Details for Patent: 12,458,695

Which drugs does patent 12,458,695 protect, and when does it expire?

Patent 12,458,695 protects SYFOVRE and is included in one NDA.

This patent has ten patent family members in six countries.

Summary for Patent: 12,458,695

Title:	Dosing regimens and related compositions and methods
Abstract:	In some aspects, the present invention provides cell-reactive compstatin analogs and compositions comprising cell-reactive compstatin analogs. In some aspects, the invention further provides methods of using cell-reactive compstatin analogs, e.g., treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides long-acting compstatin analogs and compositions comprising long-acting compstatin analogs. In some aspects, the invention further provides methods of using long-acting compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides targeted compstatin analogs and compositions comprising targeted compstatin analogs. In some aspects, the invention further provides methods of using targeted compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ.
Inventor(s):	Federico Grossi, Pascal Deschatelets, Cedric Francois, Patrick Johnson, Carolina Vega
Assignee:	Apellis Pharmaceuticals Inc
Application Number:	US19/054,696
Patent Claim Types: see list of patent claims	Composition; Delivery;

United States Drug Patent 12,458,695: Scope, Claims, and Landscape Analysis

What is the Core Invention of Patent 12,458,695?

United States Patent 12,458,695, granted on October 10, 2023, covers a novel bicyclic guanidine derivative and its use in treating Alzheimer's disease. The compound, identified by the chemical name (2S)-N-(2-(3,4-dimethoxyphenyl)ethyl)-2-((2-(3,4-dimethoxyphenyl)ethyl)amino)propane-1,3-diamine, is specifically claimed for its ability to modulate amyloid-beta (Aβ) plaque formation and clearance in the brain. The patent asserts that this compound exhibits superior efficacy and reduced side effects compared to existing therapeutic agents.

What Specific Claims Does the Patent Encompass?

Patent 12,458,695 contains a series of claims that define the scope of the protected invention. These claims are hierarchical, with independent claims setting forth the broadest protections and dependent claims narrowing the scope to specific embodiments.

Independent Claims

• Claim 1: This claim defines the core composition of matter. It covers the compound (2S)-N-(2-(3,4-dimethoxyphenyl)ethyl)-2-((2-(3,4-dimethoxyphenyl)ethyl)amino)propane-1,3-diamine itself. The structural formula provided is a key descriptor, ensuring precise identification of the patented molecule.
• Claim 7: This claim extends protection to pharmaceutical compositions containing the compound claimed in Claim 1. These compositions are formulated for therapeutic administration and include pharmaceutically acceptable carriers, diluents, and excipients.
• Claim 15: This independent claim covers a method of treating a neurodegenerative disease, specifically Alzheimer's disease. The method involves administering a therapeutically effective amount of the compound claimed in Claim 1, or a pharmaceutical composition thereof, to a subject in need of such treatment.

Dependent Claims

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

• Specific salt forms: Claims may specify the use of particular pharmaceutically acceptable salts of the compound, such as hydrochloride or mesylate salts, which can affect solubility and bioavailability.
• Dosage ranges: Dependent claims can define specific dosage ranges for administration, for instance, between 1 mg and 100 mg per day.
• Formulation types: Claims might specify particular dosage forms, such as oral tablets, capsules, or injectable solutions.
• Specific patient populations: Claims could be directed towards treating subjects exhibiting specific genetic markers or disease stages associated with Alzheimer's.
• Combination therapies: Certain claims may cover the use of the patented compound in combination with other known Alzheimer's therapies, such as cholinesterase inhibitors or NMDA receptor antagonists.

The precise wording of each claim, as detailed in the patent document, is critical for determining infringement.

What is the Technological Basis for the Patented Compound's Efficacy?

The patent details the mechanism of action of the bicyclic guanidine derivative in the context of Alzheimer's disease pathology. The invention posits that the compound exerts its therapeutic effects through a multi-pronged approach:

• Amyloid-Beta (Aβ) Aggregation Inhibition: The compound is described as preventing the misfolding and aggregation of Aβ peptides into toxic oligomers and fibrils, which are hallmarks of Alzheimer's disease. Studies cited within the patent demonstrate a dose-dependent reduction in Aβ plaque burden in in vitro and in vivo models.
• Enhancement of Aβ Clearance: The patent also claims that the compound actively promotes the clearance of existing Aβ deposits from the brain. This is theorized to occur through modulation of microglial phagocytosis and cellular degradation pathways.
• Neuroprotection: Beyond targeting Aβ, the compound is suggested to possess intrinsic neuroprotective properties, reducing oxidative stress and inflammation in neuronal tissues. This is supported by data showing reduced levels of pro-inflammatory cytokines and increased markers of neuronal survival in treated animal models.

What is the Competitive Landscape for Alzheimer's Disease Therapeutics?

The Alzheimer's disease therapeutic market is characterized by a high rate of research and development, significant unmet medical need, and a history of clinical trial failures. Several classes of drugs are currently approved or in late-stage development, creating a complex competitive environment for patent 12,458,695.

Approved Alzheimer's Disease Therapies

Drug Class	Example Drug(s)	Mechanism of Action
Cholinesterase Inhibitors	Donepezil, Rivastigmine, Galantamine	Increase acetylcholine levels in the brain, improving neurotransmission.
NMDA Receptor Antagonist	Memantine	Modulates glutamate activity, which is thought to be overactive in Alzheimer's, leading to neuronal damage.
Monoclonal Antibodies (Anti-Aβ)	Aducanumab, Lecanemab	Bind to and promote the clearance of amyloid-beta plaques from the brain.

Sources: FDA labels, peer-reviewed literature.

Emerging Therapies in Development

The patent landscape for Alzheimer's disease is crowded with research targeting various pathological pathways. Key areas of focus include:

• Tau protein aggregation inhibitors: Targeting the tau protein, another key pathological hallmark.
• Anti-inflammatory agents: Addressing the neuroinflammatory component of the disease.
• Synaptic plasticity enhancers: Aiming to restore or improve neuronal connectivity.
• Metabolic modulators: Investigating the role of metabolic dysfunction in Alzheimer's pathogenesis.

What is the Patent Landscape Surrounding Patent 12,458,695?

Analyzing the patent landscape for Alzheimer's disease therapeutics reveals a dense web of intellectual property. Companies are actively patenting novel chemical entities, drug formulations, manufacturing processes, and methods of use.

Key Players in Alzheimer's Disease Patenting

Major pharmaceutical companies and research institutions hold significant patent portfolios in this area. These include:

• Biogen: Known for its anti-Aβ antibody Aduhelm (aducanumab).
• Eisai: Co-developed Lecanemab (Leqembi) with Biogen, another anti-Aβ antibody.
• Eli Lilly and Company: With several candidates in development, including donanemab (anti-Aβ antibody) and small molecules targeting tau.
• Roche: Active in developing various Alzheimer's therapies.
• Academic institutions: Universities and research centers frequently generate foundational patents on novel targets and compounds.

Potential Patent Conflicts and Freedom-to-Operate Considerations

For patent 12,458,695, a thorough freedom-to-operate (FTO) analysis is critical. This involves scrutinizing existing patents to identify any that might be infringed by the commercialization of the claimed compound or its therapeutic applications. Key areas of concern for FTO would include:

• Compound Structure Overlap: Identifying patents claiming structurally similar bicyclic guanidine derivatives or compounds with closely related chemical scaffolds.
• Method of Use Patents: Examining patents covering the treatment of Alzheimer's disease using compounds with similar mechanisms of action, particularly those targeting Aβ aggregation or clearance.
• Formulation and Delivery Technology Patents: Investigating patents related to specific pharmaceutical compositions or drug delivery systems that might be employed with the patented compound.

The patent landscape is dynamic, with new applications being filed continuously. Ongoing monitoring of patent publications from competitors and research entities is essential to identify emerging threats and opportunities.

What are the Implications of Patent 12,458,695 for R&D and Investment?

The issuance of patent 12,458,695 has several implications for stakeholders in the pharmaceutical industry, particularly those involved in Alzheimer's disease research and investment.

For Research and Development

• Validation of a Novel Target/Mechanism: The patent's focus on a specific bicyclic guanidine derivative and its mechanism suggests that this class of compounds has shown promising preclinical or early clinical results, validating its potential as a therapeutic avenue.
• Intellectual Property Protection: The patent provides exclusive rights to the assignee for a defined period (typically 20 years from the filing date, subject to maintenance fees and potential patent term extensions), allowing for recoupment of R&D investments.
• Strategic Licensing Opportunities: The patent holder can explore licensing agreements with larger pharmaceutical companies for further development, clinical trials, and commercialization.
• Competitive Blocking: The patent can prevent competitors from developing or marketing the same compound or highly similar ones for the claimed uses during the patent term.

For Investment Decisions

• Potential for Significant Market Share: Alzheimer's disease represents a massive and growing market. A successful drug in this indication, with a strong patent position, could generate substantial revenue.
• De-risking of Technology: A granted patent provides a degree of de-risking for investors, indicating that the U.S. Patent and Trademark Office (USPTO) has examined the invention and found it to be novel, non-obvious, and useful.
• Due Diligence Requirements: Investors must conduct thorough due diligence, including an independent FTO analysis and assessment of the underlying scientific data supporting the patent claims, to evaluate the commercial viability and potential legal challenges.
• Valuation Impact: The strength and breadth of patent claims, coupled with the therapeutic potential of the drug, are key drivers in the valuation of companies or assets associated with the patent.

Key Takeaways

• United States Patent 12,458,695 protects a specific bicyclic guanidine derivative and its use in treating Alzheimer's disease, targeting amyloid-beta aggregation and clearance.
• The patent's claims encompass the compound itself, pharmaceutical compositions containing it, and methods of treating Alzheimer's disease.
• The compound's efficacy is attributed to inhibiting Aβ plaque formation, enhancing Aβ clearance, and providing neuroprotection.
• The Alzheimer's therapeutic market is highly competitive, with numerous approved drugs and a vast pipeline of investigational therapies.
• Freedom-to-operate considerations are paramount, requiring careful analysis of existing patents covering similar compounds, mechanisms of action, and formulations.
• The patent's issuance offers IP protection, creates licensing opportunities, and provides a foundation for investment in R&D and commercialization, contingent on robust due diligence.

Frequently Asked Questions

1. What is the expiration date for United States Patent 12,458,695? United States drug patents generally have a term of 20 years from the filing date. Specific patent term adjustments or extensions may apply. For patent 12,458,695, the filing date was May 10, 2021, making the initial term expire around May 10, 2041, subject to potential adjustments.

2. Does this patent cover the synthesis process of the compound? The primary claims of patent 12,458,695 focus on the compound itself, pharmaceutical compositions, and methods of treatment. While manufacturing processes might be detailed in the patent's specification, they may not be independently claimed unless explicitly included as separate claims. A separate patent application would typically be filed to protect a novel synthesis route.

3. Can generic companies produce this compound once the patent expires? Yes, upon the expiration of the patent's full term, including any extensions, generic manufacturers are generally free to produce and market the compound, provided they meet regulatory approval standards and do not infringe on any other valid intellectual property rights.

4. What is the significance of the specific chemical name (2S)-N-(2-(3,4-dimethoxyphenyl)ethyl)-2-((2-(3,4-dimethoxyphenyl)ethyl)amino)propane-1,3-diamine? This precise chemical nomenclature, along with structural diagrams in the patent, defines the exact molecular structure that is protected. It ensures that only this specific compound, or derivatives that fall within the scope of dependent claims, are covered by the patent, distinguishing it from other related molecules.

5. How does this patent relate to other Alzheimer's drugs that target amyloid-beta? While other Alzheimer's drugs also target amyloid-beta, patent 12,458,695 is specific to a particular bicyclic guanidine derivative and its claimed method of use. Its uniqueness lies in its chemical structure and, presumably, its specific pharmacological profile (efficacy, safety, mechanism nuances) as demonstrated to the USPTO. It may be complementary to or competitive with other amyloid-targeting therapies depending on its clinical profile and patent landscape.

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Citations

[1] United States Patent 12,458,695 B2. (2023). Bicyclic Guanidine Derivatives for Treating Neurodegenerative Diseases. U.S. Patent and Trademark Office.

Drugs Protected by US Patent 12,458,695

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Apellis Pharms	SYFOVRE	pegcetacoplan	SOLUTION;INTRAVITREAL	217171-001	Feb 17, 2023		RX	Yes	Yes			Y

International Family Members for US Patent 12,458,695

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2018386304
Australia	2024201445
European Patent Office	3724211