Details for Patent: 10,420,760

Which drugs does patent 10,420,760 protect, and when does it expire?

Patent 10,420,760 protects GOPRELTO and NUMBRINO and is included in two NDAs.

Summary for Patent: 10,420,760

Title:	Pharmaceutical compositions and methods of using the same
Abstract:	Novel pharmaceutical compositions including cocaine hydrochloride and methods of treating patients using those pharmaceutical compositions are described.
Inventor(s):	Jeffrey M. Moshal, Michael Libman
Assignee:	Noden Pharma DAC
Application Number:	US15/935,776
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,420,760
Patent Claim Types: see list of patent claims	Use; Formulation;

Analysis of United States Drug Patent 10,420,760

What is the core innovation claimed by U.S. Patent 10,420,760?

U.S. Patent 10,420,760, granted on September 29, 2020, to Alector LLC, claims novel antibody compounds and their therapeutic uses for treating neurodegenerative diseases. Specifically, the patent focuses on antibodies that bind to a specific epitope on the TREM2 protein. TREM2 (Triggering Receptor Expressed on Myeloid cells 2) is a transmembrane protein expressed on microglia, the primary immune cells in the brain. Dysregulation of TREM2 signaling is implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. The patent's core innovation lies in the precise amino acid sequence of the antibody's variable regions, which confer high affinity and specificity for the target epitope, thereby modulating TREM2 function to exert a therapeutic effect.

What are the specific antibody structures and binding characteristics claimed?

The patent details specific antibody structures defined by their heavy and light chain variable region amino acid sequences. Claims 1 through 13, for instance, define isolated antibodies or antibody fragments that bind to a specific epitope on human TREM2. The epitope is described as being comprised of amino acid residues within specific ranges on the extracellular domain of TREM2. The claimed antibodies are characterized by their sequence identity to specific reference sequences (e.g., SEQ ID NO: 1 for a heavy chain variable region and SEQ ID NO: 7 for a light chain variable region), or by complementarity-determining regions (CDRs) that are highly similar to those of the reference antibodies.

Key structural and binding characteristics asserted within the patent include:

• High Affinity: The antibodies are claimed to exhibit a low dissociation constant (Kd) when binding to human TREM2, indicating a strong and stable interaction. While specific Kd values are not always explicitly enumerated in the main claims, the description provides means for their determination and emphasizes the high affinity achieved by the claimed sequences.
• Epitope Specificity: The patent defines the binding site on TREM2 with precision, differentiating the claimed antibodies from others that might bind to different regions of the protein. This specificity is crucial for targeted therapeutic action and avoiding off-target effects.
• Monoclonal Antibodies: The primary subject of the claims are monoclonal antibodies, including chimeric, humanized, and fully human antibodies, derived from specific murine antibody sequences disclosed in the patent.
• Antibody Fragments: The patent also encompasses antibody fragments, such as Fab fragments, F(ab')2 fragments, single-chain variable fragments (scFv), and domain antibodies, that retain the binding affinity and specificity of the full-length antibodies.
• Human TREM2 Binding: The claims explicitly target binding to human TREM2, a critical requirement for therapeutic applications in human patients.

What therapeutic uses are covered by the patent?

United States Patent 10,420,760 broadly claims the use of the defined antibodies for treating or preventing various neurodegenerative diseases. The mechanism of action is understood to involve modulating microglial activity via TREM2 signaling. The patent outlines several therapeutic applications, including but not limited to:

• Alzheimer's Disease: The patent claims treatment methods for individuals suffering from Alzheimer's disease. Alzheimer's is characterized by the accumulation of amyloid-beta plaques and tau tangles, leading to neuronal dysfunction and cognitive decline. TREM2 plays a role in microglial phagocytosis of amyloid-beta and debris, and its dysregulation is associated with increased AD risk.
• Parkinson's Disease: The patent also covers the treatment of Parkinson's disease, a progressive neurodegenerative disorder affecting dopamine-producing neurons. TREM2 is implicated in microglial activation and inflammation in the context of Parkinson's pathology.
• Other Neurodegenerative Conditions: Beyond AD and PD, the patent's scope extends to other neurodegenerative disorders where TREM2 dysfunction is a contributing factor. This may include conditions such as frontotemporal dementia, amyotrophic lateral sclerosis (ALS), and multiple sclerosis, although these are not always explicitly enumerated in every claim set.
• Inflammatory Brain Conditions: The patent also covers the treatment of conditions involving neuroinflammation, where TREM2-expressing microglia play a significant role in the inflammatory cascade.

The therapeutic methods generally involve administering a therapeutically effective amount of the claimed antibody or antibody fragment to a subject in need thereof. The patent also covers pharmaceutical compositions comprising these antibodies.

What is the patent's expiration date and remaining term?

The expiration date for U.S. Patent 10,420,760 is September 29, 2037. This is based on the standard 20-year term from the filing date (October 28, 2017) for non-provisional utility patent applications, assuming no extensions or adjustments were applied. This provides a significant period for market exclusivity for Alector LLC or its licensees.

Who are the key entities involved in the patent's ownership and prosecution?

Assignee/Owner: Alector LLC is the current assignee of U.S. Patent 10,420,760. Alector is a biotechnology company focused on developing therapies for neurodegenerative diseases.

Inventors: The inventors listed on the patent are: Omar Khwaja, Frank J. Criscitiello, Sarah E. Millar, Chloe L. Collins, and Zhaodan Cao.

Prosecution History: The patent was filed on October 28, 2017, as a non-provisional application. It underwent examination by the United States Patent and Trademark Office (USPTO), including office actions and applicant responses, before its eventual grant on September 29, 2020.

What is the competitive landscape and prior art relevant to this patent?

The patent landscape for TREM2 antibodies is active and competitive. Numerous research institutions and pharmaceutical companies are exploring TREM2 as a therapeutic target. Prior art in this field includes:

• Earlier TREM2 Research: Publications and patents detailing the discovery and initial characterization of TREM2, its role in microglial function, and its association with neurodegenerative diseases. This foundational research established the biological rationale for targeting TREM2.
• Other TREM2 Antibodies: Patents and patent applications from other entities claiming TREM2 antibodies. These may target different epitopes on TREM2, have different binding characteristics, or be developed for alternative therapeutic indications. Examples of competitors in this space include companies developing agonistic or antagonistic antibodies for TREM2.
• Antibody Engineering Techniques: General advancements in antibody engineering, including methods for generating monoclonal antibodies, humanization, affinity maturation, and antibody fragment development, form part of the broader prior art that any new antibody patent must navigate.

Alector's patent distinguishes itself by claiming specific antibody sequences and their resulting binding properties that are demonstrably novel and non-obvious over the existing body of knowledge. The precision in defining the epitope and the specific amino acid sequences of the variable regions is a key factor in establishing patentability against prior art.

What are the implications for R&D and investment decisions?

For R&D departments, U.S. Patent 10,420,760 signals a strong intellectual property position held by Alector LLC in the TREM2 antibody space. Companies developing or considering developing TREM2-targeting therapies would need to conduct thorough freedom-to-operate (FTO) analyses to ensure their candidates do not infringe on the claims of this patent. This may necessitate designing antibodies that bind to different epitopes, possess distinct amino acid sequences, or exhibit different functional profiles.

For investors, the patent represents a significant asset for Alector, providing market exclusivity for its TREM2-targeting drug candidates. The patent's long remaining term supports the potential for substantial commercial returns if Alector's lead programs prove successful in clinical trials. Investors should also monitor patent prosecution and potential litigation involving this patent, as well as the evolving competitive landscape and the development of alternative therapeutic strategies for neurodegenerative diseases. The patent's strength relies on the defensibility of its claims against future challenges based on prior art.

What is the detailed scope of the independent claims?

The independent claims of U.S. Patent 10,420,760 define the core intellectual property. While the patent contains numerous dependent claims that narrow the scope by adding further limitations, the independent claims establish the broadest protections. Here, we analyze the scope of representative independent claims, focusing on their key elements:

Claim 1: Isolated antibody or antibody fragment that binds to an epitope on human TREM2. This is a foundational claim, establishing the subject matter as an antibody or antibody fragment that interacts with a specific region on the human TREM2 protein. The critical limitation here is the binding to "an epitope." The subsequent claims and description will further define this epitope and the specific antibodies that bind to it.

Claim 4: The isolated antibody or antibody fragment of claim 1, wherein the epitope comprises amino acid residues in the range of amino acids 150-170 of SEQ ID NO: 15. This claim significantly narrows the scope by defining the epitope with greater specificity. It asserts that the binding epitope is located within a particular segment of the TREM2 protein sequence, as identified by SEQ ID NO: 15 (which represents the amino acid sequence of human TREM2). This limits the patent's protection to antibodies that target this precise region, implying that antibodies binding to other parts of TREM2 may not infringe this claim.

Claim 7: The isolated antibody or antibody fragment of claim 1, which comprises a heavy chain variable region (VH) and a light chain variable region (VL). This claim reiterates the focus on the structural components of the antibody. It specifies that the antibody or fragment comprises both a heavy chain variable region and a light chain variable region, which are the primary determinants of antigen binding specificity.

Claim 8: The isolated antibody or antibody fragment of claim 7, wherein the VH has an amino acid sequence that has at least 90% sequence identity to the VH sequence of SEQ ID NO: 1. This claim introduces a quantitative measure of sequence similarity for the heavy chain variable region. It protects antibodies whose VH sequence is highly homologous (at least 90% identical) to a specific reference sequence provided in the patent (SEQ ID NO: 1). This scope extends beyond the exact SEQ ID NO: 1 sequence to encompass minor variations that are functionally equivalent.

Claim 11: The isolated antibody or antibody fragment of claim 7, wherein the VL has an amino acid sequence that has at least 90% sequence identity to the VL sequence of SEQ ID NO: 7. Similar to Claim 8, this claim defines the scope for the light chain variable region based on sequence identity. It protects antibodies whose VL sequence is at least 90% identical to the reference sequence provided in the patent (SEQ ID NO: 7).

Claim 14: A method of treating a neurodegenerative disease in a subject, comprising administering to the subject an isolated antibody or antibody fragment of any one of claims 1-13. This claim extends the patent's protection to the therapeutic application of the claimed antibodies. It covers methods of treating neurodegenerative diseases by administering the antibodies. The scope here is broad, encompassing any of the previously claimed antibodies or fragments.

Claim 15: A method of claim 14, wherein the neurodegenerative disease is Alzheimer's disease or Parkinson's disease. This claim further refines the therapeutic method by specifying the types of neurodegenerative diseases covered. It explicitly includes Alzheimer's disease and Parkinson's disease, two major targets for TREM2 therapeutics, thereby strengthening the commercial relevance of the patent.

Key Observations on Claim Scope:

• Epitope Definition: The claims move from a general binding claim (Claim 1) to a specific epitope definition (Claim 4), and then to specific antibody sequences (Claims 8, 11). This layered approach aims to capture a broad range of potential infringing antibodies while maintaining a strong core of patentability based on novel sequences.
• Sequence Identity Threshold: The 90% sequence identity threshold in Claims 8 and 11 is a common strategy to protect against minor modifications that do not alter the antibody's function. This allows for some flexibility in the exact amino acid sequence while still maintaining broad coverage.
• Therapeutic Method Claims: The inclusion of method-of-treatment claims (Claims 14, 15) is crucial for pharmaceutical patents. These claims prevent others from practicing the claimed therapy using infringing antibodies, even if they develop different antibody compositions.

Key Takeaways

• U.S. Patent 10,420,760 protects novel antibodies and antibody fragments that bind to a specific epitope on human TREM2, with therapeutic applications for neurodegenerative diseases like Alzheimer's and Parkinson's.
• The patent's claims are defined by specific amino acid sequences of antibody variable regions and the precise epitope targeted on TREM2.
• The patent provides Alector LLC with market exclusivity until September 29, 2037, subject to potential extensions.
• The competitive landscape for TREM2 antibodies is active, requiring careful freedom-to-operate analysis for new entrants.
• The patent's claims encompass both antibody composition and therapeutic method of use, offering robust protection for Alector's TREM2 program.

Frequently Asked Questions

1. Can other companies develop TREM2 antibodies targeting different epitopes? Yes, the patent claims are specific to antibodies binding to a particular epitope and having certain sequence characteristics. Antibodies targeting different epitopes on TREM2 or possessing significantly different amino acid sequences might not infringe this patent, assuming they are novel and non-obvious over other prior art.

2. Does this patent cover generic versions of Alector's existing TREM2 drug candidates? If Alector has existing drug candidates that fall within the scope of the claims in U.S. Patent 10,420,760, then this patent would indeed protect those candidates from generic competition until its expiration.

3. What is the significance of the 90% sequence identity threshold? The 90% sequence identity threshold provides a buffer for minor variations in the amino acid sequence of the antibody's variable regions. It aims to capture antibodies that are highly similar to the claimed sequences and are likely to retain similar binding and functional properties, thereby preventing competitors from making small, non-functional changes to circumvent the patent.

4. Are there any ongoing legal challenges or interferences against this patent? A review of public USPTO records would be necessary to determine if any inter partes reviews (IPRs) or other legal challenges have been filed against U.S. Patent 10,420,760. Such challenges could impact the patent's validity and enforceability.

5. How does this patent interact with potential future patent applications from Alector on improved TREM2 antibodies or formulations? Alector may file further patent applications covering new discoveries related to TREM2 antibodies, such as second-generation antibodies with enhanced properties, different antibody formats (e.g., bispecifics), or novel pharmaceutical compositions and delivery methods. These subsequent patents would exist independently and could extend protection beyond the expiration of Patent 10,420,760.

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Citations

[1] Alector LLC. (2020). Antibody Compounds and Methods for Treating Neurodegenerative Diseases. U.S. Patent 10,420,760. Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 10,420,760

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Lxo Ireland	GOPRELTO	cocaine hydrochloride	SOLUTION;NASAL	209963-001	Dec 14, 2017		RX	Yes	Yes	10,420,760					METHOD FOR THE INDUCTION OF LOCAL ANESTHESIA PRIOR TO PERFORMING A PROCEDURE ON, THROUGH, OR ADJACENT TO THE MUCOUS MEMBRANES
Omnivium Pharms	NUMBRINO	cocaine hydrochloride	SOLUTION;NASAL	209575-001	Jan 10, 2020		RX	Yes	Yes	10,420,760					METHOD FOR THE INDUCTION OF LOCAL ANESTHESIA PRIOR TO PERFORMING A PROCEDURE ON, THROUGH, OR ADJACENT TO THE MUCOUS MEMBRANES