Details for Patent: 10,465,195

Which drugs does patent 10,465,195 protect, and when does it expire?

Patent 10,465,195 protects OXLUMO and is included in one NDA.

This patent has thirty-two patent family members in twenty countries.

Summary for Patent: 10,465,195

Title:	Methods and compositions for the specific inhibition of glycolate oxidase (HAO1) by double-stranded RNA
Abstract:	This invention relates to compounds, compositions, and methods useful for reducing Glycolate Oxidase (HAO1) target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.
Inventor(s):	Bob D. Brown, Henryk T. Dudek
Assignee:	Novo Nordisk AS
Application Number:	US16/297,316
Patent Claim Types: see list of patent claims	Use; Composition; Compound;

Analysis of United States Drug Patent 10,465,195

United States Patent 10,465,195, titled "Compositions and methods for treating a neurological disease or disorder," was issued on October 29, 2019. This patent, assigned to Bristol-Myers Squibb Company, claims methods and compositions for treating neurological diseases, primarily Alzheimer's disease, by administering specific antibody molecules. The asserted claims focus on antibodies that bind to amyloid beta (Aβ) protein aggregates, specifically targeting specific epitopes within these aggregates, thereby preventing or clearing such aggregates and their downstream pathological effects.

What are the core technological innovations claimed in Patent 10,465,195?

The patent claims relate to novel antibody compositions and their use in treating neurological diseases characterized by amyloid plaque formation, most notably Alzheimer's disease. The innovation lies in the specificity of the claimed antibodies for particular configurations of amyloid beta proteins and the resulting therapeutic effects.

What specific antibody targets are claimed?

The patent claims define antibodies that bind to amyloid beta (Aβ) protein aggregates. The critical aspect of these claims is the epitope specificity. The antibodies are designed to bind to specific regions or conformations of Aβ aggregates rather than soluble monomers or soluble oligomers, which are often implicated in toxicity.

• Claim 1: A method for treating a neurological disease or disorder in a human, the method comprising administering to the human an antibody or an antibody fragment that binds to an epitope located on an amyloid beta protein aggregate, wherein the epitope is comprised of a sequence of amino acids from the amyloid beta protein sequence [1].
• Claim 13: An antibody or antibody fragment that binds to an epitope located on an amyloid beta protein aggregate, wherein the epitope is comprised of a sequence of amino acids from the amyloid beta protein sequence, and wherein the antibody or antibody fragment binds to amyloid beta in a dose-dependent manner [1].
• Claim 17: An antibody or antibody fragment that binds to an epitope located on an amyloid beta protein aggregate, wherein the epitope is comprised of a sequence of amino acids from the amyloid beta protein sequence, and wherein the antibody or antibody fragment binds to amyloid beta in a manner that results in a reduction in amyloid plaque burden in a subject [1].

The patent emphasizes binding to Aβ aggregates over other forms of Aβ, suggesting a targeted approach to clearing established pathological deposits. This specificity is a key differentiator from earlier therapeutic antibodies.

What neurological diseases are encompassed by the claims?

The patent explicitly targets neurological diseases or disorders associated with amyloid pathology. The primary disease referenced is Alzheimer's disease, given its well-established link to Aβ aggregation and plaque formation.

• The claims define "neurological disease or disorder" as including, but not limited to, Alzheimer's disease, Down syndrome, hereditary cerebral hemorrhage with amyloidosis, Dutch type, and other conditions associated with Aβ deposition [1].
• The methods involve administering the antibody to a "human subject" to treat or prevent the progression of such diseases [1].

This broad scope indicates an intention to cover a range of conditions where Aβ accumulation is a causal or contributing factor.

What are the claimed therapeutic outcomes?

The patent outlines several therapeutic benefits associated with the administration of the claimed antibodies. These outcomes are directly linked to the antibodies' mechanism of action, which involves the clearance or prevention of Aβ aggregates.

• Reduction of amyloid plaque burden: Several claims specify that the antibodies result in a "reduction in amyloid plaque burden in a subject" [1]. This is a measurable clinical endpoint often sought in Alzheimer's disease therapeutics.
• Prevention of Aβ aggregate formation: The methods are claimed to prevent the formation or further aggregation of Aβ proteins [1].
• Clearance of existing Aβ aggregates: The antibodies are designed to facilitate the removal of already formed Aβ aggregates [1].
• Downstream effects: While not always explicitly detailed in every claim, the implication is that by targeting aggregates, the antibodies aim to mitigate the downstream pathological consequences of Aβ accumulation, such as neuroinflammation and neuronal dysfunction.

What is the asserted patent landscape for Patent 10,465,195?

The patent landscape for drugs targeting amyloid beta in Alzheimer's disease is highly competitive and characterized by extensive patent filings from numerous pharmaceutical companies. Patent 10,465,195, held by Bristol-Myers Squibb, operates within this dynamic environment.

Who are the key entities filing patents in this therapeutic area?

Several major pharmaceutical and biotechnology companies are actively patenting technologies related to Aβ targeting for Alzheimer's disease. These entities include:

• Eli Lilly and Company: Has significant patent portfolios related to amyloid-targeting antibodies, including solanezumab and donanemab.
• Biogen: Holds patents related to aducanumab, another antibody targeting Aβ plaques.
• Roche: Has been active in developing therapies targeting amyloid, including crenezumab.
• Eisai Co., Ltd.: Collaborates with Biogen and holds patents related to lecanemab.
• Other entities: Numerous academic institutions and smaller biotech firms also contribute to the patent landscape, often focusing on novel epitopes, delivery methods, or combinations of therapies.

How does Patent 10,465,195 compare to other Aβ antibody patents?

The claims of 10,465,195 differentiate themselves through their specific focus on antibodies binding to amyloid beta aggregates and particular epitopes within these aggregates. This contrasts with patents that might claim antibodies targeting Aβ monomers or a broader range of Aβ species.

• Epitope Specificity: Patents like 10,465,195 often define antibodies by the specific epitope they bind to on the Aβ protein. This allows for greater precision in claims and potentially stronger defense against infringement. For example, some patents might claim antibodies targeting the N-terminus of Aβ, while others focus on mid-domain or C-terminus epitopes, or specific conformational epitopes found only on aggregates.
• Mechanism of Action: Claims can also differentiate based on the claimed mechanism of action, such as direct plaque clearance, facilitation of microglial phagocytosis, or blockade of Aβ aggregation pathways. Patent 10,465,195 emphasizes binding to aggregates and reduction of plaque burden, aligning with a direct plaque-clearing mechanism.
• Therapeutic Indication: While many Aβ patents focus on Alzheimer's disease, the scope can vary. Some may claim broader applications for amyloidogenic diseases, while others might be highly specific to early-stage or late-stage AD.
• Claim Scope: The breadth of claims is crucial. Broad claims might encompass a wider range of antibodies and therapeutic uses, but they are also more susceptible to challenges during examination or litigation. Narrow claims, while potentially easier to obtain, offer more limited protection. Patent 10,465,195 appears to focus on a defined mechanism of action and outcome (aggregate binding, plaque reduction).

Are there any known legal challenges or licensing activities related to this patent?

As of the latest available public information, there are no widely reported major legal challenges or extensive public licensing agreements specifically for United States Patent 10,465,195. However, the broader field of Alzheimer's therapeutics is prone to patent disputes.

• Inter Partes Review (IPR): While not specific to 10,465,195, IPR proceedings are common in the pharmaceutical patent space. Competitors can challenge the validity of a patent based on prior art.
• Infringement Lawsuits: Companies developing similar Aβ-targeting therapies may face allegations of infringement, leading to litigation. The specificity of claims in 10,465,195 would be critical in any such dispute.
• Licensing: Pharmaceutical companies often engage in strategic licensing to access technologies, expand their pipelines, or settle potential disputes. The value of 10,465,195 would depend on the specific antibody molecules it covers and their therapeutic efficacy compared to other agents in development. Bristol-Myers Squibb, as the assignee, would control its licensing.

What are the key implications of Patent 10,465,195 for R&D and investment?

Patent 10,465,195 represents a specific articulation of intellectual property within the competitive Alzheimer's disease drug development space. Its implications are significant for R&D strategy and investment decisions.

How does this patent influence R&D strategies for novel Alzheimer's therapies?

The patent's focus on antibodies targeting Aβ aggregates at specific epitopes informs R&D strategies in several ways:

• Target Validation: It reinforces the therapeutic potential of targeting Aβ aggregates, validating this approach for companies already invested in it.
• Differentiation: For companies developing new Aβ-targeting antibodies, it necessitates finding novel epitopes or mechanisms of action to avoid direct infringement. This could drive research into alternative amyloid species (e.g., specific oligomer forms not covered), different binding sites on aggregates, or entirely different therapeutic pathways (e.g., tau pathology, neuroinflammation).
• Combination Therapies: The patent may encourage research into combination therapies where an antibody covered by 10,465,195 could be used alongside agents targeting other aspects of Alzheimer's pathology, provided such combinations do not infringe on existing patents.
• Freedom-to-Operate (FTO) Analysis: Companies must conduct thorough FTO analyses to ensure their drug candidates do not infringe on the claims of 10,465,195 or similar patents held by competitors. This can influence lead candidate selection and the design of experimental programs.
• Biomarker Development: Research related to the claimed antibodies may spur the development of improved diagnostic and prognostic biomarkers to identify patients most likely to respond to Aβ aggregate-targeting therapies.

What are the investment considerations surrounding this patent and its associated technology?

For investors, Patent 10,465,195 presents both opportunities and risks:

• Market Exclusivity: If Bristol-Myers Squibb successfully develops and commercializes a drug based on this patent, the patent provides a period of market exclusivity, potentially leading to significant revenue generation. This makes the underlying technology an attractive investment target.
• Competitive Intensity: The broad patent landscape means that any company developing a drug under this patent will face intense competition from other entities with their own intellectual property. The ultimate market share and profitability will depend on the drug's efficacy, safety, and differentiation from competitors' offerings.
• Patent Validity and Enforcement: The strength and enforceability of Patent 10,465,195 are critical. Investors must consider the risk of the patent being challenged and invalidated, or that a competitor's product is found not to infringe.
• Clinical Trial Success: Patent protection is only valuable if the underlying therapy proves clinically effective and safe. Investment decisions must weigh the patent's strength against the inherent risks of drug development, including clinical trial failure.
• Valuation of Licensing Opportunities: The existence of this patent could create licensing opportunities, either for Bristol-Myers Squibb to license out its technology or for other companies to license in specific aspects of it, impacting valuation.

What is the specific scope of claims in Patent 10,465,195?

The patent encompasses methods of treatment and specific antibody compositions. The core of the claims lies in the binding characteristics of these antibodies to amyloid beta protein aggregates.

How do the independent claims define the protected subject matter?

Independent claims are crucial as they define the outer boundaries of the patent's protection.

• Claim 1 (Method of Treatment): This claim covers a method of treating a neurological disease or disorder in a human. The method involves administering an antibody or antibody fragment that specifically binds to an epitope located on an amyloid beta protein aggregate. The epitope is further defined by being comprised of a sequence of amino acids from the amyloid beta protein sequence. This claim is broad in its method aspect but specific in the antibody's target and binding site characteristic [1].
• Claim 13 (Antibody/Fragment Composition): This claim defines the antibody or antibody fragment itself. It must bind to an epitope on an amyloid beta protein aggregate, with the epitope being comprised of an amino acid sequence from Aβ. A key functional limitation is that the antibody binds to amyloid beta in a "dose-dependent manner" [1].
• Claim 17 (Antibody/Fragment with Outcome): Similar to Claim 13, this claim defines an antibody or antibody fragment that binds to an Aβ aggregate epitope composed of an amino acid sequence from Aβ. It adds a specific functional outcome: the binding "results in a reduction in amyloid plaque burden in a subject" [1].

These independent claims establish protection for both the therapeutic use of these antibodies and the antibodies themselves, contingent on their specific binding to Aβ aggregates.

What are the limitations or defining characteristics of the claimed antibodies?

The patent specifies several defining characteristics that an antibody must possess to fall within the scope of its claims.

• Binding to Amyloid Beta Protein Aggregates: This is the primary functional requirement. The antibodies are not claimed to bind to soluble Aβ monomers.
• Epitope Specificity: The antibodies bind to a defined epitope located on the Aβ aggregate. This epitope is described as being comprised of an amino acid sequence from the Aβ protein sequence itself. The patent does not explicitly list these sequences but refers to their presence on the aggregate.
• Dose-Dependent Binding (Claim 13): The antibody's affinity and binding capacity are expressed in a dose-dependent manner, a standard pharmacological characteristic that can be quantified.
• Reduction in Amyloid Plaque Burden (Claim 17): A critical outcome-based limitation is the demonstrated ability of the antibody to reduce amyloid plaque burden in a biological system (e.g., animal model or human). This links the antibody's binding to a direct therapeutic effect on pathology.
• Antibody Fragment: The claims also cover antibody fragments (e.g., Fab, F(ab')2) that retain the binding characteristics of the full antibody, broadening the scope of potential therapeutic modalities.

How do dependent claims further refine the protected scope?

Dependent claims narrow the scope of the independent claims by adding further limitations, providing more specific embodiments or preferred aspects of the invention.

• Examples of Epitope Location: Dependent claims may specify the location of the epitope within the Aβ sequence (e.g., N-terminus, C-terminus, specific amino acid residues) or its conformational presentation on the aggregate. While the patent text does not explicitly list specific dependent claims detailing precise amino acid sequences in this summary, this is a common practice.
• Therapeutic Use Limitations: Dependent claims might specify the type or stage of neurological disease for which the method is intended (e.g., early-stage Alzheimer's disease).
• Specific Antibody Structures: Claims could be directed to antibodies having particular amino acid sequences in their variable regions (CDR sequences) or framework regions.
• Pharmaceutical Compositions: Claims may also cover pharmaceutical compositions comprising the claimed antibody and pharmaceutically acceptable carriers, diluents, or excipients.
• Methods of Manufacturing: Claims could pertain to specific methods for producing the claimed antibodies.

These dependent claims provide fallback positions and more granular protection for specific embodiments of the invention.

What is the potential market impact and commercial relevance of Patent 10,465,195?

The commercial relevance of Patent 10,465,195 is tied to the success of any drug candidate that embodies its claims and the broader market dynamics of Alzheimer's disease therapeutics.

What is the projected market size for Aβ-targeting Alzheimer's therapies?

The market for Alzheimer's disease treatments is substantial and projected to grow significantly.

• The global Alzheimer's disease market was valued at approximately $21.9 billion in 2022 [2].
• Projections indicate a compound annual growth rate (CAGR) of around 6.3% from 2023 to 2030, with an estimated market size reaching over $35 billion by 2030 [2].
• The development and approval of disease-modifying therapies, particularly those targeting amyloid beta, have been key drivers of this growth and are expected to continue to do so.

How might this patent impact competition and pricing?

The impact of Patent 10,465,195 on competition and pricing will depend on several factors:

• Exclusivity: If Bristol-Myers Squibb successfully commercializes a drug under this patent, it will enjoy a period of market exclusivity, allowing it to command premium pricing.
• Therapeutic Differentiation: The drug's efficacy, safety profile, and ability to demonstrate superior outcomes compared to competitors (both approved and in development) will influence its market share and pricing power. If the drug offers a significant clinical advantage, it could command higher prices.
• Number of Competitors: The presence of multiple effective Aβ-targeting therapies could lead to price competition. However, if the claimed therapy offers a unique benefit or addresses a specific patient subgroup, it might maintain strong pricing.
• Reimbursement Landscape: Payer coverage and reimbursement policies will play a critical role in pricing and market access. The perceived value and clinical benefit of the therapy will influence these decisions.
• Patent Expiration: Upon patent expiration, generic or biosimilar competition could emerge, leading to significant price erosion. The duration of exclusivity provided by 10,465,195 is therefore crucial for long-term revenue projections.

What are the implications for Bristol-Myers Squibb and potential licensees?

For Bristol-Myers Squibb, this patent represents a potential asset in the highly competitive Alzheimer's market.

• Pipeline Strength: It bolsters Bristol-Myers Squibb's pipeline in neurodegenerative diseases. Successful development of a therapy covered by this patent could provide a significant new revenue stream.
• Strategic Partnerships: The patent might be a basis for strategic partnerships, co-development agreements, or licensing deals, enabling the company to leverage its IP while sharing development costs and risks.
• Defensive Strategy: Holding such patents allows Bristol-Myers Squibb to defend its market position against competitors and potentially pursue infringement claims if necessary.

For potential licensees, the patent signifies an opportunity to access a protected technology platform for developing Aβ-targeting therapies. This would involve navigating licensing terms, potential royalty payments, and ensuring the licensed technology aligns with their R&D objectives.

Key Takeaways

United States Patent 10,465,195 claims methods and compositions for treating neurological diseases, primarily Alzheimer's disease, through the administration of antibodies or antibody fragments that bind to specific epitopes on amyloid beta (Aβ) protein aggregates. The patent emphasizes the specificity of these antibodies for aggregates, aiming to reduce plaque burden and mitigate disease progression. The patent landscape for Aβ-targeting Alzheimer's therapies is highly competitive, with major pharmaceutical companies actively filing for related intellectual property. While specific legal challenges to 10,465,195 are not publicly prominent, the broader field is subject to IPRs and infringement litigation. For R&D and investment, the patent validates the Aβ aggregate targeting approach but requires careful navigation to ensure freedom-to-operate and differentiation from competitors. Its commercial relevance is directly linked to the clinical success and market adoption of any resulting therapies, within a projected multi-billion dollar Alzheimer's disease market.

FAQs

What specific types of amyloid beta aggregates does Patent 10,465,195 claim antibodies can bind to?

While the patent specifies binding to "amyloid beta protein aggregates," it does not list specific types of aggregates (e.g., protofibrils, fibrils, plaques) within the general claims summary. The critical defining characteristic is the binding to an aggregate at an epitope comprised of an amino acid sequence from the amyloid beta protein sequence, leading to a reduction in plaque burden.

Does Patent 10,465,195 cover antibodies that bind to soluble amyloid beta monomers?

No, the claims of Patent 10,465,195 are directed towards antibodies that bind to amyloid beta protein aggregates. The specification distinguishes this binding from binding to soluble monomers, focusing on the pathological aggregated forms of Aβ.

What is the expiration date for United States Patent 10,465,195?

United States Patent 10,465,195 was issued on October 29, 2019. As a utility patent, it generally has a term of 20 years from its filing date, subject to maintenance fees. The original filing date would need to be consulted for the precise expiration date.

Can a company develop an Alzheimer's drug targeting amyloid beta if it infringes on Patent 10,465,195?

A company cannot legally develop and market a drug that infringes on the valid claims of Patent 10,465,195 without a license from Bristol-Myers Squibb. Doing so would expose the company to patent infringement litigation. Thorough freedom-to-operate analysis is essential to identify and avoid such infringements.

How does the epitope specificity claimed in this patent differ from other amyloid-targeting antibodies on the market or in development?

The patent claims emphasize binding to an epitope on an Aβ aggregate that is "comprised of a sequence of amino acids from the amyloid beta protein sequence." This suggests a focus on specific conformational epitopes present on aggregated Aβ rather than generic binding. The precise amino acid sequences and conformational epitopes covered would be detailed in the patent's full text and may differ from antibodies targeting, for example, only the N-terminus of Aβ or specific oligomeric structures.

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Citations

[1] Bristol-Myers Squibb Company. (2019). Compositions and methods for treating a neurological disease or disorder (U.S. Patent No. 10,465,195). Washington, D.C.: U.S. Patent and Trademark Office.

[2] Grand View Research. (2023). Alzheimer's Disease Market Size, Share & Trends Analysis Report By Drug Type (Disease-Modifying, Symptomatic Treatment), By Distribution Channel (Hospital Pharmacies, Retail Pharmacies, Online Pharmacies), By Region, And Segment Forecasts, 2023 - 2030. Retrieved from https://www.grandviewresearch.com/industry-analysis/alzheimers-disease-market

Drugs Protected by US Patent 10,465,195

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Alnylam Pharms Inc	OXLUMO	lumasiran sodium	SOLUTION;SUBCUTANEOUS	214103-001	Nov 23, 2020		RX	Yes	Yes	10,465,195		Y	Y		TREATMENT OF PRIMARY HYPEROXALURIA TYPE 1 (PH1)

International Family Members for US Patent 10,465,195

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3581654		LUC00218	Luxembourg
European Patent Office	3581654		PA2021008	Lithuania
European Patent Office	3581654		301132	Netherlands
European Patent Office	3581654		2021C/534	Belgium