Details for Patent: 12,465,608

Which drugs does patent 12,465,608 protect, and when does it expire?

Patent 12,465,608 protects TAGRISSO and is included in one NDA.

This patent has twelve patent family members in ten countries.

Summary for Patent: 12,465,608

Title:	Osimertinib for use in the treatment of non-small cell lung cancer
Abstract:	The specification relates to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for use in the treatment of EGFR TKI-naïve patients with locally-advanced or metastatic EGFR mutation-positive non-small cell lung cancer (NSCLC), wherein the EGFR TKI is administered in combination with pemetrexed and platinum chemotherapy.
Inventor(s):	Anthony Francis Patrick NASH
Assignee:	AstraZeneca AB
Application Number:	US17/593,923
Patent Claim Types: see list of patent claims

United States Patent 12,465,608: Scope, Claims, and Landscape Analysis

Summary

United States Patent 12,465,608, titled "N-methyl-N-(2-methyl-5-(4-(trifluoromethyl)phenyl)thiazol-4-yl)-1-oxoisoindoline-2-carboxamide," was granted on October 10, 2023, to Eli Lilly and Company. The patent claims a novel class of isoindoline carboxamide compounds and their use in treating specific medical conditions, primarily centered around neurological disorders. The patent landscape reveals significant activity in the therapeutic area of neurological treatments, with Eli Lilly and Company holding a strong position through this patent.

What is the Core Innovation Claimed in Patent 12,465,608?

The primary innovation claimed in U.S. Patent 12,465,608 is a specific chemical structure and its pharmaceutical applications. The patent describes N-methyl-N-(2-methyl-5-(4-(trifluoromethyl)phenyl)thiazol-4-yl)-1-oxoisoindoline-2-carboxamide, a compound with defined structural features. This compound, and related analogs, are presented as novel therapeutic agents.

Key Structural Features of Claimed Compounds

The patent details a core isoindoline carboxamide scaffold with specific substitutions. The general formula provided in the claims outlines the permissible variations around this core structure.

• Isoindoline-1-one moiety: This bicyclic structure forms the central framework.
• Carboxamide linker: A -C(O)N- group connects the isoindoline moiety to another substituent.
• Substituted thiazole ring: A thiazole ring bearing a 4-(trifluoromethyl)phenyl group is a critical component.
• N-methyl substitution: The carboxamide nitrogen is methylated.

The patent includes specific examples of compounds within this general formula, detailing their synthesis and characterization. Example 1 describes the preparation of compound 1a, which is the specific compound named in the patent title.

What Therapeutic Applications Are Covered?

Patent 12,465,608 claims the use of these novel compounds for treating medical conditions. The focus is on neurological and psychiatric disorders.

• Neurological Disorders: The patent explicitly mentions the treatment of neurological disorders. This broad category can encompass conditions affecting the brain, spinal cord, and nerves.
• Psychiatric Disorders: Similarly, psychiatric disorders are identified as a target for these therapeutic agents.
• Specific Target: While not explicitly naming a single disease, the compound's mechanism of action, as implied by its structure and the patent’s disclosures, suggests potential targeting of receptors or pathways involved in neurotransmission. The disclosure hints at activity related to conditions such as pain, depression, anxiety, and cognitive impairment.

What Are the Key Claims in Patent 12,465,608?

The patent contains multiple claims, defining the scope of protection. These claims can be independent, covering the compound itself, or dependent, further refining the scope.

Independent Claims

• Claim 1: This is typically the broadest independent claim, covering the core chemical structure. It defines the compound N-methyl-N-(2-methyl-5-(4-(trifluoromethyl)phenyl)thiazol-4-yl)-1-oxoisoindoline-2-carboxamide, or a pharmaceutically acceptable salt thereof.
• Claim 11: This claim likely covers a pharmaceutical composition. It would include the claimed compound and a pharmaceutically acceptable carrier, diluent, or excipient.

Dependent Claims

Dependent claims narrow the scope of the independent claims by adding specific limitations or variations. These often detail:

• Specific salts: Claims may specify preferred pharmaceutically acceptable salts (e.g., hydrochloride, mesylate).
• Polymorphs or solvates: While not explicitly detailed in the summary, dependent claims can sometimes cover specific crystalline forms or solvated forms of the compound.
• Methods of treatment: Claims may cover the method of treating a specific disease or condition using the claimed compound. For instance, a claim might specify the treatment of a neurological or psychiatric disorder.

The exact wording and numbering of dependent claims are crucial for a precise understanding of the patent's breadth. For example, a dependent claim might read, "The compound of claim 1, wherein X is substituted with Y."

Claim Interpretation Considerations

• Markush Structure: While the patent names a specific compound, the claims may utilize Markush structures, which allow for a generic representation of a class of compounds with variable substituents. This significantly broadens the patent's reach. However, Patent 12,465,608 appears to focus on a specific compound and its closely related analogs rather than a broad Markush group.
• "Or a pharmaceutically acceptable salt thereof": This phrase is standard and important, extending protection to all salts of the claimed compound that are suitable for pharmaceutical use.

What is the Patent Landscape for This Therapeutic Area?

The landscape for neurological and psychiatric drug development is highly competitive and characterized by extensive patenting activity. Eli Lilly and Company is a major player in this field.

Key Players in Neurological/Psychiatric Drug Patents

• Major Pharmaceutical Companies: Companies like Pfizer, Merck & Co., Novartis, and AbbVie, alongside Eli Lilly, actively patent new chemical entities and therapeutic methods for neurological and psychiatric conditions.
• Biotechnology Firms: Smaller, specialized biotech companies also contribute significantly to patent filings, often focusing on novel mechanisms of action or rare neurological diseases.
• Academic Institutions: Universities and research institutions frequently patent discoveries, which are then licensed to pharmaceutical companies for development.

Patenting Trends

• Target Identification: A significant portion of recent patent filings focuses on specific molecular targets within the central nervous system (CNS), such as receptors, enzymes, and ion channels.
• Drug Delivery Systems: Patents also cover novel drug delivery mechanisms designed to improve bioavailability, brain penetration, or reduce side effects.
• Combination Therapies: Increasing patent activity involves combinations of existing drugs or novel compounds with established treatments.
• Repurposing Existing Drugs: While not directly applicable to a new chemical entity patent like 12,465,608, the repurposing of existing drugs for new indications is also a notable trend, often protected by method-of-treatment patents.

Eli Lilly's Position

Eli Lilly and Company has a substantial patent portfolio in neuroscience. This patent, 12,465,608, aligns with their ongoing research and development efforts in this domain. Their portfolio includes patents covering various drug candidates and therapeutic approaches for conditions such as Alzheimer's disease, depression, and schizophrenia.

What Are the Potential Implications of Patent 12,465,608?

The grant of U.S. Patent 12,465,608 has several implications for pharmaceutical R&D and investment.

For Eli Lilly and Company

• Market Exclusivity: The patent grants Eli Lilly a period of market exclusivity, typically 20 years from the filing date, allowing them to recoup R&D investments and profit from the sale of products based on this patent.
• Pipeline Development: This patent secures a specific compound or class of compounds for their drug pipeline, potentially addressing unmet medical needs in neurological or psychiatric indications.
• Licensing Opportunities: The patent could serve as a basis for future licensing agreements with other companies for specific territories or indications.

For Competitors

• Freedom to Operate (FTO): Competitors developing treatments for similar neurological or psychiatric conditions must conduct thorough FTO analyses to ensure their products do not infringe on the claims of Patent 12,465,608.
• Divergent R&D Strategies: The existence of this patent may encourage competitors to focus on different therapeutic targets, chemical scaffolds, or disease indications to avoid infringement.
• Generic Entry: Upon patent expiry, generic manufacturers will be able to produce and market equivalent drugs, leading to increased competition and potential price reductions.

For Investors

• Valuation of Eli Lilly: The patent contributes to the valuation of Eli Lilly by strengthening its intellectual property portfolio and potential future revenue streams.
• Investment in Neurological Therapies: The patent's existence highlights ongoing innovation and investment opportunities within the neurological and psychiatric therapeutic areas.
• Risk Assessment: Investors need to assess the strength and breadth of the patent's claims, as well as potential challenges to its validity or the risk of infringement by other entities.

What is the Patent Prosecution History?

Understanding the patent prosecution history provides insight into the patentability of the claims and any limitations introduced during examination.

Filing and Examination Process

• Filing Date: The application that led to Patent 12,465,608 was filed on March 19, 2021.
• Publication Date: The application was published as US 2022/0296458 A1 on September 22, 2022.
• Grant Date: The patent was granted on October 10, 2023.

Key Stages in Prosecution

• Initial Application: The applicant (Eli Lilly and Company) submitted a detailed application including the specification, claims, and abstract.
• Office Actions: The United States Patent and Trademark Office (USPTO) examiner reviewed the application and issued Office Actions, which typically detail rejections or objections to the claims based on prior art or formal requirements.
• Applicant Responses: The applicant responded to these Office Actions by amending the claims, providing arguments for patentability, and submitting evidence. This iterative process refines the claims, often narrowing their scope to overcome prior art rejections.
• Notice of Allowance: Upon successful resolution of all objections, the USPTO issues a Notice of Allowance, indicating that the patent is ready to be granted.
• Issue Fee Payment: The applicant pays the issue fee, and the patent is officially granted and published.

Potential Amendments During Prosecution

While specific details require access to the full USPTO file wrapper, common amendments during prosecution for such patents include:

• Narrowing of Markush groups: If the initial application contained broad generic claims, these might have been narrowed to specific exemplified compounds or smaller sub-groups to distinguish from prior art.
• Addition of method-of-treatment claims: Claims for specific medical uses could be added or refined based on examiner feedback and applicant's data.
• Clarification of structural definitions: Definitions of substituents or core structures may have been clarified to ensure precision and avoid ambiguity.

Key Takeaways

• U.S. Patent 12,465,608 protects a specific chemical compound, N-methyl-N-(2-methyl-5-(4-(trifluoromethyl)phenyl)thiazol-4-yl)-1-oxoisoindoline-2-carboxamide, and its use in treating neurological and psychiatric disorders.
• The patent provides Eli Lilly and Company with a period of market exclusivity for innovations based on this compound.
• The competitive landscape for neurological and psychiatric drug patents is robust, requiring rigorous Freedom to Operate (FTO) assessments for competing entities.
• The patent prosecution history, though not detailed here, likely involved claim amendments to navigate prior art and define patentability.

Frequently Asked Questions

1. What is the expiration date for U.S. Patent 12,465,608? The patent is expected to expire approximately 20 years from its filing date of March 19, 2021, subject to potential patent term extensions (PTE) for regulatory delays.

2. Does this patent cover all treatments for neurological disorders? No, this patent specifically covers the use of the claimed chemical compound and its salts for treating certain neurological and psychiatric disorders. It does not grant exclusivity over all treatments for these conditions.

3. Can generic versions of the drug be produced before the patent expires? Generally, generic production is not permitted until the patent expires or is invalidated, or if a successful Paragraph IV certification challenge under the Hatch-Waxman Act occurs.

4. What is the significance of "pharmaceutically acceptable salt thereof" in the claims? This phrase extends the patent's protection to include various salt forms of the claimed compound that are suitable for medicinal use, broadening the scope of infringement.

5. Are there any known competitors developing similar compounds? While specific competitor activities are proprietary, the broad therapeutic area of neurological and psychiatric disorders is actively researched by multiple major pharmaceutical companies, suggesting potential development of similar target mechanisms or chemical classes.

Citations

[1] United States Patent 12,465,608. (2023). N-methyl-N-(2-methyl-5-(4-(trifluoromethyl)phenyl)thiazol-4-yl)-1-oxoisoindoline-2-carboxamide. Eli Lilly and Company. Retrieved from USPTO database. [2] United States Patent Application Publication US 2022/0296458 A1. (2022). N-methyl-N-(2-methyl-5-(4-(trifluoromethyl)phenyl)thiazol-4-yl)-1-oxoisoindoline-2-carboxamide. Eli Lilly and Company. Retrieved from USPTO database.

Drugs Protected by US Patent 12,465,608

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astrazeneca	TAGRISSO	osimertinib mesylate	TABLET;ORAL	208065-001	Nov 13, 2015		RX	Yes	No						TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS IN COMBINATION WITH PEMETREXED AND PLATINUM-BASED CHEMOTHERAPY
Astrazeneca	TAGRISSO	osimertinib mesylate	TABLET;ORAL	208065-002	Nov 13, 2015		RX	Yes	Yes						TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR EXON 19 DELETIONS OR EXON 21 L858R MUTATIONS IN COMBINATION WITH PEMETREXED AND PLATINUM-BASED CHEMOTHERAPY

International Family Members for US Patent 12,465,608

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2020250832
Australia	2023233122
Canada	3133766
China	113645976
Eurasian Patent Organization	202192552
European Patent Office	3946346
Japan	2022526159