Novel molecule for diagnosis

Abstract

To provide a novel amyloid beta (A beta) binding molecule, especially an amyloid beta antibody or an antigen-binding fragment thereof, and / or use of them.SOLUTION: There is provided an amyloid beta binding antibody including: VH-CDR1 including a specific amino acid sequence, VH-CDR2 including a specific amino acid sequence, VH-CDR3 including a specific amino acid sequence, VL-CDR1 including a specific amino acid sequence, VL-CDR2 including a specific amino acid sequence, and VL-CDR3 including a specific amino acid sequence; or an antigen-binding fragment thereof. In one embodiment, independently of an amyloid beta peptide or a three-dimensional structure states of a seed, an amyloid beta binding antibody or an antigen binding fragment thereof selectively binds to an amyloid beta peptide or seed in a solution, or captures the amyloid beta peptide or seed.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to novel amyloid beta (Abeta, Abeta, Aβ) binding molecules, particularly amyloid beta antibodies or antigen-binding fragments thereof, and / or uses thereof. The provided molecules can also be used to determine predisposition to amyloid beta-related diseases, disorders, or conditions, monitor residual disease or condition, or predict the responsiveness of patients suffering from such diseases or conditions to treatment with certain drugs. Thus, the present invention relates to novel molecules that can be used for diagnosing amyloid beta-related diseases, disorders, or conditions. [Background technology]

[0002] Alzheimer's disease (AD) is the most common cause of dementia in older adults, affecting an estimated 15 million people worldwide, or 40% of those aged 85 and over. The disease is characterized by progressive loss of memory, speech, and movement, leading to a general decline in abilities among patients and ultimately to death. AD takes a devastating toll not only on those affected, but also on their families, friends, and caregivers.

[0003] Today, treatments focus on controlling the symptoms of AD and its various stages. Currently available AD treatment options may help delay the worsening of AD symptoms for a certain period of time. However, there is no evidence that these medical treatments have any impact on the underlying progression of the disease. There is currently no cure for AD, therefore, early AD treatment is necessary. With no currently available disease-modifying treatment options, the need for good biomarkers for early diagnosis is more essential than ever. The single most prominent and earliest biochemical hallmark of AD is the formation of extracellular amyloid beta (Aβ) plaques in the brain (Calderon-Garciduenas & Duyckaerts, 2017), which primarily contain the 42-amino acid form of Aβ. Aβ plaques are formed by 39–43 amino acid-long Aβ peptides (arising from cleavage of the amyloid precursor protein (APP)), which in their native, non-pathological form are in a random-coil conformation. During the transition to the pathological state, they change to a predominantly β-sheet secondary structure and spontaneously aggregate into insoluble deposits. Even if the exact role of Aβ in the pathogenesis of AD is still debated, it is widely accepted that soluble Aβ oligomers impair synaptic structure and function, with the minimal synaptic toxic species being dimers or small soluble multimers, but that neither Aβ monomers nor plaque cores appreciably alter neuronal viability or synaptic plasticity ( Shankar et al., 2008 ).

[0004] Down syndrome (DS), also known as trisomy 21, is one of the most common causes of intellectual disability, affecting 1 in 800 newborns. This condition is most commonly associated with the triplication of chromosome 21 (Belichenko, 2016). Subjects with DS have distinctive facial features, immune and endocrine system defects, and delayed cognitive development. A key feature of adult subjects with DS is an increased risk of developing clinical symptoms similar to Alzheimer's disease (AD), characterized by declines in specific cognitive domains suggestive of a dementia diagnosis. In fact, all subjects with DS over the age of 40 exhibit neuropathological changes similar to AD in the form of senile plaque formation and neurofibrillary tangles (Head, 2012). It is widely accepted that the neuropathology of AD-like cognitive decline is associated with the deposition of β-amyloid (Aβ) peptides followed by plaque formation, neurofibrillary tangles, vascular damage, neuroinflammation, and ultimately neuronal death. The amyloid protein precursor (APP) gene, which encodes the precursor protein of Aβ, is located on chromosome 21. In DS subjects, all or at least part of chromosome 21 is present in triplicate. This results in three copies of the APP-encoding gene, leading to the production of excessive amounts of Aβ. Increased Aβ protein production has been shown to correlate with AD-like symptoms in DS subjects and the general population that develops AD (Head, 2012). These findings conclusively demonstrate that lifelong overexpression of wild-type APP causes cognitive decline in DS subjects, similar to the amyloid cascade hypothesis used to explain AD subjects. Down syndrome-associated Alzheimer's disease is characterized by the presence of neuropathological features of Alzheimer's disease in the brain (including, in particular, the accumulation of neuritic plaques and neurofibrillary tangles in the brain), which, if sufficiently advanced, can lead to the emergence of clinical symptoms such as cognitive decline and functional impairment.

[0005] The amyloid beta-related disease, disorder or illness is a neurological disorder such as Alzheimer's disease (AD). Other examples of amyloid beta-related diseases, disorders or illnesses according to the present invention include mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-related Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease (PD), Parkinson's disease dementia (PDD), Lewy body disease, ALS (amyotrophic lateral sclerosis), adult-onset diabetes, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure. Many of these illnesses are characterized by or associated with the loss of cognitive memory ability. Thus, diseases characterized by or associated with loss of cognitive memory ability according to the present invention include AD, mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), Lewy body disease, ALS (amyotrophic lateral sclerosis), myotonic dystrophy, liver damage or failure, and inclusion body myositis (IBM).

[0006] Currently, there are no clinically validated biomarkers in patient samples (e.g., blood, cerebrospinal fluid, urine, etc.) that can be used to specifically diagnose, stratify, or monitor the progression or regression of amyloid beta-related diseases, disorders, or conditions in subjects. The majority of AD biomarker research has focused on quantitative changes in tau and Aβ proteins and altered levels of these proteins in cerebrospinal fluid from AD patients, with Aβ levels showing faster changes (Buchhave et al., 2012). There is a significant need in the AD biomarker and diagnostics field for Aβ antibodies that can be designed and optimized for specific biomarker use and specific diagnostic technology platforms. Summary of the Invention

[0007] Early diagnosis of AD and other diseases in which Aβ is associated with pathology and / or changes in body tissues can be used as a marker of disease progression is essential for early intervention. Biochemical changes in AD progress slowly, resulting in a relatively long time before the first clinical signs of the disease become visible. Even longer time elapses before a reliable diagnosis of AD is made and it can be distinguished from other forms of dementia (Knopman et al., 2001). Neurodegeneration can begin 20 or more years before reliable clinical diagnosis is possible, and symptoms of mild cognitive impairment (MCI) can be present, suggesting a prodromal stage of AD (Britt et al., 2011). While MCI is characteristic of the prodromal AD stage, it exhibits a highly variable natural history with cognitive status fluctuating over time, making it an unreliable predictor of progression toward a clinical diagnosis of AD (Gauthier et al., 2006). Changes in available tissue biomarkers that serve as surrogates for disease progression are thought to occur early in the preclinical precursor stages of AD (Robb et al., 2017). Here, we describe antibodies generated for use in Aβ biomarker assays for the early diagnosis and / or treatment of amyloid beta-related diseases, disorders, or conditions. [Brief explanation of the drawings]

[0008] [Figure 1] ACI-24-41F12-Ab3 (mouse IgG2a isotype) binds to Abeta 1-42 with a Kd of 66 pM. No binding to BSA protein was observed. Data are expressed as OD and shown as the mean ± SD of one duplicate determination. [Figure 2] Antibody ACI-31-25B1-Ab2 (mouse IgG2a isotype) binds to Abeta 1-42 with a Kd of 41 pM. No binding to BSA protein was observed. Data are expressed as OD. [Figure 3]Antibody ACI-31-30C11-Ab1 (mouse IgG2a isotype) binds to Abeta 1-42 with a Kd of 196 pM. No binding to BSA protein was observed. Data are expressed as OD. [Figure 4] Antibody ACI-31-25B1-Ab2 (mouse IgG2a isotype) captures soluble Abeta 1-42 with a Kd of 312 pM. Data are expressed as OD. [Figure 5] Antibody ACI-8041-1F11B5-Ab1 (mouse IgG2a isotype) captures soluble Abeta 1-42 with a Kd of 343 pM. Data are expressed as OD. [Figure 6] Antibody ACI-8041-9D7E1-Ab1 (mouse IgG2a isotype) captures soluble Abeta 1-42 with a Kd of 1.1 nM. Data are expressed as OD. [Figure 7] Antibody ACI-8041-10H3B11-Ab1 (mouse IgG2a isotype) captures soluble Abeta 1-42 with a Kd of 2.6 nM. Data are expressed as OD. [Figure 8] A) Indirect ELISA comparing the binding of each antibody, ACI-24-41F12-Ab3 (mouse IgG2a isotype) and ACI-31-25B1-Ab2 (mouse IgG2a / lambda isotype), to sAPP alpha, normalized to Abeta 1-42 binding. Scrambled Abeta 1-42 was used as a control and showed no binding. Antibody ACI-24-41F12-Ab3 shows binding to sAPP alpha, whereas no binding is observed with antibody ACI-31-25B1-Ab2. B) Sandwich pairing of antibodies ACI-24-41F12-Ab3 (detection) and ACI-31-25B1-Ab2 (capture) detects soluble Abeta 1-42 with a Kd of 9.7 nM, demonstrating selectivity for Abeta 1-42 over scrambled Abeta 1-42 or sAPP alpha. Data are expressed as OD or as % Abeta 1-42 bound. DETAILED DESCRIPTION OF THE INVENTION

[0009] The object of the present invention is to provide a binding molecule, particularly an amyloid beta antibody or an antigen-binding fragment thereof, that can be used in the diagnosis of diseases, disorders, or conditions associated with amyloid beta. The binding molecule of the present invention, particularly an amyloid beta antibody or an antigen-binding fragment thereof, can selectively bind to or capture any amyloid beta peptide or species in a solution, particularly in a body fluid or buffer solution. Surprisingly, it has been found that the amyloid beta antibody or an antigen-binding fragment thereof of the present invention can selectively bind to or capture any amyloid beta peptide or species in a solution, regardless of the conformational state of the amyloid beta peptide or species, and / or does not exhibit cross-reactivity to soluble amyloid precursor protein (APP), particularly soluble APP resulting from cleavage by α-secretase (referred to herein as "soluble APP alpha" or "sAPP alpha"). The term "selective binding" or "selective capture" refers to the fact that the binding molecule does not significantly bind to other species (except amyloid beta, regardless of conformational state) present in a solution (e.g., a body fluid, etc.). This may be applicable in both in vitro and in vivo situations. Selectivity is important for effective performance in the various diagnostic applications described herein. Thus, in a preferred embodiment, the binding molecules of the present invention do not significantly bind to other protein species found in plasma (including apolipoproteins, immunoglobulins, albumin, fibrinogen, etc.). That is, the binding molecules of the present invention are specific for amyloid beta, regardless of the conformational state, when bound or captured in a plasma sample. The extent of binding of the binding molecules of the present invention, particularly amyloid beta antibodies or antigen-binding fragments thereof, to unrelated non-amyloid beta proteins may be less than about 10% of the binding of the antibody to amyloid beta, as measured, for example, by radioimmunoassay (RIA). When referring to "no cross-reactivity" with sAPP alpha, this is intended to mean that there is no appreciable binding of the binding molecule to sAPP alpha.This can be measured, for example, by comparing binding to sAPP alpha with binding to Abeta 1-42. When normalized to Abeta 1-42 binding, the level of binding to sAPP alpha can be less than 10%, preferably less than 5%, or more preferably less than 3% of the binding to Abeta 1-42. Such a comparison can be performed by ELISA, e.g., indirect ELISA. A suitable assay is described in Example 3 with reference to Figure 8A. These antibodies are particularly useful in the present invention as capture and / or detection antibodies, particularly in sandwich immunoassay formats. The terms "capture" and "detect" are terms of art. The capture antibody binds and captures the antigen, typically a solid surface (to which the capture antibody is bound). The detection antibody also binds to the antigen, typically to a non-overlapping epitope, so that the capture and detection antibodies bind simultaneously. The detection antibody generates a signal for the assay. Detection can be direct (e.g., via a directly labeled antibody, such as an enzyme or fluorescent label) or indirect (e.g., using a secondary antibody that is sequentially labeled). It has been found that if one of the capture or detection antibodies is an antibody that does not have cross-reactivity to sAPP alpha, the sandwich immunoassay will be entirely specific to sAPP alpha and will not give a signal, even if the other antibody reacts with sAPP alpha.Specific antibodies that do not have cross-reactivity to sAPP alpha are shown in Table 1 (the last column, "-" indicates no binding).In some embodiments of the present invention, an antibody that does not have cross-reactivity to sAPP alpha is used as both the capture antibody and the detection antibody.This assay provides highly sensitive detection of Abeta without detecting sAPP alpha (i.e., also has excellent specificity).

[0010] Thus, some binding molecules of the present invention may exhibit low cross-reactivity with sAPP alpha. They are usefully used in combination with binding molecules of the present invention that do not exhibit cross-reactivity. Again, low cross-reactivity may be measured, for example, by comparing binding to sAPP alpha with binding to Abeta 1-42. When normalized to Abeta 1-42 binding, the level of binding to sAPP alpha may be 10-60% (e.g., about 50%) of the binding to Abeta 1-42. Such comparisons may be performed by ELISA, for example, indirect ELISA. A suitable assay is described in Example 3 with reference to Figure 8A. Results for tested antibodies of the present invention are shown in Table 1. It has been found that binding molecules with low levels of cross-reactivity to sAPP alpha may be particularly advantageous when used in combination with binding molecules that do not cross-react with sAPP alpha. Thus, a combination of a binding molecule with low levels of cross-reactivity to sAPP alpha and a binding molecule that does not cross-react with sAPP alpha may be utilized in accordance with the present invention to perform a sandwich immunoassay. In particular, binding molecules with low levels of cross-reactivity to sAPP alpha may be used as capture or detection antibodies, and binding molecules with no cross-reactivity to sAPP alpha may be used as detection or capture antibodies. A suitable assay of this type of the invention is described in Example 3 with reference to Figure 8B. Thus, for example, antibody ACI-31-25B1-Ab2 may be used as the capture antibody and ACI-24-41F12-Ab2 may be used as the detection antibody.

[0011] Some binding molecules of the present invention may exhibit high cross-reactivity with sAPP alpha. Again, this may be measured, for example, by comparing binding to sAPP alpha with binding to Abeta 1-42. When normalized to Abeta 1-42 binding, the level of binding to sAPP alpha may be 60% or more, e.g., 70-90%, e.g., approximately 80%, of the binding to Abeta 1-42. Such comparisons may be performed by ELISA, e.g., indirect ELISA. A suitable assay is described in Example 3 with reference to Figure 8A. Results for tested antibodies of the present invention are shown in Table 1. Binding molecules with high levels of cross-reactivity to sAPP alpha may be used in combination with binding molecules that do not cross-react with sAPP alpha. Thus, a combination of a binding molecule with high levels of cross-reactivity to sAPP alpha and a binding molecule that does not cross-react with sAPP alpha may be utilized in accordance with the present invention to perform a sandwich immunoassay, providing high sensitivity for Abeta and not detecting soluble APP alpha (i.e., high specificity). In such assays, selectivity is provided by binding molecules of the present invention that do not cross-react with sAPP alpha. In particular, binding molecules with a high level of cross-reactivity to sAPP alpha can be used as capture or detection antibodies, while binding molecules with no cross-reactivity to sAPP alpha can be used as detection or capture antibodies. Antibodies of the present invention with high cross-reactivity to sAPP alpha include ACI-8037-103H5-Ab2 and ACI-8037-109F4-Ab1. In one embodiment, a binding molecule, particularly an antibody, or its antigen-binding fragment comprises CDR1-VH comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17.Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0012] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37.

[0013] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47.

[0014] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 63; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 63; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0015] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0016] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87.

[0017] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97.

[0018] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0019] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 116; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 116; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117.

[0020] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 121; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 122; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 123; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 125; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 127. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 121; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 122; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 123; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 125; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 127.

[0021] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 131; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 132; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 135; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 131; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 132; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 135; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137.

[0022] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137.

[0023] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising: a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 166; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising: a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 166; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167.

[0024] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157.

[0025] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187.

[0026] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197.

[0027] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0028] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises 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. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising 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.

[0029] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44.

[0030] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64.

[0031] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74.

[0032] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84.

[0033] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises 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. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising 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.

[0034] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104.

[0035] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114.

[0036] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124.

[0037] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 and a variable region (VL) comprising the sequence of SEQ ID NO: 134.

[0038] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144.

[0039] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154.

[0040] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164.

[0041] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174.

[0042] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184.

[0043] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194.

[0044] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a light chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0045] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 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 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34.

[0046] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or a light chain variable region (VL) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or a light chain variable region (VL) having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44.

[0047] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64.

[0048] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 74. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 74.

[0049] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84.

[0050] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 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 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 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 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94.

[0051] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104.

[0052] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114.

[0053] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 or a heavy chain variable region (VH) having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 124. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 or a heavy chain variable region (VH) having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[0054] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134.

[0055] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144.

[0056] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising 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 to the amino acid sequence of SEQ ID NO: 150; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154.

[0057] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 164. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 164.

[0058] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174.

[0059] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184.

[0060] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194.

[0061] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10.

[0062] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or a heavy chain variable region (VH) having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30.

[0063] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40.

[0064] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60.

[0065] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70.

[0066] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80.

[0067] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or a heavy chain variable region (VH) having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 90. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or a heavy chain variable region (VH) having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 90.

[0068] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100.

[0069] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or a heavy chain variable region (VH) having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110.

[0070] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 or a heavy chain variable region (VH) having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 or a heavy chain variable region (VH) having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120.

[0071] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130.

[0072] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or a heavy chain variable region (VH) having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or a heavy chain variable region (VH) having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140.

[0073] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising 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 to the amino acid sequence of SEQ ID NO: 150. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising 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 to the amino acid sequence of SEQ ID NO: 150.

[0074] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or a heavy chain variable region (VH) having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or a heavy chain variable region (VH) having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160.

[0075] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or a heavy chain variable region (VH) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170.

[0076] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0077] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0078] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or a light chain variable region (VL) having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or a light chain variable region (VL) having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34.

[0079] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or a light chain variable region (VL) having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or a light chain variable region (VL) having at least 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44.

[0080] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64.

[0081] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 74. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 74.

[0082] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84.

[0083] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94.

[0084] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104.

[0085] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114.

[0086] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 124. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[0087] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134.

[0088] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144.

[0089] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154.

[0090] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 164. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 164.

[0091] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174.

[0092] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184.

[0093] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194.

[0094] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13.

[0095] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33.

[0096] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43.

[0097] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 63. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 63.

[0098] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 73. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 73.

[0099] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 83. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 83.

[0100] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93.

[0101] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103.

[0102] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113.

[0103] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 121; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 122; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 123. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 121; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 122; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 123.

[0104] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 131; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 132; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 131; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 132; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133.

[0105] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133.

[0106] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153.

[0107] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163.

[0108] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173.

[0109] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183.

[0110] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0111] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37.

[0112] In one embodiment, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47.

[0113] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0114] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

[0115] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87.

[0116] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97.

[0117] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 105; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 106; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 107.

[0118] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 116; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 116; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117.

[0119] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 125; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 127. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 125; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 127.

[0120] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 135; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 135; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137.

[0121] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137.

[0122] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157.

[0123] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157.

[0124] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187.

[0125] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197. Thus, the present invention also provides an amyloid beta binding molecule, particularly an amyloid beta antibody or antigen-binding fragment thereof, comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197.

[0126] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 20. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 22. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 24. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 27. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 38. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 48. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 50. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 56. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO:58.

[0127] In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 21. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 23. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 25. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 28. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 39. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 49. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 51. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 57. In certain embodiments, the binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a light chain (LC) comprising the amino sequence of SEQ ID NO:59.

[0128] In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 20 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 21. In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 22 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 23. In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 24 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 25. In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 27 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 28. In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 38 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 39. In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 48 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 49. In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 50 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 51. In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 56 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 57. In certain embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, comprises a heavy chain (HC) comprising the amino sequence of SEQ ID NO: 58 and comprises a light chain (LC) comprising the amino sequence of SEQ ID NO: 59.

[0129] Binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided herein in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17. Binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided herein in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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. Binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided herein in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; VH-CDR3 comprising the amino acid sequence of 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. Binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided herein in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 63; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.Binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally comprise amino acid changes in the CDR sequences compared to the CDR sequences provided herein in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. Binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally comprise amino acid changes in the CDR sequences compared to the CDR sequences provided herein in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87. Binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally comprise amino acid changes in the CDR sequences compared to the CDR sequences provided herein in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92; VH-CDR3 comprising the amino acid sequence of 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. Binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally comprise amino acid changes in the CDR sequences compared to the CDR sequences provided herein in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103; 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.The binding molecules, antibodies or antigen-binding fragments thereof included herein may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112; VH-CDR3 comprising the amino acid sequence of 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: 116; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117. The binding molecules, antibodies or antigen-binding fragments thereof included herein may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 121; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 122; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 123; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 125; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 127. The binding molecules, antibodies or antigen-binding fragments thereof included herein may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 131; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 132; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 135; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137. The binding molecules, antibodies or antigen-binding fragments thereof included herein may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137.The binding molecules, antibodies or antigen-binding fragments thereof included herein may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. The binding molecules, antibodies or antigen-binding fragments thereof included herein may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 166; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167. The binding molecules, antibodies or antigen-binding fragments thereof included herein may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172; VH-CDR3 comprising the amino acid sequence of 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: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. The binding molecules, antibodies or antigen-binding fragments thereof included herein may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided in VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; 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: 187.The binding molecules, antibodies, or antigen-binding fragments thereof may further or additionally contain amino acid changes in the CDR sequences compared to the CDR sequences provided herein, including VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197. In particular, the CDR sequences contained in the binding molecules, antibodies, or antigen-binding fragments thereof may contain one, two, or three amino acid changes with respect to the CDR sequences provided herein. An "amino acid change" may relate to an amino acid mutation, deletion, or addition. It may also relate to a chemical alteration of an amino acid, such as the formation of a non-natural amino acid.

[0130] Amino acid sequence variants of binding molecules, particularly antibodies or antigen-binding fragments thereof, provided herein, are contemplated. For example, it may be desirable to improve the binding affinity and / or other biological properties of the antibody. Amino acid sequence variants of antibodies can be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, deletions from, and / or insertions into, and / or substitutions of, residues within the amino acid sequence of the antibody. Any combination of deletions, insertions, and substitutions can be made to arrive at the final construct, as long as the final construct possesses the desired characteristics, e.g., antigen binding.

[0131] In certain embodiments, antibody variants having one or more amino acid substitutions are provided. Targeted sites for substitutional mutagenesis include CDRs and framework regions (FRs). Conservative substitutions are shown in Table A under the heading "Preferred Substitutions." More substantial changes are provided in Table A under the heading "Exemplary Substitutions" and are further described below with respect to amino acid side chain classes. Amino acid substitutions are introduced into the antibody of interest, and the products are screened for the desired activity, such as retained / improved antigen binding or improved selectivity. Table A [Table 1]

[0132] Amino acids can be grouped according to common side chain properties. (1) Hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; (2) Neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) Acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) Residues that influence chain orientation: Gly, Pro; (6) Aromatic: Trp, Tyr, Phe.

[0133] Non-conservative substitutions involve exchanging a member of one of these classes for another class.

[0134] One type of substitutional variant involves substituting one or more hypervariable region residues of a parent antibody (e.g., humanized or human antibodies). Generally, the resulting variants selected for further study exhibit alterations (e.g., improvements) in certain biological properties (e.g., increased affinity, decreased immunogenicity) compared to the parent antibody and / or substantially retain certain biological properties of the parent antibody. An exemplary substitutional variant is an affinity-matured antibody, which can be conveniently generated using, for example, phage-display-based affinity maturation techniques. Briefly, one or more CDR residues are mutated, and the mutated antibodies are displayed on phage and screened for a particular biological activity (e.g., binding affinity).

[0135] Alterations (e.g., substitutions) can be made in CDRs to, for example, improve antibody affinity. Such alterations can be made in CDR "hot spots," i.e., residues encoded by codons that undergo frequent mutation during the somatic maturation process (see, e.g., Chowdhury, Methods Mol. Biol. 207:179-196 (2008)), and / or SDRs (a-CDRs), and the resulting variant VH or VL can be tested for binding affinity. Affinity maturation by constructing and reselecting a secondary library is described, for example, in Hoogenboom et al., in Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press, Totowa, NJ, (2001)). In one embodiment of affinity maturation, diversity is introduced into the variable genes selected for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis). A secondary library is then generated. The library is then screened to identify antibody variants with the desired affinity. Another method for introducing diversity involves CDR-directed randomization, in which several CDR residues (e.g., 4-6 residues at a time) are randomized. CDR residues involved in antigen binding can be specifically identified using, for example, alanine scanning mutagenesis or modeling. CDRH3 and CDR-L3 are often particularly targeted.

[0136] In certain embodiments, substitutions, insertions, or deletions can occur within one or more CDRs, as long as such changes do not substantially reduce the antibody's ability to bind to antigen. For example, conservative changes (e.g., conservative substitutions provided herein) that do not substantially reduce binding affinity can be made in CDRs. Such changes can be outside the "hot spots" of CDRs or SDRs. In certain embodiments of the variant VH and VL sequences provided above, each CDR is unchanged or contains no more than one, two, or three amino acid substitutions.

[0137] A useful method for identifying antibody residues or regions that can be targeted for mutagenesis is called "alanine scanning mutagenesis," as described in Cunningham and Wells (1989) Science, 244: 1081-1085. In this method, target residues or groups (e.g., charged residues such as Arg, Asp, His, Lys, and Glu) are identified and replaced with neutral or negatively charged amino acids (e.g., alanine or polyalanine) to determine whether the antibody-antigen interaction is affected. Further substitutions can be introduced at amino acid positions that are functionally sensitive to the initial substitution. Alternatively, or in addition, a crystal structure of an antigen-antibody complex can be used to identify contact points between the antibody and antigen. Such contact residues and neighboring residues can be targeted as candidates for substitution or removed. Variants can be screened to determine whether they possess desired properties.

[0138] Amino acid sequence insertions include amino- and / or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing 100 or more residues, as well as intrasequence insertions of single or multiple amino acid residues. An example of a terminal insertion is an antibody with an N-terminal methionyl residue. Other insertional variants of antibody molecules include the fusion to the N- or C-terminus of the antibody of an enzyme or other label (e.g., HRP or AP), or a polypeptide which increases the serum half-life of the antibody.

[0139] Within the scope of the present invention, amyloid beta may have the sequence of Abeta 1-43 (SEQ ID NO: 3), Abeta 1-42 (SEQ ID NO: 1), Abeta 1-41 (SEQ ID NO: 4), Abeta 1-40 (SEQ ID NO: 5) or Abeta 1-39 (SEQ ID NO: 6), or a fragment thereof.

[0140] The term "amyloid beta peptides or species" refers to amyloid beta produced by cleavage of amyloid precursor protein (APP) by beta and gamma secretase activity. Thus, "amyloid beta peptides or species" refers to amyloid beta produced by the amyloidogenic pathway. However, this term also includes synthetically produced peptides. These peptides have the same amino acid sequence but are not produced by processes occurring in vivo. Methods for peptide synthesis are well known in the art and commercially available. Amyloid beta peptides or species may primarily include amyloid beta 1-42 (Abeta 1-42) or 1-43 (Abeta 1-43) and (shorter) fragments thereof. Amyloid beta peptides or species may contain post-translational modifications (PTMs), including, but not limited to, phosphorylation (e.g., phosphorylation of serine at amino acid residue 8 of amyloid beta (pS8-Abeta)), glycosylation, oligomerization, and / or proteolytic cleavage. Synthetic methods can be used to add some PTMs. This can be related to natural components, such as kinases, used in an in vitro environment. Amyloid beta peptides or species include the following amyloid beta peptides (including but not limited to): Abeta 1-38, Abeta 1-39, Abeta 1-40, pS8-Abeta 1-40, Abeta 1-42, pS8-Abeta 1-42, and Abeta 1-43, as well as shorter fragments thereof. Abeta peptide fragments include epitopes recognized by binding molecules. Amyloid beta peptides or species may be in different conformational states, such as monomers, oligomers, or fibrous structures.

[0141] Amyloid precursor protein (APP), an integral membrane protein, undergoes proteolytic degradation to generate multiple peptide fragments, some of which are released and present in samples of body fluids (herein referred to as "biological fluids"). The most prominent APP peptide fragments found in biological fluids include the Abeta family of peptides (Abeta 1-43, Abeta 1-42, Abeta 1-41, Abeta 1-40, and Abeta 1-39), which are released by the beta and gamma secretase activities of the amyloidogenic pathway. Another cleavage product of APP found in body fluids is soluble APP alpha (sAPP alpha), which is released by the alpha-secretase of the non-amyloidogenic pathway. When used in combination, for example, when paired with a secondary Abeta antibody in a sandwich assay, the binding molecules of the present invention that do not have cross-reactivity to sAPP alpha advantageously do not detect sAPP alpha.

[0142] Therefore, the binding molecules of the present invention, particularly antibodies or antigen-binding fragments thereof, have no cross-reactivity to soluble APP alpha and can selectively bind or capture any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species. Some binding molecules of the present invention, particularly antibodies or antigen-binding fragments thereof, have low reactivity to soluble APP alpha and can selectively bind or capture any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species. Some binding molecules of the present invention may exhibit high cross-reactivity to sAPP alpha. Binding molecules that exhibit no cross-reactivity, low cross-reactivity, or high cross-reactivity to soluble APP alpha may be combined for use in sandwich immunoassays, provided that one of the binding molecules of the present invention is used to demonstrate no cross-reactivity to sAPP alpha. In this case, the assay shows a total pair-specific signal for Abeta and no signal for sAPP alpha. Preferably, the solution is a body fluid or buffer solution as described herein. More preferably, the solution is a body fluid. A body fluid sample is defined as saliva, urine, nasal secretions, blood, brain and / or CSF, brain and / or ISF, more specifically blood, brain and / or CSF, or brain and / or ISF. A blood sample may be, for example, a whole blood, serum, or plasma sample, but is preferably a plasma sample.

[0143] Binding molecules of the present invention, particularly antibodies or antigen-binding fragments thereof, bind to an epitope within the amino acid sequence of SEQ ID NO: 1. SEQ ID NO: 1 is the amino acid sequence of human Abeta 1-42. It is understood that equivalent binding regions exist in non-human Abeta. Thus, for example, the mouse Abeta 1-42 amino acid sequence is 93% (39 / 42 residues) identical to the human sequence. The present invention encompasses binding molecules, particularly antibodies or antigen-binding fragments thereof, that bind to equivalent regions / peptides identified above with reference to SEQ ID NO: 1 in non-human Abeta, particularly mouse Abeta. The Abeta 1-42 amino acid sequence is identical between mouse and rat. In a specific embodiment, binding molecules of the present invention, particularly antibodies or antigen-binding fragments thereof, bind to an epitope within amino acid residues 1-8 of SEQ ID NO: 1 (SEQ ID NO: 2). In certain embodiments, binding molecules of the invention, particularly antibodies or antigen-binding fragments, bind to an epitope within amino acid residues 1-8 (SEQ ID NO:2), 1-5 (SEQ ID NO:7), 17-23 (SEQ ID NO:9), 22-35 (SEQ ID NO:29), or 26-34 (SEQ ID NO:8) of SEQ ID NO:1. In certain embodiments, amino acids 1 and 2 of Abeta 1-42 are essential for antibody binding, particularly for the antibody ACI-24-41F12-Ab2 described herein and its related antibodies (e.g., by common CDR and / or VH / VL sequences) (see SEQ ID NOs:10-25 and related embodiments). Without wishing to be bound by theory, it is believed that this antibody binds to an epitope that is unavailable in soluble APP alpha. Although soluble APP alpha contains amino acids 1-5 and 1-8 of Abeta 1-42, this antibody does not bind with high affinity to sAPP alpha.

[0144] In certain embodiments, the binding molecules of the invention, particularly antibodies or antigen-binding fragments thereof, as provided herein, have a binding affinity of ≦1 μM, ≦100 nM, ≦10 nM, ≦1 nM, ≦0.1 nM, ≦0.01 nM, or ≦0.001 nM (e.g., ≦10 μM, ≦100 nM, ≦10 nM, ≦1 nM, ≦0.1 nM, ≦0.01 nM, or ≦0.001 nM (e.g., ≦10 -8 M or less, e.g., 10 -8 M~10-13 M, e.g., 10 -9 M~10 -13 In some embodiments, a binding molecule, particularly an antibody or antigen-binding fragment thereof, that binds to human amyloid beta is provided, wherein the binding molecule, particularly an antibody or antigen-binding fragment thereof, binds to Abeta with a K of less than 100 nM, less than 10 nM, less than 1 nM, less than 200 pM, or less than 100 pM. Within the scope of the present invention, it is preferred that the K is determined using ELISA as described in Example 3 provided herein.

[0145] As used herein, the terms "binding molecule," "amyloid beta antibody," "anti-amyloid beta antibody," "Abeta antibody," or simply "antibody" refer to a binding molecule, more particularly an antibody, that can bind to Aβ monomers and / or soluble Aβ oligomers with sufficient affinity such that the binding molecule, antibody, or antigen-binding fragment thereof is useful as a diagnostic and / or therapeutic agent targeting amyloid beta. In one embodiment, the extent of binding of a binding molecule of the invention, particularly an amyloid beta antibody, or antigen-binding fragment thereof, to an unrelated, non-amyloid beta protein is less than about 10% of the binding of the antibody to amyloid beta, as measured, for example, by radioimmunoassay (RIA).

[0146] In general, the term "antibody" is used herein in the broadest sense and encompasses a variety of antibody structures, including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific, biparatopic antibodies), fully human antibodies, and antibody fragments, so long as they exhibit the desired antigen-binding activity. Antibodies within the present invention may also be chimeric antibodies, recombinant antibodies, antigen-binding fragments of recombinant antibodies, humanized antibodies, or antibodies displayed on the surface of phage or on the surface of chimeric antigen receptor (CAR) T cells.

[0147] An "antigen-binding fragment" of an antibody refers to a molecule other than an intact antibody that contains a portion of the intact antibody and binds to the antigen to which the intact antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments.

[0148] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., each antibody comprising the population is identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. The modified "monoclonal" indicates the character of the antibody as being within a substantially homogeneous population of antibodies and should not be construed as requiring production of the antibody by any particular method. Monoclonal antibodies used in accordance with the present invention may be prepared by the hybridoma method described in Kohler, Nature 256 (1975), 495.

[0149] Thus, in the context of the present invention, the term "antibody" relates to complete immunoglobulin molecules as well as to portions of such immunoglobulin molecules (i.e., "antigen-binding fragments thereof"). Furthermore, the term relates to antibody molecules that have been modified and / or altered, as described above. The term also relates to recombinantly or synthetically prepared / synthesized antibodies. The term also relates to intact antibodies, as well as antibody fragments thereof, such as separated light and heavy chains, Fab, Fv, Fab', Fab'-SH, F(ab')2, etc. 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.

[0150] The term "CDR" as used herein relates to "complementarity determining region," as is well known in the art. CDRs are the parts of immunoglobulins that determine the specificity of the molecule and contact a specific ligand. CDRs are the most variable parts of the molecule, conferring diversity to these molecules. Each V domain has three CDR regions: CDR1, CDR2, and CDR3. VH-CDR or CDR-H refers to the CDR region of the variable heavy chain, and VL-CDR or CDR-L relates to the CDR region of the variable light chain. VH refers to the variable heavy chain, and VL refers to the variable light chain. The CDR regions of Ig-derived regions may be determined as described in Kabat "Sequences of Proteins of Immunological Interest", 5th edition, NIH Publication no. 91-3242 US Department of Health and Human Services (1991); Chothia J., Mol. Biol. 196 (1987), 901-917, or Chothia, Nature 342 (1989), 877-883. The CDR sequences provided herein are defined according to Kabat. However, it will be understood by those skilled in the art that the present invention is intended to encompass binding molecules in which the CDR sequences are defined according to any useful identification / numbering method.For example, Chothia (Canonical structures for the hypervariable regions of immunoglobulins. Chothia C, Lesk AM. J Mol Biol. 1987 Aug 20; 196(4):901-17), IMGT (IMGT, the international ImMunoGeneTics database. Giudicelli V, Chaume D, Bodmer J, Muller W, Busin C, Marsh S, Bontrop R, Marc L, Malik A, Lefranc MP. Nucleic Acids Res. 1997 Jan 1; 25(1):206-11 and Unique database numbering system for immunogenetic analysis. Lefranc MP. Immunol Today. 1997 Nov; 18(11):509), MacCallum(MacCallum RM, Martin AC, Thornton JM, J Mol Biol. 1996 Oct 11; 262(5):732-45), and Martin (Abhinandan KR, Martin ACR. Analysis and improvements to Kabat and structurally correct numbering of antibody variable domains. Mol Immunol. (2008) 45:3832-9. 10.1016 / j.molimm.2008.05.022) numbering methods may be used to define CDRs.

[0151] The "Fc" region contains two heavy chain fragments containing the CH2 and CH3 domains of an antibody, held together by two or more disulfide bonds and by hydrophobic interactions of the CH3 domain.

[0152] The "Fv region" comprises the variable regions from both the heavy and light chains, but lacks the constant regions.

[0153] An "antibody that binds to an epitope" within a defined region of a protein is one that requires the presence of one or more amino acids within that region in order to bind to the protein.

[0154] In certain embodiments, one or more amino acid modifications can be introduced into the Fc region of an antibody provided herein, thereby generating an Fc region variant. The Fc region variant can include a mouse Fc region sequence, antibody isotype or class (e.g., IgG1, IgG2a, IgG2b, or IgG2c) containing an amino acid modification (e.g., substitution) at one or more amino acid positions. The Fc region variant can include a human Fc region sequence (antibody isotype or class, e.g., human IgM, IgG1, IgG2, IgG3, or IgG4 Fc region) containing an amino acid modification (e.g., substitution) at one or more amino acid positions. The antibody isotype or class refers to the type of constant domain, region, or sequence contained in its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM. Some of these can be further divided into subclasses or isotypes, e.g., IgA1, IgA2, IgG1, IgG2, IgG2a (mouse only), IgG2b (mouse only), IgG2c (mouse only), IgG3, and IgG4. The heavy chain constant domains corresponding to the different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively. The light chain constant domain, region, or sequence of an antibody is one of two major classes: kappa (κ) or lambda (λ). If the light chain class is not specified, it is considered to be the more common κ light chain. In some embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises a mouse IgG2a or chimeric (mouse / human) IgG1 isotype.

[0155] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention may be recombinantly produced. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid encodes a binding molecule, particularly an antibody or antigen-binding fragment thereof of the present invention. As used herein, the term "nucleic acid" refers to a nucleic acid molecule. In certain embodiments, a host cell or cell-free expression system is provided, wherein the host cell or cell-free expression system comprises an (isolated) nucleic acid encoding a binding molecule of the present invention, particularly an antibody or antigen-binding fragment thereof. In certain embodiments, the host cell is transfected with a vector comprising an (isolated) nucleic acid encoding a binding molecule of the present invention, particularly an antibody or antigen-binding fragment thereof. In certain embodiments, the host cell is transfected with a vector comprising an (isolated) nucleic acid encoding the heavy chain (HC) and light chain (LC) of a binding molecule of the present invention, particularly an antibody or antigen-binding fragment thereof. In one embodiment, a host cell is transfected with a) a first vector containing an (isolated) nucleic acid encoding the heavy chain (HC) of a binding molecule of the invention, particularly an antibody or antigen-binding fragment thereof, and b) a second vector containing an (isolated) nucleic acid encoding the light chain (LC) of a binding molecule of the invention, particularly an antibody or antigen-binding fragment thereof. In one embodiment, the host cell can be, but is not limited to, a Chinese hamster ovary (CHO) cell. Suitable host cells can be prokaryotes, yeast, or higher eukaryotic cells, particularly mammalian cells.Examples of useful mammalian host cell lines are the SV40-transformed monkey kidney CV1 line (COS-7, ATCC CRL1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, Graham et al., J. Gen. Virol. 36:59 (1977)); baby hamster kidney cells (BHK, ATCC CCL10); Chinese hamster ovary cells / -DHFR (CHO, Urlaub et al., Proc. Natl. Acad. Sci. USA 77:4216 (1980)); mouse Sertoli cells (TM4, Mather, Biol. Reprod. 23:243-251 (1980)); mouse myeloma cells SP2 / 0-AG14 (ATCC CRL1581; ATCC CRL8287) or NS0 (HPA culture collection no. 85110503); monkey kidney cells (CV1 ATCC CCL70); African green monkey kidney cells (VERO-76, ATCC CRL-1587); human cervical carcinoma cells (HELA, ATCC CCL2); canine kidney cells (MDCK, ATCC CCL34); buffalo rat hepatocytes (BRL3A, ATCC CRL1442); human lung cells (W138, ATCC CCL75); human hepatocytes (Hep G2, HB8065); mouse mammary tumor (MMT060562, ATCC CCL51); TRI cells (Mather et al., Annals NY Acad. Sci. 383:44-68 (1982)); MRC5 cells; FS4 cells; human hepatocellular carcinoma (Hep G2), and DSM's PERC-6 cell line. Suitable expression vectors for use with each of these host cells are also generally known in the art. The term "host cell" generally refers to a cultured cell line. Thus, whole humans into which an expression vector encoding an antigen-binding polypeptide according to the invention has been introduced are expressly excluded from the definition of "host cell."Cell-free expression systems may be based on the use of cell lysates or extracts, such as CHO cell lysates (Stech, M., Nikolaeva, O., Thoring, L. et al. Cell-free synthesis of functional antibodies using a coupled in vitro transcription-translation system based on CHO cell lysates. Sci Rep 7, 12030 (2017)).

[0156] In one embodiment, an (isolated) nucleic acid is provided, encoding a binding molecule of the invention provided herein, particularly an antibody or antigen-binding fragment thereof. In one embodiment, a host cell is provided, comprising an (isolated) nucleic acid encoding a binding molecule of the invention provided herein, particularly an antibody or antigen-binding fragment thereof. In one embodiment, a method is provided for producing an (isolated) nucleic acid encoding a binding molecule of the invention provided herein, particularly an antibody or antigen-binding fragment thereof, comprising culturing a host cell or a cell-free expression system under conditions suitable for producing the binding molecule, particularly an antibody or antigen-binding fragment thereof. In one embodiment, a method is provided for producing an (isolated) nucleic acid encoding a binding molecule of the invention provided herein, particularly an antibody or antigen-binding fragment thereof, comprising a) culturing a host cell or a cell-free expression system under conditions suitable for producing the binding molecule, particularly an antibody or antigen-binding fragment thereof, and then b) recovering the binding molecule, particularly the antibody or antigen-binding fragment thereof. Recovery of the binding molecule, particularly an antibody or antigen-binding fragment thereof, may be carried out by any suitable method as would be understood by one of skill in the art. Recovery can include purification to a desired level of purity. Recovery can include isolation of the antibody from the culture. Recovery can include, for example, the use of chromatography. Such production methods can be performed on a large scale, thereby allowing for large-scale production of the binding molecules of the invention. Binding molecules produced according to the methods of the invention are also provided, and can be considered isolated binding molecules.

[0157] As used herein, the term "isolated" means that a molecule, e.g., a nucleic acid or antibody, has been separated and / or recovered from its natural environment. In the present invention, the molecule is preferably chemically synthesized or synthesized in a cellular system different from the cell from which it naturally originates, and is therefore "isolated" from its naturally associated components. The molecule may be isolated from its natural environment, for example, by purification, or may be produced by technical methods, including, but not limited to, gene synthesis, polymerase chain reaction (PCR), vector purification, and protein (antibody) purification. Such molecules may be, inter alia, nucleic acids, such as DNA, RNA, or cDNA sequences, or peptides, antibodies, or proteins.

[0158] The present invention is not limited to isolated antibodies or isolated nucleic acids according to the above definition, but relates to the antibodies or nucleic acids per se, regardless of their origin.

[0159] The same applies to the peptides, nucleic acids, DNA, RNA, and / or cDNA sequences provided by the present invention, which are encompassed in isolated form as defined above or in any other form. Different techniques known in the art, including (but not limited to) SDS-polyacrylamide gel electrophoresis (SDS-PAGE), column chromatography, filtration, isoelectric focusing, dialysis, recrystallization, ultrafiltration, salting out, solvent precipitation, solvent extraction, distillation, and immunoprecipitation, can be used to purify, isolate, or separate the binding molecules of the present invention, in particular antibodies or antigen-binding fragments or derivatives thereof, from inside cells or outside cells (e.g., medium).

[0160] In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 18 encoding an Abeta antibody or an antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 19 encoding an Abeta antibody or an antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 52 encoding an Abeta antibody or an antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 53 encoding an Abeta antibody or an antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 54 encoding an Abeta antibody or an antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 55 encoding an Abeta antibody or an antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 68 encoding an Abeta antibody or an antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 69, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 78, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 79, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 88, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 89, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 98, encoding an Abeta antibody or antigen-binding fragment thereof.In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 99, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 108, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 109, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 118, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 119, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 128, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 129, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 138, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 139, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 148, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 149, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 158, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 159, encoding an Abeta antibody or antigen-binding fragment thereof.In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 168, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 169, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 178, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 179, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 188, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 189, encoding an Abeta antibody or antigen-binding fragment thereof. In certain embodiments, an (isolated) nucleic acid is provided, wherein the (isolated) nucleic acid comprises SEQ ID NO: 199, encoding an Abeta antibody or antigen-binding fragment thereof.

[0161] In certain embodiments, diagnostic compositions are provided comprising the binding molecules of the present invention (and provided herein), particularly antibodies or antigen-binding fragments thereof, and acceptable carriers and / or excipients. For example, the binding molecules, particularly antibodies or antigen-binding fragments thereof, may be combined with acceptable carriers or vehicles, such as sterile water or saline, vegetable oils, emulsifiers, suspending agents, surfactants, stabilizers, flavoring agents, excipients, vehicles, preservatives, and binders, as needed, and formulated into diagnostic preparations. Preferred diagnostic compositions of the present invention are compatible with the use of body fluids as test samples. Thus, diagnostic compositions may enable the direct use of body fluid samples without the need for further processing of the body fluid sample. For cell and / or tissue applications, diagnostic compositions may be formulated identically or differently in certain embodiments to facilitate the use of such samples.

[0162] In certain embodiments, a diagnostic composition is provided comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof of the invention and an acceptable carrier and / or excipient.

[0163] In one embodiment, a. a first amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species; and b. A second amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species. wherein at least one or both of the first and second antibodies exhibits no cross-reactivity to soluble amyloid precursor protein (APP), and in particular no cross-reactivity to soluble APP alpha.

[0164] One or both antibodies may be antibodies of the present invention. Either antibody may be used as a capture antibody, thus providing for binding or attachment to a solid support. The other antibody may be used as a detection antibody, thus conjugating with a suitable label. Conjugated antibodies are described herein, and that description applies mutatis mutandis.

[0165] In certain embodiments, both the first and second antibodies exhibit no cross-reactivity to soluble amyloid precursor protein (APP), and in particular no cross-reactivity to soluble APP alpha. In other embodiments, one of the first and second antibodies or antigen-binding fragments thereof exhibits cross-reactivity to soluble amyloid precursor protein (APP). The cross-reactivity may be low or high. The other antibody or antigen-binding fragment thereof exhibits no cross-reactivity to soluble amyloid precursor protein (APP). In certain embodiments, a diagnostic composition is provided comprising at least two amyloid beta-binding antibodies or antigen-binding fragments thereof and an acceptable carrier and / or excipient, wherein the amyloid beta-binding antibodies or antigen-binding fragments are: a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and / or c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. is selected from.

[0166] In certain embodiments, a diagnostic composition is provided comprising a) and b) above or a) and c) above.

[0167] In a more preferred embodiment, a diagnostic composition is provided comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof, and an acceptable carrier and / or excipient, wherein said amyloid beta binding antibodies or antigen-binding fragments are: a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; and b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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 is selected from.

[0168] In certain embodiments, a diagnostic composition is provided comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof, and an acceptable carrier and / or excipient, wherein said amyloid beta binding antibodies or antigen-binding fragments: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; 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: 34; and / or c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 is selected from.

[0169] In certain embodiments, a diagnostic composition is provided comprising a) and b) above or a) and c) above.

[0170] In a more preferred embodiment, a diagnostic composition is provided comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof, and an acceptable carrier and / or excipient, wherein said amyloid beta binding antibodies or antigen-binding fragments are: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; and 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: 34 is selected from.

[0171] In certain embodiments, a diagnostic composition is provided comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof, and an acceptable carrier and / or excipient, wherein said amyloid beta binding antibodies or antigen-binding fragments: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and / or c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154. is selected from.

[0172] In certain embodiments, a diagnostic composition is provided comprising a) and b) above or a) and c) above.

[0173] In certain embodiments, a diagnostic composition is provided comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof, and an acceptable carrier and / or excipient, wherein said amyloid beta binding antibodies or antigen-binding fragments: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; and b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34. is selected from.

[0174] In some embodiments, diagnostic compositions are provided, comprising at least one amyloid beta binding antibody or its antigen-binding fragment of the present invention, particularly an antibody or its antigen-binding fragment that does not show cross-reactivity to soluble amyloid precursor protein (APP), in combination with at least one amyloid beta antibody known in the art and acceptable carrier and / or excipient.In some embodiments, the amyloid beta antibody known in the art is a commercially available Abeta binding antibody.In some embodiments, the antibody is selected from NAB228 (Invitrogen), 6E10 (Covance), 2C8 (Invitrogen), 4G8 (Chemicon), W0-2 (Merck) and DE2 (Chemicon).Such antibody can be used as capture antibody, and the antibody of the present invention can be used as detection antibody (or vice versa).

[0175] In certain embodiments, conjugated binding molecules, particularly antibodies or antigen-binding fragments thereof, are provided, including the binding molecules described herein, particularly antibodies or antigen-binding fragments thereof, and conjugated molecules. The conjugates of the present invention may be referred to as immunoconjugates. Any suitable conjugated molecule may be used in accordance with the present invention. Suitable examples include, but are not limited to, enzymes (e.g., alkaline phosphatase or horseradish peroxidase), avidin, streptavidin, biotin, protein A / G, magnetic beads, fluorophores, radioisotopes (i.e., radioconjugates), nucleic acid molecules, detectable labels, therapeutic agents, toxins, and blood-brain barrier-penetrating moieties. Conjugation methods are well known in the art, and several techniques are commercially available for conjugating antibodies to labels or other molecules. Conjugation is typically carried out via amino acid residues (such as lysine, histidine, or cysteine) contained within the binding molecules of the present invention. These methods include the NHS (succinimidyl) ester method, the isothiocyanate method, the carbodiimide method, and the periodate method. Conjugation can be carried out, for example, by creating a fusion protein. This is suitable when the binding molecule is conjugated with another protein molecule. Therefore, a suitable genetic construct can be formed that allows the expression of the fusion of the binding molecule of the present invention with a label or other molecule. Conjugation can be carried out via a suitable linker moiety to ensure appropriate spatial separation of the antibody and the conjugated molecule (e.g., a detectable label, etc.). However, a linker may not be required in all cases.

[0176] In certain embodiments, diagnostic compositions are provided comprising an isolated binding molecule described herein, particularly an antibody or antigen-binding fragment thereof, and an acceptable carrier and / or excipient.

[0177] The binding molecules of the present invention, particularly amyloid beta-binding antibodies or antigen-binding fragments thereof, have many uses. They can be used in research applications, particularly as analytical tools or reference molecules. They can be used to detect amyloid beta aggregates, including plaques, in vitro or in vivo. The binding molecules can be used to stain amyloid beta aggregates. For example, the binding molecules can be used for histochemical detection in postmortem brain tissue. The binding molecules are typically labeled, and may be directly or indirectly labeled as described herein. Such use can be carried out with any suitable animal, particularly a mammal. Preferred subjects are humans and mice.

[0178] In some embodiments, a method for diagnosing amyloid beta-related diseases, disorders or illnesses is provided, such as Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-related Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), Lewy body disease, ALS (amyotrophic lateral sclerosis), adult-onset diabetes, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure.The method comprises administering the binding molecule of the present invention, particularly an antibody or its antigen-binding fragment, or the diagnostic composition of the present invention to a subject. More specifically, in some embodiments, provided is a method for diagnosing amyloid beta-related diseases, disorders or illnesses, wherein said amyloid beta-related diseases, disorders or illnesses are selected from the group consisting of Alzheimer's disease (AD), Down's syndrome (DS), Down's syndrome-related Alzheimer's disease, cerebral amyloid angiopathy (CAA), myotonic dystrophy and Lewy body disease.Typically, subject is a mammalian subject, preferably human.For in vivo method, binding molecule is typically labeled with a suitable label for visualization.

[0179] In certain embodiments, the binding molecules provided herein, particularly antibodies or antigen-binding fragments thereof, of the present invention are useful for detecting the presence of Abeta in biological samples. In certain embodiments, the binding molecules provided herein, particularly antibodies or antigen-binding fragments thereof, of the present invention are useful for detecting the presence of Abeta in body fluid samples. The term "body fluid sample" includes samples obtained from body fluids by further processing, such as concentration, centrifugation, and the addition of additional substances such as buffers and preservatives. In certain embodiments, the binding molecules provided herein, particularly antibodies or antigen-binding fragments thereof, of the present invention are useful for detecting the presence of pathological Abeta in biological samples. As used herein, the term "detection" encompasses quantitative and / or qualitative detection. The biological sample is typically obtained from a mammal, particularly a human. The biological sample is typically a clinical sample from a subject suspected of or being screened for amyloid beta-related disease, disorder, or condition according to any of the methods described herein. Obtaining a sample does not constitute a required step of the method of the present invention and may therefore begin with an already isolated sample. Obtaining a sample can be performed by any suitable technique, depending on the sample of interest. In certain embodiments, the biological sample comprises cells, tissues, and / or bodily fluids (such as nasal secretions, urine, blood, etc.) from a subject. Examples of suitable biological samples include cerebrospinal fluid (CSF), interstitial fluid (ISF), brain cells or tissues (e.g., cerebral cortex or hippocampus). Examples of suitable bodily fluids include cerebrospinal fluid (CSF), interstitial fluid (ISF), blood (including whole blood and derivatives such as serum and plasma), urine, and nasal secretions. In some embodiments, the biological sample is cerebrospinal fluid (CSF) or blood. In some embodiments, the biological sample is plasma.

[0180] In certain embodiments, a method for detecting Abeta in a biological sample is provided, comprising contacting the biological sample with a binding molecule of the present invention provided herein, particularly an Abeta antibody or its antigen-binding fragment, under conditions that allow the binding of the binding molecule, particularly an Abeta antibody or its antigen-binding fragment, to Abeta, and then detecting whether a complex is formed between the binding molecule, particularly an Abeta antibody or its antigen-binding fragment, and Abeta. If complex formation is detected, it can be determined that the sample contains Abeta. If there is no complex formation or the complex formation is below a predetermined threshold, it can be determined that the sample does not contain Abeta. Such a method can be an in vitro or in vivo method. Furthermore, the complex formed between the binding molecule, Abeta antibody or its antigen-binding fragment, and Abeta in the test biological sample can be compared with the complex formed in a control biological sample (e.g., a biological sample from a healthy subject). The amount of complex formed between the binding molecule, Abeta antibody or antigen-binding fragment thereof, and Abeta in the test biological sample can also be quantified and compared to the amount of complex formed in a control biological sample (e.g., a biological sample from a healthy subject) or the average amount of complex known to form in healthy subjects.

[0181] In certain embodiments, the binding molecules provided herein of the present invention, particularly antibodies or antigen-binding fragments thereof, are useful for detecting the presence of Abeta in a biological sample. In certain embodiments, the binding molecules provided herein of the present invention, in particular antibodies or antigen-binding fragments thereof, can be assayed using a variety of assays including, but not limited to, ELISA, MSD (Meso Scale Discovery Inc., USA), Luminex (Luminex Corp., USA), Alphalisa (PerkinElmer, Inc., USA), Gyrolab (Gyros Protein Technologies AB, Sweden), Simoa (Quanterix Corp., USA), Gyros® (Given et al., 2012), Singulex Erenna (EMD Millipore, Corp., USA), iR-SENSE / Immuno-InfraRed assay (Nabers et al., 2016), MITOMI (Piraino et al., 2016), immunoprecipitation coupled with liquid chromatography-mass spectrometry (IP LC-MS / MS; Shimadzu, Germany), surface plasmon resonance (SPR; Cytiva Europe, Switzerland), atomic force microscopy (AFM) (Kiio and Park, 2020), or other antibody-based assay techniques or kits for immunocapture and / or detection of targets. Thus, binding molecules, particularly antibodies or antigen-binding fragments thereof, can be used in assays to validate / screen binding molecules, Abeta or Abeta fragments, Abeta antibodies or antigen-binding fragments thereof. The binding molecules of the present invention, particularly antibodies or antigen-binding fragments thereof, can be used as detection tools and / or positive controls because they selectively bind to all Abeta species in a sample in a selective manner.In one embodiment, at least two amyloid beta antibodies or antigen-binding fragments thereof can be used as assay reagents, positive controls, biomarker detection reagents, and / or calibrators for the immunoassays described above. In one embodiment, at least two amyloid beta antibodies or antigen-binding fragments thereof can be used in an immunoassay, preferably a sandwich assay (ELISA), to produce antibody sandwich pairing, preferably the antibodies are ACI-24-41F12-Ab3, ACI-31-25B1-Ab2, and ACI-8041-5A2D4-Ab1, and even more preferably the antibodies are ACI-24-41F12-Ab3 and ACI-31-25B1-Ab2. In one embodiment, at least two amyloid beta antibodies or antigen-binding fragments thereof can be used in a sandwich assay (ELISA) to produce sandwich pairing of antibodies, wherein one antibody or antigen-binding fragment thereof is used to capture a target (including but not limited to Abeta), preferably ACI-31-25B1-Ab2, and another antibody or antigen-binding fragment thereof is used to detect the captured target, preferably ACI-24-41F12-Ab3 conjugated to a detectable label, more preferably ACI-24-41F12-Ab3.

[0182] The present invention provides a method for detecting amyloid beta in a sample obtained from a subject, comprising: a. capturing amyloid beta using an amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species, and then b. detecting the captured amyloid beta using an amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species; The present invention relates to a method in which at least one or both of the capture (a) and detection (b) antibodies or antigen-binding fragments thereof exhibit no cross-reactivity to soluble amyloid precursor protein (APP), particularly no cross-reactivity to soluble APP alpha. One or both of the capture antibody and the detection antibody can be an antibody of the present invention. The capture antibody can be provided for binding or attachment to a solid support. The detection antibody can be conjugated to a suitable label. Conjugated antibodies are described herein, and this description applies mutatis mutandis.

[0183] In some embodiments, both the capture antibody and the detection antibody do not show cross-reactivity to soluble amyloid precursor protein (APP), particularly to soluble APP alpha. In other embodiments, one of the capture and detection antibodies or their antigen-binding fragments shows cross-reactivity to soluble amyloid precursor protein (APP). The cross-reactivity may be low or high. The other antibody or its antigen-binding fragment does not show cross-reactivity to soluble amyloid precursor protein (APP).

[0184] In some embodiments, the capture antibody or antigen-binding fragment is immobilized on a solid support, such as on the surface of a well (e.g., in a multi-well plate). In some embodiments, the detection antibody or antigen-binding fragment is labeled with a detectable label.

[0185] In certain embodiments, the capture or detection (preferably, detection) amyloid beta-binding antibody or antigen-binding fragment comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. In certain embodiments, the capture or detection (preferably, detection) amyloid beta-binding antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14. In one embodiment, the capture or detection (preferably, detection) amyloid beta-binding antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0186] In one embodiment, the capture or detection (preferably capture) amyloid beta binding antibody or antigen-binding fragment comprises: a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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 b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. Includes.

[0187] Preferred capture amyloid beta binding antibodies or antigen-binding fragments include those in a) above.

[0188] In one embodiment, the capture or detection (preferably capture) amyloid beta binding antibody or antigen-binding fragment comprises: 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: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 Includes.

[0189] In one embodiment, the capture or detection (preferably capture) amyloid beta binding antibody or antigen-binding fragment comprises: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and / or b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154. Includes.

[0190] The present invention also provides a method for detecting amyloid beta in a sample obtained from a subject, the method comprising: a. Capture amyloid beta using an amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species, and that does not exhibit cross-reactivity to soluble amyloid precursor protein (APP), and in particular, does not exhibit high cross-reactivity to soluble APP alpha, and then b. Detecting captured amyloid beta using an amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species, and that exhibits (low or high) cross-reactivity to soluble amyloid precursor protein (APP), and in particular, no cross-reactivity to soluble APP alpha. The present invention relates to a method comprising:

[0191] In some embodiments, the capture antibody or antigen-binding fragment is immobilized on a solid support, such as on the surface of a well (e.g., in a multi-well plate).In some embodiments, the capture and / or detection antibody or antigen-binding fragment has high affinity for Abeta.In some embodiments, the detection antibody or antigen-binding fragment is labeled with a detectable label.In some embodiments, the capture amyloid beta-binding antibody or antigen-binding fragment is: a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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 b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. Includes.

[0192] Preferred capture amyloid beta binding antibodies or antigen-binding fragments include those in a) above.

[0193] In some embodiments, the capture amyloid beta binding antibody or antigen-binding fragment: 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: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 Includes.

[0194] In some embodiments, the capture amyloid beta binding antibody or antigen-binding fragment: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and / or The antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154. In some embodiments, the detected amyloid beta-binding antibody or antigen-binding fragment comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments, the detected amyloid beta-binding antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14. In some embodiments, the detected amyloid beta-binding antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0195] In certain embodiments, the present invention includes a method for detecting amyloid beta in a sample obtained from a subject, the method comprising capturing amyloid beta with a first amyloid beta-binding antibody or fragment thereof, and then detecting the captured amyloid beta in the sample with a second amyloid beta-binding antibody or fragment thereof, wherein each amyloid beta-binding antibody or antigen-binding fragment thereof is independently selected from ACI-24-41F12-Ab3, ACI-31-25B1-Ab2, and ACI-8041-5A2D4-Ab1, preferably the antibody is ACI-24-41F12-Ab3 or ACI-31-25B1-Ab2, more preferably ACI-24-41F12-Ab3 conjugated to a detectable label. In another embodiment of the present invention, the step of capturing amyloid beta is carried out using a first amyloid beta-binding antibody or fragment thereof selected from ACI-24-41F12-Ab3, ACI-31-25B1-Ab2, and ACI-8041-5A2D4-Ab1, preferably the antibody is ACI-24-41F12-Ab3 or ACI-31-25B1-Ab2, more preferably ACI-31-25B1-Ab2. In another embodiment of the present invention, the step of detecting captured amyloid beta is carried out using a second amyloid beta-binding antibody or fragment thereof conjugated to a detectable label and selected from ACI-24-41F12-Ab3, ACI-31-25B1-Ab2, and ACI-8041-5A2D4-Ab1, preferably ACI-24-41F12-Ab3 and ACI-31-25B1-Ab2, more preferably ACI-24-41F12-Ab3. The step of detecting captured amyloid beta in the sample is carried out using a second amyloid beta-binding antibody or fragment thereof, each amyloid beta-binding antibody or antigen-binding fragment thereof conjugated to a detectable label known in the art.

[0196] Thus, the present invention provides a method for detecting amyloid beta in a sample obtained from a subject, comprising contacting the sample with a binding molecule of the present invention, particularly an antibody or antigen-binding fragment, and then detecting the binding of the antibody or its antigen-binding fragment to detect amyloid beta in the sample. Similarly, the present invention provides a method for quantifying amyloid beta in a sample obtained from a subject, comprising contacting the sample with a binding molecule of the present invention, particularly an antibody or antigen-binding fragment, and then performing quantification based on the binding of the binding molecule to amyloid beta. This method may include comparing the amyloid beta level in the sample with the amyloid beta level in a control sample. The level in the control sample represents a known level from which the level in the test sample can be determined. Thus, the control sample is not necessarily tested simultaneously with the quantification method. However, in some embodiments, the control level is determined in parallel with the test sample. For example, quantitative ELISA, ELISA, MSD (Meso Scale Discovery Inc., USA), Luminex (Luminex Corp., USA), Alphalisa (PerkinElmer, Inc., USA), Gyrolab (Gyros Protein Technologies AB, Sweden), Simoa (Quanterix Corp., USA), Gyros® (Given et al., 2012), Singulex Erenna (EMD Millipore, Corp., USA), iR-SENSE / Immuno-InfraRed assay (Nabers et al., 2016), MITOMI (Piraino et al., 2016), immunoprecipitation coupled with liquid chromatography-mass spectrometry (IP LC-MS / MS; Shimadzu, Germany), surface plasmon resonance (SPR; Cytiva Europe, Switzerland), atomic force microscopy (AFM) (Kiio and Park, 2020) may be performed. A standard curve can be generated to allow quantification based on serial dilutions of Abeta. The diagnostic composition of the present invention can be used in such a method.The sandwich immunoassays described herein incorporating appropriate capture and detection antibodies or antigen-binding fragments thereof can be used in methods for quantifying amyloid beta in a sample obtained from a subject.

[0197] The present invention also provides a method for diagnosing amyloid beta-related diseases, disorders, and / or conditions, comprising contacting a sample with a binding molecule, particularly an antibody or antigen-binding fragment, of the present invention and then comparing the amyloid beta level in the sample with the level in a control sample. A higher amyloid beta level in the sample compared to a control level based on healthy subjects indicates amyloid beta-related diseases, disorders, and / or conditions. Additionally or alternatively, a similar or higher amyloid beta level in the sample compared to a diseased control (i.e., one or more samples from a subject suffering from amyloid beta-related diseases, disorders, and / or conditions) indicates amyloid beta-related diseases, disorders, and / or conditions. The diagnostic composition of the present invention may be used in such methods. The sandwich immunoassays described herein incorporating appropriate capture and detection antibodies or antigen-binding fragments thereof may be used in methods for diagnosing amyloid beta-related diseases, disorders, and / or conditions.

[0198] The binding molecules of the present invention are also useful in classification methods, for example, to indicate the relative stage of amyloid beta-related diseases, disorders, and / or conditions. Therefore, the present invention also provides a method for classifying amyloid beta-related diseases, disorders, and / or conditions, comprising contacting a sample from a subject with a binding molecule of the present invention, particularly an antibody or antigen-binding fragment, and then comparing the amyloid beta level in the sample with the level in a control sample to classify the disease. Control ranges representing different disease classes can be used to classify the sample. A higher level of amyloid beta in a sample compared to a control level based on healthy subjects indicates amyloid beta-related diseases, disorders, and / or conditions. A comparable or higher level of amyloid beta in a sample compared to a diseased control at a particular stage of the disease indicates the stage of amyloid beta-related diseases, disorders, and / or conditions. Such methods can be performed on subjects known to have amyloid beta-related diseases, disorders, and / or conditions, and / or on subjects not yet known to have amyloid beta-related diseases, disorders, and / or conditions. The diagnostic compositions of the invention can be used in such methods. Sandwich immunoassays as described herein incorporating appropriate capture and detection antibodies or antigen-binding fragments thereof can be used in the typing methods of the invention.

[0199] The present invention also provides methods for monitoring amyloid beta-related diseases, disorders, and / or conditions using samples from a subject at two or more time points, comprising contacting the samples with a binding molecule, particularly an antibody or antigen-binding fragment, of the present invention, and then comparing the amyloid beta levels in the samples, wherein a higher level of amyloid beta in the later sample compared to one or more earlier samples indicates the progression of amyloid beta-related diseases, disorders, and / or conditions. Similarly, the present invention provides methods for monitoring amyloid beta-related diseases, disorders, and / or conditions using samples from a subject at two or more time points, comprising contacting the samples with a binding molecule, particularly an antibody or antigen-binding fragment, of the present invention, and then comparing the amyloid beta levels in the later sample compared to one or more earlier samples, wherein a lower level of amyloid beta in the later sample compared to one or more earlier samples indicates the regression of amyloid beta-related diseases, disorders, and / or conditions. These methods also allow for the monitoring of disease progression when there is no significant change in the amyloid beta levels in the later sample compared to one or more earlier samples. Such methods are typically performed on subjects known to suffer from amyloid beta-related diseases, disorders, and / or conditions. The diagnostic compositions of the present invention may be used in such methods. The sandwich immunoassays described herein incorporating appropriate capture and detection antibodies or antigen-binding fragments thereof may be used in the monitoring methods of the present invention.

[0200] Monitoring methods are useful for determining whether a particular treatment is successful. Thus, the present invention also provides methods for monitoring amyloid beta-related diseases, disorders, and / or conditions at two or more time points using a sample from a subject, comprising contacting the sample with a binding molecule of the present invention, particularly an antibody or antigen-binding fragment, wherein a lower level of amyloid beta in the subsequent sample compared to one or more previous samples indicates successful treatment of the amyloid beta-related disease, disorder, and / or condition. The treatment can be any suitable candidate therapeutic agent, such as an antibody or small molecule therapeutic. These methods also allow for monitoring the lack of disease progression when there is no significant change in the amyloid beta level in the subsequent sample compared to one or more previous samples. This may be considered successful treatment in some circumstances. Indeed, a decrease in the rate of increase in Abeta levels between samples compared to the rate of increase before treatment may also be considered successful treatment. Such methods are typically performed on subjects known to suffer from amyloid beta-related diseases, disorders, and / or conditions. Treatment failure can be determined when the treatment does not result in a decrease in the rate of increase of Abeta levels between samples compared to the rate of increase before treatment. The diagnostic compositions of the present invention can be used in such methods. The sandwich immunoassays described herein incorporating appropriate capture and detection antibodies or antigen-binding fragments thereof can be used in the methods for monitoring treatment of the present invention.

[0201] The binding molecules of the present invention can also be used to aid in the selection of a treatment. Thus, the present invention provides a method for selecting a treatment for amyloid beta-related diseases, disorders, and / or conditions, comprising contacting samples collected before and after treatment with a binding molecule of the present invention, particularly an antibody or antigen, wherein a lower level of amyloid beta in the sample collected after treatment compared to the sample collected before treatment indicates successful treatment of the amyloid beta-related disease, disorder, and / or condition, thereby selecting the treatment. The treatment can be any suitable candidate therapeutic agent, such as an antibody or small molecule therapeutic agent. A treatment that halts disease progression can be selected if the amyloid beta level in the subsequent sample does not change significantly compared to one or more previous samples. This may be considered successful treatment in some circumstances. Indeed, a decrease in the rate of increase in Abeta levels between samples compared to the rate of increase before treatment can also be considered successful treatment. Such a method is typically performed on a subject known to have an amyloid beta-related disease, disorder, and / or condition. Treatment failure can be determined when the treatment does not result in a decrease in the rate of increase of Abeta levels between samples compared to the rate of increase before treatment. Such a treatment is not selected for treatment. Alternatively, a high level of amyloid beta in a sample collected after treatment compared to a sample collected before treatment can indicate failure of treatment of a disease, disorder, and / or condition related to amyloid beta, thereby not selecting the treatment. The diagnostic composition of the present invention can be used in such methods. The sandwich immunoassay described herein, incorporating appropriate capture and detection antibodies or antigen-binding fragments thereof, can be used in the treatment selection method of the present invention (as applied to an individual subject).

[0202] The methods of the present invention are also useful for determining whether a particular treatment is successful or not in the context of a larger controlled study, such as a clinical trial. Thus, these methods are typically applied to a treatment group of subjects compared with a group of subjects not treated with the treatment. In such a situation, a control sample not treated with the treatment is also available for comparison (placebo group). Thus, the present invention also provides a method for evaluating a candidate treatment for amyloid beta-related diseases, disorders, and / or conditions, comprising contacting samples from one or more treated subjects with a binding molecule, particularly an antibody or antigen-binding fragment, of the present invention after treatment of one or more subjects, wherein a lower level of amyloid beta in the sample compared to the level in a corresponding sample from a subject not treated with the treatment indicates successful treatment of amyloid beta-related diseases, disorders, and / or conditions. This method is typically performed on multiple (i.e., at least two) treated subjects and multiple control subjects. The treatment group and the control group may or may not be of the same size. In some embodiments, each of these may include three or more, four or more, five or more, ten or more, ten or more, or fifty or more subjects. The therapeutic agent may be any suitable candidate therapeutic agent, such as a biologic, particularly an antibody, vaccine, or small molecule therapeutic agent. The method may be performed at multiple time points on matched samples between treatment and placebo groups to monitor the efficacy of the candidate therapeutic agent over a predetermined period of time. Typically, an initial pre-treatment sample is also collected. Thus, the method may include contacting samples from one or more treated subjects and subjects not treated with the therapeutic agent with a binding molecule of the present invention, particularly an antibody or antigen-binding fragment, before treatment to determine basal amyloid beta levels. "Pre-treatment" refers to before administration of the therapeutic agent or placebo by the subject group. Thus, the binding molecules of the present invention may also be used to assist in the evaluation of candidate therapeutic agents in the context of clinical trials. Candidate therapeutic agents that result in successful treatment may be selected and ultimately approved for sale.The diagnostic compositions of the invention can be used in such methods. Sandwich immunoassays described herein incorporating appropriate capture and detection antibodies or antigen-binding fragments thereof can be used in the therapeutic selection methods of the invention (as applied in clinical trials).

[0203] According to all related methods, the disease, disorder and / or illness associated with amyloid beta can be selected from the group consisting of Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Alzheimer's disease associated with Down's syndrome, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), Lewy body disease, ALS (amyotrophic lateral sclerosis), adult-onset diabetes, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure.In certain embodiments, the disease, disorder or illness associated with amyloid beta is Alzheimer's disease (AD), Down's syndrome (DS), Alzheimer's disease associated with Down's syndrome, cerebral amyloid angiopathy (CAA), myotonic dystrophy, or Lewy body disease.

[0204] Suitable samples for use in the various methods are typically biological samples as described herein, particularly body fluids. Suitable immunoassay methods are known to those skilled in the art and include, but are not limited to, ELISA, MSD (Meso Scale Discovery Inc., USA), Luminex (Luminex Corp., USA), Alphalisa (PerkinElmer, Inc., USA), Gyrolab (USA), Gyros Protein Technologies AB, Sweden), Simoa (Quanterix Corp., USA), Gyros® (Given et al., 2012), Singulex Erenna (EMD Millipore, Corp., USA), iR-SENSE / Immuno-InfraRed assay (Nabers et al., 2016), MITOMI (Piraino et al., 2016), immunoprecipitation coupled with liquid chromatography-mass spectrometry (IP LC-MS / MS; Shimadzu, Germany), surface plasmon resonance (SPR; Cytiva Europe, Switzerland), atomic force microscopy (AFM) (Kiio and Park, 2020).

[0205] In some embodiments, the binding molecules, Abeta antibodies, or antigen-binding fragments thereof of the present invention are part of a diagnostic kit containing such binding molecules, Abeta antibodies, or antigen-binding fragments thereof. Such kits may include all components necessary for carrying out the methods and / or assays provided herein, such as buffers, detectable dyes, laboratory equipment, reaction vessels, instructions, etc. The binding molecules, particularly antibodies, or antigen-binding fragments thereof, may be conjugated with labels or other molecules described herein. They may be labeled with or express dyes or tags, such as fluorophores or fluorescent dyes, or may be attached to enzymes or solid supports (e.g., assay chips), as required for each corresponding assay technique. In further embodiments, the binding molecules, particularly antibodies, or antigen-binding fragments thereof of the present invention may be conjugated to radioisotopes (i.e., radioconjugates), nucleic acid molecules, detectable labels, therapeutic agents, toxins, or blood-brain barrier-penetrating moieties, forming immunoconjugates. The kits may be used to carry out any of the methods of the present invention and therefore may include any suitable components, including the reagents necessary to carry out these methods. The present invention further relates to kits containing the Abeta antibodies, or antigen-binding fragments thereof, of the present invention. The kit typically comprises the Abeta antibody or antigen-binding fragment thereof of the present invention in a suitable container. The Abeta antibody or antigen-binding fragment thereof may be provided in the form of a diagnostic composition ready for application, or may be provided in the kit together with suitable agents for reconstituting the product, such as physiological saline. The kit may also be provided with instructions for use. Thus, the description of the method of the present invention applies mutatis mutandis. Kits for carrying out the sandwich immunoassay of the present invention are also provided. They comprise suitable capture and detection antibodies or antigen-binding fragments thereof. Thus, the present invention provides a kit for detecting amyloid beta in a sample obtained from a subject, comprising: a. a capture amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species; and b. A detecting amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species. Including, The kit relates to a kit in which at least one of the capture and detection antibodies or antigen-binding fragments thereof is not cross-reactive with soluble amyloid precursor protein (APP), and in particular is not cross-reactive with soluble APP alpha.

[0206] One or both antibodies can be an antibody of the invention.

[0207] In certain embodiments, the capture antibody or antigen-binding fragment is immobilized on a solid support, such as on the surface of a well (e.g., in a multiwell plate), or is provided with a solid support and / or methods for immobilizing the capture antibody or antigen-binding fragment on a solid support. In certain embodiments, the detection antibody or antigen-binding fragment is directly or indirectly labeled with a detectable label or is provided with a label or means for binding the antibody to the label.

[0208] In some embodiments, both the capture antibody and the detection antibody do not exhibit cross-reactivity to soluble amyloid precursor protein (APP), particularly to soluble APP alpha. In other embodiments, one of the capture and detection antibodies or their antigen-binding fragments exhibits cross-reactivity to soluble amyloid precursor protein (APP). The cross-reactivity may be low or high. The other antibody or its antigen-binding fragment (either the capture antibody or the detection antibody) does not exhibit cross-reactivity to soluble amyloid precursor protein (APP).

[0209] In certain embodiments, the capture or detection (preferably, detection) amyloid beta-binding antibody or antigen-binding fragment comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. In certain embodiments, the capture or detection (preferably, detection) amyloid beta-binding antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14. In one embodiment, the capture or detection (preferably, detection) amyloid beta-binding antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0210] In one embodiment, the capture or detection (preferably capture) amyloid beta binding antibody or antigen-binding fragment comprises: a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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 b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. Includes.

[0211] Preferred capture amyloid beta binding antibodies or antigen-binding fragments include those in a) above.

[0212] In one embodiment, the capture or detection (preferably capture) amyloid beta binding antibody or antigen-binding fragment comprises: 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: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 Includes.

[0213] In one embodiment, the capture or detection (preferably capture) amyloid beta binding antibody or antigen-binding fragment comprises: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and / or b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154. Includes.

[0214] The present invention also provides a kit for detecting amyloid beta in a sample obtained from a subject, comprising: a. A capture amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species, and that exhibits no cross-reactivity to soluble amyloid precursor protein (APP), and in particular, high cross-reactivity to soluble APP alpha; and b. A kit comprising a detecting amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species, and that exhibits low or high cross-reactivity to soluble amyloid precursor protein (APP), and in particular, no cross-reactivity to soluble APP alpha.

[0215] In some embodiments, the capture antibody or antigen-binding fragment is immobilized on a solid support, such as on the surface of a well (e.g., in a multi-well plate), or is provided together with a solid support and / or a method for immobilizing the capture antibody or antigen-binding fragment on a solid support.In some embodiments, the detection antibody or antigen-binding fragment has high affinity for Abeta.In some embodiments, the detection antibody or antigen-binding fragment is labeled with a detectable label, or is provided together with a label and a method for directly or indirectly conjugating the antibody to a label.In some embodiments, the capture amyloid beta-binding antibody or antigen-binding fragment is: a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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 b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. Includes.

[0216] Preferred capture amyloid beta binding antibodies or antigen-binding fragments include those in a) above.

[0217] In some embodiments, the capture amyloid beta binding antibody or antigen-binding fragment: 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: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 Includes.

[0218] In some embodiments, the capture amyloid beta binding antibody or antigen-binding fragment: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and / or b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154. Includes.

[0219] In some embodiments, the detected amyloid beta-binding antibody or antigen-binding fragment comprises a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments, the detected amyloid beta-binding antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14. In some embodiments, the detected amyloid beta-binding antibody or antigen-binding fragment comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0220] The invention may be further defined in the following numbered paragraphs:

[0221] 1. An antibody or antigen-binding fragment thereof comprising a VH-CDR1 having the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 having the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 having the amino acid sequence of SEQ ID NO: 13; a VL-CDR1 having the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 having the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 having the amino acid sequence of SEQ ID NO: 17, wherein the antibody or antigen-binding fragment binds to amyloid beta.

[0222] 2. The antibody or antigen-binding fragment thereof according to Item 1, wherein the antibody or antigen-binding fragment binds to amino acid residues 1 to 8 of human amyloid beta SEQ ID NO: 1 (SEQ ID NO: 2).

[0223] 3. The antibody or antigen-binding fragment thereof according to items 1 to 2, wherein the antibody comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10.

[0224] 4. The antibody or antigen-binding fragment thereof of any preceding paragraph, wherein the antibody comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0225] 5. The antibody or antigen-binding fragment thereof of any preceding paragraph, wherein the antibody comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14.

[0226] 6. The antibody or antigen-binding fragment thereof of any preceding paragraph, wherein the antibody comprises a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 20 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 21.

[0227] 7. The antibody or antigen-binding fragment thereof of any preceding paragraph, wherein the antibody comprises a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 22 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 23.

[0228] 8. The antibody or antigen-binding fragment thereof of any preceding paragraph, wherein the antibody comprises a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 24 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 25.

[0229] 9. The antibody or antigen-binding fragment thereof of any preceding clause for use in diagnosing a disease or condition associated with amyloid beta in a subject.

[0230] 10. An antibody or antigen-binding fragment thereof according to any preceding paragraph for use in detecting amyloid beta in a sample.

[0231] 11. The antibody or antigen-binding fragment thereof according to any preceding clause for use in detecting amyloid beta in a sample, wherein the sample is a saliva, urine, blood, brain and / or CSF sample, more particularly a blood and / or CSF sample.

[0232] 12. The antibody or antigen-binding fragment thereof according to any preceding paragraph for use in diagnosing a disease or condition associated with amyloid beta, wherein the disease or condition associated with amyloid beta is selected from the group consisting of Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, disease with Lewy bodies, ALS (amyotrophic lateral sclerosis), adult-onset diabetes mellitus, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, and optic neuritis.

[0233] 13. The antibody or antigen-binding fragment thereof according to any preceding paragraph for use in diagnosing an amyloid beta-associated disease or condition, wherein the amyloid beta-associated disease or condition is Alzheimer's disease (AD), Down's syndrome, Down's syndrome-associated Alzheimer's disease, cerebral amyloid angiopathy (CAA), myotonic dystrophy, or Lewy body disease.

[0234] 14. The antibody or antigen-binding fragment thereof according to any preceding paragraph for use in diagnosing an amyloid beta-associated disease or condition, wherein the amyloid beta-associated disease or condition is Alzheimer's disease (AD).

[0235] 15. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13, for use in diagnosing an amyloid beta-associated disease or condition, wherein the amyloid beta-associated disease or condition is Down's syndrome.

[0236] 16. A diagnostic composition comprising an isolated antibody or antigen-binding fragment thereof according to any of the preceding paragraphs and an acceptable carrier and / or excipient.

[0237] 17. An isolated nucleic acid encoding the antibody according to any one of items 1 to 15.

[0238] 18. A nucleic acid comprising the nucleotide sequence provided in SEQ ID NO: 18 or SEQ ID NO: 19.

[0239] 19. A recombinant vector comprising the nucleic acid of paragraph 17 or 18.

[0240] 20. A host cell comprising the nucleic acid of paragraph 17 or 18 and / or the vector of paragraph 19.

[0241] 21. An isolated host cell expressing the antibody or antigen-binding fragment of any one of items 1 to 15.

[0242] 22. A method for producing an isolated binding molecule, in particular an antibody, comprising the steps of a) culturing a host cell according to paragraph 20 or 21 under conditions suitable for producing an antibody or antigen-binding fragment thereof, and then b) isolating said antibody or antigen-binding fragment thereof.

[0243] The invention may be further defined in the following numbered paragraphs: 1. a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; or c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; VH-CDR3 comprising the amino acid sequence of 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 An amyloid beta-binding antibody or antigen-binding fragment thereof comprising:

[0244] 2. The antibody or antigen-binding fragment thereof: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; or c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40. Item 1. The amyloid beta-binding antibody or antigen-binding fragment thereof according to Item 1, comprising:

[0245] 3. The antibody or antigen-binding fragment thereof: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; or c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any of the preceding paragraphs, comprising:

[0246] 4. The antibody or antigen-binding fragment thereof: a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; 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: 34; or c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 The amyloid beta-binding antibody or antigen-binding fragment thereof according to any of the preceding paragraphs, comprising:

[0247] 5. The antibody: a) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 20 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 21; b) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 22 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 23; c) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 24 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 25; d) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 27 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 28; e) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 38 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 39; f) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 48 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 49; or g) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 50 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 51 The amyloid beta-binding antibody or antigen-binding fragment thereof according to any of the preceding paragraphs, comprising:

[0248] 6. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any of the preceding paragraphs, which binds to an epitope within amino acid residues 1 to 5 (SEQ ID NO: 7), 1 to 8 (SEQ ID NO: 2), 22 to 35 (SEQ ID NO: 29), or 26 to 34 (SEQ ID NO: 8) of SEQ ID NO: 1, or an equivalent epitope in non-human amyloid beta.

[0249] 7. The amyloid beta-binding antibody or antigen-binding fragment thereof of any preceding clause, which is a murine, chimeric, humanized or human antibody, or antigen-binding fragment thereof.

[0250] 8. The amyloid beta-binding antibody or antigen-binding fragment thereof of any one of the preceding clauses, which is an IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3 or IgG4 antibody, or antigen-binding fragment thereof.

[0251] 9. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of the preceding clauses, which is conjugated to another molecule, particularly a detectable label.

[0252] 10. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any preceding clause for use in diagnosing an amyloid beta-related disease, disorder or condition in a subject.

[0253] 11. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any preceding paragraph for use in detecting amyloid beta in a biological sample.

[0254] 12. The amyloid beta-binding antibody or antigen-binding fragment thereof according to item 11, wherein the biological sample is a body fluid sample or a buffer solution.

[0255] 13. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 12, wherein the body fluid sample is saliva, urine, nasal secretions, blood (whole blood, plasma, and serum, preferably including plasma), a brain and / or CSF sample, a brain and / or ISF sample, more specifically a blood, brain, CSF, and / or ISF sample.

[0256] 14. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any preceding clause for use in diagnosing an amyloid beta-associated disease, disorder, or condition, wherein the amyloid beta-associated disease, disorder, or condition is selected from the group consisting of Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), disease with Lewy bodies, ALS (amyotrophic lateral sclerosis), adult-onset diabetes mellitus, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure.

[0257] 15. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any preceding paragraph for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Alzheimer's disease (AD), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cerebral amyloid angiopathy (CAA), myotonic dystrophy, or Lewy body disease.

[0258] 16. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any preceding paragraph for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Alzheimer's disease (AD).

[0259] 17. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 15, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Down's syndrome (DS).

[0260] 18. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 15, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Down's syndrome-associated Alzheimer's disease.

[0261] 19. A method for detecting amyloid beta in a sample obtained from a subject, comprising contacting the sample with an amyloid beta-binding antibody or antigen-binding fragment thereof described in any of the preceding paragraphs, and then detecting binding of the antibody or antigen-binding fragment thereof to detect amyloid beta in the sample.

[0262] 20. A method for quantifying amyloid beta in a sample obtained from a subject, comprising contacting the sample with an amyloid beta-binding antibody or antigen-binding fragment thereof described in any one of paragraphs 1 to 18, and then quantifying amyloid beta in the sample based on the level of binding of the antibody or antigen-binding fragment thereof to amyloid beta.

[0263] 21. A method for diagnosing amyloid beta-related disorders and / or diseases, comprising carrying out the method of paragraph 19 or paragraph 20, wherein a high level of amyloid beta in the sample compared to a control level based on a healthy subject indicates amyloid beta-related disease, disorder and / or disease.

[0264] 22. A method for diagnosing amyloid beta-associated diseases, disorders and / or conditions, comprising carrying out the method described in paragraph 19 or paragraph 20, wherein an identical or elevated level of amyloid beta in the sample compared to a diseased control level indicates amyloid beta-associated diseases, disorders and / or conditions.

[0265] 23. A method for classifying amyloid beta-related diseases, disorders and / or conditions, comprising: a. Carrying out the method according to paragraph 21 and / or paragraph 22, b. Classifying amyloid-beta-related diseases, disorders, and / or conditions A method comprising:

[0266] 24. A method for monitoring amyloid beta-related diseases, disorders and / or conditions at two or more time points using a sample from a subject, comprising contacting the sample with an amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of paragraphs 1 to 18; a. a higher level of amyloid beta in the subsequent sample compared to one or more previous samples indicates the progression of an amyloid beta-related disease, disorder, and / or condition; b. a lower level of amyloid beta in the subsequent sample compared to one or more previous samples indicates regression of amyloid beta-related diseases, disorders and / or conditions; and / or c. A method wherein the absence of a significant change in the level of amyloid beta in a subsequent sample compared to one or more previous samples indicates the absence of progression of a disease, disorder and / or condition associated with amyloid beta.

[0267] 25. A method for selecting a therapy for the treatment of amyloid beta-related diseases, disorders and / or conditions, comprising contacting samples collected before and after treatment with the therapy with an amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of paragraphs 1 to 18; a. a lower level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates successful treatment of the disease, disorder, and / or condition associated with amyloid beta, whereby said therapy is selected for treatment; b. no significant change in the level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates successful treatment of the disease, disorder, and / or condition associated with amyloid beta, thereby selecting said therapy for treatment; c. a decrease in the rate of increase in the level of amyloid beta between samples taken during treatment compared to samples taken before treatment indicates successful treatment of the disease, disorder, and / or condition associated with amyloid beta, thereby selecting said therapy for treatment; d. A higher level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates that the treatment for the disease, disorder, and / or condition associated with amyloid beta has failed, whereby the treatment is not selected for treatment; or e. A method wherein a failure to reduce the rate of increase in amyloid beta levels between samples taken during treatment compared to samples taken before treatment indicates failure of treatment of amyloid beta-related diseases, disorders and / or conditions, whereby said therapy is not selected for treatment.

[0268] 26. A method for evaluating candidate therapeutics for amyloid beta-associated diseases, disorders and / or conditions, comprising, after treatment of one or more subjects, contacting a sample from the treated one or more subjects with the antibody or antigen-binding fragment of any of paragraphs 1 to 18, wherein a lower level of amyloid beta in the sample compared to the level in a corresponding sample from a subject not treated with the therapeutic treatment indicates successful treatment of the amyloid beta-associated disease, disorder and / or condition.

[0269] 27. The method of paragraph 26, performed at multiple time points in matched samples between treatment and placebo groups to monitor the effectiveness of a candidate treatment over a period of time.

[0270] 28. The method of claim 26 or 27, comprising contacting samples from one or more treated subjects and subjects not treated with a therapy with the antibody or antigen-binding fragment of any of claims 1 to 18 prior to treatment with the therapy or a placebo, respectively, to determine basal levels of amyloid beta.

[0271] 29. The method according to any one of items 19 to 28, wherein the amyloid beta-associated disease, disorder, and / or condition is selected from the group consisting of Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), Lewy body disease, amyotrophic lateral sclerosis (ALS), adult-onset diabetes mellitus, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure.

[0272] 30. The method of claim 29, wherein the amyloid beta-associated disease, disorder, or condition is Alzheimer's disease (AD), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cerebral amyloid angiopathy (CAA), myotonic dystrophy, or Lewy body disease.

[0273] 31. The method according to item 29 or 30, wherein the amyloid beta-related disease, disorder or condition is Alzheimer's disease (AD).

[0274] 32. The method of item 29 or 30, wherein the amyloid beta-related disease, disorder or condition is Down's syndrome (DS).

[0275] 33. A diagnostic composition comprising the amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 18, and an acceptable carrier and / or excipient.

[0276] 34. A nucleic acid encoding the amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 18.

[0277] 35. A nucleic acid comprising the nucleotide sequence provided in SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, or SEQ ID NO:55.

[0278] 36. A recombinant vector comprising the nucleic acid of paragraph 34 or 35.

[0279] 37. A host cell comprising a nucleic acid according to paragraph 34 or 35 and / or a vector according to paragraph 36.

[0280] 38. An isolated host cell expressing the amyloid beta-binding antibody or antigen-binding fragment of any one of paragraphs 1 to 18.

[0281] 39. A method for producing an amyloid beta-binding antibody or antigen-binding fragment thereof, comprising: a. Culturing the host cell of paragraph 37 or paragraph 38 under conditions suitable for producing an amyloid beta-binding antibody or antigen-binding fragment thereof, and then b. Recovering the amyloid beta-binding antibody or antigen-binding fragment thereof. A method comprising:

[0282] 40. A kit for diagnosing a disease, disorder or condition associated with amyloid beta, or a kit for use in a method according to any one of items 19 to 32, comprising an amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 18.

[0283] 41. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of paragraphs 1 to 18 for research use, in particular as an analytical tool or reference molecule.

[0284] 42. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of paragraphs 1 to 18, for use in detecting amyloid beta aggregates, including plaques, in vitro or in vivo.

[0285] 43. An amyloid beta-binding antibody or antigen-binding fragment thereof for use according to item 42, for histochemical detection in brain tissue.

[0286] Brief explanation of figures and tables Figure 1. ACI-24-41F12-Ab3 (mouse IgG2a isotype) binds to Abeta 1-42 with a Kd of 66 pM. No binding to BSA protein was observed. Data are expressed as OD and shown as the mean ± SD of one duplicate determination. Figure 2. Antibody ACI-31-25B1-Ab2 (mouse IgG2a isotype) binds to Abeta 1-42 with a Kd of 41 pM. No binding to BSA protein was observed. Data are expressed as OD. Figure 3. Antibody ACI-31-30C11-Ab1 (mouse IgG2a isotype) binds to Abeta 1-42 with a Kd of 196 pM. No binding to BSA protein was observed. Data are expressed as OD. Figure 4. Antibody ACI-31-25B1-Ab2 (mouse IgG2a isotype) captures soluble Abeta 1-42 with a Kd of 312 pM. Data are expressed as OD. Figure 5. Antibody ACI-8041-1F11B5-Ab1 (mouse IgG2a isotype) captures soluble Abeta 1-42 with a Kd of 343 pM. Data are expressed as OD. Figure 6. Antibody ACI-8041-9D7E1-Ab1 (mouse IgG2a isotype) captures soluble Abeta 1-42 with a Kd of 1.1 nM. Data are expressed as OD. Figure 7. Antibody ACI-8041-10H3B11-Ab1 (mouse IgG2a isotype) captures soluble Abeta 1-42 with a Kd of 2.6 nM. Data are expressed as OD. Figure 8. A) Indirect ELISA comparing the binding of each antibody, ACI-24-41F12-Ab3 (mouse IgG2a isotype) and ACI-31-25B1-Ab2 (mouse IgG2a / lambda isotype), to sAPP alpha, normalized to Abeta 1-42 binding. Scrambled Abeta 1-42 was used as a control and showed no binding. Antibody ACI-24-41F12-Ab3 shows binding to sAPP alpha, while no binding is observed with antibody ACI-31-25B1-Ab2. B) Sandwich pairing of antibodies ACI-24-41F12-Ab3 (detection) and ACI-31-25B1-Ab2 (capture) detects soluble Abeta 1-42 with a Kd of 9.7 nM, demonstrating selectivity for Abeta 1-42 over scrambled Abeta 1-42 or sAPP alpha. Data are expressed as OD or as % of Abeta 1-42 binding.

[0287] Table 1. Abeta 1-42 binding regions and epitopes and their interaction with sAPP alpha. Table 2. Nucleotide sequences of the heavy and light chain variable domains (VH and VL). Table 3. Amino acid sequences of the heavy and light chain variable domains (VH and VL). Table 4. Amino acid sequences of the variable and constant regions of the heavy chain (HC) and light chain (LC). Table 5. Amino acid sequences of the heavy chain (HC) and light chain (LC) constant regions.

[0288] The invention will now be further described with reference to the following non-limiting examples. [Example]

[0289] method Example 1. Antibody generation 1.1. Preparation of Abeta liposomal vaccine composition Liposome-based antigen constructs were prepared according to the protocol published in WO2012 / 055933. A liposome vaccine containing tetrapalmitoylated human Abeta 1-15 peptide as the antigen was used to generate antibodies ACI-24-41F12-Ab2 (mouse IgG2b) and ACI-24-41F12-Ab3 (mouse IgG2a isotype and chimeric mouse / human IgG1 isotype), and a tetrapalmitoylated human Abeta 22-35 peptide as the antigen was used to generate antibodies ACI-31-25B1-Ab2 (mouse IgG2b / lambda, mouse I). ACI-8037-103H5-Ab2 (mouse IgG2a) and ACI-8037-109F4-Ab1 (mouse IgG2a) were used to generate ACI-8037-103H5-Ab2 (mouse IgG2a) and ACI-8037-109F4-Ab1 (mouse IgG2a) with tetrapalmitoylated human Abeta 5-23 peptide as antigen. Tetrapalmitoylated human Abeta 10-29 peptide was used as the antigen to generate ACI-8039-306H5-Ab1 (mouse IgG2a), ACI-8039-307F7-Ab2 (mouse IgG2a), and ACI-8039-309D9-Ab2 (mouse IgG2a). ACI-8041-1F11B5-Ab1 (mouse IgG2a), ACI-8041-2B9H5-Ab1 (mouse IgG2a), ACI-8041-3G11B3 The vaccines were used to generate ACI-8041-Ab1 (mouse IgG2a), ACI-8041-4G6D2-Ab1 (mouse IgG2a), ACI-8041-5A2D4-Ab1 (mouse IgG2a), ACI-8041-5A6H9-Ab1 (mouse IgG2a), ACI-8041-6C3C4-Ab1 (mouse IgG2a), ACI-8041-9D7E1-Ab1 (mouse IgG2a), and ACI-8041-10H3B11-Ab1 (mouse IgG2a). Mice (C57BL / 6, 9-week-old, female) were injected subcutaneously (sc) three times with a 2-week interval between each immunization (days 0, 14, and 28). Blood samples were collected and plasma prepared 7 days before the first immunization and 7 days after each immunization (days 7, 21, and 35).After the final blood draw, mice were selected based on their vaccine response, and spleen cells were used for fusion with mouse myeloma cells 65 days after the start of the study. Hybridomas that bound to the target were selected and subcloned to obtain monoclonal antibodies. These antibodies were then ranked for target binding properties, and hybridoma clones were selected for sequencing and recombinant antibody production. The following data describe the properties of ACI-24-41F12-Ab2 (a hybridoma-derived mouse IgG2b / kappa antibody), as well as a recombinant mouse IgG2a / kappa antibody (hereafter referred to as ACI-24-41F12-Ab3 (IgG2a isotype)) and a recombinant chimeric mouse / human IgG1 isotype (hereafter referred to as ACI-24-41F12-Ab3 (hIgG1 isotype)) with identical variable heavy (VH) and light (VL) chain sequences and binding properties to ACI-24-41F12-Ab2 (data not shown). The following data are representative of ACI-31-25B1-Ab2 in the form of murine IgG2a / lambda, as well as ACI-31-30C11-Ab1, ACI-8037-103H5-Ab2, ACI-8037-109F4-Ab1, ACI-8039-306H5-Ab1, ACI-8039-307F7-Ab2, ACI-8039-309D9-Ab2, and ACI-8039-309E9-Ab2, which have murine IgG2a isotype constant region heavy chains and kappa constant region light chains. Some properties of ACI-8041-1F11B5-Ab1, ACI-8041-2B9H5-Ab1, ACI-8041-3G11B3-Ab1, ACI-8041-4G6D2-Ab1, ACI-8041-5A2D4-Ab1, ACI-8041-5A6H9-Ab1, ACI-8041-6C3C4-Ab1, ACI-8041-9D7E1-Ab1, and ACI-8041-10H3B11-Ab1 are further described (Table 5).

[0290] Example 2. Preparation of Abeta 1-42 for assay Abeta 1-42 lyophilized powder (Bachem) was reconstituted to 1 mM with hexafluoroisopropanol (HFIP, Sigma). The peptide solution was sonicated at room temperature for 15 minutes, stirred overnight, and then aliquots were placed in non-siliconized microcentrifuge tubes. The HFIP was then evaporated under a stream of argon. The resulting peptide films were vacuum dried for 10 minutes and stored at -80°C until use. Alternatively, a biotinylated form of Abeta 1-42 peptide was used to assay target capture in solution. This was prepared in a similar manner as described above.

[0291] Example 3. Target Binding Antibody-target binding was assessed by enzyme-linked immunosorbent assay (ELISA). Briefly, Nunc MaxiSorp 96-well plates (Nunc) were coated with 50 μL of 10 μg / mL Abeta 1-42 or bovine serum albumin (BSA, Sigma) diluted in PBS for 18 hours at 4°C. In selected assays, full-length sAPP alpha fragment (Sigma) was additionally included by coating the wells as described above, except at 4 μg / mL (0.04 μM). The plates were then washed four times with 300 μL of PBS containing 0.05% Tween 20 (Millipore). To block nonspecific binding to the plates, a freshly prepared solution of 0.05% Tween 20 and 1% BSA in PBS was added to each well (100 μL / well), and the plates were incubated at 37°C for 1 hour. The primary antibody was diluted to 100 nM in PBS containing 1% BSA and 0.05% Tween 20 and serially diluted three-fold twice. 50 μL of the solution was added to the plate at 50 μL per well and incubated at 37°C for 1 hour. The plate was then washed four times with 300 μL of PBS containing 0.05% Tween 20. The plate was then incubated with horseradish peroxidase (HRP)-conjugated goat anti-mouse secondary IgG (Abcam) for 1 hour at 37°C. After a final washing step (four times with 300 μL of PBS containing 0.05% Tween 20), the plate was incubated with 3,3',5,5'-tetramethylbenzidine (TMB) substrate (BD Biosciences), and the reaction was stopped with stop solution (Sigma). Finally, the optical density (OD) was read at an absorbance wavelength of 450 nm using a Tecan Infinite plate reader. Measurements are expressed as the mean OD from duplicate determinations ± 1 mean standard deviation (SD).

[0292] Binding of antibodies ACI-24-41F12-Ab3 (recombinant mouse IgG2a isotype, also known as ACI-24-41F12-Ab3-rec1), ACI-31-25B1-Ab2 (mouse IgG2a / lambda isotype), and ACI-31-30C11-Ab1 (mouse IgG2a isotype) to Abeta 1-42 was assessed using an ELISA assay. Antibody ACI-24-41F12-Ab3 bound to Abeta 1-42 with a Kd of 66 pM, and no cross-reactivity was observed with BSA at the same protein concentration (Figure 1). The assay was repeated at least four times independently with comparable results. Antibody ACI-31-25B1-Ab2 bound to Abeta 1-42 with a Kd of 41 pM (Fig. 2), and antibody ACI-31-30C11-Ab1 bound with a Kd of 196 pM (Fig. 3), showing no cross-reactivity to BSA.

[0293] Using ELISA target capture assay, the binding of antibodies ACI-31-25B1-Ab2, ACI-8041-1F11B5-Ab1, ACI-8041-9D7E1-Ab1 and ACI-8041-10H3B11-Ab1 to Abeta 1-42 in solution was further evaluated as an indicator of soluble target capture in biological fluids. Briefly, Nunc MaxiSorp 96-well plates (Nunc) were coated with 50 μL of 5 μg / mL goat anti-mouse IgG, Fc-gamma fragment specific antibody (Jackson Immune Research) diluted in carbonate-bicarbonate buffer for 18 hours at 4 ° C. The plates were then washed four times with 300 μL of PBS containing 0.05% Tween 20 (Millipore). To block nonspecific binding to the plate, a freshly prepared solution of 0.05% Tween 20 and 1% BSA in PBS was added to each well (100 μL / well), and the plate was incubated at 37°C for 1 hour. The primary antibody was diluted to 5 μg / mL (33.3 nM) in PBS containing 1% BSA and 0.05% Tween 20, and 50 μL / well was added to each well. The plate was incubated at 37°C for 1 hour. The plate was then washed four times with 300 μL of PBS containing 0.05% Tween 20. Human Abeta 1-42, whose peptide C-terminus was biotinylated, was diluted to 10 μg / mL (2.2 μM) in PBS containing 1% BSA and 0.05% Tween 20, followed by three-fold serial dilutions. 50 μL was added to each well, and the plate was incubated at 37°C for 1 hour. After washing four times with 300 μL of PBS containing 0.05% Tween 20, the plate was incubated with 50 μL / well of streptavidin-HRP (R&D Systems) diluted 1:200 in PBS containing 1% BSA and 0.05% Tween 20 for 45 minutes at ambient temperature. The plate was again washed four times with 300 μL of PBS containing 0.05% Tween 20 and then incubated with 50 or 100 μL / well of 3,3',5,5'-tetramethylbenzidine (TMB) enzyme substrate (BD Bioscience) for 20 or 30 minutes at ambient temperature. The reaction was stopped with 1.2 M HCl (Sigma) solution.Finally, optical density (OD) was read at an absorbance wavelength of 450 nm using a Tecan Infinite plate reader. Measurements are expressed as OD. Antibody ACI-31-25B1-Ab2 captured Abeta 1-42 with a Kd of 312 pM in solution (Figure 4), antibody ACI-8041-1F11B5-Ab1 captured Abeta 1-42 with a Kd of 343 pM in solution (Figure 5), antibody ACI-8041-9D7E1-Ab1 captured Abeta 1-42 with a Kd of 1.1 nM in solution (Figure 6), and antibody ACI-8041-10H3B11-Ab1 captured Abeta 1-42 with a Kd of 2.6 nM in solution (Figure 7). Antibodies ACI-24-41F12-Ab3, ACI-31-30C11-Ab1, ACI-8037-103H5-Ab2, ACI-8037-109F4- Ab1, ACI-8039-306H5-Ab1, ACI-8039-307F7-Ab2, ACI-8039-309D9-Ab2, ACI-8041-2 B9H5-Ab1, ACI-8041-3G11B3-Ab1, ACI-8041-4G6D2-Ab1, ACI-8041-5A2D4-Ab1, ACI-8041-5A6H9-Ab1, and ACI-8041-6C3C4-Ab1 also captured Abeta 1-42 in solution (data not shown).

[0294] Additionally, selected antibodies were assayed to confirm their binding and selectivity for Abeta 1-42 using paired or sandwich ELISA. Briefly, Nunc MaxiSorp 96-well plates (Nunc) were coated with 50 μL of 5 μg / mL capture antibody diluted in carbonate-bicarbonate buffer for 18 hours at 4°C. Plates were then washed and blocked as described in the previous paragraph. Subsequently, analyte proteins were diluted in PBS containing 1% BSA and 0.05% Tween 20 to 666 nM for Abeta 1-42 (Bachem) and scrambled Abeta 1-42 (Anaspec) and 165 nM for sAPP alpha (Sigma), followed by three-fold serial dilutions, and 50 μL was added to each well. The plates were incubated for 2 hours at 37° C., washed as before, and incubated for 1 hour at 37° C. with 50 μL / well of biotinylated detection antibody diluted to 2 μg / mL in PBS containing 1% BSA and 0.05% Tween 20. The subsequent steps were identical to those described in the previous paragraph for Abeta 1-42 target capture, except that the incubation with TMB was performed at 100 μL / well for 30 minutes.

[0295] Sandwich ELISAs performed with selected antibody pairs detected Abeta 1-42 in solution with Kds in the 100 pM range. Figure 8A shows the results of an example sandwich ELISA using antibody ACI-24-41F12-Ab3, an N-terminal Abeta 1-42 binder that cross-reacts with sAPP alpha, and one mid-domain binder that does not bind to sAPP alpha. This demonstrates assay selectivity for soluble Abeta 1-42 over sAPP alpha, with a Kd of 9.7 nM for soluble Abeta 1-42 (Figure 8B). The sandwich pairing of antibodies ACI-24-41F12-Ab3 (detection) and ACI-31-25B1-Ab2 (capture) detects soluble Abeta 1-42. Furthermore, selectivity for soluble Abeta 1-42 was further confirmed by the complete absence of signal when scrambled Abeta 1-42, consisting of all 42 amino acids identical to those present in the human Abeta 1-42 peptide, was used as the assay analyte.

[0296] Example 4. Epitope mapping Epitope mapping of ACI-24-41F12-Ab2, ACI-31-25B1-Ab2, and ACI-31-30C11-Ab1 was performed by ELISA using a peptide library spanning the amino acid sequence of Abeta 1-42 (Mimotopes Ltd., Melbourne, Australia), consisting of 33 overlapping biotinylated peptides of 8, 9, or 10 residues each. Biotinylated Abeta 1-42 (Bachem) was used as a control peptide. Epitope mapping ELISA was performed according to the manufacturer's instructions. Briefly, streptavidin-coated plates (Nunc) were blocked with 0.1% BSA in PBS for 18 hours at 4°C on a horizontal shaker at 50 rpm. After washing with PBS containing 0.05% Tween 20, plates were coated with each peptide from the library, diluted to a final concentration of 10 μM in 0.1% BSA containing 0.1% sodium azide in PBS, for 1 hour at ambient temperature. After washing, plates were incubated with ACI-24-41F12-Ab2, ACI-31-25B1-Ab2, or ACI-31-30C11-Ab1 diluted to 1 μg / mL in 2% BSA containing 0.1% sodium azide in PBS for 1 hour at ambient temperature. Plates were washed again and incubated with alkaline phosphatase (AP)-conjugated goat anti-mouse IgG (Jackson Immune Research) for 1 hour at ambient temperature. After a final wash, plates were incubated with phosphatase substrate (pNPP, Sigma) for 2 hours, and absorbance was read at 405 nm using a plate reader (Tecan).

[0297] To determine the epitopes of ACI-24-41F12-Ab2 and ACI-31-25B1-Ab2, binding of the antibodies to 33 overlapping 8-, 9-, or 10-mer peptides covering the entire Abeta 1-42 sequence was analyzed by ELISA using streptavidin plates and terminally biotin-labeled peptides (Table 1). When the epitope was not mapped, the binding region was examined using the same assay as above, except that target peptides corresponding to different vaccine antigen sequences used to generate the antibodies were used. Binding to full-length Abeta 1-42 was used as a positive control. The epitope of ACI-24-41F12-Ab2 was mapped to the N-terminal region and identified as being within residues 1-8 of the Abeta 1-42 peptide sequence (more precisely, within amino acid residues 1-5, with amino acids 1 and 2 of Abeta 1-42 being essential for antibody binding). The epitope of ACI-31-25B1-Ab2 was mapped to the mid-domain region and identified as being within residues 22-35 of the Abeta 1-42 peptide sequence, more precisely, within amino acid residues 26-34 (Table 1). The Abeta 1-42 binding region is also essential for antibody binding to the Abeta 1-42 peptide sequence (ACI-8037-103H5-Ab2 and ACI-8037-109F4-Ab1), Abeta 1-5, ACI-8039-306H5-Ab1, ACI-8039-307F7-Ab2, ACI-8039-309D9-Ab2, ACI-8041-1F11B5-Ab1, ACI-8041-2B9H5-Ab1, and ACI-8041-3G11B. For ACI-3-Ab1, ACI-8041-4G6D2-Ab1, ACI-8041-5A2D4-Ab1, ACI-8041-5A6H9-Ab1, ACI-8041-6C3C4-Ab1, ACI-8041-9D7E1-Ab1, and ACI-8041-10H3B11-Ab1, the cross-reactivity was Abeta 17-23, and for ACI-31-30C11-Ab1, the cross-reactivity was Abeta 22-35. Cross-reactivity to sAPP alpha, which shares an identical amino acid sequence with human Abeta 1-42 between residues 1 and 16, is further shown in Table 1.Cross-reactivity was determined for antibodies ACI-24-41F12-Ab2, ACI-8037-103H5-Ab2, and ACI-8037-109F4-Ab1. Antibodies ACI-31-25B1-Ab2, ACI-31-30C11-Ab1, ACI-8039-306H5-Ab1, ACI-8039-307F7-Ab2, ACI-8039-309D9-Ab2, ACI-8041-1F11B5-Ab1, ACI-8041-2B9H5-Ab1, and ACI-8041-3 The cross-reactivity of G11B3-Ab1, ACI-8041-4G6D2-Ab1, ACI-8041-5A2D4-Ab1, ACI-8041-5A6H9-Ab1, ACI-8041-6C3C4-Ab1, ACI-8041-9D7E1-Ab1, and ACI-8041-10H3B11-Ab1 was not determined.

[0298] Table 1. Abeta 1-42 binding regions and epitopes and their interaction with sAPP alpha: [Table 2]

[0299] Example 5. Sequencing of antibody variable region genes Murine hybridoma cells were harvested and lysed using a lysis buffer containing guanidinium salts to inactivate RNases. Genomic DNA was then removed by adding RNase-free DNase to the sample. After cell disruption and genomic DNA removal, the RNA was purified using a silica-based affinity column with multiple washes and eluted from the column with RNase-free water. Once extracted, its purity and concentration were measured spectrophotometrically. The integrity of the RNA was assessed using a denaturing agarose gel, and the RNA was reverse transcribed into cDNA using reverse transcriptase (RT). Before adding the reaction mixture, the RNA was heated at 70°C for 10 minutes to disrupt the secondary structure of the RNA. The RT product was used directly for PCR amplification. For high-fidelity PCR amplification of cDNA, variable region primers corresponding to different antibody-encoding gene families were mixed with constant primers for the variable heavy (VH) and variable light (VL) domains, respectively. First, a degenerate primer pool (12 for VH and 12 for VL) was used, and depending on the results, a second pool was used to obtain PCR products. After the PCR reaction, the products were analyzed by gel electrophoresis on a 2% agarose gel stained with ethidium bromide. The PCR products for VL and VH were purified from agarose gels using Tris-acetate-EDTA (TAE), respectively. The purified fragments excised from the gel were then sequenced using dye-terminator sequencing. The same primers used for PCR were used in the sequencing reaction. Sequencing was performed in both directions, overlapping at both ends. Sequencing data was analyzed using the Ig Blast / Kabat database. The nucleotide sequences of VH and VL are shown in Table 2. The protein sequences of VH and VL and their complementarity-determining regions (CDRs) are shown in Table 3. The protein sequences of the HC and LC of mouse IgG2b, mouse IgG2a, and mouse / human chimeric IgG1 are shown in Table 4.

[0300] Table 2. Nucleotide sequences of heavy and light chain variable domains (VH and VL) [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] TIFF2025178565000007.tif15155

[0301] Table 3. Amino acid sequences of heavy and light chain variable domains (VH and VL) [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4] [Table 4-5] [Table 4-6]

[0302] Table 4. Amino acid sequences of the variable and constant regions of the heavy (HC) and light (LC) chains [Table 5-1] [Table 5-2] [Table 5-3]

[0303] Table 5. Amino acid sequences of the heavy chain (HC) and light chain (LC) mouse IgG2a / kappa isotype constant regions. [Table 6]

[0304] Aspects of the present invention are further described in the following sections: [Section 1] a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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; c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; VH-CDR3 comprising the amino acid sequence of 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; d) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 63; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; e) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; f) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87; g) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92; VH-CDR3 comprising the amino acid sequence of 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; h) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103; 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; i) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112; VH-CDR3 comprising the amino acid sequence of 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: 116; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117; j) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 121; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 122; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 123; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 125; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 127; k) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 131; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 132; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 135; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137; l) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137; m) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157; n) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 166; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167; o) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172; VH-CDR3 comprising the amino acid sequence of 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: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157; p) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187; or q) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197. 1. An amyloid beta-binding antibody or antigen-binding fragment thereof, comprising: [Section 2] the antibody or antigen-binding fragment thereof a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80; g) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence 90 of SEQ ID NO: 90; h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120; k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 or having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; or p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; Item 1. The amyloid beta-binding antibody or antigen-binding fragment thereof according to item 1. [Section 3] the antibody or antigen-binding fragment thereof a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44; d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64; e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 74; or a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84; f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 90; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; g) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104; h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114; i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 124; j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 or having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134; k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144; l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 164; n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174; o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184; or p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194. 3. The amyloid beta-binding antibody or antigen-binding fragment thereof according to item 1 or 2. [Section 4] the antibody or antigen-binding fragment thereof a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; 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: 34; c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44; d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64; e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74; f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84; g) 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; h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104; i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114; j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124; k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134; l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144; m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154; n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164; o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174; p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184; or q) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194 5. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 4. [Section 5] The antibody a) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 20 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 21; b) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 22 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 23; c) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 24 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 25; d) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 27 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 28; e) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 38 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 39; f) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 48 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 49; g) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 50 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 51; h) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 56 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 57; or i) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 58 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 59 5. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 4. [Section 6] 6. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 5, which selectively binds to or captures amyloid beta peptides or species in solution, regardless of the conformational state of the amyloid beta peptides or species. [Section 7] The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 6 above, which binds to an epitope within amino acid residues 1 to 5 (SEQ ID NO: 7), 1 to 8 (SEQ ID NO: 2), 17 to 23 (SEQ ID NO: 9), 22 to 35 (SEQ ID NO: 29), or 26 to 34 (SEQ ID NO: 8) of SEQ ID NO: 1, or an equivalent epitope in non-human amyloid beta. [Section 8] 8. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 7, which is a mouse, chimeric, humanized or human antibody, or an antigen-binding fragment thereof. [Section 9] 9. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 8, which is an IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3 or IgG4 antibody, or an antigen-binding fragment thereof. [Section 10] 10. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 9, which is conjugated to another molecule, particularly a detectable label. [Section 11] 11. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 10, for use in diagnosing amyloid beta-related disease, disorder or condition in a subject. [Section 12] 12. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 11, for use in detecting amyloid beta in a biological sample. [Section 13] Item 13. The amyloid beta-binding antibody or antigen-binding fragment thereof according to Item 12, wherein the biological sample is a body fluid sample or a buffer solution. [Section 14] 14. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 13, for use in detecting amyloid beta in a body fluid sample, wherein the body fluid sample is saliva, urine, nasal secretions, blood (whole blood, plasma, and serum, preferably including plasma), a brain and / or CSF sample, a brain and / or ISF sample, more specifically a blood, brain, CSF, and / or ISF sample. [Section 15] 15. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 14 above, for use in diagnosing amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is selected from the group consisting of Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), Lewy body disease, amyotrophic lateral sclerosis (ALS), adult-onset diabetes mellitus, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure. [Section 16] 16. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 15, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Alzheimer's disease (AD), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cerebral amyloid angiopathy (CAA), myotonic dystrophy, or Lewy body disease. [Section 17] 17. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 16, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Alzheimer's disease (AD). [Section 18] 17. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 16, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Down's syndrome (DS). [Section 19] 17. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 16, for use in diagnosing an amyloid beta-associated disease, disorder or illness, wherein the amyloid beta-associated disease, disorder or illness is Down's syndrome-associated Alzheimer's disease. [Section 20] A method for detecting amyloid beta in a sample obtained from a subject, the method comprising contacting the sample with the amyloid beta-binding antibody or antigen-binding fragment thereof described in any one of items 1 to 19 above, and then detecting binding of the antibody or antigen-binding fragment thereof to detect amyloid beta in the sample. [Section 21] A method for quantifying amyloid beta in a sample obtained from a subject, comprising contacting the sample with an amyloid beta-binding antibody or antigen-binding fragment thereof described in any one of items 1 to 19, and then quantifying amyloid beta in the sample based on the level of binding of the antibody or antigen-binding fragment thereof to amyloid beta. [Section 22] 22. A method for diagnosing amyloid beta-associated diseases, disorders and / or conditions, comprising carrying out the method described in paragraph 20 or 21 above, wherein a high level of amyloid beta in the sample compared to a control level based on a healthy subject indicates amyloid beta-associated diseases, disorders and / or conditions. [Section 23] 22. A method for diagnosing amyloid beta-related diseases, disorders and / or conditions, comprising carrying out the method described in paragraph 20 or 21 above, wherein an identical or higher level of amyloid beta in the sample compared to a diseased control level indicates amyloid beta-related diseases, disorders and / or conditions. [Section 24] 1. A method for classifying amyloid beta-related diseases, disorders and / or conditions, comprising: a. Carrying out the method described in paragraphs 22 and / or 23 above, b. Classifying amyloid-beta-related diseases, disorders, and / or conditions A method comprising: [Section 25] 20. A method for monitoring amyloid beta-related diseases, disorders and / or conditions at two or more time points using a sample from a subject, the method comprising contacting the sample with the amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of paragraphs 1 to 19 above; a. A higher level of amyloid beta in a subsequent sample compared to one or more previous samples is indicative of the progression of an amyloid beta-related disease, disorder, and / or condition; b. a lower level of amyloid beta in the subsequent sample compared to one or more previous samples indicates regression of the amyloid beta-related disease, disorder, and / or condition; and / or c. A method wherein the absence of a significant change in the level of amyloid beta in a subsequent sample compared to one or more previous samples indicates the absence of progression of a disease, disorder and / or condition associated with amyloid beta. [Section 26] A method for selecting a therapy for treating a disease, disorder and / or condition associated with amyloid beta, comprising contacting samples collected before and after treatment with the therapy with the amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 19; a. a lower level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates successful treatment of the disease, disorder, and / or condition associated with amyloid beta, thereby selecting the therapy for treatment; b. no significant change in the level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates successful treatment of the disease, disorder, and / or condition associated with amyloid beta, thereby selecting the therapy for treatment; c. a decrease in the rate of increase in the level of amyloid beta between samples taken during treatment compared to said sample taken before treatment indicates successful treatment of the disease, disorder, and / or condition associated with amyloid beta, thereby selecting said therapy for treatment; d. A higher level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates failure of treatment of an amyloid beta-related disease, disorder, and / or condition, whereby the therapy is not selected for treatment; or e. A method wherein a failure to reduce the rate of increase in amyloid beta levels between samples taken during treatment compared to said samples taken before treatment indicates failure of treatment for amyloid beta-related diseases, disorders and / or conditions, whereby said therapy is not selected for treatment. [Section 27] A method for evaluating a candidate treatment for amyloid beta-associated diseases, disorders and / or conditions, comprising, after treatment of one or more subjects, contacting a sample from one or more treated subjects with the antibody or antigen-binding fragment of any one of paragraphs 1 to 19, wherein a lower level of amyloid beta in the sample compared to the level in a corresponding sample from a subject not treated with the treatment indicates successful treatment of the amyloid-associated disease, disorder and / or condition. [Section 28] 28. The method of paragraph 27 above, performed at multiple time points in matched samples between treatment and placebo groups to monitor the effectiveness of the candidate treatment over time. [Section 29] The method of paragraph 27 or 28, comprising contacting samples from one or more treated subjects and a subject not treated with the therapy with the antibody or antigen-binding fragment of any one of paragraphs 1 to 19 before treatment with the therapy or a placebo, respectively, to determine basal levels of amyloid beta. [Section 30] 30. The method according to any one of items 20 to 29, wherein the amyloid beta-related disease, disorder and / or condition is selected from the group consisting of Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), Lewy body disease, amyotrophic lateral sclerosis (ALS), adult-onset diabetes mellitus, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure. [Section 31] 31. The method according to claim 30, wherein the amyloid beta-related disease, disorder or condition is Alzheimer's disease (AD), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cerebral amyloid angiopathy (CAA), myotonic dystrophy, or Lewy body disease. [Section 32] 32. The method according to item 30 or 31, wherein the amyloid beta-related disease, disorder or condition is Alzheimer's disease (AD). [Section 33] 32. The method according to item 30 or 31, wherein the disease, disorder or condition associated with amyloid beta is Down's syndrome (DS). [Section 34] 20. A diagnostic composition comprising the amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 19 above, and an acceptable carrier and / or excipient. [Section 35] 20. A nucleic acid encoding the amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 19. [Section 36] A nucleic acid comprising a nucleotide sequence as provided in SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:188, SEQ ID NO:189, or SEQ ID NO:199. [Section 37] 37. A recombinant vector comprising the nucleic acid according to item 35 or 36. [Section 38] A host cell comprising the nucleic acid according to paragraph 35 or 36 and / or the recombinant vector according to paragraph 37. [Section 39] 20. An isolated host cell expressing the amyloid beta-binding antibody or antigen-binding fragment according to any one of items 1 to 19. [Section 40] 1. A method for producing an amyloid beta binding antibody or antigen-binding fragment thereof, comprising: a. culturing the host cell of paragraph 38 or 39 under conditions suitable for producing an amyloid beta-binding antibody or antigen-binding fragment thereof, and b. Recovering the amyloid beta-binding antibody or antigen-binding fragment thereof A method comprising the steps of: [Section 41] A kit for diagnosing a disease, disorder or illness associated with amyloid beta, comprising the amyloid beta-binding antibody or antigen-binding fragment thereof described in any one of items 1 to 19 above and a container, or a kit for use in the method described in any one of items 20 to 33 above. [Section 42] 20. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 19, for research use, particularly as an analytical tool or reference molecule. [Section 43] 20. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of items 1 to 19, for use in detecting amyloid beta aggregates, including plaques, in vitro or in vivo. [Section 44] Item 44. The amyloid beta-binding antibody or antigen-binding fragment thereof according to Item 43, which is used for histochemical detection in brain tissue. [Section 45] A diagnostic composition comprising at least two amyloid beta-binding antibodies or antigen-binding fragments thereof according to any one of items 1 to 19 above, and an acceptable carrier and / or excipient. [Section 46] The diagnostic composition described in paragraph 45 above, wherein the two amyloid beta-binding antibodies or antigen-binding fragments selectively bind to or capture any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species, and at least one of the two amyloid beta-binding antibodies or antigen-binding fragments does not exhibit cross-reactivity with soluble APP alpha. [Section 47] A diagnostic composition comprising two amyloid beta-binding antibodies or antigen-binding fragments, the diagnostic composition comprising a first amyloid beta-binding antibody or antigen-binding fragment thereof described in any one of items 1 to 19 above, a second amyloid beta-binding antibody or antigen-binding fragment thereof that is not an antibody described in any one of items 1 to 19 above, and an acceptable carrier and / or excipient. [Section 48] 48. A diagnostic composition comprising at least two amyloid beta-binding antibodies or antigen-binding fragments thereof according to paragraph 46 or 47, and an acceptable carrier and / or excipient, wherein at least one or two of the amyloid beta-binding antibodies or antigens are: a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and / or c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157. A diagnostic composition selected from: [Section 49] 48. A diagnostic composition comprising at least two amyloid beta-binding antibodies or antigen-binding fragments thereof according to paragraph 46 or 47, and an acceptable carrier and / or excipient, wherein at least one or two of the amyloid beta-binding antibodies or antigens are: a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; and b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 co...

Claims

1. a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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; c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42; VH-CDR3 comprising the amino acid sequence of 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; d) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 63; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; e) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; f) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87; g) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:91; VH-CDR2 comprising the amino acid sequence of SEQ ID NO:92; VH-CDR3 comprising the amino acid sequence of 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; h) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 101; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 102; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 103; 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; i) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 115; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 116; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 117; j) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 121; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 122; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 123; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 125; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 127; k) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 131; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 132; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 135; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137; l) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 141; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137; m) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157; n) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 165; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 166; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 167; o) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172; VH-CDR3 comprising the amino acid sequence of 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: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157; p) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187; or q) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197 1. An amyloid beta-binding antibody or antigen-binding fragment thereof, comprising:

2. the antibody or antigen-binding fragment thereof a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80; g) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence 90 of SEQ ID NO: 90; h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120; k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 or having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; or p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; The amyloid beta-binding antibody or antigen-binding fragment thereof of claim 1, comprising:

3. the antibody or antigen-binding fragment thereof a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; b) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30 or having at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 34 or having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44; d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 64; e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 or a heavy chain variable region (VH) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74 or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 74; or a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 or a heavy chain variable region (VH) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 80; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84; f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 90 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 90; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 94 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; g) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104; h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114; i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 124; j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134; k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 or a heavy chain variable region (VH) having at least 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144; l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 150; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154 or having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 or having at least 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164 or having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 164; n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 or having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174; o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184; or p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; and a light chain variable region (VL) comprising the sequence of SEQ ID NO:

194. The amyloid beta-binding antibody or antigen-binding fragment thereof of claim 1 or 2, comprising:

4. the antibody or antigen-binding fragment thereof a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 14; 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: 34; c) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 44; d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 64; e) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 70 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 74; f) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 80 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 84; g) 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; h) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 100 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 104; i) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 110 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 114; j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 120 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 124; k) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 130 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 134; l) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 140 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 144; m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 154; n) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 160 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 164; o) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 170 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 174; p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 184; or q) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 180 and a light chain variable region (VL) comprising the sequence of SEQ ID NO: 194; The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, comprising:

5. The antibody a) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 20 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 21; b) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 22 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 23; c) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 24 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 25; d) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 27 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 28; e) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 38 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 39; f) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 48 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 49; g) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 50 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 51; h) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 56 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 57; or i) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 58 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 59; The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, comprising:

6. 6. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, which selectively binds to or captures amyloid beta peptides or species in solution, regardless of the conformational state of the amyloid beta peptides or species.

7. 7. The amyloid beta-binding antibody or antigen-binding fragment thereof of any one of claims 1 to 6, which binds to an epitope within amino acid residues 1 to 5 (SEQ ID NO:7), 1 to 8 (SEQ ID NO:2), 17 to 23 (SEQ ID NO:9), 22 to 35 (SEQ ID NO:29) or 26 to 34 (SEQ ID NO:8) of SEQ ID NO:1, or an equivalent epitope in non-human amyloid beta.

8. The amyloid beta-binding antibody or antigen-binding fragment thereof of any one of claims 1 to 7, which is a murine, chimeric, humanized or human antibody, or antigen-binding fragment thereof.

9. 9. The amyloid beta-binding antibody or antigen-binding fragment thereof of any one of claims 1 to 8, which is an IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3 or IgG4 antibody, or an antigen-binding fragment thereof.

10. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, conjugated to another molecule, in particular a detectable label.

11. 11. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 10 for use in diagnosing an amyloid beta-related disease, disorder or condition in a subject.

12. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 11 for use in detecting amyloid beta in a biological sample.

13. The amyloid beta-binding antibody or antigen-binding fragment thereof of claim 12, wherein the biological sample is a body fluid sample or a buffer solution.

14. 14. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 13, for use in detecting amyloid beta in a body fluid sample, wherein the body fluid sample is saliva, urine, nasal secretions, blood (including whole blood, plasma and serum, preferably plasma), a brain and / or CSF sample, a brain and / or ISF sample, more particularly a blood, brain, CSF and / or ISF sample.

15. 15. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 14, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is selected from the group consisting of Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), Lewy body disease, ALS (amyotrophic lateral sclerosis), adult-onset diabetes mellitus, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure.

16. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 15, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Alzheimer's disease (AD), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cerebral amyloid angiopathy (CAA), myotonic dystrophy, or Lewy body disease.

17. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Alzheimer's disease (AD).

18. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Down's syndrome (DS).

19. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, for use in diagnosing an amyloid beta-associated disease, disorder or condition, wherein the amyloid beta-associated disease, disorder or condition is Down's syndrome-associated Alzheimer's disease.

20. 20. A method for detecting amyloid beta in a sample obtained from a subject, comprising contacting the sample with an amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 19, and then detecting binding of the antibody or antigen-binding fragment thereof to detect amyloid beta in the sample.

21. A method for quantifying amyloid beta in a sample obtained from a subject, comprising contacting the sample with an amyloid beta-binding antibody or antigen-binding fragment thereof described in any one of claims 1 to 19, and then quantifying amyloid beta in the sample based on the level of binding of the antibody or antigen-binding fragment thereof to amyloid beta.

22. A method for diagnosing amyloid beta-associated diseases, disorders and / or conditions, comprising carrying out the method of claim 20 or 21, wherein a high level of amyloid beta in the sample compared to a control level based on a healthy subject indicates amyloid beta-associated diseases, disorders and / or conditions.

23. 22. A method for diagnosing amyloid beta-associated diseases, disorders and / or conditions comprising carrying out the method of claim 20 or 21, wherein an identical or elevated level of amyloid beta in the sample compared to a diseased control level indicates amyloid beta-associated diseases, disorders and / or conditions.

24. 1. A method for classifying amyloid beta-related diseases, disorders and / or conditions, comprising: a. carrying out the method of claim 22 and / or 23, b. Classifying amyloid beta-related diseases, disorders and / or conditions A method comprising:

25. 20. A method for monitoring an amyloid beta-related disease, disorder and / or condition at two or more time points using a sample from a subject, comprising contacting the sample with an amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 19, a. a higher level of amyloid beta in a subsequent sample compared to one or more previous samples is indicative of the progression of an amyloid beta-related disease, disorder, and / or condition; b. A lower level of amyloid beta in the subsequent sample compared to one or more previous samples indicates regression of the amyloid beta-related disease, disorder and / or condition; and / or c. A method wherein the absence of a significant change in the level of amyloid beta in a subsequent sample compared to one or more previous samples indicates the absence of progression of a disease, disorder and / or condition associated with amyloid beta.

26. 20. A method for selecting a therapy for the treatment of amyloid beta-related diseases, disorders and / or conditions, comprising contacting samples taken before and after treatment with said therapy with an amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 19, a. a lower level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates successful treatment of the disease, disorder, and / or condition associated with amyloid beta, thereby selecting the therapy for treatment; b. no significant change in the level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates successful treatment of the disease, disorder, and / or condition associated with amyloid beta, thereby selecting the therapy for treatment; c. a decrease in the rate of increase in the level of amyloid beta between samples taken during treatment compared to said sample taken before treatment indicates successful treatment of the disease, disorder and / or condition associated with amyloid beta, thereby selecting said therapy for treatment; d. A higher level of amyloid beta in the sample taken after treatment compared to the sample taken before treatment indicates failure of treatment of a disease, disorder, and / or condition associated with amyloid beta, whereby the therapy is not selected for treatment; or e. A method wherein a failure to reduce the rate of increase in amyloid beta levels between samples taken during treatment compared to said samples taken before treatment indicates failure of treatment of amyloid beta-related diseases, disorders and / or conditions, such that said therapy is not selected for treatment.

27. 20. A method for evaluating a candidate therapeutic for an amyloid-beta associated disease, disorder and / or condition, comprising, following treatment of one or more subjects, contacting a sample from one or more treated subjects with the antibody or antigen-binding fragment of any one of claims 1 to 19, wherein a lower level of amyloid beta in the sample compared to the level in a corresponding sample from a subject not treated with the therapeutic indicates successful treatment of an amyloid-associated disease, disorder and / or condition.

28. 28. The method of claim 27, performed at multiple time points in matched samples between treatment and placebo groups to monitor the effectiveness of the candidate therapy over time.

29. 29. The method of claim 27 or 28, comprising contacting samples from one or more treated subjects and a subject not treated with said therapy with the antibody or antigen-binding fragment of any one of claims 1 to 19 prior to treatment with said therapy or placebo, respectively, to determine basal levels of amyloid beta.

30. 30. The method of any one of claims 20 to 29, wherein the amyloid beta-associated disease, disorder and / or condition is selected from the group consisting of Alzheimer's disease (AD), mild cognitive impairment (MCI), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cardiac amyloidosis, cerebral amyloid angiopathy (CAA), multiple sclerosis, Parkinson's disease, Parkinson's disease dementia (PDD), Lewy body disease, ALS (amyotrophic lateral sclerosis), adult-onset diabetes mellitus, inclusion body myositis (IBM), ocular amyloidosis, glaucoma, macular degeneration, lattice dystrophy, optic neuritis, myotonic dystrophy, and liver damage or liver failure.

31. 31. The method of claim 30, wherein the amyloid beta-associated disease, disorder, or condition is Alzheimer's disease (AD), Down's syndrome (DS), Down's syndrome-associated Alzheimer's disease, cerebral amyloid angiopathy (CAA), myotonic dystrophy, or Lewy body disease.

32. 32. The method of claim 30 or 31, wherein the amyloid beta-related disease, disorder or condition is Alzheimer's disease (AD).

33. 32. The method of claim 30 or 31, wherein the amyloid beta-related disease, disorder or condition is Down's syndrome (DS).

34. A diagnostic composition comprising an amyloid beta binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 19, and an acceptable carrier and / or excipient.

35. A nucleic acid encoding the amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 19.

36. A nucleic acid comprising a nucleotide sequence as provided in SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:188, SEQ ID NO:189, or SEQ ID NO:

199.

37. A recombinant vector comprising the nucleic acid of claim 35 or 36.

38. A host cell comprising a nucleic acid according to claim 35 or 36 and / or a recombinant vector according to claim 37.

39. 20. An isolated host cell expressing the amyloid beta binding antibody or antigen-binding fragment of any one of claims 1 to 19.

40. 1. A method for producing an amyloid beta binding antibody or antigen-binding fragment thereof, comprising: a. culturing the host cell of claim 38 or 39 under conditions suitable for producing an amyloid beta binding antibody or antigen-binding fragment thereof; and b. Recovering the amyloid beta-binding antibody or antigen-binding fragment thereof A method comprising the steps of:

41. A kit for diagnosing a disease, disorder or condition associated with amyloid beta, comprising an amyloid beta-binding antibody or antigen-binding fragment thereof described in any one of claims 1 to 19 and a container, or a kit for use in a method described in any one of claims 20 to 33.

42. An amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 19 for research use, in particular as an analytical tool or reference molecule.

43. 20. The amyloid beta-binding antibody or antigen-binding fragment thereof according to any one of claims 1 to 19, for use in detecting amyloid beta aggregates, including plaques, in vitro or in vivo.

44. 44. The amyloid beta-binding antibody or antigen-binding fragment thereof of claim 43, for use in histochemical detection in brain tissue.

45. A diagnostic composition comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof according to any one of claims 1 to 19 and an acceptable carrier and / or excipient.

46. The diagnostic composition of claim 45, wherein the two amyloid beta-binding antibodies or antigen-binding fragments selectively bind to or capture any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species, and at least one of the two amyloid beta-binding antibodies or antigen-binding fragments does not exhibit cross-reactivity with soluble APP alpha.

47. A diagnostic composition comprising two amyloid beta-binding antibodies or antigen-binding fragments, the diagnostic composition comprising a first amyloid beta-binding antibody or antigen-binding fragment thereof according to claims 1 to 19, a second amyloid beta-binding antibody or antigen-binding fragment thereof which is not an antibody according to claims 1 to 19, and an acceptable carrier and / or excipient.

48. 48. A diagnostic composition comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof according to claim 46 or 47, and an acceptable carrier and / or excipient, wherein at least one or two of the amyloid beta binding antibodies or antigens are a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and / or c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157 A diagnostic composition selected from:

49. 48. A diagnostic composition comprising at least two amyloid beta binding antibodies or antigen-binding fragments thereof according to claim 46 or 47, and an acceptable carrier and / or excipient, wherein at least one or two of the amyloid beta binding antibodies or antigens are a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; and b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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 A diagnostic composition selected from:

50. For use in an immunoassay comprising at least two amyloid beta-binding antibodies or antigen-binding fragments thereof, a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and / or c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157 an amyloid beta-binding antibody or antigen-binding fragment selected from:

51. 1. A method for detecting amyloid beta in a sample obtained from a subject, comprising capturing amyloid beta with a first amyloid beta-binding antibody or fragment thereof, and then detecting the captured amyloid beta in the sample with a second amyloid beta-binding antibody or fragment thereof; a) each amyloid beta-binding antibody or antigen-binding fragment thereof is selected from the antibodies or antigen-binding fragments of claims 1 to 19, or b) one is an amyloid beta-binding antibody or antigen-binding fragment thereof according to claims 1 to 19, and the other is an amyloid beta-binding antibody or antigen-binding fragment thereof different from the antibody according to claims 1 to 19.

52. A method for detecting amyloid beta in a sample obtained from a subject, comprising capturing amyloid beta with a first amyloid beta-binding antibody or fragment thereof, and then detecting the captured amyloid beta in the sample with a second amyloid beta-binding antibody or fragment thereof, wherein the first and second amyloid beta-binding antibodies or antigen-binding fragments thereof are selected from claims 1 to 19, and at least one of the first and second antibodies or antigen-binding fragments thereof does not exhibit cross-reactivity with soluble APP alpha.

53. 1. A method for detecting amyloid beta in a sample obtained from a subject, comprising capturing amyloid beta with a first amyloid beta-binding antibody or fragment thereof, and then detecting the captured amyloid beta in the sample with a second amyloid beta-binding antibody or fragment thereof; each amyloid beta binding antibody or antigen-binding fragment thereof independently: a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; VH-CDR3 comprising the amino acid sequence of 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 the amino acid sequence of SEQ ID NO: 17; b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and / or c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152; VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 155; VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 156; and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 157 A method selected from the following.

54. 1. A method for detecting amyloid beta in a sample obtained from a subject, comprising capturing amyloid beta with a first amyloid beta-binding antibody or fragment thereof, and then detecting the captured amyloid beta in the sample with a second amyloid beta-binding antibody or fragment thereof; each amyloid beta binding antibody or antigen-binding fragment thereof independently: a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12; a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; and b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31; VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32; VH-CDR3 comprising the amino acid sequence of 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 A method selected from the following.

55. a. a first amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species; and b. A second amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species. A diagnostic composition comprising: A diagnostic composition wherein at least one or both of said first and second antibodies exhibits no cross-reactivity to soluble amyloid precursor protein (APP), and in particular no cross-reactivity to soluble APP alpha.

56. The diagnostic composition of claim 55, wherein at least one of the first and second antibodies or antigen-binding fragments thereof that exhibit no cross-reactivity to soluble amyloid precursor protein (APP), in particular no cross-reactivity to soluble APP alpha, is an antibody or antigen-binding fragment thereof described in any one of claims 1 to 19.

57. the first and second antibodies or antigen-binding fragments thereof exhibiting no cross-reactivity to soluble amyloid precursor protein (APP), in particular no cross-reactivity to soluble APP alpha, i. 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 ii. A heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 150 and a light chain variable region (VL) comprising the sequence of SEQ ID NO:

154.

57. The diagnostic composition of claim 56, comprising:

58. 58. The diagnostic composition of any one of claims 55 to 57, wherein one of the first and second antibodies or antigen-binding fragments thereof exhibits cross-reactivity (which may be low or high) with soluble amyloid precursor protein (APP).

59. The diagnostic composition according to claim 58, wherein the antibody or antigen-binding fragment thereof exhibiting cross-reactivity (which may be low or high) with soluble amyloid precursor protein (APP) is an antibody or antigen-binding fragment thereof according to any one of claims 1 to 19.

60. The diagnostic composition of claim 59, wherein the antibody or antigen-binding fragment thereof exhibiting cross-reactivity (which may be low or high) with soluble amyloid precursor protein (APP) comprises a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the sequence of SEQ ID NO:

14.

61. 1. A method for detecting amyloid beta in a sample obtained from a subject, comprising: a. capturing amyloid beta using an amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species; and b. Detecting the captured amyloid beta with an amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to amyloid beta peptides or species in solution, regardless of the conformational state of the amyloid beta peptides or species, and that exhibits no, low, or high cross-reactivity to soluble amyloid precursor protein (APP), and in particular no, low, or high cross-reactivity to soluble APP alpha. Including, A method wherein at least one or both of the capture and detection antibodies or antigen-binding fragments thereof exhibit no cross-reactivity to soluble amyloid precursor protein (APP), and in particular no cross-reactivity to soluble APP alpha.

62. The method of claim 61, wherein at least one of the capture and detection antibodies or antigen-binding fragments thereof that exhibit no cross-reactivity to soluble amyloid precursor protein (APP), in particular no cross-reactivity to soluble APP alpha, is an antibody or antigen-binding fragment thereof according to any one of claims 1 to 19.

63. 63. The method of claim 61 or 62, wherein one of the capture and detection antibodies or antigen-binding fragments thereof exhibits cross-reactivity (which may be low or high) with soluble amyloid precursor protein (APP).

64. The method of claim 63, wherein the antibody or antigen-binding fragment thereof exhibiting cross-reactivity (which may be low or high) with soluble amyloid precursor protein (APP) is an antibody or antigen-binding fragment thereof according to any one of claims 1 to 19.

65. A kit for detecting amyloid beta in a sample obtained from a subject, comprising: a. a capture amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species; and b. A detecting amyloid beta-binding antibody or antigen-binding fragment thereof that selectively binds to any amyloid beta peptide or species in solution, regardless of the conformational state of the amyloid beta peptide or species. wherein at least one of the capture and detection antibodies or antigen-binding fragments thereof exhibits no cross-reactivity to soluble amyloid precursor protein (APP), and in particular no cross-reactivity to soluble APP alpha.

66. 66. The kit of claim 65, wherein at least one of the capture and detection antibodies or antigen-binding fragments thereof that exhibit no cross-reactivity to soluble amyloid precursor protein (APP), in particular no cross-reactivity to soluble APP alpha, is an antibody or antigen-binding fragment thereof according to any one of claims 1 to 19.

67. 67. The kit of claim 65 or 66, wherein one of the capture and detection antibodies or antigen-binding fragments thereof exhibits cross-reactivity (which may be low or high) with soluble amyloid precursor protein (APP).

68. The kit according to claim 67, wherein the antibody or antigen-binding fragment thereof that exhibits cross-reactivity (which may be low or high) with soluble amyloid precursor protein (APP) is an antibody or antigen-binding fragment thereof according to any one of claims 1 to 19.

69. 69. The method of any one of claims 20 to 33, 51 to 54 or 61 to 64, or the kit of any one of claims 65 to 68, wherein the sample is a body fluid sample, preferably wherein the body fluid sample is saliva, urine, nasal secretions, blood (including whole blood, plasma and serum, preferably plasma), a brain and / or CSF sample, a brain and / or ISF sample, more particularly a blood, brain, CSF and / or ISF sample.

70. 61. The diagnostic composition according to any one of claims 45 to 49 or 55 to 60, further comprising a sample, in particular a body fluid sample, preferably wherein said body fluid sample is saliva, urine, nasal secretions, blood (including whole blood, plasma and serum, preferably plasma), a brain and / or CSF sample, a brain and / or ISF sample, more particularly a blood, brain, CSF and / or ISF sample.

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