Massachusetts Patent of the Month – January 2026

Patent Recognition and Overview

Patent Identification and Award

This report provides an exhaustive technical and economic analysis of United States Patent No. 12,528,767, titled “HDAC6 inhibitors and uses thereof.” Applied for on July 30, 2020, and formally granted on January 20, 2026, this intellectual property is assigned to Eikonizo Therapeutics, Inc., a biotechnology firm based in Cambridge, Massachusetts. In a significant validation of its technological novelty and commercial potential, this patent has been awarded the prestigious Massachusetts Patent of the Month. This distinction was not conferred through a traditional subjective review process but was identified through a rigorous, data-driven selection mechanism utilizing advanced Artificial Intelligence (AI) technology. The AI algorithms screened over 1,000 potential patents granted within the jurisdiction during the relevant period, evaluating them on metrics such as claim breadth, citation velocity, technological complexity, and potential for forward innovation.

Basis for Selection: Real-World Impact

The selection of Patent 12,528,767 as the Massachusetts Patent of the Month underscores its profound real-world impact. While many patents represent incremental improvements in industrial processes or software algorithms, this invention addresses a critical and unmet medical need: the treatment of devastating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s Disease (AD), and Parkinson’s Disease (PD). The AI-driven selection criteria prioritized this patent because it offers a viable solution to the historic “selectivity vs. permeability” paradox that has plagued Central Nervous System (CNS) drug discovery for decades. By engineering a small molecule that is both highly selective for the Histone Deacetylase 6 (HDAC6) enzyme and sufficiently brain-penetrant to reach therapeutic concentrations, Eikonizo Therapeutics has created a platform that transitions from palliative symptom management to potential disease modification. The “real-world impact” recognized by this award is measured in the potential to extend human life, reduce the trillion-dollar global economic burden of dementia, and provide a verified pathway for future drug development in the challenging landscape of medicinal chemistry.

The Biological Imperative: Why HDAC6?

To understand the superiority of the invention described in Patent 12,528,767, one must first appreciate the biological context. Histone Deacetylases (HDACs) are a class of enzymes that remove acetyl groups from proteins. While the name implies they act on histones (DNA packaging proteins), HDAC6 is unique among the 18 known isoforms because it is primarily cytoplasmic and acts on non-histone substrates. The most critical of these substrates is alpha-tubulin, a structural component of microtubules.

The Role of Microtubules and Axonal Transport

Microtubules act as the “railway tracks” of the cell, essential for the transport of mitochondria, proteins, and vesicles. This function is vital in neurons, which possess long axons extending up to a meter in length. Efficient transport is required to supply the synapse with energy and to remove waste products.

• Acetylation as a Traffic Signal: Acetylation of alpha-tubulin stabilizes microtubules and facilitates the binding of motor proteins like kinesin and dynein. High levels of acetylation promote efficient transport.
• The Disease State: In neurodegenerative diseases, HDAC6 becomes overactive or dysregulated. It strips acetyl groups from tubulin, destabilizing the microtubules and disrupting axonal transport. This “traffic jam” leads to synaptic starvation and the accumulation of toxic waste.

Proteostasis and Aggregate Clearance

HDAC6 also possesses a ubiquitin-binding zinc finger domain (ZnF-UBP), allowing it to bind to poly-ubiquitinated misfolded proteins. It acts as a bridge, linking these toxic aggregates to the dynein motor complex for transport to the aggressive (the cell’s trash compactor) for degradation—a process known as autophagy.

• The Therapeutic Hypothesis: By inhibiting the deacetylase activity of HDAC6, one can restore tubulin acetylation (fixing the tracks) while maintaining the enzyme’s ability to clear aggregates (taking out the trash). This dual mechanism—improving transport and enhancing clearance of toxic proteins like Tau and SOD1—is the “holy grail” for treating proteinopathies like Alzheimer’s and ALS.

Technological Superiority of Patent 12,528,767

The pharmaceutical industry has struggled for years to harness HDAC6 inhibition. Patent 12,528,767 represents a breakthrough because it solves the structural flaws of previous generations.

Structural Innovation: The Bidentate Binding Mode

The core innovation disclosed in the patent lies in the medicinal chemistry of the zinc-binding group (ZBG).

• The Limitation of Predecessors: Many early HDAC inhibitors utilized a “monodentate” binding mode, where the molecule’s hydroxamic acid group coordinated with the active site zinc ion using a single oxygen atom. While effective for some HDACs, this mode is less stable and contributes to rapid drug dissociation (short residence time).
• The Eikonizo Solution: The compounds described in Patent 12,528,767 are engineered to engage the zinc ion in a canonical bidentate hydroxamate-Zn2+ coordination. Both oxygen atoms of the hydroxamate group bind to the zinc.
• The Result: This creates a significantly tighter binding affinity and a longer residence time on the target. A drug that stays bound longer can be dosed at lower concentrations, reducing systemic exposure and the risk of side effects. Structural studies cited in the broader scientific literature regarding these compounds confirm that this bidentate mode is crucial for the high potency observed.

Optimization for Brain Penetrance (BBB Permeability)

The Blood-Brain Barrier (BBB) is a formidable defense that excludes 98% of small molecule drugs.

• Competitor Failure: Many selective HDAC6 inhibitors developed by competitors (e.g., Ricolinostat/RGN-259) are excellent drugs peripherally but fail to cross the BBB in sufficient quantities. They are substrates for P-glycoprotein (P-gp) efflux pumps, which actively pump the drug back into the bloodstream.
• Patent ‘767 Superiority: The inventors of Patent 12,528,767 (Wagner, Hooker, Ouellet) utilized a sophisticated design strategy involving the optimization of the “cap” group—the part of the molecule that sits at the entrance of the enzyme tunnel. By carefully tuning the lipophilicity (LogP) and Topological Polar Surface Area (TPSA), they created molecules that are highly permeable and are not substrates for efflux pumps.
• Evidence: This is validated by the development of [18F]EKZ-001 (Bavarostat), a radiotracer derived from this patent. First-in-human PET studies demonstrated high uptake of this tracer in the human brain, specifically in the hippocampus and cortex, proving that the chemical scaffold can effectively penetrate the CNS.

Extreme Selectivity: The Safety Advantage

Early “Pan-HDAC” inhibitors (like Vorinostat) inhibit Class I HDACs (1, 2, 3) alongside HDAC6. Inhibition of Class I HDACs is toxic, causing thrombocytopenia (low platelets), fatigue, and gastrointestinal distress because these enzymes are essential for normal cell proliferation and gene expression.

• The Benchmark: The compounds in Patent 12,528,767 exhibit >16,000-fold selectivity for HDAC6 over HDAC1, HDAC2, and HDAC3.
• The Mechanism: This selectivity is achieved through the steric bulk of the “cap” group. The entrance to the catalytic tunnel of HDAC6 is wider than that of Class I HDACs. The Eikonizo compounds are designed with a bulky cap that fits into the HDAC6 entrance but physically clashes with the narrower Class I entrances, effectively “locking out” the drug from the off-targets. This ensures the drug can be taken chronically for years—a requirement for neurodegenerative disease—without the toxicity of chemotherapy-like agents.

Competitive Benchmarking

To rigorously demonstrate the superiority of the technology, we benchmark Patent 12,528,767 against the leading competitors in the field.

Comparative Analysis: Regenacy Pharmaceuticals

Regenacy Pharmaceuticals is a strong competitor with a mature clinical pipeline. Their lead asset, Ricolinostat, has shown efficacy in diabetic peripheral neuropathy and chemotherapy-induced peripheral neuropathy.

• The Gap: However, Ricolinostat was not originally designed as a brain-penetrant molecule. While it has some permeability, it does not achieve the high Brain/Plasma ratio required to saturate HDAC6 in the deep structures of the brain (like the hippocampus) without exposing the rest of the body to very high drug levels.
• The Superiority: Patent 12,528,767 specifically addresses this gap. Eikonizo’s data indicates that their compounds (e.g., EKZ-102) can restore axonal transport in motor neurons at lower doses due to higher local concentration in the CNS. This makes the Patent ‘767 technology far superior for central neurodegeneration (ALS, AD), whereas Regenacy’s technology is superior for peripheral nerve damage.

Comparative Analysis: Chong Kun Dang (CKD)

CKD-510 is another selective HDAC6 inhibitor, recently licensed to Novartis for significant sums, highlighting the value of the target.

• The Gap: CKD-510 is primarily positioned for Charcot-Marie-Tooth (CMT) disease, a genetic disorder of the peripheral nervous system, and potential cardiovascular indications (Atrial Fibrillation).
• The Superiority: Eikonizo’s patent portfolio and published research demonstrate a specific focus on “Tauopathies.” The chemical structure of the Patent ‘767 compounds was optimized using CNS Multi-Parameter Optimization (MPO) scores to ensure they could treat Alzheimer’s type Tau pathology. While CKD-510 is a potent molecule, Eikonizo’s technology is purpose-built for the specific physicochemical challenges of the Alzheimer’s brain.

Real-World Impact and Potential

The “Massachusetts Patent of the Month” award recognizes that the impact of this patent extends beyond the laboratory.

Immediate Clinical Impact: The “Theranostic” Approach

One of the greatest failures in Alzheimer’s drug development has been the inability to prove “Target Engagement.” Many drugs failed in Phase 3 because scientists never knew if the drug actually hit the target in the patient’s brain.

• The Diagnostic Breakthrough: Patent 12,528,767 has enabled the creation of [18F]EKZ-001, a PET radiotracer. This tool allows researchers to visualize HDAC6 levels in living patients.
• Real-World Consequence: This allows for “Patient Stratification.” Clinical trials can now recruit only those patients who have high levels of HDAC6 (and thus are most likely to respond to the drug). This significantly increases the probability of trial success, potentially accelerating the approval of life-saving medicines by years.

Therapeutic Potential: Disease Modification in ALS and AD

Current treatments for ALS (Riluzole, Edaravone) extend life by only a few months. Current treatments for Alzheimer’s (Donepezil) treat symptoms but do not stop the dying of neurons.

• The Promise: The mechanism utilized by Patent 12,528,767—restoring axonal transport—addresses the root cause of neuronal death. Preclinical data in SOD1 mice (an ALS model) showed that compounds from this series could improve motor function and reduce muscle atrophy.
• Future Impact: If these results translate to humans, this technology could turn ALS from a rapidly fatal diagnosis into a manageable chronic condition, similar to how HIV is treated today. For Alzheimer’s, delaying onset by even 5 years would reduce the prevalence of the disease by 50%, saving the US healthcare system hundreds of billions of dollars.

Expansion to Other Indications

• Parkinson’s Disease: Recent grant funding (SBIR) indicates Eikonizo is applying this technology to Parkinson’s. HDAC6 inhibition aids in the clearance of alpha-synuclein aggregates (Lewy bodies), the hallmark of PD.
• Cardiorenal Disease: While the patent focuses on CNS, the chemical scaffold can be modified to prevent BBB crossing. Eikonizo is exploring these “peripherally restricted” analogs for Polycystic Kidney Disease (PKD) and Heart Failure, where HDAC6 contributes to cyst growth and cardiac fibrosis. This represents a massive secondary market for the invention.

R&D Tax Credit Analysis: The Four-Part Test

The development of the technology described in Patent 12,528,767 is a textbook example of “Qualified Research” eligible for the Research and Experimentation (R&D) Tax Credit under IRC Section 41. To claim this credit, a project must meet every component of the Four-Part Test. Below is a detailed analysis of how a project utilizing this patent technology satisfies these rigorous requirements.

Part 1: The Permitted Purpose Test

The Requirement: The research must intend to create a new or improved business component. This includes a product, process, computer software, technique, formula, or invention to be held for sale, lease, or license. The activity must relate to improving functionality, performance, reliability, or quality.

Application to Patent 12,528,767:

• Business Component: The “business components” are the novel chemical entities (NCEs) described in the patent—specifically the small molecule inhibitors (e.g., EKZ-102) and the diagnostic tracer ([18F]EKZ-001).
• New/Improved Functionality: The specific purpose of the research was to create a drug with improved bioavailability (CNS penetration) and improved safety (selectivity against Class I HDACs) compared to existing generic inhibitors like Vorinostat. The research was not for aesthetic purposes (like the color or taste of the pill) but for its functional therapeutic efficacy.
• Conclusion: The project unequivocally meets the Permitted Purpose test as it aims to develop a new pharmaceutical product with superior performance characteristics.

Part 2: The Technological in Nature Test

The Requirement: The research must fundamentally rely on principles of the “hard sciences”—physical or biological sciences, engineering, or computer science. It cannot be based on soft sciences like economics, psychology, or market research.

Application to Patent 12,528,767:

• Hard Sciences Involved: The development of these inhibitors relied on:
  • Synthetic Organic Chemistry: Designing and synthesizing complex molecular structures with specific zinc-binding capabilities.
  • Biochemistry: Conducting enzymatic assays to determine IC50 values and selectivity ratios (e.g., >16,000-fold selectivity).
  • Pharmacology & Neuroscience: Investigating the pharmacokinetics (PK) across the blood-brain barrier and pharmacodynamics (PD) in transgenic mouse models (SOD1, Tau).
• Evidence: The patent document itself is a compendium of hard science, detailing chemical synthesis routes, molecular formulas, and biological assay results.
• Conclusion: The activities utilize the principles of chemistry and biology, satisfying the Technological in Nature test.

Part 3: The Elimination of Uncertainty Test

The Requirement: The activity must be intended to discover information to eliminate technical uncertainty concerning the capability, method, or appropriate design of the business component. Uncertainty exists if the information available to the taxpayer does not establish the capability or method for achieving the result, or the appropriate design of that result.

Application to Patent 12,528,767:

• Uncertainty of Capability: At the outset, it was unknown if a small molecule could be designed that was both highly selective for HDAC6 and capable of crossing the BBB. Many prior attempts had failed (e.g., highly selective but impermeable, or permeable but toxic).
• Uncertainty of Design: The researchers faced uncertainty regarding the optimal chemical structure. Which “cap” group would provide the best fit for the enzyme entrance? What is the optimal linker length? The patent covers a genus of compounds, reflecting the investigation into finding the “appropriate design” among many possibilities.
• Uncertainty of Method: Developing the synthesis process for the radiotracer [18F]EKZ-001 involved uncertainty regarding the radio-fluorination step—specifically, how to incorporate the Fluorine-18 isotope rapidly and with high purity suitable for human injection.
• Conclusion: The project was defined by the attempt to resolve these fundamental technical uncertainties.

Part 4: The Process of Experimentation Test

The Requirement: Substantially all (at least 80%) of the activities must constitute a process of experimentation. This involves identifying a hypothesis, testing alternatives, and analyzing results (trial and error, modeling, simulation) to refine the design.

Application to Patent 12,528,767:

• Hypothesis Formulation: The inventors hypothesized that a bidentate zinc-binding group combined with a specific lipophilic cap would yield a superior inhibitor.
• Testing Alternatives: The research involved synthesizing hundreds of candidate molecules (iterative testing). Each molecule was screened in in vitro assays.
• Systematic Evaluation:
  • Step 1: Synthesize a variant.
  • Step 2: Test against HDAC6 and HDAC1 (Selectivity screen).
  • Step 3: If selective, test in microsomes for metabolic stability.
  • Step 4: If stable, test in animals for brain penetration.
• Refining the Design: Compounds that failed these steps were discarded (trial and error). Data from successful candidates (like EKZ-102) was used to further optimize the structure.
• Conclusion: The development cycle was a rigorous application of the scientific method, satisfying the Process of Experimentation test.

How Swanson Reed Can Help Claim the R&D Tax Credit

Swanson Reed, a specialist firm focused exclusively on R&D tax credits, offers a distinct advantage for high-tech companies like the assignee of Patent 12,528,767. The “Massachusetts Patent of the Month” award serves as a powerful indicator of innovation, but the IRS requires detailed substantiation to grant the credit.

Substantiation via AI Technology (TaxTrex)

The primary challenge in claiming the R&D credit is maintaining contemporaneous documentation. IRS auditors often disallow claims where the link between the expense (wages, supplies) and the specific research activity is weak.

• The TaxTrex Advantage: Swanson Reed utilizes TaxTrex, a proprietary AI-driven software platform.
• Application to Patent ‘767 Project:
  • Automated Data Collection: TaxTrex issues regular, automated surveys to the scientific staff (Inventors Wagner, Hooker, Ouellet) to capture time allocations to specific projects (e.g., “Project: CNS Penetrant HDAC6 Inhibitors”).
  • Time-Stamping: The system time-stamps these entries, providing indisputable proof that the documentation was created during the development process, not retroactively manufactured for an audit.
  • Natural Language Processing (NLP): The AI can analyze project descriptions and lab notes to automatically map them to the Four-Part Test criteria, ensuring that the “technical uncertainty” and “process of experimentation” are clearly articulated in the tax file.

Identifying Qualified Research Expenses (QREs)

Swanson Reed’s experts can help the company identify all eligible costs associated with the patent’s development:

• Wages: 100% of the taxable wages for the chemists and biologists directly performing the research, and their direct supervisors.
• Supplies: The cost of lab reagents, transgenic mice, cell lines, and chemical precursors used in the experiments.
• Contract Research: 65% of the payments made to third-party CROs (Contract Research Organizations) such as Nanosyn (for screening) or Charles River (for animal studies), provided the company retains the rights to the IP.
• Cloud Computing: Costs for AWS or Azure used to run molecular modeling simulations (computational chemistry) are also eligible.

Audit Defense and State-Specific Expertise

• Audit Readiness: Swanson Reed prepares every claim as if it will be audited. They employ a “6-Eye Review” process where every claim is reviewed by a Qualified Engineer, a Scientist, and a CPA/Enrolled Agent. For a high-profile patent like 12,528,767, they would construct a technical narrative leveraging the patent text itself to prove the “Technological in Nature” and “Uncertainty” tests were met.
• Massachusetts R&D Credit: As the patent assignee is based in Cambridge, MA, they are eligible for the Massachusetts State R&D Credit. Swanson Reed’s local presence ensures the company benefits from both Federal and State incentives, which have different calculation methods and carryforward rules.

Final Thoughts

US Patent No. 12,528,767 is more than a legal document; it is a blueprint for a potential cure for some of humanity’s most intractable diseases. Its recognition as the Massachusetts Patent of the Month is a testament to its technological sophistication and its potential to alleviate the suffering of millions of patients with ALS and Alzheimer’s.

By successfully engineering a molecule that overcomes the historical trade-off between selectivity and brain penetrance, Eikonizo Therapeutics has established a new benchmark in the field. The superiority of this technology over competitors like Regenacy and CKD is empirically grounded in the bidentate binding mode and the CNS-optimized structural design.

Furthermore, the development of this technology represents the ideal use case for the R&D Tax Credit. The rigorous scientific inquiry required to bring this patent to life perfectly aligns with the Four-Part Test. With the strategic assistance of Swanson Reed and their TaxTrex AI technology, the inventors can maximize the financial return on their innovation, ensuring that this vital research continues to progress from the lab bench to the patient’s bedside.