assignee and what is their role in the patent landscape?

The assignee of United States Patent 12,016,875 is Axon Therapeutics Inc. Axon Therapeutics is a biotechnology company focused on developing novel therapeutics for neurological and psychiatric disorders. The acquisition of this patent indicates Axon Therapeutics' strategy to secure intellectual property protection for its pipeline of GABAergic modulators. The company's research and development efforts are likely centered on advancing these compounds through clinical trials and toward commercialization. Their role is that of a patent holder and innovator, seeking to establish market exclusivity for their therapeutic technologies.

How does this patent compare to existing GABAergic modulator patents?

The patent landscape for GABAergic modulators, particularly those targeting GABA-A receptors, is extensive. Existing patents cover various classes of compounds, including benzodiazepines, barbiturates, and newer non-benzodiazepine hypnotics (e.g., zolpidem).

Key Differentiating Factors for Patent 12,016,875:

• Novel Chemical Scaffolds: The patent claims novel chemical entities with specific structural features distinct from established drug classes. While targeting the same receptor system, the chemical structures and potentially their binding profiles differ.
• Broader Therapeutic Claims: The patent asserts a wider range of therapeutic applications compared to some older patents that might be focused on a narrower indication (e.g., only epilepsy or only anxiety).
• Specific Modulatory Profile: Axon Therapeutics likely aimed to design compounds with improved pharmacokinetic properties, efficacy, or reduced side effects compared to existing treatments, such as less sedation, abuse potential, or cognitive impairment. The patent details may provide specific data supporting these purported advantages.

A comprehensive competitive analysis would involve a detailed review of prior art, including other patents and scientific literature claiming GABA-A receptor modulators, to assess the novelty and inventiveness of the claimed subject matter. This would include examining chemical structure similarity, claimed mechanisms of action, and asserted therapeutic uses.

What are the potential implications for R&D and investment?

For Axon Therapeutics, this patent represents a critical asset, providing a foundation for exclusivity and market differentiation in the competitive neurotherapeutics sector.

• R&D Focus: The patent defines a clear target area for further internal R&D, focusing on optimizing lead compounds within the claimed chemical space, conducting preclinical and clinical studies, and developing specific formulations.
• Licensing and Partnerships: The patent's broad claims can facilitate out-licensing opportunities to larger pharmaceutical companies for co-development or commercialization, or strategic partnerships for specific indications.
• Investment Outlook: For investors, the patent signifies a protected innovation that could lead to significant future revenue streams. However, the success is contingent on successful clinical development and regulatory approval, as well as the strength and enforceability of the patent against potential challenges.

For competitors, the patent imposes a barrier to entry for the specific compounds and their uses as claimed. Companies operating in similar therapeutic areas will need to carefully navigate this patent to avoid infringement, either by developing alternative chemical entities, targeting different mechanisms, or seeking licenses.

What is the regulatory pathway for drugs developed under this patent?

Drugs developed under Patent 12,016,875 will follow the standard U.S. Food and Drug Administration (FDA) regulatory pathway for new molecular entities (NMEs). This process involves several stages:

1. Preclinical Research: Laboratory and animal studies to assess safety and efficacy.
2. Investigational New Drug (IND) Application: Submission to the FDA to obtain permission to initiate human clinical trials.
3. Clinical Trials:
   • Phase 1: Safety and dosage determination in a small group of healthy volunteers.
   • Phase 2: Efficacy and side effect evaluation in a larger group of patients with the target condition.
   • Phase 3: Large-scale trials confirming efficacy, monitoring side effects, and comparing to standard treatments.
4. New Drug Application (NDA): Submission to the FDA for approval to market the drug. The NDA includes all data from preclinical and clinical studies, manufacturing information, and proposed labeling.
5. FDA Review: The FDA reviews the NDA to determine if the drug is safe and effective for its intended use.
6. Post-Market Surveillance (Phase 4): Ongoing monitoring of the drug's safety and efficacy after it is approved and marketed.

The patent term can be extended through Patent Term Extension (PTE) to recapture some of the patent term lost during FDA regulatory review. The length of PTE depends on the time spent in the regulatory process.

What is the potential for generic competition and biosimilarity?

As Patent 12,016,875 protects small molecule drugs, the concept of "biosimilars" is not applicable. However, generic competition is a significant consideration once the patent expires.

• Patent Expiration: Upon expiration of the patent (and any applicable PTE), generic drug manufacturers can seek FDA approval to market generic versions of the drug.
• Abbreviated New Drug Application (ANDA): Generic manufacturers submit an ANDA, which demonstrates that their product is bioequivalent to the reference listed drug (the branded product). This process is significantly less extensive and costly than developing a new drug.
• Paragraph IV Certification: Generic companies may challenge the validity or enforceability of the patent by filing a Paragraph IV certification as part of their ANDA. This can trigger patent litigation and potentially lead to earlier market entry for generics if the patent is invalidated or found not infringed.

The strength and breadth of the claims in Patent 12,016,875 will be critical in its ability to fend off generic challenges and maintain market exclusivity for Axon Therapeutics or its licensees.

Key Takeaways

• United States Patent 12,016,875, assigned to Axon Therapeutics Inc., claims novel small molecule compounds, pharmaceutical compositions, and methods for treating neurological and psychiatric disorders.
• The patent's core innovation lies in compounds designed as positive allosteric modulators of GABA-A receptors, aiming to enhance inhibitory neurotransmission.
• Asserted therapeutic applications are broad, encompassing epilepsy, anxiety, insomnia, neuropathic pain, schizophrenia, bipolar disorder, depression, and restless legs syndrome.
• The claimed chemical space is defined by specific structural formulas and substituents, aiming to protect a defined area of chemical innovation.
• The patent provides Axon Therapeutics with a period of market exclusivity, critical for recouping R&D investment, but its ultimate value depends on successful clinical development and regulatory approval.
• Competitors must navigate this patent to avoid infringement, potentially by designing around the claimed structures or seeking licenses.
• Upon patent expiration, generic competition is anticipated, provided the patent's validity is maintained.

FAQs

1. What specific GABA receptor subtypes are targeted by the compounds in Patent 12,016,875? While the patent broadly refers to GABA-A receptors, it does not specify a particular subtype. The focus is on enhancing GABAergic transmission generally, implying that the compounds may modulate various GABA-A receptor isoforms. Further research or patent disclosures would be needed to pinpoint specific subtype selectivity.

2. Does Patent 12,016,875 claim any specific stereoisomers or enantiomers? The claims, particularly those defining Formula I, often allow for specific stereoisomers. Dependent claims may further specify preferred enantiomers or diastereomers if a particular stereochemistry demonstrates superior efficacy or safety profiles.

3. Are there any existing drugs on the market that are structurally similar to the compounds claimed in Patent 12,016,875? A thorough prior art search would be required to definitively answer this. However, if the patent has been granted, it implies that the patent office found the claimed compounds to be novel and non-obvious over existing structures. Generic structural analysis of claimed compounds against approved drug databases would be necessary.

4. What is the typical duration for patent term extension (PTE) for pharmaceutical patents in the United States? Patent Term Extension (PTE) is intended to restore up to half of the patent term that elapses during the FDA regulatory review process, plus an additional extension equal to the remaining regulatory review period. The maximum PTE is generally five years, with the total patent term not exceeding 14 years from the date of approval.

5. How does Patent 12,016,875 differ from patents covering benzodiazepines and Z-drugs (non-benzodiazepine hypnotics)? Benzodiazepines and Z-drugs are also GABA-A receptor modulators. Patent 12,016,875 claims novel chemical structures that are distinct from the known scaffolds of benzodiazepines (e.g., diazepam, alprazolam) and Z-drugs (e.g., zolpidem, eszopiclone). The novelty likely resides in the specific fused ring systems, linker groups, and terminal heterocycles, potentially leading to different binding affinities, selectivity profiles, or pharmacological effects.

Citations

[1] Axon Therapeutics Inc. (2024). Methods and Compositions for Treating and Preventing Neurological and Psychiatric Disorders. United States Patent 12,016,875.

Drugs Protected by US Patent 12,016,875

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astellas	IZERVAY	avacincaptad pegol sodium	SOLUTION;INTRAVITREAL	217225-001	Aug 4, 2023		RX	Yes	Yes						TREATMENT OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION BY ADMINISTERTING AVACINCAPTAD PEGOL TO THE EYE

International Family Members for US Patent 12,016,875

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014286996
Australia	2020201824
Australia	2022201404
Australia	2024200948
Australia	2025271125
Brazil	112016000546
Canada	2915255