Invented by Kerry Louise Tyson, Terence Seward Baker, Georges MAIRET-COELLO, Patrick Downey, Jean-Philippe COURADE, David Edward Ormonde Knight, UCB Biopharma SRL

The market for Tau-binding antibodies has been gaining significant attention in recent years due to their potential in the treatment of neurodegenerative diseases, particularly Alzheimer’s disease. Tau proteins are known to play a crucial role in the formation of neurofibrillary tangles, which are one of the hallmarks of Alzheimer’s disease. By targeting and binding to these abnormal tau proteins, tau-binding antibodies have the potential to slow down or even halt the progression of the disease. Alzheimer’s disease affects millions of people worldwide, and with an aging population, the prevalence of the disease is expected to increase in the coming years. Currently, there are limited treatment options available for Alzheimer’s disease, and most of them only provide temporary relief from symptoms. Therefore, there is a significant unmet need for effective disease-modifying therapies that can target the underlying causes of the disease. Tau-binding antibodies offer a promising approach in this regard. These antibodies can specifically bind to abnormal tau proteins and prevent their aggregation into neurofibrillary tangles. By doing so, they can potentially reduce the toxic effects of tau pathology on brain cells and preserve cognitive function. Several pharmaceutical companies and research institutions are actively involved in the development of tau-binding antibodies. Some of the leading players in this market include Biogen, AbbVie, Eli Lilly, and Roche. These companies are investing heavily in research and development to identify and optimize tau-binding antibodies with high specificity and efficacy. Clinical trials evaluating the safety and efficacy of tau-binding antibodies are currently underway. Biogen’s aducanumab, an antibody targeting both beta-amyloid plaques and tau tangles, has shown promising results in early-stage clinical trials. The company is now conducting larger Phase III trials to further evaluate its potential as a disease-modifying therapy for Alzheimer’s disease. In addition to Alzheimer’s disease, tau-binding antibodies are also being explored for other tauopathies, such as progressive supranuclear palsy and frontotemporal dementia. These diseases are characterized by the accumulation of abnormal tau proteins in the brain and share some similarities with Alzheimer’s disease. Therefore, the market for tau-binding antibodies extends beyond Alzheimer’s disease and holds potential in addressing a broader range of neurodegenerative disorders. The market for tau-binding antibodies is expected to witness significant growth in the coming years. According to a report by Grand View Research, the global Alzheimer’s drugs market, which includes tau-targeting therapies, is projected to reach USD 12.7 billion by 2027. The increasing prevalence of Alzheimer’s disease, coupled with the growing demand for disease-modifying therapies, is driving the market growth. However, there are several challenges that need to be addressed for the successful development and commercialization of tau-binding antibodies. One of the key challenges is the delivery of these antibodies to the brain. The blood-brain barrier restricts the entry of large molecules, including antibodies, into the brain, making it difficult to achieve therapeutic concentrations. Researchers are exploring various strategies, such as the use of antibody fragments or conjugating antibodies with brain-penetrating molecules, to overcome this challenge. In conclusion, the market for tau-binding antibodies holds great promise in the field of neurodegenerative diseases, particularly Alzheimer’s disease. These antibodies have the potential to target and disrupt the formation of neurofibrillary tangles, which are a key pathological feature of the disease. With ongoing research and clinical trials, tau-binding antibodies may soon become a viable treatment option for Alzheimer’s disease and other tauopathies, providing hope for millions of patients worldwide.

The UCB Biopharma SRL invention works as follows

The present invention is a Tau-binding antibody and its binding fragments.

Background for Tau-binding antibodies

The diseases Alzheimer’s (AD) and Progressive supranuclear disease (PSP) have high unmet medical needs, high costs for health systems and high burdens for families. Clinical signs of AD include memory loss, cognitive impairment, emotional instability, and a lack of reasoning. PSP is characterized by serious gait and balance problems, vertical eye movement disturbances and cognitive issues. It can also cause depression, apathy and mild dementia. The late symptoms of PSP include blurred vision, uncontrolled eyes movements, slurred speeches, difficulty swallowing, and death.

For over a decade, AD disease modification programs targeted the amyloid beta-peptide using various mechanisms. The second hallmark of AD, intracellular Tau, has seen much less progress. “Neurofibrillary inclusions and tangles with hyperphosphorylated, aggregated Tau are the hallmarks of AD, as well as a number other tauopathies including PSP.

There is a strong correlation in these diseases between the progression of symptoms and the distribution and level of intraneural tau aggregates. Tau tangles in AD neurons first appear in transentorhinal cortex, and then spread to hippocampus or neocortex. The tangles seen in AD neurons are hyperphosphorylated insoluble Tau. “Direct toxic effects of pathological Tau species or loss of axonal transportation due to sequestration and hyperphosphorylation of functional Tau to hyperphosphorylated, aggregated forms that are no longer able to support axonal transit have been suggested to contribute to the illness.

The six main Tau isoforms, ranging in size from 352 to 441, are a result of alternative splicing. The N-terminal inserts of these isoforms are either zero, one, or two (0N,1N,2N), with three or four?repeat’ sequences at the C-terminal (3R or 4R). The repeat sequences at the C-terminus can be either three or four (3R, 4R). The Tau microtubule binding region (MTBR) is formed by the 30-32 amino acids C-terminal sequences R1, R2, and R3. Tau’s main function is thought to be the assembly and stabilization axonal cytoskeletal microtubules. Microtubules are used to form tracks that facilitate axonal transportation and cytoskeletal components for cell growth. (Clavaguera, et. al. Brain Pathology 23, 2013 342-349). Three Tau isoforms contain three microtubule-binding regions (MTBR).

Only mild or no effective treatments are available at this time for these diseases.” There is no treatment available to slow or stop the progression of the disease. There is a continuing need for new compositions and compounds that are useful in treating tauopathies.

The present invention aims to provide, inter alia, agents for diagnosing or treating tauopathies like Alzheimer’s disease or progressive supranuclear paralysis (PSP). The present invention also aims to provide methods for treating or diagnosing tauopathies, such as Alzheimer’s (AD) or Progressive supranuclear Palsy (PSP).

The independent claims are able to achieve these and other objectives, as will be apparent in the following description. The dependent claims are based on some of the specific aspects of embodiments of the invention contemplated in the present disclosure. The ensuing description may also contain other aspects or embodiments of the invention as contemplated in the present disclosure.

In a first aspect of the present disclosure, an isolated Tau binding antibody or binding fraction thereof is provided, wherein said Tau binding antibody or binding portion thereof includes

A light chain variable area comprising a CDR1 chosen from SEQ ID no. CDR2 from SEQ No. 2 or sequences that are at least 90% similar, and a CDR3 from SEQ ID no. : 3; or sequences that are at least 90% similar to them.

A heavy chain variable area comprising a CDR1 chosen from SEQ ID no. The sequences must be at least 90% similar. A CDR2 from SEQ No. 5 or sequences that are at least 90% similar, and a CDR3 from SEQ No. “6 or sequences that are at least 90% the same.

In a second aspect of the present disclosure, an isolated Tau binding antibody or binding fraction thereof is provided, wherein said Tau binding antibody or binding portion thereof includes

SEQ ID Number: 7 or sequences at least 80% identical to them, and/or” “7 or sequences that are at least 80% similar to them, and/or

SEQ ID No. “a heavy chain variable region comprising SEQ ID No.

In a third aspect of the present disclosure, an isolated Tau binding antibody or binding fraction thereof is provided, wherein said Tau binding antibody or binding portion thereof includes

SEQ ID Number: 9 or sequences at least 80% identical to them, and/or” “9 or sequences that are at least 80% similar to them, and/or”.

SEQ ID No. “10 or sequences that are at least 80% similar to them.

In a fourth aspect, the present disclosure discloses an isolated Tau binding antibody or binding fraction thereof. The Tau binding antibody or binding portion thereof comprises

SEQ ID Number: 13 or sequences at least 80% identical to them, and/or” “13 or sequences that are at least 80% similar to them, and/or”.

SEQ ID No. “16 or sequences that are at least 80% similar to them.

In a fifth aspect, the present disclosure discloses an isolated Tau binding antibody or binding fraction thereof. Said Tau binding antibody or binding component binds to amino acids 197-206 of SEQID NO: 55.

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