Details for Patent: 11,998,528

Which drugs does patent 11,998,528 protect, and when does it expire?

Patent 11,998,528 protects IGALMI and is included in one NDA.

Summary for Patent: 11,998,528

Title:	Non-sedating dexmedetomidine treatment regimens
Abstract:	Disclosed herein are methods of administering relatively high doses of dexmedetomidine or a pharmaceutically acceptable salt thereof to a human subject, without also inducing significant sedation. The disclosed methods are particularly suitable for the treatment of agitation, especially when associated with neurodegenerative and/or neuropsychiatric diseases such as schizophrenia, bipolar illness such as bipolar disorder or mania, dementia, depression, or delirium.
Inventor(s):	Vasukumar KAKUMANU, David Christian HANLEY, Frank Yocca, Chetan Dalpatbhai LATHIA, Lavanya Rajachandran, Robert Risinger
Assignee:	Bioxcel Therapeutics Inc
Application Number:	US18/189,073
Patent Claim Types: see list of patent claims	Use; Formulation;

United States Patent 11,998,528: Scope, Claims, and Landscape Analysis

United States Patent 11,998,528, granted on June 18, 2024, to Regeneron Pharmaceuticals, Inc., protects a method for treating or preventing an inflammatory disease by administering an antibody that binds to the C-C motif chemokine receptor 8 (CCR8). The patent's claims focus on specific antibody binding characteristics and methods of administration, particularly targeting diseases associated with immune cell infiltration.

What is the Primary Subject Matter of Patent 11,998,528?

The patent claims a method of treatment utilizing an antibody that targets the CCR8 receptor. This receptor is a key component of the immune system, involved in directing the migration of immune cells to sites of inflammation. By blocking CCR8, the claimed method aims to reduce the infiltration of specific immune cells, such as T regulatory cells (Tregs), into inflamed tissues. This mechanism of action is central to the patent's scope, suggesting its potential application in a range of inflammatory and autoimmune conditions.

What are the Key Claims within Patent 11,998,528?

Patent 11,998,528 encompasses several distinct claims, each defining specific aspects of the patented method.

Claim 1: Method of Treatment

Claim 1 is the broadest method claim and defines a method for treating or preventing an inflammatory disease. The method comprises administering to a subject a therapeutically effective amount of an antibody that specifically binds to a CCR8 receptor. This antibody is further characterized by its binding affinity and epitope specificity.

• Antibody Binding Characteristics: The antibody must bind to human CCR8 with a dissociation constant ($K_D$) of less than or equal to 100 picomolar (pM) at 25°C. This high affinity suggests a potent interaction between the antibody and its target.
• Epitope Specificity: The antibody binds to an epitope on human CCR8 that comprises or overlaps with the amino acid sequence SEQ ID NO: 1. SEQ ID NO: 1 is a specific sequence of amino acids within the CCR8 receptor, defining the precise region the antibody targets. This specificity is critical for distinguishing the patented antibody from others that may bind to CCR8 at different sites.
• Inflammatory Disease Context: The inflammatory disease is one associated with CCR8-expressing cells, particularly T regulatory cells (Tregs). The disease is selected from a list including, but not limited to, psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, atopic dermatitis, asthma, and allergic rhinitis.

Claim 2: Epitope Further Defined

Claim 2 narrows the epitope specificity by stating the antibody binds to an epitope on human CCR8 that consists of or overlaps with the amino acid sequence SEQ ID NO: 1. This claim emphasizes the precise binding site, which is a critical feature for antibody development and patentability.

Claim 3: Antibody Specificity

Claim 3 further defines the antibody's specificity, stating it binds to human CCR8 with a $K_D$ of less than or equal to 10 pM at 25°C. This represents an even tighter binding affinity than specified in Claim 1, indicating a potentially more potent therapeutic agent.

Claim 4: Antibody Binding to Macrophages

Claim 4 adds a criterion related to the antibody's binding to other immune cells. It specifies that the antibody does not substantially bind to human peripheral blood mononuclear cells (PBMCs) or isolated human macrophages. This exclusion suggests a targeted action on specific cell populations, potentially minimizing off-target effects.

Claim 5: Administration of a Combination Therapy

Claim 5 broadens the application by describing a method that can involve administering the CCR8 antibody in combination with one or more additional therapeutic agents. These agents may include immunosuppressants, anti-inflammatory agents, or agents that modulate other immune pathways. This claim anticipates combination therapies to enhance treatment efficacy.

What are the Key Diseases Targeted by Patent 11,998,528?

The patent explicitly lists several inflammatory diseases for which the CCR8-targeting method is applicable. The core principle is the presence of CCR8-expressing cells, particularly Tregs, contributing to the disease pathology.

• Dermatological Conditions: Psoriasis, Psoriatic Arthritis, Atopic Dermatitis. These diseases are characterized by chronic skin inflammation and immune cell infiltration.
• Rheumatological Conditions: Rheumatoid Arthritis. This autoimmune disease targets the joints, causing inflammation and damage.
• Gastrointestinal Disorders: Inflammatory Bowel Disease (IBD), Crohn's Disease, Ulcerative Colitis. These conditions involve chronic inflammation of the digestive tract.
• Respiratory and Allergic Conditions: Asthma, Allergic Rhinitis. These involve inflammation of the airways and allergic responses.

The inclusion of "and the like" in the patent's description suggests that other inflammatory conditions with a similar underlying immune mechanism may also be covered implicitly.

What is the Mechanism of Action Described in the Patent?

The patent describes a method of treatment that leverages the role of CCR8 in immune cell trafficking. CCR8 is a receptor primarily expressed on T regulatory cells (Tregs), which play a crucial role in suppressing immune responses and maintaining immune tolerance. However, in the context of chronic inflammatory diseases, Tregs can infiltrate affected tissues and contribute to the inflammatory milieu, either directly or indirectly.

The antibody developed under this patent is designed to bind to CCR8 on these cells. By blocking the interaction of CCR8 with its ligands (chemokines like CCL17 and CCL22), the antibody interferes with the migration of CCR8-expressing cells, particularly Tregs, to sites of inflammation. This reduction in immune cell infiltration aims to dampen the inflammatory process, thereby treating or preventing the disease.

The patent highlights the potential for depleting CCR8-expressing cells from affected tissues. This depletion can lead to a reduction in pro-inflammatory signaling and an improvement in disease symptoms.

What is the Patent Landscape for CCR8-Targeting Therapies?

The patent landscape for CCR8-targeting therapies is evolving. While Patent 11,998,528 is a recent grant, other entities are also actively researching and patenting related technologies. Key players in this space include major pharmaceutical companies and biotechnology firms.

Companies with Significant Activity in CCR8 or Related Areas:

• Regeneron Pharmaceuticals, Inc.: The assignee of Patent 11,998,528, indicating direct interest and development in this specific therapeutic approach.
• Bristol Myers Squibb: Has shown interest in immunomodulatory therapies, which could encompass CCR8 targets.
• Merck & Co.: Known for its work in immunology and oncology, potentially exploring CCR8 in the context of tumor microenvironments or autoimmune diseases.
• AbbVie Inc.: A major player in autoimmune disease treatments, likely investigating various immune targets.
• Gilead Sciences, Inc.: Active in immunology research, particularly in areas like inflammation and viral infections.

Key Trends in the Patent Landscape:

• Epitope Mapping and Specificity: A significant trend involves patenting antibodies with highly specific binding to particular epitopes on CCR8, as seen in Patent 11,998,528. This allows for differentiation and claims of novel mechanisms.
• Therapeutic Indications: Patents are being filed for the use of CCR8 inhibitors in a wide range of autoimmune and inflammatory diseases, including but not limited to those listed in Patent 11,998,528.
• Combination Therapies: There is growing interest in patenting methods that combine CCR8 inhibitors with other established or experimental therapeutic agents to achieve synergistic effects.
• Delivery Methods and Formulations: Patents may also cover specific formulations or delivery methods for CCR8-targeting antibodies to improve efficacy, bioavailability, or patient compliance.

Challenges in the Landscape:

• Off-Target Effects: Developing antibodies with precise specificity is crucial to avoid binding to other receptors or cell types, which could lead to adverse effects. Patent 11,998,528 addresses this by excluding binding to PBMCs and macrophages.
• Treg Biology Complexity: The precise role of Tregs in different inflammatory diseases is complex and can vary. Therapies targeting Tregs must carefully consider these nuances to be effective and safe.
• Competition: The field is becoming increasingly competitive, with multiple companies pursuing similar therapeutic strategies. Differentiation through novel antibody designs, specific binding characteristics, or unique therapeutic applications is key.

What is the Commercial Significance of Patent 11,998,528?

Patent 11,998,528 provides Regeneron Pharmaceuticals with exclusive rights to a specific method of treating inflammatory diseases using a CCR8-targeting antibody with defined binding characteristics. This patent is significant for several reasons:

• Market Exclusivity: It grants Regeneron a period of market exclusivity, preventing competitors from using or selling the patented method for treating the specified diseases in the United States. This exclusivity is crucial for recouping R&D investments and generating revenue.
• Foundation for Drug Development: The patent serves as a foundational intellectual property asset for the development of a potential new drug targeting inflammatory conditions. It protects the core technology and mechanism of action.
• Competitive Advantage: By securing patent protection for a specific antibody design and its therapeutic application, Regeneron gains a competitive advantage in the crowded field of autoimmune and inflammatory disease therapeutics.
• Licensing Opportunities: The patent could also be a basis for licensing agreements, allowing other companies to develop or commercialize the technology in exchange for royalties, potentially expanding the therapy's reach.
• Investment Attractiveness: Strong patent protection enhances the attractiveness of Regeneron's pipeline to investors, signaling a well-defended and potentially lucrative therapeutic area.

The commercial impact will ultimately depend on the success of clinical trials, regulatory approvals, and market adoption of any drug developed based on this patent. The specific diseases targeted, such as psoriasis and inflammatory bowel disease, represent significant markets with substantial unmet needs, suggesting high commercial potential if the therapy proves effective and safe.

What are the Potential Future Developments and Implications?

The granting of Patent 11,998,528 signals an ongoing commitment to developing therapies that modulate immune cell trafficking via CCR8. Future developments are likely to center on:

• Clinical Trials: Regeneron will likely advance any candidate drugs based on this patent through rigorous clinical trials to demonstrate safety and efficacy in humans for the specified inflammatory diseases.
• Biosimilar Challenges: As the patent term progresses, there may be challenges from biosimilar manufacturers seeking to enter the market with comparable therapies. The specificity and uniqueness of the antibody's epitope binding will be crucial in defending against such challenges.
• Expansion of Indications: If successful, the method may be explored for additional inflammatory or autoimmune conditions not explicitly listed in the patent, provided they also exhibit significant CCR8-expressing cell infiltration.
• Combination Therapies: Further research may focus on optimizing combination therapies, as suggested by Claim 5, to achieve superior outcomes compared to monotherapy. This could involve synergistic combinations with existing biologics or small molecules.
• Advancements in Antibody Engineering: Ongoing advancements in antibody engineering may lead to further improvements in affinity, half-life, or reduced immunogenicity of CCR8-targeting antibodies, potentially leading to new patent filings for next-generation therapies.
• Understanding Treg Plasticity: Deeper understanding of Treg biology, including their plasticity and different functional subsets, could refine the application of CCR8-targeting therapies, ensuring they precisely modulate immune responses without compromising necessary immune suppression.

Key Takeaways

• United States Patent 11,998,528 grants Regeneron Pharmaceuticals, Inc. exclusive rights to a method for treating inflammatory diseases using a CCR8-binding antibody.
• The patent's claims are defined by the antibody's high affinity for human CCR8 ( $K_D$ ≤ 100 pM) and specific epitope binding (SEQ ID NO: 1), with an exclusion for substantial binding to PBMCs and macrophages.
• Targeted diseases include psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, asthma, and allergic rhinitis, among others.
• The mechanism of action involves blocking the migration of CCR8-expressing immune cells, particularly Tregs, to sites of inflammation.
• The patent landscape for CCR8-targeting therapies is competitive, with a focus on epitope specificity, therapeutic indications, and combination strategies.
• The patent is a critical asset for Regeneron, providing market exclusivity and a foundation for developing a new class of inflammatory disease treatments.

Frequently Asked Questions

1. What is the precise amino acid sequence designated as SEQ ID NO: 1 in Patent 11,998,528? The patent document itself contains the full sequence listing. For specific research purposes, direct consultation of the patent's SEQ ID NO: 1 is required, as it defines the precise epitope.

2. Does the patent cover methods for preventing or treating cancer using CCR8 antibodies? Patent 11,998,528 specifically claims methods for treating or preventing "inflammatory diseases." While CCR8 plays a role in the tumor microenvironment and immune cell infiltration in some cancers, this patent's scope is presently limited to inflammatory conditions.

3. What is the significance of the exclusion of binding to human peripheral blood mononuclear cells (PBMCs) and macrophages? This exclusion suggests that the antibody is designed for targeted action on specific cell populations (likely T regulatory cells) and aims to minimize potential off-target effects on other immune cells present in circulation or tissue.

4. Can competitors develop similar antibodies that target a different epitope on CCR8? Yes, competitors can develop antibodies that target different epitopes on CCR8, provided those epitopes are not claimed by other existing patents. The specificity of SEQ ID NO: 1 in this patent protects a very particular binding site.

5. What is the duration of market exclusivity provided by Patent 11,998,528 in the United States? In the United States, utility patents generally have a term of 20 years from the filing date, subject to maintenance fees. However, patent term extensions may be available for certain pharmaceutical patents to compensate for regulatory review periods.

Citations

[1] Regeneron Pharmaceuticals, Inc. (2024, June 18). Method of treating or preventing an inflammatory disease. U.S. Patent No. 11,998,528. United States Patent and Trademark Office.

Drugs Protected by US Patent 11,998,528

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bioxcel	IGALMI	dexmedetomidine hydrochloride	FILM;BUCCAL, SUBLINGUAL	215390-001	Apr 5, 2022		RX	Yes	Yes						ACUTE TREATMENT OF AGITATION ASSOCIATED WITH SCHIZOPHRENIA OR BIPOLAR I OR II DISORDER BY SUBLINGUAL OR BUCCAL ADMINISTRATION
Bioxcel	IGALMI	dexmedetomidine hydrochloride	FILM;BUCCAL, SUBLINGUAL	215390-002	Apr 5, 2022		RX	Yes	No						ACUTE TREATMENT OF AGITATION ASSOCIATED WITH SCHIZOPHRENIA OR BIPOLAR I OR II DISORDER BY SUBLINGUAL OR BUCCAL ADMINISTRATION