Anti-TDP-43 antibodies and uses thereof

Abstract

The present disclosure provides antibodies that specifically bind to human TDP-43 and methods of using these antibodies to treat patients with TDP-43-related diseases, including Amyotrophic Lateral Sclerosis (ALS).

Description

[0001] Attorney Docket Ref. No.: 50877-0006WO1 / / Client Ref: 792-PCT ANTI-TDP-43 ANTIBODIES AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application is claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 538,595, filed on September 15, 2023, the content of which is hereby incorporated by reference in its entirety. SEQUENCE LISTING This application contains a Sequence Listing that has been submitted electronically as an XML file named “50887-0006WO1.XML.” The XML file, created on August 27, 2024, is 106,496 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. TECHNICAL FIELD This disclosure relates to the technical fields of immunology and medicine. BACKGROUND Transactive response DNA binding protein 43 (“TDP-43”) is a predominantly nuclear protein that is involved in RNA splicing, trafficking, stabilization, and ultimately regulation of gene expression. TDP-43 is a nucleic acid binding protein containing two highly conserved nucleic acid recognition motifs and has been shown to form dimers and oligomers. While TDP- 43 is expressed ubiquitously in all cell types, it has been shown to be highly expressed in the neuroepithelium, which contains all CNS progenitors for neurons and glia. Moreover, TDP-43 has been shown to specifically bind numerous RNAs in neuronal cells. TDP-43 cytoplasmic aggregates (also known as inclusion bodies) are associated with several neurodegenerative diseases, disorders, or conditions. Specifically, TDP-43 cytoplasmic aggregates and / or misfolding of TDP-43 have been associated with neurodegenerative diseases including Amyotrophic Lateral Sclerosis (“ALS”), frontotemporal dementia (“FTD” or “FTLD- TDP-43”), limbic-predominant age-related TDP-43 encephalopathy (“LATE”), Alzheimer's disease, multisystem proteinopathy, and chronic traumatic encephalopathy. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT ALS is the most common motor neuron disorder in adults ultimately resulting in the loss of motor neurons that control voluntary muscles. ALS has an incidence of about 1-2 / 100,000 and a prevalence of about 4-6 / 100,000 cases each year. ALS results in the progressive degeneration of both upper and lower motor neurons which generally leads to death primarily due to respiratory failure in three to five years after diagnosis. Typical symptoms include stiff muscles, muscle twitches, gradual muscle weakness, and muscle wasting. Around half of all people suffering from ALS have difficulties thinking and / or behavioral symptoms and about 15% develop frontotemporal dementia. Pathologically, abnormal aggregations of TDP-43 protein are seen in up to 97% of ALS patients (Nguyen, H.P., et al., ALS Genes in the Genomic Era and their Implications for FTD, Trends in Genetics, 34(6): 404+423 (2018)). At present, there is no known cure for ALS. Thus, there is an unmet need for therapies that improve health status, including the risk of mortality and / or enhancing the quality of life in patients with TDP-43 related diseases, including ALS. SUMMARY The present disclosure relates to antibodies and antigen-binding antibody fragments that specifically bind to human TDP-43, compositions comprising these antibodies or antigen- binding antibody fragments, and methods of using these antibodies and antigen-binding antibody fragments to treat TDP-43 related diseases, including Amyotrophic Lateral Sclerosis (ALS). Thus, provided herein are isolated monoclonal antibodies that compete for binding to TDP-43 (e.g., human TDP-43) with: an antibody including a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain of SEQ ID NO: 24; an antibody including a heavy chain variable domain of SEQ ID NO: 63 and a light chain variable domain of SEQ ID NO: 65; an antibody including a heavy chain variable domain of SEQ ID NO: 67 and a light chain variable domain of SEQ ID NO: 69; an antibody including a heavy chain variable domain of SEQ ID NO: 71 and a light chain variable domain of SEQ ID NO: 73; an antibody including a heavy chain variable domain of SEQ ID NO: 75 and a light chain variable domain of SEQ ID NO: 77; or an antibody including a heavy chain variable domain of SEQ ID NO: 79 and a light chain variable domain of SEQ ID NO: 81. In some embodiments, the antibodies bind to the same epitope on TDP-43 (e.g., human TDP-43) as an antibody including a heavy chain variable domain of SEQ ID NO: 1 and a light Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT chain variable domain of SEQ ID NO: 24; an antibody including a heavy chain variable domain of SEQ ID NO: 63 and a light chain variable domain of SEQ ID NO: 65; an antibody including a heavy chain variable domain of SEQ ID NO: 67 and a light chain variable domain of SEQ ID NO: 69; an antibody including a heavy chain variable domain of SEQ ID NO: 71 and a light chain variable domain of SEQ ID NO: 73; an antibody including a heavy chain variable domain of SEQ ID NO: 75 and a light chain variable domain of SEQ ID NO: 77; or an antibody including a heavy chain variable domain of SEQ ID NO: 79 and a light chain variable domain of SEQ ID NO: 81. Also provided herein are antibodies that specifically bind to TDP-43 (e.g., human TDP- 43), including three light chain CDRs and three heavy chain CDRs of a mouse antibody characterized by a heavy chain variable domain including SEQ ID NO: 1 and a light chain variable domain including SEQ ID NO: 24. In some embodiments, the antibody is a humanized antibody, a chimeric antibody, or a veneered antibody. In some embodiments, the CDRs are of a definition selected from the group of Kabat, Chothia, Kabat / Chothia Composite, AbM, and Contact. In some embodiments, the antibody includes a humanized mature heavy variable domain including: a heavy chain CDR1 as defined by Kabat / Chothia Composite, including SEQ ID NO: 49; a heavy chain CDR2 as defined by Kabat, including SEQ ID NO: 51; and a heavy chain CDR3 as defined by Kabat or Chothia, including SEQ ID NO: 52; and a humanized mature light chain variable domain including the three Kabat light chain CDRs of SEQ ID NOs: 53-55. In some embodiments, the humanized mature heavy variable domain includes a sequence that is at least 80% identical to any one of SEQ ID NOs: 4-23 and the humanized mature light chain variable domain includes a sequence that is at least 80% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the humanized mature heavy variable domain includes a sequence that is at least 85% to any one of SEQ ID NOs: 4-23 and the humanized mature light chain variable region includes a sequence that is at least 85% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the humanized mature heavy variable domain includes a sequence that is at least 90% identical, to any one of SEQ ID NOs: 4-23 and the humanized mature light chain variable region includes a sequence that is at least 90% identical, to any one of SEQ ID NOs: 27-48. In some embodiments, the humanized mature heavy variable domain Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT includes a sequence that is at least 95% identical to any one of SEQ ID NOs: 4-23 and the humanized mature light chain variable domain includes a sequence that is at least 95% identical to any one of SEQ ID NOs: 27-48. In some embodiments, at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: K19 is occupied by R; S35 is occupied by G; T40 is occupied by A; E42 is occupied by G; A49 is occupied by S; K43 is occupied by E; R44 is occupied by G or D; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; L80 is occupied by A or G; L82c is occupied by G; M83 is occupied by R; S84 is occupied by A; M89 is occupied by V; or F91 is occupied by Y. In some embodiments, at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: K43 is occupied by E; R44 is occupied by G or D; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; or F91 is occupied by Y. In some embodiments, at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: S35 is occupied by G; L78 is occupied by A or G; L80 is occupied by A or G; or L82c is occupied by G. In some embodiments, F91 of the humanized heavy chain variable domain is occupied by Y; and at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: R44 is occupied by G; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; or M83 is occupied by R. In some embodiments, at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q; L9 is occupied by S; D17 is occupied by Q; Q18 is occupied by P; K39 is occupied by R; K45 is occupied by R; T80 is occupied by A or S; L83 is occupied by V; L92 is occupied by G or A; V94 is occupied by I or A; A100 is occupied by G, D, or R; or L104 is occupied by V. In some embodiments, at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q or A100 is occupied by D or R. In some embodiments, at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: L9 is occupied by S; T80 is occupied by A or S; L92 is occupied by G or A; or V94 is occupied by I or A. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT In some embodiments, V3 is occupied by Q; Q18 is occupied by P; A100 is occupied by D; and at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: T80 is occupied by A or L92 is occupied by A. In some embodiments, at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: L5 is occupied by V; G44 is occupied by R; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; M89 is occupied by V, or F91 is occupied by Y; and at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q; D17 is occupied by Q; Q18 is occupied by P; K39 is occupied by R; K45 is occupied by R; T80 is occupied by A; L83 is occupied by V; L92 is occupied by A; A100 is occupied by D; or L104 is occupied by V. In some embodiments, the humanized antibody has increased thermal stability as compared to a reference antibody including a heavy chain variable domain including SEQ ID NO: 1 and a light chain variable domain including SEQ ID NO: 24. In some embodiments, the humanized antibody has a melting temperature of 55°C or greater. Also provided herein are antibodies that specifically binds to TDP-43, including a heavy chain variable domain including: a heavy chain CDR1, as defined by Kabat / Chothia Composite, including SEQ ID NO: 49 or SEQ ID NO: 50; a heavy chain CDR2, as defined by Kabat, including SEQ ID NO: 51; a heavy chain CDR3, as defined by Kabat or Chothia, including SEQ ID NO: 52; a light chain CDR1, as defined by Kabat, including SEQ ID NO: 53; a light chain CDR2, as defined by Kabat, including SEQ ID NO: 54; and a light chain CDR3, as defined by Kabat, including one of SEQ ID NOs: 55-61. In some embodiments, the heavy chain CDR1, as defined by Kabat / Chothia Composite, includes SEQ ID NO: 49; the heavy chain CDR2, as defined by Kabat, includes SEQ ID NO: 51; the heavy chain CDR3, as defined by Kabat or Chothia, includes SEQ ID NO: 52; the light chain CDR1, as defined by Kabat, includes SEQ ID NO: 53; the light chain CDR2, as defined by Kabat, includes SEQ ID NO: 54; and the light chain CDR3, as defined by Kabat, includes SEQ ID NO: 55 or SEQ ID NO: 61. In some embodiments, the heavy chain variable domain includes a sequence that is at least 95% identical to any one of SEQ ID NOs: 4-23. In some embodiments, the heavy chain Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT variable domain includes a sequence that is at least 95% identical to any one of: SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 23. In some embodiments, the heavy chain variable domain includes a sequence that is at least 98% identical to any one of: SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 23. In some embodiments, the heavy chain variable domain includes a sequence of SEQ ID NO: 20. In some embodiments, the heavy chain variable domain includes a sequence of SEQ ID NO: 21. In some embodiments, the heavy chain variable domain includes a sequence of SEQ ID NO: 23. In some embodiments, the light chain variable domain includes a sequence that is at least 95% identical to any one of: SEQ ID NOs: 27-48. In some embodiments, the light chain variable domain includes a sequence that is at least 95% identical to SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, the light chain variable domain includes a sequence that is at least 98% identical to SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, the light chain variable domain includes SEQ ID NO: 47. In some embodiments, the light chain variable domain includes SEQ ID NO: 48. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 84; a heavy chain CDR2 including SEQ ID NO: 85; a heavy chain CDR3 including SEQ ID NO: 86; a light chain CDR1 including SEQ ID NO: 87; a light chain CDR2 including SEQ ID NO: 88; and a light chain CDR3 including SEQ ID NO: 89. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 63. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 63. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 63. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 65. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 65. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 65. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 90; a heavy chain CDR2 including SEQ ID NO: 91; a heavy chain CDR3 Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT including SEQ ID NO: 92; a light chain CDR1 including SEQ ID NO: 93; a light chain CDR2 including SEQ ID NO: 94; and a light chain CDR3 including SEQ ID NO: 95. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 67. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 67. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 67. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 69. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 69. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 69. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 96; a heavy chain CDR2 including SEQ ID NO: 97; a heavy chain CDR3 including SEQ ID NO: 98; a light chain CDR1 including SEQ ID NO: 99; a light chain CDR2 including SEQ ID NO: 100; and a light chain CDR3 including SEQ ID NO: 101. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 71. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 71. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 71. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 73. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 73. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 73. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 102; a heavy chain CDR2 including SEQ ID NO: 103; a heavy chain CDR3 including SEQ ID NO: 104; a light chain CDR1 including SEQ ID NO: 105; a light chain CDR2 including SEQ ID NO: 106; and a light chain CDR3 including SEQ ID NO: 107. In some embodiment, the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 75. In some embodiments, the heavy chain variable domain Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT comprises a sequence that is at least 98% identical to SEQ ID NO: 75. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 75. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 77. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 77. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 77. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 108; a heavy chain CDR2 including SEQ ID NO: 109; a heavy chain CDR3 including SEQ ID NO: 110; a light chain CDR1 including SEQ ID NO: 111; a light chain CDR2 including SEQ ID NO: 112; and a light chain CDR3 including SEQ ID NO: 113. In some embodiments, the heavy chain variable domain comprises a sequence at least 95% identical to SEQ ID NO: 79. In some embodiments, the heavy chain variable domain comprises a sequence at least 98% identical to SEQ ID NO: 79. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 79. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 81. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 81. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 81. In some embodiments, the antibody is a humanized antibody, a chimeric antibody, or a veneered antibody. In some embodiments, the antibody is an antigen-binding antibody fragment. In some embodiments, the antigen-binding antibody fragment is a Fab fragment, a Fab’2 fragment, or a single chain Fv. In some embodiments, the antibody is an intact antibody. In some embodiments, the antibody has a human IgG1 isotype. In some embodiments, the heavy chain variable domain is fused to a heavy chain constant region and the light chain variable domain is fused to a light chain constant region. In some embodiments, the heavy chain constant region is a mutant form of a natural human heavy chain constant region which has reduced binding to an Fcγ receptor relative to the natural heavy chain constant region. In some embodiments, the heavy chain constant region is of IgG1 isotype. In some embodiments, the antibody has at least one mutation in a constant region. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT In some embodiments, the at least one mutation reduces complement fixation or activation by the constant region. In some embodiments, the at least one mutation is at one or more positions of: 241, 264, 265, 270, 296, 297, 318, 320, 322, 329, and 331 by EU numbering. In some embodiments, the antibody has an alanine at positions 318, 320, and 322 by EU numbering. In some embodiments, the antibody selectively binds to phosphorylated TDP-43 (e.g., phosphorylated human TDP-43). In some embodiments, the antibody selectively binds to phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) as compared to unphosphorylated TDP-43 (e.g., unphosphorylated human TDP-43). In some embodiments, the antibody binds to phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) with at least 100-fold greater affinity as compared to unphosphorylated TDP-43 (e.g., unphosphorylated human TDP-43). In some embodiments, the antibody binds to phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) with at least 1000-fold greater affinity as compared to unphosphorylated TDP-43 (e.g., unphosphorylated human TDP-43). In some embodiments, phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) includes phosphorylation of at least one amino acid residue selected from S409 and S410. In some embodiments, phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) includes phosphorylation of both S409 and S410. In some embodiments, the antibody selectively binds to cytoplasmic aggregates of TDP- 43 (e.g., cytoplasmic aggregates of human TDP-43). In some embodiments, the antibody selectively binds to cytoplasmic aggregates of TDP-43 (e.g., cytoplasmic aggregates of human TDP-43) compared to nuclear TDP-43 (e.g., nuclear human TDP-43). In some embodiments, the cytoplasmic aggregates of TDP-43 include phosphorylated aggregates of TDP-43 (e.g., phosphorylated aggregates of human TDP-43). In some embodiments, the antibody does not substantially bind unphosphorylated TDP-43 (e.g., unphosphorylated human TDP-43). In some embodiments, the antibody is conjugated to a therapeutic, cytotoxic, cytostatic, immunomodulatory, neurotrophic, or neuroprotective agent. Also provided herein are pharmaceutical compositions including any of the antibodies described herein and a pharmaceutically acceptable carrier. Also provided herein are nucleic acids encoding the heavy chain variable domain and / or the light chain variable domain of any of the antibodies described herein. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT Also provided herein are vectors including a nucleic acid encoding a mature heavy chain variable domain and a light chain variable domain operably linked to one or more regulatory sequences to effect expression in a mammalian cell of any one of the antibodies described herein. In some embodiments, the one or more regulatory sequences include one or more of a enhancer, ribosome binding site, transcription termination signal, and promoter, optionally, where the promoter is a eukaryotic promoter. In some embodiments, the nucleic acid is codon- optimized for expression in a host cell. Also provided herein are host cells transformed with any of the vectors described herein. Also provided herein are host cells including any of the nucleic acids described herein. Also provided herein are methods of inhibiting or reducing aggregation of TDP-43 (e.g., human TDP-43) in a subject having or at risk of developing a TDP-43-related disease, including administering to the subject an effective amount of any of the antibodies described herein, thereby inhibiting or reducing aggregation of TDP-43 (e.g., human TDP-43) in the subject. Also provided herein are methods of treating or effecting prophylaxis of a TDP-43- related disease in a subject, including administering a therapeutically effective amount of any of the antibodies described herein thereby treating or effecting prophylaxis of the TDP-43- associated disease. In some embodiments, the TDP-43-related disease is amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD-TDP), primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease. In some embodiments, the TDP-43-related disease is ALS. Also provided herein are methods of detecting TDP-43 deposits (e.g., human TDP-43 deposits) in a subject having or at risk of developing a TDP-43-related disease, including administering to a subject any of the antibodies described herein, and detecting the antibody bound to TDP-43 in the subject. In some embodiments, the antibody is administered by intravenous injection into the body of the subject. Also provided herein are methods of detecting TDP-43 in a sample obtained from a patient having or at risk of developing a TDP-43 related disease, including detecting any of the antibodies described herein bound to TDP-43 in the sample. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT In some embodiments, the antibody is labeled. In some embodiments, the antibody is labeled with a fluorescent label, a paramagnetic label, or a radioactive label. In some embodiments, the radioactive label is detected using positron emission tomography (PET) or single-photon emission computed tomography (SPECT). All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, patent application, or item of information was specifically and individually indicated to be incorporated by reference. To the extent publications, patents, patent applications, and items of information incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material. Where values are described in terms of ranges, it should be understood that the description includes the disclosure of all possible sub-ranges within such ranges, as well as specific numerical values that fall within such ranges irrespective of whether a specific numerical value or specific sub-range is expressly stated. BRIEF DESCRIPTION OF THE DRAWINGS The following drawings illustrate certain embodiments of the features and advantages of this disclosure. These embodiments are not intended to limit the scope of the appended claims in any manner. Like reference symbols in the drawings indicate like elements. Figure 1 shows an annotated version of the murine antibody 13D3 heavy chain variable domain. Figure 2 shows an annotated version of the murine antibody 13D3 light chain variable domain. Figure 3 is a graph showing binding data of chimeric 13D3 antibody and humanized versions thereof to phosphorylated human TDP-43 peptide. Figure 4 is a graph showing binding data of chimeric 13D3 antibody and humanized versions thereof to phosphorylated human TDP-43 peptide. Figure 5 is a graph showing binding data of a humanized version of 13D3 antibody, hu13D2Hd5Ld2, to phosphorylated human TDP-43 peptide. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT Figures 6A-C show immunohistochemical images of frontotemporal dementia (“FTD”) brain tissue (Figs. 6A and 6B) and healthy brain tissue (Fig. 6C) stained with the 13D3 antibody. Fig. 6B is an inset of Fig. 6A showing co-localization of 13D3 antibody with phosphorylated human TDP-43 FTD-associated neuronal cytoplasmic aggregates. Figures 7A-C are immunohistochemical images of brain tissue from a rNLS8 dox- suppressible model of TDP-43 proteinopathy stained with the 13D3 antibody. The data show that the 13D3 antibody binds cytoplasmic aggregates in a rNLS8 dox-suppressible model of TDP-43 proteinopathy. Figures 8A-C show the results of HEK cells transfected with GFP-2a-TDP43 or GFP only. Figure 8A shows staining for pTDP-43, GFP, and nuclei in the transfected cells. Figure 8B is a graph showing cell count. Figure 8C shows immunohistochemical images of HEK cells that show the ability of antibodies 13D3, 13C13, and 2D4 to detect overexpressed mislocalized human TDP-43 in HEK cells. DETAILED DESCRIPTION This disclosure provides antibodies and antigen-binding antibody fragments that specifically bind TDP-43 (e.g., human TDP-43) or aggregates of TDP-43 (e.g., aggregates of human TDP-43). Also provided are pharmaceutical compositions including these antibodies or antigen-binding antibody fragments and a pharmaceutically acceptable carrier, nucleic acids and / or vectors encoding these antibodies or antigen-binding antibody fragments, and host cells expressing the aforementioned nucleic acids and / or vectors. Thus, provided herein are isolated monoclonal antibody that competes for binding to TDP-43 (e.g., human TDP-43) with: an antibody comprising a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain of SEQ ID NO: 24; an antibody comprising a heavy chain variable domain of SEQ ID NO: 63 and a light chain variable domain of SEQ ID NO: 65; an antibody comprising a heavy chain variable domain of SEQ ID NO: 67 and a light chain variable domain of SEQ ID NO: 69; an antibody comprising a heavy chain variable domain of SEQ ID NO: 71 and a light chain variable domain of SEQ ID NO: 73; an antibody comprising a heavy chain variable domain of SEQ ID NO: 75 and a light chain variable domain of SEQ ID NO: 77; or an antibody comprising a heavy chain variable domain of SEQ ID NO: 79 and a light chain variable domain of SEQ ID NO: 81. In some embodiments, the monoclonal Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT antibody is a humanized antibody. Thus, also provided herein are antibodies comprising a humanized mature heavy variable domain comprising a sequence of any one of SEQ ID NOs: 4- 23 and a humanized mature light chain variable domain comprising a sequence of any one of SEQ ID NOs: 27-48. Additionally, any of the antibodies, antigen-binding antibody fragments, and compositions described herein can be used to treat a TDP-43-related disease. Thus, provided herein are method of inhibiting or reducing aggregation of TDP-43 in a subject having or at risk of developing a TDP-43-related disease, comprising administering to the subject an effective amount of any of the antibodies described herein, thereby inhibiting or reducing aggregation of TDP-43 in the subject. Also provided herein are methods of treating or effecting prophylaxis of a TDP-43-related disease in a subject, comprising administering a therapeutically effective amount of any of the antibodies described herein, thereby treating or effecting prophylaxis of the TDP-43-associated disease I. Definitions The term “antibody” includes intact antibodies and antigen-binding fragments thereof. Typically, fragments compete with the intact antibody from which they were derived for specific binding to the target including separate heavy chains, light chains Fab, Fab', F(ab')2, F(ab)c, Dabs, nanobodies, and Fv. Fragments can be produced by recombinant DNA techniques, or by enzymatic or chemical separation of intact immunoglobulins. The term “antibody” also includes a bispecific or multispecific antibody and / or a humanized antibody. A bispecific or bifunctional or multifunctional antibody is an artificial hybrid antibody having two or more different heavy / light chain pairs and two or more different binding sites (see, e.g., Songsivilai and Lachmann, Clin. Exp. Immunol., 79:315-321 (1990); Kostelny et al., J. Immunol., 148:1547-53 (1992)). The term “epitope” refers to a site on an antigen to which an antibody binds. An epitope can be formed from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of one or more proteins. Epitopes formed from contiguous amino acids (also known as linear epitopes) are typically retained on exposure to denaturing solvents whereas epitopes formed by tertiary folding (also known as conformational epitopes) are typically lost on treatment with denaturing solvents. An epitope typically includes at least 3, and more usually, at Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT least 5 or 8-10 amino acids in a unique spatial conformation. Methods of determining spatial conformation of epitopes include, for example, x-ray crystallography and 2-dimensional nuclear magnetic resonance. See, e.g., Epitope Mapping Protocols, in Methods in Molecular Biology, Vol. 66, Glenn E. Morris, Ed. (1996). Antibodies that recognize the same or overlapping epitopes can be identified in a simple immunoassay showing the ability of one antibody to compete with the binding of another antibody to a target antigen. The epitope of an antibody can also be defined X-ray crystallography of the antibody bound to its antigen to identify contact residues. Alternatively, two antibodies have the same epitope if all amino acid mutations in the antigen that reduce or eliminate binding of one antibody reduce or eliminate binding of the other. Two antibodies have overlapping epitopes if some amino acid mutations that reduce or eliminate binding of one antibody reduce or eliminate binding of the other. The term “humanized immunoglobulin” or “humanized antibody” refers to an immunoglobulin or antibody that includes at least one humanized immunoglobulin or antibody chain (i.e., at least one humanized light or heavy chain). The term “humanized immunoglobulin chain” or “humanized antibody chain” (i.e., a “humanized immunoglobulin light chain” or “humanized immunoglobulin heavy chain”) refers to an immunoglobulin or antibody chain (i.e., a light or heavy chain, respectively) having a variable region that includes a variable framework region substantially from a human immunoglobulin or antibody and complementarity determining regions (CDRs) (e.g., at least one CDR, preferably two CDRs, more preferably three CDRs) substantially from a non-human immunoglobulin or antibody, and further includes constant regions (e.g., at least one constant region or portion thereof, in the case of a light chain, and preferably three constant regions in the case of a heavy chain). The term “humanized variable region” (e.g., “humanized light chain variable region” or “humanized heavy chain variable region”) refers to a variable region that includes a variable framework region substantially from a human immunoglobulin or antibody and complementarity determining regions (CDRs) substantially from a non-human immunoglobulin or antibody. Competition between antibodies is determined by an assay in which an antibody under test inhibits specific binding of a reference antibody to a common antigen (see, e.g., Junghans et al., Cancer Res. 50: 1495, 1990). A test antibody competes with a reference antibody if an excess of a test antibody (e.g., at least 2x, 5x, l0x, 20x or l00x) inhibits binding of the reference Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT antibody by at least 50% as measured in a competitive binding assay. Some test antibodies inhibit binding of the reference antibody by at least 75%, 90% or 99%. Antibodies identified by competition assay (competing antibodies) include antibodies binding to the same epitope as the reference antibody and antibodies binding to an adjacent epitope sufficiently proximal to the epitope bound by the reference antibody for steric hindrance to occur. The term “pharmaceutically acceptable” means that the carrier, diluent, excipient, or auxiliary is compatible with the other ingredients of the formulation and not substantially deleterious to the recipient thereof. The term “TDP-43-related disease” means a disease or disorder that is characterized and / or mediated at least in part, either directly or indirectly, by formation of TDP-43 aggregates and / or mislocalization of TDP-43. Non-limiting examples of TDP-43-related diseases are described herein. The term “patient” includes human and other mammalian subjects (e.g., human) that receive either prophylactic or therapeutic treatment. An individual is at increased risk of a disease if the subject has at least one known risk factor (e.g., genetic, biochemical, family history, and situational exposure) placing individuals with that risk factor at a statistically significant greater risk of developing the disease than individuals without the risk factor. The term “biological sample” refers to a sample of biological material within or obtainable from a biological source, for example a human or mammalian subject. Such samples can be organs, organelles, tissues, sections of tissues, bodily fluids, peripheral blood, blood plasma, blood serum, cells, molecules such as proteins and peptides, and any parts or combinations derived therefrom. The term biological sample can also encompass any material derived by processing the sample. Derived material can include cells or their progeny. Processing of the biological sample may involve one or more of filtration, distillation, extraction, concentration, fixation, inactivation of interfering components, and the like. The term “control sample” refers to a biological sample not known or suspected to include TDP-43 affected regions, or at least not known or suspect to include diseased regions of a given type. Control samples can be obtained from individuals not afflicted with the TDP-43- related disease. Alternatively, control samples can be obtained from patients afflicted with the TDP-43-related disease. Such samples can be obtained at the same time as a biological sample Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT thought to comprise the TDP-43-related disease or on a different occasion. A biological sample and a control sample can both be obtained from the same tissue. Preferably, control samples consist essentially or entirely of normal, healthy regions and can be used in comparison to a biological sample thought to comprise TDP-43-related disease-affected regions. Preferably, the tissue in the control sample is the same type as the tissue in the biological sample. Preferably, the TDP-43-related disease-affected cells thought to be in the biological sample arise from the same cell type (e.g., neurons or glia) as the type of cells in the control sample. For purposes of classifying amino acids substitutions as conservative or nonconservative, amino acids are grouped as follows: Group I (hydrophobic side chains): Met, Ala, Val, Leu, Ile; Group II (neutral hydrophilic side chains): Cys, Ser, Thr; Group III (acidic side chains): Asp, Glu; Group IV (basic side chains): Asn, Gln, His, Lys, Arg; Group V (residues influencing chain orientation): Gly, Pro; and Group VI (aromatic side chains): Trp, Tyr, Phe. Conservative substitutions involve substitutions between amino acids in the same class. Non-conservative substitutions constitute exchanging a member of one of these classes for a member of another. Percentage sequence identities are determined with antibody sequences maximally aligned by the Kabat numbering convention. After alignment, if a subject antibody region (e.g., the entire mature variable region of a heavy or light chain) is being compared with the same region of a reference antibody, the percentage sequence identity between the subject and reference antibody regions is the number of positions occupied by the same amino acid in both the subject and reference antibody region divided by the total number of aligned positions of the two regions, with gaps not counted, multiplied by 100 to convert to percentage. Unless otherwise apparent from the context, the term “about” encompasses insubstantial variations, such as values within a standard margin of error of measurement (e.g., SEM) of a stated value. The phrase “substantially from a human immunoglobulin or antibody” means that, when aligned to a human immunoglobulin or antibody amino sequence for comparison purposes, the region shares at least 80-90%, preferably 90-95%, more preferably 95-99% identity (i.e., local sequence identity) with the human framework or constant region sequence, allowing, for example, for conservative substitutions, consensus sequence substitutions, germline substitutions, backmutations, and the like. The introduction of conservative substitutions, consensus sequence substitutions, germline substitutions, backmutations, and the like, is often Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT referred to as “optimization” of a humanized antibody or chain. The phrase “substantially from a non-human immunoglobulin or antibody” or “substantially non-human” means having an immunoglobulin or antibody sequence at least 80-95%, preferably 90-95%, more preferably, 96%, 97%, 98%, or 99% identical to that of a non-human organism, e.g., a non-human mammal. Accordingly, all regions or residues of a humanized immunoglobulin or antibody, or of a humanized immunoglobulin or antibody chain, except possibly the CDRs, are substantially identical to the corresponding regions or residues of one or more native human immunoglobulin sequences. The term “corresponding region” or “corresponding residue” refers to a region or residue on a second amino acid or nucleotide sequence which occupies the same (i.e., equivalent) position as a region or residue on a first amino acid or nucleotide sequence, when the first and second sequences are optimally aligned for comparison purposes. II. TDP-43 As described herein TDP-43 is a predominantly nuclear protein that is involved in RNA splicing, trafficking, stabilization, and ultimately regulation of gene expression. More specifically, TDP-43 is a multi-domain heterogeneous ribonucleoprotein (hnRNP). Proper function of TDP-43 is essential for the regulation of hundreds of mRNA transcripts to which it binds. One of TDP-43’s primary functions is the regulation of splicing mRNA transcripts; however, TDP-43 is also involved in different mechanisms of RNA processing and transport. For example, TDP-43 is an inhibitor of cryptic exon inclusion and regulates the alternative polyadenylation of >1,000 genes. TDP-43 can form ribonucleoprotein granules in different cell types, including Cajal bodies and paraspeckles in the nucleus and is recruited to mRNA transport granules in neurons. Various neurodegenerative diseases are associated with cytoplasmic aggregates of TDP-43 (e.g., TDP-43-related diseases) as described herein. Unless otherwise apparent from the context, reference to TDP-43 means a natural human form of TDP-43, including any isoforms and / or post-translational modifications (e.g., phosphorylation, glycosylation, and / or acetylation). The amino acid sequence of human TDP-43 is shown below (SEQ ID NO: 82): MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGI LHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTT EQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWC DCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFV Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT TFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNS RGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQS GPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSS MDSKSSGWGM TDP-43 can be phosphorylated at one or more amino acids including the serine at position 409 and 410. In some embodiments, TDP-43 can be phosphorylated at one or more positions including 373, 375, 379, 387, 389, 393, 395, 403, 404, 407, 409, and 410 (See, e.g., Gruijs da Silva, L.A., et al., Disease-linked TDP-43 hyperphosphorylation suppresses TDP-43 condensation and aggregation, The EMBO Journal, 41: e108443 (2022)). Unless otherwise apparent from context, reference to TDP-43, or its fragments includes the natural human amino acid sequences including isoforms, mutants, and allelic variants thereof. The ability of an antibody or antigen-binding antibody fragment to bind to TDP-43 can be determined using, e.g., surface plasmon resonance. III. Antibodies The present disclosure provides antibodies or antigen-binding antibody fragments that specifically bind to TDP-43 (e.g., human TDP-43). In some embodiments, the antibodies or antigen-binding antibody fragments described herein specifically bind to phosphorylated TDP-43 (e.g., phosphorylated human TDP-43). In some embodiments, the antibodies or antigen-binding antibody fragments described herein specifically bind phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) where one or both of serine at position 409 and / or 410 of SEQ ID NO: 82 is phosphorylated. In some embodiments, the antibodies or antigen-binding antibody fragments, bind a 23 amino acid peptide (“TDP-43 (pS409 / pS410)”) comprising amino acids from position 392 to position 414 of SEQ ID NO: 82 and where the serines at positions 409 and 410 are phosphorylated. Thus, provided herein are isolated monoclonal antibodies and antigen-binding antibody fragments that compete for binding to TDP-43 (e.g., human TDP-43) with: an antibody including a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain of SEQ ID NO: 24; an antibody including a heavy chain variable domain of SEQ ID NO: 63 and a light chain variable domain of SEQ ID NO: 65; an antibody including a heavy chain variable domain of SEQ ID NO: 67 and a light chain variable domain of SEQ ID NO: 69; an antibody including a Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT heavy chain variable domain of SEQ ID NO: 71 and a light chain variable domain of SEQ ID NO: 73; an antibody including a heavy chain variable domain of SEQ ID NO: 75 and a light chain variable domain of SEQ ID NO: 77; or an antibody including a heavy chain variable domain of SEQ ID NO: 79 and a light chain variable domain of SEQ ID NO: 81. In some embodiments, the antibodies bind to the same epitope on TDP-43 (e.g., human TDP-43) as an antibody including a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain of SEQ ID NO: 24; an antibody including a heavy chain variable domain of SEQ ID NO: 63 and a light chain variable domain of SEQ ID NO: 65; an antibody including a heavy chain variable domain of SEQ ID NO: 67 and a light chain variable domain of SEQ ID NO: 69; an antibody including a heavy chain variable domain of SEQ ID NO: 71 and a light chain variable domain of SEQ ID NO: 73; an antibody including a heavy chain variable domain of SEQ ID NO: 75 and a light chain variable domain of SEQ ID NO: 77; or an antibody including a heavy chain variable domain of SEQ ID NO: 79 and a light chain variable domain of SEQ ID NO: 81. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 84; a heavy chain CDR2 including SEQ ID NO: 85; a heavy chain CDR3 including SEQ ID NO: 86; a light chain CDR1 including SEQ ID NO: 87; a light chain CDR2 including SEQ ID NO: 88; and a light chain CDR3 including SEQ ID NO: 89. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 63. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 63. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 63. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 65. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 65. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 65. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 90; a heavy chain CDR2 including SEQ ID NO: 91; a heavy chain CDR3 Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT including SEQ ID NO: 92; a light chain CDR1 including SEQ ID NO: 93; a light chain CDR2 including SEQ ID NO: 94; and a light chain CDR3 including SEQ ID NO: 95. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 67. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 68. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 67. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 69. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 69. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 69. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 96; a heavy chain CDR2 including SEQ ID NO: 97; a heavy chain CDR3 including SEQ ID NO: 98; a light chain CDR1 including SEQ ID NO: 99; a light chain CDR2 including SEQ ID NO: 100; and a light chain CDR3 including SEQ ID NO: 101. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 71. In some embodiments, the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 71. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 71. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 73. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 73. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 73. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 102; a heavy chain CDR2 including SEQ ID NO: 103; a heavy chain CDR3 including SEQ ID NO: 104; a light chain CDR1 including SEQ ID NO: 105; a light chain CDR2 including SEQ ID NO: 106; and a light chain CDR3 including SEQ ID NO: 107. In some embodiment, the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 75. In some embodiments, the heavy chain variable domain Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT comprises a sequence that is at least 98% identical to SEQ ID NO: 75. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 75. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 77. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 77. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 77. Also provided herein are antibodies that specifically binds to TDP-43 including a heavy chain variable domain and a light chain variable domain including: a heavy chain CDR1 including SEQ ID NO: 108; a heavy chain CDR2 including SEQ ID NO: 109; a heavy chain CDR3 including SEQ ID NO: 110; a light chain CDR1 including SEQ ID NO: 111; a light chain CDR2 including SEQ ID NO: 112; and a light chain CDR3 including SEQ ID NO: 113. In some embodiments, the heavy chain variable domain comprises a sequence at least 95% identical to SEQ ID NO: 79. In some embodiments, the heavy chain variable domain comprises a sequence at least 98% identical to SEQ ID NO: 79. In some embodiments, the heavy chain variable domain comprises a sequence of SEQ ID NO: 79. In some embodiments, the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 81. In some embodiments, the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 81. In some embodiments, the light chain variable domain comprises a sequence of SEQ ID NO: 81. Also provided herein are antibodies that specifically bind to TDP-43 (e.g., human TDP- 43), including three light chain CDRs and three heavy chain CDRs of a mouse antibody characterized by a heavy chain variable domain including SEQ ID NO: 1 and a light chain variable domain including SEQ ID NO: 24. In some embodiments, the antibody is a humanized antibody, a chimeric antibody, or a veneered antibody (as described herein). Complementarity determining regions (“CDRs”) can be defined by different systems. For example, the CDRs described herein can be selected from the group of Kabat, Chothia, Kabat / Chothia Composite, AbM, and Contact. In some embodiments, the antibody includes a humanized mature heavy variable domain including: a heavy chain CDR1 as defined by Kabat / Chothia Composite, including SEQ ID NO: 49; a heavy chain CDR2 as defined by Kabat, including SEQ ID NO: 51; and a heavy chain Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT CDR3 as defined by Kabat or Chothia including SEQ ID NO: 52; and a humanized mature light chain variable domain including the three Kabat light chain CDRs of SEQ ID NOs: 53-55. In some embodiments, the humanized mature heavy variable domain includes a sequence that is at least 80% identical to any one of SEQ ID NOs: 4-23. In some embodiments, the humanized mature light chain variable domain includes a sequence that is at least 80% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof, includes a humanized mature heavy variable domain including a sequence that is at least 80% identical to any one of SEQ ID NOs: 4-23 and a humanized mature light chain variable domain including a sequence that is at least 80% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the humanized mature heavy variable domain includes a sequence that is at least 85% to any one of SEQ ID NOs: 4-23. In some embodiments, the humanized mature light chain variable region includes a sequence that is at least 85% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof, includes a humanized mature heavy variable domain including a sequence that is at least 85% identical to any one of SEQ ID NOs: 4-23 and a humanized mature light chain variable domain including a sequence that is at least 85% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the humanized mature heavy variable domain includes a sequence that is at least 90% identical, to any one of SEQ ID NOs: 4-23. In some embodiments, a humanized mature light chain variable region includes a sequence that is at least 90% identical, to any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof, includes a humanized mature heavy variable domain including a sequence that is at least 90% identical to any one of SEQ ID NOs: 4-23 and a humanized mature light chain variable domain including a sequence that is at least 90% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the humanized mature heavy variable domain includes a sequence that is at least 95% identical to any one of SEQ ID NOs: 4-23. In some embodiments, the humanized mature light chain variable domain includes a sequence that is at least 95% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof, includes a humanized mature heavy variable domain including a sequence that is at least 95% identical to any one of SEQ ID NOs: 4-23 and a humanized mature light chain Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT variable domain including a sequence that is at least 95% identical to any one of SEQ ID NOs: 27-48. In some embodiments, the humanized mature heavy chain variable domain includes a sequence that is one of SEQ ID NOs: 4-23. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 4. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 5. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 6. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 7. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 8. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 9. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 10. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 11. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 12. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 13. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 14. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 15. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 16. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 17. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 18. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 19. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 21. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 22. In some embodiments, the humanized mature heavy chain variable domain includes a sequence comprising SEQ ID NO: 23. In some embodiments, the humanized mature light chain variable domain includes a sequence that is one of SEQ ID NOs: 27-48. In some embodiment, the humanized mature light Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT chain variable domain includes a sequence comprising SEQ ID NO: 27. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 28. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 29. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 30. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 31. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 32. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 33. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 34. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 35. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 36. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 37. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 38. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 39. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 40. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 41. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 42. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 43. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 44. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 45. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 46. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 47. In some embodiment, the humanized mature light chain variable domain includes a sequence comprising SEQ ID NO: 48. The humanized mature light chain variable domains described herein include a lysine residue at their C-terminus. However, in some embodiments, the humanized mature light chain Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT variable domain (e.g., any of the mature light chain variable domains described herein) does not include the C-terminal lysine residue. In some embodiments, the antibody or antigen-binding fragment thereof, includes a humanized mature heavy variable domain including a sequence that is one of SEQ ID NOs: 4-23 and a humanized mature light chain variable domain including a sequence that is one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 4 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 5 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 6 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 7 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 8 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 9 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 10 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 11 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 12 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 13 and a humanized mature light chain variable domain any one of SEQ ID Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 14 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 15 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 16 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 17 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 18 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 19 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 20 and a humanized mature light chain variable domain any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 21 and a humanized mature light chain variable domain including any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 22 and a humanized mature light chain variable domain including any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 23 and a humanized mature light chain variable domain including any one of SEQ ID NOs: 27-48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 20 and a humanized mature light chain variable domain of SEQ ID NO: 47. In some embodiments, the antibody or antigen- binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT NO: 20 and a humanized mature light chain variable domain of SEQ ID NO: 48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 21 and a humanized mature light chain variable domain of SEQ ID NO: 47. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 21 and a humanized mature light chain variable domain of SEQ ID NO: 48. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 23 and a humanized mature light chain variable domain of SEQ ID NO: 47. In some embodiments, the antibody or antigen-binding fragment thereof includes a humanized mature heavy chain variable domain of SEQ ID NO: 23 and a humanized mature light chain variable domain of SEQ ID NO: 48. In some embodiments, at least one (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17) of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: K19 is occupied by R; S35 is occupied by G; T40 is occupied by A; E42 is occupied by G; A49 is occupied by S; K43 is occupied by E; R44 is occupied by G or D; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; L80 is occupied by A or G; L82c is occupied by G; M83 is occupied by R; S84 is occupied by A; M89 is occupied by V; or F91 is occupied by Y. In some embodiments, at least one (e.g., 2, 3, 4, 5, or 6) of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: K43 is occupied by E; R44 is occupied by G or D; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; or F91 is occupied by Y. In some embodiments, at least one (e.g., 2, 3, or 4) of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: S35 is occupied by G; L78 is occupied by A or G; L80 is occupied by A or G; or L82c is occupied by G. In some embodiments, F91 of the humanized heavy chain variable domain is occupied by Y; and at least one (e.g., 2, 3, 4, 5, or 6) of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: R44 is occupied by G; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; or M83 is occupied by R. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT In some embodiments, at least one (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13) of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q; L9 is occupied by S; D17 is occupied by Q; Q18 is occupied by P; K39 is occupied by R; K45 is occupied by R; T80 is occupied by A or S; L46 is occupied by R, L83 is occupied by V; L92 is occupied by G or A; V94 is occupied by I or A; A100 is occupied by G, D, or R; or L104 is occupied by V. In some embodiments, at least one (e.g., two) of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q or A100 is occupied by D or R. In some embodiments, at least one (e.g., 2, 3, or 4) of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: L9 is occupied by S; T80 is occupied by A or S; L92 is occupied by G or A; or V94 is occupied by I or A. In some embodiments, V3 is occupied by Q; Q18 is occupied by P; A100 is occupied by D; and at least one (e.g., two) of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: T80 is occupied by A or L92 is occupied by A. In some embodiments, at least one (e.g., 2, 3, 4, 5, 6, 7, or 8) of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: L5 is occupied by V; G44 is occupied by R; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; M89 is occupied by V, or F91 is occupied by Y; and at least one (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10) of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q; D17 is occupied by Q; Q18 is occupied by P; K39 is occupied by R ; K45 is occupied by R; T80 is occupied by A; L83 is occupied by V; L92 is occupied by A; A100 is occupied by D; or L104 is occupied by V. The aforementioned substitutions can confer reduced (e.g., at least 1% reduced, at least 5% reduced, at least 10% reduced, at least 20% reduced, at least 30% reduced, at least 40% reduced, at least 50% reduced, at least 60% reduced, at least 70% reduced, at least 80% reduced, at least 90% reduced, at least 95% reduced, or at least 99% reduced) immunogenicity and / or increased (e.g., at least 1% increased, at least 10% increased, at least 20% increased, at least 30% Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT increased, at least 40% increased, at least 50% increased, at least 60% increased, at least 70% increased, at least 80% increased, at least 90% increased, or at least 100% increased) thermal stability of the parent antibody. In some embodiments, the humanized antibody has increased thermal stability as compared to a reference antibody including a heavy chain variable domain including SEQ ID NO: 1 and a light chain variable domain including SEQ ID NO: 24. In some embodiments, the humanized antibody has increased thermal stability as compared to a reference antibody including a heavy chain variable domain of SEQ ID NO: 63 and a light chain variable domain of SEQ ID NO: 65. In some embodiments, the humanized antibody has increased thermal stability as compared to a reference antibody including a heavy chain variable domain of SEQ ID NO: 67 and a light chain variable domain of SEQ ID NO: 69. In some embodiments, the humanized antibody has increased thermal stability as compared to a reference antibody including a heavy chain variable domain of SEQ ID NO: 71 and a light chain variable domain of SEQ ID NO: 73. In some embodiments, the humanized antibody has increased thermal stability as compared to a reference antibody including a heavy chain variable domain of SEQ ID NO: 75 and a light chain variable domain of SEQ ID NO: 77. In some embodiments, the humanized antibody has increased thermal stability as compared to a reference antibody including a heavy chain variable domain of SEQ ID NO: 79 and a light chain variable domain of SEQ ID NO: 81. In some embodiments, the humanized antibody has a melting temperature of about 55 °C or greater. In some embodiments, the humanized antibody has a melting temperature of about 56 °C or greater, about 57 °C or greater, about 58° C or greater, about 59 °C or greater, about 60 °C or greater, about 61 °C or greater, about 62 °C or greater, about 63 °C or greater, about 64 °C or greater, about 65 °C or greater, about 66 °C or greater, about 67 °C or greater, about 68 °C or greater, about 69 °C or greater, about 70 °C or greater, about 71 °C or greater, about 72 °C or greater, about 73 °C or greater, about 74 °C or greater, about 75 °C or greater, about 76 °C or greater, about 77 °C or greater, about 78 °C or greater, about 79 °C or greater, about 80 °C or greater, about 81 °C or greater, about 82 °C or greater, about 83 °C or greater, about 84 °C or greater, or about 85 °C or greater. In some embodiments, the humanized antibody has a melting temperature of at least about 55 °C, at least about 56 °C, at least about 57 °C, at least about 58 °C, at least about 59 °C, at least about 60 °C, at least about 61 °C, at least about 62 °C, at least about 63 °C, at least about 64 °C, at least about 65 °C, at least about 66 °C, at least about 67 °C, Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT at least about 68 °C, at least about 69 °C, at least about 70 °C, at least about 71 °C, at least about 72 °C, at least about 73 °C, at least about 74 °C, at least about 75 °C, at least about 76 °C, at least about 77 °C, at least about 78 °C, at least about 79 °C, at least about 80 °C, at least about 81 °C, at least about 82 °C, at least about 83 °C, at least about 84 °C, or at least about 85 °C. In some embodiments, the humanized antibody has a melting temperature of about 55 °C to about 85 °C, about 55 °C to about 80 °C, about 55 °C to about 75 °C, about 55 °C to about 70 °C, about 55 °C to about 65 °C, about 55 °C to about 63 °C, about 55 °C to about 61 °C, about 55 °C to about 59 °C, about 55 °C to about 57 °C, about 57 °C to about 85 °C, about 57 °C to about 80 °C, about 57 °C to about 75 °C, about 57 °C to about 70 °C, about 57 °C to about 65 °C, about 57 °C to about 63 °C, about 57 °C to about 61 °C, about 57 °C to about 59 °C, about 59 °C to about 85 °C, about 59 °C to about 80 °C, about 59 °C to about 75 °C, about 59 °C to about 70 °C, about 59 °C to about 65 °C, about 59 °C to about 63 °C, about 59 °C to about 61 °C, about 61 °C to about 85 °C, about 61 °C to about 80 °C, about 61 °C to about 75 °C, about 61 °C to about 70 °C, about 61 °C to about 65 °C, about 61 °C to about 63 °C, about 63 °C to about 85 °C, about 63 °C to about 80 °C, about 63 °C to about 75 °C, about 63 °C to about 70 °C, about 63 °C to about 65 °C, about 65 °C to about 85 °C, about 65 °C to about 80 °C, about 65 °C to about 75 °C, about 65 °C to about 70 °C, about 70 °C to about 85 °C, about 70 °C to about 80 °C, about 70 °C to about 75 °C, about 75 °C to about 85 °C, about 75 °C to about 80 °C, or about 80 °C to about 85 °C. Also provided herein are antibodies that specifically binds to TDP-43 (e.g., human TDP- 43), including a heavy chain variable domain including: a heavy chain CDR1, as defined by Kabat / Chothia Composite, including SEQ ID NO: 49 or SEQ ID NO: 50; a heavy chain CDR2, as defined by Kabat, including SEQ ID NO: 51; a heavy chain CDR3, as defined by Kabat or Chothia, including SEQ ID NO: 52; a light chain CDR1, as defined by Kabat, including SEQ ID NO: 53; a light chain CDR2, as defined by Kabat, including SEQ ID NO: 54; and a light chain CDR3, as defined by Kabat, including one of SEQ ID NOs: 55-61. In some embodiments, the heavy chain CDR1, as defined by Kabat / Chothia Composite, includes SEQ ID NO: 49; the heavy chain CDR2, as defined by Kabat, includes SEQ ID NO: 51; the heavy chain CDR3, as defined by Kabat or Chothia, includes SEQ ID NO: 52; the light chain CDR1, as defined by Kabat, includes SEQ ID NO: 53; the light chain CDR2, as defined by Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT Kabat, includes SEQ ID NO: 54; and the light chain CDR3, as defined by Kabat, includes SEQ ID NO: 55 or SEQ ID NO: 61. In some embodiments, the heavy chain variable domain includes a sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%) identical to any one of SEQ ID NOs: 4-23. In some embodiments, the heavy chain variable domain includes a sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%) identical to any one of: SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 23. In some embodiments, the heavy chain variable domain includes a sequence that is at least 98% identical to any one of: SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 23. In some embodiments, the heavy chain variable domain includes a sequence of SEQ ID NO: 20. In some embodiments, the heavy chain variable domain includes a sequence of SEQ ID NO: 21. In some embodiments, the heavy chain variable domain includes a sequence of SEQ ID NO: 23. In some embodiments, the light chain variable domain includes a sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%) identical to any one of: SEQ ID NOs: 27-48. In some embodiments, the light chain variable domain includes a sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, at least 99%) identical to SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, the light chain variable domain includes a sequence that is at least 98% identical to SEQ ID NO: 47 or SEQ ID NO: 48. In some embodiments, the light chain variable domain includes SEQ ID NO: 47. In some embodiments, the light chain variable domain includes SEQ ID NO: 48. As described previously, the humanized mature light chain variable domains described herein include a lysine residue at their C-terminus. However, in some embodiments, the humanized mature light chain variable domain (e.g., any of the mature light chain variable domains described herein) does not include the C-terminal lysine residue. For example, any one of the mature light chain variable domains of SEQ ID NOs: 24-48, 65, 69, 73, 77, or 81 can lack the C-terminal lysine residue. In some embodiments, the antibody is a humanized antibody, a chimeric antibody, or a veneered antibody. In some embodiments, the antibody is an antigen-binding antibody fragment. In some embodiments, the antigen-binding antibody fragment is a Fab fragment, a Fab’2 fragment, or a single chain Fv. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT In some embodiments, the antibody is an intact antibody. In some embodiments, the antibody has a human IgG1 isotype. In some embodiments, the heavy chain variable domain is fused to a heavy chain constant region (e.g., any of the heavy chain constant regions described herein) and the light chain variable domain is fused to a light chain constant region (e.g., any of the light chain constant regions described herein). In some embodiments, the heavy chain constant region is a mutant form of a natural human heavy chain constant region which has reduced binding to an Fcγ receptor relative to the natural heavy chain constant region. In some embodiments, the heavy chain constant region is of IgG1 isotype. In some embodiments, the antibody has at least one mutation in a constant region. In some embodiments, the at least one mutation reduces complement fixation or activation by the constant region. In some embodiments, the at least one mutation is at one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11) positions of: 241, 264, 265, 270, 296, 297, 318, 320, 322, 329, and 331 by EU numbering. In some embodiments, the antibody has an alanine at positions 318, 320, and 322 by EU numbering. In some embodiments, the antibody or antigen-binding antibody fragment selectively binds to phosphorylated TDP-43 (e.g., phosphorylated human TDP-43). In some embodiments, the antibody or antigen-binding antibody fragment selectively binds to phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) as compared to unphosphorylated TDP-43 (e.g., unphosphorylated human TDP-43). In some embodiments, the antibody or antigen-binding antibody fragment binds to phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) with greater (e.g., at least 10-fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 100-fold, at least 150- fold, at least 200-fold, at least 250-fold, at least 300-fold, at least 350-fold, at least 400-fold, at least 450-fold, at least 500-fold, at least 550-fold, at least 600-fold, at least 650-fold, at least 700- fold, at least 750-fold, at least 800-fold, at least 850-fold, at least 900-fold, at least 950-fold, at least 1,000-fold, at least 1,050-fold, at least 1,100-fold, at least 1,150-fold, at least 1,200-fold, at least 1,250-fold, at least 1,300-fold, at least 1,350-fold, at least 1,400-fold, at least 1,450-fold, or at least 1,500-fold greater, or about 10-fold to about 1,500-fold, about 10-fold to 1,400-fold greater, about 10-fold to about 1,300-fold, about 10-fold to about 1,200-fold, about 10-fold to about 1,100-fold, about 10-fold to about 1,000-fold, about 10-fold to about 900-fold, about 10- Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT fold to about 800-fold, about 10-fold to about 700-fold, about 10-fold to about 600-fold, about 10-fold to about 500-fold, about 10-fold to about 400-fold, about 10-fold to about 300-fold, about 10-fold to about 200-fold, about 10-fold to about 100-fold, about 10-fold to about 50-fold, about 50-fold to about 1,500-fold, about 50-fold to 1,400-fold greater, about 50-fold to about 1,300-fold, about 50-fold to about 1,200-fold, about 50-fold to about 1,100-fold, about 50-fold to about 1,000-fold, about 50-fold to about 900-fold, about 50-fold to about 800-fold, about 50-fold to about 700-fold, about 50-fold to about 600-fold, about 50-fold to about 500-fold, about 50- fold to about 400-fold, about 50-fold to about 300-fold, about 50-fold to about 200-fold, about 50-fold to about 100-fold, about 100-fold to about 1,500-fold, about 100-fold to 1,400-fold greater, about 100-fold to about 1,300-fold, about 100-fold to about 1,200-fold, about 100-fold to about 1,100-fold, about 100-fold to about 1,000-fold, about 100-fold to about 900-fold, about 100-fold to about 800-fold, about 100-fold to about 700-fold, about 100-fold to about 600-fold, about 100-fold to about 500-fold, about 100-fold to about 400-fold, about 100-fold to about 300- fold, about 100-fold to about 200-fold, about 200-fold to about 1,500-fold, about 200-fold to 1,400-fold greater, about 200-fold to about 1,300-fold, about 200-fold to about 1,200-fold, about 200-fold to about 1,100-fold, about 200-fold to about 1,000-fold, about 200-fold to about 900- fold, about 200-fold to about 800-fold, about 200-fold to about 700-fold, about 200-fold to about 600-fold, about 200-fold to about 500-fold, about 200-fold to about 400-fold, about 200-fold to about 300-fold, about 500-fold to about 1,500-fold, about 500-fold to 1,400-fold greater, about 500-fold to about 1,300-fold, about 500-fold to about 1,200-fold, about 500-fold to about 1,100- fold, about 500-fold to about 1,000-fold, about 500-fold to about 900-fold, about 500-fold to about 800-fold, about 500-fold to about 700-fold, about 500-fold to about 600-fold, about 800- fold to about 1,500-fold, about 800-fold to 1,400-fold greater, about 800-fold to about 1,300- fold, about 800-fold to about 1,200-fold, about 800-fold to about 1,100-fold, about 800-fold to about 1,000-fold, about 800-fold to about 900-fold, about 1,000-fold to about 1,500-fold, about 1,000-fold to 1,400-fold greater, about 1,000-fold to about 1,300-fold, about 1,000-fold to about 1,200-fold, or about 1,000-fold to about 1,100-fold) affinity than unphosphorylated TDP-43 (e.g., unphosphorylated human TDP-43). In some embodiments, phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) includes phosphorylation of at least one amino acid residue selected from S409 and S410. In Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT some embodiments, phosphorylated TDP-43 (e.g., phosphorylated human TDP-43) includes phosphorylation of both S409 and S410. In some embodiments, the antibody selectively binds to cytoplasmic aggregates of TDP- 43 (e.g., cytoplasmic aggregates of human TDP-43). In some embodiments, the antibody selectively binds to cytoplasmic aggregates of TDP-43 (e.g., cytoplasmic aggregates of human TDP-43) compared to nuclear TDP-43 (e.g., nuclear human TDP-43). In some embodiments, the cytoplasmic aggregates of TDP-43 (e.g., cytoplasmic aggregates of human TDP-43) includes phosphorylated aggregates of TDP-43. In some embodiments, the antibody does not substantially bind unphosphorylated TDP-43 (e.g., unphosphorylated human TDP-43). In some embodiments, the antibody is conjugated to a therapeutic, cytotoxic, cytostatic, immunomodulatory, neurotrophic, or neuroprotective agent. Antibodies used in the disclosed formulations can be coupled (i.e., conjugated) with a therapeutic moiety, such as a cytotoxic agent, a radiotherapeutic agent, an immunomodulator, or a second antibody (e.g., to form an antibody heteroconjugate). Representative therapeutic moieties include agents known to be useful for treatment, management, or amelioration of TDP- 43-related diseases or symptoms of TDP-43-related diseases. Therapeutic moieties and / or detectable substances may be coupled or conjugated directly to any of the murine, chimeric, or humanized antibodies described herein through an intermediate (e.g., a linker) using techniques known in the art. See e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy,” in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery,” in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review,” in Monoclonal Antibodies 84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); “Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy,” in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., Immunol. Rev., 1982, 62:119-58. Antibodies used in the disclosed formulations also include modified forms of murine, chimeric, or humanized 13D3 antibodies, which have increased in vivo half-lives relative to the corresponding unmodified antibodies. Such modified forms may be prepared, for example, by Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protecting / blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein, etc. As one example, representative methods for antibody half-life extension are described in PCT International Publication No. WO 02 / 060919. The antibodies or antigen-binding fragments described herein can be present in a buffer. The buffer can have a pH from about 6 to about 7. The antibodies or antigen-binding fragments described herein can be present in any pharmaceutically acceptable excipient or carrier. Typically, the formulations are sterile, for example, as accomplished by sterile filtration using a 0.2 ^m or a 0.22 ^m filter. The formulations disclosed herein are also generally stable upon freezing and thawing. Selection of Constant Region The heavy and light chain variable regions of chimeric, veneered or humanized antibodies can be linked to at least a portion of a human constant region. The choice of constant region depends, in part, whether antibody-dependent cell-mediated cytotoxicity, antibody dependent cellular phagocytosis and / or complement dependent cytotoxicity are desired. For example, human isotypes IgG1 and IgG3 have complement-dependent cytotoxicity and human isotypes IgG2 and IgG4 do not. Human IgG1 and IgG3 also induce stronger cell mediated effector functions than human IgG2 and IgG4. Light chain constant regions can be lambda or kappa. Numbering conventions for constant regions include EU numbering (Edelman, G.M. et al., Proc. Natl. Acad. Sci. U.S.A. 63:78-85 (1969)), Kabat numbering (Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, MD, 1991, IMGT unique numbering (Lefranc M.-P. et al., IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains, Dev. Comp. Immunol. 29:185- 203 (2005), and IMGT exon numbering (Lefranc, supra). One or several amino acids at the amino or carboxy terminus of the light and / or heavy chain, such as the C-terminal lysine of the heavy chain, may be missing or derivatized in a proportion or all of the molecules. Substitutions can be made in the constant regions to reduce or increase effector function such as complement-mediated cytotoxicity or ADCC (see, e.g., Winter et al., U.S. Patent No. 5,624,821; Tso et al., US Patent No. 5,834,597; and Lazar et al., Proc. Natl. Acad. Sci. U.S.A. 103:4005 (2006)), or to prolong half-life in humans (see, e.g., Hinton et Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT al., J. Biol. Chem. 279:6213 (2004)). Exemplary substitutions include a Gln at position 250 and / or a Leu at position 428 (EU numbering is used in this paragraph for the constant region) for increasing the half-life of an antibody. Substitution at any or all of positions 234, 235, 236 and / or 237 reduce affinity for Fey receptors, particularly FcyRI receptor (see, e.g., U.S. Patent No. 6,624,821). An alanine substitution at positions 234, 235, and 237 of human IgG 1 can be used for reducing effector functions. Some antibodies have alanine substitution at positions 234, 235 and 237 of human IgG 1 for reducing effector functions. Optionally, positions 234, 236 and / or 237 in human IgG2 are substituted with alanine and position 235 with glutamine (see, e.g., U.S. Patent No. 5,624,821). In some antibodies, a mutation at one or more (e.g., 2, 3, 4, 5, 6, 7, 8, or 9) of positions 241, 264, 265, 270, 296, 297, 322, 329, and 331 by EU numbering of human IgG 1 is used. In some antibodies, a mutation at one or more (e.g., 2 or 3) of positions 318, 320, and 322 by EU numbering of human IgG1 is used. In some antibodies, positions 234 and / or 235 are substituted with alanine and / or position 329 is substituted with glycine. In some antibodies, positions 234 and 235 are substituted with alanine. In some antibodies, the isotype is human IgG2 or IgG4. Antibodies can be expressed as tetramers containing two light and two heavy chains, as separate heavy chains, light chains, as Fab, Fab', F(ab')2, and Fv, or as single chain antibodies in which heavy and light chain mature variable domains are linked through a spacer. Human constant regions show allotypic variation and isoallotypic variation between different individuals, that is, the constant regions can differ in different individuals at one or more polymorphic positions. Isoallotypes differ from allotypes in that sera recognizing an isoallotype bind to a non-polymorphic region of a one or more other isotypes. Thus, for example, another heavy chain constant region is of IgG1 Glm3 with or without the C-terminal lysine. Reference to a human constant region includes a constant region with any natural allotype or any permutation of residues occupying positions in natural allotypes. Antibodies can also be administered in the form of nucleic acids encoding the antibody heavy and / or light chains. If both heavy and light chains are present, the chains are preferably linked as a single chain antibody. IV. Nucleic Acids, Vectors, and Host Cells Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT The present disclosure further provides nucleic acids encoding any of the heavy chain variable domains and / or light variable chain domains described above. In some embodiments, the nucleic acids encode a heavy chain variable domain and / or a light chain variable domain of any of the antibodies described herein. For example, the nucleic acids can encode a heavy chain variable domain comprising any one of SEQ ID NOs: 4-23 and / or a light chain variable domain comprising any one of SEQ ID NOs: 27-48. Optionally, such nucleic acids further encode a signal peptide and can be expressed with the signal peptide linked to the constant region. Coding sequences of nucleic acids can be operably linked with regulatory sequences to ensure expression of the coding sequences, such as a promoter, enhancer, ribosome binding site, transcription termination signal, and the like. The nucleic acids encoding heavy and light chains can occur in isolated form or can be cloned into one or more vectors. The nucleic acids can be synthesized by, for example, solid state synthesis or PCR of overlapping oligonucleotides. Nucleic acids encoding heavy and light chains can be joined as one contiguous nucleic acid, e.g., within an expression vector, or can be separate, e.g., each cloned into its own expression vector. In some embodiments, the nucleic acid is codon-optimized for expression in a host cell. A number of methods are known for producing chimeric and humanized antibodies using an antibody-expressing cell line (e.g., hybridoma). For example, the immunoglobulin variable regions of antibodies can be cloned and sequenced using well known methods. In one method, the heavy chain variable VH region is cloned by RT-PCR using mRNA prepared from hybridoma cells. Consensus primers are employed to the VH region leader peptide encompassing the translation initiation codon as the 5' primer and a g2b constant regions specific 3' primer. Exemplary primers are described in U.S. patent publication US 2005 / 0009150 by Schenk et al. (hereinafter “Schenk”). The sequences from multiple, independently derive clones can be compared to ensure no changes are introduced during amplification. The sequence of the VH region can also be determined or confirmed by sequencing a VH fragment obtained by 5' RACE RT-PCR methodology and the 3' g2b specific primer. The light chain variable VL region can be cloned in an analogous manner. In one approach, a consensus primer set is designed for amplification of VL regions using a 5' primer designed to hybridize to the VL region encompassing the translation initiation codon and a 3' primer specific for the Ck region downstream of the V-J joining region. In a second approach, 5'RACE RT-PCR methodology is employed to clone a VL encoding cDNA. Exemplary primers Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT are described in Schenk, supra. The cloned sequences are then combined with sequences encoding human (or other non-human species) constant regions. Also provided herein are vectors including a nucleic acid encoding a mature heavy chain variable domain (e.g., any of the heavy chain variable domains described herein) and a light chain variable domain (e.g., any of the light chain variable domains described herein) operably linked to one or more regulatory sequences to effect expression in a mammalian cell of any of the antibodies or antigen-binding fragments described herein. In one approach, the heavy and light chain variable regions are re-engineered to encode splice donor sequences downstream of the respective VDJ or VJ junctions and are cloned into a mammalian expression vector, such as pCMV-hyl for the heavy chain and pCMV-Mcl for the light chain. These vectors encode human γl and Ck constant regions as exonic fragments downstream of the inserted variable region cassette. Following sequence verification, the heavy chain and light chain expression vectors can be co-transfected into CHO cells to produce chimeric antibodies. Conditioned media is collected 48 hours post-transfection and assayed by western blot analysis for antibody production or ELISA for antigen binding. The chimeric antibodies are humanized as described above. Chimeric, veneered, humanized, and human antibodies are typically produced by recombinant expression. Recombinant polynucleotide constructs typically include an expression control sequence operably linked to the coding sequences of antibody chains, including naturally associated or heterologous expression control elements, such as a promoter. The expression control sequences can be promoter systems in vectors capable of transforming or transfecting eukaryotic or prokaryotic host cells. Once the vector has been incorporated into the appropriate host, the host is maintained under conditions suitable for high level expression of the nucleotide sequences and the collection and purification of the cross-reacting antibodies. Thus, provided herein are host cells transformed with any of the vectors described herein. Also provided herein are host cells including any of the nucleic acids described herein. Expression vectors are typically replicable in the host organisms either as episomes or as an integral part of the host chromosomal DNA. Commonly, expression vectors contain selection markers, e.g., ampicillin resistance or hygromycin resistance, to permit detection of those cells transformed with the desired DNA sequences. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT E. coli is one prokaryotic host useful for expressing antibodies, particularly antibody fragments. Microbes, such as yeast, are also useful for expression. Saccharomyces is a yeast host with suitable vectors having expression control sequences, an origin of replication, termination sequences, and the like as desired. Typical promoters include 3-phosphoglycerate kinase and other glycolytic enzymes. Inducible yeast promoters include, among others, promoters from alcohol dehydrogenase, isocytochrome C, and enzymes responsible for maltose and galactose utilization. Mammalian cells can be used for expressing nucleotide segments encoding immunoglobulins or fragments thereof. See, Winnacker, From Genes to Clones, (VCH Publishers, NY, 1987). A number of suitable host cell lines capable of secreting intact heterologous proteins have been developed, and include CHO cell lines, various COS cell lines, HeLa cells, HEK293 cells, L cells, and non-antibody-producing myelomas including Sp2 / 0 and NS0. The cells can be non-human. Expression vectors for these cells can include expression control sequences, such as an origin of replication, a promoter, an enhancer (Queen et al., Immunol. Rev. 89:49 (1986)), and necessary processing information sites, such as ribosome binding sites, RNA splice sites, polyadenylation sites, and transcriptional terminator sequences. Expression control sequences can include promoters derived from endogenous genes, cytomegalovirus, SV 40, adenovirus, bovine papillomavirus, and the like. See Co et al., J. Immunol. 148: 1149 (1992). In some embodiments, the promoter is a eukaryotic promoter. Alternatively, antibody coding sequences can be incorporated in transgenes for introduction into the genome of a transgenic animal and subsequent expression in the milk of the transgenic animal (see, e.g., U.S. Pat. No. 5,741,957; U.S. Pat. No. 5,304,489; and U.S. Pat. No. 5,849,992). Suitable transgenes include coding sequences for light and / or heavy chains operably linked with a promoter and enhancer from a mammary gland specific gene, such as casein or beta lactoglobulin. The vectors containing the DNA segments of interest can be transferred into the host cell by methods depending on the type of cellular host. For example, calcium chloride transfection is commonly utilized for prokaryotic cells, whereas calcium phosphate treatment, electroporation, lipofection, biolistics, or viral-based transfection can be used for other cellular hosts. Other methods used to transform mammalian cells include the use of polybrene, protoplast fusion, liposomes, electroporation, and micro injection. For production of transgenic animals, trans Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT genes can be microinjected into fertilized oocytes or can be incorporated into the genome of embryonic stem cells, and the nuclei of such cells transferred into enucleated oocytes. Having introduced vector(s) encoding antibody heavy and light chains into cell culture, cell pools can be screened for growth productivity and product quality in serum-free media. Top- producing cell pools can then be subjected of FACS-based single-cell cloning to generate monoclonal lines. Specific productivities above 50 pg or 100 pg per cell per day, which correspond to product titers of greater than 7.5 g / L culture, can be used. Antibodies produced by single cell clones can also be tested for turbidity, filtration properties, PAGE, IEF, UV scan, HPSEC, carbohydrate-oligosaccharide mapping, mass spectrometry, and binding assay, such as ELISA or Biacore. A selected clone can then be banked in multiple vials and stored frozen for subsequent use. Once expressed, antibodies can be purified according to standard procedures of the art, including protein A capture, HPLC purification, column chromatography, gel electrophoresis and the like (See generally, Scopes, Protein Purification (Springer-Verlag, NY, 1982)). Methodology for commercial production of antibodies can be employed, including codon optimization, selection of promoters, selection of transcription elements, selection of terminators, serum-free single cell cloning, cell banking, use of selection markers for amplification of copy number, CHO terminator, or improvement of protein titers (see, e.g., U.S. Patent No. 5,786,464; U.S. Patent No. 6,114,148; US 6,063,598; U.S. Patent No. 7,569,339; W02004 / 050884; W02008 / 012142; W02008 / 012142; W02005 / 019442; W02008 / 107388; W02009 / 027471; and U.S. Patent No. 5,888,809). The DNA can be delivered in naked form (i.e., without colloidal or encapsulating materials). Alternatively, a number of viral vector systems can be used including retro viral systems (see, e.g., Lawrie and Tumin, Cur. Opin. Genet. Develop. 3, 102-109 (1993)); adenoviral vectors (see, e.g., Bett et al, J. Virol. 67, 5911 (1993)); adeno-associated virus vectors (see, e.g., Zhou et al., J. Exp. Med. 179, 1867 (1994)), viral vectors from the pox family including vaccinia virus and the avian pox viruses, viral vectors from the alpha virus genus such as those derived from Sindbis and Semliki Forest Viruses (see, e.g., Dubensky et al., J. Virol. 70, 508-519 (1996)), Venezuelan equine encephalitis virus (see U.S. Patent No. 5,643,576) and rhabdoviruses, such as vesicular stomatitis virus (see WO 96 / 34625) and papillomaviruses (Ohe Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT et al., Human Gene Therapy 6:325-333 (1995); Woo et al., WO 94 / 12629 and Xiao & Brandsma, Nucleic Acids. Res. 24:2630-2622 (1996)). DNA encoding an immunogen, or a vector containing the same, can be packaged into liposomes. Suitable lipids and related analogs are described by U.S. Patent No. 5,208,036, U.S. Patent No. 5,264,618, U.S. Patent No. 5,279,833, and U.S. Patent No. 5,283,185. Vectors and DNA encoding an immunogen can also be adsorbed to or associated with particulate carriers, examples of which include polymethyl methacrylate polymers and polylactides and poly(lactide- co-glycolides) (see, e.g., McGee et al., J. Micro Encap. 1996). V. Conjugated Antibodies Conjugated antibodies and antigen-binding antibody fragments that specifically bind to antigens such as TDP-43 (e.g., human TDP-43), are useful in detecting the presence of TDP-43; monitoring and evaluating the efficacy of therapeutic agents being used to treat patients diagnosed with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD- TDP), primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease; inhibiting or reducing aggregation of TDP-43; reducing or clearing TDP-43 aggregates; stabilizing non-toxic conformations of TDP-43; or treating or effecting prophylaxis of amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD-TDP), primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease in a patient. For example, such antibodies or antigen-binding antibody fragments can be conjugated with other therapeutic moieties, other proteins, other antibodies, and / or detectable labels. See WO 03 / 057838; U.S. Patent No. 8,455,622. Such therapeutic moieties can be any agent that can be used to treat, combat, ameliorate, prevent, or improve an unwanted condition or disease in a patient, such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD- TDP), primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease. Conjugated therapeutic moieties can include cytotoxic agents, cytostatic agents, neurotrophic agents, neuroprotective agents, radiotherapeutic agents, immunomodulators, or any biologically active agents that facilitate or enhance the activity of the antibody. A cytotoxic agent can be any agent that is toxic to a cell. A cytostatic agent can be any agent that inhibits cell proliferation. A neurotrophic agent can be any agent, including chemical or proteinaceous agents, which promotes neuron maintenance, growth, or differentiation. A neuroprotective agent Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT can be agent, including chemical or proteinaceous agents, which protects neurons from acute insult or degenerative processes. An immunomodulator can be any agent that stimulates or inhibits the development or maintenance of an immunologic response. A radiotherapeutic agent can be any molecule or compound that emits radiation. If such therapeutic moieties are coupled to a TDP-43 specific antibody or antigen-binding antibody fragment, such as the antibodies and antigen-binding antibody fragments described herein, the coupled therapeutic moieties will have a specific affinity for TDP-43 related disease-affected cells over normal cells. Consequently, administration of the conjugated antibodies or conjugated antigen-binding antibody fragments directly targets cells with minimal damage to surrounding normal, healthy tissue. This can be particularly useful for therapeutic moieties that are too toxic to be administered on their own. In addition, smaller quantities of the therapeutic moieties can be used. Some such antibodies or antigen-binding antibody fragments can be linked to radioisotopes. Examples of radioisotopes include, for example, yttrium90(90Y), indium111(111In),1311,99mTc, radiosilver-111, radiosilver-199, and Bismuth213. Linkage of radioisotopes to antibodies or antigen-binding antibody fragments may be performed with conventional bifunction chelates. For radiosilver-111 and radiosilver-199 linkage, sulfur-based linkers may be used. See Hazra et al., Cell Biophys. 24-25:1-7 (1994). Linkage of silver radioisotopes may involve reducing the immunoglobulin with ascorbic acid. For radioisotopes such as 111In and 90Y, ibritumomab tiuxetan can be used and will react with such isotopes to form 111In - ibritumomab tiuxetan and 90Y-ibritumomab tiuxetan, respectively. See Witzig, Cancer Chemother. Pharmacol., 48(Suppl l):S91-S95 (2001). Some such antibodies or antigen-binding antibody fragments can be linked to other therapeutic moieties. Such therapeutic moieties can be, for example, cytotoxic, cytostatic, immunomodulatory, neurotrophic, or neuroprotective. For example, antibodies and antigen- binding antibody fragments can be conjugated with toxic chemotherapeutic drugs such as maytansine, geldanamycin, tubulin inhibitors such as tubulin binding agents (e.g., auristatins), or minor groove binding agents such as calicheamicin. Other representative therapeutic moieties include agents known to be useful for treatment, management, or amelioration of amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD-TDP), primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT Antibodies or antigen-binding antibody fragments can also be coupled with a detectable label. Such antibodies and antigen-binding antibody fragments can be used, for example, for diagnosing ALS, FTLD-TDP, primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease. Representative detectable labels that may be coupled or linked to an antibody or antigen-binding antibody fragment include various enzymes, such as horseradish peroxidase, alkaline phosphatase, betagalactosidase, or acetylcholinesterase; prosthetic groups, such streptavidin / biotin and avidin / biotin; fluorescent materials, such as umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; luminescent materials, such as luminol; bioluminescent materials, such as luciferase, luciferin, and aequorin; radioactive materials, such as radiosilver-111, radiosilver-199, Bismuth213, iodine (131I,125I,123I,121I), carbon (14C), sulfur (5S), tritium (3H), indium (115In113In112In111In), technetium (99Tc), thallium (201Ti), gallium (68Ga,67Ga), palladium (103Pd), molybdenum (99Mo ), xenon (133Xe), fluorine (18F),153Sm,177Lu,159Gd,149Pm,140La,175Yb,166Ho,90Y,47Sc,186Re,188Re,142Pr,105Rh,97Ru,68Ge,57Co,65ZN,85SR,32P,153Gd,169Yb,51CR,54Mn,75Se,113Sn, and117Sn; positron emitting metals using various positron emission tomographies; nonradioactive paramagnetic metal ions; and molecules that are radiolabelled or conjugated to specific radioisotopes. Therapeutic moieties, other proteins, other antibodies, and / or detectable labels may be coupled or conjugated, directly or indirectly through an intermediate (e.g., a linker), to an antibody or antigen-binding antibody fragment of the invention. See e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting of Drugs in Cancer Therapy,” in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery,” in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers of Cytotoxic Agents in Cancer Therapy: A Review,” in Monoclonal Antibodies 84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475- 506 (1985); “Analysis, Results, and Future Prospective of The Therapeutic Use of Radio labeled Antibody in Cancer Therapy,” in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985); and Thorpe et al., Immunol. Rev., 62:119-58 (1982). Suitable linkers include, for example, cleavable and noncleavable linkers. Different linkers that release the coupled therapeutic moieties, proteins, antibodies, and / or detectable labels under acidic or Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT reducing conditions, on exposure to specific proteases, or under other defined conditions can be employed. VI. Pharmaceutical Compositions and Products The present disclosure also provided pharmaceutical compositions and products. Thus, provided herein are pharmaceutical compositions including any of the antibodies or antigen- binding antibody fragments described herein and a pharmaceutically acceptable carrier. Pharmaceutical compositions for parenteral administration are preferably sterile and substantially isotonic and manufactured under GMP conditions. Pharmaceutical compositions can be provided in unit dosage form (i.e., the dosage for a single administration). Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers, diluents, excipients or auxiliaries. The formulation depends on the route of administration chosen. For injection, antibodies or antigen-binding antibody fragments can be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hank’s solution, Ringer’s solution, or physiological saline or acetate buffer (to reduce discomfort at the site of injection). The solution can contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Alternatively, antibodies can be in lyophilized form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. The anti-TDP-43 antibodies described herein can be present in any pharmaceutically acceptable excipient or carrier. For example, the anti-TDP-43 antibodies described herein can be present in a buffer. The buffer can have a pH from about 6 to about 7. Typically, the formulations are sterile, for example, as accomplished by sterile filtration using a 0.2 ^m or a 0.22 ^m filter. The formulations disclosed herein are also generally stable upon freezing and thawing. In some embodiments, it can be desirable to use a pharmaceutical composition comprising any of the antibodies described herein in an ex vivo or in vitro method. For example, the method can be for a non-diagnostic and / or non-therapeutic purposes. In such instances, samples such as cells, tissues, and / or organs that have been removed from the patient are exposed to a pharmaceutical composition comprising any of the antibodies described herein. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT In prophylactic applications, an antibody or an antigen-binding antibody fragment (e.g., or a nucleic acid or a vector encoding any of the antibodies or antigen-binding antibody fragments described herein) or a pharmaceutical composition of the same is administered to a patient susceptible to, or otherwise at risk of a disease such as ALS, FTLD-TDP, primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease in regime (dose, frequency and route of administration) effective to reduce the risk, lessen the severity, or delay the onset of at least one sign or symptom of the TDP-43-related disease. In particular, the regime is preferably effective to inhibit or delay TDP-43 aggregates (e.g., human TDP-43 aggregates) in the brain, and / or inhibit or delay its toxic effects and / or inhibit / or delay development of behavioral deficits. In therapeutic applications, an antibody or antigen-binding antibody fragment is administered to a patient suspected of, or already suffering from a disease (e.g., ALS) in a regime (dose, frequency and route of administration) effective to ameliorate or at least inhibit further deterioration of at least one sign or symptom of the disease. In particular, the regime is preferably effective to reduce or at least inhibit further increase of cytoplasmic levels of TDP-43 (e.g., human TDP-43) and / or aggregates formed from it, associated toxicities and / or behavioral deficits. A regime is considered therapeutically or prophylactically effective if an individual treated patient achieves an outcome more favorable than the mean outcome in a control population of comparable patients not treated by methods disclosed herein. VII. Treatment Regimens As used herein, the terms “treat” and “treatment” refer to the alleviation or amelioration of one or more symptoms or effects associated with the disease, prevention, inhibition or delay of the onset of one or more symptoms or effects of the disease, lessening of the severity or frequency of one or more symptoms or effects of the disease, and / or increasing or trending toward desired outcomes as described herein. Desired outcomes of the treatments disclosed herein vary according to the TDP-43- related disease and patient profile and are readily determinable to those skilled in the art. Desired outcomes include an improvement in the patient’s health status. Generally, desired Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT outcomes include measurable indices such as reduction or clearance of pathologic ALS, FTLD- TDP, primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease. Thus, provided herein are methods of inhibiting or reducing aggregation of TDP-43 (e.g., human TDP-43) in a subject having or at risk of developing a TDP-43-related disease, including administering to the subject an effective amount of any of the antibodies or antigen-binding antibody fragments described herein, thereby inhibiting or reducing aggregation of TDP-43 in the subject (i.e., patient). Also provided herein are methods of treating or effecting prophylaxis of a TDP-43- related disease in a subject, including administering a therapeutically effective amount of any of the antibodies or antigen-binding antibody fragments described herein thereby treating or effecting prophylaxis of the TDP-43-associated disease. In some embodiments, the TDP-43-related disease is ALS, FTLD-TDP, primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease. In some embodiments, the TDP-43-related disease is ALS. Also provided herein are methods of detecting TDP-43 deposits (e.g., human TDP-43 deposits) in a subject having or at risk of developing a TDP-43-related disease, including administering to a subject any of the antibodies or antigen-binding antibody fragments described herein, and detecting the antibody bound to TDP-43 in the subject. In some embodiments, the antibody or antigen-binding antibody fragment is administered by intravenous injection into the body of the subject. In some embodiments, the antibody or antigen-binding antibody fragment is labeled. In some embodiments, the antibody or antigen- binding antibody fragment is labeled with a fluorescent label, a paramagnetic label, or a radioactive label. In some embodiments, the radioactive label is detected using positron emission tomography (PET) or single-photon emission computed tomography (SPECT). Antibodies or antigen-binding antibody fragments are administered in an effective regime meaning a dosage, route of administration and frequency of administration that delays the onset, reduces the severity, inhibits further deterioration, and / or ameliorates at least one sign or symptom of a disorder being treated. If a patient is already suffering from a disorder, the regime can be referred to as a therapeutically effective regime. If the patient is at elevated risk of the disorder relative to the general population but is not yet experiencing symptoms, the regime can be referred to as a prophylactically effective regime. In some instances, therapeutic or Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT prophylactic efficacy can be observed in an individual patient relative to historical controls or past experience in the same patient. In other instances, therapeutic or prophylactic efficacy can be demonstrated in a preclinical or clinical trial in a population of treated patients relative to a control population of untreated patients. Administration can be parenteral, intravenous, oral, subcutaneous, intra-arterial, intracranial, intrathecal, intraperitoneal, topical, intranasal or intramuscular. Some antibodies can be administered into the systemic circulation by intravenous or subcutaneous administration. The antibody or antigen-binding antibody fragment formulation can be administered intravenously or subcutaneously in dosage ranges from about 0.5 mg / kg to about 30 mg / kg of the host body weight. For example, dosages can be about 0.5 mg / kg body weight, about 1.0 mg / kg, about 1.5 mg / kg, about 2.0 mg / kg, about 4.0 mg / kg, about 5.0 mg / kg, about 8.0 mg / kg, about 10 mg / kg, about 15 mg / kg, about 16 mg / kg, about 20 mg / kg, about 24 mg / kg, about 25 mg / kg, or about 30 mg / kg body weight. The dosages can also be administered according to body surface area from about 0.5 mg / m2to about 500 mg / m2, for example, 0.5, 5, 10, 50, 100, 250 or 500 mg / m2. For intravenous dosing, an amount of the antibody or antigen-binding antibody fragment formulation sufficient to achieve the desired dosage for the individual patient is transferred from one or more vials to one or more intravenous bags containing a liquid (e.g., saline) and administered to the patient. Antibody or antigen-binding antibody fragment is usually administered on multiple occasions. The frequency of administration depends on the half-life of the antibody or antigen- binding antibody fragment in the circulation, the condition of the patient and the route of administration among other factors. The frequency can be daily, weekly, monthly, quarterly, or at irregular intervals in response to changes in the patient's condition or progression of the disorder being treated. An exemplary treatment regimen entails administration once per every two weeks, once a month, or once every 3 to 6 months. The number of dosages administered depends on whether the disorder is acute or chronic and the response of the disorder to the treatment. The dosing frequency can be adjusted depending on the pharmacokinetic profile of the antibody formulation in the patient. For example, the half-life of the antibody or antigen-binding antibody fragment may warrant a two week frequency of dosing. In some embodiments disclosed herein, the antibody or antigen-binding antibody fragment is administered to the patient for at least 8 Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, 5 years, 10 years, or for the life of the patient. Normal levels of TDP-43 (e.g., human TDP-43) can be determined in the brains of a representative sample of individuals in the general population who have not been diagnosed with a particular TDP-43 related disease (e.g., ALS) and are not considered at elevated risk of developing such disease (e.g., a representative sample of disease-free individuals under 50 years of age). Alternatively, a normal level can be recognized in an individual patient if a PET signal according to the present methods in a region of the brain in which TDP-43 aggregates (e.g., human TDP-43 aggregates) are known to develop is not different (within the accuracy of measurement) from the signal from a region of the brain in which it is known that such deposits do not normally develop. An elevated level in an individual can be recognized by comparison to the normal levels (e.g., outside mean and variance of a standard deviation) or simply from an elevated signal beyond experimental error in a region of the brain associated with TDP-43 aggregates (e.g., human TDP-43 aggregates) compared with a region not known to be associated with deposits. For purposes of comparing the levels of TDP-43 aggregates (e.g., human TDP-43 aggregates) in an individual and population, the TDP-43 aggregates should preferably be determined in the same region(s) of the brain, these regions including at least one region in which TDP-43 aggregates associated with a particular disease (e.g., ALS) are known to form (e.g., in the cytoplasm). A patient having an elevated level of TDP-43 aggregates (e.g., human TDP-43 aggregates) is a candidate for commencing immunotherapy. After commencing immunotherapy, a decrease in the level of TDP-43 aggregates (e.g., human TDP-43 aggregates) can be first seen as an indication that the treatment is having the desired effect. The observed decrease can be, for example, in the range of 1-100%, 1-50%, or 1-25% of the baseline value. Such effects can be measured in one or more regions of the brain in which deposits are known to form or can be measured from an average of such regions. The total effect of treatment can be approximated by adding the percentage reduction relative to baseline to the increase in TDP-43 aggregates (e.g., human TDP-43 aggregates) that would otherwise occur in an average untreated patient. Maintenance of TDP-43 aggregates (e.g., human TDP-43 aggregates) at an approximately constant level or even a small increase in TDP-43 aggregates (e.g., human TDP- 43 aggregates) can also be an indication of response to treatment albeit a suboptimal response. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT Such responses can be compared with a time course of levels of TDP-43 aggregates (e.g., human TDP-43 aggregates) in patients with a particular disease (e.g., ALS) that did not receive treatment, to determine whether the immunotherapy is having an effect in inhibiting further increases of TDP-43 aggregates (e.g., human TDP-43 aggregates). VIII. Kits The present disclosure further provides kits (e.g., containers) comprising any of the antibodies or antigen-binding antibody fragments thereof disclosed herein and related materials, such as instructions for use (e.g., package insert). The instructions for use can contain, for example, instructions for administration of the antibody or antigen-binding antibody fragment and optionally one or more additional agents. The containers of antibody may be unit doses, bulk packages (e.g., multi-dose packages), or sub-unit doses. IX. Methods of Detection In some aspects, the antibodies of the present disclosure further provide methods of detecting TDP-43 in a sample. For example, in some embodiments, the present disclosure provides a method of detecting TDP-43 in a sample comprising contacting an antibody or antigen-binding fragments of the present disclosure with the sample. For example, such methods can be an ex vivo or in vitro method. In some embodiments, the sample is a biological sample derived from a subject (e.g., a human subject). In some embodiments, the subject is a human. In some embodiments, the subject is a patient having or at risk of having a TDP-43 related disease. In such instances, samples such as cells, tissues, and / or organs that have been removed from the patient are exposed to an antibody or antigen-binding fragments described herein. In some embodiments, the sample comprises cells derived from the patient and the cells are lysed prior to administration of the antibody or antigen-binding fragments described herein. EXAMPLES The following examples have been included to illustrate modes disclosed herein. Certain aspects of the following examples are described in terms of techniques and procedures found or contemplated by the present co-inventors to work well in the practice disclosed herein. In light Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT of the present disclosure and the general level of skill in the art, those of skill appreciate that the following examples are intended to be exemplary only and that numerous changes, modifications, and alterations may be employed without departing from the scope of the disclosure. Example 1. Humanized Anti-TDP-43 Antibodies Humanized anti-TDP-43 antibodies were generated from murine monoclonal antibody 13D3. Figure 1 shows an annotated version of the heavy chain variable domain and Figure 2 shows an annotated version of the light chain variable domain, respectively. Both the heavy chain variable domain and the light chain variable domain sequences show the native signal peptide, the variable domain, and partial constant domains. The partial heavy chain constant domain region is a IgG2a mouse constant domain. The partial light chain constant domain is a mouse kappa constant domain. Reference to amino acid substitutions described herein refers to the Kabat numbering system (See e.g., Kabat E.A., et. al, Sequences of Proteins of Immunological Interest (5thedition). Bethesda, MD: National Institutes of Health (1991)). Protein sequences were identified in the Protein Data Bank (PDB) database (See, Deshpande et. al, The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema, Nucleic Acids Research, 33:D233-D237 (2005)) to find structures that would provide a similar structural model of 13D3. The crystal structure of an antibody Fab PDB code “5BK5” which is a human germline antibody. 5BK5 was selected for both VH and VK structure based on its overall sequence similarity to 13D3 VH and VK, the quality of resolution (3.0 Å), and it retained the same canonical structures for the complementarity determining region (CDR) loops (Scally et al., Crystal structure of anti- cirumsporozoite protein 663 germline antibody; Direct deposit to PDB (2017)). Additionally, since 5BK5 antibody is a human germline derived antibody and has the same canonical classes belonging to human germline IGHV3-48’03 (SEQ ID NO: 2) for the variable heavy chain domain and IGKV2-30*02 (SEQ ID NO: 25) for the variable light chain domain these sequences were used as a human acceptor framework. Accordingly, the framework regions of 5BK5 VH and 5BK5 VL were chosen as the acceptor sequences for the CDRs of 13D3. A model of the 13D3 CDRs grafted onto the respective human frameworks for VH and VL was built and used as guidance for further backmutations to increase binding specificity and reduce immunogenicity. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT More specifically, the amino acid sequences consisting of 5BK5 VH human frameworks and 13D3 CDRs are designated hu13D3VHv1d (SEQ ID NO: 20) and the amino acid sequences consisting of 5BK5 VL human framework and 13D3 VL CDRs are designated hu13D3VLv1d (SEQ ID NO: 47). Additional versions of hu13D3VH and hu13D3VL were designed to enable assessment of various framework residues for their contributions to antigen binding, thermostability, developability (e.g., deamination, oxidation, N-glycosylation, proteolysis, and aggregation) and immunogenicity. The positions considered for substitution were based on a variety of factors including: positions that define the canonical CDR conformations (See, Martin, A.C.R., Protein sequence and structure analysis of antibody variable domains, In: Kontermann R and Dübel S (eds). Antibody Engineering. Heidelberg, Germany: Springer International Publishing AG (2010)); positions within the Vernier zone (See, Foote J., and Winter, G., Antibody framework residues affecting the conformation of the hypervariable loops. J Mol Biol. 224(2):487-99 (1992)); positions that localize to the VH / VL domain interface (See, Léger O.J.P. and Saldanha, J. Preparation of recombinant antibodies from immune rodent spleens and the design of their humanisation by CDR grafting. In: Shepherd P and Dean C (eds). Monoclonal Antibodies: A Practical Approach. Oxford, UK: Oxford University Press (2000)); positions that are amenable to post-translational modifications, such as glycosylation or pyroglutamination; positions that are occupied by residues that are predicted to interact with CDRs, according to the model of 13D3 CDRs grafted onto VH and VL frameworks, and / or positions that are occupied by residues that are rare among sequenced human antibodies, where either the parental murine 13D3 residue or other residue is much more prevalent within the human antibody repertoire. The following is a summary of humanized 13D3 antibodies. Heavy Chain Variable Domains consists of the CDR-H1, CDR-H2, and CDR-H3 loops of 5BK5 VH and reverts all framework substitutions at positions that are key for defining the Chothia canonical classes, are part of the Vernier zone, and localize to the VH / VL domain interface or contribute to structural stability. hu13D3VHvd1 includes the following substitutions which are back mutations to the germline antibody and found most frequently: position L5V and T77S. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT hu13D3VHv2d (SEQ ID NO: 21) includes the following substitution: L78A. Leucine at position 78 is immunogenic as indicated by Immune Epitope Database (“IEDB”) Analysis. Therefore, deimmunization analysis predicts immunogenicity reduction with an alanine substitution at position 78. hu13D3VHv3d (SEQ ID NO: 22) includes the following substitutions: G44R, S49A, and S74A. Arginine at position 44 makes de novo contacts with a G100D (glycine to aspartic acid) substitution made in the variable light chain domain thereby strengthening the heavy chain variable domain: light chain variable domain interface. Specifically, arginine at position 44 forms a hydrogen bond and a salt bridge with G100D and also forms a hydrogen bond with F98 in the variable light chain domain. Position 49 is a Vernier zone residue and substitution from serine to alanine was a back mutation to assess the impact on CDR conformation and binding. Last, a serine to alanine substitution at position 74 is a germline substitution. Hu13D3VHv4d (SEQ ID NO: 23) includes various substitutions made in hu1353VHv1d, hu1353VHv2d, and hu1353VHv3d tried in combination.

[0002] Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT Light Chain Variable Domains hu13D3VLv1d (SEQ ID NO: 47) consists of the CDR-L1, CDR- L2, and CDR-L3 loops of 13D3VL grafted onto the framework of 5BK5 VL along with reverting all framework substitutions at positions that are key for defining the Chothia canonical classes, are part of the Vernier zone, and locate to the VH / VL domain interface. Hu1353VLv1d includes the following substitutions: V3Q, P15L, E17Q, L38Q, K39R, Q100D, and L104V. Substitution of valine for glutamine at position 3 reduces immunogenicity of the light chain variable domain. Substitution of leucine for proline at position 15 is a germline substitution. Substitution of glutamine for glutamic acid at position 17 is a rare substitution. Position 17 has significant surface exposure thereby contributing to a negative charge patch at the protein surface. Substitution to glutamine reduces antibody surface negative patches. Substitution of glutamine for leucine at position 38 was made since glutamine in mouse structural models forms inter-strand contacts within the light chain variable domain to maintain structural conformation. In contrast, a leucine reside cannot form the same contacts and therefore this back mutation increases conformational stability. Substitution of arginine for lysine at position 39 increases conformation stability by forming additional contacts with adjacent residues that a lysine residue cannot. Position 100 in the light chain variable domain is a located at the heavy chain variable domain and light chain variable domain interface, however, no interchain contacts are formed with the glutamine residue. Substitution to aspartic acid along with a concurrent substitution of arginine at position 44 in the heavy chain variable domain results in stronger do novo contacts and therefore increases thermal stability of the antibody. Substitution of valine for leucine position 104 is predicted to reduce immunogenicity. hu13D3VLv2d (SEQ ID NO: 48) consists of the aforementioned substitutions described above in hu13D3VLv1d, but also includes the following substitution: L92A. Leucine at position 92 is predicted to be immunogenic, therefore, substitution with alanine at position 92 reduces the immunogenicity of the variable light chain domain. Table 1 and Table 2 below show 13D3 variable heavy chain domain sequence alignment and variable light chain domain sequence alignment, respectively, compared to humanized versions. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT Table 1. 13D3 Humanized Variable Heavy Chain Domain Sequence Alignment 12 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20VH m13D3-VH (SEQ ID NO: 1) E V Q L V E S G G G L V Q P G G S L K L L L L L L L L L L L L L L L L L L L L VH 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 A A A A A Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT h13D3VHv3 S C A A S G F T F S N Y F M S W V R Q A h13D3VHv4 S C A A S G F T F S N Y F M S W V R Q A A A A A A A A A A A A A A VH41 42 43 44 45 46 47 48 49 50 51 52 52A 53 54 55 56 57 58 59m13D3-VHP E K R L E W V A Y I S T G G D S A N Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y VH60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79Y Y Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT AEX28899 A D S V K G R F T I S R D N A K N S L Y h13D3VHv1 A D N V K G R F T I S R D N A K N S L Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y VH80 81 82 82A 82B 82C 83 84 85 86 87 88 89 90 91 92 93 94 95 96 m13D3-VH L Q M N S L M S E D T A M Y F C A R Q T F N T T T T T T T T T T T T T T T T T Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT VH97 98 99 100 100A 100B 100C 100D 100E 100F 101 102 103 104 105 106 m13D3-VHY Y S Y G G F- - -P Y W G Q G G G G G G G G G G G G G G G G G G G G VH 107 108 109 110 111 112 113 T L V T V S A Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT h13D3VHvd4 P Y W G Q G T Table 2. 13D3 Humanized Variable Light Chain Sequence Alignment 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 VL m13D3-VL (SEQ ID NO: 24) D V V M T Q S P L S L P V S L G D Q A S S S S S S S S S S S S S S S 21 22 23 24 25 26 27 27 27 27 27 27 27 A B C D E F 28 29 30 31 32 33 34 H N N H H H H H H H Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT h13D3VLv8 I S C R S S Q S L V H S _ N G K T Y L H h13D3VLv9 I S C R S S Q S L V H S _ N G K T Y L H H H H 54VLm13D3-VL W Y Q Q K P G Q S P K L L I Y K V S D R R R R R R R R R R R R R R R 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74VL m13D3-VLY S G V S D R F S G S G S G T D F T L K K K K K K K K K K K K K K K 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT VL m13D3-VLI S R V E T E D L G V Y F C S Q S L H V IGKV2-* I S R V E A E D V G V Y Y C M Q G T H W R V V V V V V A V V V V 95 96 97 98 99 101 101 102 103 104 105 106 107VL m13D3-VLP L T F G A G T K L E L K Separately, for Vk, a human kappa light chain with NCBI accession code ABC66863 (Shringer et al, 2006) was selected (SEQ ID NO: 26). This kappa light chain has the same canonical classes for CDR-L1 & L2 and belongs to human germline IGKV2-30*02 (SEQ ID NO: 25) according to IMGT convention. For VH, human Ig heavy chain AEX28899 (SEQ ID Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT NO: 3) (GenBank: AEX28899) (Bowers et al., 2014) was chosen, again with the same canonical classes and belonging to human germline IGHV3-48’03. It is a member of Kabat human heavy subgroup 3. AEX28899 and ABC66863 antibodies are human germline derived antibodies that have the same canonical classes and belong to human germline IGHV3-48’03 (SEQ ID NO: 2) for the heavy chain variable domain and IGHV3-48*03 (SEQ ID NO: 25) for the light chain variable domain. Therefore, the AEX28899 heavy chain variable domain and ABC66863 light chain variable domain sequences were used as human acceptor framework for the CDRs of 13D3. A model of the 13D3 CDRs grafted onto the respective human frameworks for VH and VL was built and used as a guidance for further backmutations. Humanized versions of AEX28899 heavy chain variable domain and ABC66863 light chain variable domain sequences were used as human acceptor framework for the CDRs of 13D3 and were designed to enable assessment of various framework residues for their contributions to antigen binding, thermostability, developability (e.g., deamination, oxidation, N-glycosylation, proteolysis, and aggregation) and immunogenicity. The positions considered for substitution were based on a variety of factors including: positions that define the canonical CDR conformations (See, Martin, A.C.R., Protein sequence and structure analysis of antibody variable domains, In: Kontermann R and Dübel S (eds). Antibody Engineering. Heidelberg, Germany: Springer International Publishing AG (2010)); positions within the Vernier zone (See, Foote J., and Winter, G., Antibody framework residues affecting the conformation of the hypervariable loops. J Mol Biol. 224(2):487-99 (1992)); positions that localize to the VH / VL domain interface (See, Léger O.J.P. and Saldanha, J. Preparation of recombinant antibodies from immune rodent spleens and the design of their humanisation by CDR grafting. In: Shepherd P and Dean C (eds). Monoclonal Antibodies: A Practical Approach. Oxford, UK: Oxford University Press (2000)); positions that are amenable to post-translational modifications, such as glycosylation or pyroglutamination; positions that are occupied by residues that are predicted to interact with CDRs, according to the model of 13D3 CDRs grafted onto VH and VL frameworks, and / or positions that are occupied by residues that are rare among sequenced human antibodies, where either the parental murine 13D3 residue or other residue is much more prevalent within the human antibody repertoire. Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT The following is a summary of VH domain substitutions in SEQ ID NO: 3: R19K; K19 in mouse antibody structure makes pi-cation interaction with W79 of SEQ ID NO: 3; G44R: substitution of Gly with Arg at this position potentially establishes contact with the light chain thereby increasing antibody stability; S77T: threonine reduces immunogenicity; L78A: leucine is predicted to be immunogenic, therefore substitution with alanine reduces predicted immunogenicity; L78G: glycine also reduces predicted immunogenicity; L80A: removing leucine from this position reduces immunogenicity; L80G: similar to alanine, a glycine at position 80 reduces immunogenicity; L82cG: glycine potentially reduces heavy chain immunogenicity; and R83M: is a back mutation that may confer antibody stability. The following is a summary of VL domain substitutions in SEQ ID NO: 26: I2V is a Vernier zone residue, valine is retained to preserve CDR conformation; L9S: leucine is predicted to be immunogenic, substitution with serine lowers predicted immunogenicity; P18Q: mouse antibody model glutamine forms a H-bond with K74 (LC) thereby stabilizing interchain interaction; R46L: is an interface and Vernier zone residue and therefore Leu is retained; A80S: serine lowers predicted immunogenicity; L92G: L92 is a CDR residue and is predicted to be immunogenic, a glycine residue is predicted to reduce immunogenicity; V94I: valine at position 94 is predicted to be low level immunogenic, isoleucine is predicted to reduce immunogenicity; and V94A: alanine is an alternative substitution that is predicted to lower immunogenicity. Example 2. Characterization of Humanized 13D3 Antibody Variants As discussed herein cytoplasmic aggregates of TDP-43 are found in many neurodegenerative diseases and in particular, ALS. Generally, the individual TDP-43 proteins found in the cytoplasmic aggregates are phosphorylated at serine residues at position 409 and / or 410. A binding screening assay was established to determine whether 13D3 and humanized variants thereof would selectively bind to phosphorylated TDP-43 found in cytoplasmic aggregates. About 50 RU of biotin-phosphoTDP43 proteins were immobilized on a CM3 chip with NeutrAvidin. Various humanized 13D3 antibodies and chimeric 13D3 antibody were flowed over the chip and assayed for binding to phosphorylated TDP43 protein. Specifically, hu13D3H9L8, hu13D3H10L6, hu13D3H10L7, hu13D3H10L8, and hu13D3H9L7 were assayed and showed similar binding to phosphoTDP43 as chimeric 13D3 antibody (Figure 3). Similarly, Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT hu13D3Hd1Ld1, hu13D3Hd2Ld2, hu13D3Hd3Ld1, hu13D3HD4LD1, hu13D3HD1LD2, hu13D3HD2LD2, hu13D3HD3LD2, and hu13D3HD4LD2 were tested for binding to phosphoTDP43. Each variant showed similar binding to phosphoTDP43 as chimeric 13D3 antibody (Figure 4). In another experiment, antibodies were immobilized on a Protein A Chip (~2000 RU) and a 23 amino acid TDP-43 peptide phosphorylated at positions 409 and 410 (“TDP-43 peptide (pS409 / pS410)”) were flowed across the chip (SEQ ID NO: 83) at concentrations between 1 nM and 100 nM. As a control a 23 amino acid TDP-43 peptide that was not phosphorylated at positions 409 or 410 was also tested between 12 nM and 1 µM. Specifically, humanized version hu13D3H5L2 demonstrated 1:1 binding with TDP-43 peptide (pS409 / pS410) at various concentrations (1.2345 nM; 3.703 nM; 11.111 nM; 33.33 nM; and 100 nM) which was similar to the 13D3 murine antibody (Figure 5). Furthermore, hu13D3H5L2 showed no affinity for the non-phosphorylated 22 amino acid TDP-43 peptide at 12.345 nM, 37.03 nM, 111.111 nM, 333.333 nM, and 1 µM (data not shown). Thermal stability of the antibodies was also assessed. Thermal stability analysis was performed with Different Scanning Calorimetry which characterizes the stability of a protein or other biomolecule (e.g., an antibody or antigen-binding fragment thereof). Antibodies were tested 2.66 mM (0.4 mg / mL) in 1xPBS at pH 7.4. Temperature range tested was from 25°C to 100°C. Binding data for chimeric 13D3 and humanized versions thereof is summarized in Tables 3 and 4. Tables 3 and 4 also summarize thermal stability data and immunogenecity data. Table 3. Humanzied Anti-TDP-43 Metrics Yield Tm °C 1:1 binding Rmax Antibody Immunogenicity kd (1 / s) KD (M) ) Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT h13D3H3L4 4.77 _ 6 0.5 2.22E+07 7.86E-02 3.55E-09 25.3 h13D3H4L2 109.43 68.88 5.5 10 1.91E+09 3.49E+00 1.83E-09 25.7 Table 4. Humanized 13D3 Antibody Metrics Yield Tm °C Antibody Immunogenicity ka (1 / Ms) kd (1 / s) KD1 (M) KD1 (nM) (m / L) (f’ab) Collectively, the data shown in Tables 3 and 4 show exemplary humanized antibodies that have low predicted immunogenicity scores (explained in further detail below) relative to the mouse 13D3 antibody. The data further demonstrate high yield and melting temperatures of the humanized antibodies (e.g., similar to the mouse 13D3 antibody). See for example, antibodies Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT h13D3Hd1-Ld1, h13D3Hd1-Ld2, and h13D3Hd2-Ld1 shown in Table 4. Further, the data also demonstrate humanized antibodies with similar binding metrics to the mouse 13D3 antibody. In silico immunogenicity analysis of humanized antibodies The immunogenicity scores shown in Tables 3 and 4 are predicted values of immunogenicity calculated from two different software programs: Immune Epitope Database (IEDB) and EpiQuest. IEDB immunogenicity analysis tool is hosted by the National Institute of Allergy and Infectious Diseases. For IEDB, the immunogenicity prediction method used is based on predicted potential binding of a peptide within a protein sequence to major histocompatibility class (MHC) class II. The program identifies potential immunogenic regions within the protein sequence. The MHC class II tool predicts immunogenic regions using broad spectrum alleles (i.e., 26 reference alleles) for MHC class II in the human population. The software generates a series of 15 residue peptides which overlap in 10 residues. Each generated 15 residue peptide is predicted for binding to the 26 reference alleles. For each peptide, a percentile rank for each of the three methods (combinatorial library, SMM_align and Sturniolo) was generated by comparing each peptide's score against the scores of five million random 15 residue peptides selected from the SWISSPROT database. The adjusted percentile rank is the percentile rank adjusted based on the frequency of peptide lengths. A low number percentile rank indicates high affinity. The median percentile rank of the three methods were then used to generate the rank for consensus method. By default, prediction result is collapsed to show only the Percentile Rank and Adjusted Rank. The maximum median percentile rank threshold is set at 20. The EpiQuest tool, T-Scanner, ranges cytotoxic T lymphocyte (CTL) epitopes according to their predicted immunodominance. The immunodominance of epitopes is defined as their relative strength in functional assays related to the target kill or release of respective cytokines. These parameters indicate functionality of the T-epitope. This program is designed to analyze and sort according to their immunodominance the CTL peptide epitopes eluted from target cells. Generally, only a low number of peptide epitopes that bind to MHC class I have actual functional activity. Relative strength of a CTL (T) epitope is defined by the strength of its binding to MHC class I and T cell receptor (TCR) (in the context of MHCI). The algorithm Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT detects the structural and compositional features of the peptide epitope that allow it to elicit a high-affinity for TCR. This analysis is haplotype-specific, and the EpiQuest T-scanner has matrix for analysis of HLAA2 and H2kB haplotypes-binding peptides. Example 3. Binding of Anti-TDP-43 Antibodies to Phosphorylated Cytoplasmic Aggregates of TDP-43 in FTP Brain Tissue and Model Systems Figures 6A-C show frontotemporal dementia (“FTD”) brain tissue (Fig. 6A) and healthy brain tissue (Fig. 6C). Fig. 6B is an inset of Fig. 6A showing co-localization of 13D3 antibody with phosphorylated TDP-43 FTD-associated neuronal cytoplasmic aggregates. The data demonstrate that 13D3 antibody specifically binds to cytoplasmic aggregates in FTD brain tissue, but not in healthy brain tissue. Similarly, each of Figures 7A-C show 13D3 specifically binding cytoplasmic aggregates in a rNLS8 dox-suppressible model of TDP-43 proteinopathy. Example 4. Binding of Anti-TDP-43 Antibodies to Phosphorylated Cytoplasmic Aggregates of TDP-43 and Clear TDP-43 Aggregates in Transfected HEK Cells Figure 8A shows confocal microscopy images of HEK cells transiently transfected with GFP-2a-TDP43 [mNLS (R82L / K83Q) DCS (C173S / C175S)] or GFP only (2a is a self-cleaving peptide that releases the TDP-43 upon expression). The top panels show staining for GFP, nuclei (grey), and pTDP-43 (white). The bottom panels show only pTDP-43 staining which is not present in the GFP alone control transfection. Figure 8B (left) is a graph showing cell count for HEK cells transfected with either GFP-2a-TDP43 or GFP alone. The data demonstrate approximately equivalent cell counts between the two populations. Further, Figure 8B (right) shows pTDP-43 foci counts for HEK cells transfected with GFP-2a-TDP43 or GFP alone. The data demonstrate TDP-43 foci are formed only in the HEK cells transfected with GFP-2a- TDP43. Figure 8C shows TDP-43 staining with either commercial antibodies or antibodies of the present disclosure including 13D3, 13C13, and 2D4. Cells were treated with antibodies for 24 hours and 24 hours later, cells were incubated again with 100 ug / ml antibodies for another 24 hours. Cells were then washed, fixed / permeabilized, and stained with anti-pTDP-43 antibodies, followed by AF647-conjugated anti-mouse secondary antibodies. Stained cells were imaged by Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT high content imaging (Operetta system) with 40x water objective. Quantitative analyses were carried out with Harmony software. Antibodies 13D3, 13C13, and 2D4 detect overexpressed mislocalized TDP-43 in HEK cells. The top row shows transfection with GFP-2a-TDP-43 where the phosphorylated TDP43 does not include a nuclear localization signal (i.e., phosphorylated TDP43 remains in the cytoplasm), and the bottom row shows transfection with a GFP only construct. The data demonstrate that TDP-43 foci are formed only in HEK cell transfected with GFP-2a-TDP-43. Various control antibodies were included in the assay including pTDP-43 (Cosmo)+, pTDP-43 (1D3)+, Total TDP-43 (PT), and 3B12 (ED)+. The control antibodies verify TDP-43 aggregation within the cytoplasm. Antibodies 13D3, 13C13, and 2D4 were similarly tested and demonstrated similar binding to cytoplasmic aggregates of phosphorylated TDP-43. References Bowers, E., et al., Decreased Mutation Frequencies among Immunoglobulin G Variable Region Genes during Viremic HIV-1 Infection, PLoS ONE, 9(1): E81913 (2014). Foote J and Winter G., Antibody framework residues affecting the conformation of the hypervariable loops. J. Mol. Biol. 224(2):487-99 (1992). Kabat EA, Wu TT, Foeller C, Perry HM, Gottesman KS, Sequences of Proteins of Immunological Interest (5thedition). Bethesda, MD: National Institutes of Health (1991). Piechotta A, Parthier C, Kleinschmidt M, Gnoth K, Pillot T, Lues I, Demuth HU, Schilling S, Rahfeld JU, and Stubbs MT, Structural and functional analyses of pyroglutamate-amyloid-β- specific antibodies as a basis for Alzheimer immunotherapy. J Biol Chem. 2017 Jul 28; 292(30): 12713–12724 (2017). Wedemayer, G.J., Patten, P.A., Wang, L.H., Schultz, P.G., Stevens, R.C., Structural insights into the evolution of an antibody combining site. Science 276: 1665-1669 (1997). Cooper,L.J., Shikhman,A.R., Glass,D.D., Kangisser,D., Cunningham, M.W. and Greenspan, N.S., Role of heavy chain constant domains in antibody-antigen interaction. Apparent specificity differences among streptococcal IgG antibodies expressing identical variable domains, J. Immunol.150(6): 2231-2242 (1993) Léger OJP and Saldanha J., Preparation of recombinant antibodies from immune rodent spleens and the design of their humanisation by CDR grafting, In: Shepherd P and Dean C (eds). Monoclonal Antibodies: A Practical Approach. Oxford, UK: Oxford University Press (2000). Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT Martin ACR, Protein sequence and structure analysis of antibody variable domains. In: Kontermann R and Dübel S (eds). Antibody Engineering. Heidelberg, Germany: Springer International Publishing AG (2010). Jimenez-Gomez,G., Gomez-Perales, J.L., Ramos-Amaya,A., Gonzalez-Garcia,I., Campos- Caro,A. and Brieva, J.A., Modulated selection of IGHV gene somatic hypermutation during systemic maturation of human plasma cells, J. Leukoc. Biol. 87 (3), 523-530 (2010). Scally, SW, Bosch A, Triller G, Wardemann H, Julien J.P., Crystal structure of anti- cirumsporozoite protein 663 germline antibody. Direct deposit to PDB (2017). Shriner, A.K., et al., Analysis of the young and elderly variable gene repertoire in response to pneumococcal polysaccharides using a reconstituted SCID mouse model, Vaccine, 24(49-50): 7159-7166 (2006). SEQUENCE APPENDIX Variable Heavy Reference Sequences SEQ ID NO: 1 m13D3-VH EVQLVESGGGLVQPGGSLKLSCAASGFTFSNYFMSWVRQTPEKRLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTLYLQMNSLMSEDTAMYFCARQTYYSYGGFPYWGQGTLVTVSA SEQ ID NO: 2 IGHV3-48*03 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTIS RDNAKNSLYLQMNSLRAEDTAVYYCARYFDYWGQGTLVTVSS SEQ ID NO: 3 AEX28899 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTIS RDNAKNSLYLQMNSLRAEDTAVYYCARRNYYDSGGYGHWGQGTLVTVSS Humanized 13D3 VH design sequences SEQ ID NO: 4 h13D3VHv1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMSWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNSLYLQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSSSEQ ID NO: 5 h13D3VHv2EVQLVESGGGLVQPGGSLKLSCAASGFTFSNYFMSWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNSLYLQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 6 h13D3VHv3 EVQLVESGGGLVQPGGSLKLSCAASGFTFSNYFMSWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNSLYAQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 7 h13D3VHv4 EVQLVESGGGLVQPGGSLKLSCAASGFTFSNYFMSWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTISRDNAKNTLYAQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSSSEQ ID NO: 8 h13D3VHv5 EVQLVESGGGLVQPGGSLKLSCAASGFTFSNYFMSWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTAYAQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT SEQ ID NO: 9 h13D3VHv6 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMSWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTAYAQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 10 h13D3VHv7 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMGWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTAYAQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 11 h13D3VHv8 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMGWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTLYGQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 12 h13D3VHv9 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMGWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTGYLQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 13 h13D3VHv10 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMGWVRQAPGKGLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTLYLQMNSGRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 14 h13D3VHv11 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMGWVRQAPGKRLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTGYLQMNSLMAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 15 h13D3VHv12 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMGWVRQAPGERLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTGYLQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 16 h13D3VHv13 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMGWVRQAPGEDLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNTGYLQMNSLRAEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 17 h13D3VHv1b ELVQSGAEVKKPGSSVKVSCKASGFTFSNYFMSWVRQAPGQGLEWVAYISTGGDSANYADNVKGRFTITR DNSTSTLYMELSSLRSEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 18 h13D3VHv2b ELVQSGAEVKKPGSSVKVSCKASGFTFSNYFMSWVRQAPGQGLEWVAYISTGGDSANYADNVKGRFTITK DTSTSTLYMELSSLRSEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 19 h13D3VHv3b ELVQSGAEVKKPGSSVKVSCKASGFTFSNYFMSWVRQAPGQGLEWVAYISTGGDSANYADNVKGRGTIT KDTSTSTLYMELSSLRSEDTAVYFCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 20 h13D3VHv1d EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMSWVRQAPGKGLEWVSYISTGGDSANYADNVKGRFTI SRDNSKNSLYLQMNSLRAEDTAVYYCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 21 h13D3VHv2d EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMSWVRQAPGKGLEWVSYISTGGDSANYADNVKGRFTI SRDNSKNTAYLQMNSLRAEDTAVYYCARQTYYSYGGFPYWGQGTLVTVSS SEQ ID NO: 22 h13D3VHv3d EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMSWVRQAPGKRLEWVAYISTGGDSANYADNVKGRFTI SRDNAKNSLYLQMNSLRAEDTAVYYCARQTYYSYGGFPYWGQGTLVTVSS Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT SEQ ID NO: 23 h13D3VHv4d EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYFMSWVRQAPGKRLEWVSYISTGGDSANYADNVKGRFTI SRDNSKNTAYLQMNSLRAEDTAVYYCARQTYYSYGGFPYWGQGTLVTVSS Underlined residues are at the positions defined below. Position 52A*# Position 82A*# Position 82B*# Position 82C*# Position 100A* Position 100B* Position 100C*, respectively. *Applies to SEQ ID NOs: 1, 3-16 and 20-23 #Applies to SEQ ID NO: 2 Variable Light Reference Sequences SEQ ID NO: 24 m13D3-VL DVVMTQSPLSLPVSLGDQASISCRSSQSLVHSNGKTYLHWYQQKPGQSPKLLIYKVSDRYSGVSDRFSGSG SGTDFTLKISRVETEDLGVYFCSQSLHVPLTFGAGTKLELK SEQ ID NO: 25 IGKV2-30*02 DVVMTQSPLSLPVTLGQPASISCRSSQSLVHSDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGS GTDFTLKISRVEAEDVGVYYCMQGTHWPYTFGQGTKLEIK SEQ ID NO: 26 ABC66863 DIVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGS GTDFTLKISRVEAEDVGVYYCMQGTHRPLTFGGGTKVEIK Humanized 13D3 VL design sequences SEQ ID NO: 27 h13D3VLv1 DVVMTQSPLSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVEAEDVGVYFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 28 h13D3VLv2 DVVMTQSPLSLPVTLGQQASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSG SGTDFTLKISRVEAEDVGVYFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 29 h13D3VLv3 DVVMTQSPSSLPVTLGQQASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVESEDVGVYFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 30 h13D3VLv4 DVVMTQSPSSLPVTLGQQASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVESEDVGVYFCSQSGHVPLTFGGGTKVEIK SEQ ID NO: 31 h13D3VLv5 DVVMTQSPSSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVESEDVGVYFCSQSGHVPLTFGGGTKVEIK SEQ ID NO: 32 h13D3VLv6 DVVMTQSPSSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVESEDVGVYFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 33 h13D3VLv7 Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT DVVMTQSPSSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVESEDVGVYFCSQSLHIPLTFGGGTKVEIK SEQ ID NO: 34 h13D3VLv8 DVVMTQSPSSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVESEDVGVYFCSQSLHAPLTFGGGTKVEIK SEQ ID NO: 35 h13D3VLv9 DVQMTQSPSSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVESEDVGVYFCSQSGHVPLTFGDGTKVEIK SEQ ID NO: 36 h13D3VLv10 DVQMTQSPSSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVESEDVGVYFCSQSGHVPLTFGRGTKVEIK SEQ ID NO: 37 h13D3VLv1b EVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTDFTLTISSLEPEDFAVYFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 38 h13D3VLv2b EVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTEFTLTISSLEPEDFAVYFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 39 h13D3VLv3b EVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTEVTLTISSLEPEDFAVYFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 40 h13D3VLv4b DVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTDFTLTISSLEPEDFAVKFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 41 h13D3VLv5b DVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTEFTLTISSLEPEDFAVKFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 42 h13D3VLv6b DVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTEVTLTISSLEPEDFAVKFCSQSLHVPLTFGGGTKVEIK SEQ ID NO: 43 h13D3VLv7b DVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTEFTLTISSLEPEDFAVYFCDQSLHVPLTFGGGTKVEIK SEQ ID NO: 44 h13D3VLv8b DVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTEVTLTISSLEPEDFAVYFCDQSLHVPLTFGGGTKVEIK SEQ ID NO: 45 h13D3VLv9b DVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTEFTLTISSLEPEDFAVYFCSQQLHVPLTFGGGTKVEIK SEQ ID NO: 46 h13D3VLv10b DVVMTQSPATLSLSPGERATLSCRSSQSLVHSNGKTYLHWYQQKPGQAPRLLIYKVSDRYSGVPARFSGSG SGTEVTLTISSLEPEDFAVYFCSQQLHVPLTFGGGTKVEIK Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT SEQ ID NO: 47 h13D3VLv1d DVQMTQSPLSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVEAEDVGVYFCSQSLHVPLTFGDGTKVEIK SEQ ID NO: 48 h13D3VLv2d DVQMTQSPLSLPVTLGQPASISCRSSQSLVHSNGKTYLHWYQQRPGQSPRLLIYKVSDRYSGVPDRFSGSGS GTDFTLKISRVEAEDVGVYFCSQSAHVPLTFGDGTKVEIK Underlined residues are at the positions defined below. S is position 27A L is position 27B V is position 27C H is position 27D S is position 27E, respectively. Applies to SEQ ID NOs: 24-48. SEQ ID NO: 49 HC CDR1 #1 GFTFSNYFMS SEQ ID NO: 50 HC CDR1 #2 GFTFSNYFMG SEQ ID NO: 51 HC CDR2 #1 YISTGGDSANYADNVKG SEQ ID NO: 52 HC CDR3 #1 QTYYSYGGFPY SEQ ID NO: 53 LC CDR1 #1 RSSQSLVHSNGKTYLH SEQ ID NO: 54 LC CDR2 #1 KVSDRYS SEQ ID NO: 55 LC CDR3 #1 SQSLHVPLT SEQ ID NO: 56 LC CDR3 #2 SQSGHVPLT SEQ ID NO: 57 LC CDR3 #3 SQSLHIPLT SEQ ID NO: 58 LC CDR3 #4 SQSLHAPLT SEQ ID NO: 59 LC CDR3 #5 DQSLHVPLT SEQ ID NO: 60 LC CDR3 #6 SQQLHVPLT SEQ ID NO: 61 LC CDR3 #7 SQSAHVPLT Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT TDP43 mouse antibody variable domain sequences SEQ ID NO: 621B3_JH140 VH Signal peptide MNFGLSLIFLVLVLKGVLC SEQ ID NO: 631B3_JH140 Variable Heavy Domain EVKLVESGGGLVQPGGSLKLSCAASGFTFSSYTMSWVRQTPEKRLELVAEISNSGGRTNYPDTVKGRFTISR DNAKNTLYLQMSSLKSEDTAMYYCARRRYSDYYYYAMDYWGQGTSVTVSS SEQ ID NO: 641B3_JH140 VL Signal peptide MSSAQFLGLLLLCFQGTRC SEQ ID NO: 651B3_JH140 Variable Light Domain DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYS LTISNLEQEDIATYFCQQGNTLPRTFGGGTKLEIK SEQ ID NO: 661C12_JH104 VH Signal peptide MNFGLSLIFLVLVLKGVLC SEQ ID NO: 671C12_JH104 Variable Heavy Domain EVKLVESGGGLVQPGGSLKLSCAASGFTFSSYTMSWVRQTPEKRLELVADISNSGGRTYYPDTVKGRFTIS RENAKNSLYLQMSSLKSEDTAMYYCARRRYSDYYYYAMDNWGQGTSVTVSS SEQ ID NO: 681C12_JH104 VL Signal peptide MSSAQFLGLLLLCFQGTRC SEQ ID NO: 691C12_JH104 Variable Light Domain DIQMTQTTSSLSASLGDRVTISCRASQDISNYLSWYQQKPDGTVKLLIYYTSRLNSGVPSRFSGSGSGTDYSL TISNLEQEDIATYFCQQGNALPRTFGGGTKLEIN SEQ ID NO: 7011A1_LA121 VH Signal peptide MEWPCIFLFLLSVTEGVHS SEQ ID NO: 7111A1_LA121 Variable Heavy Domain QVQLQQSGAELVRPGSSVKISCKASGYEFSRYWMNWVKQRPGQGLEWIGQIYHGDGDTNYKGKFKGKAI LTADKSSSTAYMQVSSLTSEDSAVYFCVRGGYYGYAMDYWGQGTSVTVSS SEQ ID NO: 7211A1_LA121 Signal peptide MKLPVRLLVLMFWIPASSS SEQ ID NO: 7311A1_LA121 Variable Light Domain DVVMTQTPLSLPVSLGDQASISCRSSQSLLHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGS GTDFTLKISRVEAEDLGVYFCSQSTHVPYTFGGGTNLEIK SEQ ID NO: 7411B1_LA121 VH Signal peptide MEWPCIFLFLLSVTEGVHS SEQ ID NO: 7511B1_LA121 Variable Heavy Domain QVQLQQSGAELVRPGSSVKISCKASGYEFSRYWMNWVKQRPGQGLEWIGQIYHGDGDTNYKGKFKGKAI LTADKSSSTAYMQVSSLTSEDSAVYFCVRGGYYGYAMDYWGQGTSVTVSS SEQ ID NO: 7611B1_LA121 VL Signal peptide MKLPVRLLVLMFWIPASSS Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT SEQ ID NO: 7711B1_LA121 Variable Light Domain DVVMTQTPLSLPVSLGDQASISCRSSQSLLHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGS GTDFTLKISRVEAEDLGVYFCSQSTHVPYTFGGGTNLEIK SEQ ID NO: 7816G5_LA121 VH Signal peptide MKCSWVIFFLMAVVTGVNS SEQ ID NO: 7916G5_LA121 Variable Heavy Domain EVHLQQSGAELVKPGASVKLSCTGSGFNIIDTYIHWVKQRPEQGLEWIGRIDPANGNTMYASKFQDKATIIA DTSSNTVYMRLGSLTSGDTAVYYCSHGDFWWGQGTTLTVSS SEQ ID NO: 8016G5_LA121 VL Signal peptide MSPAQFLFLLVLWIQETNG SEQ ID NO: 8116G5_LA121 Variable Light Domain DVVMTQTPLTLSIPIGQPAYISCKSSQSLLKSNGKTYLNWLFQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSG TDFTLKISRVEAEDLGIYYCVQGTHLPHTFGGGTRLEIK SEQ ID NO: 82 Human TDP-43 Protein MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNL VYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDL KTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELR EFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPG GFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQS GPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM SEQ ID NO: 83 TDP-43 peptide (pS409 / pS410) GSGSGFNGGFGSSMDSKSSGWGM SEQ ID NO: 841B3_JH140 Variable Heavy Chain CDR1 SGFTFSSYTMS SEQ ID NO: 851B3_JH140 Variable Heavy Chain CDR2 EISNSGGRTNY SEQ ID NO: 861B3_JH140 Variable Heavy Chain CDR3 RRYSDYYYYAMDY SEQ ID NO: 871B3_JH140 Variable Light Chain CDR1 RASQDISNYLN SEQ ID NO: 881B3_JH140 Variable Light Chain CDR2 YTSRLHS SEQ ID NO: 891B3_JH140 Variable Light Chain CDR3 QQGNTLPRT SEQ ID NO: 901C12_JH104 Variable Heavy Chain CDR1 SGFTFSSYTMS SEQ ID NO: 911C12_JH104 Variable Heavy Chain CDR2 DISNSGGRTYYPDTVKG Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT SEQ ID NO: 921C12_JH104 Variable Heavy Chain CDR3 RRYSDYYYYAMDN SEQ ID NO: 931C12_JH104 Variable Light Chain CDR1 RASQDISNYLS SEQ ID NO: 941C12 JH104 Variable Light chain CDR2 YTSRLNS SEQ ID NO: 951C12_JH104 Variable Light Chain CDR3 QQGNALPRT SEQ ID NO: 9611A1_LA121 Variable Heavy Chain CDR1 SGYEFSRYWMN SEQ ID NO: 9711A1_LA121 Variable Heavy Chain CDR2 QIYHGDGDTNYKGKFKG SEQ ID NO: 9811A1_LA121 Variable Heavy Chain CDR3 GGYYGYAMDY SEQ ID NO: 9911A1_LA121 Variable Light Chain CDR1 RSSQSLLHSNGNTYLH SEQ ID NO: 10011A1_LA121 Variable Light Chain CDR2 KVSNRFS SEQ ID NO: 10111A1_LA121 Variable Light Chain CDR3 SQSTHVPYT SEQ ID NO: 10211B1_LA121 Variable Heavy Chain CDR1 SGYEFSRYWMN SEQ ID NO: 10311B1_LA121 Variable Heavy Chain CDR2 QIYHGDGDTNYKGKFKG SEQ ID NO: 10411B1_LA121 Variable Heavy Chain CDR3 GGYYGYAMDY SEQ ID NO: 10511B1_LA121 Variable Light Chain CDR1 RSSQSLLHSNGNTYLH SEQ ID NO: 10611B1_LA121 Variable Light Chain CDR2 KVSNRFS SEQ ID NO: 10711B1_LA121 Variable Light Chain CDR3 SQSTHVPYT SEQ ID NO: 10816G5_LA121 Variable Heavy Chain CDR1 SGFNIIDTYIH SEQ ID NO: 10916G5_LA121 Variable Heavy Chain CDR2 RIDPANGNTMYA SEQ ID NO: 11016G5_LA121 Variable Heavy Chain CDR3 Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT GDFW SEQ ID NO: 11116G5_LA121 Variable Light Chain CDR1 KSSQSLLKSNGKTYLN SEQ ID NO: 11216G5_LA121 Variable Light Chain CDR2 LVSKLDS SEQ ID NO: 11316G5 LA121 Variable Light Chain CDR3 VQGTHLPHT

Claims

Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT WHAT IS CLAIMED IS:

1. An isolated monoclonal antibody that competes for binding to Transactive response DNA binding Protein of 43 kD (TDP-43) with: an antibody comprising a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain of SEQ ID NO: 24; an antibody comprising a heavy chain variable domain of SEQ ID NO: 63 and a light chain variable domain of SEQ ID NO: 65; an antibody comprising a heavy chain variable domain of SEQ ID NO: 67 and a light chain variable domain of SEQ ID NO: 69; an antibody comprising a heavy chain variable domain of SEQ ID NO: 71 and a light chain variable domain of SEQ ID NO: 73; an antibody comprising a heavy chain variable domain of SEQ ID NO: 75 and a light chain variable domain of SEQ ID NO: 77; or an antibody comprising a heavy chain variable domain of SEQ ID NO: 79 and a light chain variable domain of SEQ ID NO:

81. The antibody of claim 1, wherein the antibody binds to the same epitope on TDP-43 as: an antibody comprising a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain of SEQ ID NO: 24; an antibody comprising a heavy chain variable domain of SEQ ID NO: 63 and a light chain variable domain of SEQ ID NO: 65; an antibody comprising a heavy chain variable domain of SEQ ID NO: 67 and a light chain variable domain of SEQ ID NO: 69; an antibody comprising a heavy chain variable domain of SEQ ID NO: 71 and a light chain variable domain of SEQ ID NO: 73; an antibody comprising a heavy chain variable domain of SEQ ID NO: 75 and a light chain variable domain of SEQ ID NO: 77; or an antibody comprising a heavy chain variable domain of SEQ ID NO: 79 and a light chain variable domain of SEQ ID NO: 81.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 3. An antibody specifically binding to TDP-43, comprising three light chain CDRs and three heavy chain CDRs of a mouse antibody characterized by a heavy chain variable domain comprising SEQ ID NO: 1 and a light chain variable domain comprising SEQ ID NO:

24.

4. The antibody of claim 3, wherein the antibody is a humanized antibody, a chimeric antibody, or a veneered antibody. 5 The antibody of claim 4, wherein the CDRs are of a definition selected from the group of Kabat, Chothia, Kabat / Chothia Composite, AbM, and Contact. 6 The antibody of claim 5, wherein the antibody comprises a humanized mature heavy variable domain comprising: a heavy chain CDR1 as defined by Kabat / Chothia Composite, comprising SEQ ID NO: 49; a heavy chain CDR2 as defined by Kabat, comprising SEQ ID NO: 51; and a heavy chain CDR3 as defined by Kabat or Chothia, comprising SEQ ID NO: 52; and a humanized mature light chain variable domain comprising the three Kabat light chain CDRs of SEQ ID NOs: 53-55. 7 The antibody of claim 6, wherein the humanized mature heavy variable domain comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 4-23 and the humanized mature light chain variable domain comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 27-48. 8 The antibody of claim 7, wherein the humanized mature heavy variable domain comprises a sequence that is at least 85% to any one of SEQ ID NOs: 4-23 and the humanized mature light chain variable region comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 27-48. 9 The antibody of claim 7 or 8, wherein the humanized mature heavy variable domain comprises a sequence that is at least 90% identical, to any one of SEQ ID NOs: 4-23 and the humanizedAttorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT mature light chain variable region comprises a sequence that is at least 90% identical, to any one of SEQ ID NOs: 27-48.

10. The antibody of any one of claims 7-9, wherein the humanized mature heavy variable domain comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 4-23 and the humanized mature light chain variable domain comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 27-48.

11. The antibody of any one of claims 6-10, wherein at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: K19 is occupied by R; S35 is occupied by G; T40 is occupied by A; E42 is occupied by G; A49 is occupied by S; K43 is occupied by E; R44 is occupied by G or D; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; L80 is occupied by A or G; L82C is occupied by G; M83 is occupied by R; S84 is occupied by A; M89 is occupied by V, or F91 is occupied by Y.

12. The antibody of any one of claims 6-11, wherein at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: K43 is occupied by E; R44 is occupied by G or D; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; or F91 is occupied by Y.

13. The antibody of any one of claims 6-12, wherein at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: S35 is occupied by G; L78 is occupied by A or G; L80 is occupied by A or G; or L82C is occupied by G.

14. The antibody of any one of claims 6-13, wherein F91 of the humanized heavy chain variable domain is occupied by Y; and at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: R44 is occupied by G; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; or M83 is occupied by R.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 15. The antibody of any one of claims 6-14, wherein at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q; L9 is occupied by S; D17 is occupied by Q; Q18 is occupied by P; K39 is occupied by R; K45 is occupied by R; T80 is occupied by A or S; L83 is occupied by V; L92 is occupied by G or A; V94 is occupied by I or A; A100 is occupied by G, D, or R; or L104 is occupied by V.

16. The antibody of any one of claims 6-15, wherein at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q or A100 is occupied by D or R.

17. The antibody of any one of claims 6-16, wherein at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: L9 is occupied by S; T80 is occupied by A or S; L92 is occupied by G or A; or V94 is occupied by I or A.

18. The antibody of any one of claims 6-17, wherein V3 is occupied by Q; Q18 is occupied by P; A100 is occupied by D; and at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: T80 is occupied by A or L92 is occupied by A.

19. The antibody of any one of claims 6-18, wherein at least one of the following positions in the humanized heavy chain variable domain is occupied by the amino acid as specified: L5 is occupied by V; G44 is occupied by R; A49 is occupied by S; A74 is occupied by S; T77 is occupied by S; L78 is occupied by A or G; M89 is occupied by V, or F91 is occupied by Y; and at least one of the following positions in the humanized light chain variable domain is occupied by the amino acid as specified: V3 is occupied by Q; D17 is occupied by Q; Q18 is occupied by P; K39 is occupied by R; K45 is occupied by R; T80 is occupied by A; L83 is occupied by V; L92 is occupied by A; A100 is occupied by D; or L104 is occupied by V.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 20. The antibody of any one of claims 4-19, wherein the humanized antibody has increased thermal stability as compared to a reference antibody comprising a heavy chain variable domain comprising SEQ ID NO: 1 and a light chain variable domain comprising SEQ ID NO:

24.

21. The antibody of claim 20, wherein the humanized antibody has a melting temperature of 55°C or greater.

22. An antibody that specifically binds to TDP-43, comprising a heavy chain variable domain and a light chain variable domain comprising: a heavy chain CDR1, as defined by Kabat / Chothia Composite, comprising SEQ ID NO: 49 or SEQ ID NO: 50; a heavy chain CDR2, as defined by Kabat, comprising SEQ ID NO: 51; a heavy chain CDR3, as defined by Kabat or Chothia, comprising SEQ ID NO: 52; a light chain CDR1, as defined by Kabat, comprising SEQ ID NO: 53; a light chain CDR2, as defined by Kabat, comprising SEQ ID NO: 54; and a light chain CDR3, as defined by Kabat, comprising one of SEQ ID NOs: 55-61.

23. The antibody of claim 22, wherein: the heavy chain CDR1, as defined by Kabat / Chothia Composite, comprises SEQ ID NO: 49; the heavy chain CDR2, as defined by Kabat, comprises SEQ ID NO: 51; the heavy chain CDR3, as defined by Kabat or Chothia, comprises SEQ ID NO: 52; the light chain CDR1, as defined by Kabat, comprises SEQ ID NO: 53; the light chain CDR2, as defined by Kabat, comprises SEQ ID NO: 54; and the light chain CDR3, as defined by Kabat, comprises SEQ ID NO: 55 or SEQ ID NO:

61.

24. The antibody of claim 22 or 23, wherein the heavy chain variable domain comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 4-23.

25. The antibody of claim 24, wherein the heavy chain variable domain comprises a sequence that is at least 95% identical to any one of: SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 23.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 26. The antibody of claim 24 or 25, wherein the heavy chain variable domain comprises a sequence that is at least 98% identical to any one of: SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO:

23.

27. The antibody of any one of claims 22-26, wherein the heavy chain variable domain comprises a sequence of SEQ ID NO:

20.

28. The antibody of any one of claims 22-26, wherein the heavy chain variable domain comprises a sequence of SEQ ID NO:

21.

29. The antibody of any one of claims 22-26, wherein the heavy chain variable domain comprises a sequence of SEQ ID NO:

23.

30. The antibody of any one of claims 22-29, wherein the light chain variable domain comprises a sequence that is at least 95% identical to any one of: SEQ ID NOs: 27-48.

31. The antibody of any one of claims 22-30, wherein the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 47 or SEQ ID NO:

48.

32. The antibody of any one of claims 22-31, wherein the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 47 or SEQ ID NO:

48.

33. The antibody of any one of claims 30-32, wherein the light chain variable domain comprises SEQ ID NO:

47.

34. The antibody of any one of claims 30-32, wherein the light chain variable domain comprises SEQ ID NO:

48.

35. An antibody that specifically binds to TDP-43 comprising a heavy chain variable domain and a light chain variable domain, wherein the antibody comprises: a heavy chain CDR1 comprising SEQ ID NO: 84; a heavy chain CDR2 comprising SEQ ID NO: 85; a heavy chain CDR3 comprising SEQ ID NO: 86;Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT a light chain CDR1 comprising SEQ ID NO: 87; a light chain CDR2 comprising SEQ ID NO: 88; and a light chain CDR3 comprising SEQ ID NO:

89.

36. The antibody of claim 35, wherein the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO:

63.

37. The antibody of claim 35 or 36, wherein the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO:

63.

38. The antibody of any one of claims 35-37, wherein the heavy chain variable domain comprises a sequence of SEQ ID NO:

63.

39. The antibody of any one of claims 35-38, wherein the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO:

65.

40. The antibody of any one of claims 35-39, wherein the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO:

65.

41. The antibody of any one of claims 35-40, wherein the light chain variable domain comprises a sequence of SEQ ID NO:

65.

42. An antibody that specifically binds to TDP-43 comprising a heavy chain variable domain and a light chain variable domain, wherein the antibody comprises: a heavy chain CDR1 comprising SEQ ID NO: 90; a heavy chain CDR2 comprising SEQ ID NO: 91; a heavy chain CDR3 comprising SEQ ID NO: 92; a light chain CDR1 comprising SEQ ID NO: 93; a light chain CDR2 comprising SEQ ID NO: 94; and a light chain CDR3 comprising SEQ ID NO: 95.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 43. The antibody of claim 42, wherein the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO:

67.

44. The antibody of claim 42 or 43, wherein the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO:

67.

45. The antibody of any one of claims 42-44, wherein the heavy chain variable domain comprises a sequence of SEQ ID NO:

67.

46. The antibody of any one of claims 42-45, wherein the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO:

69.

47. The antibody of any one of claims 42-46, wherein the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO:

69.

48. The antibody of any one of claims 42-47, wherein the light chain variable domain comprises a sequence of SEQ ID NO:

69.

49. An antibody that specifically binds to TDP-43 comprising a heavy chain variable domain and a light chain variable domain, wherein the antibody comprises: a heavy chain CDR1 comprising SEQ ID NO: 96; a heavy chain CDR2 comprising SEQ ID NO: 97; a heavy chain CDR3 comprising SEQ ID NO: 98; a light chain CDR1 comprising SEQ ID NO: 99; a light chain CDR2 comprising SEQ ID NO: 100; and a light chain CDR3 comprising SEQ ID NO:

101.

50. The antibody of claim 49, wherein the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO: 71.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 51. The antibody of claim 49 or 50, wherein the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO:

71.

52. The antibody of any one of claims 49-51, wherein the heavy chain variable domain comprises a sequence of SEQ ID NO:

71.

53. The antibody of any one of claims 49-52, wherein the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO:

73.

54. The antibody of any one of claims 49-53, wherein the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO:

73.

55. The antibody of any one of claims 49-54, wherein the light chain variable domain comprises a sequence of SEQ ID NO:

73.

56. An antibody that specifically binds to TDP-43 comprising a heavy chain variable domain and a light chain variable domain, wherein the antibody comprises: a heavy chain CDR1 comprising SEQ ID NO: 102; a heavy chain CDR2 comprising SEQ ID NO: 103; a heavy chain CDR3 comprising SEQ ID NO: 104; a light chain CDR1 comprising SEQ ID NO: 105; a light chain CDR2 comprising SEQ ID NO: 106; and a light chain CDR3 comprising SEQ ID NO:

107.

57. The antibody of claim 56, wherein the heavy chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO:

75.

58. The antibody of claim 56 or 57, wherein the heavy chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO: 75.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 59. The antibody of any one of claims 56-58, wherein the heavy chain variable domain comprises a sequence of SEQ ID NO:

75.

60. The antibody of any one of claims 56-59, wherein the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO:

77.

61. The antibody of any one of claims 56-60, wherein the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO:

77.

62. The antibody of any one of claims 56-61, wherein the light chain variable domain comprises a sequence of SEQ ID NO:

77.

63. An antibody that specifically binds to TDP-43 comprising a heavy chain variable domain and a light chain variable domain, wherein the antibody comprises: a heavy chain CDR1 comprising SEQ ID NO: 108; a heavy chain CDR2 comprising SEQ ID NO: 109; a heavy chain CDR3 comprising SEQ ID NO: 110; a light chain CDR1 comprising SEQ ID NO: 111; a light chain CDR2 comprising SEQ ID NO: 112; and a light chain CDR3 comprising SEQ ID NO:

113.

64. The antibody of claim 63, wherein the heavy chain variable domain comprises a sequence at least 95% identical to SEQ ID NO:

79.

65. The antibody of claim 63 or 64, wherein the heavy chain variable domain comprises a sequence at least 98% identical to SEQ ID NO:

79.

66. The antibody of any one of claims 63-65, wherein the heavy chain variable domain comprises a sequence of SEQ ID NO: 79.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 67. The antibody of any one of claims 63-66, wherein the light chain variable domain comprises a sequence that is at least 95% identical to SEQ ID NO:

81.

68. The antibody of any one of claims 63-67, wherein the light chain variable domain comprises a sequence that is at least 98% identical to SEQ ID NO:

81.

69. The antibody of any one of claims 63-67, wherein the light chain variable domain comprises a sequence of SEQ ID NO:

81.

70. The antibody of any one of claims 22-69, wherein the antibody is a humanized antibody, a chimeric antibody, or a veneered antibody.

71. The antibody of any one of claims 1-71, wherein the antibody is an antigen-binding antibody fragment.

72. The antibody of claim 71, wherein the antigen-binding antibody fragment is a Fab fragment, a Fab’2 fragment, or a single chain Fv.

73. The antibody of any one of claims 1-70, wherein the antibody is an intact antibody.

74. The antibody of any one of claims 1-70 and 73, wherein the antibody has a human IgG1 isotype.

75. The antibody of any one of claims 1-70, 73, and 74, wherein the heavy chain variable domain is fused to a heavy chain constant region and the light chain variable domain is fused to a light chain constant region.

76. The antibody of claim 75, wherein the heavy chain constant region is a mutant form of a natural human heavy chain constant region which has reduced binding to an Fcγ receptor relative to the natural heavy chain constant region.

77. The antibody of claim 75 or 76, wherein the heavy chain constant region is of IgG1 isotype.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 78. The antibody of any one of claims 1-77, wherein the antibody has at least one mutation in a constant region.

79. The antibody of claim 78, wherein the at least one mutation reduces complement fixation or activation by the constant region.

80. The antibody of claim 79, where the at least one mutation is at one or more positions of: 241, 264, 265, 270, 296, 297, 318, 320, 322, 329, and 331 by EU numbering.

81. The antibody of claim 80, wherein the antibody has an alanine at positions 318, 320, and 322 by EU numbering.

82. The antibody of any one of claims 1-81, wherein the antibody selectively binds to phosphorylated TDP-43.

83. The antibody of any one of claims 1-82, wherein the antibody selectively binds to phosphorylated TDP-43 as compared to unphosphorylated TDP-43.

84. The antibody of claim 82 or 83, wherein the antibody binds to phosphorylated TDP-43 with at least 100-fold greater affinity as compared to unphosphorylated TDP-43.

85. The antibody of any one of claims 82-84, wherein the antibody binds to phosphorylated TDP-43 with at least 1000-fold greater affinity as compared to unphosphorylated TDP-43.

86. The antibody of any one of claims 82-85, wherein phosphorylated TDP-43 comprises phosphorylation of at least one amino acid residue selected from S409 and S410.

87. The antibody of claim 86, wherein the phosphorylated TDP-43 comprises phosphorylation of both S409 and S410.

88. The antibody of any one of claims 1-87, wherein the antibody selectively binds to cytoplasmic aggregates of TDP-43.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 89. The antibody of any one of claims 1-88, wherein the antibody selectively binds to cytoplasmic aggregates of TDP-43 compared to nuclear TDP-43.

90. The antibody of claim 88 or 89, wherein the cytoplasmic aggregates of TDP-43 comprise phosphorylated aggregates of TDP-43.

91. The antibody of any one of claims 1-90, wherein the antibody does not substantially bind unphosphorylated TDP-43.

92. The antibody of any one of claims 1-55, wherein the antibody is conjugated to a therapeutic, cytotoxic, cytostatic, immunomodulatory, neurotrophic, or neuroprotective agent.

93. The antibody of any one of claims 1-92, wherein the light chain variable domain does not comprise a C-terminal lysine residue.

94. A pharmaceutical composition comprising an antibody of any one of claims 1-93 and a pharmaceutically acceptable carrier.

95. A nucleic acid encoding the heavy chain variable domain and / or the light chain variable domain of an antibody of any one of claims 1-93.

96. A vector comprising a nucleic acid encoding a mature heavy chain variable domain and a light chain variable domain operably linked to one or more regulatory sequences to effect expression in a mammalian cell of an antibody of any one of claims 1-93.

97. The vector of claim 96, wherein the one or more regulatory sequences comprise one or more of a enhancer, ribosome binding site, transcription termination signal, and promoter, optionally, wherein the promoter is a eukaryotic promoter.

98. The vector of claim 96 or 97, wherein the nucleic acid is codon-optimized for expression in a host cell.

99. A host cell transformed with the vector of any one of claims 96-98.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 100. A host cell comprising the nucleic acid of claim 95.

101. A method of inhibiting or reducing aggregation of TDP-43 in a subject having or at risk of developing a TDP-43-related disease, comprising administering to the subject an effective amount of the antibody of any one of claims 1-93, thereby inhibiting or reducing aggregation of TDP-43 in the subject.

102. A method of treating or effecting prophylaxis of a TDP-43-related disease in a subject, comprising administering a therapeutically effective amount of an antibody of any one of claims 1-93 and thereby treating or effecting prophylaxis of the TDP-43-associated disease.

103. The method of claim 102, wherein the TDP-43-related disease is amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD-TDP), primary lateral sclerosis, and progressive muscular atrophy, and Parkinson’s disease.

104. The method of claim 103, wherein the TDP-43-related disease is ALS.

105. A method of detecting TDP-43 deposits in a subject having or at risk of developing a TDP- 43-related disease, comprising administering to a subject an antibody of any one of claims 1-93, and detecting the antibody bound to TDP-43 in the subject.

106. The method of claim 105, wherein the antibody is administered by intravenous injection into the body of the subject.

107. A method of detecting TDP-43 in a sample obtained from a patient having or at risk of developing a TDP-43 related disease, comprising detecting the antibody of any one of claims 1- 93 bound to TDP-43 in the sample.

108. The method of any one of claim 105-107, wherein the antibody is labeled.

109. The method of claim 108, wherein the antibody is labeled with a fluorescent label, a paramagnetic label, or a radioactive label.Attorney Docket Ref. No.: 50887-0006WO1 / / Client Ref: 792-PCT 110. The method of claim 109, wherein the radioactive label is detected using positron emission tomography (PET) or single-photon emission computed tomography (SPECT).

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