Novel molecules for therapy and diagnosis

Abstract

The present invention is in the field of adaptor protein Apoptosis-associated speck-like protein (ASC) containing a caspase recruitment domain, ASC-dependent inflammasome and the propagation of inflammation in disease.The present invention relates to ASC-binding molecules, particularly anti-ASC antibodies or antigen-binding fragments thereof, and their uses.The present invention provides diagnostic tools, means and methods for preventing, alleviating and / or treating diseases, disorders and / or abnormalities associated with ASC-dependent inflammasome activation in disease, particularly extracellular ASC and / or ASC specks that may be associated with multiple pathologies.

Description

[Technical Field]

[0001] Inflammasomes are multiprotein, high-molecular-weight complexes that activate inflammatory caspases and release the cytokine IL-1β in response to pathogens and danger signals. They play a key role in inflammatory and immune responses. These complexes assemble in response to various danger signals, including molecules from infectious agents (pathogen-associated molecular patterns, PAMPs), as well as altered host molecules, products of sterile inflammation and tissue injury, and environmental factors (danger-associated molecular patterns, DAMPs). The inflammasome family consists of NALP1-14, IPAF, and NAIP1-6, and each family member provides specificity for different PAMPs / DAMPs, including nucleic acids, bacterial proteins, metabolites, protein aggregates, and toxin activity (Sharma and Kanneganti 2016). Inflammasomes typically consist of a sensor (cytoplasmic pattern recognition receptor, PRR) and an adaptor protein called apoptosis-associated speck (ASC, also known as PYCARD), which contains a caspase recruitment domain (CARD), and an effector such as the protease caspase-1 (Broz and Dixit 2016). ASC is a 22-kDa adaptor protein with an N-terminal pyrin domain (PYD) and a C-terminal CARD. Multiprotein inflammasome oligomeric complexes form through homodimeric interactions between the N-terminal pyrin of the NLR, the N-terminal pyrin of the ASC, and the C-terminal CARD of the ASC and the N-terminal CARD of procaspase-1. This facilitates ASC polymerization to form long helical filaments, which condense into intracellular polymers known as ASC specks (Fernandes-Alnemri, Wu et al. 2007). This complex induces the activation of procaspase-1 into active caspases, which cleave the inactive pro-IL-1β and pro-IL-18 forms into bioactive cytokines that activate downstream inflammatory pathways.

[0002] ASC (PYCARD) functions as a central adaptor protein for multiple inflammasomes from the NLR (NLRP1, NLRP3, NLRP6, NLRP7, NLRC4, NLRC5, NAIP2, NAIP5, and NAIP6) family, hematopoietic interferon (HIN), and absent in melanoma 2 (AIM2) (Guo, Callaway et al. 2015). While ASC speck formation is best described for the NLRP3 inflammasome, evidence exists for ASC speck formation for other inflammasomes, including NLRC4 (Franklin, Bossaller et al. 2014) and NLRP1 (Gong, Robinson et al. 2021).

[0003] Within cells, the primary function of ASC specks is the activation and regulation of caspase-1 activity. In addition to their intracellular functions, NLRP3 / ASC complexes exert multiple activities in the extracellular space, where they are released upon pyroptotic cell death and remain active and stable (reviewed in Franklin, Latz et al. 2018). ASC specks can sustain inflammatory responses in the extracellular space by recruiting procaspase-1 and IL-1β, which can provide an alternative antigen presentation mechanism and capture microorganisms and cellular debris for subsequent clearance by neutrophils. Furthermore, ASC specks possess prion-like properties and can propagate inflammation to recipient phagocytic cells. ASC specks taken up by recipient cells can further aggregate soluble ASC in the cytoplasm and induce IL-1β production (Baroja-Mazo, Martin-Sanchez et al. 2014, Franklin, Bossaller et al. 2014).

[0004] Inflammasome activation is associated with the pathogenesis of multiple inflammatory conditions, including autoimmune, autoinflammatory, metabolic, and neurodegenerative diseases, and the presence of ASC specks has been described in patient-derived material (reviewed in de Souza et al., 2021). In particular, extracellular ASCs or ASC specks have been detected in the lungs of patients with inflammatory lung diseases (Franklin, Bossaller et al. 2014), plasma of patients with cryopyrin-associated periodic fever syndromes (CAPS) (Baroja-Mazo, Martin-Sanchez et al. 2014) and serum (Rowczenio, Pathak et al. 2018), serum from pustular fibrosis and systemic autoimmune diseases (SAIDs) (Scambler, Jarosz-Griffiths et al. 2019), serum from Schnitzler syndrome (Rowczenio, Pathak et al. 2018), myelodysplastic syndrome (Basiorka, McGraw et al. 2018), serum from patients with psoriasis (Forouzandeh, Besen et al. 2020), and serum from nonalcoholic steatohepatitis (NASH) (Cyr, Keane et al. 2020) and atherosclerotic plaques (Paramel Varghese, Folkersen et al. 2016). In CNS diseases, ASC or ASC-specks have been found in Alzheimer's disease brain tissue in the core of amyloid plaques (Venegas, Kumar et al. 2017), CSF of patients with traumatic brain injury (Adamczak, Dale et al. 2012), stroke (Kerr, Garcia-Contreras et al. 2018), and serum of patients with multiple sclerosis (Keane, Dietrich et al. 2018).Additional evidence suggests that ASC specs may be involved in the pathogenesis of allergic asthma (Lee, Ishitsuka et al. 2021), systemic lupus erythematosus (SLE) (Franklin, Bossaller et al. 2014), some cancers (Protti and De Monte 2020), and viral infections, including HIV-1 (Ahmad, Mishra et al. 2018), SARS-CoV-2 (Rodrigues, de Sa et al. 2021, Toldo, Bussani et al. 2021), and hepatitis B virus (Xie, Ding et al. 2020).

[0005] The presence of extracellular ASC and ASC specks in multiple pathologies makes them attractive targets for therapeutic intervention and diagnosis. Franklin's study (Franklin, Bossaller et al. 2014) demonstrated that ASC specks are accessible to peripherally delivered antibodies in vivo following inflammasome activation. Furthermore, the use of anti-ASC mAbs demonstrated protection in models of traumatic brain and spinal cord injury (de Rivero Vaccari, Lotocki et al. 2008, de Rivero Vaccari, Lotocki et al. 2009) and multiple sclerosis (Desu, Plastini et al. 2020). However, another study suggested that anti-ASC antibodies exacerbated the inflammatory response in a crystal-induced peritoneal inflammation model (Franklin, Bossaller et al. 2014). The latter study used a polyclonal ASC antibody, which complicates data interpretation and the development of potential therapeutics. Therefore, additional studies are needed to understand the effectiveness of antibodies targeting different epitopes of ASC for preventing the spread of inflammation.

[0006] Furthermore, there is a need to identify and develop specific anti-ASC monoclonal antibodies with therapeutic potential for anti-inflammatory treatment and diagnosis. Additionally, detecting inflammasome components as potential biomarkers could be useful for patient identification, stratification, and longitudinal follow-up. Currently, few such diagnostic tools exist (only one assay reported by Keane, Dietrich et al. 2018). Therefore, discovering and developing specific high-affinity monoclonal antibodies (mAbs) against distinct epitopes of the ASC protein would allow for the exploration of their potential as biomarkers for ASC. Furthermore, this would ultimately lead to better clinical trial design and enable the development of novel therapeutics.

[0007] The present invention provides specific, high-affinity mAbs or fragments and derivatives thereof that specifically bind to ASC or ASC specks for use as anti-inflammatory treatments and diagnostics for diseases associated with inflammasome activation and propagation. The mAbs of the present invention target distinct epitopes of ASC and are capable of inhibiting ASC polymerization and propagation in vitro and in vivo. Such mAbs are useful in treating diseases, injuries, or disorders associated with the accumulation of extracellular ASC specks. Antibodies against ASC are expected to neutralize extracellular ASC specks, subsequently attenuating the propagation of inflammatory signaling and ultimately providing functional improvement. [Background technology]

[0008] WO2019122270 relates to ligands that interact with neurodegenerative disease and apoptosis-associated speck-like proteins containing CARD.

[0009] US Patent Application Publication No. 2009104200 describes antibodies that specifically bind to at least one component (e.g., ASC, NALP1) in a mammalian inflammasome (e.g., the NALP1 inflammasome) for modulating inflammasome activity and inflammation in the central nervous system. Summary of the Invention

[0010] In one embodiment, an ASC binding molecule that binds to ASC specks and / or unpolymerized ASC is provided.

[0011] In one embodiment, the ASC binding molecule preferentially binds to ASC specks compared to non-polymerized ASC. In one embodiment, the ASC binding molecule preferentially binds to non-polymerized ASC compared to ASC specks. In one embodiment, the ASC binding molecule binds to ASC specks but does not bind to non-polymerized ASC. In one embodiment, the ASC binding molecule binds to non-polymerized ASC but does not bind to ASC specks.

[0012] In one embodiment, the ASC binding molecule prevents or inhibits ASC polymerization. In one embodiment, ASC polymerization is measured in vitro, preferably by an ASC polymerization assay.

[0013] In one embodiment, the ASC-binding molecule prevents or inhibits the propagation of ASC-dependent inflammation. In one embodiment, the propagation of inflammation is measured in vitro or in vivo.

[0014] In one embodiment, the prevention or inhibition of inflammation propagation is prevention or inhibition of IL-1β release, which in one embodiment is measured in vitro, preferably in an assay using phagocytic cells such as macrophages or microglia.

[0015] In one embodiment, the ASC binding molecule increases the uptake of ASC extracellular specks by phagocytic cells such as macrophages or microglia.

[0016] In one embodiment, the ASC binding molecule prevents or inhibits the accumulation of ASC and / or ASC specks.

[0017] In one embodiment, the accumulation of ASC or ASC specs is intracellular or extracellular.

[0018] In one embodiment, the ASC binding molecule binds to an epitope of human ASC of SEQ ID NO: 1; and / or mouse ASC of SEQ ID NO: 2. In one embodiment, the epitope is in the ASC PYD domain or the ASC CARD domain.

[0019] In one embodiment, the ASC binding molecule prevents, reduces, or inhibits demyelination.

[0020] In one embodiment, preventing, reducing, or inhibiting demyelination is improving the demyelination score in vivo.

[0021] In one embodiment, the ASC binding molecule increases spleen mass in vivo.

[0022] In one embodiment, the ASC binding molecule reduces reactive microglia levels in vivo.

[0023] In one embodiment, the ASC binding molecule reduces ASC and / or cleaved caspase-1 (capase-1) protein levels in vivo.

[0024] In one embodiment, the ASC binding molecule comprises the amino acid residues: a) L9, D10, E13, N14, E18 and E19, b) L9, D10, E13 and N14, c) E13 and N14, d) Q79, E80, G83 and Q84; or e) E18, E19, V30, P31, N71, R74, D75, G77, Q79 and E80 The present invention binds to an epitope in the ASC PYD domain comprising, consisting essentially of, or consisting of:

[0025] The amino acids are listed with reference to the amino acid sequence of human ASC in SEQ ID NO: 1. The ASC binding molecule comprises the amino acid residue numbers of human ASC in SEQ ID NO: 1: a) 9, 10, 13, 14, 18 and 19, b) 9, 10, 13 and 14, c) 13 and 14, d) 79, 80, 83 and 84, or e) 18, 19, 30, 31, 71, 74, 75, 77, 79 and 80 The ASC PYD domain may be capable of binding to an epitope in the ASC PYD domain comprising, consisting essentially of, or consisting of:

[0026] As described in Example 11, epitopes can be defined using alanine scanning mutagenesis. Mutants of ASC, particularly the PYD domain of PYCARD, can also be used. The binding of ASC-binding molecules to mutants can be measured by suitable immunoassays, such as ELISA. The residues listed are residues that are crucial for binding, and this can be defined as any suitable loss of binding, for example, retention of 30% or less of binding compared to wild-type controls in the presence of alanine mutations at those positions.

[0027] Alternatively, the ASC binding molecule may comprise the amino acid residues: a.K174 and D175, b.I115, D116, R119, A120, K174, D175, S184, Q185, S186 and Y187, c.I115, D116, N170, W171, T172, K174, D175, S186 and Y187, d.Y137, e.R119, A120, L178, Q179, S186 and Y187, or f.R119, A120, K174, D175, S186 and Y187 The ASC CARD domain may comprise, consist essentially of, or consist of an epitope in the ASC CARD domain.

[0028] The amino acids are listed with reference to the amino acid sequence of human ASC in SEQ ID NO: 1. The ASC binding molecule comprises the amino acid residue numbers of human ASC in SEQ ID NO: 1: a.174, 175, b. 115, 116, 119, 120, 174, 175, 184, 186 and 187, c.115, 116, 170, 171, 172, 174, 175, 186 and 187, d.137, e. 119, 120, 178, 179, 186 and 187, or f. 119, 120, 174, 175, 186 and 187 The ASC CARD domain may comprise, consist essentially of, or consist of an epitope in the ASC CARD domain.

[0029] As described in Example 13, epitopes can be defined using alanine mutagenesis. ASC mutants, particularly the CARD domain of PYCARD, can also be used. The binding of ASC binding molecules to mutants can be determined by a suitable immunoassay, such as ELISA. The residues listed are essential for binding, which can be defined as any suitable loss of binding, for example, retention of 30% or less of binding compared to wild-type controls in the presence of alanine mutations at that position.

[0030] In one embodiment, the ASC-binding molecule of the present invention comprises: a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, VH-CDR3 comprising the amino acid sequence NEV (Asn-Glu-Val), 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; or b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 23, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; or c. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, 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 d. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, 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; or e. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 53, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 57; or 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: 63, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; or g. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 71, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, 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: 76, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; or h. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 81, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 82, 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: 86, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87; or i. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97; or j. 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; or k. 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; or l. 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: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137; or m. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 147; or n. 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; or o. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, 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; or p. 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: 176, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177; or q. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182, 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: 185, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187; or r. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 191, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197; or s. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or t. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 217; or u. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 221, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 226, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227; or v. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237; or w. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 241, 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: 243, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 245, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 246, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247; or x. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 251, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257; or y. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 266, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267; or z. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or aa. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287; or bb. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 291, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 292, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 293, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 295, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 297; or cc. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 71, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 305, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 307; or dd. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312, VH-CDR3 comprising the amino acid sequence RDY (Arg-Asp-Tyr), VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 317; or ee. 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: 322, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327; or ff. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 331, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 337; or gg. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347; or hh. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 331, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 337; or ii. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, a VH-CDR3 comprising the amino acid sequence RDY (Arg-Asp-Tyr), a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367; or jj. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 375, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 377; or kk. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 381, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387; or ll. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 392, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 Includes.

[0031] In one embodiment, the ASC-binding molecule of the present invention comprises: a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 10, 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: 10; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 14; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 20, 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: 20; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 24, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 24; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 30, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 34, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 40, or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 44, 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: 44; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 50, 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: 50; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 54, 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: 54; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 60, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 64; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 70, 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: 70; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 74, 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: 74; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 80, 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: 80; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 84, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 90, 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: 90; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 94, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 110, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) comprising the amino acid 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; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 120, 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: 120; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 124, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 130, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 134, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 134; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 140, or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 144, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 144; or n. a heavy chain variable region (VH) comprising the amino acid 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 amino acid sequence of SEQ ID NO: 154, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 160, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 164, 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: 164; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 170, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 174, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 174; or q. a heavy chain variable region (VH) comprising the amino acid 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 amino acid sequence of SEQ ID NO: 184, 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: 184; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 190, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 190; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 194; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 204; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 210, 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: 210; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 214, 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: 214; or u. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 220, or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 220; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 224, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 224; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 230, or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 230; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 234, or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 234; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 240, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 240; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 244, 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: 244; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 250, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 250; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 254, 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: 254; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 260, 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: 260; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 264, 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: 264; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 270, 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: 270; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 274, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 274; or aa. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 280, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 280; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 284, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 284; or bb. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 290, 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: 290; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 294, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 294; or cc. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 300, 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: 300; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 304, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 304; or dd. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 310, 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: 310; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 314, 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: 314; or ee. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 320, 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: 320; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 324, or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 324; or ff. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 330, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 330; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 334, 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: 334; or gg. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 340, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 340; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 344, or a light chain variable region (VL) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 344; or hh. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 350, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 350; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 354, 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: 354; or ii. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 360, 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: 360; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 364, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 364; or jj. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 370, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 370; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 374, or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 374; or kk. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 380, or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 380; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 384, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 384; or ll. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 390, 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: 390; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 394. Includes.

[0032] In one embodiment, the ASC-binding molecule of the present invention comprises: a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 10 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 20, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 24; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 30, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 40, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 44; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 50, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 54; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 60, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 64; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 70, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 74; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 80, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 84; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 90, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 94; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 110, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 114; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 120, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 124; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 130, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 134; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 140, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 144; or n. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 150, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 154; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 160, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 164; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 170, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 174; or q. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 180, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 184; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 190, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 194; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 210, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 214; or u. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 220, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 224; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 230, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 234; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 240, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 244; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 250, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 254; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 260, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 264; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 270, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 274; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 280, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 284; or bb. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 290, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 294; or cc. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 300, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 304; or dd. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 310, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 314; or ee. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 320, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 324; or ff. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 330, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 334; or gg. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 340, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 344; or hh. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 350, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 354; or ii. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 360, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 364; or jj. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 370, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 374; or kk. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 380 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 384; or ll. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 390 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 394 Includes.

[0033] In one embodiment, the ASC binding molecule is an anti-ASC antibody or an antigen-binding fragment thereof. In one embodiment, the ASC binding molecule, preferably an anti-ASC antibody or an antigen-binding fragment thereof, is a monoclonal antibody or an antigen-binding fragment thereof. In one embodiment, the anti-ASC antibody or an antigen-binding fragment thereof of the present invention is an IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3, or IgG4 antibody or an antigen-binding fragment thereof, preferably human IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3, or IgG4.

[0034] In one embodiment, the ASC binding molecule is selected from the group consisting of ACI-8016-416E6G4-AB1, ACI-8016-402H11C9-Ab1, ACI-8016-203B12C3-AB1, ACI-8016-421B10C12D2-AB1, ACI-8016-417E12A8-AB1, ACI-8016-413G10A5-AB1, ACI-8016-407E10A9-AB1, ACI-8016-203G8B10-AB1, ACI-8016-401H9B7-AB1, ACI-8016- 16-1112B3D7-AB1, ACI-8018-2221B7F1-AB1, ACI-8019-2314F6H11-AB1, ACI-8016-207E8B2-AB1, ACI-8016-2A1B12-AB1, ACI-8016-17H1G 2-AB1, ACI-8016-18F4C12-AB1, ACI-8016-23E5F7-AB1, ACI-8016-23E5F7-AB2, ACI-8016-26A1G2-AB1, ACI-8016-32B6C7-AB1, ACI-8016- 22D3A6-AB1, ACI-8016-31F10C5-AB1, ACI-8016-19E6D4-AB1, ACI-8016-3E6B11-AB1, ACI-8016-11A3F3-AB1, ACI-8016-14G5B8-AB1, ACI -8016-22A10F8-AB1, ACI-8016-27A1G4-AB1, ACI-8016-29C5E11-AB1, ACI-8016-7G3B5-AB1, ACI-8016-2504F3D9-AB1, ACI-8016-2516A8C and ACI-8016-2626B9D3-AB1, or ACI-8016-2629E8D1-AB1, or an antibody-binding fragment thereof.

[0035] In one embodiment, the ASC-binding molecule is a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or c. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or d. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or e. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or f. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or g. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 may include:

[0036] In one embodiment, the ASC-binding molecule is a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; or b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; or c. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; or d. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203 Includes.

[0037] In one embodiment, the ASC-binding molecule is a. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or b. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 may include:

[0038] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 470, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 470, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 490, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 490, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 500, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 500, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 510, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 510, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or n. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 530, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 530, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 540, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 540, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or q. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or u. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or aa. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or bb. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424. may include:

[0039] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 470, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 470, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 490, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 490, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 500, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 500, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 510, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 510, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or n. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 530, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 530, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 540, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 540, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or q. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or u. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or aa. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or bb. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424. may include:

[0040] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 470 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 490 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 500 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 510 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or n. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 530 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 540 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or q. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or u. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or aa. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 may include:

[0041] In one embodiment, the ASC-binding molecule is a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or c. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 may include:

[0042] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 204 or the amino acid sequence of SEQ ID NO: 204; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424. may include:

[0043] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 201; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424. may include:

[0044] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or e. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 may include:

[0045] In one aspect, there is provided an immunoconjugate comprising an ASC-binding molecule according to the invention.

[0046] In one embodiment, the ASC-binding molecule of the invention or the immunoconjugate of the invention is for use in human or veterinary therapy.

[0047] In one embodiment, the ASC binding molecule or immunoconjugate for use in the present invention is for the prevention, alleviation or treatment of a disease, disorder or condition associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs.

[0048] In one embodiment, the ASC binding molecule or immunoconjugate of the invention is for use in the prevention of a disease, disorder, or condition associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs.

[0049] In one embodiment, the ASC binding molecule or immunoconjugate of the invention is for use in delaying the onset of a disease, disorder, or condition associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs.

[0050] In one embodiment, the ASC binding molecule or immunoconjugate of the invention is for use in alleviating a disease, disorder, or condition associated with the accumulation of ASC or ASC specs, preferably extracellular ASC specs.

[0051] In one embodiment, the ASC binding molecule or immunoconjugate of the invention is for use in treating a disease, disorder, or condition associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs.

[0052] In one embodiment, the ASC binding molecule or immunoconjugate of the invention is for use in preventing, alleviating or treating a disease, disorder or condition associated with demyelination.

[0053] In one embodiment, the ASC-binding molecule or immunoconjugate for use in the present invention is for use in a disease, disorder, or condition associated with the accumulation of ASC or ASC specs, preferably ASC specs, more preferably extracellular ASC specs, selected from a central nervous system disease or a peripheral inflammatory condition. The central nervous system disease is preferably Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, or chronic traumatic encephalopathy. The peripheral inflammatory condition is preferably nonalcoholic steatohepatitis (NASH), cryopyrin-associated periodic fever syndrome (CAPS), chronic obstructive pulmonary disease (COPD), gout, psoriasis, acne, hidradenitis suppurativa (HS), inflammatory bowel disease (IBD) (e.g., ulcerative colitis or Crohn's disease), edema (DME), geographic atrophy (GA), coronavirus-associated respiratory distress syndrome (CARDS), or Sjögren's syndrome.

[0054] In one embodiment, a method of treatment in human or veterinary medicine is provided comprising administering to a subject an ASC-binding molecule of the invention or an immunoconjugate of the invention.

[0055] In one embodiment, the methods of the invention include preventing, alleviating, or treating a disease, disorder, or condition associated with the accumulation of ASCs and / or ASC specs, preferably extracellular ASC specs.

[0056] In one embodiment, the methods of the invention include the prevention of a disease, disorder, or condition associated with the accumulation of ASCs and / or ASC specs, preferably extracellular ASC specs.

[0057] In one embodiment, the methods of the invention involve alleviating a disease, disorder, or condition associated with the accumulation of ASCs and / or ASC specs, preferably extracellular ASC specs.

[0058] In one embodiment, the methods of the invention include treatment of a disease, disorder, or condition associated with the accumulation of ASCs or ASC specs, preferably ASC specs, more preferably extracellular ASC specs.

[0059] In one embodiment, the methods of the invention involve delaying the onset of a disease, disorder or condition associated with the accumulation of ASCs and / or ASC specs, preferably extracellular ASC specs.

[0060] In one embodiment, the methods of the present invention include preventing, alleviating, or treating a disease, disorder, or condition associated with demyelination.

[0061] In one embodiment, the method of the present invention is for treating a disease, disorder, or condition associated with the accumulation of ASCs or ASC specs, preferably ASC specs, more preferably extracellular ASC specs, selected from central nervous system diseases or peripheral inflammatory conditions. The central nervous system disease is preferably Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, or chronic traumatic encephalopathy. The peripheral inflammatory condition is preferably nonalcoholic steatohepatitis (NASH), cryopyrin-associated periodic fever syndrome (CAPS), chronic obstructive pulmonary disease (COPD), gout, acne, hidradenitis suppurativa (HS), psoriasis, inflammatory bowel disease (IBD) (e.g., ulcerative colitis or Crohn's disease), edema (DME), geographic atrophy (GA), coronavirus-associated respiratory distress syndrome (CARDS), or Sjögren's syndrome.

[0062] In one embodiment, the method of the present invention includes preventing or reducing demyelination in a subject. The method may include administering an ASC-binding molecule described herein or an immunoconjugate described herein to the subject. In one embodiment, preventing or reducing demyelination is improving the in vivo demyelination score.

[0063] In one embodiment, the method of the present invention comprises reducing the level of reactive microglia in a subject. The method may comprise administering to the subject an ASC-binding molecule described herein or an immunoconjugate described herein.

[0064] In one embodiment, the method of the present invention comprises reducing ASC and / or cleaved caspase-1 protein levels in a subject. The method may comprise administering to the subject an ASC-binding molecule described herein or an immunoconjugate described herein.

[0065] In one embodiment, the method of the present invention comprises reducing the level of infiltrating CD4+ T cells in the spinal cord of a subject. The method may comprise administering to the subject an ASC-binding molecule described herein or an immunoconjugate described herein.

[0066] In one aspect, there is provided an ASC-binding molecule of the present invention or an immunoconjugate of the present invention for use in diagnosis. The diagnosis can be in vivo diagnosis or in vitro diagnosis.

[0067] In one embodiment, the present invention provides an ASC-binding molecule or an immunoconjugate of the present invention for use in diagnosing a disease, disorder, or condition associated with ASC-dependent inflammation. The diagnosis can be in vivo diagnosis or in vitro diagnosis.

[0068] In one embodiment, a method for detecting non-polymerized ASC and / or ASC specks in a sample obtained from a subject is provided, comprising contacting the sample with an ASC binding molecule of the present invention and detecting binding of the ASC binding molecule to non-polymerized ASC and / or ASC specks in the sample.

[0069] In one aspect, a method for quantifying non-polymerized ASC and / or ASC specks in a sample obtained from a subject is provided, comprising contacting the sample with an ASC binding molecule of the present invention or an immunoconjugate of the present invention, and quantifying the non-polymerized ASC and / or ASC specks in the sample based on the binding level of the ASC binding molecule to the non-polymerized ASC and / or ASC specks.

[0070] In one aspect, a method for diagnosing a disease, disorder, or condition associated with ASC-dependent inflammation is provided, comprising quantifying non-polymerized ASC and / or ASC specks in a sample obtained from a subject according to the present invention, wherein a higher level of non-polymerized ASC and / or ASC specks in the sample compared to a control level based on healthy subjects indicates a disease, disorder, or condition associated with ASC-dependent inflammation.

[0071] In one embodiment, a diagnostic composition is provided comprising an ASC-binding molecule of the invention or an immunoconjugate of the invention and an acceptable carrier and / or excipient. The diagnostic composition of the invention can be used in all relevant methods according to the invention.

[0072] In one aspect, a pharmaceutical composition is provided comprising an ASC-binding molecule of the invention or an immunoconjugate of the invention, and a pharmaceutically acceptable carrier and / or excipient.

[0073] In one aspect, there is provided a nucleic acid encoding an ASC-binding molecule of the invention or an immunoconjugate of the invention. The pharmaceutical composition of the invention can be used in all relevant methods according to the invention.

[0074] In one aspect, the sequences of SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:98, SEQ ID NO:99, 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, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO: 228, SEQ ID NO:229, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:338, SEQ ID NO:339, SEQ ID NO:348, SEQ ID NO:349, SEQ ID NO:358, SEQ ID NO:359, SEQ ID NO:368, SEQ ID NO:369, SEQ ID NO:378, SEQ ID NO:379, SEQ ID NO:388, SEQ ID NO:389, SEQ ID NO:398 and SEQ ID NO:399.

[0075] Additionally or alternatively, there is provided a nucleic acid comprising the nucleotide sequence of SEQ ID NO:408, SEQ ID NO:418, SEQ ID NO:428, SEQ ID NO:438, SEQ ID NO:448, SEQ ID NO:458, SEQ ID NO:468, SEQ ID NO:478, SEQ ID NO:488, SEQ ID NO:498, SEQ ID NO:508, SEQ ID NO:518, SEQ ID NO:528, SEQ ID NO:538, SEQ ID NO:548, SEQ ID NO:409, SEQ ID NO:419, SEQ ID NO:429 and SEQ ID NO:439, SEQ ID NO:558 and SEQ ID NO:559.

[0076] In one embodiment, a nucleic acid is provided that comprises the nucleotide sequence provided in SEQ ID NO:200, SEQ ID NO:204, SEQ ID NO:429, SEQ ID NO:439, SEQ ID NO:448, SEQ ID NO:468, SEQ ID NO:488 and SEQ ID NO:528.

[0077] In one aspect, a recombinant vector comprising a nucleic acid of the invention is provided.

[0078] In one aspect, a host cell comprising a nucleic acid of the invention and / or a recombinant vector of the invention is provided.

[0079] In one aspect, an isolated host cell expressing an ASC-binding molecule of the invention or an immunoconjugate of the invention is provided.

[0080] In one aspect, a method for producing an ASC binding molecule is provided, comprising culturing a host cell of the present invention under conditions suitable for producing the ASC binding molecule, and recovering the ASC binding molecule.

[0081] In one aspect, there is provided a kit for diagnosing a disease, disorder, or condition associated with ASC-dependent inflammation, or a kit for use in a method of the present invention, comprising any one ASC-binding molecule of the present invention or an immunoconjugate of the present invention and a container. [Brief explanation of the drawings]

[0082] [Figure 1]Analysis of human and mouse ASC target engagement by ASC mAbs by immunoblot. ASC mAbs were analyzed by WB on a human monocyte cell line (H.Monoc) and mouse macrophage cell lysates (J774.A1) using recombinant human (Rec H) and mouse (Rec M) ASC proteins (MBP-tagged or N-terminal 10xHis-tagged and C-terminal Myc-tagged) as positive controls and human monocyte ASC KO cell lysate (H.ASC KO) as a negative control. The respective mAbs used for detection are indicated at the bottom of each immunoblot. Molecular weight markers are indicated on the left in kDa (kilodaltons). Arrows indicate the expected molecular weight of ASC and recombinant ASC proteins. [Figure 2] Human ASC target engagement by ASC mAbs. Representative images showing cytoplasmic ASC and ASC specks labeled by selected ASC mAbs analyzed by immunofluorescence in human monocytes. Arrows indicate ASC specks. Inset shows a higher magnification image. [Figure 3] Representative polymerization kinetics of human ASCs in the presence of decreasing amounts of mAb. Each plot shows the polymerization kinetics in the presence of serial dilutions of the tested mAb (concentration range 200 nM to 0.09 nM, 1 / 3 dilution). Each antibody was tested in n=2 or n=3 experiments. FA - fluorescence anisotropy. [Figure 4] Evaluation of antibody-driven uptake of ASC polymer. Representative images of pHrodo fluorescence in human monocytic cells treated with human ASC polymer for 3 hours in the presence of mAb. The name of the mAb is indicated at the top of each image. The graph shows the kinetics of the fluorescent signal monitored every hour for 22 hours. Pol-hASC polymer. [Figure 5]Inhibition of IL-1β release by ASC mAb in a human monocyte cell line treated with hASC polymer. Human monocytes differentiated into macrophages were primed and treated with hASC polymer preincubated with different concentrations of anti-ASC mAb, or 420 nM IgG2a isotype control, or 42 nM ACI-8016-401H9B7-AB1 (internal reference). IL-1β levels were determined by AlphaLISA and expressed as a percentage of the control; 0% and 100% correspond to hASC polymer incubated with buffer and isotype control mAb, respectively. Representative results are shown for ACI-8016-401H9B7-AB1 (A), ACI-8016-18F4C12-AB1 (B), and ACI-8016-31F10C5-AB1. IC50 values ​​(nM) were obtained from nonlinear regression (curve fit) using GraphPad software. Pol-hASC polymer, ref-ACI-8016-401H9B7-AB1. Data for each concentration are shown as mean ± SD. [Figure 6] Epitope mapping of ASC mAb. Binding of ASC antibody to alanine mutants of the PYD domain of PYCARD was measured by ELISA. Alanine mutants were captured using anti-MBP antibody, and binding of ASC antibody was detected with anti-mouse IgG2a-HRP antibody. Binding responses were normalized to hPYD-WT for each antibody. Mutations showing at least a 70% reduction in binding define critical / particularly important binding residues for each antibody. [Figure 7] Epitope mapping of ASC mAb specific for the CARD domain. Binding of CARD antibodies to alanine mutants of PYCARD is measured by ELISA. Alanine mutants were captured using anti-MBP antibody, and binding of CARD antibodies was detected with anti-mouse IgG2a-HRP antibody. Binding responses are normalized to human PYCARD-WT for each antibody. Mutations that show at least a 70% reduction in binding define critical / particularly important binding residues for each antibody. [Figure 8]Effect of ASC mAbs on DMNI clinical score progression and spleen size. A) Clinical course of MOG35-55-induced DMNI in C57BL / 6 mice treated with ASC-targeting mAbs (ACI-8016-18F4C12-AB1 and ACI-8016-32B6C7-AB1) or an IgG2a isotype control mAb at 30 mg / kg by ip injection on days 8, 11, and 13 post-immunization. Results are expressed as the mean daily clinical score ± SEM for 12 mice / group. B) Mean maximum score (MMS), the score considered the highest clinical score achieved by a mouse within the framework of the study. Results are expressed as MMS ± SD for 12 mice / group; *p<0.05, one-way ANOVA, Dunnett's multiple comparison test. C) Spleen weight normalized to body weight for 12 mice / group on day 17 post-immunization. *p<0.05, one-way ANOVA, Dunnett's multiple comparison test (B and C), ns—not significantly different. [Figure 9] Effect of ASC mAb on DMNI pathology. A) Demyelination score expressed as loss of MBP staining in the spinal cord of mice treated with ACI-8016-32B6C7-AB1 or IgG2a isotype control mAb. Results are expressed as demyelination score ± SEM for 12 mice / group. B) CD4 and C) Iba1 immunoreactive (IR) area in the spinal cord of mice treated with ACI-8016-32B6C7-AB1 or IgG2a isotype control mAb. Results are expressed as IR area (%) of total tissue area ± SEM for 12 mice / group. *p<0.05, **p<0.01, Student's t-test. [Figure 10] Effect of ASC mAb on inflammasome-associated proteins. ASC (A) and cleaved caspase-1 (B) spinal cord (thoracic-lumbar division) protein expression calculated as fold change relative to the IgG2a isotype control group. Values ​​correspond to the corrected area (total area normalized to protein concentration assessed by JESS software). Results are expressed as arbitrary units (AU) ± SEM for 12 mice / group. *p<0.05, unpaired t-test. DETAILED DESCRIPTION OF THE INVENTION

[0083] The present invention provides ASC-binding molecules that have a variety of useful properties.

[0084] In one embodiment, the ASC binding molecule preferentially binds to ASC specks compared to non-polymerized ASC. In another embodiment, the ASC binding molecule preferentially binds to non-polymerized ASC compared to ASC specks. In another embodiment, the ASC binding molecule preferentially binds to ASC specks and does not bind to non-polymerized ASC. In another embodiment, the ASC binding molecule preferentially binds to non-polymerized ASC and does not bind to ASC specs. A suitable assay for assessing preferential binding is provided in Example 6, and the results are shown in Table 8 (immunofluorescence for human ASC) and Table 9 (immunofluorescence for mouse ASC).

[0085] In some embodiments, the binding molecule binds to unpolymerized ASC and does not bind to ASC specks.

[0086] In some embodiments, the ASC binding molecule prevents or inhibits ASC polymerization. The ASC binding molecule can inhibit human ASC polymerization and / or mouse ASC polymerization. ASC polymerization can be measured in vitro, preferably by ASC polymerization assay. In one embodiment, the ASC binding molecule inhibits human ASC polymerization with an IC50 of less than 33 nM, preferably 20 nM, more preferably 6.3 nM, and even more preferably less than 3.1 nM. In one embodiment, the ASC binding molecule inhibits mouse ASC polymerization with an IC50 of less than 61 nM, preferably 35.7 nM, and more preferably less than 22 nM. The IC50 of ASC polymerization can be measured, for example, according to the recombinant ASC polymerization assay of Example 7.

[0087] In some embodiments, the ASC binding molecule may have functional efficacy in inhibiting recombinant ASC polymerization of human ASC (IC50 of approximately 5 nM) and / or mouse ASC (IC50 of approximately 30 nM). A suitable assay for assessing ASC polymerization is disclosed in Example 7.

[0088] In some embodiments, the ASC-binding molecule prevents or inhibits ASC-dependent propagation of inflammation. ASC-dependent propagation of inflammation can be measured in vitro or in vivo. In one embodiment, the prevention or inhibition of ASC-dependent propagation of inflammation is prevention or inhibition of IL-1β release. In one embodiment, the anti-ASC antibody or antigen-binding fragment thereof inhibits IL-1β release with an IC50 of less than 60 nM, preferably 42 nM, more preferably 33 nM, and even more preferably 17 nM, according to a suitable assay disclosed in Example 9. In one embodiment, the anti-ASC antibody inhibits IL-1β release by at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% compared to a control. In some embodiments, the control can be an isotype control antibody.

[0089] In some embodiments, ASC binding molecule increases the uptake of ASC extracellular specks by phagocytic cells such as macrophages or microglia.Uptake can be evaluated in phagocytic cells such as macrophages or microglia differentiated from human monocyte cell line.Examples 8 and 9 provide suitable means for demonstrating the evaluation of macrophage uptake.

[0090] In some embodiments, the ASC binding molecule prevents or inhibits the accumulation of ASC and / or ASC specks. The accumulation of ASC specks can be intracellular or extracellular. Accumulation can be measured by conventional means such as Western blotting or immunofluorescence. Accumulation can also be measured by a combination of means selected from the examples disclosed herein.

[0091] In one embodiment, the ASC binding molecule prevents, reduces, or inhibits demyelination.

[0092] The term "demyelination" is intended to encompass damage to the protective covering (myelin sheath) that surrounds nerve fibers in the brain, the eye (optic nerve), and the nerves leading to the spinal cord. When the myelin sheath is damaged, nerve impulses slow or stop, causing neurological problems.

[0093] In one embodiment, the ASC binding molecule reduces demyelination by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, or at least 85% compared to a control (no ASC binding molecule administered).

[0094] In one embodiment, the ASC binding molecule prevents demyelination in more than 10% of the test region (e.g., from samples collected from the cervical, thoracic, and / or lumbar regions of the spinal cord). In one embodiment, the ASC binding molecule prevents demyelination in more than 15% of the treated region. That is, the ASC binding molecule maintains demyelination of nerve fibers at less than 10% or less than 15% over a period of time. Preferably, the ASC binding molecule maintains demyelination of nerve fibers at less than 5% over a period of time. The period of time can be at least 1 week, at least 1 month, at least 1 year, at least 2 years, at least 5 years, at least 10 years, at least 15 years, at least 20 years, or the period for which the ASC binding molecule is administered to the subject. Thus, in one embodiment, the ASC binding molecule can delay demyelination of nerve fibers for at least 1 week, at least 1 month, at least 1 year, at least 2 years, at least 5 years, at least 10 years, at least 15 years, at least 20 years, or the period for which the ASC binding molecule is administered to the subject. In one embodiment, the ASC-binding molecule can delay the onset of a disease, disorder, or condition associated with demyelination of nerve fibers by at least 1 week, at least 1 month, at least 1 year, at least 2 years, at least 5 years, at least 10 years, at least 15 years, at least 20 years, or the period during which the ASC-binding molecule is administered to the subject. In one embodiment, the ASC-binding molecule that prevents, reduces, or inhibits demyelination is ACI-8016-32B6C7-AB1.

[0095] In one embodiment, preventing, reducing, or inhibiting demyelination is improving the in vivo demyelination score. The score may be based on a scale of 0 to 5 as follows: 0 - No demyelination (less than 2% demyelinated area) 1-2-5% demyelinated area 2-6-19% demyelinated area 3-20-29% demyelinated area 4-30-50% demyelinated area 5->50% demyelinated area.

[0096] Thus, the term "improving the demyelination score" can mean reducing the score. For example, the score can be reduced from 3 to 1, such that the demyelinated area is reduced to 2-5%.

[0097] Scores may depend on clinical improvement as follows: 0 - No obvious change in the motor function of the mice compared to non-immunized mice 1-Limp tail; 2-drooping tail and weakness of hind limbs; 3 - Drooping tail and complete paralysis of hind limbs (most common); or Drooping tail with paralysis of one front limb and one back limb; or both 4 - drooping tail, complete paralysis of the hind limbs and partial paralysis of the forelimbs; 5 - Complete paralysis of the hind limbs and complete paralysis of the forelimbs, no movement in the cage; or the mouse rolls spontaneously in the cage; or the mouse is found dead due to paralysis.

[0098] The ASC binding molecule can increase spleen mass in vivo. For example, the spleen mass can be increased by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% compared to a control (not administering the ASC binding molecule, for example, using an IgG2 isotype control according to Figure 8C). In one embodiment, the ASC binding molecule reduces the level of infiltrating CD4+ T cells that have escaped from the spleen. In one embodiment, the ASC binding molecule reduces the level of infiltrating CD4+ T cells in the spinal cord in vivo. For example, the ASC-binding molecule may reduce the level of infiltrating CD4+ T cells in the spinal cord by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 95%, or at least 100% compared to a control (no ASC-binding molecule administered, e.g., using an IgG2 isotype control according to Figure 9B). In one embodiment, the ASC-binding molecule that reduces the level of infiltrating CD4+ T cells in the spinal cord is ACI-8016-32B6C7-AB1 or ACI-8016-18F4C12-AB1.

[0099] In one embodiment, the ASC binding molecule reduces reactive microglia levels in vivo. For example, the ASC binding molecule can reduce reactive microglia levels by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 95%, or at least 100% compared to a control (not administered with the ASC binding molecule, for example, using an IgG2 isotype control according to Figure 9C). In one embodiment, the ASC binding molecule that reduces reactive microglia levels in vivo is ACI-8016-32B6C7-AB1.

[0100] In one embodiment, the ASC-binding molecule reduces ASC and / or cleaved caspase-1 protein levels in vivo. For example, the ASC-binding molecule can reduce ASC and / or cleaved caspase-1 protein levels by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 95%, or at least 100%, compared to a control (not administered the ASC-binding molecule, for example, using an IgG2 isotype control according to Figure 10). In one embodiment, the ASC-binding molecule that reduces ASC and / or cleaved caspase-1 protein levels in vivo is ACI-8016-32B6C7-AB1.

[0101] In one embodiment, the ASC binding molecule comprises the amino acid residues: a) L9, D10, E13, N14, E18 and E19, b) L9, D10, E13 and N14, c) E13 and N14, d) Q79, E80, G83 and Q84; or e) E18, E19, V30, P31, N71, R74, D75, G77, Q79 and E80 The present invention binds to an epitope in the ASC PYD domain comprising, consisting essentially of, or consisting of:

[0102] The amino acids are described with reference to the amino acid sequence of human ASC in SEQ ID NO: 1. ASC binding molecules contain the amino acid residue numbers of human ASC in SEQ ID NO: 1: a) 9, 10, 13, 14, 18 and 19, b) 9, 10, 13 and 14, c) 13 and 14, d) 79, 80, 83 and 84, or e) 18, 19, 30, 31, 71, 74, 75, 77, 79 and 80 The ASC PYD domain may comprise, consist essentially of, or consist of an epitope in the ASC PYD domain.

[0103] As described in Example 11, epitopes can be defined using alanine scanning mutagenesis. ASC, particularly mutants of the PYD domain of PYCARD, can be used. The binding of ASC binding molecules to mutants can be measured by suitable immunoassays such as ELISA. The residues listed are crucial for binding, which can be defined as any suitable loss of binding, for example, the retention of 30% or less of binding compared to wild-type control in the presence of alanine mutation at that position.

[0104] Alternatively, the ASC binding molecule may comprise the amino acid residues: a) K174 and D175, b) I115, D116, R119, A120, K174, D175, S184, Q185, S186 and Y187, c) I115, D116, N170, W171, T172, K174, D175, S186 and Y187, d) Y137, e) R119, A120, L178, Q179, S186 and Y187, or f) R119, A120, K174, D175, S186 and Y187 The ASC CARD domain may comprise, consist essentially of, or consist of an epitope in the ASC CARD domain.

[0105] The amino acids are described with reference to the amino acid sequence of human ASC in SEQ ID NO: 1. ASC binding molecules contain the amino acid residue numbers of human ASC in SEQ ID NO: 1: a) 174 and 175, b) 115, 116, 119, 120, 174, 175, 184, 186 and 187, c) 115, 116, 170, 171, 172, 174, 175, 186 and 187, d) 137, e) 119, 120, 178, 179, 186 and 187, or f) 119, 120, 174, 175, 186 and 187 The ASC CARD domain may comprise, consist essentially of, or consist of an epitope in the ASC CARD domain.

[0106] As described in Example 13, epitopes can be defined using alanine mutagenesis. Mutants of the CARD domain of ASC, particularly PYCARD, can also be used. The binding of ASC binding molecules to mutants can be measured by suitable immunoassays, such as ELISA. The residues listed are crucial for binding, and this can be defined as any suitable loss of binding, for example, retention of 30% or less of binding compared to wild-type control, in the presence of alanine mutation at that position.

[0107] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 174 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0108] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 175 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0109] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 115 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0110] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 116 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0111] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 119 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0112] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 120 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0113] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 170 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0114] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 184 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0115] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 186 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0116] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 187 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0117] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 171 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0118] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 172 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0119] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 137 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0120] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 178 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0121] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 179 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0122] In one preferred embodiment, the ASC binding molecule is capable of binding to an epitope comprising, consisting essentially of, or consisting of amino acid residues 174 and 175 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0123] In one embodiment, the ASC binding molecule can bind to an epitope comprising amino acid residues 115 and 116 with reference to the amino acid sequence of human ASC of SEQ ID NO:1.

[0124] In one embodiment, the ASC binding molecule can bind to an epitope comprising amino acid residues 119 and 120 with reference to the amino acid sequence of human ASC of SEQ ID NO:1.

[0125] In one embodiment, the ASC binding molecule can bind to an epitope comprising amino acid residues 170, 171, and 172 with reference to the amino acid sequence of human ASC of SEQ ID NO:1.

[0126] In one embodiment, the ASC binding molecule can bind to an epitope comprising amino acid residues 186 and 187 with reference to the amino acid sequence of human ASC of SEQ ID NO:1.

[0127] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residues 115, 116, 119, 120, 174, 175, 184, 186, and 187 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0128] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residues 115, 116, 170, 171, 172, 174, 175, 186, and 187 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0129] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residue 137 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0130] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residues 119, 120, 178, 179, 186, and 187 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0131] In one embodiment, the ASC binding molecule can bind to an epitope comprising, consisting essentially of, or consisting of amino acid residues 119, 120, 174, 175, 186, and 187 with reference to the amino acid sequence of human ASC in SEQ ID NO:1.

[0132] In one embodiment, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, 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 NEV (Asn-Glu-Val), 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; or b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 23, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; or c. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, 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 d. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, 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; or e. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 53, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 57; or 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: 63, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; or g. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 71, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, 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: 76, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; or h. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 81, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 82, 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: 86, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87; or i. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97; or j. 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; or k. 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; or l. 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: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137; or m. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 147; or n. 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; or o. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, 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; or p. 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: 176, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177; or q. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 181, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 182, 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: 185, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187; or r. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 191, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197; or s. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or t. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 217; or u. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 221, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 226, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227; or v. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237; or w. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 241, 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: 243, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 245, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 246, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247; or x. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 251, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257; or y. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 266, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267; or z. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or aa. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287; or bb. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 291, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 292, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 293, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 295, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 297; or cc. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 71, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 305, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 307; or dd. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312, VH-CDR3 comprising the amino acid sequence RDY (Arg-Asp-Tyr), VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 317; or ee. 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: 322, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327; or ff. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 331, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 337; or gg. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347; or hh. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 331, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 337; or ii. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, a VH-CDR3 comprising the amino acid sequence RDY (Arg-Asp-Tyr), a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367; or jj. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 375, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 377; or kk. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 381, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387; or ll. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 392, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 Includes.

[0133] In one embodiment, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 11, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and VH-CDR3 comprising the amino acid sequence NEV (Asn-Glu-Val); or b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 23; or c. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; or d. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; or e. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 53; or f. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 63; or g. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 71, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; or h. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 81, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 82, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; or i. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93; or j. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 112, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 113; or k. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 121, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 122, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 123; or l. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 131, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 132, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 133; or m. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 111, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143; or n. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 151, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; or o. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 162, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 163; or p. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173; 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, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 183; or r. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 191, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193; or s. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; or t. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 211, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 212, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 213; or u. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 221, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223; or v. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233; or w. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 241, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 243; or x. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 251, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253; or y. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263; or z. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; or aa. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283; or bb. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 291, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 292, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 293; or cc. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 71, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303; or dd. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 312, and VH-CDR3 comprising the amino acid sequence RDY (Arg-Asp-Tyr); or ee. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 322, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323; or ff. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 331, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333; or gg. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323; or hh. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 331, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353; or ii. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, and VH-CDR3 comprising the amino acid sequence RDY (Arg-Asp-Tyr); or jj. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373; or kk. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 381, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383; or ll. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 392, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 393 The heavy chain variable region comprises:

[0134] In one embodiment, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, a. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; or b. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; or c. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; or d. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47; or e. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 57; or f. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 65, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; or g. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 75, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; or h. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 86, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87; or i. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97; or j. 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; or k. 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; or l. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 135, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137; or m. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 147; or n. 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; or o. 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; or p. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177; or q. a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 185, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187; or r. a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 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; or s. a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or t. a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 215, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 217; or u. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 226, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227; or v. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237; or w. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 245, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 246, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247; or x. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257; or y. a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 266, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267; or z. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or aa. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287; or bb. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 295, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 297; or cc. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 305, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 126, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 307; or dd. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 317; or ee. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327; or ff. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 337; or gg. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347; or hh. a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 337; or ii. a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367; or ii. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 375, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 377; or kk. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387; or ll. VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 The light chain variable region (VL) comprises:

[0135] In one embodiment of the present invention, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 10, 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: 10; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 14; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 20, 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: 20; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 24, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 24; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 30, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 34, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 40, or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 44, 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: 44; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 50, 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: 50; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 54, 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: 54; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 60, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 64; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 70, 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: 70; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 74, 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: 74; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 80, 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: 80; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 84, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 90, 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: 90; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 94, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 110, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) comprising the amino acid 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; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 120, 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: 120; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 124, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 130, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 134, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 134; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 140, or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 144, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 144; or n. a heavy chain variable region (VH) comprising the amino acid 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 amino acid sequence of SEQ ID NO: 154, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 160, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 164, 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: 164; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 170, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 174, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 174; or q. a heavy chain variable region (VH) comprising the amino acid 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 amino acid sequence of SEQ ID NO: 184, 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: 184; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 190, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 190; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 194; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 204; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 210, 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: 210; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 214, 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: 214; or u. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 220, or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 220; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 224, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 224; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 230, or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 230; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 234, or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 234; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 240, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 240; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 244, 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: 244; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 250, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 250; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 254, 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: 254; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 260, 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: 260; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 264, 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: 264; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 270, 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: 270; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 274, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 274; or aa. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 280, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 280; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 284, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 284; or bb. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 290, 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: 290; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 294, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 294; or cc. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 300, 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: 300; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 304, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 304; or dd. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 310, 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: 310; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 314, 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: 314; or ee. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 320, 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: 320; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 324, or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 324; or ff. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 330, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 330; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 334, 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: 334; or gg. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 340, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 340; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 344, or a light chain variable region (VL) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 344; or hh. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 350, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 350; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 354, 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: 354; or ii. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 360, 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: 360; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 364, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 364; or jj. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 370, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 370; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 374, or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 374; or kk. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 380, or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 380; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 384, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 384; or ll. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 390, 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: 390; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 394. Includes.

[0136] In one embodiment of the present invention, the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 10, 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: 10; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 20, 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: 20; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 24; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 30, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 34; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 40, or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 44; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 50, 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: 50; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 54; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 60, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 64; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 70, 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: 70; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 74; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 80, 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: 80; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 84; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 90, 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: 90; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 94; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 110, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 114; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 120, 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: 120; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 124; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 130, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 134; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 140, or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 144; or n. a heavy chain variable region (VH) comprising the amino acid 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 amino acid sequence of SEQ ID NO: 154; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 160, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 164; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 170, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 174; or q. a heavy chain variable region (VH) comprising the amino acid 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 amino acid sequence of SEQ ID NO: 184; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 190, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 190; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 194; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 210, 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: 210; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 214; or u. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 220, or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 220; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 224; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 230, or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 230; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 234; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 240, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 240; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 244; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 250, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 250; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 254; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 260, 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: 260; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 264; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 270, 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: 270; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 274; or aa. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 280, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 280; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 284; or bb. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 290, 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: 290; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 294; or cc. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 300, 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: 300; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 304; or dd. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 310, 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: 310; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 314; or ee. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 320, 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: 320; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 324; or ff. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 330, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 330; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 334; or gg. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 340, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 340; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 344; or hh. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 350, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 350; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 354; or ii. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 360, 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: 360; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 364; or jj. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 370, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 370; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 374; or kk. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 380, or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 380; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 384; or ll. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 390, 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: 390; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 394. Includes.

[0137] In one embodiment of the present invention, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 10, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 14; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 20, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 24, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 24; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 30, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 40 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 44, 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: 44; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 50 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 54, 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: 54; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 60, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 64; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 70 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 74, 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: 74; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 80, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 84, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 90, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 94, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 110 and a light chain variable region (VL) comprising the amino acid 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; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 120, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 124, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 130, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 134, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 134; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 140, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 144; or n. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 150, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 154, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 160, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 164, 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: 164; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 170, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 174, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 174; or q. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 180, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 184, 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: 184; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 190, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 194; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 204; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 210, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 214, 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: 214; or u. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 220, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 224, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 224; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 230, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 234, or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 234; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 240, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 244, 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: 244; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 250, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 254, 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: 254; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 260, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 264, 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: 264; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 270, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 274, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 274; or aa. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 280, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 284, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 284; or bb. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 290, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 294, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 294; or cc. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 300, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 304, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 304; or dd. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 310, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 314, 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: 314; or ee. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 320, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 324, or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 324; or ff. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 330, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 334, 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: 334; or gg. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 340, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 344, or a light chain variable region (VL) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 344; or hh. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 350, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 354, 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: 354; or ii. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 360, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 364, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 364; or jj. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 370 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 374, or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 374; or kk. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 380, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 384, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 384; or ll. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 390, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 394. Includes.

[0138] In one embodiment, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, comprises a heavy chain variable region comprising a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203.

[0139] In one embodiment, an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof of the present invention, may comprise a light chain variable region (VL) comprising a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207.

[0140] In one embodiment, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, comprises a VH-CDR1 having the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 having the amino acid sequence of SEQ ID NO: 202, and a VH-CDR3 having the amino acid sequence of SEQ ID NO: 203, a VL-CDR1 having the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 having the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 having the amino acid sequence of SEQ ID NO: 207.

[0141] In one embodiment of the present invention, the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) that may comprise the amino acid sequence of SEQ ID NO: 200, 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: 200; and a light chain variable region (VL) that comprises the amino acid sequence of SEQ ID NO: 204.

[0142] In one embodiment of the present invention, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 204; or

[0143] In one embodiment of the present invention, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the present invention, may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, or a heavy chain variable region having at least 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 204.

[0144] In certain embodiments, the ASC-binding molecule of the present invention is a monoclonal antibody or an antigen-binding fragment thereof.

[0145] In certain embodiments, the anti-ASC antibody or antigen-binding fragment thereof of the present invention is an IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3, or IgG4 antibody or antigen-binding fragment thereof. The anti-ASC antibody or antigen-binding fragment thereof is human or mouse, preferably human IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3, or IgG4. In one embodiment, the ASC-binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof, is a human IgG4 isotype containing the S228P mutation.

[0146] In certain embodiments, the antibodies provided herein are selected from the group consisting of ACI-8016-416E6G4-AB1, ACI-8016-402H11C9-Ab1, ACI-8016-203B12C3-AB1, ACI-8016-421B10C12D2-AB1, ACI-8016-417E12A8-AB1, ACI-8016-413G10A5-AB1, ACI-8016-407E10A9-AB1, ACI-8016-203G8B10-AB1, ACI-8016-40 1H9B7-AB1, ACI-8016-1112B3D7-AB1, ACI-8018-2221B7F1-AB1, ACI-8019-2314F6H11-AB1, ACI-8016-207E8B2-AB1, ACI-8016-2A1B1 2-AB1, ACI-8016-17H1G2-AB1, ACI-8016-18F4C12-AB1, ACI-8016-23E5F7-AB1, ACI-8016-23E5F7-AB2, ACI-8016-26A1G2-AB1, ACI-80 16-32B6C7-AB1, ACI-8016-22D3A6-AB1, ACI-8016-31F10C5-AB1, ACI-8016-19E6D4-AB1, ACI-8016-3E6B11-AB1, ACI-8016-11A3F3-A B1, ACI-8016-14G5B8-AB1, ACI-8016-22A10F8-AB1, ACI-8016-27A1G4-AB1, ACI-8016-29C5E11-AB1, ACI-8016-7G3B5-AB1, ACI-8016 -2504F3D9-AB1, ACI-8016-2516A8C6-AB1, ACI-8016-2602H6F10-AB1, ACI-8016-2609F4A9-AB1, ACI-8016-2610H7D3-AB1, ACI-8016-2614C3B2-AB1, ACI-8016-2617C3A8-AB1, ACI-8016-2622E12F11-AB1, ACI-8016-2626B9D3-AB1, or ACI-8016-2629E8D1-AB1. In one embodiment, the antibody provided herein can be selected from Table 17.

[0147] In certain embodiments, the antibody provided herein is selected from ACI-8016-32B6C7-AB1 and ACI-8016-18F4C12-AB1.

[0148] In certain preferred embodiments, the antibody provided herein is ACI-8016-32B6C7-AB1.

[0149] In one embodiment, the ASC-binding molecule is a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or d) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or e) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or f) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or g) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 may include:

[0150] In one embodiment, the ASC-binding molecule is a) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; or b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; or c) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; or d) VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 472, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203 may include:

[0151] In one embodiment, the ASC-binding molecule is a) a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or b) VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 may include:

[0152] In one embodiment, the ASC-binding molecule is a) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or b) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414, or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or c) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or d) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or e) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or f) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or g) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or h) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 470 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 470, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or i) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or j) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 490 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 490, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or k) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 500 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 500, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or l) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 510, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 510, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or m) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or n) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 530 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 530, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or o) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 540 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 540, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or p) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or q) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or r) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or s) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or t) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or u) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or v) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or w) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or x) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or y) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or z) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or aa) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or bb) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 or having at least 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424. may include:

[0153] In one embodiment, the ASC-binding molecule is a) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or b) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or c) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or d) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or e) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or f) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or g) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or h) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 470 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 470, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or i) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or j) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 490 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 490, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or k) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 500 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 500, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or l) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 510 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 510, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or m) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or n) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 530 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 530, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or o) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 540 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 540, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or p) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or q) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or r) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or s) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or t) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or u) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or v) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or w) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or x) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or y) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or z) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or aa) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or bb) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 or having at least 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424. may include:

[0154] In one embodiment, the ASC-binding molecule is a) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or b) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or c) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or d) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or e) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or f) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or g) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or h) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 470 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or i) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or j) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 490 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or k) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 500 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or l) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 510 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or m) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or n) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 530 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or o) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 540 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or p) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or q) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or r) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or s) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or t) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or u) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or v) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or w) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or x) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or y) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or z) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or aa) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or bb) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424 may include:

[0155] In one embodiment, the ASC-binding molecule is a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; c. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207 may include:

[0156] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424. may include:

[0157] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424. may include:

[0158] In one embodiment, the ASC-binding molecule is a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or d. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424. may include:

[0159] In one preferred embodiment, the ASC binding molecule may comprise a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207.

[0160] In one preferred embodiment, the ASC binding molecule may comprise a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207.

[0161] In one preferred embodiment, the ASC binding molecule may comprise a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207.

[0162] In one embodiment, the ASC binding molecule may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434.

[0163] In one embodiment, the ASC binding molecule may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434.

[0164] In one embodiment, the ASC binding molecule may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434.

[0165] In one embodiment, the ASC binding molecule may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:480 or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:424 or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:424.

[0166] In one embodiment, the ASC binding molecule may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:434.

[0167] In one embodiment, the ASC binding molecule may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:434.

[0168] In one embodiment, the ASC binding molecule may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:434.

[0169] In one embodiment, the ASC binding molecule may comprise a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:424.

[0170] The ASC binding molecule can be a heterohybrid anti-ASC antibody or an antigen-binding fragment thereof. The heterohybrid anti-ASC antibody can be a humanized or chimeric anti-ASC antibody.

[0171] The ASC binding molecule can be a monoclonal antibody or its antigen-binding fragment.The heterohybrid anti-ASC antibody can also be a monoclonal antibody.For example, the ASC binding molecule can be a humanized anti-ASC antibody that binds to ASC speck and / or unpolymerized ASC.

[0172] The ASC binding molecule can be a heterohybrid anti-ASC antibody or an antigen-binding fragment thereof. The heterohybrid anti-ASC antibody can be a humanized or chimeric anti-ASC antibody.

[0173] The ASC binding molecule can be a monoclonal antibody or its antigen-binding fragment.The heterohybrid anti-ASC antibody can also be a monoclonal antibody.For example, the ASC binding molecule can be a humanized anti-ASC antibody that binds to ASC speck and / or unpolymerized ASC.

[0174] The ASC binding molecule may exhibit an affinity constant KD in the range of about 49 pM to about 1010 pM with respect to human ASC. The ASC binding molecule may further exhibit a binding rate ka in the range of about 2.09E+04 1 / Ms to about 1.08E+05 1 / Ms with respect to human ASC.

[0175] Additionally, the ASC binding molecule may exhibit a dissociation rate, kd, with respect to human ASC, ranging from about 4.82E-06 1 / s to about 2.11E-05 1 / s.

[0176] The values ​​of the equilibrium dissociation constant (KD), dissociation rate constant (kd) and association rate constant (ka) can be determined by surface plasmon resonance.

[0177] The ASC-binding molecule, which may be an antibody or antibody-binding fragment thereof, may be selected from Table 20. For example, the antibody or antibody-binding fragment thereof may comprise the sequence defined by ACI-8016-32B6C7-AB1, ACI-8016-2629E8D1-AB1, ACI-8016-2504F3D9-AB1, ACI-8016-18F4C12-AB1, ACI-8016-2622E12F11-AB1, ACI-8016-2609F4A9-AB1.

[0178] The antibody or antigen-binding fragment thereof may comprise the sequence defined by ACI-8016-32B6C7-AB1.

[0179] The antibody or antigen-binding fragment thereof may comprise the sequence defined by ACI-8016-2629E8D1-AB1.

[0180] The antibody or antigen-binding fragment thereof may comprise the sequence defined by ACI-8016-2504F3D9-AB1.

[0181] The antibody or antigen-binding fragment thereof may comprise the sequence defined by ACI-8016-18F4C12-AB1.

[0182] The antibody or antigen-binding fragment thereof may comprise the sequence defined by ACI-8016-2622E12F11-AB1.

[0183] The antibody or antigen-binding fragment thereof may comprise the sequence defined by ACI-8016-2609F4A9-AB1.

[0184] The ASC binding molecule can be an antibody or antibody-binding fragment thereof according to Table 19 or Table 20. For example, the antibody or antibody-binding fragment thereof can comprise the sequence defined by hACI-8016-32B6C7-AB1_H5L4, hACI-8016-32B6C7-AB1_H7L4, hACI-8016-32B6C7-AB1_H13L4, or hACI-8016-32B6C7-AB1_H9L3.

[0185] For example, according to one embodiment, antibodies or antigen-binding fragments thereof of the sequence defined by hACI-8016-32B6C7-AB1_H5L4, hACI-8016-32B6C7-AB1_H7L4, hACI-8016-32B6C7-AB1_H13L4 or hACI-8016-32B6C7-AB1_H9L3 may be preferred based on KD, potency, and functionality, which demonstrate a favorable developability profile.

[0186] In one embodiment, the antibody or antigen-binding fragment thereof may comprise the sequence defined by hACI-8016-32B6C7-AB1_H5L4.

[0187] In one embodiment, the antibody or antibody-binding fragment thereof may comprise the sequence defined by hACI-8016-32B6C7-AB1_H7L4. In one embodiment, the antibody or antibody-binding fragment thereof may comprise the sequence defined by hACI-8016-32B6C7-AB1_H13L4.

[0188] In one embodiment, the antibody or antigen-binding fragment thereof may comprise the sequence defined by hACI-8016-32B6C7-AB1_H9L3.

[0189] In one embodiment, the binding affinity to ASC, such as ASC specks and / or non-polymerized ASC, can be assessed by determining the equilibrium dissociation constant (KD, also called affinity constant or dissociation constant) using surface plasmon resonance (SPR; Biacore 8K, GE Healthcare Life Sciences). For a detailed description of a suitable SPR method that can be used, see Example 11.

[0190] ASC-binding molecules, particularly heterohybrid anti-ASC antibodies or antigen-binding fragments thereof, may have an equilibrium dissociation constant (KD) for binding ASC, particularly human ASC, of ​​<10 nM, ≦1 nM, ≦100 pM, ≦10 pM, or ≦1 pM (e.g., 10-8 or less, e.g., 10-8 M to 10-13 M, e.g., 10-9 M to 10-11 M). For example, heterohybrid anti-ASC antibodies of the invention may have a KD for human ASC of 2000 pM or less, and in certain embodiments, 1500 pM or less, e.g., 1250 pM or less, and preferably 1050 pM or less. This is demonstrated for ASC-binding molecules of the invention in Example 11 with reference to Table 21.

[0191] The ASC binding molecules of the present invention may have a KD of 1050 pM or less for human ASC, a KD of 150 pM or less for human ASC, a KD of 100 pM or less for human ASC, a KD of 90 pM or less for human ASC, a KD of 80 pM or less for human ASC, a KD of 70 pM or less for human ASC, a KD of 60 pM or less for human ASC, or a KD of 50 pM or less for human ASC.

[0192] The ASC-binding molecule of the present invention has a dissociation rate (kd) of 9.5E-06 1 / s or less for human ASC, a dissociation rate (kd) of 9.0E-06 1 / s or less for human ASC, a dissociation rate (kd) of 8.5E-06 1 / s or less for human ASC, a dissociation rate (kd) of 8E-06 1 / s or less for human ASC, a dissociation rate (kd) of 7.5E-06 1 / s or less for human ASC, a dissociation rate (kd) of 7E-06 1 / s or less for human ASC, a dissociation rate (kd) of 6.5E-06 1 / s or less for human ASC, a dissociation rate (kd) of 6E-06 1 / s or less for human ASC, a dissociation rate (kd) of 5.5E-06 1 / s or less for human ASC, and a dissociation rate (kd) of 5E-06 1 / s or less for human ASC. It may have a dissociation rate (kd) of 1 / s or less for human ASC, a dissociation rate (kd) of 4.5E-06 1 / s or less for human ASC, a dissociation rate (kd) of 4E-06 1 / s or less for human ASC, or a dissociation rate (kd) of 3.5E-05 1 / s or less for human ASC.

[0193] The ASC-binding molecules of the present invention have an association rate (ka) of 2E+5 1 / Ms or less with respect to human ASC, an association rate (ka) of 1.5E+5 1 / Ms or less, an association rate (ka) of 1E+5 1 / Ms or less, an association rate (ka) of 9.5E+4 1 / Ms or less, an association rate (ka) of 9E+4 1 / Ms or less, an association rate (ka) of 8.5E+4 1 / Ms or less, an association rate (ka) of 8E+4 1 / Ms or less, an association rate (ka) of 7.5E+4 1 / Ms or less, an association rate (ka) of 7E+4 1 / Ms or less, an association rate (ka) of 6.5E+4 1 / Ms or less, an association rate (ka) of 6E+4 1 / Ms or less, an association rate (ka) of 5.5E+4 1 / Ms or less, an association rate (ka) of 5E+4 1 / Ms or less. It may have an association rate (ka) of 1 / M s or less, an association rate (ka) of 4.5E+4 1 / M s or less, an association rate (ka) of 4E+4 1 / M s or less, an association rate (ka) of 3.5E+4 1 / M s or less, an association rate (ka) of 3E+4 1 / M s or less.

[0194] In some embodiments, the ASC binding molecule may exhibit an equilibrium dissociation constant KD with respect to human ASC in the range of about 40 pM to about 1020 pM. The ASC binding molecule may further exhibit an association constant ka value with respect to human ASC in the range of about 2.0E+04 1 / Ms to about 1.0E+05 1 / Ms. Additionally, the ASC binding molecule may exhibit a dissociation rate kd with respect to human ASC in the range of about 4.0E-06 1 / s to about 2.0E-05 1 / s. The values ​​of the equilibrium dissociation constant (KD), dissociation rate constant (kd), and association rate constant (ka) may be determined by surface plasmon resonance.

[0195] The ASC binding molecule that is an antibody or an antibody-binding fragment thereof may include the sequences defined by ACI-8016-32B6C7-AB1, ACI-8016-2629E8D1-AB1, ACI-8016-2504F3D9-AB1, ACI-8016-18F4C12-AB1, ACI-8016-2622E12F11-AB1, ACI-8016-2609F4A9-AB1 listed in Table 20.

[0196] In some embodiments, the ASC binding molecules of the present invention are for use in human or veterinary therapy. In one embodiment, the ASC binding molecules of the present invention are for the prevention, alleviation, treatment, and / or diagnosis of a disease, disorder, or condition associated with the activation of ASC-dependent inflammation. In one embodiment, the ASC binding molecules for use in the present invention are for the prevention, alleviation, treatment, and / or diagnosis of a disease, disorder, or condition associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs. In one embodiment, the ASC binding molecules of the present invention are for use in preventing a disease, disorder, or condition associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs. In one embodiment, the ASC binding molecules or immunoconjugates of the present invention are for use in delaying the onset of a disease, disorder, or condition associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs. In one embodiment, the ASC binding molecules of the present invention are for use in alleviating a disease, disorder, or condition associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs. In one embodiment, the ASC-binding molecule of the present invention is for use in treating a disease, disorder, or condition associated with the accumulation of unpolymerized ASC or ASC specs, preferably ASC specs, more preferably extracellular unpolymerized ASC and / or extracellular ASC specs. In one embodiment, the ASC-binding molecule or immunoconjugate of the present invention is for use in preventing, alleviating, or treating a disease, disorder, or condition associated with demyelination. In one embodiment, the disease, disorder, or condition associated with the accumulation of ASC or ASC specs, preferably ASC specs, more preferably extracellular ASC specs, is selected from a disease of the central nervous system or a peripheral inflammatory condition. The disease of the central nervous system is preferably Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, or chronic traumatic encephalopathy.The peripheral inflammatory condition is preferably non-alcoholic steatohepatitis (NASH), cryopyrin-associated periodic fever syndrome (CAPS), chronic obstructive pulmonary disease (COPD), gout, acne, hidradenitis suppurativa (HS), psoriasis, inflammatory bowel disease (IBD) (e.g., ulcerative colitis or Crohn's disease), edema (DME), geographic atrophy (GA), coronavirus-associated respiratory distress syndrome (CARDS), or Sjogren's syndrome.

[0197] In additional embodiments, the ASC binding molecules, particularly the anti-ASC antibodies or antigen-binding fragments thereof of the present invention, are envisioned for the prevention, alleviation, treatment, and / or diagnosis of diseases, disorders, or conditions associated with the accumulation of ASC or ASC specs, preferably ASC specs, more preferably extracellular ASC specs, or diseases involving inflammasome activation.

[0198] In one embodiment, the methods of the invention involve delaying the onset of a disease, disorder or condition associated with the accumulation of ASCs and / or ASC specs, preferably extracellular ASC specs.

[0199] In one embodiment, the methods of the present invention include preventing, alleviating, or treating a disease, disorder, or condition associated with demyelination.

[0200] Diseases envisioned in accordance with the present invention include diseases of the central nervous system (CNS), pain, diseases of the lungs and airways, cardiovascular diseases, liver diseases, metabolic and renal diseases, skin diseases, reproductive disorders, autoinflammatory and autoimmune diseases, cancer, infectious diseases, and peripheral inflammatory conditions.

[0201] CNS disease can be Parkinson's disease, Alzheimer's disease, age-related cognitive impairment, mild cognitive impairment, frontotemporal dementia, amyotrophic lateral sclerosis, traumatic brain injury, chronic traumatic encephalopathy, spinal cord injury, stroke, intracerebral hemorrhage, multiple sclerosis, sepsis-related encephalopathy, cerebral ischemia, subarachnoid hemorrhage, epilepsy, acrylamide poisoning, opioid-induced neuroinflammation, chronic migraine, perioperative neurocognitive disorder, post-stroke cognitive dysfunction, post-cardiac arrest cognitive impairment, social isolation-induced cognitive impairment, anxiety, multiple system atrophy, Pick's disease, progressive isolated aphasia, or dementia with Lewy bodies, and post-traumatic stress disorder.Preferably, CNS disease is Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, chronic traumatic encephalopathy.

[0202] The pain may be neuropathic pain.

[0203] The lung and airway disease can be allergic rhinitis, chronic obstructive pulmonary disease, cystic fibrosis, acute respiratory distress syndrome, steroid-resistant asthma, asthma, ischemia-reperfusion lung injury, particulate matter-induced lung injury, radiation pneumonitis, pulmonary hypertension, sarcoidosis.

[0204] The cardiovascular disease may be atherosclerosis, heart failure, hypertension, myocardial infarction, atrial fibrillation, cardiac damage induced by metabolic dysfunction, heart failure, vascular endothelial dysfunction, gastrointestinal disease such as colitis, inflammatory bowel disease.

[0205] The liver disease can be acute liver failure, circadian immune regulation, nonalcoholic steatohepatitis (NASH), ischemia-reperfusion liver injury, idiosyncratic drug-induced liver injury, or liver fibrosis.

[0206] The metabolic and renal disease can be diabetic encephalopathy, diabetes-related atherosclerosis, insulin resistance, islet transplant rejection, chronic crystalline nephropathy, renal fibrosis, ischemia / reperfusion renal injury, obesity-related renal disease, renal hypertension, focal segmental glomerulosclerosis, diabetic nephropathy, IgA nephropathy.

[0207] The skin disease may be psoriasis, acne, or hidradenitis suppurativa.

[0208] The reproductive disorder may be premature birth.

[0209] The autoinflammatory and autoimmune disease may be familial Mediterranean fever, cryopyrin-associated periodic fever syndrome (CAPS), Schnitzler syndrome, myelodysplastic syndrome, rheumatoid arthritis, sickle cell disease, valosin-containing protein (VCP)-associated disease, gout, systemic lupus erythematosus, or psoriatic arthritis.

[0210] The infectious disease can be a disease caused by bacteria, viruses, or parasites, such as human immunodeficiency virus-1 (HIV-1), coronavirus disease (COVID)-19, hepatitis B.

[0211] The peripheral inflammatory condition can be non-alcoholic steatohepatitis (NASH), cryopyrin-associated periodic fever syndrome (CAPS), chronic obstructive pulmonary disease (COPD), gout, acne, hidradenitis suppurativa (HS), inflammatory bowel disease (IBD) (e.g., ulcerative colitis or Crohn's disease), edema (DME), geographic atrophy (GA), coronavirus-associated respiratory distress syndrome (CARDS), or Sjogren's syndrome.

[0212] In one embodiment, the method of the present invention includes preventing or reducing demyelination in a subject. The method may include administering an ASC-binding molecule described herein or an immunoconjugate described herein to the subject. In one embodiment, preventing or reducing demyelination is improving the in vivo demyelination score.

[0213] In one embodiment, the method of the present invention comprises reducing the level of reactive microglia in a subject. The method may comprise administering to the subject an ASC-binding molecule described herein or an immunoconjugate described herein.

[0214] In one embodiment, the method of the present invention comprises reducing ASC and / or cleaved caspase-1 protein levels in a subject. The method may comprise administering to the subject an ASC-binding molecule described herein or an immunoconjugate described herein.

[0215] In one embodiment, the method of the present invention comprises reducing the level of infiltrating CD4+ T cells in the spinal cord of a subject. The method may comprise administering to the subject an ASC-binding molecule described herein or an immunoconjugate described herein.

[0216] The present invention also relates to compositions comprising ASC-binding molecules, particularly the anti-ASC antibodies or antigen-binding fragments thereof of the present invention described herein. The present invention further relates to immunotherapeutic and / or immunodiagnostic methods of using such compositions in the prevention, diagnosis, and / or treatment of ASC speck-associated diseases, disorders, or conditions, wherein an effective amount of the composition is administered to a subject in need thereof.

[0217] In some embodiments, the present invention encompasses ASC binding molecules, particularly the anti-ASC antibodies and antigen-binding fragments thereof described herein that specifically bind to ASC, and the use of these binding molecules to diagnose, prevent, alleviate, and / or treat diseases, disorders, or conditions associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs. The methods and compositions disclosed herein have application in diagnosing, preventing, alleviating, and / or treating diseases, disorders, or conditions associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs.

[0218] In another embodiment, an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof of the present invention described herein, is contacted with a sample to detect, diagnose, and / or monitor a disease, disorder, or condition associated with the accumulation of ASC and / or ASC specks, preferably extracellular ASC specks.

[0219] In one embodiment, the present invention encompasses ASC-binding molecules, particularly anti-ASC antibodies or antigen-binding fragments thereof described herein, which specifically bind to ASC specks and / or unpolymerized ASC, and the use of these molecules, particularly these antibodies, to detect the presence of ASC in a sample. Thus, ASC-binding molecules, particularly anti-ASC antibodies or antigen-binding fragments thereof, can be used to screen clinical samples, particularly body fluids, especially human blood, CSF, interstitial fluid (ISF), and / or urine, for the presence of ASC in the sample, for example, by using ELISA-based or surface-compatible assays. The methods and compositions of the present invention also have application in diagnosing preclinical disease and / or monitoring disease progression and / or treatment effectiveness. Many suitable immunoassay formats are known. Thus, methods (e.g., ELISA, MSD (Meso Scale Discovery), HTRF (Homogeneous Time Resolved Fluorescence), and AlphaLISA) may be performed for diagnostic purposes. Alternatively, methods may be performed for monitoring purposes. Increased levels over time may indicate disease progression. A decrease in levels over time may indicate regression of the disease. The method can also be used to monitor therapy, particularly to monitor the effectiveness of a particular treatment. The method of quantifying ASC in a suitable sample using the binding molecules of the present invention may also be used to select a therapy (for further treatment of the subject). In this way, a method of personalized treatment is envisioned. In a preferred embodiment, the therapy comprises an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof of the present invention, typically in the form of a pharmaceutical composition as described herein.

[0220] In other embodiments, the present invention provides methods for preventing, alleviating, and / or treating diseases, disorders, or conditions associated with ASC-dependent inflammasomes. According to one embodiment, the method of the present invention comprises administering to a subject an effective concentration of an ASC-binding molecule, particularly an anti-ASC antibody of the present invention or an antigen-binding fragment thereof specific for ASC described herein. In another embodiment, the present invention provides methods for preventing, alleviating, and / or treating inflammasome-associated diseases. According to some embodiments, an ASC-binding molecule, particularly an anti-ASC antibody of the present invention specific for ASC or an antigen-binding fragment thereof described herein, is administered to treat, alleviate, and / or prevent diseases defined herein.

[0221] In some embodiments, there is provided an immunoconjugate comprising an (isolated) antibody described herein and a therapeutic agent. In some embodiments, there is provided a labeled antibody comprising an antibody described herein and a detectable label.

[0222] In some embodiments, a pharmaceutical composition is provided comprising an (isolated) antibody described herein and a pharmaceutically acceptable carrier.

[0223] In some embodiments, the ASC binding molecule, particularly the anti-ASC antibody or antigen-binding fragment thereof of the invention, is linked to a detectable label.

[0224] In some embodiments, the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is part of an immunoconjugate in which the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is covalently linked to another suitable therapeutic agent.

[0225] In some embodiments, the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, or an immunoconjugate comprising same, is present as a composition comprising the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof.

[0226] In some embodiments, the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is part of a pharmaceutical composition comprising the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or an immunoconjugate in which the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is covalently linked to another suitable therapeutic agent, or a composition described herein.

[0227] In some embodiments, the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is part of a detection and / or diagnostic kit comprising the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, or an immunoconjugate in which the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, is covalently linked to another suitable therapeutic agent, or a composition described herein.

[0228] Kits containing the binding molecules of the present invention are also provided. In particular, such kits can be useful for carrying out the diagnostic methods of the present invention (including classification, monitoring, and treatment selection methods). Thus, kits for diagnosing diseases, disorders, and / or abnormalities associated with ASC-dependent inflammasomes or for use in the methods of the present invention are provided, which include ASC-binding molecules, particularly anti-ASC antibodies or antigen-binding fragments thereof of the present invention. Such kits can include all components necessary to carry out the methods provided herein. Typically, each component is stored separately within a single overall package. Suitable additional components for inclusion in the kit include, for example, buffers, detectable dyes, laboratory equipment, reaction vessels, instructions for use, and the like. The instructions can be tailored to the specific method for using the kit. Appropriately labeled ASC-binding molecules, particularly anti-ASC antibodies or antigen-binding fragments thereof of the present invention, can also be provided and included in such kits.

[0229] In some embodiments, the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is part of an immunotherapeutic method for the prevention or treatment of a disease, disorder, or condition associated with ASC, particularly associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs or ASC spec complexes that propagate inflammation, in which an effective amount of the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, or an immunoconjugate in which the ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, is covalently linked to another therapeutic agent, or a composition described herein, is administered to a subject in need thereof.

[0230] In some embodiments, an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, or an immunoconjugate in which an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, is covalently linked to another suitable therapeutic agent, or a composition described herein, is administered to a subject in need thereof and used to diagnose, prevent, alleviate, or treat a disease, disorder, or condition associated with ASC, particularly associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs.

[0231] In other embodiments, the present invention relates to any method of detecting, diagnosing, or monitoring a disease, disorder, or condition associated with ASC, in particular associated with ASC and / or ASC specs, preferably extracellular ASC specs.

[0232] Preferably, the ASC-associated disease disorder or condition is associated with the inflammation-propagating ASC speck complex disclosed herein.

[0233] In some embodiments, ASC binding molecules, particularly anti-ASC antibodies or their antigen-binding fragments, are used in methods for diagnosing preclinical disease, or for monitoring disease progression and treatment effectiveness, or for predicting response, or for selecting subjects who may respond to treatment with ASC binding molecules, particularly anti-ASC antibodies or their antigen-binding fragments.The methods can be carried out using human blood or urine samples.Most preferably, the methods are based on ELISA or involve surface-compatible assays.

[0234] In some embodiments, an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, or an immunoconjugate in which an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment, is covalently linked to another suitable therapeutic agent, or a composition described herein, is administered to a subject in need thereof and used in the manufacture of a medicament for treating a disease, disorder, and / or abnormality associated with ASC, particularly associated with the accumulation of ASC and / or ASC specs, preferably extracellular ASC specs.

[0235] Pharmaceutical formulations of ASC-binding molecules, particularly anti-ASC antibodies or antigen-binding fragments, or immunoconjugates described herein, are prepared by mixing such antibodies or immunoconjugates having the desired degree of purity with one or more appropriate pharmaceutically acceptable carriers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Pharmaceutically acceptable carriers are generally non-toxic to recipients at the dosages and concentrations used, and include, but are not limited to, buffers such as phosphate, citric acid, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (e.g., octadecyldimethylbenzylammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl, or benzyl alcohol; alkyl parabens, such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) ) polypeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or non-ionic surfactants such as polyethylene glycol (PEG). Exemplary pharmaceutically acceptable carriers herein further include interstitial drug dispersion agents, such as soluble neutral activated hyaluronidase glycoproteins (sHASEGPs), such as human soluble PH-20 hyaluronidase glycoproteins, e.g., rHuPH20 (HYLENEX®, Baxter International, Inc.).Certain exemplary sHASEGPs and methods, including rHuPH20, are described in U.S. Patent Application Publication Nos. 2005 / 0260186 and 2006 / 0104968. In one embodiment, a sHASEGP is combined with one or more additional glycosaminoglycanases, such as chondroitinases.

[0236] Exemplary lyophilized antibody or immunoconjugate formulations are described in U.S. Patent No. 6,267,958. Aqueous antibody or immunoconjugate formulations include those described in U.S. Patent No. 6,171,586 and WO2006 / 044908, the latter formulations comprising a histidine-acetate buffer.

[0237] The formulations herein may also contain more than one active ingredient as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other.

[0238] The active ingredient may be entrapped in microcapsules, colloidal pharmacokinetic systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules), or macroemulsions, prepared, for example, by coacervation techniques or interfacial polymerization, such as hydroxymethylcellulose or gelatin microcapsules and poly(methyl methacrylate) microcapsules, respectively. Such techniques are disclosed in Remington's Pharmaceutical Sciences, 16th edition, Osol, A. Ed. (1980).

[0239] Sustained-release preparations can also be prepared.The preferred example of sustained-release preparation comprises the semi-permeable matrix of solid hydrophobic polymer that contains antibody or immunoconjugate, and this matrix is ​​in the form of shaped product, for example, film or microcapsule.The preparation that is used for in vivo administration is generally sterile.Sterility can be easily achieved, for example, by filtering through sterile filtration membrane.

[0240] Any of the ASC binding molecules, particularly the anti-ASC antibodies or antigen-binding fragments or immunoconjugates thereof provided herein, can be used in methods, eg, therapeutic methods.

[0241] In another aspect, an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate, is provided for use as a pharmaceutical. In a further aspect, an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate, is provided for use in a method of treatment. In certain embodiments, an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate, is provided for use in the prevention, diagnosis, and / or treatment of diseases associated with the accumulation of ASC and / or ASC specks, preferably extracellular ASC specks. In a preferred embodiment of the present invention, an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate, is provided for use in the prevention, diagnosis, and / or treatment of diseases, disorders, and / or abnormalities, particularly those associated with the accumulation of ASC and / or ASC specks, preferably extracellular ASC specks.

[0242] In a further aspect, the present invention provides the use of an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or an immunoconjugate, in the manufacture or preparation of a medicament. In one such embodiment, the method further comprises administering to the individual an effective amount of at least one additional therapeutic agent, for example, as described below.

[0243] A "subject" or "individual" according to any of the above embodiments may be an animal, a mammal, preferably a human.

[0244] In a further aspect, the present invention provides pharmaceutical formulations comprising an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate provided herein, for use in, for example, any of the above-mentioned therapeutic methods. In one embodiment, the pharmaceutical formulation comprises an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate provided herein, and a pharmaceutically acceptable carrier. In another embodiment, the pharmaceutical formulation comprises an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate provided herein, and at least one additional therapeutic agent.

[0245] The antibodies or immunoconjugates of the present invention can be used alone or in combination with other agents in therapy. For example, the ASC binding molecules, particularly the anti-ASC antibodies or antigen-binding fragments thereof or immunoconjugates of the present invention, can be co-administered with at least one additional therapeutic agent.

[0246] Such combination therapy as described above encompasses combined administration (where two or more therapeutic agents are contained in the same or separate formulations) and separate administration, in which case administration of the antibody (a preferred type of ASC-specific binding molecule) or immunoconjugate of the present invention may occur before, simultaneously with, and / or after administration of the additional therapeutic agent and / or adjuvant.

[0247] ASC-binding molecules, particularly anti-ASC antibodies or their antigen-binding fragments or immunoconjugates of the present invention (and any additional therapeutic agents) can be administered by any suitable means, including parenteral, intrapulmonary, and intranasal administration, and, if desired for localized treatment, intralesional, intrauterine, or intravesicular administration. Parenteral injection includes intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. Dosage can be administered by any suitable route, for example, by injection, for example, intravenous or subcutaneous injection, depending in part on whether administration is short-term or long-term. Various administration schedules are contemplated herein, including, but not limited to, single administration or multiple administrations over various time periods, bolus administration, and pulse infusion.

[0248] ASC-binding molecules, particularly anti-ASC antibodies or antigen-binding fragments thereof, or immunoconjugates of the present invention, are formulated, dosed, and administered in a manner consistent with the principles of good medicine. Factors to consider in this context include the specific disease, disorder, and / or disorder associated with ASC, particularly the inflammation-propagating ASC-speck complex, or the disease being treated, the specific mammal being treated, the clinical condition of the individual subject, the cause of the ASC-related, particularly the inflammation-propagating ASC-speck complex-related disease, disorder, and / or disorder, the drug delivery site, administration method, administration schedule, and other factors known to physicians. ASC-binding molecules, particularly anti-ASC antibodies or antigen-binding fragments thereof, or immunoconjugates thereof, need not, but may, be formulated with one or more drugs currently used to prevent or treat ASC-related, particularly the inflammation-propagating ASC-speck complex-related disease, disorder, and / or disorder (interchangeably referred to as a condition), or the disease in question. The effective amount of such other agents will depend on the amount of antibody or immunoconjugate present in the formulation, the type of disease, disorder, and / or abnormality or condition associated with ASC, particularly the inflammation-propagating ASC-speck complex, and other factors discussed above. They will generally be used in the same dosages and by the routes of administration described herein, or at about 1-99% of the dosages described herein, or at any dosage and by any route empirically / clinically determined to be appropriate.

[0249] For the prevention or treatment of disease, the appropriate dosage of an ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate of the invention (when used alone or in combination with one or more other additional therapeutic agents) will depend on the type of disease being treated, the type of antibody or immunoconjugate, the severity and course of the disease, whether the antibody or immunoconjugate is administered for preventive or therapeutic purposes, previous treatments, the subject's medical history and response to the antibody or immunoconjugate, and the discretion of the attending physician. The ASC-binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, or immunoconjugate is suitably administered to the subject once or over a series of treatments.

[0250] Another aspect of the present invention provides an article of manufacture containing materials useful for the treatment, prevention, and / or diagnosis of the above-mentioned diseases, disorders, or conditions associated with ASC, particularly those associated with the accumulation of ASC and / or ASC specks, preferably extracellular ASC specks. The article of manufacture includes a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, etc. The container can be formed from a variety of materials, such as glass or plastic. The container holds a composition, alone or in combination with another composition, effective for treating, preventing, and / or diagnosing a disease, disorder, and / or abnormality associated with ASC, particularly those associated with the accumulation of ASC and / or ASC specks, preferably extracellular ASC specks, and can have a sterile access port (e.g., the container can be an intravenous solution bag or vial with a stopper pierceable by a hypodermic needle). At least one active agent in the composition is an antibody or immunoconjugate of the present invention. The label or package insert indicates that the composition is used for treating the selected condition.

[0251] Furthermore, the product may include (a) a first container containing a composition comprising an ASC-binding molecule, particularly an anti-ASC antibody or its antigen-binding fragment or immunoconjugate of the present invention; and (b) a second container containing a composition comprising an additional therapeutic agent. The product of this embodiment of the present invention may further include a package insert indicating that the composition can be used to treat a specific condition. Alternatively or additionally, the product may further include a second (or third) container containing a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution, or dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, fillers, needles, and syringes.

[0252] In a further embodiment, the invention relates to a method for reducing ASC speck levels, comprising administering a binding molecule of the invention, an immunoconjugate of the invention, a composition of the invention, or a pharmaceutical composition of the invention.

[0253] The present invention further relates to a method for detecting ASC or ASC specks, comprising contacting a sample with a binding molecule of the present invention.

[0254] In some embodiments, pharmaceutical compositions are provided comprising an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof according to the invention, and a pharmaceutically acceptable carrier and / or excipient.

[0255] In some embodiments, nucleic acid molecules encoding ASC binding molecules, particularly anti-ASC antibodies or antigen-binding fragments thereof of the invention, are provided.

[0256] In some embodiments, a. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 18 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 19; or b. A heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 28 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 29; or c. A heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 38 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 39; or d. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 48 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 49; or e. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 58 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 59; or f. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 68 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 69; or g. A heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 78 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 79; or h. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 88 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 89; or i. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 98 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 99; or j. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 118 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 119; or k. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 128 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 129; or l. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 138 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 139; or m. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 148 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 149; or n. A heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 158 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 159; or o. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 168 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 169; or p. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 178 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 179; or q. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 188 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 189; or r. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 198 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 199; or s. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 208 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 209; or t. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 218 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 219; or u. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 228 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 229; or v. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 238 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 239; or w. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 248 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 249; or x. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 258 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 259; or y. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 268 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 269; or z. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 278 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 279; or aa. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 288 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 289; or bb. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 298 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 299; or cc. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 308 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 309; or dd. A heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 318 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 319; or ee. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 328 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 329; or ff. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 338 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 339; or gg. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 348 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 349; or hh. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 358 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 359; or ii. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 368 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 369; or jj. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 378 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 379; or kk. a heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 388 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 389; or 11. A heavy chain variable region (VH) encoding the sequence of SEQ ID NO: 398 and a light chain variable region (VL) encoding the sequence of SEQ ID NO: 399 There exists a nucleic acid molecule comprising the nucleotide sequence described as:

[0257] The present invention also relates to antibodies that compete for binding to ASC with the antibodies defined above by reference to their amino acid sequences. Thus, these antibodies bind to the same epitope as the antibody they compete for binding with. Suitable competition assays are described herein and are known to those skilled in the art.

[0258] In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 18 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 19 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 28 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 29 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 38 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 39 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 48 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 49 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 58 encoding an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 59 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 68 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 69 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 78 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 79 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 88 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 89 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 98 encoding an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 99 that encodes an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 118 encoding an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 119 encoding an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 128 encoding an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 129 encoding an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 138 encoding an ASC binding molecule, particularly an anti-ASC antibody or antigen-binding fragment thereof, is provided. In some embodiments, an (isolated) nucleic acid comprising SEQ ID NO: 139 encoding an ASC binding molecule, particularly an anti-ASC antibody or an...

Claims

1. 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 NEV (Asn-Glu-Val), a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; or b. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 23, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; or c. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; or d. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 47; or e. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 53, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 57; or f. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 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: 66, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; or g. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 71, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, 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: 76, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; or h. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 81, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 82, 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: 86, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 87; or i. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 92, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 93, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 97; or j. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 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; or k. 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; or l. 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: 135, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 137; or m. 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: 142, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 143, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 145, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 147; or n. 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; or 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; or p. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 171, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 172, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 173, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 175, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 176, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 177; or 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: 185, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 187; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 191, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 192, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 193, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 195, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 196, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 197; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:211, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:212, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:213, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:215, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:217; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 221, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 222, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 223, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 225, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 226, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 227; or v. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 231, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 232, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 233, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 235, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 236, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 237; or w. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 241, 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: 243, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 245, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 246, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 247; or x. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 251, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 252, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 253, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 255, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 256, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 257; or y. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 261, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 262, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 263, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 265, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 266, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 267; or z. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 271, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 272, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 275, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 276, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 281, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 152, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 283, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 285, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 286, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 287; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:291, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:292, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:293, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:295, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:26, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:297; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 71, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 302, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 303, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 305, 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: 307; or dd. 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: 312, a VH-CDR3 comprising the amino acid sequence RDY (Arg-Asp-Tyr), a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 317; or 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: 322, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 327; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 331, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 332, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 333, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 335, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 337; or VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 161, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 342, VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 323, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 326, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 347; or hh. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 331, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 352, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 353, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 336, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 337; or ii. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 361, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 362, a VH-CDR3 comprising the amino acid sequence RDY (Arg-Asp-Tyr), a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 315, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 186, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 367; or a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 371, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 372, a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 373, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 375, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 376, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 377; or kk. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 381, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 382, ​​a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 383, a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 385, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 386, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 387; or 11. VH-CDR1 comprising the amino acid sequence of SEQ ID NO:271, VH-CDR2 comprising the amino acid sequence of SEQ ID NO:392, VH-CDR3 comprising the amino acid sequence of SEQ ID NO:393, VL-CDR1 comprising the amino acid sequence of SEQ ID NO:335, VL-CDR2 comprising the amino acid sequence of SEQ ID NO:276, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:207 wherein the binding molecule is an anti-ASC antibody or an antigen-binding fragment thereof, or a humanized anti-ASC antibody or an antigen-binding fragment thereof.

2. a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 10, 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: 10; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 14; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 20, 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: 20; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 24, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 24; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 30, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 34, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 40, or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 44, 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: 44; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 50, 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: 50; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 54, 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: 54; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 60, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 60; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 64; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 70, 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: 70; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 74, 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: 74; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 80, 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: 80; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 84, or a light chain variable region (VL) having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 90, 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: 90; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 94, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 110, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and a light chain variable region (VL) comprising the amino acid 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; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 120, 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: 120; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 124, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 130, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 130; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 134, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 134; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 140, or a heavy chain variable region (VH) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 140; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 144, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 144; or n. a heavy chain variable region (VH) comprising the amino acid 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 amino acid sequence of SEQ ID NO: 154, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 154; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 160, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 160; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 164, 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: 164; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 170, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 170; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 174, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 174; or a heavy chain variable region (VH) comprising the amino acid 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 amino acid sequence of SEQ ID NO: 184, 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: 184; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 190, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 190; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 194; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, or a heavy chain variable region (VH) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 200; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 204; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 210, 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: 210; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 214, 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: 214; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 220, or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 220; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 224, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 224; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 230, or a heavy chain variable region (VH) having at least 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 230; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 234, or a light chain variable region (VL) having at least 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 234; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 240, or a heavy chain variable region (VH) having at least 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 240; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 244, 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: 244; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 250, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 250; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 254, 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: 254; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 260, 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: 260; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 264, 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: 264; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 270, 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: 270; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 274, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 274; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 280, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 280; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 284, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 284; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 290, 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: 290; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 294, or a light chain variable region (VL) having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 294; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 300, 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: 300; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 304, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 304; or dd. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 310, 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: 310; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 314, 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: 314; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 320, 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: 320; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 324, or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 324; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 330, or a heavy chain variable region (VH) having at least 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 330; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 334, 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: 334; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 340, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 340; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 344, or a light chain variable region (VL) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 344; or hh. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 350, or a heavy chain variable region (VH) having at least 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 350; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 354, 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: 354; or ii. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 360, 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: 360; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 364, or a light chain variable region (VL) having at least 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 364; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 370, or a heavy chain variable region (VH) having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 370; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 374, or a light chain variable region (VL) having at least 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 374; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 380, or a heavy chain variable region (VH) having at least 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 380; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 384, or a light chain variable region (VL) having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 384; or 11. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 390 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: 390; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:

394. The ASC-binding molecule of claim 1 , comprising:

3. a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 10, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 20, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 24; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 30, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 34; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 40, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 44; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 50, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 54; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 60, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 64; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 70, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 74; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 80, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 84; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 90, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 94; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 110, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 114; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 120, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 124; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 130, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 134; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 140, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 144; or n. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 150, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 154; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 160, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 164; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 170, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 174; or q. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 180, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 184; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 190, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 194; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 200, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 204; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 210, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 214; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 220, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 224; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 230, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 234; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 240, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 244; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 250, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 254; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 260, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 264; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 270, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 274; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 280, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 284; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 290, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 294; or cc. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 300, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 304; or dd. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 310, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 314; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 320, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 324; or ff. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 330, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 334; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 340, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 344; or hh. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 350, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 354; or ii. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 360, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 364; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 370, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 374; or kk. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 380, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 384; or 11. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 390, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:

394. The ASC-binding molecule of claim 1 , comprising:

4. a. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 202, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203, VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or b. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or c. A VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 412, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or d. VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or e. a VH-CDR1 comprising the amino acid sequence of SEQ ID NO: 201, a VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 462, and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 203; a VL-CDR1 comprising the amino acid sequence of SEQ ID NO: 435, a VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 206, and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 207; or f. VH-CDR1 comprising the amino acid sequence of SEQ ID NO:201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO:472, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO:205, VL-CDR2 comprising the amino acid sequence of SEQ ID NO:206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:207; or g. VH-CDR1 comprising the amino acid sequence of SEQ ID NO:201, VH-CDR2 comprising the amino acid sequence of SEQ ID NO:472, and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:203; VL-CDR1 comprising the amino acid sequence of SEQ ID NO:435, VL-CDR2 comprising the amino acid sequence of SEQ ID NO:206, and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:207 wherein said one CDR optionally comprises one amino acid substitution, wherein said binding molecule is an anti-ASC antibody or an antigen-binding fragment thereof.

5. a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:414, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:414; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 440, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:450, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:434; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 460, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:470, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:470, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:434; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:490, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:490, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:434; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 500, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 500, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:510, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:510, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:434; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 434; or n. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 530, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 530, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:540, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:540, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:424; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:414, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:414; or q. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:424; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:410, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:410, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:434, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:434; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 404; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 420, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:404, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:404; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 414; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 400, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:450, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:450, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:424; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 480, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 520, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 424; or bb. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430, or having at least 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 430, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424, or having at least 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:

424. The ASC-binding molecule of claim 4, comprising:

6. a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or b. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or c. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or d. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or e. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 440 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or f. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or g. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 460 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or h. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 470 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or i. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or j. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 490 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or k. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 500 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or l. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 510 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or m. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or n. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 530 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or o. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 540 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or p. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or q. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or r. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or s. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 410 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 434; or t. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or v. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 404; or w. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 414; or x. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 400 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or y. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 450 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or z. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 480 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 520 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 424; or bb. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 430 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:

424. The ASC-binding molecule of claim 4, comprising:

7. 10. The ASC binding molecule of claim 1, which binds to ASC specks and / or non-polymerized ASC, optionally comprising: a) preferentially binds to ASC specks compared to non-polymerized ASC; or b) preferentially binds to non-polymerized ASC compared to ASC specks; or c) binds to ASC specks but not to non-polymerized ASC; or d) binds to unpolymerized ASC but not to ASC specks; ASC binding molecule.

8. a) preventing or inhibiting ASC polymerization, optionally as measured in vitro, preferably by an ASC polymerization assay; and / or b) preventing or inhibiting the propagation of ASC-dependent inflammation, optionally (i) where the propagation of inflammation is measured in vitro or in vivo, and / or (ii) where the prevention or inhibition of the propagation of inflammation is the prevention or inhibition of IL-1β release, optionally where the IL-1β release is measured in vitro, preferably in an assay using phagocytic cells such as macrophages or microglia; and / or c) increasing the uptake of ASC extracellular specks by phagocytic cells such as macrophages or microglia; and / or d) preventing or inhibiting the accumulation of ASCs and / or ASC specks, optionally whether the accumulation of ASCs or ASC specks is intracellular or extracellular; and / or e) preventing, reducing or inhibiting demyelination, optionally wherein said prevention, reduction or inhibition of demyelination improves the demyelination score in vivo; and / or f) reducing reactive microglia levels in vivo; and / or g) reducing ASC and / or cleaved caspase-1 protein levels in vivo; and / or h) Infiltrating CD4 in the spinal cord in vivo ＋ reducing T cell levels, The ASC-binding molecule of claim 1 .

9. a) a human ASC of SEQ ID NO: 1; and / or b) Mouse ASC of SEQ ID NO: 2 optionally, the epitope is within the ASC PYD domain or the ASC CARD domain; The ASC-binding molecule of claim 1 .

10. Amino acid residue number: a) 174 and 175; b) 115, 116, 119, 120, 174, 175, 184, 186 and 187; c) 115, 116, 170, 171, 172, 174, 175, 186 and 187; d) 137; e) 119, 120, 178, 179, 186 and 187; or f) 119, 120, 174, 175, 186 and 187 2. The ASC binding molecule of claim 1, which binds to an epitope in the ASC CARD domain comprising, consisting essentially of, or consisting of: Optionally, the epitope in the ASC CARD domain comprises the amino acid residues: a) K174 and D175; b) I115, D116, R119, A120, K174, D175, S184, Q185, S186 and Y187; c) I115, D116, N170, W171, T172, K174, D175, S186 and Y187; d) Y137; e) R119, A120, L178, Q179, S186 and Y187; or f) R119, A120, K174, D175, S186 and Y187 comprising, consisting essentially of, or consisting of, Optionally, the amino acid residues are the same as those of human ASC (SEQ ID NO: 1): ASC binding molecule.

11. Amino acid residue number: a) 9, 10, 13, 14, 18 and 19; b) 9, 10, 13 and 14; c) 13 and 14; d) 79, 80, 83 and 84; or e) 18, 19, 30, 31, 71, 74, 75, 77, 79 and 80 2. The ASC binding molecule of claim 1, which binds to an epitope in the ASC PYD domain comprising, consisting essentially of, or consisting of: Optionally, the epitope in the ASC CARD domain comprises the amino acid residues: a) L9, D10, E13, N14, E18 and E19; b) L9, D10, E13 and N14; c) E13 and N14; d) Q79, E80, G83 and Q84; or e) E18, E19, V30, P31, N71, R74, D75, G77, Q79 and E80 comprising, consisting essentially of, or consisting of, Optionally, the amino acid residues are the same as those of human ASC (SEQ ID NO: 1): ASC binding molecule.

12. a) a heterohybrid anti-ASC antibody or antigen-binding fragment thereof, optionally wherein the heterohybrid anti-ASC antibody is a humanized antibody or antigen-binding fragment thereof; and / or b) is a monoclonal antibody or an antigen-binding fragment thereof; and / or c) an IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3, or IgG4 antibody or antigen-binding fragment thereof, preferably human IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3, or IgG4; The ASC-binding molecule of claim 1 .

13. 5. The ASC binding molecule of claim 4, which binds to ASC specks and / or non-polymerized ASC, optionally comprising: a) preferentially binds to ASC specks compared to non-polymerized ASC; or b) preferentially binds to non-polymerized ASC compared to ASC specks; or c) binds to ASC specks but not to non-polymerized ASC; or d) binds to unpolymerized ASC but not to ASC specks; ASC binding molecule.

14. a) preventing or inhibiting ASC polymerization, optionally as measured in vitro, preferably by an ASC polymerization assay; and / or b) preventing or inhibiting the propagation of ASC-dependent inflammation, optionally (i) where the propagation of inflammation is measured in vitro or in vivo, and / or (ii) where the prevention or inhibition of the propagation of inflammation is the prevention or inhibition of IL-1β release, optionally where the IL-1β release is measured in vitro, preferably in an assay using phagocytic cells such as macrophages or microglia; and / or c) increasing the uptake of ASC extracellular specks by phagocytic cells such as macrophages or microglia; and / or d) preventing or inhibiting the accumulation of ASCs and / or ASC specks, optionally whether the accumulation of ASCs or ASC specks is intracellular or extracellular; and / or e) preventing, reducing or inhibiting demyelination, optionally wherein said prevention, reduction or inhibition of demyelination improves the demyelination score in vivo; and / or f) reducing reactive microglia levels in vivo; and / or g) reducing ASC and / or cleaved caspase-1 protein levels in vivo; and / or h) Infiltrating CD4 in the spinal cord in vivo ＋ reducing T cell levels, The ASC-binding molecule of claim 4.

15. a) a human ASC of SEQ ID NO: 1; and / or b) Mouse ASC of SEQ ID NO: 2 optionally, the epitope is within the ASC CARD domain; The ASC-binding molecule of claim 4.

16. 5. The ASC binding molecule of claim 4, which binds to an epitope in the ASC CARD domain comprising, consisting essentially of, or consisting of amino acid residues 174 and 175, Optionally, the epitope in the ASC CARD domain comprises, consists essentially of, or consists of amino acid residues K174 and D175. ASC binding molecule.

17. a) a heterohybrid anti-ASC antibody or antigen-binding fragment thereof, optionally wherein the heterohybrid anti-ASC antibody is a humanized antibody or antigen-binding fragment thereof; and / or b) is a monoclonal antibody or an antigen-binding fragment thereof; and / or c) an IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3, or IgG4 antibody or antigen-binding fragment thereof, preferably human IgA, IgD, IgE, IgM, IgG1, IgG2, IgG2a, IgG2b, IgG3, or IgG4; The ASC-binding molecule of claim 4.

18. 18. An immunoconjugate comprising an ASC-binding molecule according to any one of claims 1 to 17.

19. A pharmaceutical composition comprising an ASC binding molecule according to any one of claims 1 to 17 or an immunoconjugate comprising an ASC binding molecule according to any one of claims 1 to 17 for use in human or veterinary therapy.

20. A pharmaceutical composition comprising an ASC binding molecule described in any one of claims 1 to 17 or an immunoconjugate comprising an ASC binding molecule described in any one of claims 1 to 17 for use in preventing, alleviating, treating, or delaying the onset of a disease, disorder, or condition associated with the accumulation of ASCs and / or ASC specks, preferably extracellular ASC specks.

21. A pharmaceutical composition comprising an ASC binding molecule described in any one of claims 1 to 17 or an immunoconjugate comprising an ASC binding molecule described in any one of claims 1 to 17 for use in preventing, alleviating, or treating a disease, disorder, or condition associated with demyelination.

22. A disease, disorder, or condition associated with the accumulation of ASCs or ASC specs, preferably ASC specs, more preferably extracellular ASC specs, a) a central nervous system disease, preferably Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury or chronic traumatic encephalopathy; or b) peripheral inflammatory conditions, preferably non-alcoholic steatohepatitis (NASH), cryopyrin-associated periodic fever syndrome (CAPS), rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), gout, acne, hidradenitis suppurativa (HS), psoriasis, psoriatic arthritis, inflammatory bowel disease (IBD), edema (DME), geographic atrophy (GA), coronavirus-associated respiratory distress syndrome (CARDS), or Sjogren's syndrome The pharmaceutical composition according to claim 20, wherein the compound is selected from any one of the following:

23. a) reducing the level of reactive microglia in a subject; and / or b) reducing ASC and / or cleaved caspase-1 protein levels in a subject; and / or c) Infiltrating CD4 in the spinal cord of a subject ＋ Reduces T cell levels 20. A pharmaceutical composition comprising an ASC binding molecule according to any one of claims 1 to 17 or an immunoconjugate comprising an ASC binding molecule according to any one of claims 1 to 17 for use in treating a patient with atopic dermatitis.

24. A pharmaceutical composition comprising an ASC binding molecule described in any one of claims 1 to 17 or an immunoconjugate comprising an ASC binding molecule described in any one of claims 1 to 17 for use in diagnosis, optionally for use in the diagnosis of a disease, disorder, or condition associated with ASC-dependent inflammation.

25. A method for detecting non-polymerized ASCs and / or ASC specks in a sample obtained from a subject, the method comprising contacting the sample with an ASC binding molecule described in any one of claims 1 to 17, and detecting binding of the ASC binding molecule to non-polymerized ASCs and / or ASC specks in the sample.

26. A method for quantifying non-polymerized ASCs and / or ASC specks in a sample obtained from a subject, comprising contacting the sample with an ASC binding molecule described in any one of claims 1 to 17 or an immunoconjugate comprising the ASC binding molecule described in any one of claims 1 to 17, and quantifying the non-polymerized ASCs and / or ASC specks in the sample based on the binding level of the ASC binding molecule to the non-polymerized ASCs and / or ASC specks.

27. A pharmaceutical composition comprising an ASC binding molecule described in any one of claims 1 to 17 for use in a method for diagnosing a disease, disorder, or condition associated with ASC-dependent inflammation, said method comprising carrying out the method described in claim 26, wherein a higher level of non-polymerized ASC and / or ASC specks in the sample compared to a control level based on healthy subjects indicates a disease, disorder, or condition associated with ASC-dependent inflammation.

28. A diagnostic composition comprising an ASC binding molecule described in any one of claims 1 to 17 or an immunoconjugate comprising an ASC binding molecule described in any one of claims 1 to 17, and a pharmaceutically acceptable carrier and / or excipient.

29. A pharmaceutical composition comprising an ASC binding molecule described in any one of claims 1 to 17 or an immunoconjugate comprising an ASC binding molecule described in any one of claims 1 to 17, and a pharmaceutically acceptable carrier and / or excipient.

30. 18. A nucleic acid encoding an ASC binding molecule of any one of claims 1 to 17 or an immunoconjugate comprising the ASC binding molecule of any one of claims 1 to 17, comprising SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 98, SEQ ID NO: 99, 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, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:248, SEQ ID NO:249 , SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:338, SEQ ID NO:339, SEQ ID NO:348, SEQ ID NO:349, SEQ ID NO:358, SEQ ID NO:359, SEQ ID NO:368, SEQ ID NO:369, SEQ ID NO:378, SEQ ID NO:379, SEQ ID NO:38 8, a nucleic acid comprising the nucleotide sequence provided in SEQ ID NO:389, SEQ ID NO:398, SEQ ID NO:399, SEQ ID NO:408, SEQ ID NO:409, SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:428, SEQ ID NO:429, SEQ ID NO:438, SEQ ID NO:439, SEQ ID NO:448, SEQ ID NO:458, SEQ ID NO:468, SEQ ID NO:478, SEQ ID NO:488, SEQ ID NO:498, SEQ ID NO:508, SEQ ID NO:518, SEQ ID NO:528, SEQ ID NO:538, SEQ ID NO:548, SEQ ID NO:558 and SEQ ID NO:

559.

31. A recombinant vector comprising the nucleic acid of claim 30.

32. (a) a nucleic acid encoding an ASC binding molecule of any one of claims 1 to 17 or an immunoconjugate comprising the ASC binding molecule of any one of claims 1 to 17, comprising SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 98, SEQ ID NO: 99, 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, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO: No. 298, SEQ ID NO: 299, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 358, SEQ ID NO: 359, SEQ ID NO: 368, SEQ ID NO: 369, SEQ ID NO: 378, SEQ ID NO: 379, SEQ ID NO: 388, SEQ ID NO: 389, SEQ ID NO: 398, SEQ ID NO: 399, SEQ ID NO: 408, SEQ ID NO: 409, SEQ ID NO: 418, SEQ ID NO: 419, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 448 458, SEQ ID NO:468, SEQ ID NO:478, SEQ ID NO:488, SEQ ID NO:498, SEQ ID NO:508, SEQ ID NO:518, SEQ ID NO:528, SEQ ID NO:538, SEQ ID NO:548, SEQ ID NO:558 and SEQ ID NO:559, and / or a nucleic acid encoding an ASC binding molecule of any one of claims 1 to 17 or an immunoconjugate comprising an ASC binding molecule of any one of claims 1 to 17, wherein the nucleic acid comprises the nucleotide sequence provided in SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:48,SEQ ID NO:49, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:98, SEQ ID NO:99, 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, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:308, SEQ ID NO:3 18. A host cell comprising: (a) a recombinant vector comprising a nucleic acid comprising a nucleotide sequence as provided in SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 358, SEQ ID NO: 359, SEQ ID NO: 368, SEQ ID NO: 369, SEQ ID NO: 378, SEQ ID NO: 379, SEQ ID NO: 388, SEQ ID NO: 389, SEQ ID NO: 398, SEQ ID NO: 399, SEQ ID NO: 408, SEQ ID NO: 409, SEQ ID NO: 418, SEQ ID NO: 419, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 448, SEQ ID NO: 458, SEQ ID NO: 468, SEQ ID NO: 478, SEQ ID NO: 488, SEQ ID NO: 498, SEQ ID NO: 508, SEQ ID NO: 518, SEQ ID NO: 528, SEQ ID NO: 538, SEQ ID NO: 548, SEQ ID NO: 558, and SEQ ID NO: 559; or (b) expressing the ASC-binding molecule of any one of claims 1 to 17.

33. The following steps: a. culturing the host cell of claim 32 under conditions suitable for producing an ASC-binding molecule; and b. Recovering the ASC-binding molecule A method for producing an ASC-binding molecule, comprising:

34. A kit comprising an ASC binding molecule described in any one of claims 1 to 17 or an immunoconjugate comprising the ASC binding molecule described in any one of claims 1 to 17, and a container, for use in diagnosing a disease, disorder, or condition associated with ASC-dependent inflammation, or in a method for detecting non-polymerized ASC and / or ASC specks in a sample obtained from a subject, the method comprising contacting the sample with the ASC binding molecule and detecting binding of the ASC binding molecule to non-polymerized ASC and / or ASC specks in the sample, or in a method for quantifying non-polymerized ASC and / or ASC specks in a sample obtained from a subject, the method comprising contacting the sample with the ASC binding molecule or immunoconjugate and quantifying non-polymerized ASC and / or ASC specks in the sample based on the level of binding of the ASC binding molecule to non-polymerized ASC and / or ASC specks.

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