New molecules for therapy and diagnosis

Abstract

The present invention relates to novel molecules useful for preventing, alleviating, treating and / or diagnosing diseases, disorders and abnormalities associated with alpha-synuclein (a-synuclein, A-synuclein, a synuclein, A-syn, alpha-syn, aSyn, a-syn) aggregates, including but not limited to Lewy bodies and / or Lewy neurites, such as Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD; Lewy body dementia (DLB) ("pure" Lewy body dementia, Parkinson's disease dementia (PDD)) or diffuse Lewy body disease. The present invention relates to alpha-synuclein binding molecules, in particular alpha-synuclein antibodies or antigen-binding fragments or derivatives thereof and uses thereof. The molecules of the present invention can also be used to determine a predisposition to such a disorder, disease or abnormality, to monitor a residual disorder, disease or abnormality, or to predict the responsiveness of a patient having such a disorder, disease or abnormality to a treatment with a certain drug.

Description

Technical Field

[0001] This invention relates to novel molecules that can be used for the prevention, mitigation, treatment, and / or diagnosis of diseases, conditions, and abnormalities associated with α-synuclein (α-synuclein, A-synuclein, α-synuclein, A-syn, α-syn, aSyn, α-syn) aggregates, including but not limited to: Lewy bodies and / or Lewy neurites, such as Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD; dementia with Lewy body (DLB) (“pure” Lewy body dementia), Parkinson's disease dementia (PDD)), or diffuse Lewy body disease. This invention relates to α-synuclein-binding molecules, particularly α-synuclein antibodies or their antigen-binding fragments or derivatives thereof, and their uses. The molecules of this invention can also be used to determine a predisposition to such a condition, disease, or abnormality, monitor residual conditions, diseases, or abnormalities, or predict the responsiveness of a patient with such a condition, disease, or abnormality to treatment with a certain drug. Background Technology

[0002] Many degenerative diseases are associated with the extracellular or intracellular deposition of amyloid or amyloid-like proteins, which contribute to disease pathogenesis and progression. The best-characterized amyloid protein for forming extracellular aggregates is β-amyloid (Aβ).

[0003] Amyloid proteins that primarily form intracellular aggregates include, but are not limited to, α-synuclein, tau, and huntingtin (htt). Diseases involving α-synuclein aggregates are generally classified as synucleinopathy (or α-synucleinosis), and these include, but are not limited to, Parkinson's disease (PD). Synucleinopathy includes: Parkinson's disease (sporadic, familial with α-synuclein mutations, familial with mutations other than α-synuclein, pure autonomic failure, and Lewy body dysphagia), Lewy body dementia (LBD);Lewy body dementia (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 mutation, familial Alzheimer's disease with PS-1, PS-2 or other mutations, familial British dementia, Lewy body variants of Alzheimer's disease, and Down syndrome. Synucleinic diseases involving α-synuclein-producing neuronal aggregates and glial cell aggregates include, but are not limited to: multiple system atrophy (Shy-Drager syndrome, striatal substantia nigra degeneration, and olivary pontocerebellar atrophy). Other diseases that may present with α-synuclein immunoreactive foci include: traumatic brain injury, chronic traumatic encephalopathy, boxing dementia, tauopathy (Pick's disease, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration and Niemann-Pick type C1 disease, frontotemporal dementia with Parkinsonism linked to chromosome 17), motor neuron disease, Huntington's disease, amyotrophic lateral sclerosis (sporadic, familial and Guam-type ALS-dementia complex), axonal dystrophy, neurodegenerative diseases with type 1 brain iron deposition (Hallervorden-Spatz syndrome), prions, and Creutzfeldt-Jakob disease. Disease), ataxia-telangiectasia, Meige's syndrome, subacute sclerosing panencephalitis, Gerstmann-Straussler-Scheinker disease, inclusion body myositis, Gaucher disease, Krabbe disease and other lysosomal storage diseases (including Kufor-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;Kovariet al.,Acta Neuropathol.2007,114(3),295-8;Saito et al.,J Neuropathol ExpNeurol.2004,63(4),323-328;McKee et al.,Brain,2013,136(Pt 1),43-64;Puschmannet al.,Parkinsonism Relat Disord 2012,18S1,S24-S27;Usenovic et al.,JNeurosci.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.,JPathol.2014;232:509-521,Lippa et al.,Ann Neurol.1999 Mar;45(3):353-7;Schmitzet 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 etal.,J Neuropathol Exp Neurol.2004,80; th annual meeting,vol.63;Askanas et al.,JNeuropathol Exp Neurol.2000 Jul;59(7):592-8)。

[0004] α-synuclein is a 140-amino acid-long cytoplasmic protein that is abundantly expressed in the CNS and located primarily at the presynaptic terminal (Burré J., J Parkinsons Dis. 2015; 5(4): 699-713). α-synuclein is a naturally unfolded protein, but after association with lipid vesicles or membranes, it adopts a predominantly helical secondary structure (Iwai et al., Biochemistry 1995, 34(32), 10139-10145). The physiological functions of α-synuclein remain elusive. The association between α-synuclein and synaptic vesicles and their presynaptic localization indicate that α-synuclein regulates synaptic activity and plasticity, neurotransmitter release, dopamine production and metabolism, vesicle transport, maintenance of the synaptic vesicle pool, and molecular 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 to 60, which contains 11-mer, amphiphilic, incompletely repeating residues with highly conserved hexamer (KTKEGV). This region is involved in regulating the association and internalization of α-synuclein with the lipid membrane; 2) the hydrophobic non-β-amyloid beta component (NAC) domain spanning residues 61 to 95; which is crucial for α-synuclein fibrosis; and 3) the C-terminal region spanning residues 96 to 140, which is highly acidic and proline-rich, with no obvious structural bias.

[0006] It has been shown that α-synuclein undergoes several post-translational modifications, including truncation, phosphorylation, ubiquitination, sumoylation, oxidation, nitration, acetylation, glycosylation, and / or transglutaminase covalent 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.). al., J Biol Chem. 2006, 281(15): 9919-24; Ruzafa et al., PlosOne 2017 12(5): e0178576; Ischiropoulos et al., Ann NY AcadSci. 2003, 991, 93-100; Munch et al., J Chem Neuroanat. 2000; 20: 253-257; Marotta et al., Chembiochem. 2012; 13: 2665-2670). Most of these modifications involve residues in the C-terminal region.

[0007] Several phosphorylation sites were detected in the C-terminal regions of Tyr-125, -133, and -136, as well as Ser-129 (Negro et al., FASEB J 2002, 16(2), 210-212). Extensive phosphorylation of α-synuclein and selective phosphorylation at Ser-129 are evident in synucleinopathy lesions (including Lewy bodies) (Fujiwara et al., NatCell Biol 2002, 4(2); 160-164). Other post-translational modifications at the C-terminus, 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), can affect α-synuclein aggregation. The role of proteolytic truncation of the C-terminal region in α-synuclein fibrillation in various neurodegenerative diseases has been reported (Rochet et al., Biochemistry 2000, 39(35), 10619-10626). Full-length and partially truncated α-synuclein proteins, as well as insoluble α-synuclein aggregates, have been detected in highly purified Lewis bodies (Crowther et al., FEBS Lett 1998, 436(3), 309-312).

[0008] Aberrant protein aggregation is a common feature of brain aging and several neurodegenerative diseases, although its exact role in disease progression remains to be determined. In in vitro models, α-synucleins readily assemble 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-synucleins and their mutant forms (e.g., A53T and A30P) have a random coil conformation and do not form obvious secondary structures in aqueous solution at low concentrations; however, at higher concentrations, they tend to self-aggregate to produce amyloid fibrils (Wood et al., J Biol Chem 1999, 274(28), 19509-19512). Some differences in aggregation behavior between PD-related mutants and wild-type proteins have been documented. Monomeric α-synuclein aggregates form stable fibrils in vitro through a metastable oligomer state (i.e., primary fibrils) (Volles et al., Biochemistry 2002, 41(14), 4595-4602).

[0009] Parkinson's disease (PD) is the most common neurodegenerative motor disorder. PD is primarily an idiopathic disease, although in at least 5% of PD patients, the pathology is associated with mutations in one or more specific genes. Several point mutations in the α-synuclein gene (A30P, E46K, H50Q, G51D, A53T) have been described, leading to familial PD with autosomal dominant inheritance. Furthermore, double and triplet duplications of the α-synuclein gene have been described in patients with PD, highlighting the role of α-synuclein in the pathogenesis of PD (Lesage et al., Hum. Mol. Genet., 2009, 18, R48-59). The pathogenesis of PD remains elusive; however, mounting evidence suggests that the pathogenic folding of α-synuclein contributes to the formation of amyloid-like fibrils. In fact, PD is characterized by the presence of intracellular α-synuclein aggregates called Lewy bodies in substantia nigra neurons, and the death of dopaminergic neurons in the substantia nigra and elsewhere. α-synuclein is a naturally occurring unfolded presynaptic protein that can misfold and aggregate into larger oligomers and fibrillary forms, which is involved in the pathogenesis of PD. Studies have shown that the small soluble oligomers and protofibrillary forms of α-synuclein are the most neurotoxic (Lashuel et al., J. Mol. Biol., 2002, 322, 1089-102), but the precise role of α-synuclein in neuronal cytotoxicity remains to be clarified (review: Cookson, Annu. Rev. Biochem., 2005, 74, 29-52).

[0010] Recent evidence from cellular and animal models suggests that pathological and / or aggregated α-synuclein can spread from one neuron to another. Once inside the new cell, 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, the transsynaptic spread of pathological and / or aggregated α-synuclein can explain the progressive development of Lewy pathological conditions in brain regions with anatomically defined connections in PD, first described by Braak et al. (Braak et al., Neurobiol. Aging. 2003; 24: 197-211).

[0011] Therefore, the intercellular diffusion of pathological and / or aggregated α-synuclein makes immunotherapy a compelling target for novel therapies aimed at alleviating, treating, delaying, or halting the progression of PD and other synucleinogenic diseases. The antibodies described herein inhibit and / or delay the inoculation and / or spontaneous aggregation of α-synuclein, and this functional characteristic would allow them to bind to α-synuclein seeds in the extracellular space to neutralize the seeds and thus delay or inhibit the spread of α-synuclein aggregates or promote the clearance of these diffused substances. Since only symptomatic treatments are currently available, developing such treatments for PD and other synucleinogenic diseases would address an unmet medical need.

[0012] The diagnosis of Parkinson's disease is primarily clinical and depends on the presence of a specific set of symptoms and signs (the initial core features being bradykinesia, rigidity, resting tremor, and postural instability), a slow progression, and a response to pharmacological treatment. Postmortem neuropathological analysis provides final confirmation of the diagnosis. Strategies are being developed to apply the latest advances in the etiology of Parkinson's disease to the development of biochemical and imaging biomarkers (Schapira, Curr OpinNeurol 2013; 26(4): 395-400). Such biomarkers, which have been studied in various bodily fluids (cerebrospinal fluid, CSF, plasma, saliva), include α-synuclein levels and DJ-1, Tau, and Abeta, as well as neurofilaments, interleukins, osteopontin, and hypocrontin (Schapira, Curr Opin Neurol 2013; 26(4): 395-400), but so far, none of these biomarkers, alone or in combination, can be used as definitive diagnostic tests. Antibodies that selectively recognize and bind to certain pathological structures of α-synuclein for diagnostic applications have the potential to serve as biomarkers with high sensitivity and specificity. To our knowledge, despite the critical need for Parkinson's disease research and drug development, there are currently no approved biomarkers on the market for monitoring pathological α-synuclein levels or available for clinical trials (Eberling et al., J Parkinsons Dis. 2013; 3(4): 565-7).

[0013] Existing technology

[0014] WO2017 / 207739 provides an antibody that specifically binds to human α-synuclein with high affinity and reduces the diffusion of α-synuclein in vivo. Summary of the Invention

[0015] One object of the present invention is to provide an α-synuclein binding molecule that can be used to treat, alleviate and / or prevent diseases, symptoms or abnormalities associated with α-synuclein aggregates, such as Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD; Lewy body dementia (DLB) (“pure” Lewy body dementia, Parkinson's disease dementia (PDD)) or diffuse Lewy body disease.

[0016] In another aspect, an object of the present invention is to provide molecules that can be used to diagnose diseases, conditions, or abnormalities associated with α-synuclein aggregates, monitor the progression of diseases, conditions, or abnormalities associated with α-synuclein aggregates, and / or monitor the drug activity against diseases, conditions, or abnormalities associated with α-synuclein aggregates, including but not limited to: Lewy bodies, Lewy neurites, and / or glial cell cytoplasmic inclusions, such as Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD; Lewy body dementia (DLB) (“pure” Lewy body dementia, Parkinson's disease dementia (PDD)) or diffuse Lewy body disease.

[0017] This invention generally relates to α-synuclein binding molecules that inhibit and / or delay seeded and / or spontaneous α-synuclein aggregation.

[0018] In one embodiment, the present invention relates to an α-synuclein binding molecule, which

[0019] (i) Inhibition and / or delay of inoculation and / or spontaneous α-synuclein aggregation; and

[0020] (ii) It is able to recognize and bind pathological and / or aggregated α-synuclein proteins, particularly human α-synuclein, in vitro and / or in vivo.

[0021] Therefore, in its broadest aspect, this invention relates to binding molecules, particularly antibodies or antigen-binding fragments thereof, that bind to α-synuclein. In a preferred embodiment of the invention, the binding molecule, particularly an antibody or antigen-binding fragment thereof, inhibits and / or delays the aggregation of seeded and / or spontaneous α-synuclein aggregates, and is capable of recognizing and binding pathological and / or aggregated α-synuclein, particularly human α-synuclein, in vitro and / or in vivo. α-synuclein is a soluble protein that, under certain conditions, has a tendency to spontaneously aggregate and form soluble oligomers or soluble / insoluble primary or mature fibrils or detergent-insoluble aggregates. Seeded α-synuclein aggregation is an aggregation promoted by pathological α-synuclein (i.e., so-called "seeds").

[0022] The α-synuclein binding molecules of the present invention, particularly antibodies or their antigen-binding fragments, block intercellular diffusion and / or delay and / or inhibit the aggregation of α-synuclein or its fragments. Therefore, the α-synuclein binding molecules of the present invention inhibit and / or delay the aggregation of α-synuclein in seeded and / or gray hair; and are capable of recognizing and binding pathological and / or aggregated α-synuclein, particularly human α-synuclein, in vitro and in vivo. The α-synuclein binding molecules of the present invention inhibit and / or delay the aggregation of seeded and / or spontaneous α-synuclein; and are capable of recognizing and binding pathological and / or aggregated α-synuclein, particularly human α-synuclein, in vitro and in vivo.

[0023] In this invention, it is preferred that the α-synuclein binding molecule, particularly an antibody or its antigen-binding fragment, additionally has one or more, preferably two or more, more preferably three or more, more preferably four or more, or even more preferably all of the functional features (i) to (vi):

[0024] (i) Reduce pathological α-synuclein levels in vivo; and / or

[0025] (ii) Reduce phosphorylated α-synuclein levels in vivo; and / or

[0026] (iii) Reducing and / or delaying the accumulation and / or inoculation of pathological α-synuclein in vivo; and / or

[0027] (iv) Demonstrating recovery of neuronal loss in vivo; and / or

[0028] (v) Reduce the spread of pathological α-synuclein in vivo; and / or

[0029] (vi) Reduces and / or delays cellular uptake of pathological and / or aggregated α-synuclein in vivo.

[0030] In this invention, it is preferred that the α-synuclein binding molecule, particularly an antibody or its antigen-binding fragment, additionally has one or more, preferably two or more, more preferably three or more, more preferably four or more, or even more preferably all of the functional features (i) to (vi):

[0031] (i) Reduce pathological α-synuclein levels in vitro; and / or

[0032] (ii) Reduce phosphorylated α-synuclein levels in vitro; and / or

[0033] (iii) Reducing and / or delaying the aggregation and / or inoculation of pathological α-synuclein in vitro; and / or

[0034] (iv) Demonstrating recovery of neuronal loss in vitro; and / or

[0035] (v) Reduces the diffusion of pathological α-synuclein in vitro; and / or

[0036] (vi) Reduce and / or delay cellular uptake of pathological and / or aggregated α-synuclein in vitro.

[0037] In particular, the α-synuclein binding molecules of the present invention, especially antibodies or antigen-binding fragments thereof, inhibit and / or delay the aggregation of α-synuclein or fragments thereof.

[0038] In one embodiment, the α-synuclein binding molecule of the present invention, particularly an antibody or its antigen-binding fragment, inhibits the formation of α-synuclein aggregates, including but not limited to Lewy bodies, Lewy neurites, and / or glial cell cytoplasmic inclusion bodies.

[0039] The α-synuclein binding molecules of the present invention, particularly antibodies or their antigen-binding fragments, can selectively bind aggregated α-synuclein and / or pathological α-synuclein, preferentially over non-aggregated α-synuclein and / or non-pathological α-synuclein (e.g., monomeric α-synuclein).

[0040] In some embodiments of the present invention, the antibody is a monoclonal antibody. In some embodiments, the antibody is a mouse, murine-derived, human, humanized, or chimeric antibody.

[0041] In some embodiments of the invention, the antibody having the binding characteristics of the antibody described herein, or its antigen-binding fragment or derivative, is an antibody having variable regions VH and / or VL, respectively, as shown in the amino acid sequences below: 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: 164; SEQ ID NO: 170 and SEQ ID NO: 184; SEQ ID NO: 194; SEQ ID NO: 140 and SEQ ID NO: 194; 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: 194; SEQ ID NO: 100 and SEQ ID NO: 194; SEQ ID NO: 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: 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; 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: 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: 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 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 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 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 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.

[0042] Therefore, the present invention also provides α-synuclein binding antibodies having variable regions VH and / or VL, respectively, as shown in the amino acid sequences below: 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 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 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: 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: 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 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 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 SEQ ID NO: 624; SEQ ID 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: 690 and SEQ ID NO: 614. NO: 624; SEQ ID NO: 700 and SEQ ID NO: 614; SEQ ID NO: 700 and SEQ ID NO: 624; SEQ ID 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.

[0043] In some implementations, the antibody comprises:

[0044] a) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 12; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 13; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 15; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0045] b) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 22; and VH-CDR3 containing the amino acid sequence YSY; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 25; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 26; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 27; or

[0046] c) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 32; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 33; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 35; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 36; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 37; or

[0047] d) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 41; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 42; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 43; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 45; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 46; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 47; or

[0048] e) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 52; and VH-CDR3 containing the amino acid sequence YSF; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 55; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 56; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 27; or

[0049] f) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 61; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 62; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 43; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 65; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 46; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 67; or

[0050] g) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 72; and VH-CDR3 containing the amino acid sequence YSY; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 75; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 76; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 77; or

[0051] h) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 32; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 33; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 85; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 36; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 87; or

[0052] i) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 91; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 92; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 93; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 95; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 97; or

[0053] j) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 101; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 102; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 103; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0054] k) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 111; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 112; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 113; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 115; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 117; or

[0055] l) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 281; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 282; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 283; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 285; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 286; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 287; or

[0056] m) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 192; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 193; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 195; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 197; or

[0057] n) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 141; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 142; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 143; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 145; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0058] o) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 152; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 153; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0059] p) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 161; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 162; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 163; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 165; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 167; or

[0060] q) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 171; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 172; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 173; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 175; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 176; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 177; or

[0061] r) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 181; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 182; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 183; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 15; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 187; or

[0062] s) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 201; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 202; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 153; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 206; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0063] t) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 211; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 212; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 213; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 215; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 216; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 217; or

[0064] u) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 222; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 223; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 225; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 227; or

[0065] v) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 231; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 232; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 233; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 235; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 236; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 237; or

[0066] w) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 242; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 243; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 225; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 247; or

[0067] x) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 252; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 253; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 255; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 256; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 257; or

[0068] y) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 261; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 262; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 263; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 265; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 176; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 267; or

[0069] z) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 271; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 272; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 273; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 275; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 276; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 277; or

[0070] aa) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 301; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 302; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 303; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 15; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 307; or

[0071] bb) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 311; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 312; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 313; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 315; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 46; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 67; or

[0072] cc) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 321; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 322; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 323; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 325; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 326; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 327; or

[0073] dd) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 332; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 333; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 335; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 336; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or or

[0074] ee) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 341; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 342; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 343; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 345; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 346; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 347; or

[0075] ff) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 352; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 353; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 355; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 356; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 357; or

[0076] gg) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 361; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 362; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 363; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 365; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 367; or

[0077] (hh) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 371; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 372; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 373; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 345; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 376; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 347; or

[0078] ii) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 382; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 383; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 385; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 386; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 387; or

[0079] (jj) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 382; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 393; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 395; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 356; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 357; or

[0080] (kk) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 382; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 393; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 405; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 356; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 357; or

[0081] ll) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 411; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 412; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 413; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0082] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 421; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 422; and VH-CDR3 containing the amino acid sequence GNY; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 425; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 426; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 427; or

[0083] nn) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 431; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 432; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 433; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 435; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 436; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 437; or

[0084] oo) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 442; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 443; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0085] pp) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 461; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 462; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 463; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 465; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 467; or

[0086] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 141; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 472; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 473; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 475; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 476; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 477; or

[0087] rr) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 481; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 482; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 483; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 165; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 487; or

[0088] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 141; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 492; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 493; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 495; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 496; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 497; or

[0089] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 502; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 503; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 336; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0090] (uu) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 311; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 512; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 513; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 515; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 516; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 517; or

[0091] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 521; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 522; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 463; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 525; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 467; or

[0092] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 371; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 532; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 533; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 345; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 376; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 537; or

[0093] xx) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 341; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 542; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 543; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 345; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 376; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 347; or

[0094] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 551; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 552; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 553; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 555; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 557; or

[0095] zz) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 551; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 552; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 563; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 565; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 557; or

[0096] aaa) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 571; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 202; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 573; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0097] bbb) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 581; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 582; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 583; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 585; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 586; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 587; or

[0098] (ccc) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 13; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 615; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0099] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 13; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 625; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0100] (eee) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 663; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 615; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0101] (fff) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 673; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 615; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0102] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 683; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 615; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0103] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 683; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 625; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17.

[0104] These α-synuclein binding antibodies can constitute different aspects of the present invention.

[0105] In some embodiments, an isolated nucleic acid is provided, wherein the isolated nucleic acid encodes an antibody or an antigen-binding fragment or derivative thereof described herein. In some embodiments, a host cell is provided, wherein the host cell contains an isolated nucleic acid encoding an antibody or an antigen-binding fragment or derivative thereof described herein. In some embodiments, a method for producing an antibody or an antigen-binding fragment or derivative thereof is provided, comprising culturing the host cell under conditions suitable for producing the antibody or an antigen-binding fragment or derivative thereof.

[0106] In some embodiments, an immunoconjugate is provided, wherein the immunoconjugate comprises the isolated antibody, its antigen-binding fragment or derivative as described herein, and a therapeutic agent. In some embodiments, a labeled antibody, its antigen-binding fragment or derivative is provided, comprising the antibody, its antigen-binding fragment or derivative as described herein, and a detectable label.

[0107] In some embodiments, a pharmaceutical composition is provided comprising the isolated antibody, its antigen-binding fragment or derivative as described herein, and a pharmaceutically acceptable carrier and / or excipient.

[0108] As used herein, the term "isolated" means that a chemical compound, such as a nucleic acid or antibody, has been isolated and / or recovered from its natural environment. In this invention, the chemical compound is preferably chemically synthesized, or synthesized in a cellular system different from the cells of its natural origin, and thus "isolated" from its naturally related components. The chemical compound can be isolated from its natural environment, for example, through purification, or produced by technical processes, including but not limited to, gene synthesis, polymerase chain reaction (PCR), vector purification, and protein (antibody) purification. Such chemical compounds can in particular be nucleic acid, DNA-, RNA-, or cDNA- sequences, or peptides, antibodies, or proteins.

[0109] This invention is not limited to antibodies isolated according to the above definition, but also relates to antibodies themselves regardless of their source.

[0110] This also applies to the peptide, nucleic acid, DNA, RNA and / or cDNA sequences provided in this invention, whether they are contained in a separate form (as defined above) or in any other form.

[0111] In some implementations, methods are provided for preventing, mitigating, and / or treating diseases, conditions, or abnormalities associated with α-synuclein aggregates or pathological α-synuclein, such as Parkinson's disease (sporadic, familial with α-synuclein mutations, familial with mutations other than α-synuclein, pure autonomic failure, and Lewy body dysphagia), Lewy body dementia (LBD; Lewy body dementia (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 variants of Alzheimer's disease, multiple system atrophy (Shad syndrome, striatal substantia nigra degeneration, and olivary pontocerebellar atrophy), inclusion body myositis, trauma, etc. Brain injury, chronic traumatic encephalopathy, boxing dementia, tau proteinosis (Pick disease, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, chromosome 17-linked frontotemporal dementia with Parkinson's syndrome and Niemann-Pick C1 disease), Down syndrome, Kreutzfeldt-Jacob disease, Huntington's disease, motor neuron disease, amyotrophic lateral sclerosis (sporadic, familial and Guam-type ALS dementia complex), axonal dystrophy, neurodegenerative diseases with brain iron deposition type 1 (Halverden-Schpattz syndrome), prions, Gerstmann-Straussler-Schainkel disease, ataxia-telangiectasia, syphilis syndrome, subacute sclerosing panencephalitis, Gaucher disease, Krab disease and other lysosomal storage diseases (including Kufor-Rakeb syndrome and Sanfilippo syndrome) or rapid eye movement (REM) sleep behavior disorders. According to one embodiment, the method of the present invention includes administering to a subject in need an effective concentration or effective amount of the binding molecule of the present invention, particularly an antibody or its antigen-binding fragment or derivative thereof, that binds to the α-synuclein described herein (e.g., a full-length antibody or an α-synuclein-binding fragment or derivative of an antibody).

[0112] In some implementations, methods are provided for enabling subjects with synucleinopathy to maintain motor function or improve motor deficits (including reduction of bradykinesia, rigidity, resting tremor, or postural instability), comprising administering to the subject an antibody described herein or an antigen-binding fragment or derivative thereof, or a pharmaceutical composition comprising an antibody described herein or an antigen-binding fragment or derivative thereof.

[0113] In some embodiments, methods are provided for enabling subjects with synucleinosis to maintain or improve their cognitive abilities, including administering to the subject an antibody described herein or an antigen-binding fragment or derivative thereof, or a pharmaceutical composition comprising an antibody described herein or an antigen-binding fragment or derivative thereof.

[0114] In some embodiments, the isolated antibodies or antigen-binding fragments or derivatives thereof described herein are provided for use as medicaments. In some embodiments, the isolated antibodies or antigen-binding fragments or derivatives thereof described herein are provided for use in alleviating, preventing, and / or treating synucleinosis in a subject. In some embodiments, the antibodies or antigen-binding fragments or derivatives thereof described herein are provided for use in the preparation of medicaments for the prevention, alleviation, and / or treatment of diseases, conditions, and / or abnormalities associated with α-synuclein aggregates.

[0115] In some implementations, diseases, symptoms, and / or abnormalities associated with α-synuclein aggregates are synucleinopathies. In some implementations, synucleinopathies include Parkinson's disease (sporadic, familial with α-synuclein mutations, familial with mutations other than α-synuclein, pure autonomic failure, and Lewy body dysphagia), Lewy body dementia (LBD; Lewy body dementia (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 variants of Alzheimer's disease, multiple system atrophy (Shadow syndrome, striatal-nigrostriatal degeneration, and olivary-pontocerebellar atrophy), inclusion body myositis, traumatic brain injury, chronic traumatic encephalopathy, boxing dementia, and tau proteinopathy (dermal proteinopathy). Klebsiella pneumoniae, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, chromosome 17-linked frontotemporal dementia with Parkinson's syndrome and Niemann-Pick C1 disease, Down syndrome, Kreutzfeldt-Jacob disease, Huntington's disease, motor neuron disease, amyotrophic lateral sclerosis (sporadic, familial and Guam-type ALS dementia complex), axonal dystrophy, neurodegenerative disease with brain iron deposition type 1 (Halverden-Schpattz syndrome), prions, Gerstmann-Straussler-Schainkel disease, ataxia-telangiectasia, syphilis syndrome, subacute sclerosing panencephalitis, Gaucher disease, Krabby disease and other lysosomal storage diseases (including Kufor-Rakeb syndrome and Sanfilippo syndrome) or rapid eye movement (REM) sleep behavior disorders.

[0116] More specifically, synucleinopathies are selected from Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD; Lewy body dementia (DLB) ("pure" Lewy body dementia), Parkinson's disease dementia (PDD)) and diffuse Lewy body disease.

[0117] In some embodiments, methods are provided for detecting α-synuclein aggregates (including, but not limited to, Lewy bodies, Lewy neurites, and / or glial cell cytoplasmic inclusions), comprising contacting a sample with an antibody or its antigen-binding fragment or derivative 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.

[0118] In some embodiments, a method is provided for evaluating the ability of α-synuclein-binding molecules to inhibit and / or delay seeding and / or spontaneous α-synuclein aggregation, the method comprising the steps of: contacting α-synuclein-binding molecules with α-synuclein aggregates (seeds); allowing α-synuclein-binding molecules to bind to α-synuclein aggregates to form an immune complex; adding α-synuclein monomeric protein and a detectable dye, particularly a fluorescent dye, to the immune complex; and determining the time to reach the half-maximum signal of the detectable dye, particularly the signal of the fluorescent dye, relative to seeding aggregation in the absence of binding molecules, wherein an increase in the time to reach the half-maximum signal of the detectable dye in the presence of binding molecules relative to seeding aggregation in the absence of binding molecules indicates that the α-synuclein-binding molecules are capable of inhibiting and / or delaying seeding and / or graying α-synuclein aggregation.

[0119] In other embodiments, a method is provided for selecting / screening α-synuclein-binding molecules capable of inhibiting and / or delaying the aggregation of α-synuclein and / or spontaneously occurring α-synuclein, the method comprising the steps of: contacting the α-synuclein-binding molecules with α-synuclein aggregates (seeds); allowing the α-synuclein-binding molecules to bind to the α-synuclein aggregates to form an immune complex; adding α-synuclein monomeric protein and a detectable dye, particularly a fluorescent dye, to the immune complex; and selecting α-synuclein-binding molecules capable of inhibiting and / or delaying the aggregation of α-synuclein and / or spontaneously occurring α-synuclein based on the signal of the detectable dye, particularly the fluorescent dye, determined in the absence and presence of the α-synuclein-binding molecules.

[0120] In some embodiments, methods are provided for evaluating or selecting α-synuclein-binding molecules capable of inhibiting and / or delaying the inoculation of and / or spontaneous α-synuclein aggregation, wherein the detectable dye is thioflavin (ThT), which binds to the β-sheet structure of the aggregated protein.

[0121] In some embodiments, methods are provided for evaluating or selecting α-synuclein-binding molecules capable of inhibiting and / or delaying the aggregation of α-synuclein in seeded and / or gray hair, wherein the α-synuclein monomeric protein is covalently linked to a detectable dye, particularly a fluorescent dye, and / or wherein the signal of the detectable dye, particularly the fluorescent dye, is quenched upon the formation of protein aggregates. Other detection methods are also contemplated within the scope of this invention, including, for example, fluorescence resonance energy transfer (FRET) assays. Dyes, particularly fluorescent dyes, are known to those skilled in the art. Some examples include, for example, green fluorescent protein, yellow fluorescent protein, etc.

[0122] In some embodiments, if, in step d) of the invention, the inoculation and / or spontaneous α-synuclein aggregation in the presence of an α-synuclein binding molecule is inhibited and / or delayed by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, or 300% compared to the absence of an α-synuclein binding molecule, then the α-synuclein binding molecule is evaluated as capable of inhibiting and / or delaying the inoculation and / or spontaneous α-synuclein aggregation, or selected accordingly. Alternatively, if the α-synuclein binding molecule causes an aggregation half-life (τ1 / 2 value) of the inoculated aggregation to be at least 10% higher than the aggregation in the absence of the binding molecule, then the α-synuclein binding molecule can be evaluated as capable of inhibiting and / or delaying the inoculation and / or spontaneous α-synuclein aggregation.

[0123] In some embodiments, methods for determining or evaluating the ability of α-synuclein binding molecules to delay and / or inhibit the aggregation of inoculated α-synuclein include the following steps:

[0124] (i) Incubating cells containing and / or expressing monomeric α-synuclein reporter protein with a composition containing an α-synuclein binding molecule and a transduction agent capable of delivering the α-synuclein binding molecule into the cells.

[0125] (ii) Incubating cells with a composition containing α-synuclein aggregates (seeds) and a transduction reagent; and

[0126] (iii) Determine the de novo aggregation of α-synuclein reporter proteins to identify or evaluate the ability of α-synuclein binding molecules to delay and / or inhibit the aggregation of seeded α-synuclein.

[0127] In methods for determining or evaluating the ability of α-synuclein-binding molecules to delay and / or inhibit the aggregation of seeded α-synuclein, the composition comprising the α-synuclein-binding molecule and the transduction reagent are premixed prior to incubation with cells containing and / or expressing monomeric α-synuclein reporter proteins. In some embodiments, methods for determining or evaluating the ability of α-synuclein-binding molecules to delay and / or inhibit cellular uptake of pathological and / or aggregated α-synuclein include the following steps:

[0128] (i) Incubate cells containing and / or expressing monomeric α-synuclein together with α-synuclein binding molecules.

[0129] (ii) Incubating cells with α-synuclein aggregates (seeds); and

[0130] (iii) Determine the de novo aggregation of α-synuclein to identify or evaluate the ability of α-synuclein binding molecules to delay and / or inhibit the cellular uptake of pathological and / or aggregated α-synuclein.

[0131] In some embodiments of the present invention, the α-synuclein binding molecule of a method for determining or evaluating the ability of an α-synuclein binding molecule to delay and / or inhibit the aggregation of inoculated α-synuclein preferably comprises an α-synuclein antibody or an antigen-binding fragment or derivative thereof, more preferably comprising the antibody or an antigen-binding fragment or derivative thereof of the present invention.

[0132] In some embodiments of the present invention, the transduction reagents in (i) and (ii) of the method for determining or evaluating the ability of α-synuclein binding molecules to delay and / or inhibit the aggregation of seeded α-synuclein may be the same or different, preferably the transduction reagents are different, and more preferably the transduction reagent in (i) contains Ab-DeliverIN. TM And the transduction reagent in (ii) contains Lipofectamine TM 2000.

[0133] In some embodiments of the invention, step (iii) of the method for determining or evaluating the ability of α-synuclein binding molecules to delay and / or inhibit the aggregation of seeded α-synuclein includes immunohistochemistry, microscopy, biochemistry or flow cytometry detection methods, preferably immunohistochemistry, more preferably immunohistochemistry in which the fluorescence of fluorescently labeled α-synuclein expressed by said cells is measured.

[0134] In some embodiments of the present invention, a method for determining or evaluating the ability of α-synuclein binding molecules to delay and / or inhibit the aggregation of seeded α-synuclein includes the following steps:

[0135] (i) Incubating cells containing and / or expressing monomeric α-synuclein reporter protein with a composition containing an α-synuclein binding molecule and a transduction agent capable of delivering the α-synuclein binding molecule into the cells.

[0136] (ii) Incubating cells with a composition containing α-synuclein aggregates (seeds) and a transduction reagent; and

[0137] (iii) Determine the de novo aggregation of α-synuclein reporter proteins to identify or evaluate the ability of α-synuclein binding molecules to delay and / or inhibit the aggregation of seeded α-synuclein.

[0138] The incubation time in step (i) is up to 12 hours, preferably 5 hours, and the incubation time in step (ii) is at least 12 hours, preferably 96 hours, and the transduction reagent in (i) is Ab-DeliverIN. TM And the transduction reagent in (ii) is Lipofectamine. TM 2000.

[0139] Therefore, in the context of this invention, the term "transduction reagent" (or "transfection reagent") as used herein primarily refers to a formulation capable of forming a non-covalent complex with a target molecule for intracellular transport. Examples of transduction reagents include, but are not limited to, Ab-DeliverIN. TM Lipofectamine TM 2000, Xfect TM Transfection reagent, ViaFect TM Transfection reagent, polyethylenimine (PEI) cell transfection reagent, or FuGENE TM .

[0140] In some embodiments, if the aggregation of inoculated α-synuclein 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 an α-synuclein binding molecule compared to the absence of such a molecule, then the α-synuclein binding molecule is evaluated as capable of delaying and / or inhibiting the aggregation of inoculated α-synuclein using the method of the present invention. Alternatively, if the α-synuclein binding molecule results in a reduction of at least 10% in the level of aggregated α-synuclein relative to the level of aggregated α-synuclein in the absence of the binding molecule, then the α-synuclein binding molecule can be evaluated as capable of delaying and / or inhibiting the aggregation of inoculated α-synuclein.

[0141] Within the scope of this invention, α-synuclein may have the sequence of SEQ ID NO: 1. α-synuclein aggregates are β-sheet-rich assemblages of polymerized α-synuclein monomers, which can form soluble oligomers or soluble / insoluble primary or mature fibrils. These soluble oligomers or soluble / insoluble primary or mature fibrils aggregate into intracellular deposits and have been detected as a series of Lewy pathological conditions in Parkinson's disease and other synucleinogenic disorders. Under physiological conditions, α-synuclein does not employ an ordered tertiary structure but is classified as a naturally occurring unfolded protein, existing as a mixture of dynamic and flexible structural conformations. Wrapped α-synuclein can form polymeric intermediate oligomer structures, ultimately assembling into highly ordered fibrous aggregates.

[0142] As used in this article, the term "aggregated α-synuclein" refers to insoluble or soluble oligomeric and / or polymeric structures composed of misfolded monomers and / or polymers and / or assemblies of monomers of α-synuclein.

[0143] Pathological α-synucleins are misfolded, aggregated, or post-translational modified α-synucleins and are a major component of Lewy pathology. Lewy pathology can be detected by the following morphologies: Lewy bodies, Lewy neurites, premature Lewy bodies or pallid bodies, and perinuclear deposits with diffuse, granular, punctate, or pleomorphic patterns. Furthermore, pathological α-synucleins are a major component of intracellular fibrillary inclusions (also known as glial cell cytoplasmic inclusions) detected in oligodendrocytes and intracellular fibrillary inclusions (also known as neuronal cytoplasmic inclusions) detected in neuronal cell bodies, axons, and nuclei, and are a histological marker of multisystem atrophy. Pathological α-synucleins in Lewy pathology typically show a marked increase in post-translational modifications such as phosphorylation, ubiquitination, nitration, and truncation.

[0144] Seeds are polymeric structures rich in β-sheets, composed of α-synuclein, or (i.e., other than α-synuclein) other amyloidogenic proteins (e.g., Tau, amyloid β), which can accelerate the aggregation kinetics of α-synuclein by elongating growing polymers and / or by acting as templates for monomer nucleation on the seed surface.

[0145] Spontaneous aggregation of α-synuclein is an aggregation process that occurs without the addition of seeds. α-synuclein is a soluble protein that, under certain conditions, has a tendency to spontaneously aggregate and form soluble oligomers, soluble / insoluble primary or mature fibrils, or detergent-insoluble aggregates.

[0146] Lewy bodies are abnormal protein aggregates that develop within nerve 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. The classic brainstem Lewy body is an eosinophilic cytoplasmic inclusion body composed of a dense nucleus surrounded by a halo of radiating fibrils 5 to 10 nm wide; its main structural component is α-synuclein. Cortical Lewy bodies differ due to the absence of this halo. The presence of Lewy bodies is a hallmark of Parkinson's disease.

[0147] Lewy neurites are abnormal neuronal processes in diseased neurons, containing granular material, abnormal α-synuclein filaments similar to those found in Lewy bodies, punctate, tortuous structures, and axonal spheroids. Like Lewy bodies, Lewy neurites are characteristic of α-synucleinosis disorders such as Lewy body dementia, Parkinson's disease, and multiple system atrophy.

[0148] Glial cell cytoplasmic inclusions (also known as Papp-Lantos inclusions) consist of insoluble α-synuclein filamentous aggregates detected in oligodendrocytes in the white matter of the brain in multiple system atrophy (MSA). α-synuclein aggregates in neuronal cell bodies, axons, and nuclei, collectively known as neuronal cytoplasmic inclusions, are a characteristic cytopathological feature of MSA. The detection of glial cell cytoplasmic inclusions is considered a marker for the neuropathological diagnosis of MSA.

[0149] An α-synuclein binding molecule is a molecule that binds to pathological and / or aggregated α-synuclein, 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. This epitope can be a linear epitope or a non-linear epitope. Preferably, the antigen-binding molecule of the present invention binds to an epitope within the following amino acid residues of the human α-synuclein of SEQ ID NO: 1:

[0150] No. 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).

[0151] More preferably, the antigen-binding molecule of the present invention binds to epitopes within amino acid residues 124-131 (SEQ ID NO: 7), 128-135 (SEQ ID NO: 8), or 131-140 (SEQ ID NO: 9) of the human α-synuclein protein of SEQ ID NO: 1. Even more preferably, the antigen-binding molecule of the present invention can bind to epitopes containing amino acids 126 and 127 of the human α-synuclein protein of SEQ ID NO: 1 (as key residues for binding). In another embodiment, the antigen-binding molecule of the present invention binds to nonlinear epitopes within amino acid residues of the human α-synuclein protein of SEQ ID NO: 1.

[0152] Other α-synuclein binding molecules may also include multivalent molecules, multispecific molecules (e.g., biparatopic antibodies), fusion molecules, aptamers, avimers, or other naturally occurring or recombinant molecules. Illustrative antigen-binding molecules that can be used in this invention include antibody-like molecules. Antibody-like molecules are molecules that can exhibit function 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, DARPin (WO 2002 / 020565), affibody (WO 1995 / 001937), Avimer (WO 2004 / 044011; WO 2005 / 040229), Adnectin (WO 2002 / 032925), and fynomer (WO2013 / 135588).

[0153] As used herein, "antigen-binding molecule" refers to any molecule that can bind specifically or selectively to an antigen. Binding molecules may include or may be antibodies or fragments thereof. An α-synuclein binding molecule is a molecule that binds to α-synuclein, such as an α-synuclein antibody or fragment thereof, at a specific recognition site or epitope.

[0154] As used herein, the terms “α-synuclein antibody,” “anti-α-synuclein antibody,” and “antibody that binds to pathological and / or aggregated α-synuclein,” or simply “antibody,” refer to an antibody capable of binding with sufficient affinity to pathological α-synuclein and / or aggregated α-synuclein, including but not limited to Lewy bodies, Lewy neurites, or glial cell cytoplasmic inclusions, such that the antibody can be used as a therapeutic and / or diagnostic agent targeting α-synuclein. In one embodiment, the α-synuclein antibody of the present invention binds to less than about 10% of the antibody’s binding to α-synuclein, as measured, for example, by radioimmunoassay (RIA).

[0155] Generally, the term "antibody" is used in the broadest sense herein and encompasses 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, provided they exhibit the desired antigen-binding activity. Antibodies within the scope of this invention may also 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 bacteriophages or on the surface of chimeric antigen receptor (CAR) T cells.

[0156] An antibody “antigen-binding fragment” refers to a molecule that contains a portion of the complete antibody and binds to an antigen that binds to the complete antibody, distinct from the complete antibody. Some examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; biantibodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments.

[0157] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e., the individual antibodies constituting that population are identical except for the possibility of naturally occurring mutations present in small amounts. Monoclonal antibodies are highly specific, targeting a single antigenic site. The modifier "monoclonal" indicates the antibody's characteristics within a substantially homogeneous population of antibodies and should not be construed as requiring the antibody to be produced by any particular method. As described above, the monoclonal antibody used according to the invention can be prepared by the hybridoma method described in Kohler, Nature 256 (1975), 495.

[0158] Therefore, in the context of this invention, the term "antibody" refers to a complete immunoglobulin molecule and a portion thereof (i.e., "its antigen-binding fragment"). Furthermore, as discussed above, the term refers to modified and / or altered antibody molecules. The term also refers to antibodies that are recombinantly or synthetically produced / synthesized. The term further refers to complete antibodies and antibody fragments thereof, such as isolated 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.

[0159] Humanized antibodies are modified antibodies, also known as reconstructed human antibodies. Humanized antibodies are constructed by transferring the CDR of an antibody derived from an immunized animal to the complementarity-determining region of a human antibody. Conventional genetic recombination techniques for such purposes are known (see European Patent Application Publication No. EP 239400; International Publication No. WO 96 / 02576; Sato K. et al., Cancer Research 1993, 53: 851-856; International Publication No. WO 99 / 51743).

[0160] As used herein, the term "CDR" refers to "complementarity-determining region," which is well-known in the art. A CDR is a part of an immunoglobulin that determines the specificity of the molecule and contacts a specific ligand. The CDR is the most variable part of the molecule and contributes to the diversity of these molecules. Three CDR regions are present in each V domain: CDR1, CDR2, and CDR3. VH-CDR or CDR-H indicates the CDR region of a variable heavy chain, and VL-CDR or CDR-L refers to the CDR region of a variable light chain. VH signifies the variable heavy chain, and VL signifies the variable light chain. The CDR region of the Ig source region can be determined as described in Kabat, “Sequences of Proteins of Immunological Interest,” 5th edition, NIH Publication No. 91-3242, Department of Health and Human Services (1991); Chothia J., Mol. Biol. 196 (1987), 901-917; or Chothia, Nature 342 (1989), 877-883.

[0161] The “Fc” region contains two heavy chain segments with CH2 and CH3 domains containing the antibody. The two heavy chain segments are held together by two or more disulfide bonds and by hydrophobic interactions through the CH3 domain.

[0162] The “Fab’ fragment” comprises a light chain and a portion of a heavy chain, the portion of which contains a VH domain and a CH1 domain and also contains a region between the CH1 and CH2 domains, such that interchain disulfide bonds can be formed between the two heavy chains of the two Fab’ fragments to form the F(ab’)2 molecule.

[0163] The “F(ab')2 segment” comprises two light chains and two heavy chains, the heavy chains containing a portion of a constant region between the CH1 and CH2 domains, such that interchain disulfide bonds are formed between the two heavy chains. Therefore, the F(ab')2 segment consists of two Fab' segments held together by disulfide bonds between the two heavy chains.

[0164] The “Fv region” contains variable regions from both the heavy and light chains, but lacks constant regions.

[0165] Therefore, in the context of this invention, antibody molecules or antigen-binding fragments thereof are provided that are humanized and can be successfully used in pharmaceutical compositions.

[0166] "Antibodies that bind to epitopes in protein-defined regions" are antibodies that require the presence of one or more amino acids in that region to bind to the protein.

[0167] In some embodiments, the "antibody that binds to an epitope in a protein-defined region" is identified by mutation analysis, wherein an amino acid of the protein is mutated, and the binding of the antibody to the resulting modified protein (e.g., a modified protein containing the epitope) is determined to be at least 20% of the binding to the unmodified protein. In some embodiments, the "antibody that binds to an epitope in a protein-defined region" is identified by mutation analysis, wherein an amino acid of the protein is mutated, and the binding of the antibody to the resulting modified protein (e.g., a modified protein containing 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 some embodiments, antibody binding is determined by FACS, WB, or by a suitable binding assay such as ELISA.

[0168] In the context of this invention, the term "binding with" defines the binding (interaction) of at least two "antigen interaction sites" to each other. According to the invention, the term "antigen interaction site" defines a motif of a polypeptide, i.e., a portion of the antibody or antigen-binding fragment of the invention, which exhibits the ability to specifically interact with a specific antigen or a specific set of antigens in α-synuclein. The binding / interaction should also be understood to define "specific recognition." According to the invention, the term "specifically recognize" means that the antibody is capable of specifically interacting with and / or binding to at least two amino acids (also referred to as "key residues") of α-synuclein as defined herein, particularly interacting with / binding to at least two amino acids within the following residues of human α-synuclein of SEQ ID NO: 1:

[0169] No. 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).

[0170] The residues can form linear or nonlinear epitopes. Preferably, the antigen-binding molecule of the present invention binds to epitopes within amino acid residues 124-131 (SEQ ID NO: 7), 128-135 (SEQ ID NO: 8), or 131-140 (SEQ ID NO: 9) of the human α-synuclein protein of SEQ ID NO: 1. Even more preferably, the antigen-binding molecule of the present invention can bind to epitopes containing amino acids 126 and 127 of the human α-synuclein protein of SEQ ID NO: 1 (as key residues for binding). The antigen-binding molecule of the present invention can also bind to nonlinear epitopes within amino acid residues of the human α-synuclein protein of SEQ ID NO: 1.

[0171] The cross-reactivity of the antigen-binding molecules under investigation, particularly groups of antibodies or their antigen-binding fragments, can be tested, for example, by assessing the binding of the group of antibodies or their antigen-binding fragments to the target (poly)peptide and to many (poly)peptides that are more or less (structurally and / or functionally) closely related, under normal 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, their antigen-binding fragments, etc.) that bind to certain α-synuclein structures as defined herein, such as specific epitopes or (poly)peptides / proteins of α-synuclein as defined herein, but not to or substantially not to any other epitopes or (poly)peptides of the same α-synuclein, are considered specific to the target epitope or (poly)peptide / protein and are selected for further studies according to the methods provided herein. These methods may include, in particular, studies of binding, blocking, and competition with structurally and / or functionally closely related molecules. These binding studies also include FACS analysis, surface plasmon resonance (SPR, e.g., using BIACORE™), analytical ultracentrifugation, isothermal titration calorimetry, fluorescence anisotropy, fluorescence spectroscopy, or determination via binding to radiolabeled ligands.

[0172] Therefore, specificity can be determined experimentally using methods known in the art and those described herein. Such methods include, but are not limited to, Western blotting, ELISA, RIA, ECL, IRMA assays, and peptide scanning.

[0173] Those skilled in the art will understand that epitopes may be contained in α-synuclein, but may also be contained in their degradation products or may be chemically synthesized peptides. Only amino acid positions are indicated to show the location of the corresponding amino acid sequence within the α-synuclein sequence. This invention covers all peptides containing epitopes. The peptide may be part of a polypeptide longer than 100 amino acids, or may be a small peptide with fewer than 100, preferably fewer than 50, more preferably fewer than 25, and even more preferably fewer than 18 amino acids. The amino acids of such peptides may be natural or non-natural amino acids (e.g., β-amino acids, γ-amino acids, D-amino acids) or combinations thereof. Furthermore, this invention may cover the corresponding retro-inverso peptide of the epitope. The peptide may be unbound or bound. It may be bound to, for example, small molecules (e.g., drugs or fluorophores), high molecular weight polymers (e.g., polyethylene glycol (PEG), polyethyleneimine (PEI), hydroxypropylmethacrylate (HPMA), etc.), or proteins, fatty acids, sugar moieties, or may be intercalated into a membrane. To test whether the antibodies discussed and the antibodies of the present invention recognize the same or similar epitopes, many assays are known in the art, some of which (e.g., "alanine scanning mutagenesis") are described in the examples below.

[0174] Whether an antibody recognizes the same epitope as or overlaps with the epitope recognized by another antibody presented herein can be confirmed by competition between the two antibodies for that epitope. Competition between antibodies can be achieved using techniques such as enzyme-linked immunosorbent assay (ELISA), fluorescence energy transfer method (FRET), and fluorometric microvolume assay technology. Evaluation is performed using a competitive binding assay. The amount of antibody binding to the antigen is indirectly related to the binding ability of candidate competing antibodies (test antibodies) that competitively bind to the same or overlapping epitopes. In other words, as the amount or affinity of test antibodies targeting the same or overlapping epitopes increases, the amount of antibody binding to the antigen decreases, while the amount of test antibody binding to that antigen increases. Specifically, appropriately labeled antibodies and test antibodies are simultaneously added to the antigen, and the binding antibody is subsequently detected using the label. The amount of antibody binding to the antigen can be easily determined by pre-labeling the antibody. There are no particular limitations on the labeling, and the labeling method is selected based on the assay technique used. Some specific examples of labeling methods include fluorescent labeling, radioactive labeling, and enzyme labeling.

[0175] In this document, "antibody binding to overlapping epitopes" or "antibody binding to the same epitope" refers to a test antibody that, at a concentration typically 100 times higher than that of the unlabeled antibody, preferably 80 times higher, more preferably 50 times higher, even more preferably 30 times higher, and still more preferably 10 times higher (at which concentration the binding of the unlabeled antibody would reduce the binding amount of the labeled antibody by 50% (IC50)), can reduce the binding amount of the labeled antibody by at least 50%. The epitope recognized by the antibody can be analyzed by methods known to those skilled in the art, and for example, by Western blotting, etc.

[0176] In some embodiments, the antibody comprises:

[0177] a) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 10; or

[0178] b) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 20 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 20; or

[0179] c) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 30 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 30; or

[0180] d) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 40 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 40; or

[0181] e) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 50 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 50; or

[0182] f) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 60 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 60; or

[0183] g) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 70 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 70; or

[0184] h) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 90 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 90; or

[0185] i) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 100 or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 100; or

[0186] j) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 110 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 110; or

[0187] k) A heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 280; or

[0188] l) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 290 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 290; or

[0189] m) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 140 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 140; or

[0190] n) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 150 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 150; or

[0191] o) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 160 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 160; or

[0192] p) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 170 or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 170; or

[0193] q) A heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 180; or

[0194] r) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 190 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 with the amino acid sequence of SEQ ID NO: 190; or

[0195] s) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 200 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 200; or

[0196] t) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 210 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 210; or

[0197] u) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 220 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 220; or

[0198] v) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 230 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 230; or

[0199] w) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 240 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 240; or

[0200] x) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 250 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 250; or

[0201] y) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 260 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 260; or

[0202] z) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 270 or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 270; or

[0203] aa) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 300 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 300; or

[0204] bb) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 310 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 310; or

[0205] cc) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 320 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 320; or

[0206] dd) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 330 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 330; or

[0207] ee) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 340 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 340; or

[0208] ff) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 350 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 350; or

[0209] gg) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 360 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 360; or

[0210] hh) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 370 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 370; or

[0211] ii) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 380 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 380; or

[0212] jj) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 390 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 390; or

[0213] kk) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 400 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 400; or

[0214] ll) A heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 410; or

[0215] The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 420 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 420; or

[0216] nn) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 430 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 430; or

[0217] oo) A heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 440; or

[0218] pp) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 450 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 450; or

[0219] qq) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 460 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 460; or

[0220] rr) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 470 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 470; or

[0221] ss) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 480 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 480; or

[0222] tt) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 490 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 490; or

[0223] uu) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 500 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 with the amino acid sequence of SEQ ID NO: 500; or

[0224] vv) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 510 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 with the amino acid sequence of SEQ ID NO: 510; or

[0225] ww) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 520 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 520; or

[0226] xx) A heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 530; or

[0227] yy) a heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 540; or

[0228] zz) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 550 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 550; or

[0229] aaa) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 560 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 with the amino acid sequence of SEQ ID NO: 560; or

[0230] bbb) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 570 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 570; or

[0231] ccc) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 580 or a heavy chain variable region (VH) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 580; or

[0232] ddd) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 590 or a heavy chain variable region (VH) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 590; or

[0233] eee) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 600 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 600; or

[0234] fff) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 610 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 610; or

[0235] ggg) contains a heavy chain variable region (VH) of the sequence of SEQ ID NO: 620 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 620; or

[0236] (hhh) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 630 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 with the amino acid sequence of SEQ ID NO: 630; or

[0237] iii) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 640 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 with the amino acid sequence of SEQ ID NO: 640; or

[0238] jjj) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 650 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 with the amino acid sequence of SEQ ID NO: 650; or

[0239] kkk) contains a heavy chain variable region (VH) of the sequence of SEQ ID NO: 660 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 660; or

[0240] lll) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 670 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 670; or

[0241] The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 680 or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 680; or

[0242] nnn) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 690 or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 690; or

[0243] ooo) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 700 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 with the amino acid sequence of SEQ ID NO: 700; or

[0244] ppp) contains a heavy chain variable region (VH) of the sequence of SEQ ID NO: 710 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 with the amino acid sequence of SEQ ID NO: 710; or

[0245] The heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 720.

[0246] In some embodiments, the antibody comprises:

[0247] a) A light chain variable region (VL) containing the sequence of SEQ ID NO: 14 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 14; or

[0248] b) A light chain variable region (VL) containing the sequence of SEQ ID NO: 24 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 24; or

[0249] c) A light chain variable region (VL) containing the sequence of SEQ ID NO: 34 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 34; or

[0250] d) A light chain variable region (VL) containing the sequence of SEQ ID NO: 44 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 44; or

[0251] e) A light chain variable region (VL) containing the sequence of SEQ ID NO: 54 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 54; or

[0252] f) A light chain variable region (VL) containing the sequence of SEQ ID NO: 64 or a light chain variable region (VL) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 64; or

[0253] g) A light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or a light chain variable region (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 74; or

[0254] h) A light chain variable region (VL) containing the sequence of SEQ ID NO: 84 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 84; or

[0255] i) a light chain variable region (VL) containing the sequence of SEQ ID NO: 94 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 94; or

[0256] j) A light chain variable region (VL) containing the sequence of SEQ ID NO: 104 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 104; or

[0257] k) The light chain variable region (VL) containing the sequence of SEQ ID NO: 114; or

[0258] l) The light chain variable region (VL) containing the sequence of SEQ ID NO: 284; or

[0259] m) A light chain variable region (VL) containing the sequence of SEQ ID NO: 194 or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 194; or

[0260] n) A light chain variable region (VL) containing the sequence of SEQ ID NO: 144 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 144; or

[0261] o) a light chain variable region (VL) containing the sequence of SEQ ID NO: 154 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 154; or

[0262] p) A light chain variable region (VL) containing the sequence of SEQ ID NO: 174 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 174; or

[0263] q) The light chain variable region (VL) containing the sequence of SEQ ID NO: 184; or

[0264] r) A light chain variable region (VL) containing the sequence of SEQ ID NO: 204 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 204; or

[0265] s) A light chain variable region (VL) containing the sequence of SEQ ID NO: 214 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 214; or

[0266] t) A light chain variable region (VL) containing the sequence of SEQ ID NO: 224 or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 224; or

[0267] u) A light chain variable region (VL) containing the sequence of SEQ ID NO: 234 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 234; or

[0268] v) A light chain variable region (VL) containing the sequence of SEQ ID NO: 244 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 244; or

[0269] w) A light chain variable region (VL) containing the sequence of SEQ ID NO: 254 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 254; or

[0270] x) A light chain variable region (VL) containing the sequence of SEQ ID NO: 264 or a light chain variable region (VL) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 264; or

[0271] y) A light chain variable region (VL) containing the sequence of SEQ ID NO: 274 or a light chain variable region (VL) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 274; or

[0272] z) A light chain variable region (VL) containing the sequence of SEQ ID NO: 304 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 304; or

[0273] aa) A light chain variable region (VL) containing the sequence of SEQ ID NO: 314 or a light chain variable region (VL) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 314; or

[0274] bb) A light chain variable region (VL) containing the sequence of SEQ ID NO: 324 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 324; or

[0275] cc) a light chain variable region (VL) containing the sequence of SEQ ID NO: 334 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 334; or

[0276] dd) A light chain variable region (VL) containing the sequence of SEQ ID NO: 344 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 344; or

[0277] ee) a light chain variable region (VL) containing the sequence of SEQ ID NO: 354 or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 354; or

[0278] ff) A light chain variable region (VL) containing the sequence of SEQ ID NO: 364 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 364; or

[0279] gg) a light chain variable region (VL) containing the sequence of SEQ ID NO: 374 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 374; or

[0280] hh) a light chain variable region (VL) containing the sequence of SEQ ID NO: 384 or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 384; or

[0281] ii) A light chain variable region (VL) containing the sequence of SEQ ID NO: 394 or a light chain variable region (VL) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 394; or

[0282] jj) A light chain variable region (VL) containing the sequence of SEQ ID NO: 404 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 404; or

[0283] kk) contains the light chain variable region (VL) of the sequence SEQ ID NO: 414; or

[0284] ll) A light chain variable region (VL) containing the sequence of SEQ ID NO: 424 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 424; or

[0285] The light chain variable region (VL) containing the sequence of SEQ ID NO: 434 or the light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 434; or

[0286] nn) a light chain variable region (VL) containing the sequence of SEQ ID NO: 464 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 464; or

[0287] oo) A light chain variable region (VL) containing the sequence of SEQ ID NO: 474 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 474; or

[0288] pp) containing the light chain variable region (VL) of the sequence SEQ ID NO: 484; or

[0289] qq) A light chain variable region (VL) containing the sequence of SEQ ID NO: 494 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 494; or rr) A light chain variable region (VL) containing the sequence of SEQ ID NO: 504 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 504; or

[0290] ss) a light chain variable region (VL) containing the sequence of SEQ ID NO: 514 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 514; or

[0291] tt) a light chain variable region (VL) containing the sequence of SEQ ID NO: 524 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 524; or

[0292] uu) contains the light chain variable region (VL) of the sequence SEQ ID NO: 544; or

[0293] vv) A light chain variable region (VL) containing the sequence of SEQ ID NO: 554 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 554; or

[0294] ww) a light chain variable region (VL) containing the sequence of SEQ ID NO: 564 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 564; or

[0295] xx) A light chain variable region (VL) containing the sequence of SEQ ID NO: 574 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 574; or

[0296] yy) contains a light chain variable region (VL) of the sequence of SEQ ID NO: 584 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 584; or

[0297] zz) A light chain variable region (VL) containing the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0298] aaa) A light chain variable region (VL) containing the sequence of SEQ ID NO: 624 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0299] bbb) A light chain variable region (VL) containing the sequence of SEQ ID NO: 634 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 634; or

[0300] ccc) contains a light chain variable region (VL) of the sequence of SEQ ID NO: 644 or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 644.

[0301] In some embodiments, the antibody comprises:

[0302] a) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 10 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 14; or

[0303] b) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 20 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 24; or

[0304] c) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 30 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 34; or

[0305] d) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 40 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 44; or

[0306] e) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 50 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 54; or

[0307] f) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 60 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 64; or

[0308] g) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 70 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 74; or

[0309] h) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 30 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 84; or

[0310] i) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 90 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 94; or

[0311] j) The heavy chain variable region (VH) of the sequence containing SEQ ID NO: 100 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 104; or

[0312] k) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 110 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 114; or

[0313] l) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 280 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 284; or

[0314] m) the heavy chain variable region (VH) containing the sequence of SEQ ID NO: 290 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 194; or

[0315] n) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 140 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 144; or

[0316] o) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 150 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 154; or

[0317] p) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 160 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 164; or

[0318] q) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 170 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 174; or

[0319] r) the heavy chain variable region (VH) containing the sequence of SEQ ID NO: 180 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 184; or

[0320] s) the heavy chain variable region (VH) containing the sequence of SEQ ID NO: 190 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 194; or

[0321] t) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 200 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 204; or

[0322] u) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 210 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 214; or

[0323] v) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 220 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 224; or

[0324] w) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 230 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 234;

[0325] x) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 240 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 244; or

[0326] y) the heavy chain variable region (VH) containing the sequence of SEQ ID NO: 250 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 254; or

[0327] z) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 260 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 264; or

[0328] aa) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 270 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 274; or

[0329] bb) the heavy chain variable region (VH) containing the sequence of SEQ ID NO: 300 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 304; or

[0330] cc) the heavy chain variable region (VH) containing the sequence of SEQ ID NO: 310 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 314; or

[0331] dd) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 320 and the light chain variable region (VL) of the sequence of SEQ ID NO: 324; or

[0332] ee) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 330 and the light chain variable region (VL) of the sequence of SEQ ID NO: 334; or

[0333] ff) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 340 and the light chain variable region (VL) of the sequence of SEQ ID NO: 344; or

[0334] gg) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 350 and the light chain variable region (VL) of the sequence of SEQ ID NO: 354; or

[0335] hh) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 360 and the light chain variable region (VL) of the sequence of SEQ ID NO: 364; or

[0336] ii) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 370 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 374; or

[0337] jj) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 380 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 384; or

[0338] kk) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 390 and the light chain variable region (VL) of the sequence of SEQ ID NO: 394; or

[0339] ll) the heavy chain variable region (VH) containing the sequence of SEQ ID NO: 400 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 404; or

[0340] mm) containing the heavy chain variable region (VH) of the sequence of SEQ ID NO: 410 and the light chain variable region (VL) of the sequence of SEQ ID NO: 414; or

[0341] nn) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 420 and the light chain variable region (VL) of the sequence of SEQ ID NO: 424; or

[0342] oo) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 430 and the light chain variable region (VL) of the sequence of SEQ ID NO: 434; or

[0343] pp) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 440 and the light chain variable region (VL) of the sequence of SEQ ID NO: 414; or

[0344] qq) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 450 and the light chain variable region (VL) of the sequence of SEQ ID NO: 424; or

[0345] rr) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 460 and the light chain variable region (VL) of the sequence of SEQ ID NO: 464; or

[0346] ss) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 470 and the light chain variable region (VL) of the sequence of SEQ ID NO: 474; or

[0347] tt) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 480 and the light chain variable region (VL) of the sequence of SEQ ID NO: 484; or

[0348] uu) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 490 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 494; or

[0349] vv) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 500 and the light chain variable region (VL) of the sequence of SEQ ID NO: 504; or

[0350] ww) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 510 and the light chain variable region (VL) of the sequence of SEQ ID NO: 514; or

[0351] xx) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 520 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 524; or

[0352] yy) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 530 and the light chain variable region (VL) of the sequence of SEQ ID NO: 534; or

[0353] zz) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 540 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 544; or

[0354] aaa) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 550 and the light chain variable region (VL) of the sequence of SEQ ID NO: 554; or

[0355] bbb) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 560 and the light chain variable region (VL) of the sequence of SEQ ID NO: 564; or

[0356] ccc) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 570 and the light chain variable region (VL) of the sequence of SEQ ID NO: 574; or

[0357] ddd) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 580 and the light chain variable region (VL) of the sequence of SEQ ID NO: 584; or

[0358] eee) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 590 and the light chain variable region (VL) of the sequence of SEQ ID NO: 474; or

[0359] fff) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 600 and the light chain variable region (VL) of the sequence of SEQ ID NO: 554; or

[0360] ggg) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 610 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0361] hhh) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 610 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 624; or

[0362] iii) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 610 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 634; or

[0363] jjj) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 610 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 644; or

[0364] kkk) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 620 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0365] lll) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 620 and the light chain variable region (VL) of the sequence of SEQ ID NO: 624; or

[0366] mmm) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 620 and the light chain variable region (VL) of the sequence of SEQ ID NO: 634; or

[0367] nnn) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 620 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 644; or

[0368] ooo) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 630 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 614; or

[0369] ppp) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 630 and the light chain variable region (VL) of the sequence of SEQ ID NO: 624; or

[0370] qqq) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 630 and the light chain variable region (VL) of the sequence of SEQ ID NO: 634; or

[0371] rrr) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 630 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 644; or

[0372] The sss) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 640 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0373] The ttt) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 640 and the light chain variable region (VL) of the sequence of SEQ ID NO: 624; or

[0374] uuu) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 640 and the light chain variable region (VL) of the sequence of SEQ ID NO: 634; or

[0375] VVV) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 640 and the light chain variable region (VL) of the sequence of SEQ ID NO: 644; or

[0376] www) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 650 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 614; or

[0377] xxx) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 650 and the light chain variable region (VL) of the sequence of SEQ ID NO: 624; or

[0378] yyy) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 650 and the light chain variable region (VL) of the sequence of SEQ ID NO: 634; or

[0379] zzz) contains the heavy chain variable region (VH) of the sequence containing SEQ ID NO: 650 and the light chain variable region (VL) of the sequence containing SEQ ID NO: 644; or

[0380] aaaa) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 660 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0381] bbbb) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 670 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0382] The cccc sequence contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 680 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0383] dddd) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 690 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0384] The sequence eeee contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 690 and the light chain variable region (VL) of the sequence of SEQ ID NO: 624; or

[0385] The sequence ffff contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 700 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0386] The sequence gggg contains the heavy chain variable region (VH) of the sequence SEQ ID NO: 700 and the light chain variable region (VL) of the sequence SEQ ID NO: 624; or

[0387] hhhh) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 710 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0388] iiii) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 710 and the light chain variable region (VL) containing the sequence of SEQ ID NO: 624; or

[0389] jjjj) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 720 and the light chain variable region (VL) of the sequence of SEQ ID NO: 614; or

[0390] kkkk) contains the heavy chain variable region (VH) of the sequence of SEQ ID NO: 720 and the light chain variable region (VL) of the sequence of SEQ ID NO: 624.

[0391] In some embodiments, the antibody comprises:

[0392] a) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 14 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 14;

[0393] b) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 20 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 24;

[0394] c) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 30 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 34 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 34;

[0395] d) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 40 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 44 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 44;

[0396] e) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 50 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 54;

[0397] f) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 64;

[0398] g) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 74;

[0399] h) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 30 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 84 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 84;

[0400] i) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 90 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 90; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 94 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 94; or

[0401] j) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 104; or

[0402] k) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 110 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 114; or

[0403] l) a heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 280; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 284; or

[0404] m) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 290 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 194; or

[0405] n) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 140 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 144 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 144; or

[0406] o) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 150 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 150; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 154 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 154; or

[0407] p) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 160 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 164; or

[0408] q) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 174; or

[0409] r) a heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 184; or

[0410] s) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 190 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 with 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 a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 194; or

[0411] t) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 200 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 204; or

[0412] u) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 210 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 214; or

[0413] v) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 220 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 224; or

[0414] w) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 230 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 230; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 234 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 234; or

[0415] x) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 240 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 244; or

[0416] y) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 250 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 254; or

[0417] z) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 260 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 264; or

[0418] aa) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 270 or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 274; or

[0419] bb) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 300 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 300; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 304 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 304; or

[0420] cc) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 310 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 310; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 314 or a light chain variable region (VL) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 314; or

[0421] dd) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 320 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 320; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 324 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 324; or

[0422] ee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 330 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 334; or

[0423] ff) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 340 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 340; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 344 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 344; or

[0424] gg) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 350 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 350; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 354 or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 354; or

[0425] hh) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 360 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 360; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 364 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 364; or

[0426] ii) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 370 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 374; or

[0427] jj) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 380 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 384; or

[0428] kk) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 390 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 390; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 394 or a light chain variable region (VL) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 394; or

[0429] ll) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 400 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 400; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 404 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 404; or

[0430] The heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 410; and the light chain variable region (VL) containing the sequence of SEQ ID NO: 414; or

[0431] nn) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 420 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 420; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 424 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 424; or

[0432] oo) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 430 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 430; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 434 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 434; or

[0433] pp) a heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 440; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 414; or

[0434] qq) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 450 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 450; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 424 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 424; or

[0435] rr) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 460 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 460; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 464 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 464; or

[0436] ss) comprising the heavy chain variable region (VH) of the sequence of SEQ ID NO: 470 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 470; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 474 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 474; or

[0437] tt) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 480 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 480; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 484; or

[0438] uu) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 490 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 490; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 494 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 494; or

[0439] vv) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 500 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 with 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 a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 504; or

[0440] ww) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 510 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 with the amino acid sequence of SEQ ID NO: 510; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 514 or a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 514; or

[0441] xx) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 520 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 520; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 524 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 524; or

[0442] yy) a heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 530; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 534; or

[0443] zz) A heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 540; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 544; or

[0444] aaa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 550 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 554; or

[0445] bbb) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 560 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 with 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 a light chain variable region (VL) having at least 98% or 99% sequence identity with the amino acid sequence of SEQ ID NO: 564; or

[0446] ccc) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 570 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 570; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 574 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 574; or

[0447] ddd) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 580 or a heavy chain variable region (VH) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 580; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 584 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 584; or

[0448] eee) includes a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 590 or a heavy chain variable region (VH) having at least 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 590; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 474 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 474; or

[0449] fff) The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 600 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 600; and the light chain variable region (VL) containing the sequence of SEQ ID NO: 554 or a light chain variable region (VL) having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 554; or

[0450] ggg) contains a heavy chain variable region (VH) of the sequence of SEQ ID NO: 610 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 610; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0451] hhh) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 610 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 610; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 624 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0452] iii) A heavy chain variable region (VH) containing the sequence of SEQ ID NO: 610 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 610; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 634 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 634; or

[0453] jjj) The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 610 or a heavy chain variable region (VH) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 610; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 644; or

[0454] kkk) contains a heavy chain variable region (VH) of the sequence of SEQ ID NO: 620 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 620; and a light chain variable region (VL) contains a sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0455] lll) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0456] The heavy chain variable region (VH) containing the sequence of SEQ ID NO: 620 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 620; and the light chain variable region (VL) containing the sequence of SEQ ID NO: 634 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 634; or

[0457] nnn) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 620 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 644; or

[0458] ooo) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 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 with 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 a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0459] ppp) The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 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 with the amino acid sequence of SEQ ID NO: 630; and the 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%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0460] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 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 with the amino acid sequence of SEQ ID NO: 630; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 634; or

[0461] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 630 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 with the amino acid sequence of SEQ ID NO: 630; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 644 or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 644; or

[0462] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 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 with the amino acid sequence of SEQ ID NO: 640; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0463] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 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 with the amino acid sequence of SEQ ID NO: 640; and the 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%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0464] uuu) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 640 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 with 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 a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 634; or

[0465] VVV) comprises a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 640 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 with the amino acid sequence of SEQ ID NO: 640; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 644 or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 644; or

[0466] www) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 650 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 with the amino acid sequence of SEQ ID NO: 650; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0467] xxx) a heavy chain variable region (VH) containing the sequence of SEQ ID NO: 650 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 with the amino acid sequence of SEQ ID NO: 650; and a light chain variable region (VL) containing the sequence of SEQ ID NO: 624 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0468] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 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 with the amino acid sequence of SEQ ID NO: 650; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 634 or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 634; or

[0469] zzz) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 650 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 with 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 a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 644; or

[0470] aaaa) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 660 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with 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 a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0471] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 670 or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 670; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0472] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 680 or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 680; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0473] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 690; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0474] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 690 or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 690; and the 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%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0475] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 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 with the amino acid sequence of SEQ ID NO: 700; and the light chain variable region (VL) comprising the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0476] The heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 700 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 with the amino acid sequence of SEQ ID NO: 700; and the 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%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0477] (hhhh) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 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 with 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 a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0478] iiii) A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 710 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 with 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 a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624; or

[0479] jjjj) The heavy chain variable region (VH) containing 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 with the amino acid sequence of SEQ ID NO: 720; and the light chain variable region (VL) containing the sequence of SEQ ID NO: 614 or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 614; or

[0480] The 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 with the amino acid sequence of SEQ ID NO: 720; and the 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%, or 99% sequence identity with the amino acid sequence of SEQ ID NO: 624.

[0481] In some embodiments, the antibody comprises:

[0482] a) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 12; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 13;

[0483] b) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 22; and VH-CDR3 containing the amino acid sequence YSY;

[0484] c) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 32; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 33;

[0485] d) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 41; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 42; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 43;

[0486] e) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 52; and VH-CDR3 containing the amino acid sequence YSF;

[0487] f) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 61; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 62; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 43;

[0488] g) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 72; and VH-CDR3 containing the amino acid sequence YSY;

[0489] h) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 91; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 92; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 93; or

[0490] i) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 101; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 102; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 103; or

[0491] j) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 111; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 112; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 113; or

[0492] k) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 281; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 282; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 283; or

[0493] l) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 192; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 193; or

[0494] m) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 141; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 142; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 143; or

[0495] n) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 152; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 153; or

[0496] o) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 161; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 162; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 163; or

[0497] p) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 171; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 172; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 173; or

[0498] q) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 181; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 182; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 183; or

[0499] r) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 201; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 202; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 153; or

[0500] s) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 211; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 212; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 213; or

[0501] t) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 222; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 223; or

[0502] u) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 231; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 232; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 233; or

[0503] v) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 242; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 243; or

[0504] w) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 252; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 253; or

[0505] x) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 261; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 262; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 263; or

[0506] y) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 271; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 272; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 273; or

[0507] z) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 301; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 302; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 303; or

[0508] aa) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 311; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 312; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 313; or

[0509] bb) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 321; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 322; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 323; or

[0510] cc) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 332; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 333; or

[0511] dd) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 341; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 342; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 343; or

[0512] (ee) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 352; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 353; or

[0513] ff) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 361; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 362; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 363; or

[0514] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 371; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 372; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 373; or

[0515] (hh) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 382; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 383; or

[0516] ii) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 382; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 393; or

[0517] (jj) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 411; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 412; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 413; or

[0518] (kk) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 421; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 422; and VH-CDR3 containing the amino acid sequence GNY; or

[0519] ll) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 431; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 432; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 433; or

[0520] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 442; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 443; or

[0521] nn) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 461; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 462; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 463; or

[0522] oo) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 141; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 472; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 473; or

[0523] pp) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 481; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 482; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 483; or

[0524] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 141; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 492; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 493; or

[0525] rr) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 502; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 503; or

[0526] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 311; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 512; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 513; or

[0527] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 521; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 522; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 463; or

[0528] (uu) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 371; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 532; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 533; or

[0529] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 341; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 542; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 543; or

[0530] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 551; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 552; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 553; or

[0531] xx) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 551; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 552; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 563; or

[0532] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 571; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 202; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 573; or

[0533] zz) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 581; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 582; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 583; or

[0534] aaa) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 13; or

[0535] (bbb) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 663; or

[0536] (ccc) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 673; or

[0537] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 683.

[0538] In some implementations, the antibody comprises:

[0539] a) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 15; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17;

[0540] b) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 25; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 26; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 27;

[0541] c) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 35; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 36; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 37;

[0542] d) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 45; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 46; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 47;

[0543] e) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 55; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 56; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 27;

[0544] f) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 65; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 46; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 67;

[0545] g) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 75; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 76; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 77;

[0546] h) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 85; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 36; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 87;

[0547] i) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 95; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 97;

[0548] j) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0549] k) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 115; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 117; or

[0550] l) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 285; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 286; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 287; or

[0551] m) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 195; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 197; or

[0552] n) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 145; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0553] o) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 165; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 167; or

[0554] p) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 175; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 176; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 177; or

[0555] q) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 15; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 187; or

[0556] r) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 206; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0557] s) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 215; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 216; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 217; or

[0558] t) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 225; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 227.

[0559] u) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 235; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 236; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 237; or

[0560] v) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 225; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 247; or

[0561] w) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 255; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 256; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 257; or

[0562] x) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 265; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 176; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 267; or

[0563] y) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 275; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 276; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 277; or

[0564] z) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 15; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 307; or

[0565] aa) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 315; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 46; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 67; or

[0566] bb) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 325; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 326; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 327; or

[0567] cc) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 335; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 336; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0568] dd) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 345; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 346; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 347; or

[0569] (ee) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 355; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 356; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 357; or

[0570] ff) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 365; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 367; or

[0571] VL-CDR1 containing the amino acid sequence of SEQ ID NO: 345; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 376; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 347; or

[0572] (hh) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 385; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 386; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 387; or

[0573] ii) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 395; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 356; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 357; or

[0574] (jj) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 405; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 356; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 357; or

[0575] (kk) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 425; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 426; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 427; or

[0576] ll) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 435; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 436; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 437; or

[0577] VL-CDR1 containing the amino acid sequence of SEQ ID NO: 465; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 467; or

[0578] nn) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 475; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 476; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 477; or

[0579] oo) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 165; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 487; or

[0580] pp) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 495; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 496; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 497; or

[0581] VL-CDR1 containing the amino acid sequence of SEQ ID NO: 105; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 336; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 107; or

[0582] rr) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 515; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 516; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 517; or

[0583] VL-CDR1 containing the amino acid sequence of SEQ ID NO: 525; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 467; or

[0584] VL-CDR1 containing the amino acid sequence of SEQ ID NO: 345; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 376; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 347; or

[0585] (uu) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 555; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 557; or

[0586] w) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 565; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 557; or

[0587] VL-CDR1 containing the amino acid sequence of SEQ ID NO: 585; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 586; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 587; or

[0588] xx) VL-CDR1 containing the amino acid sequence of SEQ ID NO: 615; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17; or

[0589] VL-CDR1 containing the amino acid sequence of SEQ ID NO: 625; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 containing the amino acid sequence of SEQ ID NO: 17.

[0590] In some implementations, the antibody comprises:

[0591] a) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 11; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 12; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 13; 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 an amino acid sequence having sequence identity with SEQ ID NO: 17; or

[0592] b) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 21; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 22; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with amino acid sequence YSY; 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 an amino acid sequence having sequence identity with SEQ ID NO: 27; or

[0593] c) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 31; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 32; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 33; 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; or

[0594] d) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 41; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 42; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 43; 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; or

[0595] e) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 21; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 52; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with the amino acid sequence YSF; 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; or

[0596] f) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 61; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 62; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 43; 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; or

[0597] g) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 21; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 72; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with amino acid sequence YSY; 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; or

[0598] h) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 31; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 32; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 33; 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; or

[0599] i) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 91; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 92; and VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 93; 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; or

[0600] i) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 101; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 102; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 103; or 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

[0601] k) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 111; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 112; VH-CDR3 comprising an amino acid sequence having 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 113; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117; or

[0602] l) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 281; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 282; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 287; or

[0603] m) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 31; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 192; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 193; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 197; or

[0604] n) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 141; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 142; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 143; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 17; or

[0605] o) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 151; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 152; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 153; 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 an amino acid sequence having sequence identity with SEQ ID NO: 107; or

[0606] p) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 161; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 162; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 167; or

[0607] q) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 171; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 172; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 173; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 177; or

[0608] r) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 181; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 182; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 183; 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 an amino acid sequence having sequence identity with SEQ ID NO: 187; or

[0609] s) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 201; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 202; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 107; or

[0610] t) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 211; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 212; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 217; or

[0611] u) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 31; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 222; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 223; 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 an amino acid sequence having sequence identity with SEQ ID NO: 227; or

[0612] v) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 231; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 232; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 233; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 237; or

[0613] w) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 31; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 242; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 243; 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 an amino acid sequence having sequence identity with SEQ ID NO: 247; or

[0614] x) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 31; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 252; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 253; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 257; or

[0615] y) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 261; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 262; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 263; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 267; or

[0616] z) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 271; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 272; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 277; or

[0617] aa) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 301; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 302; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 303; 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 an amino acid sequence having sequence identity with SEQ ID NO: 307; or

[0618] bb) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 311; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 312; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 313; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 67; or

[0619] cc) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 321; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 322; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 323; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 325; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 327; or

[0620] dd) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 151; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 332; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 333; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 107; or

[0621] (ee) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 341; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 342; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 343; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 346; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 347; or

[0622] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 351; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 352; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 357; or

[0623] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 361; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 362; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 363; 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 an amino acid sequence having sequence identity with SEQ ID NO: 367; or

[0624] (hh) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 371; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 372; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 373; 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 an amino acid sequence having sequence identity with SEQ ID NO: 347; or

[0625] ii) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 351; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 382; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 383; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 387; or

[0626] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 351; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 382; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 393; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 395; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 357; or

[0627] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 351; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 382; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 357; or

[0628] ll) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 411; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 412; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 107; or

[0629] VH-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 421; VH-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 422; VH-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with the amino acid sequence GNY; VL-CDR1 containing the amino acid sequence of SEQ ID NO: 425; VL-CDR2 containing the amino acid sequence of SEQ ID NO: 426; and VL-CDR3 containing an amino acid sequence having sequence identity with SEQ ID NO: 427; or

[0630] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 431; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 432; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 437; or

[0631] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 151; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 442; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 107; or

[0632] pp) comprising VH-CDR1 having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 461; VH-CDR2 having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 462; VH-CDR3 having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 463; VL-CDR1 having the amino acid sequence of SEQ ID NO: 465; VL-CDR2 having the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 having the amino acid sequence of SEQ ID NO: 467; or

[0633] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 141; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 472; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 473; 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 an amino acid sequence having sequence identity with SEQ ID NO: 477; or

[0634] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 481; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 482; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 483; 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 an amino acid sequence having sequence identity with SEQ ID NO: 487; or

[0635] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 141; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 492; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 497; or

[0636] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 151; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 502; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 107; or

[0637] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 311; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 512; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 517; or

[0638] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 521; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 522; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 463; 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 an amino acid sequence having sequence identity with SEQ ID NO: 467; or

[0639] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 371; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 532; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 537; or

[0640] xx) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 341; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 542; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 347; or

[0641] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 551; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 552; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 553; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 555; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising an amino acid sequence having sequence identity with SEQ ID NO: 557; or

[0642] zz) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 551; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 552; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 557; or

[0643] (aaa) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 571; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 202; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 573; 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 an amino acid sequence having sequence identity with SEQ ID NO: 107; or

[0644] (bbb) VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 581; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 582; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 583; 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 an amino acid sequence having sequence identity with SEQ ID NO: 587; or

[0645] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 11; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 612; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 17; or

[0646] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 11; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 612; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 13; 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 an amino acid sequence having sequence identity with SEQ ID NO: 17; or

[0647] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 11; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 612; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 663; 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 an amino acid sequence having sequence identity with SEQ ID NO: 17; or

[0648] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 11; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 612; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 17; or

[0649] VH-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 11; VH-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 612; VH-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with 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 an amino acid sequence having sequence identity with SEQ ID NO: 17; or

[0650] VH-CDR1 contains an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 11; VH-CDR2 contains an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 612; VH-CDR3 contains an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 683; VL-CDR1 contains the amino acid sequence of SEQ ID NO: 625; VL-CDR2 contains the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 contains an amino acid sequence having sequence identity with SEQ ID NO: 17.

[0651] In some implementations, the antibody comprises:

[0652] a) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 12; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 13; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 15; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 17; or

[0653] b) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 22; VH-CDR3 containing the amino acid sequence YSY; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 25; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 26; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 27; or

[0654] c) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 32; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 33; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 35; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 36; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 37; or

[0655] d) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 41; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 42; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 43; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 45; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 46; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 47; or

[0656] e) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 52; VH-CDR3 containing the amino acid sequence YSF; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 55; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 56; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 27; or

[0657] f) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 61; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 62; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 43; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 65; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 46; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 67; or

[0658] g) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 21; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 72; VH-CDR3 containing the amino acid sequence YSY; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 75; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 76; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 77; or

[0659] h) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 32; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 33; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 85; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 36; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 87; or

[0660] i) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 91; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 92; and VH-CDR3 containing the amino acid sequence of SEQ ID NO: 93; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 95; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 96; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 97; or

[0661] j) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 101; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 102; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 103; or VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 105; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 106; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 107; or VH-CDR1 containing the amino acid sequence of SEQ ID NO: 111; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 112; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 113; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 105; VH-CDR1 containing the amino acid sequence of SEQ ID NO: 101; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 102; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 103; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 105; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 106; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 107; VH-CDR1 containing the amino acid sequence of SEQ ID NO: 111; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 112; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 113; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 1 VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 115; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 106; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 117; or

[0662] l) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 281; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 282; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 283; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 285; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 286; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 287; or

[0663] m) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 192; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 193; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 195; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 96; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 197; or

[0664] n) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 141; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 142; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 143; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 145; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 17; or

[0665] o) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 152; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 153; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 105; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 106; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 107; or

[0666] p) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 161; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 162; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 163; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 165; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 167; or

[0667] q) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 171; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 172; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 173; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 175; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 176; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 177; or

[0668] r) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 181; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 182; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 183; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 15; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 187; or

[0669] s) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 201; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 202; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 153; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 105; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 206; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 107; or

[0670] t) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 211; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 212; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 213; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 215; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 216; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 217; or

[0671] u) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 222; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 223; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 225; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 96; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 227; or

[0672] v) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 231; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 232; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 233; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 235; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 236; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 237; or

[0673] w) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 242; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 243; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 225; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 96; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 247; or

[0674] x) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 31; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 252; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 253; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 255; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 256; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 257; or

[0675] y) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 261; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 262; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 263; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 265; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 176; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 267; or

[0676] z) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 271; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 272; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 273; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 275; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 276; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 277; or

[0677] aa) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 301; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 302; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 303; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 15; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 307; or

[0678] bb) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 311; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 312; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 313; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 315; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 46; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 67; or

[0679] cc) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 321; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 322; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 323; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 325; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 326; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 327; or

[0680] dd) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 151; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 332; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 333; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 335; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 336; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 107; or

[0681] (ee) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 341; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 342; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 343; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 345; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 346; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 347; or

[0682] 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 with SEQ ID NO: 355; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 356; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 357; or

[0683] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 361; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 362; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 363; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 365; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 367; or

[0684] (hh) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 371; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 372; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 373; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 345; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 376; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 347; or

[0685] ii) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 382; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 383; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 385; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 386; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 387; or

[0686] (jj) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 351; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 382; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 393; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 395; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 356; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 357; or

[0687] 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 with SEQ ID NO: 405; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 356; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 357; or

[0688] ll) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 411; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 412; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 413; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 105; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 106; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 107; or

[0689] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 421; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 422; VH-CDR3 containing the amino acid sequence GNY; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 425; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 426; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 427; or

[0690] The following are examples of amino acid sequences: VH-CDR1 containing the amino acid sequence of SEQ ID NO: 431; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 432; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 433; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 435; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 436; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 437; or

[0691] 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 with SEQ ID NO: 105; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 106; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 107; or

[0692] pp) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 461; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 462; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 463; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 465; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 467; or

[0693] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 141; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 472; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 473; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 475; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 476; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 477; or

[0694] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 481; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 482; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 483; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 165; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 487; or

[0695] 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 with SEQ ID NO: 495; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 496; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 497; or

[0696] 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 with SEQ ID NO: 105; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 336; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 107; or

[0697] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 311; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 512; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 513; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 515; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 516; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 517; or

[0698] VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 521; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 522; 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 with SEQ ID NO: 525; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 467; or

[0699] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 371; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 532; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 533; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 345; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 376; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 537; or

[0700] xx) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 341; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 542; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 543; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 345; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 376; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 347; or

[0701] 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: 553; VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 555; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 557; or

[0702] zz) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 551; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 552; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 563; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 565; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 557; or

[0703] aaa) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 571; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 202; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 573; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 105; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 106; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 107; or

[0704] (bbb) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 581; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 582; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 583; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 585; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 586; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 587; or

[0705] (ccc) VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 13; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 615; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 17; or

[0706] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 13; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 625; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 17; or

[0707] 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: 663; VL-CDR1 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 615; VL-CDR2 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 comprising an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 17; or

[0708] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 673; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 615; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 17; or

[0709] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 683; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 615; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 17; or

[0710] VH-CDR1 containing the amino acid sequence of SEQ ID NO: 11; VH-CDR2 containing the amino acid sequence of SEQ ID NO: 612; VH-CDR3 containing the amino acid sequence of SEQ ID NO: 683; VL-CDR1 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 625; VL-CDR2 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 16; and VL-CDR3 containing an amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity with SEQ ID NO: 17.

[0711] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0712] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22; (c) VH-CDR3 comprising the amino acid sequence YSY; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27.

[0713] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37.

[0714] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47.

[0715] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52; (c) VH-CDR3 comprising the amino acid sequence YSF; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27.

[0716] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67.

[0717] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72; (c) VH-CDR3 comprising the amino acid sequence YSY; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 76; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77.

[0718] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87.

[0719] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97.

[0720] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0721] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117.

[0722] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 282; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287.

[0723] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197.

[0724] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0725] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0726] In some embodiments, the α-synuclein antibody comprises at least one, two, or three CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; and (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163.

[0727] In some embodiments, the α-synuclein antibody comprises at least four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167.

[0728] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177.

[0729] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187.

[0730] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0731] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 216; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 217.

[0732] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227.

[0733] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237.

[0734] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 242; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 243; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247.

[0735] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257.

[0736] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267.

[0737] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 273; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 277.

[0738] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 301; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 307.

[0739] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 313; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67.

[0740] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 321; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 322; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 325; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327.

[0741] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0742] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 343; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 346; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347.

[0743] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 355; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357.

[0744] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 363; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 365; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367.

[0745] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347.

[0746] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387.

[0747] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 395; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357.

[0748] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 351; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 405; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 356; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 357.

[0749] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 411; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 413; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0750] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 421; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 422; (c) VH-CDR3 comprising the amino acid sequence GNY; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 425; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 426; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 427.

[0751] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 431; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 432; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 433; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 436; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 437.

[0752] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 442; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 443; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0753] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 461; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 465; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467.

[0754] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 473; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 475; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 476; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 477.

[0755] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 481; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 482; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 483; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 487.

[0756] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 492; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 493; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 495; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 496; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 497.

[0757] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 502; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 503; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0758] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 311; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 512; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 513; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 515; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 516; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 517.

[0759] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 521; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 522; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 463; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 525; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 467.

[0760] In some embodiments, the α-synuclein antibody comprises at least one, two, or three CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 532; and (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 533.

[0761] In some embodiments, the α-synuclein antibody comprises at least four, five, or six CDRs selected from the following: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 532; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 533; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 537.

[0762] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 341; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 542; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 543; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 345; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347.

[0763] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 553; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 555; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557.

[0764] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 551; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 552; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 563; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 565; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 557.

[0765] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 571; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 573; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0766] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 581; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 582; (c) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 583; (d) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 585; (e) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 586; and (f) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 587.

[0767] In some embodiments, the α-synuclein antibody comprises at least one, two, three, four, five, or six CDRs selected from: (a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; (b) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 612; (c) VH-CDR3 comprising the amino...

Claims

1. An alpha-synuclein binding molecule which is an antibody or antigen binding fragment thereof which: (i) inhibits and / or delays seeded and / or spontaneous alpha-synuclein aggregation; and (ii) is capable of recognizing and binding pathological and / or aggregated alpha-synuclein in vitro and / or in vivo, and which comprises: a) a VH-CDR1 consisting of the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 consisting of the amino acid sequence of SEQ ID NO: 32; and a VH-CDR3 consisting of the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 consisting of the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 consisting of the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 consisting of the amino acid sequence of SEQ ID NO: 37; or b) a VH-CDR1 consisting of the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 consisting of the amino acid sequence of SEQ ID NO: 32; and a VH-CDR3 consisting of the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 consisting of the amino acid sequence of SEQ ID NO: 85; a VL-CDR2 consisting of the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 consisting of the amino acid sequence of SEQ ID NO: 87; or c) a VH-CDR1 consisting of the amino acid sequence of SEQ ID NO: 91; a VH-CDR2 consisting of the amino acid sequence of SEQ ID NO: 92; and a VH-CDR3 consisting of the amino acid sequence of SEQ ID NO: 93; a VL-CDR1 consisting of the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 consisting of the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 consisting of the amino acid sequence of SEQ ID NO: 97; or d) a VH-CDR1 consisting of the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 consisting of the amino acid sequence of SEQ ID NO: 192; and a VH-CDR3 consisting of the amino acid sequence of SEQ ID NO: 193; a VL-CDR1 consisting of the amino acid sequence of SEQ ID NO: 195; a VL-CDR2 consisting of the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 consisting of the amino acid sequence of SEQ ID NO: 197; or e) a VH-CDR1 consisting of the amino acid sequence of SEQ ID NO:31; a VH- CDR2 consisting of the amino acid sequence of SEQ ID NO:222; and a VH-CDR3 consisting of the amino acid sequence of SEQ ID NO:223; a VL-CDR1 consisting of the amino acid sequence of SEQ ID NO:225; a VL-CDR2 consisting of the amino acid sequence of SEQ ID NO:96; and a VL-CDR3 consisting of the amino acid sequence of SEQ ID NO:227; or f) a VH-CDR1 consisting of the amino acid sequence of SEQ ID NO:31; a VH- CDR2 consisting of the amino acid sequence of SEQ ID NO:242; and a VH-CDR3 consisting of the amino acid sequence of SEQ ID NO:243; a VL-CDR1 consisting of the amino acid sequence of SEQ ID NO:225; a VL-CDR2 consisting of the amino acid sequence of SEQ ID NO:96; and a VL-CDR3 consisting of the amino acid sequence of SEQ ID NO:247; or g) a VH-CDR1 consisting of the amino acid sequence of SEQ ID NO:31; a VH- CDR2 consisting of the amino acid sequence of SEQ ID NO:252; and a VH-CDR3 consisting of the amino acid sequence of SEQ ID NO:253; a VL-CDR1 consisting of the amino acid sequence of SEQ ID NO:255; a VL-CDR2 consisting of the amino acid sequence of SEQ ID NO:256; and a VL-CDR3 consisting of the amino acid sequence of SEQ ID NO:

257.

2. The alpha-synuclein binding molecule of claim 1, wherein the alpha-synuclein binding molecule is capable of recognizing and binding pathological and / or aggregated human alpha-synuclein in vitro and / or in vivo.

3. The alpha-synuclein binding molecule of claim 1, which reduces pathological alpha- synuclein levels in vivo and / or in vitro.

4. The alpha-synuclein binding molecule of claim 1, which reduces phosphorylated alpha- synuclein levels in vivo and / or in vitro.

5. The alpha-synuclein binding molecule of claim 1, which delays aggregation and seeding of pathological alpha-synuclein in vivo and / or in vitro.

6. The alpha-synuclein binding molecule of claim 1, which shows recovery of neuronal loss in vivo and / or in vitro.

7. The alpha-synuclein binding molecule of claim 1, which reduces pathological alpha- synuclein spreading in vivo and / or in vitro.

8. The alpha-synuclein binding molecule of claim 1, which inhibits and / or delays cellular uptake of pathological and / or aggregated alpha-synuclein in vivo and / or in vitro.

9. The alpha-synuclein binding molecule of claim 1, which upon pre-incubation with alpha-synuclein seed results in an at least 10% increase in the aggregation half-life (t1 / 2 value) of seeded aggregation relative to seeded aggregation in the absence of the binding molecule.

10. The alpha-synuclein binding molecule of claim 9, wherein alpha-synuclein aggregation is monitored by Thioflavin T (ThT) fluorescence assay.

11. The alpha-synuclein binding molecule of claim 1, which binds to pathological and / or aggregated alpha-synuclein in Lewy bodies and Lewy neurites in the context of Parkinson’s Disease (PD).

12. The alpha-synuclein binding molecule of claim 1, which binds to pathological and / or aggregated alpha-synuclein in glial cytoplasmic inclusions in the context of Multiple System Atrophy (MSA).

13. The alpha-synuclein binding molecule of claim 1, which binds to an epitope within the following amino acid residues of human alpha-synuclein of SEQ ID NO: 1: 127-140 (SEQ ID NO: 135), 128-135 (SEQ ID NO: 8), or 131-140 (SEQ ID NO: 9).

14. The alpha-synuclein binding molecule of claim 1, which is an antibody or antibody binding fragment thereof, comprising: a. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or a heavy chain variable region (VH) having at least 94% 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 a light chain variable region (VL) having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 34; or b. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or a heavy chain variable region (VH) having at least 94% 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 a light chain variable region (VL) having at least 94% sequence identity to the amino acid sequence of SEQ ID NO: 84; or c. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or a heavy chain variable region (VH) having at least 94% 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 a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or d. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 190 or a heavy chain variable region (VH) having at least 88% 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 a light chain variable region (VL) having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 194; or e. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 220 or a heavy chain variable region (VH) having at least 97% 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 a light chain variable region (VL) having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 224; or f. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 240 or a heavy chain variable region (VH) having at least 96% 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 a light chain variable region (VL) having at least 94% sequence identity to the amino acid sequence of SEQ ID NO: 244; or g. a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 250 or a heavy chain variable region (VH) having at least 90% 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 a light chain variable region (VL) having at least 94% sequence identity to the amino acid sequence of SEQ ID NO:

254.

15. The alpha-synuclein binding molecule of claim 1, which is an antibody or antibody binding fragment thereof, comprising: a. 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 b. 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 c. 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 d. 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 e. 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 f. 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 g. 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. g. 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.

16. The alpha-synuclein binding molecule of claim 1, which is a monoclonal antibody or antigen-binding fragment thereof.

17. The alpha-synuclein binding molecule of claim 1, which is a murine antibody, a chimeric antibody, a humanized antibody, or a human antibody, or an antigen-binding fragment thereof.

18. The alpha-synuclein binding molecule of claim 1, which is an IgA, IgD, IgE, IgM, IgGl, IgG2, IgG2a, IgG2b, IgG3, or IgG4 antibody or an antigen-binding fragment thereof.

19. The alpha-synuclein binding molecule of claim 1, wherein the binding molecule is an IgG4 isotype comprising a S228P mutation.

20. Use of the alpha-synuclein binding molecule of claim 1 for the manufacture of a medicament for human or veterinary treatment, wherein the treatment is for a disease, disorder, or abnormality associated with alpha-synuclein selected from the group consisting of Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD), and diffuse Lewy body disease.

21. Use of the alpha-synuclein binding molecule of claim 1 for the manufacture of a medicament for the prevention, alleviation, treatment of a disease, disorder, and abnormality associated with alpha-synuclein and / or for a diagnostic agent for the diagnosis of a disease, disorder, and abnormality associated with alpha-synuclein, wherein the disease or disorder or abnormality is selected from the group consisting of Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD), and diffuse Lewy body disease.

22. Use according to claim 21, wherein the aggregates are Lewy bodies, Lewy neurites, and / or glial cytoplasmic inclusions.

23. Use according to claim 21 for the prevention and / or slowing down and / or halting and / or preserving and / or ameliorating motor abilities or motor deficits, cognitive abilities or cognitive deficits, or behavioral disorders in a subject suffering from a synucleinopathy selected from the group consisting of Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD), and diffuse Lewy body disease.

24. Use according to claim 23, wherein the synucleinopathy is multiple system atrophy (MSA) and the binding molecule is used for: (i) ameliorating motor abilities; and / or (ii) ameliorating cognitive deficits; and / or (iii) ameliorating behavioral disorders; and / or (iv) ameliorating REM sleep disorders.

25. Use according to claim 23, wherein the synucleinopathy is Parkinson's disease, Lewy body dementia (LBD), or diffuse Lewy body disease and the binding molecule is used for: (i) ameliorating motor abilities; and / or (ii) ameliorating cognitive deficits; and / or (iii) ameliorating behavioral disorders; and / or (iv) ameliorating REM sleep disorders.

26. Use of the alpha-synuclein binding molecule of claim 1 in the manufacture of a medicament for preventing a disease, disorder, and abnormality associated with alpha-synuclein, wherein the disease or disorder or abnormality is selected from the group consisting of Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD), and diffuse Lewy body disease.

27. Use of the alpha-synuclein binding molecule of claim 1 in the manufacture of a medicament for alleviating a disease, disorder, and abnormality associated with alpha-synuclein, wherein the disease or disorder or abnormality is selected from the group consisting of Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD), and diffuse Lewy body disease.

28. Use of the alpha-synuclein binding molecule of claim 1 in the manufacture of a medicament for treating a disease, disorder, and abnormality associated with alpha-synuclein, wherein the disease or disorder or abnormality is selected from the group consisting of Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD), and diffuse Lewy body disease.

29. Use of the alpha-synuclein binding molecule of claim 1 in the manufacture of a diagnostic reagent for diagnosing a disease, disorder, and abnormality associated with alpha-synuclein, wherein the disease or disorder or abnormality is selected from the group consisting of Parkinson's disease, multiple system atrophy, Lewy body dementia (LBD), and diffuse Lewy body disease.

30. A pharmaceutical composition comprising the alpha-synuclein binding molecule of claim 1 and a pharmaceutically acceptable carrier and / or excipient.

31. A nucleic acid encoding the alpha-synuclein binding molecule of claim 1.

32. The nucleic acid of claim 31, wherein the nucleic acid comprises the nucleotide sequence provided in SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 89, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 199, SEQ ID NO: 198, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 258, or SEQ ID NO:

259.

33. A recombinant vector comprising the nucleic acid of claim 31 or 32.

34. A host cell comprising the nucleic acid of claim 31 or 32 and / or the vector of claim 33.

35. An isolated host cell expressing the alpha-synuclein binding molecule of claim 1.

36. A method for producing an isolated alpha-synuclein binding molecule comprising the steps of: a) culturing the host cell of claim 34 under conditions suitable for production of the alpha-synuclein binding molecule, and b) isolating the alpha-synuclein binding molecule.

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