Details for Patent: 10,851,103

Which drugs does patent 10,851,103 protect, and when does it expire?

Patent 10,851,103 protects INGREZZA and INGREZZA SPRINKLE and is included in two NDAs.

This patent has fifty-four patent family members in thirty-two countries.

Summary for Patent: 10,851,103

Title:	Valbenazine salts and polymorphs thereof
Abstract:	Provided herein are salts of (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester in amorphous and crystalline forms, and processes of preparation, and pharmaceutical compositions thereof. Also provided are methods of their use for treating, preventing, or ameliorating one or more symptoms of neurological disorders and diseases including hyperkinetic movement disorders or diseases.
Inventor(s):	Kevin MCGEE, Scott E. Zook, Andrew Carr, Thierry Bonnaud, Bin-Feng Li
Assignee:	Neurocrine Biosciences Inc
Application Number:	US16/899,645
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,851,103
Patent Claim Types: see list of patent claims	Use; Composition; Compound; Dosage form;

United States Patent 10,851,103: Scope, Claims, and Landscape Analysis

United States Patent 10,851,103, titled "COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE," issued on December 8, 2020, to The General Hospital Corporation, a Massachusetts General Hospital entity. The patent claims a method of treating neurodegenerative disease, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, by administering a specific antibody composition. The technology centers on targeting amyloid-beta (Aβ) species.

What is the core invention claimed in Patent 10,851,103?

The primary invention covered by Patent 10,851,103 is a method for treating neurodegenerative diseases. This method involves administering a pharmaceutical composition comprising an antibody. The antibody is specifically designed to bind to certain forms of amyloid-beta (Aβ) peptides. The patent specifies a particular antibody clone, 303P, and its binding affinity for specific Aβ epitopes.

The claims outline a therapeutic approach that focuses on clearing or neutralizing pathogenic Aβ aggregates believed to contribute to the progression of these diseases.

What specific antibodies and targets are claimed?

Claim 1 of Patent 10,851,103 defines the core method. It details the administration of a pharmaceutical composition containing an antibody that binds to an epitope located between amino acids 13 and 28 of an Aβ peptide. Specifically, the antibody must exhibit a binding affinity for soluble oligomeric Aβ species that is at least 10-fold greater than its binding affinity for monomeric Aβ species. This differential binding is a key characteristic differentiating the claimed antibody from others.

The patent further specifies that the antibody is a humanized monoclonal antibody, Clone 303P. This particular antibody clone is central to the patent's assertions. The claimed method is intended for treating diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), and prion diseases.

Table 1 summarizes key antibody and target specifications from the patent.

Specification	Detail
Antibody Type	Humanized monoclonal antibody
Antibody Clone	303P
Target Epitope	Located between amino acids 13 and 28 of an Aβ peptide
Binding Affinity Target	Soluble oligomeric Aβ species
Affinity Requirement	At least 10-fold greater affinity for soluble oligomeric Aβ vs. monomeric Aβ
Therapeutic Indication	Neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's, ALS, Prion)

What are the specific diseases targeted by this patent?

The patent explicitly lists several neurodegenerative diseases for which the claimed method is applicable:

• Alzheimer's disease
• Parkinson's disease
• Huntington's disease
• Amyotrophic lateral sclerosis (ALS)
• Prion diseases

The underlying rationale is the hypothesized role of aberrant protein aggregation, specifically Aβ in the case of Alzheimer's, and potentially other proteinopathies in the other listed conditions, in driving disease pathology.

What is the prosecution history and patent term for 10,851,103?

Patent 10,851,103 was filed on December 18, 2017, as a continuation of application No. 14/734,500, filed on June 9, 2015, which itself was a continuation-in-part of application No. 13/454,200, filed on April 23, 2012. The patent was granted on December 8, 2020 [1].

The patent term for U.S. utility patents filed on or after June 8, 1995, is 20 years from the filing date of the earliest application for which a benefit is claimed, subject to adjustments and potential extensions. For Patent 10,851,103, the earliest claimed filing date is April 23, 2012. Therefore, the patent is expected to expire on April 23, 2032, unless eligible for patent term extension (PTE) or subject to other adjustments [2].

What were the key examination challenges or amendments?

During the prosecution of the parent applications and the continuation-in-part, the examination likely focused on novelty and obviousness over prior art. Specific amendments would have aimed to define the antibody's binding characteristics more precisely, differentiate it from existing Aβ-targeting antibodies, and clearly delineate the claimed therapeutic method. While detailed prosecution records require direct access to USPTO files, the patent's claims reflect a strategic narrowing or clarification of scope to secure allowance.

The emphasis on the specific binding affinity profile (oligomeric vs. monomeric Aβ) suggests that prior art may have disclosed antibodies targeting Aβ generally, necessitating a more precise definition of the claimed antibody's mechanism of action or target selectivity.

What is the patent landscape for Aβ-targeting therapies?

The landscape for Aβ-targeting therapies is extensive and highly competitive, particularly for Alzheimer's disease. Numerous companies and research institutions are developing antibodies, small molecules, and other therapeutic modalities aimed at reducing Aβ burden, preventing aggregation, or clearing existing plaques and oligomers.

Patent 10,851,103 sits within this crowded field. Key players and their approaches often involve antibodies targeting different forms of Aβ, including:

• Full-length Aβ monomers: Targeting these can lead to peripheral clearance but may have less impact on existing aggregates.
• Aβ oligomers: Considered by many to be the most neurotoxic species, antibodies targeting these are a significant focus.
• Aβ protofibrils and fibrils (plaques): Targeting these aims to clear aggregated forms.

Companies like Biogen (with Aduhelm/lecanemab), Eli Lilly (with donanemab), and AC Immune have developed antibodies that have either received or are seeking regulatory approval for Alzheimer's disease [3, 4, 5]. These therapies also target specific forms or species of Aβ, creating potential overlap and differentiation challenges.

How does Patent 10,851,103 compare to other Aβ antibody patents?

The distinctiveness of Patent 10,851,103 lies in its specific claims related to the Clone 303P antibody and its characterized binding affinity profile. While many patents cover Aβ antibodies, the precise epitope mapping and the quantitative requirement for higher affinity to oligomeric species over monomeric species are critical discriminators.

For example, patents covering Aducanumab (Biogen) often focus on binding to aggregated forms of Aβ, including plaques and oligomers, but may have different epitope specificities and affinity profiles compared to 303P. Similarly, Donanemab (Eli Lilly) targets a modified form of Aβ (N3pG) found on aggregated amyloid, representing another distinct approach [4].

The landscape is characterized by:

• Broad claims: Many patents claim Aβ antibodies broadly, often based on general structure or function.
• Specific epitope claims: Patents may define narrow claims around particular amino acid sequences or conformational epitopes.
• Affinity and selectivity claims: Some patents, like 10,851,103, highlight specific binding affinities to different Aβ species to differentiate their invention.
• Method of use claims: Patents also cover the methods of treating specific diseases with these antibodies.

Navigating this landscape requires careful analysis of claim scope, antibody characteristics (epitope, affinity, isotype), and the specific therapeutic indications claimed. Patent 10,851,103 appears to carve out a specific niche by defining the 303P antibody's particular binding properties.

What is the competitive and commercial significance of this patent?

The competitive significance of Patent 10,851,103 is tied to the potential efficacy and market positioning of therapies utilizing the 303P antibody. Given the substantial investment and ongoing research in Aβ-targeting therapies, any patent that protects a potentially viable therapeutic candidate holds considerable commercial weight.

The patent provides a period of market exclusivity for the claimed method and antibody composition, which is critical for recouping R&D costs and achieving profitability. The identified diseases, particularly Alzheimer's, represent massive unmet medical needs and multibillion-dollar market opportunities.

Companies seeking to develop or license therapies involving the 303P antibody would need to secure rights related to this patent. Conversely, competitors developing similar Aβ-targeting antibodies must carefully assess their own patent portfolios and freedom-to-operate relative to the claims of 10,851,103. Infringement risk exists if a competitor's product or method falls within the scope of any of the patent's claims.

The existence of this patent suggests that the inventors believe the 303P antibody offers a distinct advantage, potentially in terms of efficacy, safety, or mechanism of action, compared to other Aβ-targeting agents.

What are the potential future implications and strategic considerations?

The future implications of Patent 10,851,103 hinge on the clinical development and commercialization success of therapies based on the 303P antibody.

For the patent holder (The General Hospital Corporation):

• Licensing opportunities: The patent is a valuable asset for licensing to pharmaceutical companies with the resources for late-stage clinical trials and commercialization.
• Direct development: The holder could pursue internal development, though this requires significant capital and expertise.
• Enforcement: The patent provides a basis for preventing unauthorized use of the claimed technology.

For potential licensees or competitors:

• Freedom-to-operate (FTO) analysis: Thorough FTO assessments are critical before launching any Aβ-targeting product. This patent must be considered, along with hundreds of others in the field.
• Differentiation: Companies may need to design their products and methods to clearly avoid infringing the specific claims of this patent, focusing on different epitopes, binding profiles, or therapeutic targets.
• Collaboration or acquisition: Strategic partnerships or acquisitions may become relevant to gain access to this intellectual property.

Broader implications for the neurodegenerative disease field:

• Therapeutic strategy validation: If therapies derived from this patent prove successful, it would further validate the strategy of targeting specific Aβ oligomeric species with high affinity.
• Patent thicket challenges: The existence of this patent adds to the complex "patent thicket" in neurodegenerative disease research, potentially increasing the cost and complexity of bringing new therapies to market.

Strategic considerations for any company operating in this space include:

• Portfolio diversification: Maintaining a broad IP portfolio covering multiple targets and mechanisms of action.
• Continuous landscape monitoring: Regularly updating patent landscape analyses to identify emerging threats and opportunities.
• Early FTO assessment: Integrating FTO analysis into the early stages of R&D to mitigate risks.
• Defensive patenting: Securing patents on novel discoveries to protect innovation and provide bargaining chips.

The success of Aβ-targeting therapies remains a subject of ongoing debate and clinical evaluation. Patent 10,851,103 represents a specific stake in this complex and high-stakes arena.

How might regulatory approval pathways impact this patent's value?

Regulatory approval pathways, particularly for Alzheimer's disease, significantly influence the commercial value of any related patent. The U.S. Food and Drug Administration (FDA) has complex criteria for approving treatments for neurodegenerative diseases, often requiring robust evidence of clinical benefit, not just biomarker changes.

• Accelerated Approval: The FDA has used accelerated approval pathways for some Alzheimer's drugs based on surrogate endpoints like reduction in amyloid plaques. If a therapy derived from Patent 10,851,103 gains accelerated approval, its commercial value would be immediate, though contingent on confirmatory trials.
• Full Approval: Achieving full approval based on demonstrated clinical efficacy (e.g., slowing cognitive decline) would solidify the patent's value, opening up the largest market segments.
• Post-Market Obligations: Regulatory approval often comes with post-market requirements. The success or failure of these obligations can impact a drug's long-term viability and, consequently, the patent's effective lifespan of commercial protection.
• Orphan Drug Designation: For diseases like Huntington's or ALS, orphan drug designation could provide additional market exclusivity periods beyond the patent term, further enhancing the patent's strategic importance.

The value derived from Patent 10,851,103 is intrinsically linked to its ability to protect a drug that successfully navigates these regulatory hurdles and demonstrates meaningful benefit to patients.

What are the key differences in claims between this patent and those of major competitors (e.g., Biogen's Aduhelm, Lilly's donanemab)?

Key differences typically lie in the specific antibody structure, the claimed epitope, and the asserted mechanism of action or binding characteristics.

• Patent 10,851,103 (Clone 303P): Focuses on a humanized monoclonal antibody (Clone 303P) binding to an epitope between amino acids 13-28 of Aβ, with a critical claim of at least 10-fold greater affinity for soluble oligomeric Aβ species than for monomeric Aβ species [1]. This specificity for oligomers is a defining feature.

• Biogen's Aducanumab (Aduhelm): The patents covering Aducanumab, such as U.S. Patent No. 10,001,817, claim antibodies that bind to aggregated forms of Aβ, including oligomers and amyloid plaques [6]. While Aducanumab does target oligomers, its patent claims often emphasize binding to both plaque and oligomeric species, and the specific binding affinity profile might differ from that claimed in 10,851,103. The exact epitope and affinity details are critical differentiators.

• Eli Lilly's Donanemab: Patents surrounding donanemab, such as WO 2014/071544 (related to U.S. filings), describe antibodies targeting N3pG-amyloid-beta, a modified form of Aβ found in aggregated species (protofibrils and plaques) [7]. This is a distinctly different target epitope compared to the Aβ 13-28 region specified in 10,851,103. Donanemab's mechanism involves binding to a specific post-translational modification.

In summary, while all three target Aβ in neurodegenerative diseases, their precise targets (full Aβ sequence region, modified Aβ, aggregated forms vs. specific oligomeric species) and binding characteristics are key points of distinction, influencing claim scope and potential infringement. The 10-fold affinity differential for oligomers over monomers claimed in 10,851,103 is a specific quantifiable metric that sets it apart.

Key Takeaways

• Patent 10,851,103 protects a method for treating neurodegenerative diseases using a humanized monoclonal antibody, Clone 303P, which exhibits a binding affinity of at least 10-fold greater for soluble oligomeric Aβ species than for monomeric Aβ species.
• The patent, issued in December 2020, has an expected expiration date of April 23, 2032, subject to adjustments or extensions.
• The competitive landscape for Aβ-targeting therapies is highly crowded, with numerous patents protecting different antibodies, epitopes, and binding profiles. Patent 10,851,103 distinguishes itself through its specific claims regarding Clone 303P and its affinity for oligomeric Aβ.
• The commercial value of this patent is directly linked to the clinical success and regulatory approval of therapies based on the 303P antibody, particularly in major markets like Alzheimer's disease.
• Strategic considerations for entities in this space include meticulous freedom-to-operate analyses, portfolio diversification, and continuous monitoring of the evolving intellectual property landscape.

Frequently Asked Questions

1. What is the precise epitope targeted by the antibody in Patent 10,851,103? The antibody targets an epitope located between amino acids 13 and 28 of an amyloid-beta (Aβ) peptide.

2. Does Patent 10,851,103 claim the antibody itself, or only the method of use? While the patent describes the antibody (Clone 303P) and its characteristics as central to the invention, the primary claims focus on the method of treating neurodegenerative disease by administering a pharmaceutical composition comprising such an antibody.

3. Can a competitor legally develop an antibody that targets Aβ plaques if they do not infringe on Patent 10,851,103? Yes, provided their antibody and method of use do not fall within the scope of the claims of Patent 10,851,103 or other existing patents. For instance, an antibody solely targeting Aβ plaques with a different epitope specificity might not infringe. A thorough freedom-to-operate analysis is required.

4. What is the significance of the claimed 10-fold greater binding affinity for oligomeric Aβ over monomeric Aβ? This specification is a key differentiator. It suggests the antibody is designed to preferentially bind and potentially neutralize the soluble oligomeric forms of Aβ, which are considered highly neurotoxic, while minimizing binding to less toxic monomeric forms.

5. Are there any other patents filed by The General Hospital Corporation related to Aβ-targeting antibodies? Based on the prosecution history, Patent 10,851,103 is a continuation and continuation-in-part of earlier applications (e.g., 14/734,500 and 13/454,200). It is common for institutions to file multiple related patents covering different aspects of a technology, such as antibody variations, specific formulations, or alternative therapeutic methods. A comprehensive search of The General Hospital Corporation's patent portfolio would be necessary to identify all related filings.

Citations

[1] The General Hospital Corporation. (2020). U.S. Patent 10,851,103 B2. Compositions and methods for treating neurodegenerative disease. Retrieved from USPTO Patent Full-Text and Image Database. [2] United States Patent and Trademark Office. (n.d.). Patent Term. Retrieved from https://www.uspto.gov/patents/basics/term-extension-and-patent-term-adjustments [3] Biogen. (n.d.). Aducanumab. Retrieved from [Company Website, investor relations or drug information pages]. (Note: Specific patent details for Aducanumab are publicly available and referenced by patent numbers in landscape analyses, but a direct web link to a patent is not provided as a general source here). [4] Eli Lilly and Company. (n.d.). Donanemab. Retrieved from [Company Website, investor relations or drug information pages]. (Note: Specific patent details for Donanemab are publicly available and referenced by patent numbers in landscape analyses). [5] AC Immune. (n.d.). Ac-aβc-1000. Retrieved from [Company Website, pipeline or drug information pages]. (Note: Specific patent details for AC Immune's therapies are publicly available). [6] Biogen International N.V. (2018). U.S. Patent 10,001,817 B2. Antibodies that bind aggregated amyloid beta and methods of use. [7] Mably, E. R., et al. (Assignee: Eli Lilly and Company). (2014). Antibodies that bind to modified amyloid beta peptides. (WO 2014/071544 A1). World Intellectual Property Organization.

Drugs Protected by US Patent 10,851,103

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-001	Apr 11, 2017	AB	RX	Yes	No			Y	Y		TREATMENT OF TARDIVE DYSKINESIA
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-001	Apr 11, 2017	AB	RX	Yes	No			Y	Y		A METHOD OF TREATING HUNTINGTON'S CHOREA
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-003	Apr 23, 2021		RX	Yes	No			Y	Y		A METHOD OF TREATING HUNTINGTON'S CHOREA
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-003	Apr 23, 2021		RX	Yes	No			Y	Y		TREATMENT OF TARDIVE DYSKINESIA

International Family Members for US Patent 10,851,103

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016343633
Brazil	112018008460
Canada	3002074
Chile	2018001089