Anti-TDP-43 binding molecules and uses thereof
Inventors
SEREDENINA, TAMARA • Ziehm, Tamar Magdalena • Afroz, Tariq
Assignees
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Publication Number
US-12600766-B2
Publication Date
2026-04-14
Expiration Date
Abstract
The present invention is in the field of transactive response DNA binding protein with a molecular weight of 43 kDa (TARDB or also TDP-43). The invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or an antigen-binding fragment or a derivative thereof and uses thereof. The present invention provides means and methods to diagnose, prevent, alleviate and/or treat a disease, disorder and/or abnormality associated with TDP-43 aggregates including but not limited to Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Chronic Traumatic Encelopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE).
Core Innovation
The invention provides a TDP-43 binding molecule that binds misfolded aggregated TDP-43 and non-aggregated physiological TDP-43. The binding encompasses post-translationally modified and truncated forms of TDP-43, as well as aggregated and non-aggregated species, and the target includes TDP-43 regions or epitopes within human TDP-43 with enumerated amino acid residue ranges.
The binding molecules comprise specific antigen-binding regions, including VH-CDR1, VH-CDR2, and VH-CDR3, together with VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences. Multiple alternative sets of CDR amino acid sequences are provided, and the molecule may comprise a humanized antibody or an antigen-binding fragment thereof.
The document further includes nucleic acid embodiments encoding anti-TDP-43 antibody VH and VL sequences, and downstream composition and use language for immunoconjugates, detectable labels, diagnostic kits, pharmaceutical compositions, and therapeutic and immunodiagnostic uses for TDP-43 proteinopathies. The stated disease coverage includes ALS, FTD and spectrum, Alzheimer’s disease, Parkinson’s disease, Chronic Traumatic Encephalopathy, and limbic-predominant age-related TDP-43 encephalopathy.
Claims Coverage
The independent claim set covers three inventive features: the TDP-43 binding molecule, a pharmaceutical composition, and nucleic acid encoding embodiments.
TDP-43 binding molecule defined by specified VH/VL CDR sequences and humanized formats
A TDP-43 binding molecule that binds misfolded aggregated TDP-43 and non-aggregated physiological TDP-43, comprising specified VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences and specified VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences, with multiple alternative CDR combinations, or a humanized antibody or an antigen-binding fragment thereof.
Pharmaceutical composition comprising the TDP-43 binding molecule
A pharmaceutical composition including the TDP-43 binding molecule together with a pharmaceutically acceptable carrier or excipient.
Nucleic acid encoding anti-TDP-43 antibody VH and VL sequences
A nucleic acid molecule that either encodes the TDP-43 binding molecule or comprises nucleotide sequences encoding specified Heavy Chain Variable Region and Light Chain Variable Region sequences identified by SEQ ID numbers.
The claims center on a TDP-43 binding molecule defined by enumerated VH/VL CDR amino acid sequences, with humanized antibody or antigen-binding fragment scope, and extend to nucleic acid and pharmaceutical composition embodiments.
Stated Advantages
Blocks cell-to-cell propagation of TDP-43.
Disaggregates TDP-43 aggregates.
Inhibits TDP-43 seeding and aggregation.
Documented Applications
diagnostic kit use in TDP-43 proteinopathies, including frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, Chronic Traumatic Encephalopathy, and limbic-predominant age-related TDP-43 encephalopathy
therapeutic and immunodiagnostic uses for TDP-43 proteinopathies, including frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, Chronic Traumatic Encephalopathy, and limbic-predominant age-related TDP-43 encephalopathy
immunoconjugates and labeled antibodies for detection or diagnostic use related to TDP-43 proteinopathies
Diagnostics, classification, and monitoring using biofluid quantification and immunoassays, including ELISA and other immunoassay formats.
Therapeutic use cases including immunoconjugates, labeled antibodies, kits, and pharmaceutical compositions.
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