Novel molecules for therapy and diagnosis

Abstract

The present invention relates to novel molecules that may be used for the prevention, mitigation, treatment, and / or diagnosis of diseases, disorders, and conditions associated with α-synuclein (alpha-synuclein, A-synuclein, a-synuclein, A-Syn, α-Syn, aSyn, a-Syn) aggregates, including, but not limited to, Lewy bodies and / or Lewy neurites, such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies [LBD; dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)], or diffuse Lewy body disease. The present invention relates to α-synuclein binding molecules, in particular α-synuclein antibodies or antigen-binding fragments or derivatives thereof, and uses thereof. The molecules may also be used to determine predisposition to such disorders, diseases, or conditions, monitor residual disability, diseases, or conditions, or predict the responsiveness of patients suffering from such disorders, diseases, or conditions to treatment with particular pharmaceutical agents.

Description

[Technical field]

[0001] The present invention relates to novel molecules that may be used for the prevention, mitigation, treatment, and / or diagnosis of diseases, disorders, and disorders associated with α-synuclein (alpha-synuclein, A-synuclein, a-synuclein, A-Syn, α-Syn, aSyn, a-Syn) aggregates, including but not limited to Lewy bodies and / or Lewy neurites, such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies [LBD; Dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)] or diffuse Lewy body disease. The present invention relates to α-synuclein binding molecules, in particular α-synuclein antibodies or antigen-binding fragments or derivatives thereof, and uses thereof. The molecules may also be used to determine predisposition to such disorders, diseases or disorders, monitor residual disorders, diseases or disorders, or predict the responsiveness of patients suffering from such disorders, diseases or disorders to treatment with a particular pharmaceutical agent. [Background technology]

[0002] Many degenerative diseases are associated with extracellular or intracellular deposits of amyloid or amyloid-like proteins that contribute to the pathogenesis and progression of the disease. The best-characterized amyloid protein that forms extracellular aggregates is amyloid beta (Aβ).

[0003] Amyloid-like proteins that predominantly form intracellular aggregates include, but are not limited to, α-synuclein, tau, and huntingtin (htt). Diseases associated with α-synuclein aggregates are generally classified as synucleinopathies (or α-synucleinopathies), including, but not limited to, Parkinson's disease (PD). Synucleinopathies include Parkinson's disease (sporadic, familial with α-synuclein mutations, familial with non-α-synuclein mutations, pure dysautonomia, and Lewy body dysphagia), Lewy body dementia [LBD; dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)], diffuse Lewy body disease (DLBD), sporadic Alzheimer's disease, familial Alzheimer's disease with APP mutations, familial Alzheimer's disease with PS-1, PS-2, or other mutations, familial British dementia, Lewy body variant of Alzheimer's disease, and Down's syndrome. Synucleinopathies associated with neuronal and glial aggregates of α-synuclein include, but are not limited to, multiple system atrophy (Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy). Other diseases that may have α-synuclein immunoreactive lesions include traumatic brain injury, chronic traumatic encephalopathy, dementia pugilistica, tauopathies (Pick's disease, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, Niemann-Pick disease type C1, and frontotemporal dementia with parkinsonism linked to chromosome 17), motor neuron diseases, Huntington's disease, amyotrophic lateral sclerosis (sporadic, familial, and the ALS-dementia complex of Guam). Guam)], optic atrophy, neurodegeneration with cerebral iron deposition type 1 (Hallervorden-Spatz syndrome), prion diseases, Creutzfeldt-Jakob disease, ataxia-telangiectasia, Meige syndrome, subacute sclerosing panencephalitis, Gerstmann-Straussler-Scheinker disease, inclusion body myositis, Gaucher disease, Krabbe disease and other lysosomal storage disorders (including Kufour-Rakeb syndrome and Sanfilippo syndrome), and rapid eye movement (REM) sleep behavior disorder (Jellinger, Mov Disord 2003, 18 Suppl.6, S2-12; Galvin et al., JAMA Neurology 2001, 58 (2), 186-190; Kovari et al., Acta Neuropathol.2007, 114(3), 295-8; Saito et al., J Neuropathol Exp Neurol.2004, 63(4), 323-328; McKee et al., Brain, 2013, 136(Pt 1), 43-64; Puschmann et al., Parkinsonism Relat Disord 2012, 18S1, S24-S27; Usenovic et al., J Neurosci.2012, 32(12), 4240-4246; Winder-Rhodes et al., Mov Disord.2012, 27(2), 312-315; Ferman et al., J Int Neuropsychol Soc.2002, 8(7), 907-914; Smith et al., J Pathol.2014;232:509-521, Lippa et al., Ann Neurol.1999 Mar;45(3):353-7; Schmitz et al., Mol Neurobiol.2018 Aug 22; Charles et al., Neurosci Lett.2000 Jul 28;289(1):29-32; Wilhelmsen et al., Arch Neurol.2004 Mar;61(3):398-406; Yamaguchi et al., J Neuropathol Exp Neurol.2004, 80. th annual meeting, vol.63; Askanas et al., J Neuropathol Exp Neurol.2000 Jul;59(7):592-8)。

[0004] Alpha-synuclein is a 140 amino acid long cytoplasmic protein that is abundantly and predominantly expressed in the CNS and localized to presynaptic terminals (Burre J., J Parkinsons Dis.2015;5(4):699-713). Alpha-synuclein is a natively unfolded protein, but when associated with lipid vesicles or membranes, it adopts a mostly helical secondary structure (Iwai et al., Biochemistry 1995, 34(32), 10139-10145). The physiological function of Alpha-synuclein remains unclear. The association of α-synuclein with synaptic vesicles and its presynaptic localization suggest that α-synuclein regulates synaptic activity and plasticity, neurotransmitter release, dopamine production and metabolism, vesicle trafficking, synaptic vesicle pool maintenance and chaperone-like activity (Cabin et al., J Neurosci. 2002;22:8797-8807; Chandra et al., Cell. 2005;123:383-396).

[0005] The sequence of α-synuclein can be divided into three main domains: 1) the N-terminal region, consisting of residues 1-60, containing an 11-mer amphipathic imperfect repeat with a highly conserved hexamer (KTKEGV). This region is involved in regulating the association of α-synuclein to lipid membranes and its internalization; 2) the hydrophobic non-amyloid beta component (NAC) domain, spanning residues 61-95. This domain is essential for α-synuclein fibrillization; 3) the C-terminal region, spanning residues 96-140. This region is highly acidic, rich in proline, and has no clear structural propensity.

[0006] α-Synuclein has been shown to undergo several post-translational modifications, including truncation, phosphorylation, ubiquitination, sumoylation, oxidation, nitration, acetylation, glycosylation, glycosylation, and / or covalent transglutaminase cross-linking (Fujiwara et al., Nat Cell Biol 2002, 4(2), 160-164; Hasegawa et al., J Biol Chem 2002, 277(50), 49071-49076; Li et al., Proc Natl Acad Sci USA 2005, 102(6), 2162-2167; Oueslati et al., Prog Brain Res 2010, 183, 115-145; Schmid et al., J Biol Chem 2009, 284(19), 13128-13142; Dorval et al., J Biol Chem 2009, 284(19), 13128-13142; al., J Biol Chem.2006, 281(15):9919-24; Ruzafa et al., PlosOne 2017 12(5):e0178576; Ischiropoulos et al., Ann NY Acad Sci.2003, 991, 93-100; Munch et al., J Chem Neuroanat.2000;20:253-257; Marotta et al., Chembiochem.2012;13:2665-2670). The majority of these modifications involve residues within the C-terminal region.

[0007] Several phosphorylation sites have been detected in the carboxyl-terminal region at Tyr-125, -133, and -136, as well as at Ser-129 (Negro et al., FASEB J 2002, 16(2), 210-212). Extensive and selective phosphorylation of α-synuclein at Ser-129 is evident in synucleinopathy lesions, including Lewy bodies (Fujiwara et al., Nat Cell Biol 2002, 4(2); 160-164). Other post-translational modifications at the carboxyl terminus may affect α-synuclein aggregation, including glycosylation at Ser-129 (McLean et al., Neurosci Lett 2002, 323(3), 219-223) and nitration at Tyr-125, -133, and -136 (Takahashi et al., Brain Res 2002, 938(1-2), 73-80). Proteolytic truncation of the carboxyl terminal region has been reported to play a role in α-synuclein fibril formation in various neurodegenerative diseases (Rochet et al., Biochemistry 2000, 39(35), 10619-10626). Full-length as well as partially truncated, insoluble aggregates of α-synuclein have been detected in highly purified Lewy bodies (Crowther et al., FEBS Lett 1998, 436(3), 309-312).

[0008] Although a clear role in the disease process has not been defined, abnormal protein aggregation is a common feature in the aging brain and in several neurodegenerative diseases. In in vitro models, α-synuclein readily assembles into filaments similar to those isolated from the brains of patients with Lewy body dementia and familial PD (Crowther et al., FEBS Lett 1998, 436(3), 309-312). α-synuclein and its mutant forms (e.g., A53T and A30P) have a random coil conformation and do not form significant secondary structures in aqueous solutions at low concentrations, but are prone to self-aggregation at higher concentrations, giving rise to amyloid fibrils (Wood et al., J Biol Chem 1999, 274(28), 19509-19512). Some differences have been documented in the aggregation behavior of PD-binding mutant and wild-type proteins. Monomeric α-synuclein aggregates form stable fibrils in vitro via a metastable oligomeric (i.e., prefibrillar) state (Volles et al., Biochemistry 2002, 41(14), 4595-4602).

[0009] Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Although PD is primarily idiopathic, in at least 5% of PD patients, pathology is associated with mutations in one or several specific genes. Several point mutations (A30P, E46K, H50Q, G51D, A53T) in the α-synuclein gene causing familial PD with autosomal dominant inheritance have been described. Furthermore, duplications and triplications of the α-synuclein gene have been described in patients with PD, emphasizing the role of α-synuclein in PD pathogenesis (Lesage et al., Hum.Mol.Genet., 2009, 18, R48-59). Although the pathogenesis of PD remains unclear, increasing evidence suggests a role for pathogenic misfolding of the α-synuclein protein leading to the formation of amyloid-like fibrils. Indeed, PD is characterized by the presence of intracellular α-synuclein aggregate structures, called Lewy bodies, in substantia nigra neurons and the death of dopaminergic neurons in the substantia nigra and elsewhere. α-synuclein is a natively unfolded presynaptic protein that can misfold and aggregate into larger oligomeric and fibrillar forms that are associated with the pathogenesis of PD. Although studies have implicated small soluble oligomeric and prefibrillar forms of α-synuclein as the most neurotoxic species (Lashuel et al., J. Mol.Biol., 2002, 322, 1089-102), the exact role of α-synuclein in neuronal toxicity remains unclear (reviewed in Cookson, Annu.Rev. Biochem., 2005, 74, 29-52).

[0010] Recent evidence from cell and animal models suggests that pathological and / or aggregated α-synuclein can spread from one neuron to another. Once inside new cells, α-synuclein aggregates act as seeds, recruiting endogenous α-synuclein and promoting protein aggregation (Luk et al., Science. 2012, 338(6109):949-5; Tran et al., Cell Rep. 2014, 7(6):2054-65). Furthermore, transsynaptic spread of pathological and / or aggregated α-synuclein may explain the progressive progression of Lewy pathology through defined, anatomically connected brain regions in PD, first described by Braak and colleagues (Braak et al., Neurobiol. Aging. 2003; 24:197-211).

[0011] As a result, the intercellular diffusion of pathological and / or aggregated α-synuclein presents immunotherapy as a powerful target for new therapeutic approaches aimed at alleviating, treating, slowing or halting the progression of PD and other synucleinopathies. The antibodies described herein inhibit and / or slow seed-dependent and / or spontaneous α-synuclein aggregation. This functional feature would allow the antibodies described herein to bind and inactivate species of α-synuclein in the extracellular space, thus slowing or inhibiting the growth of α-synuclein aggregates or facilitating the clearance of these diffusing species. The development of such a treatment for PD and other synucleinopathies would address an unmet medical need, since currently only symptomatic treatments are available.

[0012] The diagnosis of Parkinson's disease is primarily clinical and depends on the presence of a specific set of symptoms and signs (early core features are bradykinesia, rigidity, resting tremor and impaired postural reflexes), a slowly progressive course, and a response to drug treatment. Final confirmation of the diagnosis is made by postmortem neuropathological analysis. Strategies are being developed to apply recent advances in the pathogenesis of Parkinson's disease to the development of biochemical and imaging biomarkers (Schapira, Curr Opin Neurol 2013; 26(4):395-400). Such biomarkers that have been investigated in different body fluids [cerebrospinal fluid (CSF), plasma, saliva] include α-synuclein levels as well as DJ-1, Tau and Abeta, as well as neurofilament proteins, interleukins, osteopontin and hypochroncin (Schapira, Curr Opin Neurol 2013; 26(4):395-400), but none of these biomarkers, alone or in combination, can be used as definitive diagnostic tests. Antibodies for diagnostic use that selectively recognize and bind to specific pathological structures of α-synuclein would have the potential to be used as biomarkers with high sensitivity and specificity. To the best of our knowledge, no approved biomarkers for monitoring pathological α-synuclein levels are currently commercially available or available for clinical trials, despite the significant need for Parkinson's research and drug development (Eberling et al., J Parkinsons Dis.2013; 3(4):565-7).

[0013] Prior Art WO 2017 / 207739 provides antibodies that specifically bind to human α-synuclein with high affinity and reduce the diffusion of α-synuclein in vivo. Summary of the Invention [Problem to be solved by the invention]

[0014] It is an object of the present invention to provide alpha-synuclein binding molecules that may be used for the treatment, amelioration, and / or prevention of diseases, disorders, or conditions associated with alpha-synuclein aggregates, such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies [LBD; dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)] or diffuse Lewy body disease.

[0015] In another aspect, it is an object of the present invention to provide molecules that may be used to diagnose, monitor disease progression, and / or monitor drug activity against diseases, disorders, or conditions associated with α-synuclein aggregates, including but not limited to Lewy bodies, Lewy neurites, and / or glial cytoplasmic inclusions, such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies [LBD; dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)] or diffuse Lewy body disease. [Means for solving the problem]

[0016] The present invention relates generally to alpha-synuclein binding molecules that inhibit and / or delay seed-dependent and / or spontaneous alpha-synuclein aggregation.

[0017] In one embodiment, the present invention provides (i) inhibiting and / or delaying seed-dependent and / or spontaneous alpha-synuclein aggregation; and (ii) α-synuclein binding molecules capable of recognizing and binding to pathological and / or aggregated α-synuclein, in particular human α-synuclein, in vitro and / or in vivo.

[0018] Thus, in its broadest aspect, the present invention relates to a binding molecule, in particular an antibody or an antigen-binding fragment thereof, that binds to α-synuclein. In a preferred embodiment of the present invention, the binding molecule, in particular an antibody or an antigen-binding fragment thereof, inhibits and / or delays the aggregation of seed-dependent and / or spontaneous α-synuclein aggregation and is capable of recognizing and binding to pathological and / or aggregated α-synuclein, in particular human α-synuclein, in vitro and / or in vivo. α-synuclein is a soluble protein that has a tendency under certain conditions to spontaneously aggregate and form soluble oligomers or soluble / insoluble pre- or mature fibrils or detergent-insoluble aggregates. Seed-dependent α-synuclein aggregation is the aggregation accelerated by pathological α-synuclein, the so-called "seed".

[0019] The alpha-synuclein binding molecules of the invention, in particular antibodies or antigen-binding fragments thereof, block cell-to-cell diffusion and / or delay and / or inhibit aggregation of alpha-synuclein protein or fragments thereof. Thus, the alpha-synuclein binding molecules of the invention inhibit and / or delay seed-dependent and / or spontaneous alpha-synuclein aggregation and are capable of recognizing and binding to pathological and / or aggregated alpha-synuclein, in particular human alpha-synuclein, in vitro and in vivo. The alpha-synuclein binding molecules of the invention inhibit and / or delay seed-dependent and / or spontaneous alpha-synuclein aggregation and are capable of recognizing and binding to pathological and / or aggregated alpha-synuclein, in particular human alpha-synuclein, in vitro or in vivo.

[0020] In the present invention, it is preferred that the α-synuclein binding molecule, in particular an antibody or antigen-binding fragment thereof, further has one or more, preferably two or more, more preferably three or more, more preferably four or more, and even more preferably all, of the functional features (i) to (vi). (i) reducing pathological alpha-synuclein levels in vivo; and / or (ii) reducing phosphorylated alpha-synuclein levels in vivo; and / or (iii) reducing and / or delaying pathological alpha-synuclein aggregation and / or seeding in vivo; and / or (iv) demonstrating reversal of neuronal loss in vivo; and / or (v) reducing the spread of pathological alpha-synuclein in vivo; and / or (vi) reducing and / or delaying cellular uptake of pathological and / or aggregated α-synuclein in vivo.

[0021] In the present invention, it is preferred that the α-synuclein binding molecule, in particular an antibody or antigen-binding fragment thereof, further has one or more, preferably two or more, more preferably three or more, more preferably four or more, and even more preferably all, of the functional features (i) to (vi). (i) reducing pathological alpha-synuclein levels in vitro; and / or (ii) reducing phosphorylated alpha-synuclein levels in vitro; and / or (iii) reducing and / or delaying pathological alpha-synuclein aggregation and / or seeding in vitro; and / or (iv) demonstrating reversal of neuronal loss in vitro; and / or (v) reducing the spread of pathological alpha-synuclein in vitro; and / or (vi) reducing and / or delaying cellular uptake of pathological and / or aggregated alpha-synuclein in vitro.

[0022] In particular, the alpha-synuclein binding molecules of the invention, particularly antibodies or antigen-binding fragments thereof, inhibit and / or delay aggregation of alpha-synuclein protein or fragments thereof.

[0023] In one embodiment, the α-synuclein binding molecules of the invention, particularly antibodies or antigen-binding fragments thereof, inhibit the formation of α-synuclein aggregates, including but not limited to Lewy bodies, Lewy neurites, and / or glial cytoplasmic inclusions.

[0024] The alpha-synuclein binding molecules of the invention, particularly antibodies or antigen-binding fragments thereof, may selectively bind to aggregated alpha-synuclein and / or pathological alpha-synuclein in preference to non-aggregated alpha-synuclein and / or non-pathological alpha-synuclein (such as monomeric alpha-synuclein).

[0025] In some embodiments of the invention, the antibody is a monoclonal antibody, hi some embodiments, the antibody is a murine antibody, a murinized antibody, a human antibody, a humanized antibody, or a chimeric antibody.

[0026] In some embodiments of the invention, the antibodies, or antigen-binding fragments or derivatives thereof having binding characteristics of the antibodies described herein, are selected from the group consisting of SEQ ID NO:10 and SEQ ID NO:14, SEQ ID NO:20 and SEQ ID NO:24, SEQ ID NO:30 and SEQ ID NO:34, SEQ ID NO:40 and SEQ ID NO:44, SEQ ID NO:50 and SEQ ID NO:54, SEQ ID NO:60 and SEQ ID NO:64, SEQ ID NO:70 and SEQ ID NO:74, SEQ ID NO:30 and SEQ ID NO:84, SEQ ID NO:90 and SEQ ID NO:94, SEQ ID NO:100 and SEQ ID NO:104, SEQ ID NO:110 and SEQ ID NO:114, SEQ ID NO:280 and SEQ ID NO:284, SEQ ID NO:285 and SEQ ID NO:286, SEQ ID NO:287 and SEQ ID NO:289, SEQ ID NO:300 and SEQ ID NO:304, SEQ ID NO:305 and SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310 and SEQ ID NO:314, SEQ ID NO:315 and SEQ ID NO:316, SEQ ID NO:317 and SEQ ID NO:318, SEQ ID NO:319 and SEQ ID NO:320, SEQ ID NO:321 and SEQ ID NO:322, SEQ ID NO:323 and SEQ ID NO:324, SEQ ID NO:325 and SEQ ID NO:326, SEQ ID NO:327 and SEQ ID NO:328, SEQ ID NO:329 and SEQ ID NO:330, SEQ ID NO:331 and SEQ ID NO:33 SEQ ID NO:290 and SEQ ID NO:194, SEQ ID NO:140 and SEQ ID NO:144, SEQ ID NO:150 and SEQ ID NO:154, SEQ ID NO:160 and SEQ ID NO:164, SEQ ID NO:170 and SEQ ID NO:174, SEQ ID NO:180 and SEQ ID NO:184, SEQ ID NO:190 and SEQ ID NO:194, SEQ ID NO:200 and SEQ ID NO:204, SEQ ID NO:210 and SEQ ID NO:214, SEQ ID NO:220 and SEQ ID NO:224, SEQ ID NO:230 and SEQ ID NO:234, SEQ ID NO:240 and SEQ ID NO:244, SEQ ID NO:250 and SEQ ID NO:254, SEQ ID NO:260 and SEQ ID NO:264, SEQ ID NO:270 and SEQ ID NO: No. 274, SEQ ID NO: 300 and SEQ ID NO: 304, SEQ ID NO: 310 and SEQ ID NO: 314, SEQ ID NO: 320 and SEQ ID NO: 324, SEQ ID NO: 330 and SEQ ID NO: 334, SEQ ID NO: 340 and SEQ ID NO: 344, SEQ ID NO: 350 and SEQ ID NO: 354, SEQ ID NO: 360 and SEQ ID NO: 364, SEQ ID NO: 370 and SEQ ID NO: 374, SEQ ID NO: 380 and SEQ ID NO: 384, SEQ ID NO: 390 and SEQ ID NO: 394, SEQ ID NO: 400 and SEQ ID NO: 404, SEQ ID NO: 410 and SEQ ID NO: 414, SEQ ID NO: 420 and SEQ ID NO: 424, SEQ ID NO: 430 and SEQ ID NO: 434, SEQ ID NO: 44 0 and SEQ ID NO:414, SEQ ID NO:450 and SEQ ID NO:424, SEQ ID NO:460 and SEQ ID NO:464, SEQ ID NO:470 and SEQ ID NO:474, SEQ ID NO:480 and SEQ ID NO:484, SEQ ID NO:490 and SEQ ID NO:494, SEQ ID NO:500 and SEQ ID NO:504, SEQ ID NO:510 and SEQ ID NO:514, SEQ ID NO:520 and SEQ ID NO:524, SEQ ID NO:530 and SEQ ID NO:534, SEQ ID NO:540 and SEQ ID NO:544, SEQ ID NO:550 and SEQ ID NO:554, SEQ ID NO:560 and SEQ ID NO:564, SEQ ID NO:570 and SEQ ID NO:574, SEQ ID NO:580 and SEQ ID NO:584,SEQ ID NO:590 and SEQ ID NO:474, SEQ ID NO:600 and SEQ ID NO:554, SEQ ID NO:610 and SEQ ID NO:614, SEQ ID NO:610 and SEQ ID NO:624, SEQ ID NO:610 and SEQ ID NO:634, SEQ ID NO:610 and SEQ ID NO:644, SEQ ID NO:620 and SEQ ID NO:614, SEQ ID NO:620 and SEQ ID NO:624, SEQ ID NO:620 and SEQ ID NO:634, SEQ ID NO:620 and SEQ ID NO:644, SEQ ID NO:630 and SEQ ID NO:614, SEQ ID NO:630 and SEQ ID NO:624, SEQ ID NO:630 and SEQ ID NO:634, SEQ ID NO:630 and SEQ ID NO:644, SEQ ID NO:640 and SEQ ID NO:614, SEQ ID NO:640 and SEQ ID NO:624, SEQ ID NO:640 and SEQ ID NO:634, SEQ ID NO:640 and SEQ ID NO:64 The antibody has the variable region VH and / or VL of the amino acid sequences shown in SEQ ID NO:644, SEQ ID NO:650 and SEQ ID NO:614, SEQ ID NO:650 and SEQ ID NO:624, SEQ ID NO:650 and SEQ ID NO:634, SEQ ID NO:650 and SEQ ID NO:644, SEQ ID NO:660 and SEQ ID NO:614, SEQ ID NO:670 and SEQ ID NO:614, SEQ ID NO:680 and SEQ ID NO:614, SEQ ID NO:690 and SEQ ID NO:614, SEQ ID NO:690 and SEQ ID NO:624, SEQ ID NO:700 and SEQ ID NO:614, SEQ ID NO:700 and SEQ ID NO:624, SEQ ID NO:710 and SEQ ID NO:614, SEQ ID NO:710 and SEQ ID NO:624, SEQ ID NO:720 and SEQ ID NO:614, and SEQ ID NO:720 and SEQ ID NO:624, respectively.

[0027] Thus, the present invention relates to SEQ ID NO:10 and SEQ ID NO:14, SEQ ID NO:20 and SEQ ID NO:24, SEQ ID NO:30 and SEQ ID NO:34, SEQ ID NO:40 and SEQ ID NO:44, SEQ ID NO:50 and SEQ ID NO:54, SEQ ID NO:60 and SEQ ID NO:64, SEQ ID NO:70 and SEQ ID NO:74, SEQ ID NO:30 and SEQ ID NO:84, SEQ ID NO:90 and SEQ ID NO:94, SEQ ID NO:100 and SEQ ID NO:104, SEQ ID NO:110 and SEQ ID NO:114, SEQ ID NO:280 and SEQ ID NO:284, SEQ ID NO:290 and SEQ ID NO:194, SEQ ID NO:140 and SEQ ID NO:144, SEQ ID NO:150 and SEQ ID NO:154, SEQ ID NO:160 and SEQ ID NO:164, SEQ ID NO:170 and SEQ ID NO:174, SEQ ID NO:180 and SEQ ID NO:184, SEQ ID NO:190 and SEQ ID NO:194, SEQ ID NO:200 and SEQ ID NO:204, SEQ ID NO:210 and SEQ ID NO:214, SEQ ID NO:220 and SEQ ID NO:224, SEQ ID NO:230 and SEQ ID NO:234, SEQ ID NO:240 and SEQ ID NO:244, SEQ ID NO:250 and SEQ ID NO:254, SEQ ID NO:260 and SEQ ID NO:264, SEQ ID NO:270 and SEQ ID NO:274, SEQ ID NO:300 and SEQ ID NO:304, SEQ ID NO:310 and SEQ ID NO:314, SEQ ID NO:320 and SEQ ID NO: No. 324, SEQ ID NO: 330 and SEQ ID NO: 334, SEQ ID NO: 340 and SEQ ID NO: 344, SEQ ID NO: 350 and SEQ ID NO: 354, SEQ ID NO: 360 and SEQ ID NO: 364, SEQ ID NO: 370 and SEQ ID NO: 374, SEQ ID NO: 380 and SEQ ID NO: 384, SEQ ID NO: 390 and SEQ ID NO: 394, SEQ ID NO: 400 and SEQ ID NO: 404, SEQ ID NO: 410 and SEQ ID NO: 414, SEQ ID NO: 420 and SEQ ID NO: 424, SEQ ID NO: 430 and SEQ ID NO: 434, SEQ ID NO: 440 and SEQ ID NO: 414, SEQ ID NO: 450 and SEQ ID NO: 424, SEQ ID NO: 460 and SEQ ID NO: 464, SEQ ID NO: 47 0 and SEQ ID NO:474, SEQ ID NO:480 and SEQ ID NO:484, SEQ ID NO:490 and SEQ ID NO:494, SEQ ID NO:500 and SEQ ID NO:504, SEQ ID NO:510 and SEQ ID NO:514, SEQ ID NO:520 and SEQ ID NO:524, SEQ ID NO:530 and SEQ ID NO:534, SEQ ID NO:540 and SEQ ID NO:544, SEQ ID NO:550 and SEQ ID NO:554, SEQ ID NO:560 and SEQ ID NO:564, SEQ ID NO:570 and SEQ ID NO:574, SEQ ID NO:580 and SEQ ID NO:584, SEQ ID NO:590 and SEQ ID NO:474, SEQ ID NO:600 and SEQ ID NO:554, SEQ ID NO:610 and SEQ ID NO:614,SEQ ID NO:610 and SEQ ID NO:624, SEQ ID NO:610 and SEQ ID NO:634, SEQ ID NO:610 and SEQ ID NO:644, SEQ ID NO:620 and SEQ ID NO:614, SEQ ID NO:620 and SEQ ID NO:624, SEQ ID NO:620 and SEQ ID NO:634, SEQ ID NO:620 and SEQ ID NO:644, SEQ ID NO:630 and SEQ ID NO:614, SEQ ID NO:630 and SEQ ID NO:624, SEQ ID NO:630 and SEQ ID NO:634, SEQ ID NO:630 and SEQ ID NO:644, SEQ ID NO:640 and SEQ ID NO:614, SEQ ID NO:640 and SEQ ID NO:624, SEQ ID NO:640 and SEQ ID NO:634, SEQ ID NO:640 and SEQ ID NO:644, SEQ ID NO:650 and SEQ ID NO:614, SEQ ID NO:650 and Also provided are alpha-synuclein binding antibodies having variable regions VH and / or VL of the amino acid sequences shown in SEQ ID NO:624, SEQ ID NO:650 and SEQ ID NO:634, SEQ ID NO:650 and SEQ ID NO:644, SEQ ID NO:660 and SEQ ID NO:614, SEQ ID NO:670 and SEQ ID NO:614, SEQ ID NO:680 and SEQ ID NO:614, SEQ ID NO:690 and SEQ ID NO:614, SEQ ID NO:690 and SEQ ID NO:624, SEQ ID NO:700 and SEQ ID NO:614, SEQ ID NO:700 and SEQ ID NO:624, SEQ ID NO:710 and SEQ ID NO:614, SEQ ID NO:710 and SEQ ID NO:624, SEQ ID NO:720 and SEQ ID NO:614, SEQ ID NO:720 and SEQ ID NO:624, respectively.

[0028] In some embodiments, the antibody comprises: a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, a VH-CDR3 comprising the amino acid sequence YSY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or c) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or d) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47, or e) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, a VH-CDR3 comprising the amino acid sequence YSF, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or f) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or g) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, a VH-CDR3 comprising the amino acid sequence YSY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77, or h) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87, or i) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97, or j) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or k) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117, or l) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 282, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287, or m) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197, or n) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or o) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or p) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167, or q) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177, or r) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187, or s) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or t) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 216, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 217, or u) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227, or v) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237, or w) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 242, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 243, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247, or x) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257, or y) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267, or z) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 273, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 277, or aa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 301, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 307, or bb) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 313, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or cc) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 321, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 322, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 325, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327, or dd) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or ee) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 343, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 346, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347, or ff) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 355, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357, or gg) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 363, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 365, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367, or hh) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347, or ii) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387, or jj) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 395, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357, or kk) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 405, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357, or ll) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 411, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 413, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or mm) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 421, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 422, a VH-CDR3 comprising the amino acid sequence GNY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 425, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 426, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 427, or nn) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 431, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 432, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 433, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 436, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 437, or oo) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 442, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 443, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or pp) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 461, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 465, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467, or qq) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 473, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 475, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 476, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 477, or rr) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 481, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 482, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 483, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 487, or ss) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 492, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 493, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 495, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 496, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 497, or tt) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 502, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 503, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or uu) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 512, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 513, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 515, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 516, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 517, or vv) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 521, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 522, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 525, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467, or ww) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 532, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 533, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 537, or xx) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 542, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 543, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347, or yy) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 553, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 555, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557, or zz) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 563, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 565, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557, or aaa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 571, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 573, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or bbb) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 581, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 582, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 583, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 585, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 586, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 587, or ccc) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or ddd) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or eee) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 663, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or fff) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 673, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or ggg) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or hhh) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0029] These alpha-synuclein binding antibodies may constitute separate aspects of the invention.

[0030] In some embodiments, an isolated nucleic acid is provided that encodes an antibody, or antigen-binding fragment or derivative thereof, as described herein. In some embodiments, a host cell is provided that comprises an isolated nucleic acid that encodes an antibody, or antigen-binding fragment or derivative thereof, as described herein. In some embodiments, a method of producing an antibody, or antigen-binding fragment or derivative thereof, is provided, the method comprising culturing a host cell under conditions suitable for producing the antibody, or antigen-binding fragment or derivative thereof.

[0031] In some embodiments, an immunoconjugate is provided comprising an isolated antibody, antigen-binding fragment or derivative thereof described herein and a therapeutic agent. In some embodiments, a labeled antibody, antigen-binding fragment or derivative thereof is provided comprising an antibody, antigen-binding fragment or derivative thereof described herein and a detectable label.

[0032] In some embodiments, a pharmaceutical composition is provided that comprises an isolated antibody, antigen-binding fragment, or derivative thereof described herein and a pharma- ceutical acceptable carrier and / or excipient.

[0033] As used herein, the term "isolated" means that a compound, such as a nucleic acid or an antibody, may be separated and / or recovered from its natural environment. In the present invention, the compound is preferably chemically synthesized or synthesized in a cellular system different from the naturally occurring cell, and is therefore "isolated" from its naturally associated components. The compound may be, for example, isolated from its natural environment by purification or may be produced by a technical process, including but not limited to gene synthesis, polymerase chain reaction (PCR), vector purification, and protein (antibody) purification. Such a compound may be, inter alia, a nucleic acid, DNA, RNA, or cDNA sequence, or a peptide, antibody, or protein.

[0034] The present invention is not limited to isolated antibodies as defined above, but also relates to such antibodies regardless of their origin.

[0035] The same applies to the peptides, nucleic acids, DNA, RNA and / or cDNA sequences provided by the present invention, including in isolated form, as defined above, or in any other form.

[0036] In some embodiments, the present invention is directed to Parkinson's disease (sporadic, familial with alpha-synuclein mutations, familial with non-alpha-synuclein mutations, pure dysautonomia, and Lewy body dysphagia), Lewy body dementia [LBD; dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)], diffuse Lewy body disease (DLBD), sporadic Alzheimer's disease, familial Alzheimer's disease with APP mutations, familial Alzheimer's disease with PS-1, PS-2 or other mutations, familial British dementia, Lewy body dementia, Bea body variants, multiple system atrophy (Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy), inclusion body myositis, traumatic brain injury, chronic traumatic encephalopathy, dementia pugilistica, tauopathies (Pick's disease, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia with parkinsonism linked to chromosome 17, and Niemann-Pick disease type C1), Down's syndrome, Creutzfeldt-Jakob disease, Huntington's disease, motor neuron disease, amyotrophic lateral sclerosis (sporadic, familial, ALS-dementia complex of Guam) Methods are provided for preventing, alleviating and / or treating diseases, disorders or conditions associated with α-synuclein aggregates or pathological α-synuclein, such as α-synuclein complex of Guam), optic atrophy, neurodegeneration with cerebral iron deposition type 1 (Hallervorden-Spatz syndrome), prion diseases, Gerstmann-Straussler-Scheinker disease, ataxia-telangiectasia, Meige syndrome, subacute sclerosing panencephalitis, Gaucher disease, Krabbe disease, and other lysosomal storage disorders (including Kufour-Rakeb syndrome and Sanfilippo syndrome), or rapid eye movement (REM) sleep behavior disorder. According to one embodiment, the method of the invention comprises administering to a subject in need thereof an effective concentration or amount of a binding molecule of the invention, particularly an antibody or antigen-binding fragment or derivative thereof (e.g., a full-length antibody, or an α-synuclein-binding fragment or derivative of an antibody) that binds α-synuclein, as described herein.

[0037] In some embodiments, provided is a method of preserving motor capability or improving motor impairment in a subject suffering from a synucleopathy, including bradykinesia, rigidity, resting tremor, or impaired postural reflexes, comprising administering to a subject in need thereof an antibody, or antigen-binding fragment or derivative thereof, as described herein, or a pharmaceutical composition comprising an antibody, or antigen-binding fragment or derivative thereof, as described herein.

[0038] In some embodiments, a method of preserving or increasing cognitive ability in a subject suffering from a synucleinopathy is provided, comprising administering to a subject in need thereof an antibody or antigen-binding fragment or derivative thereof described herein, or a pharmaceutical composition comprising an antibody or antigen-binding fragment or derivative thereof described herein.

[0039] In some embodiments, the isolated antibodies or antigen-binding fragments or derivatives thereof described herein are provided for use as a medicament. In some embodiments, the isolated antibodies or antigen-binding fragments or derivatives thereof described herein are provided for use in ameliorating, preventing, and / or treating a synucleinopathy in a subject. In some embodiments, the use of the antibodies or antigen-binding fragments or derivatives thereof described herein is provided for the manufacture of a medicament for preventing, ameliorating, and / or treating a disease, disorder, and / or condition associated with α-synuclein aggregates.

[0040] In some embodiments, the disease, disorder and / or condition associated with α-synuclein aggregates is a synucleinopathy. In some embodiments, the synucleinopathy is Parkinson's disease (sporadic, familial with α-synuclein mutations, familial with non-α-synuclein mutations, pure dysautonomia, and Lewy body dysphagia), Lewy body dementia [LBD; dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)], diffuse cortical Lewy body disease (DLBD), sporadic Alzheimer's disease, familial Alzheimer's disease with APP mutations, familial Alzheimer's disease with PS-1, PS-2 or other mutations, familial British dementia, Alzheimer's disease ... Lewy body variant of Luxheimer's disease, multiple system atrophy (Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy), inclusion body myositis, traumatic brain injury, chronic traumatic encephalopathy, dementia pugilistica, tauopathies (Pick's disease, frontotemporal dementia, progressive supranuclear palsy, basal ganglia degeneration, frontotemporal dementia with parkinsonism linked to chromosome 17, and Niemann-Pick disease type C1), Down's syndrome, Creutzfeldt-Jakob disease, Huntington's disease, motor neuron disease, amyotrophic lateral sclerosis (sporadic, familial, ALS-dementia complex of Guam) complex of Guam), optic atrophy, neurodegeneration with cerebral iron deposition type 1 (Hallervorden-Spatz syndrome), prion diseases, Gerstmann-Sträussler-Scheinker disease, ataxia-telangiectasia, Meige syndrome, subacute sclerosing panencephalitis, Gaucher disease, Krabbe disease, and other lysosomal storage disorders (including Kufour-Rakeb syndrome and Sanfilippo syndrome), or rapid eye movement (REM) sleep behavior disorder.

[0041] More particularly, the synucleinopathy is selected from Parkinson's disease, multiple system atrophy, Lewy body dementia [LBD; dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)], and diffuse Lewy body disease.

[0042] In some embodiments, a method is provided for detecting α-synuclein aggregates, including but not limited to Lewy bodies, Lewy neurites, and / or glial cytoplasmic inclusions, comprising contacting a sample with an antibody or antigen-binding fragment or derivative thereof described herein and detecting the presence of the aggregates using methods known in the art. In some embodiments, the sample is a brain sample, a cerebrospinal fluid sample, or a blood sample.

[0043] In some embodiments, methods are provided for evaluating an α-synuclein binding molecule for its ability to inhibit and / or delay seed-dependent and / or spontaneous α-synuclein aggregation, comprising the steps of contacting the α-synuclein binding molecule with α-synuclein aggregates (seeds); allowing the α-synuclein binding molecule to bind to the α-synuclein aggregates to form an immunological complex; adding α-synuclein monomer protein and a detectable dye, particularly a fluorescent dye, to the immunological complex; and determining the time to reach a half-maximum signal of the detectable dye, particularly a fluorescent dye, compared to seed-dependent aggregation in the absence of binding molecule, where an increase in the time to reach a half-maximum signal of the detectable dye in the presence of binding molecule compared to seed-dependent aggregation in the absence of binding molecule indicates that the α-synuclein binding molecule is capable of inhibiting and / or delaying the seed-dependent and / or spontaneous α-synuclein aggregation.

[0044] In a further embodiment, a method is provided for selecting / screening an α-synuclein binding molecule capable of inhibiting and / or delaying seed-dependent and / or spontaneous α-synuclein aggregation, comprising the steps of contacting an α-synuclein binding molecule with α-synuclein aggregates (seeds); binding the α-synuclein binding molecule to the α-synuclein aggregates to form an immunological complex; adding α-synuclein monomer protein and a detectable dye, particularly a fluorescent dye, to the immunological complex; and selecting the α-synuclein binding molecule as one capable of inhibiting and / or delaying seed-dependent and / or spontaneous α-synuclein aggregation based on the signal of the detectable dye, particularly the fluorescent dye, determined in the absence and presence of the α-synuclein binding molecule.

[0045] In some embodiments, methods are provided for evaluating or selecting alpha-synuclein binding molecules capable of inhibiting and / or delaying seed-dependent and / or spontaneous alpha-synuclein aggregation, wherein the detectable dye is thioflavin (ThT), which binds to β-sheet structures of the aggregating protein.

[0046] In some embodiments, methods are provided for evaluating or selecting alpha-synuclein binding molecules capable of inhibiting and / or delaying seed-dependent and / or spontaneous alpha-synuclein aggregation, where alpha-synuclein monomer protein is covalently linked to a detectable dye, particularly a fluorescent dye, and / or the signal of the detectable dye, particularly a fluorescent dye, is the quenching of the signal / fluorescence emission upon the formation of protein aggregates. Other detection methods, including, for example, fluorescence resonance energy transfer (FRET) assays, are also contemplated within the scope of the present invention. Dyes, particularly fluorescent dyes, are known to those skilled in the art. Fluorescent dyes include, for example, green fluorescent protein, yellow fluorescent protein, etc.

[0047] In some embodiments, an α-synuclein binding molecule is assessed or selected in step d) of the present invention as being capable of inhibiting and / or delaying seed-dependent and / or spontaneous α-synuclein aggregation if seed-dependent and / or spontaneous α-synuclein aggregation is inhibited and / or delayed by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, or 300%, respectively, in the presence of the α-synuclein binding molecule compared to the absence of the α-synuclein binding molecule. Alternatively, an α-synuclein binding molecule can be assessed as being capable of inhibiting and / or delaying seed-dependent and / or spontaneous α-synuclein aggregation if it causes at least a 10% increase in the aggregation half-time (τ value) of seed-dependent aggregation compared to seed-dependent aggregation in the absence of the binding molecule.

[0048] In some embodiments, a method for determining or evaluating an alpha-synuclein binding molecule for its ability to delay and / or inhibit seed-dependent alpha-synuclein aggregation comprises: (i) incubating a cell containing and / or expressing a monomeric α-synuclein reporter protein with a composition comprising an α-synuclein binding molecule and a transduction reagent capable of delivering the α-synuclein binding molecule to the cell; (ii) incubating the cells with a composition comprising alpha-synuclein aggregates (seeds) and a transduction reagent; and (iii) determining de novo aggregation of the alpha-synuclein reporter protein to determine or assess the ability of the alpha-synuclein binding molecule to delay and / or inhibit seed-dependent alpha-synuclein aggregation.

[0049] In methods for determining or evaluating an α-synuclein binding molecule for its ability to delay and / or inhibit seed-dependent α-synuclein aggregation, a composition comprising an α-synuclein binding molecule and a transduction reagent is pre-mixed prior to incubation with cells containing and / or expressing a monomeric α-synuclein reporter protein. In some embodiments, methods for determining or evaluating an α-synuclein binding molecule for its ability to delay and / or inhibit cellular uptake of pathological and / or aggregated α-synuclein include: (i) incubating cells containing and / or expressing monomeric alpha-synuclein with an alpha-synuclein binding molecule; (ii) incubating the cells with α-synuclein aggregates (seeds); and (iii) determining de novo aggregates of α-synuclein to determine or evaluate the ability of said α-synuclein binding molecule to delay and / or inhibit cellular uptake of pathological and / or aggregated α-synuclein; Includes.

[0050] In some embodiments of the invention, the alpha-synuclein binding molecule for the methods of determining or evaluating an alpha-synuclein binding molecule for its ability to delay and / or inhibit seed-dependent alpha-synuclein aggregation preferably comprises an alpha-synuclein antibody or an antigen-binding fragment or derivative thereof, more preferably an antibody or an antigen-binding fragment or derivative thereof of the invention.

[0051] In some embodiments of the invention, the transfection reagents in (i) and (ii) of the method of determining or evaluating an α-synuclein binding molecule for its ability to delay and / or inhibit seed-dependent α-synuclein aggregation may be the same or different, preferably the transfection reagents are different, more preferably the transfection reagent in (i) comprises Ab-DeliverIN™ and the transfection reagent in (ii) comprises Lipofectamine™ 2000.

[0052] In some embodiments of the invention, step (iii) of the method of determining or evaluating α-synuclein binding molecules for their ability to delay and / or inhibit seed-dependent α-synuclein aggregation comprises immunohistochemistry, microscopy, biochemistry or flow cytometry detection methods, preferably immunohistochemistry, more preferably immunohistochemistry by measuring the fluorescence of fluorescently labeled α-synuclein expressed by the cells.

[0053] In some embodiments of the invention, a method for determining or evaluating an alpha-synuclein binding molecule for its ability to delay and / or inhibit seed-dependent alpha-synuclein aggregation comprises: (i) incubating a cell containing and / or expressing a monomeric α-synuclein reporter protein with a composition comprising an α-synuclein binding molecule and a transduction reagent capable of delivering the α-synuclein binding molecule to the cell; (ii) incubating the cells with a composition comprising alpha-synuclein aggregates (seeds) and a transduction reagent; and (iii) determining de novo aggregation of the alpha-synuclein reporter protein to determine or evaluate the ability of the alpha-synuclein binding molecule to delay and / or inhibit seed-dependent alpha-synuclein aggregation. Including, The incubation time in step (i) is up to 12 hours, preferably 5 hours, and said incubation time in step (ii) is at least 12 hours, preferably 96 hours, the transfection reagent in (i) is Ab-DeliverIN™ and the transfection reagent in (ii) is Lipofectamine™ 2000.

[0054] Thus, in the context of the present invention, the term "transduction reagent" (or "transfection reagent") as used herein primarily refers to a preparation capable of forming a non-covalent complex with a molecule of interest to be transported into a cell. Transduction reagents include, but are not limited to, Ab-DeliverIN™, Lipofectamine™ 2000, Xfect™ Transfection Reagent, ViaFect™ Transfection Reagent, Polyethylenimine (PEI) Cell Transfection Reagent, or FuGENE™.

[0055] In some embodiments, an α-synuclein binding molecule is assessed as being capable of delaying and / or inhibiting seed-dependent α-synuclein aggregation using the methods of the invention if seed-dependent α-synuclein aggregation is delayed and / or inhibited by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, or 300% in the presence of the α-synuclein binding molecule compared to the absence of the α-synuclein binding molecule being assessed. Alternatively, an α-synuclein binding molecule may be assessed as being capable of delaying and / or inhibiting seed-dependent α-synuclein aggregation if the α-synuclein binding molecule causes at least a 10% decrease in the level of aggregated α-synuclein compared to the level of aggregated α-synuclein in the absence of the binding molecule.

[0056] Within the scope of the present invention, α-synuclein may have the sequence of SEQ ID NO: 1. α-synuclein aggregates are multimeric β-sheet-rich assemblies of α-synuclein monomers that can form either soluble oligomers or soluble / insoluble prefibrils or mature fibrils that coalesce into intracellular deposits detected as a range of Lewy pathologies in Parkinson's disease and other synucleinopathies. α-synuclein under physiological conditions is classified as a non-natively folded protein that does not adopt an ordered tertiary structure, but rather can exist as a mixture of dynamic and flexible structural conformations. Misfolded α-synuclein can form multimeric intermediate oligomeric structures that ultimately assemble into higher-order fibrillar aggregates.

[0057] As used herein, the term "aggregated α-synuclein" refers to insoluble or soluble oligomeric and / or polymeric structures composed of misfolded monomers and / or multimers and / or assemblies of monomers of α-synuclein.

[0058] Pathological α-synuclein is misfolded or aggregated or post-translationally modified α-synuclein, which is the main component of Lewy pathology. Lewy pathology can be detected as having the following morphologies: Lewy bodies, Lewy neurites, immature Lewy bodies or pale bodies or perinuclear deposits with diffuse, granular, punctate or polymorphic patterns. In addition, pathological α-synuclein is a major component of intracellular fibrillar inclusions, also called glial cytoplasmic inclusions, detected in oligodendrocytes, and in neuronal cell bodies, axons and nuclei (also called neuronal cytoplasmic inclusions), which are histological hallmarks of multiple system atrophy. Pathological α-synuclein in Lewy pathology often shows substantial increases in post-translational modifications, such as phosphorylation, ubiquitination, nitration, and truncation.

[0059] The seeds are multimeric β-sheet rich structures composed of α-synuclein and may also be composed (i.e., in addition to α-synuclein) of other amyloidogenic proteins (e.g., Tau, amyloid β), which may accelerate the aggregation kinetics of α-synuclein by elongating the growing multimers and / or by acting as templates for the nucleation of monomers on the seed surface.

[0060] Spontaneous aggregation of α-synuclein is an aggregation process that proceeds without the addition of seeds. α-synuclein is a soluble protein that has the tendency, under certain conditions, to spontaneously aggregate and form soluble oligomers or soluble / insoluble prefibrils or mature fibrils or detergent-insoluble aggregates.

[0061] Lewy bodies are abnormal aggregates of proteins that develop in neuronal cells in Parkinson's disease (PD), Lewy body dementia, and other synucleinopathies. Lewy bodies appear as spherical masses that replace other cellular components. Morphologically, Lewy bodies can be classified as brainstem or cortical type. Classical brainstem Lewy bodies are eosinophilic intracytoplasmic inclusions consisting of a dense core surrounded by a 5-10 nm wide radial fibrillar halo, the major structural component of which is α-synuclein. Cortical Lewy bodies differ by lacking the halo. The presence of Lewy bodies is a hallmark of Parkinson's disease.

[0062] Lewy neurites are abnormal neurites in diseased neurons that contain granular material, abnormal α-synuclein filaments similar to those seen in Lewy bodies, punctate, varicose structures, and axonal spherules. Like Lewy bodies, Lewy neurites are a hallmark of α-synucleinopathies such as dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy.

[0063] Glial cytoplasmic inclusions (also called Papp-Lantos inclusions) consist of insoluble α-synuclein filamentous aggregates detected in oligodendrocytes in the white matter of the brain in multiple system atrophy. α-synuclein aggregates in neuronal cell bodies, axons and nuclei, called neuronal cytoplasmic inclusions, are a characteristic cytopathological feature of multiple system atrophy. Detection of glial cytoplasmic inclusions is considered characteristic evidence for the neuropathological diagnosis of multiple system atrophy.

[0064] An α-synuclein-binding molecule is a molecule that binds to pathological and / or aggregated α-synuclein protein, such as an α-synuclein antibody or a fragment thereof, at a specific recognition site or epitope. The antigen-binding molecule of the present invention binds to an epitope within the amino acid sequence of SEQ ID NO: 1. The epitope may be a linear or non-linear epitope. Preferably, the antigen-binding molecule of the present invention binds to amino acid residues 1 to 15 (SEQ ID NO: 121), 10 to 24 (SEQ ID NO: 122), 28 to 42 (SEQ ID NO: 124), 36 to 40 (SEQ ID NO: 2), 37 to 51 (SEQ ID NO: 125), 51 to 57 (SEQ ID NO: 3), 51 to 58 (SEQ ID NO: 136), 65 to 74 (SEQ ID NO: 4), 65 to 81 (SEQ ID NO: 5), 81 to 120 (SEQ ID NO: 6) of human α-synuclein in SEQ ID NO: 1. More preferably, the antigen-binding molecule of the present invention binds to an epitope within amino acid residues 124 to 131 (SEQ ID NO: 7), 128 to 135 (SEQ ID NO: 8), or 131 to 140 (SEQ ID NO: 9) of human α-synuclein of SEQ ID NO: 1. Even more preferably, the antigen-binding molecule of the present invention binds to an epitope comprising amino acids 126 and 127 of human α-synuclein of SEQ ID NO: 1 as important residues for binding. In another embodiment, the antigen binding molecule of the present invention binds to a non-linear epitope within the amino acid residues of human α-synuclein of SEQ ID NO:1.

[0065] Other alpha-synuclein binding molecules may also include multivalent molecules, multispecific molecules (e.g., diabodies or biparatopic antibodies), fusion molecules, aptamers, avimers, or other naturally occurring or recombinantly produced molecules. Exemplary antigen-binding molecules useful in the present invention include antibody-like molecules. Antibody-like molecules are molecules that can exhibit functions by binding to target molecules (see, for example, Current Opinion in Biotechnology 2006, 17:653-658; Current Opinion in Biotechnology 2007, 18:1-10; Current Opinion in Structural Biology 1997, 7:463-469; Protein Science 2006, 15:14-27), and include, for example, DARPins (WO 2002 / 020565), Affibodies (WO 1995 / 001937), Avimers (WO 2004 / 044011; WO 2005 / 040229), Adnectins (WO 2002 / 032925), and fynomers (WO 2013 / 135588).

[0066] As used herein, an "antigen binding molecule" is any molecule capable of specifically or selectively binding to an antigen. A binding molecule may include or be an antibody or a fragment thereof. An alpha-synuclein binding molecule is a molecule that binds to an alpha-synuclein protein at a specific recognition site, epitope, such as an alpha-synuclein antibody or a fragment thereof.

[0067] As used herein, the terms "α-synuclein antibody," "anti-α-synuclein antibody," and "antibody that binds pathological and / or aggregated α-synuclein," or simply "antibody," refer to an antibody that can bind with sufficient affinity to pathological α-synuclein and / or aggregated α-synuclein, including but not limited to Lewy bodies, Lewy neurites, or glial cytoplasmic inclusions, which antibodies are useful as therapeutic and / or diagnostic agents in targeting α-synuclein. In one embodiment, the extent of binding of an α-synuclein antibody of the invention to unrelated non-α-synuclein proteins is less than about 10% of the binding of the antibody to α-synuclein as measured, for example, by radioimmunoassay (RIA).

[0068] In general, the term "antibody" is used herein in its broadest sense to encompass a variety of antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), fully human antibodies, and antibody fragments, so long as they exhibit the desired antigen-binding activity. Antibodies within the present invention may be chimeric antibodies (especially mouse VH and VL regions fused with human constant domains), recombinant antibodies, antigen-binding fragments of recombinant antibodies, humanized antibodies, or antibodies displayed on the surface of phage or presented on the surface of chimeric antigen receptor (CAR) T cells.

[0069] An "antigen-binding fragment" of an antibody refers to a molecule other than an intact antibody that contains a portion of an intact antibody and binds to the antigen to which the intact antibody binds. Antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments.

[0070] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies that make up the population are identical except for possible natural mutations that may be present in minor amounts. Monoclonal antibodies are directed against a single antigenic site and are highly specific. The modification "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and should not be construed as requiring production of the antibody by any particular method. As noted above, the monoclonal antibodies used in accordance with the present invention may be produced by the hybridoma method described in Kohler, Nature 256 (1975), 495.

[0071] Thus, in the context of the present invention, the term "antibody" relates to complete immunoglobulin molecules as well as to parts of such immunoglobulin molecules (i.e. "antigen-binding fragments thereof"). Furthermore, the term relates to modified and / or altered antibody molecules, as described above. The term also relates to recombinantly or synthetically produced / synthesized antibodies. The term also relates to intact antibodies, as well as antibody fragments thereof, such as separated light and heavy chains, Fab, Fv, Fab', Fab'-SH, F(ab')2. The term "antibody" also includes, but is not limited to, fully human antibodies, chimeric antibodies, humanized antibodies, CDR-grafted antibodies, and antibody constructs, such as single chain Fv (scFv) or antibody fusion proteins.

[0072] Humanized antibodies are modified antibodies, also called reshaped human antibodies. Humanized antibodies are constructed by transferring the CDRs of antibodies from immunized animals to the complementarity determining regions of human antibodies. Conventional recombinant gene technology for such purposes is known (see EP 239400; WO 96 / 02576; Sato K. et al., Cancer Research 1993, 53:851-856; WO 99 / 51743).

[0073] The term "CDR" as used herein relates to "complementarity determining region" as it is known in the art. CDRs are the parts of immunoglobulins that determine the specificity of the molecule and contact a particular ligand. CDRs are the most variable parts of the molecule and contribute to the diversity of these molecules. There are three CDR regions in each V domain: CDR1, CDR2 and CDR3. VH-CDR or CDR-H denotes the CDR region of the variable heavy chain and VL-CDR or CDR-L relates to the CDR region of the variable light chain. VH means variable heavy chain and VL means variable light chain. The CDR regions of Ig derived regions can be determined as described in Kabat "Sequences of Proteins of Immunological Interest", 5th edit. NIH Publication no. 91-3242 USDepartment of Health and Human Services (1991); Chothia J., Mol.Biol.196 (1987), 901-917 or Chothia, Nature 342 (1989), 877-883.

[0074] The "Fc" region comprises two heavy chain fragments comprising the CH2 and CH3 domains of an antibody. The two heavy chain fragments are held together by two or more disulfide bonds and hydrophobic interactions of the CH3 domain.

[0075] A "Fab' fragment" contains one light chain and a portion of one heavy chain containing the VH domain and the CH1 domain, as well as the region between the CH1 and CH2 domains, and an interchain disulfide bond can be formed between the two heavy chains of two Fab' fragments to form an F(ab')2 molecule.

[0076] An "F(ab')2 fragment" contains two light chains and two heavy chains that contain a portion of the constant region between the CH1 and CH2 domains, with an interchain disulfide bond formed between the two heavy chains. Thus, an F(ab')2 fragment is composed of two Fab' fragments held together by disulfide bonds between the two heavy chains.

[0077] The "Fv region" comprises the variable regions from both the heavy and light chains, but lacks the constant regions.

[0078] Thus, in the context of the present invention, there is provided an antibody molecule or an antigen-binding fragment thereof which has been humanized and which can be successfully used in a pharmaceutical composition.

[0079] An "antibody that binds to an epitope" within a defined region of a protein is an antibody that requires the presence of one or more amino acids within that region in order to bind to the protein.

[0080] In certain embodiments, "antibodies that bind to an epitope" within a defined region of a protein are identified by mutational analysis in which amino acids of the protein are mutated, and the binding of the antibody to the resulting modified protein (e.g., a modified protein that contains the epitope) is determined to be at least 20% of the binding to the unmodified protein. In some embodiments, "antibodies that bind to an epitope" within a defined region of a protein are identified by mutational analysis in which amino acids of the protein are mutated, and the binding of the antibody to the resulting modified protein (e.g., a modified protein that contains the epitope) is determined to be at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of the binding to the unmodified protein. In certain embodiments, antibody binding is determined by a suitable binding assay, such as FACS, WB, or ELISA.

[0081] When used in the context of the present invention, the term "binding to" defines the binding (interaction) of at least two "antigen interaction sites" with each other. The term "antigen interaction site" defines, according to the present invention, a motif of a polypeptide, i.e., a part of an antibody or an antigen-binding fragment of the present invention, which shows a capacity of specific interaction with a certain antigen or a certain group of antigens of α-synuclein. Said binding / interaction is also understood to define a "specific recognition". The term "specifically recognize" means, according to the present invention, that the antibody is able to specifically interact and / or bind with at least two amino acids (also known as "critical residues") of α-synuclein as defined herein, in particular residues 1 to 15 (SEQ ID NO: 121), 10 to 24 (SEQ ID NO: 122), 28 to 42 (SEQ ID NO: 124), 36 to 40 (SEQ ID NO: 2), 37 to 51 (SEQ ID NO: 125), 51 to 57 (SEQ ID NO: 3), 51 to 58 (SEQ ID NO: 136), 65 to 74 (SEQ ID NO: 137) of human α-synuclein of SEQ ID NO: 1. This means that the antigen-binding molecule of the present invention can interact with and / or bind to at least two amino acids within amino acid residues 124 to 131 (SEQ ID NO: 7), 127 to 140 (SEQ ID NO: 135), 128 to 135 (SEQ ID NO: 8), or 131 to 140 (SEQ ID NO: 9) of human α-synuclein in SEQ ID NO: 1. The residues may form a linear or non-linear epitope. Preferably, the antigen-binding molecule of the present invention binds to an epitope within amino acid residues 124 to 131 (SEQ ID NO: 7), 128 to 135 (SEQ ID NO: 8), or 131 to 140 (SEQ ID NO: 9) of human α-synuclein in SEQ ID NO: 1. Even more preferably, the antigen-binding molecule of the present invention can bind to an epitope that includes amino acids 126 and 127 of human α-synuclein of SEQ ID NO: 1 as important residues for binding. The antigen-binding molecule of the present invention can also bind to a non-linear epitope within the amino acid residues of human α-synuclein of SEQ ID NO: 1.

[0082] The cross-reactivity of the antigen-binding molecules under consideration, in particular a panel of antibodies or antigen-binding fragments thereof, can be tested, for example, by evaluating the binding of said panel of antibodies or antigen-binding fragments thereof to the (poly)peptide of interest as well as to several more or less (structurally and / or functionally) closely related (poly)peptides under standard conditions (see, for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, (1988) and Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, (1999)). Only those constructs (i.e. antibodies, antigen-binding fragments thereof, etc.) that bind to a particular structure of α-synuclein as defined herein, e.g. a specific epitope or (poly)peptide / protein of α-synuclein as defined herein, but do not or essentially do not bind to any of the other epitopes or (poly)peptides of the same α-synuclein, are considered to be specific for the epitope or (poly)peptide / protein of interest and are selected for further studies according to the methods provided herein. These methods may include, inter alia, binding studies, blocking studies, and competition studies with structurally and / or functionally closely related molecules. These binding studies include by FACS analysis, surface plasmon resonance (e.g., SPR with BIACORE™), analytical ultracentrifugation, isothermal titration calorimetry, fluorescence polarization, fluorescence spectroscopy, or radiolabeled ligand binding assays.

[0083] Thus, specificity can be determined experimentally by methods known in the art and described herein, including, but not limited to, Western blot, ELISA test, RIA test, ECL test, IRMA test, and peptide scan.

[0084] A person skilled in the art will understand that the epitopes may be contained in the α-synuclein protein or in its degradation products, or may be chemically synthesized peptides. The amino acid positions are shown only to indicate the position of the corresponding amino acid sequence in the sequence of the α-synuclein protein. The present invention encompasses all peptides that contain the epitopes. The peptides may be part of a polypeptide more than 100 amino acids long, or may be small peptides less than 100 amino acids, preferably less than 50 amino acids, more preferably less than 25 amino acids, even more preferably less than 18 amino acids. The amino acids of such peptides may be natural or unnatural amino acids (e.g., β-amino acids, γ-amino acids, D-amino acids) or combinations thereof. Furthermore, the present invention may encompass retro-inverso peptides of each of the epitopes. The peptides may be unlinked or linked. For example, it may be bound to a small molecule (e.g., a drug or a fluorophore), a high molecular weight polymer (e.g., polyethylene glycol (PEG), polyethyleneimine (PEI), hydroxypropyl methacrylate (HPMA), etc.), or a protein, fatty acid, sugar moiety, or may be inserted into a membrane. To test whether the antibody under consideration and the antibody of the present invention recognize the same or similar epitope, many assays are known in the art, some of which (e.g., "alanine scanning mutagenesis") are described in the Examples below.

[0085] Whether an antibody recognizes the same epitope as that recognized by another antibody provided herein or recognizes an overlapping epitope can be confirmed by the competition between the two antibodies for the epitope. Competition between antibodies can be evaluated by competitive binding assays using such means as enzyme-linked immunosorbent assay (ELISA), fluorescence energy transfer (FRET), and fluorescence microassay technology (FMAT®). The amount of antibody that binds to the antigen indirectly correlates with the binding ability of a competing candidate antibody (test antibody) that competitively binds to the same or overlapping epitope. In other words, as the amount or affinity of the test antibody to the same or overlapping epitope increases, the amount of antibody bound to the antigen decreases and the amount of the test antibody bound to the antigen increases. In detail, an appropriately labeled antibody and a test antibody are added to the antigen simultaneously, and then the bound antibody is detected using a label. The amount of antibody bound to the antigen can be easily determined by labeling the antibody in advance. The label is not particularly limited, and the labeling method is selected according to the assay technology used. Specific labeling methods include fluorescent labeling, radiolabeling, and enzyme labeling.

[0086] As used herein, "antibodies that bind to overlapping epitopes" or "antibodies that bind to the same epitope" refer to a test antibody that can reduce the binding amount of a labeled antibody by at least 50% at a concentration that is usually 100-fold, preferably 80-fold, more preferably 50-fold, even more preferably 30-fold, and even more preferably 10-fold higher than the concentration of unlabeled antibody at the time of binding that reduces the binding amount of the labeled antibody by 50% (IC50). The epitope recognized by an antibody can be analyzed by a method known to those skilled in the art, for example, by Western blotting.

[0087] In some embodiments, the antibody comprises: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10, or b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 20 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 20; or c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; or d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; or e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 50 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 50; or f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; or g) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; or h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 90; or i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; or j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; or k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 280 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 280; or l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 290 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 290; or m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; or n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; or o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; or p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170, or q) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; or r) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 190 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 190; or s) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 200 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200; or t) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 210 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 210; or u) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 220 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 220; or v) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 230 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 230; or w) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 240 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 240; or x) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 250 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 250, or y) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 260 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 260; or z) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 270 or having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 270; or aa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 300 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 300; or bb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 310 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 310; or cc) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 320 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 320, or dd) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 330 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 330; or ee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 340 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 340; or ff) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 350 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 350, or gg) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 360 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 360; or hh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 370 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 370; or ii) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 380 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 380; or jj) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 390 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 390; or kk) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 400 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400; or ll) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 410 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410; or mm) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 420 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420; or nn) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 430 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430; or oo) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 440 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440; or pp) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 450 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450; or qq) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 460 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460; or rr) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 470 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 470; or ss) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 480 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480; or tt) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 490 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 490; or uu) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 500 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 500; or vv) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 510 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 510, or ww) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 520 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520; or xx) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 530 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 530; or yy) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 540 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 540; or zz) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 550 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 550; or aaa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 560 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 560; or bbb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 570 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 570; or ccc) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 580 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 580, or ddd) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 590 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 590; or eee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 600 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 600; or fff) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 610, or ggg) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620; or hhh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630; or iii) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640; or jjj) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650; or kkk) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 660 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 660; or lll) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 670 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 670; or mmm) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 680 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 680; or nnn) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 690; or ooo) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 700; or ppp) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 710; or qqq) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO:720 or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:720.

[0088] In some embodiments, the antibody comprises: a) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 14, or b) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 24 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 24; or c) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; or d) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44; or e) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 54 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 54; or f) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64; or g) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 74; or h) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; or i) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or j) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 104; or k) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114, or l) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 284, or m) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 194; or n) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 144; or o) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; or p) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 174; or q) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184, or r) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 204 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 204; or s) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 214 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 214; or t) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 224 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 224; or u) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 234 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 234; or v) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 244 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 244; or w) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 254 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 254; or x) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 264 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 264; or y) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 274 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 274; or z) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 304 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 304; or aa) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 314 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 314, or bb) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 324 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 324; or cc) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 334 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 334, or dd) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 344 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 344; or ee) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 354 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 354; or ff) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 364 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 364; or gg) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 374 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 374; or hh) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 384 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 384; or ii) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 394 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 394; or jj) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 404 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or kk) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414; or ll) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or mm) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 434 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or nn) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 464 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 464; or oo) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 474 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 474; or pp) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 484; or qq) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 494 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 494; or rr) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 504 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 504; or ss) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 514 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 514; or tt) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 524 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 524; or uu) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 544; or vv) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 554; or ww) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 564 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 564; or xx) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 574 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 574; or yy) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 584 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 584; or zz) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or aaa) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; or bbb) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; or ccc) a light chain variable region (VL) comprising the sequence of SEQ ID NO:644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:644.

[0089] In some embodiments, the antibody comprises: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14, or b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 20 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 24, or c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34, or d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44, or e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 50 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 54, or f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64, or g) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74, or h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84, or i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94, or j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104, or k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114, or l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 280 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 284, or m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 290 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194, or n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144, or o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154, or p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164, or q) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174, or r) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184, or s) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 190 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194, or t) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 200 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 204, or u) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 210 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 214, or v) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 220 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 224, or w) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 230 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 234, or x) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 240 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 244, or y) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 250 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 254, or z) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 260 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 264, or aa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 270 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 274, or bb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 300 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 304, or cc) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 310 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 314, or dd) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 320 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 324, or ee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 330 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 334, or ff) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 340 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 344, or gg) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 350 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 354, or hh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 360 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 364; or ii) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 370 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 374, or jj) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 380 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 384, or kk) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 390 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 394; or ll) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 404, or mm) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414, or nn) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424, or oo) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 434, or pp) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 440 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414, or qq) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 450 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424, or rr) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 460 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 464, or ss) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 470 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 474, or tt) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 484, or uu) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 490 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 494; or vv) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 500 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 504, or ww) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 510 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 514, or xx) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 524, or yy) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 530 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 534; or zz) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 540 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 544, or aaa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 550 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554, or bbb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 560 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 564, or ccc) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 570 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 574, or ddd) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 580 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 584; or eee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 590 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 474, or fff) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 600 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554, or ggg) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614; or hhh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624; or iii) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634; or jjj) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644; or kkk) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or lll) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or mmm) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634, or nnn) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644; or ooo) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or ppp) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or qqq) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634, or rrr) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644; or sss) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or tt) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or uuu) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634, or vvv) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644, or www) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or xxx) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or yyy) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634; or zzz) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644; or aaaa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 660 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or bbbb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 670 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or cccc) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 680 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or dddd) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614; or eeee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624; or ffff) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or gggg) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624; or hhhh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or iiii) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or jjjj) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 720 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614; or kkkk) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 720 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624.

[0090] In some embodiments, the antibody comprises: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 14; b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 20 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 20, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 24 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 24; c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44; e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 50 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 50, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 54 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 54; f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64; g) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 74; h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 90, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 100, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 104, or k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114, or l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 280 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 280, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 284, or m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 290 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 290, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 194; or n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 144, or o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; or p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or a heavy chain variable region (VH) having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164, or q) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 174, or r) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184, or s) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 190 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 190, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 194, or t) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 200 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 204 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 204, or u) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 210 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 210, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 214 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 214, or v) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 220 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 220, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 224 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 224; or w) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 230 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 230, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 234 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 234, or x) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 240 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 240, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 244 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 244, or y) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 250 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 250, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 254 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 254, or z) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 260 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 260, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 264 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 264, or aa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 270 or having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 270, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 274 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 274, or bb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 300 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 300, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 304 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 304, or cc) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 310 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 310, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 314 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 314, or dd) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 320 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 320, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 324 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 324; or ee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 330 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 330, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 334 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 334; or ff) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 340 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 340, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 344 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 344, or gg) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 350 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 350, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 354 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 354; or hh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 360 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 360, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 364 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 364; or ii) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 370 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 370, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 374 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 374; or jj) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 380 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 380, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 384 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 384; or kk) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 390 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 390, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 394 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 394; or ll) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 400 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 404 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404, or mm) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 410 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414, or nn) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 420 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or oo) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 430 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 434 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434, or pp) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 440 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414; or qq) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 450 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or rr) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 460 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 464 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 464; or ss) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 470 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 470, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 474 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 474; or tt) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 480 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 484, or uu) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 490 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 490, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 494 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 494; or vv) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 500 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 500, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 504 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 504, or ww) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 510 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 510, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 514 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 514, or xx) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 520 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 524 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 524; or yy) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 530 or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 530, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 534; or zz) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 540 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 540, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 544, or aaa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 550 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 550, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 554; or bbb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 560 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 560, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 564 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 564; or ccc) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 570 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 570, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 574 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 574, or ddd) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 580 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 580, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 584 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 584; or eee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 590 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 590, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 474 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 474; or fff) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 600 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 600, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 554, or ggg) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 610, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or hhh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 610, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; or iii) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 610, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; or jjj) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 610, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 644; or kkk) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or lll) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624, or mmm) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 634, or nnn) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 644; or ooo) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614, or ppp) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; or qqq) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; or rrr) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 644; or sss) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614, or ttt) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; or uuu) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; or vvv) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 644, or www) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or xxx) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624, or yyy) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; or zzz) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 644; or aaaa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 660 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 660, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or bbbb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 670 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 670, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or cccc) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 680 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 680, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614, or dddd) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 690, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or eeee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 690, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; or ffff) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 700, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614, or gggg) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 700, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; or hhhh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 710, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or iiii) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 710, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624, or jjjj) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 720 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 720, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; or kkkk) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 720 or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 720, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98% and 99% sequence identity to the amino acid sequence of SEQ ID NO: 624.

[0091] In some embodiments, the antibody comprises: a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and VH-CDR3 comprising the amino acid sequence YSY; c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; d) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; e) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and VH-CDR3 comprising the amino acid sequence YSF; f) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; g) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, and VH-CDR3 comprising the amino acid sequence YSY; h) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93, or i) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103, or j) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113; or k) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 282, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283; or l) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193; or m) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143, or n) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; or o) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163, or p) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173; or q) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183, or r) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, or s) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213, or t) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223, or u) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233, or v) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 242, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 243, or w) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253; or x) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263, or y) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 273; or z) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 301, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303; or aa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 313, or bb) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 321, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 322, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, or cc) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333, or dd) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 343, or ee) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353; or ff) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 363, or gg) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373, or hh) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383; or ii) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393; or jj) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 411, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 413, or kk) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 421, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 422, and VH-CDR3 comprising the amino acid sequence GNY, or ll) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 431, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 432, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 433, or mm) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 442, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 443, or nn) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 461, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, or oo) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 473, or pp) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 481, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 482, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 483, or qq) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 492, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 493, or rr) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 502, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 503, or ss) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 512, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 513, or tt) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 521, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 522, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, or uu) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 532, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 533, or vv) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 542, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 543, or ww) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 553, or xx) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 563, or yy) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 571, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 573; or zz) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 581, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 582, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 583, or aaa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, or bbb) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 663, or ccc) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 673, or ddd) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683.

[0092] In some embodiments, the antibody comprises: a) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; b) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; c) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47; e) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; f) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; g) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; h) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87; i) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97; j) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107; or k) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117, or l) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287; or m) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197, or n) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or o) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167, or p) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177; or q) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187, or r) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or s) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 216, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 217, or t) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227; u) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237, or v) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247, or w) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257; or x) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267, or y) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 277; or z) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 307, or aa) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or bb) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 325, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327, or cc) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or dd) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 346, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347, or ee) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 355, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357; or ff) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 365, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367, or gg) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347, or hh) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387; or ii) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 395, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357, or jj) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 405, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357; or kk) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 425, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 426, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 427, or ll) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 436, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 437, or mm) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 465, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467, or nn) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 475, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 476, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 477, or oo) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 487, or pp) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 495, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 496, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 497, or qq) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or rr) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 515, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 516, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 517, or ss) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 525, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467, or tt) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347; or uu) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 555, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557, or vv) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 565, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557, or ww) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 585, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 586, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 587, or xx) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or yy) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0093] In some embodiments, the antibody comprises: a) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 11, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 12, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 13, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 having the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 17, or b) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 21, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 22, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to the amino acid sequence YSY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 27, or c) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 31, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 32, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 33, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or d) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 41, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 42, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 43, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47, or e) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 21, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 52, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to the amino acid sequence YSF, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 27, or f) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 61, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 62, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 43, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or g) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 21, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 72, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to the amino acid sequence YSY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77, or h) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 31, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 32, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 33, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87, or i) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 91, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 92, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 93, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97, or j) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 101, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 102, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 103, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or k) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 111, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 112, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 113, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117, or l) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 281, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 282, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 283, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 287, or m) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 31, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 192, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 193, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 197, or n) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 141, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 142, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 143, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 17, or o) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 151, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 152, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 153, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 107, or p) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 161, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 162, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 163, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 167, or q) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 171, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 172, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 173, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 177, or r) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 181, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 182, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 183, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 187, or s) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 201, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 202, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 153, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 107, or t) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 211, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 212, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 213, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 216, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 217, or u) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 31, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 222, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 223, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 227, or v) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 231, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 232, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 233, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 237, or w) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 31, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 242, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 243, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 247, or x) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 31, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 252, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 253, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 257, or y) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 261, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 262, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 263, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 267, or z) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 271, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 272, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 273, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 277, or aa) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 301, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 302, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 303, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 307, or bb) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 311, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 312, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 313, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 67, or cc) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 321, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 322, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 323, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 325, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 327, or dd) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 151, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 332, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 333, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 107, or ee) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 341, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 342, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 343, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 346, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 347, or ff) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 351, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 352, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 353, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 355, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 357, or gg) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 361, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 362, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 363, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 365, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 367, or hh) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 371, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 372, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 373, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 347, or ii) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 351, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 382, ​​a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 383, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 387, or jj) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 351, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 382, ​​a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 393, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 395, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 357, or kk) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 351, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 382, ​​a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 393, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 405, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 357, or ll) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 411, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 412, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 413, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 107, or mm) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 421, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 422, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to the amino acid sequence GNY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 425, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 426, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 427, or nn) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 431, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 432, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 433, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 436, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 437, or oo) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 151, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 442, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 443, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 107, or pp) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 461, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 462, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 463, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 465, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 467, or qq) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 141, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 472, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 473, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 475, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 476, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 477, or rr) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 481, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 482, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 483, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 487, or ss) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 141, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 492, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 493, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 495, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 496, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 497, or tt) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 151, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 502, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 503, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 107, or uu) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 311, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 512, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 513, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 515, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 516, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 517, or vv) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 521, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 522, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 463, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 525, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 467, or ww) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 371, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 532, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 533, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 537, or xx) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 341, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 542, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 543, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 347, or yy) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 551, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 552, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 553, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 555, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 557, or zz) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 551, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 552, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 563, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 565, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 557, or aaa) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 571, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 202, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 573, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 107, or bbb) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 581, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 582, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 583, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 585, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 586, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 587, or ccc) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 11, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 612, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 13, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 17, or ddd) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 11, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 612, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 13, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 17, or eee) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 11, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 612, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 663, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 17, or fff) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 11, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 612, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 673, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 17, or ggg) a VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 11, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 612, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 683, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 17, or hhh) A VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 11, a VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 612, a VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 683, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence with sequence identity to SEQ ID NO: 17.

[0094] In some embodiments, the antibody comprises: a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 15, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 17, or b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, a VH-CDR3 comprising the amino acid sequence YSY, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 25, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 26, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 27, or c) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 35, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 36, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 37, or d) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 45, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 47, or e) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, a VH-CDR3 comprising the amino acid sequence YSF, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 55, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 56, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 27, or f) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 65, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 67, or g) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, a VH-CDR3 comprising the amino acid sequence YSY, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 75, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 76, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 77, or h) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 85, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 36, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 87, or i) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 95, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 96, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 97, or j) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 105, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 106, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 107, or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 115, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 106, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 117, or l) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 282, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 285, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 286, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 287, or m) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 195, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 96, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 197, or n) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 145, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 17, or o) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 105, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 106, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 107, or p) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 165, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 167, or q) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 175, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 176, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 177, or r) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 15, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 187, or s) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 105, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 206, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 107, or t) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 215, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 216, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 217, or u) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 225, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 96, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 227, or v) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 235, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 236, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 237, or w) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 242, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 243, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 225, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 96, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 247, or x) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 255, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 256, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 257, or y) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 265, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 176, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 267, or z) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 273, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 275, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 276, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 277, or aa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 301, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 15, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 307, or bb) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 313, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 315, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 67, or cc) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 321, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 322, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 325, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 326, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 327, or dd) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 335, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 336, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 107, or ee) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 343, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 345, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 346, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 347, or ff) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 355, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 356, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 357, or gg) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 363, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 365, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 367, or hh) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 345, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 376, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 347, or ii) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 385, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 386, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 387, or jj) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 395, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 356, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 357, or kk) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 405, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 356, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 357, or ll) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 411, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 413, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 105, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 106, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 107, or mm) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 421, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 422, a VH-CDR3 comprising the amino acid sequence GNY, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 425, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 426, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 427, or nn) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 431, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 432, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 433, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 435, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 436, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 437, or oo) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 442, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 443, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 105, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 106, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 107, or pp) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 461, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 465, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 467, or qq) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 473, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 475, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 476, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 477, or rr) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 481, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 482, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 483, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 165, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 487, or ss) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 492, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 493, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 495, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 496, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 497, or tt) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 502, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 503, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 105, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 336, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 107, or uu) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 512, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 513, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 515, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 516, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 517, or vv) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 521, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 522, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 525, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 467, or ww) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 532, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 533, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 345, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 376, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 537, or xx) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 542, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 543, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 345, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 376, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 347, or yy) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 553, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 555, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 557, or zz) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 563, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 565, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 16, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 557, or aaa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 571, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 573, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 105, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 106, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 107, or bbb) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 581, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 582, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 583, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 585, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 586, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 587, or ccc) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 615, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 17, or ddd) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 625, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 17, or eee) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 663, a VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 615, a VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and a VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 17, or fff) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 673, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 615, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 16, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95% or 100% sequence identity to SEQ ID NO: 17, or ggg) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 615, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 17, or hhh) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683, VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 625, VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 16, and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 17.

[0095] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0096] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, (c) a VH-CDR3 comprising the amino acid sequence YSY, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27.

[0097] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37.

[0098] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47.

[0099] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, (c) a VH-CDR3 comprising the amino acid sequence YSF, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27.

[0100] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67.

[0101] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, (c) a VH-CDR3 comprising the amino acid sequence YSY, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77.

[0102] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87.

[0103] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97.

[0104] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0105] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117.

[0106] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 282, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287.

[0107] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197.

[0108] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0109] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0110] In some embodiments, the alpha-synuclein antibody comprises at least one, two, or three CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, and (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163.

[0111] In some embodiments, the alpha-synuclein antibody comprises at least four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167.

[0112] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177.

[0113] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187.

[0114] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0115] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 216, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 217.

[0116] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227.

[0117] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237.

[0118] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 242, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 243, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247.

[0119] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257.

[0120] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267.

[0121] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 273, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 277.

[0122] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 301, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 307.

[0123] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 313, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67.

[0124] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 321, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 322, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 325, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327.

[0125] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0126] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 343, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 346, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347.

[0127] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 355, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357.

[0128] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 363, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 365, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367.

[0129] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347.

[0130] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​(c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387.

[0131] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​(c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 395, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357.

[0132] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​(c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 405, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357.

[0133] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 411, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 413, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0134] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 421, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 422, (c) a VH-CDR3 comprising the amino acid sequence GNY, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 425, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 426, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 427.

[0135] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 431, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 432, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 433, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 436, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 437.

[0136] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 442, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 443, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0137] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 461, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 465, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467.

[0138] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472; (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 473; (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 475; (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 476; and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 477.

[0139] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 481, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 482, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 483, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 487.

[0140] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 492; (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 493; (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 495; (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 496; and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 497.

[0141] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 502, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 503, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0142] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 512, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 513, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 515, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 516, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 517.

[0143] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 521, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 522, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 525, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467.

[0144] In some embodiments, the alpha-synuclein antibody comprises at least one, two, or three CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 532, and (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 533.

[0145] In some embodiments, the alpha-synuclein antibody comprises at least four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 532, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 533, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 537.

[0146] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 542, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 543, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347.

[0147] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 553, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 555, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557.

[0148] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 563, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 565, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557.

[0149] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 571, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 573, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0150] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 581, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 582, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 583, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 585, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 586, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 587.

[0151] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0152] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0153] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 663, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0154] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 673, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0155] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0156] In some embodiments, the alpha-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from (a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, (b) a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, (c) a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683, (d) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, (e) a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and (f) a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0157] In some embodiments, the alpha-synuclein antibody is selected from the group consisting of (a) SEQ ID NOs: 11, 21, 31, 41, 61, 91, 101, 111, 141, 151, 161, 171, 181, 201, 211, 231, 261, 271, 281, 301, 311, 321, 341, 351, 361, 371, 411, 421, 431, 461, 481, 521, 551, 571, and 581. (b) VH-CDR1 comprising the selected amino acid sequence; (c) SEQ ID NO: 12, 22, 32, 42, 52, 62, 72, 92, 102, 112, 142, 152, 162, 172, 182, 192, 202, 212, 222, 232, 242, 252, 262, 272, 282, 302, 312, 322, 332, 342, 352, 362, 372, 382, ​​412, 422, 432; 442, 462, 472, 482, 492, 502, 512, 522, 532, 542, 552, 582, and 612, and (c) a VH-CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 13, YSY, 33, 43, YSF, 93, 103, 113, 143, 153, 163, 173, 183, 193, 213, 223, 233, 243, 253, 263, 273, 283. , 303, 313, 323, 333, 343, 353, 363, 373, 383, 393, 413, GNY, 433, 443, 463, 473, 483, 493, 503, 513, 533, 543, 553, 563, 573, 583, 663, 673 and 683.

[0158] In some embodiments, the alpha-synuclein antibody is selected from the group consisting of (a) SEQ ID NOs: 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 145, 165, 175, 195, 215, 225, 235, 255, 265, 275, 285, 315, 325, 335, 345, 355, 365, 385 , 395, 405, 425, 435, 465, 475, 495, 515, 525, 555, 565, 585, 615 and 625; (b) SEQ ID NOs: 16, 26, 36, 46, 56, 76, 96, 106, 176, 206, 216, 236, 256, 276, 286; , 326, 336, 346, 356, 376, 386, 426, 436, 476, 496, 516 and 586; and (c) a VL-CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 17, 27, 37, 47, 67, 77, 87, 97, 107, 117, 167, 177, 187, 197, 217, 227, 237, 247, 257, 267, 277, 287, 307, 327, 347, 357, 367, 387, 427, 437, 467, 477, 487, 497, 517, 537, 557 and 587.

[0159] In another embodiment, the alpha-synuclein antibody is selected from the group consisting of SEQ ID NO: 10, 20, 30, 40, 50, 60, 70, 90, 100, 110, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990, 1000, 1010, 1 and 720.

[0160] In certain embodiments, the heavy chain variable domain (VH) is selected from the group consisting of (a) SEQ ID NOs: 11, 21, 31, 41, 61, 91, 101, 111, 141, 151, 161, 171, 181, 201, 211, 231, 261, 271, 281, 301, 311, 321, 341, 351, 361, 371, 411, 421, 431, 461, 481, 521, 551, 571, and 581. (b) VH-CDR1 comprising the selected amino acid sequence; (c) SEQ ID NO: 12, 22, 32, 42, 52, 62, 72, 92, 102, 112, 142, 152, 162, 172, 182, 192, 202, 212, 222, 232, 242, 252, 262, 272, 282, 302, 312, 322, 332, 342, 352, 362, 372, 382, ​​412, 422, 432; 442, 462, 472, 482, 492, 502, 512, 522, 532, 542, 552, 582, and 612, and (c) a VH-CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 13, YSY, 33, 43, YSF, 93, 103, 113, 143, 153, 163, 173, 183, 193, 213, 223, 233, 243, 253, 263, 273, 283. , 303, 313, 323, 333, 343, 353, 363, 373, 383, 393, 413, GNY, 433, 443, 463, 473, 483, 493, 503, 513, 533, 543, 553, 563, 573, 583, 663, 673 and 683.

[0161] In another embodiment, the alpha-synuclein antibody comprises a light chain variable domain (VL) selected from SEQ ID NOs: 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 144, 154, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 464, 474, 484, 494, 504, 514, 524, 544, 554, 564, 574, 584, 614, 624, 634 and 644, including post-translational modifications of that sequence.

[0162] In certain embodiments, the light chain variable domain (VL) is selected from the group consisting of: (a) SEQ ID NO: 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 145, 165, 175, 195, 215, 225, 235, 255, 265, 275, 285, 315, 325, 335, 345, 355, 365, 385 , 395, 405, 425, 435, 465, 475, 495, 515, 525, 555, 565, 585, 615 and 625; (b) SEQ ID NOs: 16, 26, 36, 46, 56, 76, 96, 106, 176, 206, 216, 236, 256, 276, 286; , 326, 336, 346, 356, 376, 386, 426, 436, 476, 496, 516 and 586; and (c) a VL-CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 17, 27, 37, 47, 67, 77, 87, 97, 107, 117, 167, 177, 187, 197, 217, 227, 237, 247, 257, 267, 277, 287, 307, 327, 347, 357, 367, 387, 427, 437, 467, 477, 487, 497, 517, 537, 557 and 587.

[0163] In some embodiments, the present invention relates to ACI-7067-1101C8-Ab2, ACI-7067-1102G3-Ab1, ACI-7067-1106A8-Ab2, ACI-7067-1107G5-Ab2, ACI-7067-1108H1-Ab1, ACI-7067-1111B12-Ab2, ACI-7067-1112H8-Ab2, ACI-7067-1108B11-Ab2, ACI-7067-1113D10-Ab1, ACI-7067-1116F2-Ab1, ACI-7067-1206E5-Ab1, ACI-7079-2501B11-Ab3, ACI-7079-2501D10-Ab1, ACI-7079-2501G2-Ab2, ACI-7079-2503C6-Ab1, ACI-7079-2504A6-Ab1, ACI-7079-2506E2-Ab2, ACI-7079-2506F3-Ab1, ACI-7079-2507B3-Ab1, ACI-7079-2511B3-Ab3, ACI-7079-2601B6-Ab1, ACI-7079-2602G4-Ab4, ACI-7079-2603C1-Ab3, ACI-7079-2603F3-Ab1, ACI-7079-2605B3-Ab2, ACI-7079-2606A6-Ab2, ACI-7079-2509E5-Ab2, ACI-7087-4119E10-Ab2, ACI-7087-4125E6-Ab1, ACI-7088-4301D5-Ab2, ACI-7088-4301E12-Ab2, ACI-7088-4301H3-Ab2, ACI-7088-4303A1-Ab1, ACI-7088-4303A3-Ab1, ACI-7088-4303B6-Ab2, ACI-7088-4303H6-Ab1, ACI-7088-4305H7-Ab1, ACI-7088-4317A4-Ab1, ACI-7089-4409F1-Ab1, ACI-7089-4415G5-Ab1, ACI-7089-4417G6-Ab1, ACI-7089-4418C5-Ab1, ACI-7089-4418F6-Ab1, ACI-8033-5A12-Ab1, ACI-8033-25A3-Ab1, ACI-8033-1G10-Ab1, ACI-8033-19A2-Ab1, ACI-8033-8C10-Ab1, ACI-8033-7A2-Ab1,ACI-8033-1A12-Ab1、ACI-8033-4F3-Ab1、ACI-8033-17F5-Ab1、ACI-8033-18C11-Ab1、ACI-8033-18D12-Ab1、ACI-8033-1F8-Ab1、ACI-803 3-22E5-Ab1、ACI-8033-27D8-Ab1、ACI-8033-21C8-Ab1、hACI-7067-1101C8-Ab2_H1L1、hACI-7067-1101C8-Ab2_H1L2、hACI-7067-1101C8 -Ab2_H1L3、hACI-7067-1101C8-Ab2_H1L4、hACI-7067-1101C8-Ab2_H2L1、hACI-7067-1101C8-Ab2_H2L2、hACI-7067-1101C8-Ab2_H2L3、hACI-7067-1101C8-Ab2_H2L4、hACI-7067-1101C8-Ab2_H3L1、hACI-7067-1101C8-Ab2_H3L2、hACI-7067-1101C8-Ab2_H3L3、hACI-7067-11 01C8-Ab2_H3L4、hACI-7067-1101C8-Ab2_H4L1、hACI-7067-1101C8-Ab2_H4L2、hACI-7067-1101C8-Ab2_H4L3、hACI-7067-1101C8-Ab2_H4L4、hACI-7067-1101C8-Ab2_H5L1、hACI-7067-1101C8-Ab2_H5L2、hACI-7067-1101C8-Ab2_H5L3、hACI-7067-1101C8-Ab2_H5L4、hACI-706 7-1101C8-Ab2_H6L1、hACI-7067-1101C8-Ab2_H7L1、hACI-7067-1101C8-Ab2_H8L1、hACI-7067-1101C8-Ab2_H9L1、hACI-7067-1101C8-Ab2_H9L2、hACI-7067-1101C8-Ab2_H10L1、hACI-7067-1101C8-Ab2_H10L2、hACI-7067-1101C8-Ab2_H11L1、hACI-7067-1101C8-Ab2_H11L2、In certain preferred embodiments, the antibody is selected from hACI-7067-1101C8-Ab2_H5L1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H9L1, hACI-7067-1101C8-Ab2_H9L2, hACI-7067-1101C8-Ab2_H5L1, hACI-7067-1101C8-Ab2_H8 ...1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H8L1, h 10L1, hACI-7067-1101C8-Ab2_H10L2, hACI-7067-1101C8-Ab2_H11L1, hACI-7067-1101C8-Ab2_H11L2, hACI-7067-1101C8-Ab2_H12L1 and hACI-7067-1101C8-Ab2_H12L2. As demonstrated herein, these humanized antibodies exhibit advantageous affinity for α-synuclein, expression levels, and sequence identity to the human acceptor framework. All of these antibodies delay seed-dependent aggregation. In certain preferred embodiments, the antibody may be selected from hACI-7067-1101C8-Ab2_H5L1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H9L1, hACI-7067-1101C8-Ab2_H9L2, and hACI-7067-1101C8-Ab2_H10L1. As demonstrated herein, these humanized antibodies show improved affinity for aggregated forms of α-synuclein compared to the chimeric antibody cACI-7067-1101C8-Ab2. In certain preferred embodiments, the antibody may be selected from hACI-7067-1101C8-Ab2_H5L1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H9L1, hACI-7067-1101C8-Ab2_H9L2, hACI-7067-1101C8-Ab2_H10L1, and hACI-7067-1101C8-Ab2_H10L2. As demonstrated herein, these humanized antibodies show efficacy in delaying alpha-synuclein aggregation compared to the chimeric antibody cACI-7067-1101C8-Ab2.

[0164] In some embodiments, the antibodies are ACI-7067-1101C8-Ab2, ACI-7067-1102G3-Ab1, ACI-7067-1106A8-Ab2, ACI-7067-1107G5-Ab2, ACI-7067-1108H1-Ab1, ACI-7067-1111B12-Ab2, ACI-7067-1112H8-Ab2, ACI-7067-1108B11-Ab2, ACI-7067-1113D10-Ab1, ACI-7067-1116F2-Ab1, ACI-7067-1206E5-Ab1, ACI-7079-2501B11-Ab3, ACI-7079-2501D10-Ab1, ACI-7079-2501G2-Ab2, ACI-7079-2503C6-Ab1, ACI-7079-2504A6-Ab1, ACI-7079-2506E2-Ab2, ACI-7079-2506F3-Ab1, ACI-7079-2507B3-Ab1, ACI-7079-2511B3-Ab3, ACI-7079-2601B6-Ab1, ACI-7079-2602G4-Ab4, ACI-7079-2603C1-Ab3, ACI-7079-2603F3-Ab1, ACI-7079-2605B3-Ab2, ACI-7079-2606A6-Ab2, ACI-7079-2509E5-Ab2, ACI-7087-4119E10-Ab2, ACI-7087-4125E6-Ab1, ACI-7088-4301D5-Ab2, ACI-7088-4301E12-Ab2, ACI-7088-4301H3-Ab2, ACI-7088-4303A1-Ab1, ACI-7088-4303A3-Ab1, ACI-7088-4303B6-Ab2, ACI-7088-4303H6-Ab1, ACI-7088-4305H7-Ab1, ACI-7088-4317A4-Ab1, ACI-7089-4409F1-Ab1, ACI-7089-4415G5-Ab1, ACI-7089-4417G6-Ab1, ACI-7089-4418C5-Ab1, ACI-7089-4418F6-Ab1, ACI-8033-5A12-Ab1, ACI-8033-25A3-Ab1, ACI-8033-1G10-Ab1, ACI-8033-19A2-Ab1, ACI-8033-8C10-Ab1, ACI-8033-7A2-Ab1,ACI-8033-1A12-Ab1、ACI-8033-4F3-Ab1、ACI-8033-17F5-Ab1、ACI-8033-18C11-Ab1、ACI-8033-18D12-Ab1、ACI-8033-1F8-Ab1、ACI-803 3-22E5-Ab1、ACI-8033-27D8-Ab1、ACI-8033-21C8-Ab1、hACI-7067-1101C8-Ab2_H1L1、hACI-7067-1101C8-Ab2_H1L2、hACI-7067-1101C8 -Ab2_H1L3、hACI-7067-1101C8-Ab2_H1L4、hACI-7067-1101C8-Ab2_H2L1、hACI-7067-1101C8-Ab2_H2L2、hACI-7067-1101C8-Ab2_H2L3、hACI-7067-1101C8-Ab2_H2L4、hACI-7067-1101C8-Ab2_H3L1、hACI-7067-1101C8-Ab2_H3L2、hACI-7067-1101C8-Ab2_H3L3、hACI-7067-11 01C8-Ab2_H3L4、hACI-7067-1101C8-Ab2_H4L1、hACI-7067-1101C8-Ab2_H4L2、hACI-7067-1101C8-Ab2_H4L3、hACI-7067-1101C8-Ab2_H4L4、hACI-7067-1101C8-Ab2_H5L1、hACI-7067-1101C8-Ab2_H5L2、hACI-7067-1101C8-Ab2_H5L3、hACI-7067-1101C8-Ab2_H5L4、hACI-706 7-1101C8-Ab2_H6L1、hACI-7067-1101C8-Ab2_H7L1、hACI-7067-1101C8-Ab2_H8L1、hACI-7067-1101C8-Ab2_H9L1、hACI-7067-1101C8-Ab2_H9L2、hACI-7067-1101C8-Ab2_H10L1、hACI-7067-1101C8-Ab2_H10L2、hACI-7067-1101C8-Ab2_H11L1、hACI-7067-1101C8-Ab2_H11L2、It binds to the same or similar epitope (whole or partly overlapping epitope) as an antibody selected from hACI-7067-1101C8-Ab2_H12L1 and hACI-7067-1101C8-Ab2_H12L2. In certain preferred embodiments, the antibody binds to the same or similar epitope (whole or partly overlapping epitope) as an antibody selected from hACI-7067-1101C8-Ab2_H5L1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H9L1, hACI-7067-1101C8-Ab2_H9L2, hACI-7067-1101C8-Ab2_H10L1, hACI-7067-1101C8-Ab2_H12L2. The humanized antibodies bind to the same or similar epitope (overlapping epitope in whole or in part) as an antibody selected from hACI-7067-1101C8-Ab2_H10L2, hACI-7067-1101C8-Ab2_H11L1, hACI-7067-1101C8-Ab2_H11L2, hACI-7067-1101C8-Ab2_H12L1 and hACI-7067-1101C8-Ab2_H12L2. As demonstrated herein, these humanized antibodies show favorable affinity for alpha-synuclein, expression levels, and sequence identity to the human acceptor framework. All of these antibodies delay seed-dependent aggregation. In certain preferred embodiments, the antibody binds to the same or similar epitope (overlapping epitope in whole or in part) as an antibody selected from hACI-7067-1101C8-Ab2_H5L1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H9L1, hACI-7067-1101C8-Ab2_H9L2 and hACI-7067-1101C8-Ab2_H10L1. As demonstrated herein, these humanized antibodies show improved affinity for aggregated forms of alpha-synuclein compared to the chimeric antibody cACI-7067-1101C8-Ab2. In certain preferred embodiments, the antibody is hACI-7067-1101C8-Ab2_H5L1, hACI-7067-1101C8-Ab2_H8L1, hACI-7067-1101C8-Ab2_H9L1, hACI-7067-1101C8-Ab2_H9L2,The humanized antibodies bind to the same or similar epitope (overlapping epitopes in whole or in part) as an antibody selected from hACI-7067-1101C8-Ab2_H10L1 and hACI-7067-1101C8-Ab2_H10L2. As demonstrated herein, these humanized antibodies show efficacy in delaying α-synuclein aggregation compared to the chimeric antibody cACI-7067-1101C8-Ab2.

[0165] In some embodiments, an isolated antibody is provided that binds to the same or similar epitope comprising the sequence of SEQ ID NO:2. In some embodiments, an isolated antibody i...

Claims

1. (i) inhibiting and / or delaying seed-dependent and / or spontaneous human α-synuclein aggregation; and (ii) an α-synuclein binding molecule capable of recognizing and binding to pathological and / or aggregated human α-synuclein in vitro and / or in vivo, comprising: a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, a VH-CDR3 comprising the amino acid sequence YSY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or c) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or d) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47, or e) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, a VH-CDR3 comprising the amino acid sequence YSF, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or f) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or g) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:72, a VH-CDR3 comprising the amino acid sequence YSY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:75, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:76, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:77, or h) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87, or i) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97, or j) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or k) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117, or l) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 282, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287, or m) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197, or n) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or o) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or p) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167, or q) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177, or r) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187, or s) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or t) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 216, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 217, or u) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227, or v) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237, or w) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 242, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 243, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247, or x) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257, or y) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267, or aa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 301, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 307, or bb) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 313, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or cc) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 321, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 322, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 325, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327, or dd) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or ee) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 343, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 346, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347, or ff) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 355, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357, or gg) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 363, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 365, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367, or hh) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347, or ii) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387, or jj) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 395, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357, or kk) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 405, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357, or ll) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 411, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 413, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or mm) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 421, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 422, a VH-CDR3 comprising the amino acid sequence GNY, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 425, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 426, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 427, or nn) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 431, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 432, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 433, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 436, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 437, or oo) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 442, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 443, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or pp) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 461, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 465, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467, or rr) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 481, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 482, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 483, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 487, or ss) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 492, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 493, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 495, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 496, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 497, or tt) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 502, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 503, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107, or uu) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 512, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 513, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 515, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 516, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 517, or vv) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 521, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 522, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 525, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467, or ww) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 532, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 533, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 537, or xx) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 542, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 543, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347, or yy) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 553, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 555, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557, or zz) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 563, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 565, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557, or aaa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:571, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:573, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:105, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:106, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:107, or bbb) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 581, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 582, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 583, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 585, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 586, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 587; or ccc) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or ddd) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or eee) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 663, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or fff) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 673, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or ggg) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 615, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or hhh) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 683, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 625, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:

17. An alpha-synuclein binding molecule comprising:

2. reducing pathological alpha-synuclein levels in vivo and / or in vitro, and optionally The α-synuclein binding molecule of claim 1, which reduces phosphorylated α-synuclein levels in vivo and / or in vitro.

3. In vivo and / or in vitro a) delaying the aggregation and seeding of pathological α-synuclein; and / or b) exhibiting reversal of neuronal loss; and / or c) reducing the propagation of pathological α-synuclein; and / or d) delaying cellular uptake of pathological and / or aggregated alpha-synuclein.

4. 4. The α-synuclein binding molecule of any one of claims 1 to 3, wherein the α-synuclein binding molecule, upon pre-incubation with α-synuclein seeds, causes at least a 10% increase in the aggregation half-time (τ value) of seed-dependent aggregation compared to seed-dependent aggregation in the absence of the binding molecule, where optionally α-synuclein aggregation is monitored by a Thioflavin T (ThT) fluorescence assay.

5. 5. An alpha-synuclein binding molecule according to any one of claims 1 to 4, which binds to pathological and / or aggregated alpha-synuclein in Lewy bodies and Lewy neurites in the context of Parkinson's disease (PD); and / or binds to pathological and / or aggregated alpha-synuclein in glial cytoplasmic inclusions in the context of multiple system atrophy (MSA).

6. or binds to an epitope within amino acid residues 1-15 (SEQ ID NO:121), 10-24 (SEQ ID NO:122), 28-42 (SEQ ID NO:124), 36-40 (SEQ ID NO:2), 37-51 (SEQ ID NO:125), 51-57 (SEQ ID NO:3), 51-58 (SEQ ID NO:136), 65-74 (SEQ ID NO:4), 65-81 (SEQ ID NO:5), 81-120 (SEQ ID NO:137), 82-96 (SEQ ID NO:130), 91-105 (SEQ ID NO:131), 93-95 (GFV), 100-114 (SEQ ID NO:132), 109-123 (SEQ ID NO:133), 118-132 (SEQ ID NO:134), 124-131 (SEQ ID NO:7), 127-140 (SEQ ID NO:135), 128-135 (SEQ ID NO:8) or 131-140 (SEQ ID NO:9) of human alpha-synuclein of SEQ ID NO:1; The α-synuclein binding molecule of any one of claims 1 to 5, which binds to a non-linear epitope in human α-synuclein of SEQ ID NO:

1.

7. a. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 14; or b. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 20 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 20, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 24 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 24; or c. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; or d. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44; or e. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 50 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 50, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 54 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 54; f. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64; g. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 74; h. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; i. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 90, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or j. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 100, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 104; k. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114, or l. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 280 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 280, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 284; or m. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 290 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 290, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 194; n. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 144; o. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; p. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164, or a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 174; r. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184; or s. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 190 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 190, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 194; t. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 200 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 204 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 204; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO:210 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:210, and a light chain variable region (VL) comprising the sequence of SEQ ID NO:214 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:214; or v. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 220 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 220, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 224 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 224; or w. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 230 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 230, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 234 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 234; x. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 240 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 240, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 244 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 244; y. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 250 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 250, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 254 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 254; z. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 260 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 260, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 264 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 264; bb. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 300 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 300, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 304 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 304; or cc. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 310 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 310, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 314 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 314; dd. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 320 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 320, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 324 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 324; or ee. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 330 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 330, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 334 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 334; or ff. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 340 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 340, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 344 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 344; A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 350 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 350, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 354 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 354, or hh. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 360 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 360, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 364 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 364; ii. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 370 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 370, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 374 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 374; jj. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 380 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 380, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 384 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 384; kk. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 390 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 390, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 394 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 394; ll. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 400 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 404 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; mm. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 410 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414, or nn. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 420 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 424, or oo. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 430 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 434 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; pp. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 440 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414, or a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 450 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; rr. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 460 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 464 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 464; tt. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 480 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 484, or A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 490 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 490, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 494 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 494, or vv. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 500 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 500, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 504 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 504; A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 510 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 510, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 514 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 514, or xx. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 520 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 524 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 524; yy. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 530 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 530, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 534; or zz. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 540 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 540, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 544, or aaa. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 550 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 550, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 554; bbb. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 560 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 560, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 564 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 564; ccc. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 570 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 570, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 574 or having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 574; ddd. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 580 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 580, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 584 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 584; or fff. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 600 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 600, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 554, or A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 610, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614, or hhh. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 610, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; iii. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 610, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO:610 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:610, and a light chain variable region (VL) comprising the sequence of SEQ ID NO:644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:644; kkk. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; mmm. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; nnn. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 620, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 644; ooo. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614, or ppp. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624, or a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 630, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 644; sss. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614, or a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 640, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 644; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; xxx. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 634; zzz. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 or having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 650, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 644; aaaa. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 660 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 660, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 670 or having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 670, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 680 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 680, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; A heavy chain variable region (VH) comprising the sequence of SEQ ID NO:690 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:690, and a light chain variable region (VL) comprising the sequence of SEQ ID NO:614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:614, or eeee. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 or having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 690, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624, or A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 700, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614, or A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 700, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624, or hhhh. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 710, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; iii. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 710, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 624; a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 720 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 720, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 720 or having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 720, and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:

624. The α-synuclein binding molecule of any one of claims 1 to 6, which is an antibody or an antigen-binding fragment thereof comprising:

8. a. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14, or b. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 20 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 24, or c. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34, or d. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44; or e. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 50 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 54; or f. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64, or g. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74, or h. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84, or i. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94, or j. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104, or k. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114, or l. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 280 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 284, or m. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 290 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194, or n. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144, or o. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154, or p. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164, or q. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174, or r. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184, or s. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 190 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194, or t. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 200 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 204, or u. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 210 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 214, or v. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 220 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 224, or w. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 230 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 234; or x. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 240 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 244, or y. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 250 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 254, or z. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 260 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 264, or bb. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 300 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 304, or cc. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 310 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 314, or dd. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 320 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 324, or ee. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 330 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 334, or ff. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 340 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 344, or gg. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 350 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 354, or hh. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 360 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 364; or ii. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 370 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 374; or jj. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 380 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 384; or kk. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 390 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 394, or ll. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 404, or mm. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414, or nn. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424, or oo. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 434, or pp. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 440 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 414, or a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 450 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 424, or rr. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 460 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 464, or tt. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 484, or A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 490 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 494, or vv. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 500 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 504, or A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 510 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 514, or xx. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 524, or yy. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 530 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 534, or zz. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 540 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 544, or aaa. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 550 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554, or bbb. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 560 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 564, or ccc. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 570 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 574, or ddd. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 580 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 584, or fff. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 600 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 554, or ggg. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or hhh. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or iii. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634; or jjj. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644, or kkk. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or III. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or mmm. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634, or nnn. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644, or ooo. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or ppp. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634, or rrr. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644, or sss. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or ttt. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634, or vvv. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644, or www. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or xxx. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or yyy. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 634, or zzz. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644, or aaaa. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 660 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or bbbb. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 670 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or cccc. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 680 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or dddd. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or eeee. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or ffff. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624, or hhhh. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614, or iii. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624; or jjjj. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 720 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 614; or kkkk. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 720 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 624 The α-synuclein binding molecule of any one of claims 1 to 7, which is an antibody or an antibody-binding fragment thereof comprising:

9. The α-synuclein binding molecule of any one of claims 1 to 8, which is a monoclonal, murine, chimeric or humanized antibody or antigen-binding fragment thereof.

10. 10. The alpha-synuclein binding molecule of any one of claims 1 to 9, which is an IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3 or IgG4 antibody or antigen-binding fragment thereof, or is an IgG4 isotype comprising a S228P mutation.

11. An alpha-synuclein binding molecule according to any one of claims 1 to 10 for use in human or veterinary therapy.

12. 12. An alpha-synuclein binding molecule according to any one of claims 1 to 11 for use in the prevention, mitigation, treatment and / or diagnosis of diseases, disorders and conditions associated with alpha-synuclein, in particular pathological alpha-synuclein and / or aggregated alpha-synuclein, An α-synuclein binding molecule, optionally wherein the aggregated α-synuclein is in the form of Lewy bodies, Lewy neurites, and / or glial cytoplasmic inclusions.

13. The disease, disorder or abnormality is a. Synucleinopathy; and / or b. Parkinson's Disease (PD) (sporadic, familial with α-synuclein mutations, familial with non-α-synuclein mutations, pure dysautonomia, and Lewy body dysphagia), Lewy body dementia [LBD; Dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)], Diffuse Lewy body disease (DLBD), Sporadic Alzheimer's Disease, Familial Alzheimer's Disease with APP mutations, Familial Alzheimer's Disease with PS-1, PS-2 or other mutations, Familial British Dementia, Lewy body variant of Alzheimer's Disease, Multiple system atrophy (MSA) (Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy), inclusion body myositis, traumatic brain injury, chronic traumatic encephalopathy, dementia pugilistica, tauopathies (Pick's disease, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia with parkinsonism linked to chromosome 17, and Niemann-Pick disease type C1), Down's syndrome, Creutzfeldt-Jakob disease, Huntington's disease, motor neuron disease, amyotrophic lateral sclerosis [sporadic, familial, ALS-dementia complex of Guam] 13. The α-synuclein binding molecule of claim 12, wherein the α-synuclein binding molecule is selected from the group consisting of cerebrovascular disease, ...

14. The alpha-synuclein binding molecule of claim 13 for preventing, and / or slowing, and / or arresting, and / or maintaining, and / or ameliorating motor ability or motor impairment, cognitive ability or cognitive impairment, or behavioral impairment in a subject suffering from a synucleinopathy.

15. the synucleinopathy is Parkinson's disease, Lewy body dementia [LBD; dementia with Lewy bodies (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)], diffuse Lewy body disease, or multiple system atrophy (MSA), and the binding molecule (i) improving athletic performance; and / or (ii) improving cognitive impairment, and / or (iii) amelioration of behavioral disorders, and / or (iv) Improvement of REM sleep disorder The α-synuclein binding molecule of claim 14, which is a binding molecule for

16. An alpha-synuclein binding molecule according to any one of claims 1 to 10 for use in diagnosis.

17. 17. An alpha-synuclein binding molecule according to claim 16 for use in the diagnosis of diseases, disorders and abnormalities associated with alpha-synuclein, in particular pathological alpha-synuclein and / or aggregated alpha-synuclein.

18. A pharmaceutical composition comprising an α-synuclein binding molecule according to any one of claims 1 to 10 and a pharma- ceutically acceptable carrier and / or excipient.

19. A nucleic acid encoding an α-synuclein binding molecule according to any one of claims 1 to 10, or SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:89, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:298, SEQ ID NO:199, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO: No. 188, SEQ ID NO: 189, SEQ ID NO: 198, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 268, SEQ ID NO: 269, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 358, SEQ ID NO: 359, SEQ ID NO: 368, SEQ ID NO: 369, SEQ ID NO. No. 378, SEQ ID NO: 379, SEQ ID NO: 388, SEQ ID NO: 389, SEQ ID NO: 398, SEQ ID NO: 399, SEQ ID NO: 408, SEQ ID NO: 409, SEQ ID NO: 418, SEQ ID NO: 419, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 448, SEQ ID NO: 449, SEQ ID NO: 458, SEQ ID NO: 459, SEQ ID NO: 468, SEQ ID NO: 469, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO: 498, SEQ ID NO: 499, SEQ ID NO: 508, SEQ ID NO: 509, SEQ ID NO: 518, SEQ ID NO: 519, SEQ ID NO: 528, SEQ ID NO: 529, SEQ ID NO: 538, SEQ ID NO: A nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO:539, SEQ ID NO:548, SEQ ID NO:549, SEQ ID NO:558, SEQ ID NO:559, SEQ ID NO:568, SEQ ID NO:569, SEQ ID NO:578, SEQ ID NO:579, SEQ ID NO:588, SEQ ID NO:589, SEQ ID NO:608, SEQ ID NO:609, SEQ ID NO:618, SEQ ID NO:619, SEQ ID NO:628, SEQ ID NO:629, SEQ ID NO:638, SEQ ID NO:639, SEQ ID NO:648, SEQ ID NO:649, SEQ ID NO:658, SEQ ID NO:668, SEQ ID NO:678, SEQ ID NO:688, SEQ ID NO:698, SEQ ID NO:708, SEQ ID NO:718 or SEQ ID NO:

728.

20. A recombinant vector comprising the nucleic acid of claim 19.

21. 21. A host cell comprising a nucleic acid according to claim 19 and / or a vector according to claim 20.

22. An isolated host cell expressing an α-synuclein binding molecule, particularly an antibody, according to any one of claims 1 to 10.

23. 23. A method for producing an isolated alpha-synuclein binding molecule, particularly an antibody, comprising the steps of a) culturing a host cell according to claim 21 or 22 under conditions suitable for producing said alpha-synuclein binding molecule, particularly said antibody, and b) isolating said alpha-synuclein binding molecule, particularly said antibody.

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