Antigen binding molecules that bind BDCA-2

Abstract

The present invention relates antigen binding molecules, particularly antibodies, fragments and variants thereof, that bind to BDCA-2 (CLEC4C), and the use of said antigen binding molecules in treating and / or preventing inflammatory disorders and immune disorders such as autoimmune diseases, wherein the antigen binding molecule comprises an lgG1 Fc with the following substitution: M252Y / S254T / T256E.

Description

[0001] ANTIGEN BINDING MOLECULES THAT BIND BDCA-2

[0002] Cross Reference to Related Applications

[0003] This application claims the benefit of U.S. Provisional Application No. 63 / 626,933 titled “Antigen Binding Molecules That Bind BDCA-2,” filed January 30, 2024, the entire contents of which is incorporated herein by reference.

[0004] Incorporation-By-Reference of Material Submitted Electronically

[0005] Incorporated by reference in its entirety herein is a computer-readable nucleotide / amino acid sequence listing submitted concurrently herewith and identified as follows: One 122,651 Byte XML file named “772414.XML” dated January 28, 2025.

[0006] Field of the invention

[0007] The present invention relates antigen binding molecules, particularly antibodies, fragments and variants thereof, that bind to BDCA-2 (CLEC4C), and the use of said antigen binding molecules in treating and / or preventing inflammatory disorders and immune disorders such as autoimmune diseases.

[0008] Background to the invention

[0009] It is critical for the immune system to avoid the recognition of self-DNA and self-RNA while retaining the ability to sense microbial nucleic acids. The innate immune system appears to have elaborated several distinct mechanisms to discriminate pathogen-derived exogenous nucleic acids and host-derived self-nucleic acids. However, there is considerable emerging evidence that Toll-like receptors (TLR) recognition of self-nucleic acids occurs under certain circumstances although the innate immune system evolves distinct mechanisms to prevent self-recognition. The chronically activated plasmacytoid dendritic cells (pDCs) and the IFN-a that they produce in response to self-nucleic acids are contributing factors in the pathogenesis of some autoimmune diseases, such as Scleroderma (SSc), Systemic Lupus Erythematosus (SLE), and Sjogren syndrome psoriasis (Bekic Z, et al. Ann Rheum Dis 2016;75:1567-73; Fei T, et al. Sci China Life Sci. 2010; 53: 172-182; van Bon L, et al. Current Opinion in Rheumatology 2011 ;23:505- 510; Banchereau J and Pascual V. Immunity 2006;25:383-392).

[0010] Plasmacytoid dendritic cells (pDC) are bone marrow-derived cells specialized in the secretion of type I IFN (Colonna M, et al. Nat. Immunol. 2004;5:1219-1226; Gilliet M, et al. Nat. Rev. Immunol. 2008;8: 594-606). pDC are mainly found in peripheral blood and in primary and secondary lymphoid organs. pDC promptly detect viral nucleic acids, which are endocytosed and delivered to endosomes containing TLR7 and TLR9. Engagement of these receptors results in the immediate release of type I IFN, providing a very early defence against viral infections (Swiecki M and Colonna M. Immunol. Rev. 2010;234:142-162). pDC also secrete type I IFN in response to endogenous nucleic acids that are released during cell necrosis and / or apoptosis or are bound to antinuclear autoantibodies.

[0011] Substantial evidence has pointed to the involvement of self-nucleic acid recognition in inflammatory and autoimmune diseases. In particular the contribution of TLRs to autoimmunity has been highlighted in multiple disease models. The best example is the role played by TLR9 and TLR7 in lupus following the accumulation of self-DNA / RNA via immune complexes (Barrat FJ et al. J. Exp. Med. 2005,202:1131 -1139; Hagberg N and Ronnblom L Scand. J. Immunol. 2015,82:199-207). Another example is the importance of self-antimicrobial peptides in promoting autoimmunity (Lande R et al. Nature 2007, 449; 564-569). It has been shown that the overexpression of TLRs alone is sufficient to induce autoimmunity in otherwise wild type animals, as shown for TLR7 or TLR8 (Deane, JA et al. Immunity 2007;27:801-810; Guiducci C, et al. J. Exp. Med. 2013;210:2903- 2919).

[0012] SSc is a multisystem, fibrosing disorder in which vasculopathy, autoimmunity, and inflammation lead to diverse life altering and life-threatening clinical manifestations. SSc has the highest degree of morbidity and mortality of the rheumatic diseases with a 10-year mortality rate of 23 to 45% (Mayes MD, et al. Arthritis Rheum. 2003;48:2246-2255). The female predominance is about 4:1 , and the usual age of onset is 35 to 55 years. The pathophysiology of SSc is not completely understood, but substantial evidence shows interplay between immunologic derangement, endothelial dysfunction, and profibrotic mechanisms. Evidence is pointing to the role of pDC in SSc. pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of IFNa and CXCL4, which are both hallmarks of the disease. Ah Kioon et al. (Sci. Transl. Med. 2018;10:eaam8458) demonstrated that the secretion of CXCL4 is due to the aberrant presence of TLR8 on pDCs of SSc patients, which is not seen in healthy donors and that CXCL4 primarily acts by potentiating TLR8- but also TLR9-induced IFN production by pDCs. Other studies on IFN inducible chemokines in SSC (Liu X, et al. Arthritis Rheum. 2013;65:226-35) and the report on CXCL4 as biomarker of SSc (van Bon L, et al. N Engl J Med. 2014;370:433-43), a growing interest has built on the role of IFN in the progression and early phases of SSc. Another recent paper shows that the IFN signature (previously associated with active SSc) is present before the onset of clinical fibrosis (Brkic Z et al. Ann Rheum Dis. 2016;75:1567-73). In addition, in vivo data has shown that depleting pDCs can prevent disease in a mouse model of scleroderma and could revert fibrosis in mice with established disease (Ah Kioon et al. Sci. Transl. Med. 2018; 10: eaam8458). pDC express multiple receptors that inhibit type I IFN secretion, preventing immune surveillance. One of these receptors is CLEC4C, also known as blood dendritic cell antigen-2 (BDCA-2) and CD303 (Dzionek A, et al. J. Exp. Med. 2001 ;194:1823-1834). CLEC4C is a type II transmembrane glycoprotein that belongs to the C-type lectin (CTLs) superfamily (Crocker PR et al. Nat Rev Immunol. 2007; 7:255-66). BDCA-2 is the most specific marker for human pDC and is only expressed in primates. BDCA-2 consists of a single extracellular carbohydrate recognition domain, a transmembrane region, and a short cytoplasmic domain without an obvious signaling motif. BDCA-2 transmits intracellular signals through an associated transmembrane adaptor, the FceRy, which recruits the protein tyrosine kinase Syk, inducing protein tyrosine phosphorylation and calcium mobilization (Cao W, et al. PLoS Biol. 2007;5:e248). Although it promotes cellular activation in other lymphoid and myeloid cells, the FceRy-Syk signaling pathway interferes with TLR7 and 9-induced activation of pDC, inhibiting type I IFN secretion (Dzionek A, et al. J. Exp. Med. 2001 ;194:1823-1834). pDCs are abnormally activated in peripheral blood or diseased sites and produce IFNa in large amounts, as well as other inflammatory cytokines and chemokines, in autoimmune diseases such as SLE, SSc, polymyositis and dermatomyositis, psoriasis, Sjogren’s syndrome, rheumatoid arthritis, Grave’s disease and Hashimoto’s disease (Li et al. Front Immunol. 2017;8:1268; Eloranta et al. Arthritis Rheum. 2013;65:853-863).

[0013] Summary of the invention

[0014] Provided herein is an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising an IgG 1 Fc with the following substitutions: M252Y / S254T / T256E (also referred to as “YTE”).

[0015] In a first aspect of the invention there is provided an antigen binding molecule or fragment or variant thereof comprising a means for binding BDCA-2 (CLEC4C), and an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0016] In a second aspect of the invention there is provided an antigen binding molecule or fragment or variant thereof comprising a heavy chain variable region and / or a light chain variable region, each comprising 3 CDR regions, wherein the antigen binding molecule binds to BDCA-2 (CLEC4C), and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0017] In a third aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule has an equilibrium dissociation constant (KD) for BDCA-2 (CLEC4C) of less than about 2nM, and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E. In some embodiments, the antigen binding molecule has an equilibrium dissociation constant (KD) for BDCA-2 (CLEC4C) of less than about 0.01 nM.

[0018] In a fourth aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule has a half maximal inhibitory concentration (IC50) for inhibition of IFN secretion of less than about 2nM, and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E. In some embodiments, the antigen binding molecule has a half maximal inhibitory concentration (IC50) for inhibition of IFN secretion of less than about 0.1 nM. In a fifth aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule has an IC90 for inhibition of IFN secretion of less than about 20nM, and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E. In some embodiments, the antigen binding molecule has an IC90 for inhibition of IFN secretion of less than about 5nM.

[0019] In a sixth aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule comprises a VHCDR3 comprising the amino acid sequence of any one of SEQ ID NOs 48, 28, 8, 38, 58, 68 and 78; and / or a VLCDR3 comprising the amino acid sequence of any one of SEQ ID NOs 34, 24, 44, 4, 14, 54, 64 and 74, and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0020] In a seventh aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule comprises: a VHCDR1 comprising the amino acid sequence of any one of SEQ ID NOs 46, 49, 26, 29, 6, 9, 16, 19, 36, 39, 56, 59, 66, 69, 76 and 79; a VHCDR2 comprising the amino acid sequence of any one of SEQ ID NOs 47, 50, 27, 30, 7, 10, 17, 20, 37, 40, 57, 60, 67, 70, 77 and 80; and a VHCDR3 comprising the amino acid sequence of any one of SEQ ID NOs 48, 28, 8, 18, 38, 58, 68 and 78; and / or a VLCDR1 comprising the amino acid sequence of any one of SEQ ID NOs 32, 22, 42, 2, 12, 52, 62 and 72; a VLCDR2 comprising the amino acid sequence of any one of SEQ ID NOs 33, 23, 43, 3, 13, 53, 63 and 73; and a VLCDR3 comprising the amino acid sequence of any one of SEQ ID NOs 34, 24, 44, 4, 14, 54, 64 and 74; and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0021] In an eighth aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule comprises a heavy chain variable region having the amino acid sequence selected from the group consisting of SEQ ID NO:45, SEQ ID NO: 25, SEQ ID NO: 5, SEQ ID NO: 15, SEQ ID NO: 35, SEQ ID NO: 55, SEQ ID NO: 65 and SEQ ID NO: 75, and / or a light chain variable region having the amino acid sequence selected from the group consisting of SEQ ID NO: 31 , SEQ ID NO: 21 , SEQ ID NO: 41 , SEQ ID NO: 1 , SEQ ID NO: 11 , SEQ ID NO: 51 , SEQ ID NO: 61 and SEQ ID NO: 71 ; and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0022] In a ninth aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule is an antibody that specifically binds to BDCA-2 (CLEC4C) comprising a variable region selected from the group consisting of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06, 28B01 , and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitution: M252Y / S254T / T256E. The present invention also provides fragments and variants derived from said antibodies.

[0023] In a further aspect of the invention there is provided an antigen binding molecule or fragment or variant thereof that binds to BDCA-2 (CLEC4C) and competes for binding to BDCA-2 (CLEC4C) with an antigen binding molecule of any of the first to ninth aspects of the invention; wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0024] In a further aspect of the invention, there is provided an antigen binding molecule that specifically binds to an epitope of BDCA-2 (CLEC4C) that is bound by an antigen binding molecule of any of the first to ninth aspects of the invention, wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0025] In a further aspect of the invention, there is provided an antigen binding molecule that specifically binds to BDCA-2 (CLEC4C) and inhibits the binding of BDCA-2 (CLEC4C) to an antigen binding molecule of any of the first to ninth aspects of the invention, wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0026] In a further aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising 1 to 10, 1 to 5, or 1 to 2 amino acid substitutions from the antigen binding molecule of any the first to ninth aspects of the invention, and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitutions: M252Y / S254T / T256E.

[0027] In a further aspect of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the anti-BDCA-2 (CLEC4C) antigen binding molecule is a humanised or deimmunised derivative of an anti-BDCA-2 (CLEC4C) antigen binding molecule of the invention.

[0028] In a further aspect of the invention, there is provided an affinity matured mutant of an antigen binding molecule or antibody of the invention.

[0029] In a further aspect of the invention there is provided a pharmaceutical composition comprising an antigen binding molecule of the invention, or a fragment, variant or affinity matured mutant thereof.

[0030] In a still further aspect of the invention there is provided the antigen binding molecules or pharmaceutical compositions of the invention for use in medicine.

[0031] In another aspect, there is provided the antigen binding molecules or pharmaceutical compositions of the invention for use in preventing and / or treating an inflammatory disorder or disease.

[0032] In another aspect, there is provided the use of antigen binding molecules or pharmaceutical compositions of the invention for the manufacture of a medicament for use in treatment of an inflammatory disorder or disease.

[0033] In a further aspect, there is provided a method of treating or preventing an inflammatory disorder or disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antigen binding molecule or pharmaceutical composition of the invention.

[0034] Also provided are nucleic acids encoding the antigen binding molecules of the invention. There is also provided a vector or a plasmid comprising the nucleic acids of the invention. The invention also provides a host cell comprising a nucleic acid, vector or plasmid of the invention.

[0035] The invention also provides methods of producing cell that expresses an anti-BDCA-2 (CLEC4C) antigen binding molecule, comprising transfecting said cell with a plasmid or vector of the invention The invention also provides methods for the production of an anti-BDCA-2 (CLEC4C) antigen binding molecule, comprising culturing a host cell of the invention in a cell culture medium under conditions to express the encoding nucleic acid sequence of the plasmid or vector inside the cell, and optionally collecting the anti-BDCA-2 (CLEC4C) antigen binding molecule from the cell supernatant.

[0036] The invention also provides kits comprising an anti-BDCA-2 (CLEC4C) antigen binding molecule or other aspect of the invention, optionally further comprising instructions for use.

[0037] Brief Description of the Drawings

[0038] Figure 1 is a graph depicting the results of culturing pDCs with various concentrations of lgG1 isotype control, 3E5 lgG1 , 3E5 lgG1 -YTE, and Anti-MHC II positive control.

[0039] Figure 2 is a graph depicting the results of stimulating PBMCs that had been incubated with lgG1 isotype, lgG1 -YTE isotype, 3E5 lgG2, and 3E5 lgG1 -YTE at various concentrations with CpG ODN2216.

[0040] Figure 3A is a graph depicting the results of measuring surface expression of BDCA2 in cultures of pDCs treated with various concentrations of IgG 1 isotype control, 3E5 IgG 1 , or 3E5 lgG1 -YTE.

[0041] Figure 3B is a graph depicting the results of measuring surface expression of CD32a in cultures of pDCs treated with various concentrations of IgG 1 isotype control, 3E5 IgG 1 , or 3E5 lgG1 -YTE.

[0042] Figure 4 is graphs depicting the results of measuring T cells that were I FN y+, TNFa+, IFNy+TNFa+, CD25+, or CD71 + after co-culturing the T cells with pDCs that were not stimulated, or stimulated with CpG and 10 nM of IgG 1 isotype control, 3E5 lgG1 , or 3E5 lgG1 -YTE.

[0043] Detailed description

[0044] As used herein, an “antigen binding molecule” is a member of a pair of molecules which have binding specificity for one another. The members of an antigen binding pair may be naturally derived or wholly or partially synthetically produced. One member of the pair of molecules has an area on its surface, which may be a protrusion or a cavity, which specifically binds to and is therefore complementary to a particular spatial and polar organisation of the other member of the pair of molecules. Thus, the members of the pair have the property of binding specifically to each other. Examples of types of antigen binding pairs are antigen-antibody, biotin-avidin, hormone-hormone receptor, receptor-ligand and enzyme-substrate. The present invention is generally concerned with antigen-antibody type interactions.

[0045] The antigen binding molecule used in the present invention binds specifically to BDCA-2 (CLEC4C) or an epitope of BDCA-2 (CLEC4C), and is referred to as an “anti-BDCA-2 antigen binding molecule,” “anti-BDCA-2 binding molecule,” “BDCA-2 antigen binding molecule,” or “BDCA-2 binding molecule,” which terms are interchangeable. The binding affinity of the antigen binding molecule to BDCA-2 (CLEC4C) or an epitope of BDCA-2 (CLEC4C) can be measured using the dissociation constant (KD). The binding affinity of the antigen binding molecule to BDCA-2 (CLEC4C) or an epitope of BDCA-2 (CLEC4C) can be measured using the association constant (Ka). The KD value of the antigen binding molecule for an epitope of BDCA-2 (CLEC4C) bound by a antigen binding molecule of the invention will be lower than the KD value of the antigen binding molecule for an alternative epitope of BDCA-2 (CLEC4C) or a non-BDCA-2 (CLEC4C) epitope.

[0046] Antigen binding molecules which bind to BDCA-2 (CLEC4C) include anti-BDCA-2 (CLEC4C) antibodies and antigen-binding fragments thereof. The antigen binding molecule used in the present invention is typically an antibody.

[0047] The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e. , molecules that contain an antigen binding site that specifically binds an antigen, whether natural or partly or wholly synthetically produced. The term also covers any polypeptide or protein having a binding domain which is, or is homologous to, an antibody binding domain. Antibodies may be polyclonal or monoclonal. These can be derived from natural sources, or they may be partly or wholly synthetically produced. Antibodies are polypeptides that typically contain two identical heavy chains and two identical light chains, which are smaller than the heavy chains. In mammals there are two types of light chain, which are called lambda (A) and kappa (K). Each of the heavy chains and each of the light chains are composed of a variable region and a constant region. The heavy chain variable region is referred to as the VH region and the light chain variable region is referred to as the VL region. For kappa light chains, the VL region can also be referred to as the VK region. Each of the variable regions of the heavy and light chains comprise three complementarity determining regions (CDRs), CDR1 , CDR2 and CDR3. These are named VLCDR1 , VLCDR2, VLCDR3, VHCDR1 , VHCDR2 and VHCDR3 respectively. Examples of antibodies are the immunoglobulin isotypes (e.g., IgG, IgE, IgM, IgD and IgA) and their isotypic subclasses; fragments which comprise an antigen binding domain, such as Fab, F(ab’)2, Fv, scFv, dAb, Fd; and diabodies.

[0048] Fragments of antibodies and antigen binding molecules

[0049] The antigen binding molecule of the invention can be a fragment of an antibody, specifically an antigen binding fragment of an antibody conjugated to an Fc region comprising the YTE mutation. The antigen binding fragments comprise one or more antigen binding regions. It has been shown that fragments of a whole antibody can perform the function of binding antigens. Examples of binding fragments are (i) the Fab fragment consisting of VL, VH, CL and CH1 domains; (ii) the Fd fragment consisting of the VH and CH1 domains; (iii) the Fv fragment consisting of the VL and VH domains of a single antibody; (iv) the dAb fragment (Ward, E.S. et al., Nature 341 :544-546 (1989)) which consists of a VH domain; (v) isolated CDR regions; (vi) F(ab’)2 fragments, a bivalent fragment comprising two linked Fab fragments; (vii) single chain Fv molecules (scFv), wherein a VH domain and a VL domain are linked by a peptide linker which allows the two domains to associate to form an antigen binding site (Bird et al., Science 242:423-426 (1988); Huston et al., PNAS USA 85:5879-5883 (1988)); (viii) bispecific single chain Fv dimers (PCT / US92 / 09965) and (ix) “diabodies”, multivalent or multispecific fragments constructed by gene fusion (WO94 / 13804; P. Hollinger et al., Proc. Natl. Acad. Sci. USA 90: 6444-6448 (1993)). Typically, the fragment is a Fab, F(ab’)2 or Fv fragment or an scFv molecule.

[0050] Diabodies are multimers of polypeptides, each polypeptide comprising a first domain comprising a binding region of an immunoglobulin light chain and a second domain comprising a binding region of an immunoglobulin heavy chain, the two domains being linked (e.g. by a peptide linker) but unable to associated with each other to form an antigen binding site: antigen binding sites are formed by the association of the first domain of one polypeptide within the multimer with the second domain of another polypeptide within the multimer (WO94 / 13804).

[0051] Where bispecific antibodies are to be used, these may be conventional bispecific antibodies, which can be manufactured in a variety of ways (Hollinger & Winter, Current Opinion Biotechnol. 4:446-449 (1993)), e.g. prepared chemically or from hybrid hybridomas, or may be any of the bispecific antibody fragments mentioned below. It may be preferable to use scFv dimers or diabodies rather than whole antibodies. Diabodies and scFv can be constructed without an Fc region, using only variable domains, potentially reducing the effects of anti-idiotypic reaction. Other forms of bispecific antibodies include the single chain “Janusins” described in Traunecker et al., EMBO Journal 10:3655-3659 (1991 ).

[0052] A bispecific antibody is one which can bind to two target molecules simultaneously, such as two antigens or two epitopes. Bispecific antibodies may also be referred to as dual binding antibodies. Examples of bispecific antibody formats include, but are not limited to; (mAb)2, Fcab, F(mAb’)2, quadromas, scFv (single chain variable fragments), bsDb (bispecific diabodies), scBsDb (single chain bispecific diabodies), BiTE (bispecific T cell engagers), DART (dual affinity re-targeting antibodies), charge pairs, tandem antibodies, tandem scFv-Fc, Fab-scFv-Fc, Fab-scFv, minibodies, zybodies, DNL-F(ab)3 (dock-and- lock trivalent Fabs), bssdAb (bispecific single domain antibodies) and knobs-in-holes.

[0053] Bispecific diabodies, as opposed to bispecific whole antibodies, may also be useful because they can be readily constructed and expressed in E. coli. Diabodies (and many other polypeptides such as antibody fragments) of appropriate binding specificities can be readily selected using phage display (WO94 / 13804) from libraries. If one arm of the diabody is to be kept constant, for instance, with a specificity directed against antigen X, then a library can be made where the other arm is varied and an antibody of appropriate specificity selected.

[0054] The antigen binding molecules of the invention may be provided in a format that allows crosslinking between adjacent antigen-binding molecules. For example, antigen binding molecules comprising an Fc region (such as those in a monoclonal antibody format) allow cross-linking between the Fc regions of two adjacent molecules (and hence cross-linking between adjacent BDCA-2 molecules due to co-localisation). In some cases, this may promote internalisation of BDCA2 and inhibition of IFN secretion. In other embodiments, the antigen binding molecules may be provided in a format that does not allow for crosslinking between adjacent antigen-binding molecules. For example, antigen binding molecules lacking an Fc region (such as those in a Fab format, or similar), may not crosslink. Nevertheless, it has been demonstrated that the antigen-binding molecules of the invention (specifically, antigen binding molecules having the sequences disclosed herein) are still able to promote internalisation of BDCA2 and inhibition of IFN secretion in a dosedependent manner, even when provided in a format that does not permit crosslinking. This means both types of antigen binding molecules (those formats allowing for crosslinking and those formats that do not allow for cross-linking) can be provided, increasing the utility and functionality of the antigen binding molecules of the present invention.

[0055] Furthermore, in some embodiments, the antigen-binding molecules of the invention are able to promote internalisation of BDCA2 and inhibition of IFN secretion in a dosedependent manner, even when the antigen-binding molecules are provided in a format that bind in a monovalent manner to BDCA2. For example, antigen-binding molecules in a Fab format, which bind to BDCA-2 in a monovalent manner (i.e. a ratio of one antigenbinding molecule to one BDCA2 molecule), have been shown to promote internalisation of BDCA2 and inhibition of IFN secretion in a dose-dependent manner.

[0056] Accordingly, in some embodiments, the antigen-binding molecules bind BDCA2 in a monovalent manner (i.e. a ratio of one antigen-binding molecule to one BDCA2 molecule). In some embodiments, the antigen-binding molecules do not cross-link with one another. Fab formats achieve both these aims, since they neither cross-link with each other (due to the lack of an Fc region) and they bind their antigen in a monovalent manner. In some embodiments, the present invention provides antigen-binding molecules having sequences that promote internalisation of BDCA2 and inhibition of IFN secretion (in vitro or in vivo). In some embodiments, the antibodies include the ability to promote internalisation of BDCA2 and inhibition of IFN secretion regardless of the ability of the antigen-binding molecules to cross-link with each other (and hence co-localise BDCA2 molecules) and regardless of the binding valency (i.e. monovalent or bivalent binding).

[0057] Identity and homology

[0058] “Identity” as known in the art is the relationship between two or more polypeptide sequences or two or more polynucleotide sequences, as determined by comparing the sequences. In the art, identity also means the degree of sequence relatedness between polypeptide or polynucleotide sequences, as the case may be, as determined by the match between strings of such sequences. While there exist a number of methods to measure identity between two polypeptides or two polynucleotide sequences, methods commonly employed to determine identity are codified in computer programs. Preferred computer programs to determine identity between two sequences include, but are not limited to, GCG program package (Devereux, et al., Nucleic Acids Research, 12, 387 (1984), BLASTP, BLASTN, and FASTA (Atschul et al., J. Molec. Biol. 215, 403 (1990)).

[0059] One can use a program such as the CLUSTAL program to compare amino acid sequences. This program compares amino acid sequences and finds the optimal alignment by inserting spaces in either sequence as appropriate. It is possible to calculate amino acid identity or similarity (identity plus conservation of amino acid type) for an optimal alignment. A program like BLASTx will align the longest stretch of similar sequences and assign a value to the fit. It is thus possible to obtain a comparison where several regions of similarity are found, each having a different score. Both types of identity analysis are contemplated in the present invention.

[0060] The percent identity of two amino acid sequences or of two nucleic acid sequences is determined by aligning the sequences for optimal comparison purposes (e.g., gaps can be introduced in the first sequence for best alignment with the sequence) and comparing the amino acid residues or nucleotides at corresponding positions. The “best alignment” is an alignment of two sequences which results in the highest percent identity. The percent identity is determined by the number of identical amino acid residues or nucleotides in the sequences being compared (i.e., % identity = number of identical positions / total number of positions x 100). Generally, references to % identity herein refer to % identity along the entire length of the molecule, unless the context specifies or implies otherwise.

[0061] The determination of percent identity between two sequences can be accomplished using a mathematical algorithm known to those of skill in the art. An example of a mathematical algorithm for comparing two sequences is the algorithm of Karlin and Altschul (1990) Proc. Natl. Acad. Sci. USA 87:2264-2268, modified as in Karlin and Altschul (1993) Proc. Natl. Acad. Sci. USA 90:5873-5877. The NBLAST and XBLAST programs of Altschul, et al. (1990) J. Mol. Biol. 215:403-410 have incorporated such an algorithm. BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to nucleic acid molecules of the invention. BLAST protein searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to protein molecules of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilised as described in Altschul et al. (1997) Nucleic Acids Res. 25:3389-3402. Alternatively, PSI-Blast can be used to perform an iterated search which detects distant relationships between molecules (Id.). When utilising BLAST, Gapped BLAST, and PSI-Blast programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. See http: / / www.ncbi.nlm.nih.gov. Another example of a mathematical algorithm utilised for the comparison of sequences is the algorithm of Myers and Miller, CABIOS (1989). The ALIGN program (version 2.0) which is part of the CGC sequence alignment software package has incorporated such an algorithm. Other algorithms for sequence analysis known in the art include ADVANCE and ADAM as described in Torellis and Robotti (1994) Comput. Appl. Biosci., 10 :3-5; and FASTA described in Pearson and Lipman (1988) Proc. Natl. Acad. Sci. 85:2444-8. Within FASTA, ktup is a control option that sets the sensitivity and speed of the search.

[0062] Typically, the amino acid sequence of the CDRs of the antigen binding molecules provided in the invention have at least 70% identity, for example using the default parameters of the BLAST computer program (Atschul et al., J. Mol. Biol. 215, 403-410 (1990)) provided by HGMP (Human Genome Mapping Project), at the amino acid level, to the amino acid sequences of the CDRs described below. More typically, the CDR sequence has at least 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or at least 99% identity, at the amino acid level, to the sequences shown below. Typically, each of the CDR sequences of the antigen binding molecule used in the invention has this level of identity to the amino acid sequences of the CDRs set out below. Alternatively, any 1 , 2, 3, 4 or 5 of the CDRs of the antigen binding molecule used in the invention has this level of identity to the amino acid sequences of the CDRs set out below.

[0063] The amino acid sequence of the VH and VL regions of the antigen binding molecules provided in the invention have at least 70% identity, for example using the default parameters of the BLAST computer program (Atschul et al., J. Mol. Biol. 215, 403-410 (1990)) provided by HGMP (Human Genome Mapping Project), at the amino acid level, to the amino acid sequences of the VH and VL regions described below. More typically, the VH and VL regions have at least 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or at least 99% identity, at the amino acid level, to the sequences shown below. Typically, each of the VH and VL regions of the antigen binding molecule used in the invention has this level of identity to the amino acid sequences of the VH and VL regions set out below. Alternatively, only one of the VH and VL regions of the antigen binding molecule used in the invention has this level of identity to the amino acid sequences of the VH and VL regions set out below.

[0064] Identity (e.g., percent identity or % identity) as used herein is interchangeable with “homology” and “similarity”. References to particular % identities apply equally to % homology and % similarity. Homology and similarity may be determined using appropriate algorithms, such as FASTA, BLAST and Gapped BLAST. Software for performing these analyses are publicly available.

[0065] In some embodiments, in particular for any embodiments referencing sequences having a particular sequence identity to a reference sequence, the % sequence identity may be calculated without the sequence of all 6 CDRs of the specified heavy or light chain variable region. In such embodiments, the variations in sequence occur only in the framework regions of the variable region. Variants

[0066] The present invention also extends to variants of peptide sequences referred to below. As used herein the term “variant” relates to proteins that have a similar amino acid sequence and / or that retain the same function. For instance, the term “variant” encompasses proteins or polypeptides which include one or more amino acid additions, deletions, substitutions or the like. An example of a variant of the present invention is a protein comprising a peptide as defined below, apart from the substitution of one or more amino acids with one or more other amino acids. Amino acid substitutions may be made to, for example, reduce or eliminate liabilities in the amino acid sequences. Alternatively, amino acid substitutions may be made to improve antigen affinity or to humanise or deimmunise the antibodies, if required. Affinity matured variants, humanised variants and deimmunised variants of the specified antibodies are provided herein, as well as variants comprising amino acid substitutions to reduce or eliminate any liabilities in the sequences of the antibodies.

[0067] As noted above, in some embodiments, any substitutions may occur only in the framework regions. In such embodiments, the original CDR sequences are retained, but variation may occur in one or more framework regions.

[0068] Variant antigen-binding molecules having the one or more amino acid substitutions may retain the functional activity (for example EC50, IC50, IC90 and / or Kd) of the antigenbinding molecule from which the variant antigen-binding molecule is derived. Variant antigen-binding molecules of the invention can be used and formulated in the same ways as described for the antigen-binding molecules from which they are derived.

[0069] Substitutions

[0070] The skilled person is aware that various amino acids have similar properties. One or more such amino acids of a substance can often be substituted by one or more other such amino acids without eliminating a desired activity of that substance.

[0071] Thus, the amino acids glycine, alanine, valine, leucine and isoleucine can often be substituted for one another (amino acids having aliphatic side chains). Of these possible substitutions it is preferred that glycine and alanine are used to substitute for one another (since they have relatively short side chains) and that valine, leucine and isoleucine are used to substitute for one another (since they have larger aliphatic side chains which are hydrophobic). Other amino acids which can often be substituted for one another include: phenylalanine, tyrosine and tryptophan (amino acids having aromatic side chains); lysine, arginine and histidine (amino acids having basic side chains); aspartate and glutamate (amino acids having acidic side chains); asparagine and glutamine (amino acids having amide side chains); and cysteine and methionine (amino acids having sulphur containing side chains).

[0072] Substitutions of this nature are often referred to as “conservative” or “semi- conservative” amino acid substitutions.

[0073] Using the three letter and one letter codes the naturally occurring amino acids may be referred to as follows: glycine (G or Gly), alanine (A or Ala), valine (V or Vai), leucine (L or Leu), isoleucine (I or lie), proline (P or Pro), phenylalanine (F or Phe), tyrosine (Y or Tyr), tryptophan (W or Trp), lysine (K or Lys), arginine (R or Arg), histidine (H or His), aspartic acid (D or Asp), glutamic acid (E or Glu), asparagine (N or Asn), glutamine (Q or Gin), cysteine (C or Cys), methionine (M or Met), serine (S or Ser) and Threonine (T or Thr). Where a residue may be aspartic acid or asparagine, the symbols Asx or B may be used. Where a residue may be glutamic acid or glutamine, the symbols Glx or Z may be used. References to aspartic acid include aspartate, and glutamic acid include glutamate, unless the context specifies otherwise.

[0074] Amino acid deletions or insertions can also be made relative to the amino acid sequence for the fusion protein referred to below. Thus, for example, amino acids which do not have a substantial effect on the activity of the polypeptide, or at least which do not eliminate such activity, can be deleted. Such deletions can be advantageous since the overall length and the molecular weight of a polypeptide can be reduced whilst still retaining activity. This can enable the amount of polypeptide required for a particular purpose to be reduced - for example, dosage levels can be reduced.

[0075] In some embodiments, the following amino acids can be exchange for each other for conservative amino acid substitutions:

[0076] Therefore, references to “conservative” amino acid substitutions refer to amino acid substitutions in which one or more of the amino acids in the sequence of the antibody (e.g. in the CDRs or in the VH or VL sequences) is substituted with another amino acid in the same class as indicated above. Conservative amino acid substitutions may be preferred in the CDR regions to minimise adverse effects on the function of the antibody. However, conservative amino acid substitutions may also occur in the framework regions.

[0077] Amino acid changes relative to the sequence given below can be made using any suitable technique e.g. by using site-directed mutagenesis or solid-state synthesis.

[0078] It should be appreciated that amino acid substitutions or insertions within the scope of the present invention can be made using naturally occurring or non-naturally occurring amino acids, although naturally occurring amino acids may be preferred. Whether or not natural or synthetic amino acids are used, it may be preferred that only L- amino acids are present.

[0079] In one embodiment of the invention there is provided antigen binding molecule, or antigen binding fragment thereof, of the invention comprising from 1 to 10, preferably from 1 to 5, amino acid substitutions in the antibody binding domain or antigen binding domains. For example, in one embodiment of the invention, there is provided an anti-BDCA-2 (CLEC4C) antibody or antigen binding fragment thereof, wherein the anti-BDCA-2 (CLEC4C) antibody antigen binding fragment thereof comprises the 6 CDR regions of an antibody selected from the group consisting of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06 and 28B01 , wherein the antigen binding molecule has from 1 to 10 amino acid substitutions across all of its CDR regions, preferably from 1 to 5 amino acid substitutions. In a further embodiment of the invention, there is provided an anti-BDCA-2 (CLEC4C) antigen binding molecule or antigen binding fragment thereof, wherein the anti-BDCA-2 (CLEC4C) antibody antigen binding fragment thereof comprises the VH and VL sequences of an antibody selected from the group consisting of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06 and 28B01 , wherein the antigen binding molecule has from 1 to 10 amino acid substitutions across its VH and VL sequences, preferably from 1 to 5 amino acid substitutions. In a still further embodiment of the invention, there is provided an anti-BDCA-2 (CLEC4C) antibody, wherein the anti-BDCA-2 (CLEC4C) antibody is an antibody selected from the group consisting of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06 and 28B01 , wherein the antibody has from 1 to 10 amino acid substitutions, preferably from 1 to 5 amino acid substitutions. Substitutions are of course substitutions with reference to the original CDR or variable chain sequences of the starting antibody.

[0080] In some embodiments, the one or more amino acid substitutions are in the CDR region or regions. In other embodiments, the one or more amino acid substitutions are in the framework regions, i.e. in the variable heavy and light chains but not in the CDR region or regions. In other embodiments, the one or more amino acid substitutions may be at any position in the variable heavy and / or variable light regions. In some embodiments, the amino acid substitutions do not occur in a CDR sequence.

[0081] In some embodiments, the amino acid substitutions do not adversely affect the binding specificity and / or affinity of the antibody. Accordingly, the variant antibody may have the same or superior functional profile as the antibody from which is it derived. Affinity Matured Variants

[0082] Other variants that are within the scope of the present invention include antigen binding molecules of the invention that are modified to have increased affinity for BDCA-2 (CLEC4C). In one embodiment, the antigen binding molecule of the invention is an affinity-matured antibody. In one embodiment, the antigen binding molecules of the invention are humanised affinity-matured antibodies.

[0083] Any known methods can be used to increase the affinity of the antigen binding molecules of the invention to generate affinity-matured antibodies or humanised affinity-matured antibodies with an increased affinity for BDCA-2 (CLEC4C).

[0084] The present invention provides affinity matured variants of the provided antigen binding agents. The affinity matured variants bind to BDCA-2 (CLEC4C) with greater affinity than the parental antibody. Preferably the produced antibody binds to BDCA-2 (CLEC4C) with at least 20%, at least 30%, at least 40%, more preferably at least 50% greater affinity than the parental antibody binds to BDCA-2 (CLEC4C), for example as measured by the Kd.

[0085] In some embodiments the invention provides a method of preparing antigen binding molecules of the invention comprising providing an antigen binding molecule as herein described (e.g., anti-BDCA-2 (CLEC4C) binding molecule or antibody or an antigen binding fragment or variant thereof), and subjecting the antibody to affinity maturation, wherein the antibody produced binds to BDCA-2 (CLEC4C) with greater affinity than the parental antibody. Preferably the produced antibody binds to BDCA-2 (CLEC4C) with at least 20%, at least 30%, at least 40%, more preferably at least 50% greater affinity than the parental antibody binds to BDCA-2 (CLEC4C), for example as measured by the Kd. Methods for measuring affinity are known in the art and described in the Examples below. The affinity matured antibodies produced by such methods can be formulated and used as described herein for the other anti-BDCA-2 (CLEC4C) binding molecules.

[0086] Affinity maturation may be carried out according to any suitable method known to the skilled person. For example, in vitro antibody display systems are widely used for the generation of specific antibodies with high affinity. In these systems, the phenotype (i.e. , the antibody fragment) is coupled to the genotype (i.e., the antibody gene) allowing the direct determination of the sequence of the antibody. Several systems have been developed to achieve display of antibody repertoires to allow subsequent selection of binders and by increasing the stringency of selection allows for the selection of higher and higher affinity variants. The antibody fragments can be expressed in yeast, ribosomes, phage display particles or by direct coupling to DNA.

[0087] Current antibody affinity maturation methods belong to two mutagenesis categories: stochastic and non-stochastic. Error-prone polymerase chain reaction (PCR), mutator bacterial strains, and saturation mutagenesis are typical examples of stochastic mutagenesis methods. Non-stochastic techniques often use alanine-scanning or site- directed mutagenesis to generate limited collections of specific variants. In addition, shuffling approaches to obtain shuffled variants of the parent antibody can also be used to improve antibodies’ affinity further.

[0088] Accordingly, in one embodiment of the invention, the method of affinity maturation is selected from the group consisting of stochastic mutagenesis (for example error-prone polymerase chain reaction (PCR), mutator bacterial strains, or saturation mutagenesis), non-stochastic mutagenesis (for example alanine-scanning or site-directed mutagenesis), shuffling (for example DNA shuffling, chain shuffling or CDR shuffling) and the use of the CRISPR-Cas9 system to introduce modifications.

[0089] Affinity maturation methods are described in, for example, Rajpal et al., Proc Natl Acad Sci USA, 2005, 102(24):8466-71 , Steinwand et al., MAbs, 2014, 6(1 ):204-18, as well as in Handbook of Therapeutic Antibodies, Wiley, 2014, Chapter s, Antibody Affinity (pages 115-140).

[0090] In some embodiments there is provided a method of preparing a pharmaceutical composition comprising providing an antibody prepared according to a method above, (i.e. for producing an antibody by affinity maturation) and co-formulating the antibody with at least one or more pharmaceutically acceptable excipients. The antibody used in the preparation of the pharmaceutical composition can be an affinity matured variant of 3E05, 21 E06, 25E06 or 28B01. The antibody used in the preparation of the pharmaceutical composition can also be an affinity matured variant of 3E05_var12, 3E05_var6, 3E05_var14, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15 or 3E05_var16. The pharmaceutical compositions produced by such methods can be used in the methods of treatment of the present invention as described herein for the other anti- BDCA-2 (CLEC4C) binding molecules.

[0091] There are therefore provided antigen binding molecules that are affinity matured mutants or variants of the antigen binding molecules of the invention. For example, in one embodiment there is provided an affinity-matured variant of an antibody selected from the group consisting of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06 and 28B01 . Generally, the affinity matured mutants have a higher affinity for BDCA-2 (CLEC4C) (in particular human BDCA-2 (CLEC4C)) than the parent antibody (the antibody from which the mutant is derived). Also provided by the present invention are antigen binding molecules and antibodies obtainable or obtained by affinity maturation of an antigen binding molecule or antibody of the invention.

[0092] Other variants

[0093] The antigen binding molecule of the invention is typically an antibody, more typically a monoclonal antibody. In a preferred embodiment, the monoclonal antibody of the present invention is a humanised antibody. In some embodiments, the antibody is a fully-human monoclonal antibody, in which the human constant region is employed.

[0094] Methods for the production of monoclonal antibodies are well known to the skilled person, for examples as described in Frenzel et al., “Expression of Recombinant Antibodies”, Front Immunol, 2013, 4:217, the contents of which is hereby incorporated by reference.

[0095] The monoclonal antibodies of the present invention can be humanised by modifying the amino acid sequence of the antibody. Methods to reduce the immunogenicity of the antigen binding molecules of the invention include CDR grafting on to a suitable antibody framework scaffold or variable surface residues remodelling, e.g. by site-directed mutagenesis or other commonly used molecular biological techniques (Roguska et al Protein Eng. 9 895-904 (1996)). Other methods applicable can include the identification of potential T-cell epitopes within the molecule, and the subsequent removal of these e.g. by site-directed mutagenesis (de-immunisation). Humanisation of the antigen binding molecule may be desired where the molecule is to be used as a therapeutic agent. Humanisation of the CDR regions or of the surrounding framework sequence can be carried out as desired.

[0096] It is possible to take monoclonal and other antibodies and use techniques of recombinant DNA technology to produce other antibodies or chimeric molecules which retain the specificity of the original antibody. Such techniques may involve introducing DNA encoding the immunoglobulin variable region, or the complementary determining regions (CDRs), of an antibody to the constant regions, or constant regions plus framework regions, of a different immunoglobulin. A hybridoma or other cell producing an antibody may be subject to genetic mutation or other changes, which may or may not alter the binding specificity of antibodies produced.

[0097] In one embodiment, the heavy chain variable region and / or the light chain variable region are at least 85% humanised, at least 90% humanized, at least 95% humanized, at least 96% humanized, at least 97% humanized, at least 98% humanized or at least 99% humanized. In some embodiments, the antibodies are conservatively humanised, for example to retain better antigen binding. In such conservatively humanised antibodies, fewer antibody substations may be made, compared to humanised antibodies.

[0098] The antigen binding molecules of the invention are, in some embodiments, deimmunised, for example using methods described in Jones et al., “Deimmunization of monoclonal antibodies”, Methods Mol Biol, 2009, 525:405-23, the contents of which are hereby incorporated by reference. Deimmunisation removes T-cell epitopes from the sequences using a combined immunological and molecular biology technique.

[0099] In some embodiments of the invention, there is therefore provided a deimmunised anti-BDCA-2 (CLEC4C) antigen binding molecule or antigen binding fragment thereof, wherein the anti-BDCA-2 (CLEC4C) antigen binding molecule or antigen binding fragment thereof comprises deimmunised variants of the 6 CDR regions of an antibody selected from the group consisting of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06 and 28B01. In a further embodiment of the invention, there is provided a deimmunised anti-BDCA-2 (CLEC4C) antigen binding molecule or antigen binding fragment thereof, wherein the anti-BDCA-2 (CLEC4C) antigen binding molecule or antigen binding fragment thereof comprises deimmunised variants of the VH and / or VL sequences from an antibody selected from the group consisting of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06 and 28B01 . In a still further embodiment of the invention, there is provided a deimmunised anti-BDCA-2 (CLEC4C) antibody, wherein the anti-BDCA-2 (CLEC4C) antibody is a deimmunised variant of an antibody selected from the group consisting of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06 and 28B01.

[0100] The antigen binding molecules and antigen binding fragments thereof are based on 4 parental antibodies 3E05, 21 E06, 25E06 and 28B01. In addition to the parental antibodies, the invention is particularly concerned with humanised and deimmunised derivatives of one of the parental antibodies, 3E05, including 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13,

[0101] 3E05_var15 and 3E05_var16. In preferred embodiments, the invention is particularly concerned with humanised and deimmunised derivatives of 3E05, including 3E05_var12, 3E05_var6 and 3E05_var14. However, humanised and deimmunised derivatives of the remaining 3 parental antibodies are also provided. The invention is also based on antibody-fragments comprising one more antigen binding domains from the parental or humanised / deimmunised antibodies of the invention, as well as further variants such as antigen binding domains containing 1 or more conservative amino acid substitutions (such as from 1 to 10, or preferably from 1 to 5 substitutions) and affinity matured variants of the antigen binding molecules of the invention. All of the antigen binding molecules of the invention specifically bind BDCA-2 (CLEC4C). Humanised and deimmunised variants of antibodies provided herein may have at least 90% sequence identity, for example at least 95% sequence identity to the original, parental, sequence(s) that is / are humanised or deimmunised.

[0102] The antigen binding molecules described herein are lgG1 and comprise the following substitution in the heavy chain Fc region: M252Y / S254T / T256E, which refer to positions in the heavy chain lgG1 Fc region according to Ell numbering. For instance, the antigen binding molecules can comprise a heavy chain of SEQ ID NO: 93, wherein the positions 252, 254, and 256 in Ell numbering corresponds to residues at positions 258, 260, and 262 in SEQ ID NO: 93 (i.e., M252Y / S254T / T256E in EU numbering is M258Y / S260T / T262E in SEQ ID NO: 94). In some embodiments, the antigen binding molecule comprises a heavy chain of SEQ ID NO: 93 and a light chain of SEQ ID NO: 94.

[0103] "Specific binding", "bind specifically", and "specifically bind" are understood to mean that the anti-BDCA-2 (CLEC4C) antigen binding molecule has a dissociation constant (Kd) for BDCA-2 (CLEC4C) of less than about 10’6M, 10’7M, 10’8M, 10’9M, 1 O’10M, 10’11M or 10’12M. In a preferred embodiment, the dissociation constant is less than 10’8M, for instance in the range of 10’9M, 10’10M, 10’11M or 10’12M. In accordance with some embodiments of the invention, "Specific binding", "bind specifically", and "specifically bind" may refer to affinity and / or avidity. In some embodiments, the affinity of the anti-BDCA-2 (CLEC4C) antigen binding molecule is from 10’8to 10’6M (for example about 10-7M). In some embodiments of the invention, the avidity of the anti-BDCA-2 (CLEC4C) antigen binding molecule is about from 10’10to 10’8M (for example about 10’9M). In some embodiments of the invention, the affinity and / or avidity of the anti-BDCA-2 (CLEC4C) antigen binding molecule is about from 1 nM to 700 nM, or about from 1 to 600 nM, or about from 1 to 500 nM, or about from 1 to 400 nM, or about from 1 to 300 nM.

[0104] Manufacturing liabilities

[0105] Therapeutic proteins such as antibodies are heterogenous and complex by nature due to chemical modifications and post-translational modifications (PTMs). Modifications can be caused by a number of factors such as the host cell system, processes used in manufacture or conditions during storage or manufacture. Modifications can relate to the chemical stability of the molecule itself or the aggregation potential and the effect this has on intrinsic physical stability of the antibody. Amino acid motifs or residues in a given antibody sequence that may undergo spontaneous modification during manufacture or storage are referred to as liabilities. Accordingly, mutations may be made to the antibody sequence to address the liabilities to reduce the susceptibility of the antibody to modification and degradation.

[0106] Such modifications as a result of liabilities in the antibody sequences may include glycosylation, deamidation, oxidation and variations of C- and N- termini. Such modifications may arise during manufacture. Certain residues and structural or sequence motifs are more liable to certain modifications. Examples of such liabilities to modification include Asn N-linked glycosylation, Ser / Thr O-linked glycosylation, Asn deamidation, Asp isomerisation / fragmentation, Lys glycation, Met / Trp oxidation, free thiol groups, pyroglutamates, C-terminal Lys.

[0107] A skilled person is aware that computational tools can be used to predict and identify structural and sequence liabilities which could potentially result in modifications. To minimise the occurrence of modifications alterations to the manufacturing process can be made. Protein engineering may also be considered to reduce the risk. For example, selective mutation of these liabilities can help to identify and reduce the risk of a modification endangering the stability of an antibody.

[0108] Aspartic acid residues (Asp) may undergo spontaneous modification. Asp containing motifs, such as Asp-Gly sequences may undergo spontaneous isomerization to form isoaspartic acid. Formation of isoaspartate may debilitate or completely abrogate the binding of the antibody. This is of additional importance if the Asp residue appears in the CDR of an antibody.

[0109] Aspartic acid residues (Asp) can therefore be substituted with any naturally occurring amino acid to reduce this liability to modification. Optionally, aspartic acid residues (Asp) can be substituted with alanine (Ala), glutamine (Gin) or glutamic acid (Glu) to reduce this liability to modification. Optimization of production / formulation can also be investigated to reduce isomerization. Alternatively, Asp-Gly motifs may be modified by substituting the glycine residue with another naturally occurring amino acid to inhibit deamidation, rather than by substitution of the Asp residue. Methionine residues (Met) may undergo spontaneous modification. The presence of methionine (Met) in a CDR, especially if exposed to solvent, can create a problem if the methionine is oxidized and this interferes with binding. Methionine residues can therefore be substituted with any other naturally occurring amino acid to reduce this liability to modification. Methionine residues may preferably be substituted with Ala or Leu. Optimization of production / formulation can also be investigated to reduce oxidation.

[0110] Therefore, variant antibodies derived from any of 3E05_var12, 3E05_var6, 3E05_var14, 3E05, 3E05_var1 , 3E05_var2, 3E05_var3, 3E05_var4, 3E05_var5, 3E05_var7, 3E05_var8, 3E05_var9, 3E05_var10, 3E05_var11 , 3E05_var13, 3E05_var15, 3E05_var16, 21 E06, 25E06 and 28B01 but comprising one or more amino substitutions to address one or more of any potential liabilities as described above are also provided herein.

[0111] For example, for any antigen binding molecules defined by one or more amino acid sequences herein, if there are one or more Met residues present, the one or more Met residues may each and independently be substituted with an Ala residue or a Leu residue. If there are one or more Asp residues present, the one or more Asp residues may each and independently be substituted with an Ala residue, a Gin residue, or a Glu residue.

[0112] Summary of antigen binding molecules provided

[0113] Provided herein is a BDCA-2 antigen binding molecule comprising an IgG 1 Fc region with the following substitutions: M252Y / S254T / T256E.

[0114] The BDCA-2 antigen binding molecule comprises a means for binding the BDCA-2 antigen. Means for binding BDCA-2 include immunoglobulin variable region sequences described herein. Examples of BDCA-2 antigen binding variable regions are provided in the following sections, with identification of the assigned SEQ ID NO in the accompanying sequence listing. Antigen binding variants, derivatives and fragments thereof are also provided. Thus, as additional aspects and embodiments of the disclosure, the BDCA-2 binding molecule can comprise any of the variable region disclosed herein and an lgG1 Fc region comprising the substitutions: M252Y / S254T / T256E: Table 1. Summary of parental mouse antibodies and conservatively humanised, humanised and deimmunised versions of two parental antibodies

[0115] Table 2 - Combination of humanised / deimmunised heavy and light chain variable regions produces 16 antibodies derived from the 3E05 parent antibody

[0116] In some embodiments, the BDCA-2 binding agent comprises a heavy and light chain variable region of Table 1 or Table 2, or at least the CDRs thereof, and an IgG 1 Fc region comprising the substitutions: M252Y / S254T / T256E. The CDRs of a given Ig sequence can be determined by any of several conventional numbering schemes, such as Kabat, Chothia, Martin (Enhanced Chothia), IGMT, or AHo (these are commonly used names for numbering schemes widely known in the field and described in published literature see, e.g., Kabat, et al., Sequences of Proteins of Immunological Interest, U.S. Department of Health and Human Services, NIH (1991) describing the “Kabat” numbering scheme; Chothia, et al., Canonical Structures for the Hypervariable Regions of Immunoglobulins, J. Mol. Biol., 196:901-917 (1987) and Al-Lazikani et al., Standard Conformations for the Canonical Structures of Immunoglobulins, J. Mol. Biol., 273:927 - 948 (1997) describing the “Chothia” numbering scheme; Abhinandan et al., Analysis and Improvements to Kabat and Structurally Correct Numbering of Antibody Variable Domains, Mol. Immunol., 45: 3832 - 3839 (2008) describing the “Martin” or “Enhanced Chothia” numbering scheme; Lefranc et al., The IMGT unique numbering for immunoglobulins, T cell Receptors and Ig-like domains, The Immunologist, 7: 132-136 (1999) and Lefranc et al., IMGT unique numbering for immunoglobulin and T cell receptor variable domains and I superfamily V-like domains, Dev. Comp. Immunol., 27: 55 - 77 (2003) describing the “IMGT” numbering scheme; and Honegger et al., Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool, J. Mol. Biol. 309: 657 - 670 (2001 ) describing the “AHo” numbering scheme). The various embodiments of variable region and CDR sequences of the BDCA- 2 binding agent are discussed in more detail in the following sections.

[0117] Antigen binding molecules comprising a VHCDR3 and / or a VLCDR3 region

[0118] In one embodiment, an antibody, fragment or variant thereof, is provided comprising a heavy chain variable region comprising a VHCDR3 comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 48, 28, 8, 18, 38, 58, 68 and 78, and / or a light chain variable region comprising a VLCDR3 comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 34, 24, 44, 4, 14, 54, 64 and 74. Certain amino acid substitutions may be made to provide one or more variant antibodies as described herein.

[0119] 3E05

[0120] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8) and / or a light chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 4). In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8) and / or a light chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 4).

[0121] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8) and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4). In a particular embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYDGGLYYAMDY (SEQ ID NO: 8) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQTNEDPPT (SEQ ID NO: 4).

[0122] Amino acid substitutions may be made to provide variant antibodies derived from 3E05, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4), optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0123] In one embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYDGGLYYAMDY (SEQ ID NO: 8) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQTNEDPPT (SEQ ID NO: 4), optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0124] 3E05 var 1, 5, 9 and 13

[0125] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) and / or a light chain variable region comprising the amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In one embodiment, the heavy chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) and / or the light chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0126] In one embodiment, an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In a particular embodiment, an antibody, fragment or variant thereof is provided, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYDGGLYYAMDY (SEQ ID NO: 18) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQTNEDPPT (SEQ ID NO: 14).

[0127] Amino acid substitutions may be made to provide variant antibodies derived from 3E05 var 1 , 5, 9 or 13, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14), optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0128] In one embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYDGGLYYAMDY (SEQ ID NO: 18) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQTNEDPPT (SEQ ID NO: 14), optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0129] 3E05 var 2, 6, 10 and 14 In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) and / or a light chain variable region comprising the amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In one embodiment, the heavy chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) and / or the light chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0130] In one embodiment, an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In a particular embodiment, an antibody, fragment or variant thereof is provided, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYDGGLYYAMDY (SEQ ID NO: 28) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQTNEDPPT (SEQ ID NO: 14).

[0131] Amino acid substitutions may be made to provide variant antibodies derived from 3E05 var 2, 6, 10 or 14, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14), optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0132] In one embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYDGGLYYAMDY (SEQ ID NO: 28), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14), optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0133] 3E05 var 3, 7, 11 and 15

[0134] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) and / or a light chain variable region comprising the amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In one embodiment, the heavy chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) and / or the light chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0135] In one embodiment, an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In a particular embodiment, an antibody, fragment or variant thereof is provided, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYDGGLYYAMDY (SEQ ID NO: 38) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQTNEDPPT (SEQ ID NO: 14).

[0136] Amino acid substitutions may be made to provide variant antibodies derived from 3E05 var 3, 7, 11 or 15, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14), optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0137] In one embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYDGGLYYAMDY (SEQ ID NO: 38), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14), optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0138] 3E05 ar 4, 8, 12 and 16

[0139] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) and / or a light chain variable region comprising the amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In one embodiment, the heavy chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) and / or the light chain variable region comprises an amino acid sequence having at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0140] In one embodiment, an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In a particular embodiment, an antibody, fragment or variant thereof is provided, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYEGGLYYAMDY (SEQ ID NO: 48) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQTNEDPPT (SEQ ID NO: 14).

[0141] Amino acid substitutions may be made to provide variant antibodies derived from 3E05 var 4, 8, 12 or 16, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14), optionally comprising 1 or 2 amino acid substitutions.

[0142] The amino acid substitutions may be conservative amino acid substitutions.

[0143] In one embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HDYYEGGLYYAMDY (SEQ ID NO: 48) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQTNEDPPT (SEQ ID NO: 14), optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0144] 21E06

[0145] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58) and / or a light chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 54). In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58) and / or a light chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 54).

[0146] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58) and / or a light chain variable region comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54). In a particular embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HLYYGDYFYVMDY (SEQ ID NO: 58) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQSNEDPPT (SEQ ID NO: 54). Amino acid substitutions may be made to provide variant antibodies derived from 21 E06, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54), optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0147] In one embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HLYYGDYFYVMDY (SEQ ID NO: 58) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQSNEDPPT (SEQ ID NO: 54), optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0148] 25E06

[0149] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68) and / or a light chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 64). In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68) and / or a light chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 64).

[0150] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68) and / or a light chain variable region comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64). In a particular embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HHYSHYFWYFDV (SEQ ID NO: 68) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQSNEDPPT (SEQ ID NO: 64).

[0151] Amino acid substitutions may be made to provide variant antibodies derived from 25E06, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64), optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0152] In one embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HHYSHYFWYFDV (SEQ ID NO: 68) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQSNEDPPT (SEQ ID NO: 64), optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0153] 28B01

[0154] In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78) and / or a light chain variable region comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 74). In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78) and / or a light chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 74). In one embodiment, an antigen binding molecule, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78) and / or a light chain variable region comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74). In a particular embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HHYSNYFWYFDV (SEQ ID NO: 78) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQSNEDPPT (SEQ ID NO: 74).

[0155] Amino acid substitutions may be made to provide variant antibodies derived from 28B01 , for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78), optionally comprising 1 or 2 amino acid substitutions, and / or a light chain variable region comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74), optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0156] In one embodiment, the antigen binding molecule is an antibody or fragment or variant thereof, wherein the VHCDR3 region of said antibody or fragment or variant thereof is HHYSNYFWYFDV (SEQ ID NO: 78) and / or the VLCDR3 region of said antibody or fragment or variant thereof is QQSNEDPPT (SEQ ID NO: 74), optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0157] Heavy and / or light chain CDRs

[0158] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising: a VHCDR1 comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 46, 49, 26, 29, 6, 9, 16, 19, 36, 39, 56, 59, 66, 69, 76 and 79; a VHCDR2 comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 47, 50, 27, 30, 7, 10, 17, 20, 37, 40, 57, 60, 67, 70, 77 and 80; and a VHCDR3 comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 48, 28, 8, 18, 38, 58, 68 and 78; and a light chain variable region comprising: a VLCDR1 comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 32, 22, 42, 2, 12, 52, 62 and 72; a VLCDR2 comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 33, 23, 43, 3, 13, 53, 63 and 73; and a VLCDR3 comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 34, 24, 44, 4, 14, 54, 64 and 74.

[0159] Certain amino acid substitutions may be made to provide one or more variant antibodies as described herein.

[0160] 3E05

[0161] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 6), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 7) and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 4). In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 9), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 10) and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 4).

[0162] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 6), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 7) and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 4).

[0163] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 9), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 10) and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 4).

[0164] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 6), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 7) and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4).

[0165] Amino acid substitutions may be made to provide variant antibodies derived from 3E05, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 6) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 7) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 3) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0166] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 6), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 7) and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0167] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 9), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 10), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4).

[0168] Amino acid substitutions may be made to provide variant antibodies derived from 3E05, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 9) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 10) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 3) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0169] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 9), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 10), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0170] 3E05 var 12

[0171] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0172] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0173] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0174] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0175] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0176] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 12, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0177] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0178] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 12, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0179] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0180] Antigen binding molecules of or derived from 3E05_var12 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM, an IC50 for IFN secretion of less than about 0.5M, and / or an IC90 for IFN secretion of less than about 5nM. In a specific embodiment, antigen binding molecules of or derived from 3E05_var12 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM, an IC50 for IFN secretion of less than about 0.2nM, and / or an IC90 for IFN secretion of less than about 2nM

[0181] 3E05 var 6

[0182] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0183] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0184] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0185] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0186] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0187] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 6, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0188] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0189] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0190] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 6, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0191] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu. Antigen binding molecules of or derived from 3E05_var6 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM, an IC50 for IFN secretion of less than about 0.5M, and / or an IC90 for IFN secretion of less than about 5nM. In a specific embodiment, antigen binding molecules of or derived from 3E05_var6 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM, an IC50 for IFN secretion of less than about 0.1 nM, and / or an IC90 for IFN secretion of less than about 1 nM

[0192] 3E05 var 14

[0193] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0194] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0195] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0196] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0197] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0198] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 14, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0199] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0200] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0201] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 14, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0202] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0203] Antigen binding molecules of or derived from 3E05_var14 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM, an IC50 for IFN secretion of less than about 0.5M, and / or an IC90 for IFN secretion of less than about 5nM. In a specific embodiment, antigen binding molecules of or derived from 3E05_var14 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM, an IC50 for IFN secretion of less than about 0.2nM, and / or an IC90 for IFN secretion of less than about 2nM

[0204] 3E05 var 1

[0205] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0206] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0207] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0208] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0209] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0210] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 1 , for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0211] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0212] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 1 , for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0213] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0214] Antigen binding molecules of or derived from 3E05_var1 (for example antibodies having one or more amino acid substitutions) may have a Ko of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0215] 3E05 var 2

[0216] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0217] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0218] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0219] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0220] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0221] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 2, for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0222] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0223] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 2, for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) optionally comprising 1 or 2 amino acid substitutions, and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0224] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0225] Antigen binding molecules of or derived from 3E05_var2 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.5nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0226] 3E05 var 3

[0227] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0228] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0229] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0230] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0231] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0232] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 3, for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0233] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0234] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0235] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 3, for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0236] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0237] Antigen binding molecules of or derived from 3E05_var3 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0238] 3E05 var 4

[0239] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0240] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0241] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0242] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 14). In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0243] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 4, for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0244] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0245] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14).

[0246] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 4, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0247] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0248] Antigen binding molecules of or derived from 3E05_var4 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0249] 3E05 var 5

[0250] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0251] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0252] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0253] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0254] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0255] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 5, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0256] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0257] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 5, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0258] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0259] Antigen binding molecules of or derived from 3E05_var5 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0260] 3E05 var 7

[0261] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0262] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0263] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0264] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0265] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0266] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 7, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0267] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0268] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24). Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 7, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0269] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0270] Antigen binding molecules of or derived from 3E05_var7 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0271] 3E05 var 8

[0272] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0273] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0274] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0275] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0276] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0277] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 8, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0278] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0279] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24).

[0280] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 8, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0281] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0282] Antigen binding molecules of or derived from 3E05_var8 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0283] 3E05 var 9

[0284] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0285] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0286] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0287] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34). In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0288] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 9, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0289] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0290] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0291] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 9, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0292] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0293] Antigen binding molecules of or derived from 3E05_var9 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0294] 3E05 var 10

[0295] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0296] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0297] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0298] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0299] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0300] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 10, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0301] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0302] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 10, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0303] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0304] Antigen binding molecules of or derived from 3E05_var10 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 1 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0305] 3E05 var 11

[0306] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0307] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0308] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0309] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0310] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34).

[0311] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 11 , for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0312] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0313] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34). Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 11 , for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0314] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0315] Antigen binding molecules of or derived from 3E05_var11 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 1 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0316] 3E05 var 13

[0317] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0318] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0319] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0320] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0321] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0322] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 13, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0323] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0324] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0325] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 13, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0326] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0327] Antigen binding molecules of or derived from 3E05_var13 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0328] 3E05 var 15

[0329] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0330] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0331] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0332] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44). In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0333] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 15, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0334] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0335] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0336] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 15, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0337] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0338] Antigen binding molecules of or derived from 3E05_var15 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0339] 3E05 var 16

[0340] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0341] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0342] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0343] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0344] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0345] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 16, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0346] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44).

[0347] Amino acid substitutions may be made to provide variant antibodies derived from 3E05_var 16, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0348] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), and a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0349] Antigen binding molecules of or derived from 3E05_var16 (for example antibodies having one or more amino acid substitutions) may have a KD of less than about 0.01 nM. Such antigen binding molecules may additionally or alternatively exhibit an IC50 for IFN secretion of less than about 0.5nM and / or an IC90 for IFN secretion of less than about 5nM.

[0350] 21E06

[0351] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTIS (SEQ ID NO: 56), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGDNAYYPDSVKG (SEQ ID NO: 57), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 54).

[0352] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 59), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGDN (SEQ ID NO: 60), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 54).

[0353] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTIS (SEQ ID NO: 56), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGDNAYYPDSVKG (SEQ ID NO: 57), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 54).

[0354] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 59), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGDN (SEQ ID NO: 60), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 54).

[0355] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTIS (SEQ ID NO: 56), a VHCDR2 comprising the amino acid sequence YISSGGDNAYYPDSVKG (SEQ ID NO: 57), and a VHCDR3 comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54).

[0356] Amino acid substitutions may be made to provide variant antibodies derived from 21 E06, for example an antibody, fragment or variant thereof is provided comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTIS (SEQ ID NO: 56) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGDNAYYPDSVKG (SEQ ID NO: 57) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 53) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0357] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTIS (SEQ ID NO: 56), a VHCDR2 comprising the amino acid sequence YISSGGDNAYYPDSVKG (SEQ ID NO: 57), and a VHCDR3 comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54). optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0358] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 59), a VHCDR2 comprising the amino acid sequence SSGGDN (SEQ ID NO: 60), and a VHCDR3 comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54). Amino acid substitutions may be made to provide variant antibodies derived from 21 E06, for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 59) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGDN (SEQ ID NO: 60) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 53) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0359] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 59), a VHCDR2 comprising the amino acid sequence SSGGDN (SEQ ID NO: 60), and a VHCDR3 comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54). optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0360] 25E06

[0361] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SYTMS (SEQ ID NO: 66), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISGVGGDTYYPDSVKG (SEQ ID NO: 67), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 64).

[0362] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 69), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SGVGGD (SEQ ID NO: 70), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 64).

[0363] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence SYTMS (SEQ ID NO: 66), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISGVGGDTYYPDSVKG (SEQ ID NO: 67), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 64).

[0364] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSSY (SEQ ID NO: 69), a VHCDR2 comprising at least 90% identity to the amino acid sequence SGVGGD (SEQ ID NO: 70), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 64).

[0365] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 66), a VHCDR2 comprising the amino acid sequence YISGVGGDTYYPDSVKG (SEQ ID NO: 67), and a VHCDR3 comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64).

[0366] Amino acid substitutions may be made to provide variant antibodies derived from 25E06, for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 66) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISGVGGDTYYPDSVKG (SEQ ID NO: 67) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 63) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0367] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 66), a VHCDR2 comprising the amino acid sequence YISGVGGDTYYPDSVKG (SEQ ID NO: 67), and a VHCDR3 comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0368] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 69), a VHCDR2 comprising the amino acid sequence SGVGGD (SEQ ID NO: 70), and a VHCDR3 comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64).

[0369] Amino acid substitutions may be made to provide variant antibodies derived from 25E06, for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 69) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SGVGGD (SEQ ID NO: 70) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 63) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0370] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 69), a VHCDR2 comprising the amino acid sequence SGVGGD (SEQ ID NO: 70), and a VHCDR3 comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0371] 28B01 In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YYTMS (SEQ ID NO: 76), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence YISSGGDNAYYPDSVRG (SEQ ID NO: 77), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 74).

[0372] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence GFTFSYY (SEQ ID NO: 79), a VHCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence SSGGDN (SEQ ID NO: 80), and a VHCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and / or a light chain variable region comprising a VLCDR1 comprising the at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 74).

[0373] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence YYTMS (SEQ ID NO: 76), a VHCDR2 comprising at least 90% identity to the amino acid sequence YISSGGDNAYYPDSVRG (SEQ ID NO: 77), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 74).

[0374] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising at least 90% identity to the amino acid sequence GFTFSYY (SEQ ID NO: 79), a VHCDR2 comprising at least 90% identity to the amino acid sequence SSGGDN (SEQ ID NO: 80), and a VHCDR3 comprising at least 90% identity to the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and / or a light chain variable region comprising a VLCDR1 comprising the at least 90% identity to amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising at least 90% identity to the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising at least 90% identity to the amino acid sequence QQSNEDPPT (SEQ ID NO: 74).

[0375] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence YYTMS (SEQ ID NO: 76), a VHCDR2 comprising the amino acid sequence YISSGGDNAYYPDSVRG (SEQ ID NO: 77), and a VHCDR3 comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74). Amino acid substitutions may be made to provide variant antibodies derived from 28B01 , for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence YYTMS (SEQ ID NO: 76) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence YISSGGDNAYYPDSVRG (SEQ ID NO: 77) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 73) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0376] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence YYTMS (SEQ ID NO: 76), a VHCDR2 comprising the amino acid sequence YISSGGDNAYYPDSVRG (SEQ ID NO: 77), and a VHCDR3 comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0377] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSYY (SEQ ID NO: 79), a VHCDR2 comprising the amino acid sequence SSGGDN (SEQ ID NO: 80), and a VHCDR3 comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74).

[0378] Amino acid substitutions may be made to provide variant antibodies derived from 28B01 , for example an antibody, fragment or variant thereof is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSYY (SEQ ID NO: 79) optionally comprising 1 or 2 amino acid substitutions, a VHCDR2 comprising the amino acid sequence SSGGDN (SEQ ID NO: 80) optionally comprising 1 or 2 amino acid substitutions, and a VHCDR3 comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78) optionally comprising 1 or 2 amino acid substitutions; and / or a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72) optionally comprising 1 or 2 amino acid substitutions, a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 73) optionally comprising 1 or 2 amino acid substitutions and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74) optionally comprising 1 or 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions.

[0379] In one embodiment, an antibody, fragment or variant thereof, is provided comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSYY (SEQ ID NO: 79), a VHCDR2 comprising the amino acid sequence SSGGDN (SEQ ID NO: 80), and a VHCDR3 comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74); optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu.

[0380] Heavy and / or light chain variable regions

[0381] In one embodiment, the invention provides an antigen binding molecules, in particular an antibody that binds to BDCA-2 (CLEC4C), comprising a heavy chain variable region having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 45, SEQ ID NO: 25, SEQ ID NO: 5, SEQ ID NO: 15, SEQ ID NO: 35, SEQ ID NO: 55, SEQ ID NO: 65 and SEQ ID NO: 75, and / or a light chain variable region having at least 70%, 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an amino acid sequence selected from the group consisting of consisting SEQ ID NO: 31 , SEQ ID NO: 21 , SEQ ID NO: 41 , SEQ ID NO: 1 , SEQ ID NO: 11 , SEQ ID NO: 51 , SEQ ID NO: 61 and SEQ ID NO: 71.

[0382] In one embodiment, the antibody binds to BDCA-2 (CLEC4C) and comprises a heavy chain variable region having the amino acid sequence selected from the group consisting of SEQ ID NO: 45, SEQ ID NO: 25, SEQ ID NO: 5, SEQ ID NO: 15, SEQ ID NO: 35, SEQ ID NO: 55, SEQ ID NO: 65 and SEQ ID NO: 75, and / or a light chain variable region having the amino acid sequence selected from the group consisting of SEQ ID NO: 31 , SEQ ID NO: 21 , SEQ ID NO: 41 , SEQ ID NO: 1 , SEQ ID NO: 11 , SEQ ID NO: 51 , SEQ ID NO: 61 and SEQ ID NO: 71.

[0383] In one embodiment, the antibody binds to BDCA-2 (CLEC4C) and comprises a heavy chain variable region having the amino acid sequence selected from the group consisting of SEQ ID NO: 45, SEQ ID NO: 25, SEQ ID NO: 5, SEQ ID NO: 15, SEQ ID NO: 35, SEQ ID NO: 55, SEQ ID NO: 65 and SEQ ID NO: 75, and / or a light chain variable region having the amino acid sequence selected from the group consisting of SEQ ID NO: 31 , SEQ ID NO: 21 , SEQ ID NO: 41 , SEQ ID NO: 1 , SEQ ID NO: 11 , SEQ ID NO: 51 , SEQ ID NO: 61 and SEQ ID NO: 71 , optionally wherein the Met residues are each independently substituted with an amino acid selected from the group consisting of Ala and Leu, and / or the Asp residues are each independently substituted with an amino acid selected from the group consisting of Ala, Gin and Glu. In one embodiment, an antigen binding molecule, for example an antibody, variant or fragment thereof is provided, wherein the antigen binding molecule comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:

[0384] (a) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 31 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 45 and SEQ ID NO: 31 , respectively);

[0385] (b) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 21 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 25 and SEQ ID NO: 21 , respectively);

[0386] (c) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 41 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 25 and SEQ ID NO: 41 , respectively);

[0387] (d) a VH comprising the amino acid sequence of SEQ ID NO: 5 and a VL comprising the amino acid sequence of SEQ ID NO: 1 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 5 and SEQ ID NO: 1 , respectively);

[0388] (e) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 11 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 15 and SEQ ID NO: 11 , respectively);

[0389] (f) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 11 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 25 and SEQ ID NO: 11 , respectively);

[0390] (g) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 11 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 35 and SEQ ID NO: 11 , respectively);

[0391] (h) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 11 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 45 and SEQ ID NO: 11 , respectively);

[0392] (i) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 21 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 15 and SEQ ID NO: 21 , respectively);

[0393] (j) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 21 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 35 and SEQ ID NO: 21 , respectively);

[0394] (k) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 21 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 45 and SEQ ID NO: 21 , respectively);

[0395] (l) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 31 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 15 and SEQ ID NO: 31 , respectively);

[0396] (m) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 31 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 25 and SEQ ID NO: 31 , respectively);

[0397] (n) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 31 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 35 and SEQ ID NO: 31 , respectively);

[0398] (o) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 41 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 15 and SEQ ID NO: 41 , respectively);

[0399] (p) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 41 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 35 and SEQ ID NO: 41 , respectively); (q) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 41 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 45 and SEQ ID NO: 41 , respectively);

[0400] (r) a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 51 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 55 and SEQ ID NO: 51 , respectively);

[0401] (s) a VH comprising the amino acid sequence of SEQ ID NO: 65 and a VL comprising the amino acid sequence of SEQ ID NO: 61 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 65 and SEQ ID NO: 61 , respectively); and

[0402] (t) a VH comprising the amino acid sequence of SEQ ID NO: 75 and a VL comprising the amino acid sequence of SEQ ID NO: 71 (or comprising VH and VL sequences that are at least 90% identical to SEQ ID NO: 75 and SEQ ID NO: 71 , respectively).

[0403] In one embodiment, an antigen binding molecule, for example an antibody, variant or fragment thereof is provided, wherein the antigen binding molecule comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:

[0404] (a) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 31 ;

[0405] (b) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 21 ;

[0406] (c) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 41 ;

[0407] (d) a VH comprising the amino acid sequence of SEQ ID NO: 5 and a VL comprising the amino acid sequence of SEQ ID NO: 1 ;

[0408] (e) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 11 ;

[0409] (f) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 11 ; (g) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 11 ;

[0410] (h) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 11 ;

[0411] (i) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 21 ;

[0412] (j) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 21 ;

[0413] (k) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 21 ;

[0414] (l) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 31 ;

[0415] (m) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 31 ;

[0416] (n) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 31 ;

[0417] (o) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 41 ;

[0418] (p) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 41 ;

[0419] (q) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 41 ;

[0420] (r) a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 51 ;

[0421] (s) a VH comprising the amino acid sequence of SEQ ID NO: 65 and a VL comprising the amino acid sequence of SEQ ID NO: 61 ; and

[0422] (t) a VH comprising the amino acid sequence of SEQ ID NO: 75 and a VL comprising the amino acid sequence of SEQ ID NO: 71 .

[0423] In one embodiment, an antigen binding molecule, for example an antibody, variant or fragment thereof is provided, wherein the antigen binding molecule comprises a heavy chain variable region and a light chain variable region selected from the group consisting of: (a) a VH comprising the amino acid sequence of SEQ ID NO: 45 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 31 optionally comprising up to 5 amino acid substitutions;

[0424] (b) a VH comprising the amino acid sequence of SEQ ID NO: 25 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 21 optionally comprising up to 5 amino acid substitutions;

[0425] (c) a VH comprising the amino acid sequence of SEQ ID NO: 25 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 41 optionally comprising up to 5 amino acid substitutions;

[0426] (d) a VH comprising the amino acid sequence of SEQ ID NO: 5 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 1 optionally comprising up to 5 amino acid substitutions;

[0427] (e) a VH comprising the amino acid sequence of SEQ ID NO: 15 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 11 optionally comprising up to 5 amino acid substitutions;

[0428] (f) a VH comprising the amino acid sequence of SEQ ID NO: 25 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 11 optionally comprising up to 5 amino acid substitutions;

[0429] (g) a VH comprising the amino acid sequence of SEQ ID NO: 35 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 11 optionally comprising up to 5 amino acid substitutions;

[0430] (h) a VH comprising the amino acid sequence of SEQ ID NO: 45 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 11 optionally comprising up to 5 amino acid substitutions;

[0431] (i) a VH comprising the amino acid sequence of SEQ ID NO: 15 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 21 optionally comprising up to 5 amino acid substitutions;

[0432] (j) a VH comprising the amino acid sequence of SEQ ID NO: 35 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 21 optionally comprising up to 5 amino acid substitutions;

[0433] (k) a VH comprising the amino acid sequence of SEQ ID NO: 45 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 21 optionally comprising up to 5 amino acid substitutions;

[0434] (l) a VH comprising the amino acid sequence of SEQ ID NO: 15 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 31 optionally comprising up to 5 amino acid substitutions;

[0435] (m) a VH comprising the amino acid sequence of SEQ ID NO: 25 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 31 optionally comprising up to 5 amino acid substitutions;

[0436] (n) a VH comprising the amino acid sequence of SEQ ID NO: 35 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 31 optionally comprising up to 5 amino acid substitutions;

[0437] (o) a VH comprising the amino acid sequence of SEQ ID NO: 15 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 41 optionally comprising up to 5 amino acid substitutions;

[0438] (p) a VH comprising the amino acid sequence of SEQ ID NO: 35 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 41 optionally comprising up to 5 amino acid substitutions;

[0439] (q) a VH comprising the amino acid sequence of SEQ ID NO: 45 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 41 optionally comprising up to 5 amino acid substitutions; (r) a VH comprising the amino acid sequence of SEQ ID NO: 55 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 51 optionally comprising up to 5 amino acid substitutions;

[0440] (s) a VH comprising the amino acid sequence of SEQ ID NO: 65 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 61 optionally comprising up to 5 amino acid substitutions; and

[0441] (t) a VH comprising the amino acid sequence of SEQ ID NO: 75 optionally comprising up to 5 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 71 optionally comprising up to 5 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. The amino acid substitutions may occur only in one or more framework regions. In some embodiments, the amino acid substitutions may be conservative amino acid substitutions and occur only in one or more framework regions.

[0442] In one embodiment, an antigen binding molecule, for example an antibody, variant or fragment thereof is provided, wherein the antigen binding molecule comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:

[0443] (a) a VH comprising the amino acid sequence of SEQ ID NO: 45 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 31 optionally comprising up to 2 amino acid substitutions;

[0444] (b) a VH comprising the amino acid sequence of SEQ ID NO: 25 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 21 optionally comprising up to 2 amino acid substitutions;

[0445] (c) a VH comprising the amino acid sequence of SEQ ID NO: 25 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 41 optionally comprising up to 2 amino acid substitutions;

[0446] (d) a VH comprising the amino acid sequence of SEQ ID NO: 5 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 1 optionally comprising up to 2 amino acid substitutions; (e) a VH comprising the amino acid sequence of SEQ ID NO: 15 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 11 optionally comprising up to 2 amino acid substitutions;

[0447] (f) a VH comprising the amino acid sequence of SEQ ID NO: 25 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 11 optionally comprising up to 2 amino acid substitutions;

[0448] (g) a VH comprising the amino acid sequence of SEQ ID NO: 35 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 11 optionally comprising up to 2 amino acid substitutions;

[0449] (h) a VH comprising the amino acid sequence of SEQ ID NO: 45 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 11 optionally comprising up to 2 amino acid substitutions;

[0450] (i) a VH comprising the amino acid sequence of SEQ ID NO: 15 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 21 optionally comprising up to 2 amino acid substitutions;

[0451] (j) a VH comprising the amino acid sequence of SEQ ID NO: 35 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 21 optionally comprising up to 2 amino acid substitutions;

[0452] (k) a VH comprising the amino acid sequence of SEQ ID NO: 45 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 21 optionally comprising up to 2 amino acid substitutions;

[0453] (l) a VH comprising the amino acid sequence of SEQ ID NO: 15 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 31 optionally comprising up to 2 amino acid substitutions;

[0454] (m) a VH comprising the amino acid sequence of SEQ ID NO: 25 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 31 optionally comprising up to 2 amino acid substitutions;

[0455] (n) a VH comprising the amino acid sequence of SEQ ID NO: 35 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 31 optionally comprising up to 2 amino acid substitutions;

[0456] (o) a VH comprising the amino acid sequence of SEQ ID NO: 15 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 41 optionally comprising up to 2 amino acid substitutions; (p) a VH comprising the amino acid sequence of SEQ ID NO: 35 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 41 optionally comprising up to 2 amino acid substitutions;

[0457] (q) a VH comprising the amino acid sequence of SEQ ID NO: 45 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 41 optionally comprising up to 2 amino acid substitutions;

[0458] (r) a VH comprising the amino acid sequence of SEQ ID NO: 55 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 51 optionally comprising up to 2 amino acid substitutions;

[0459] (s) a VH comprising the amino acid sequence of SEQ ID NO: 65 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 61 optionally comprising up to 2 amino acid substitutions; and

[0460] (t) a VH comprising the amino acid sequence of SEQ ID NO: 75 optionally comprising up to 2 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID NO: 71 optionally comprising up to 2 amino acid substitutions. The amino acid substitutions may be conservative amino acid substitutions. The amino acid substitutions may occur only in one or more framework regions. In some embodiments, the amino acid substitutions may be conservative amino acid substitutions and occur only in one or more framework regions.

[0461] In one embodiment, an antigen binding molecule, for example an antibody, variant or fragment thereof is provided, wherein the antigen binding molecule comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:

[0462] (a) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 31 ;

[0463] (b) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 21 ;

[0464] (c) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 41 ;

[0465] (d) a VH comprising the amino acid sequence of SEQ ID NO: 5 and a VL comprising the amino acid sequence of SEQ ID NO: 1 ;

[0466] (e) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 11 ; (f) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 11 ;

[0467] (g) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 11 ;

[0468] (h) a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 11 ; a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 21 ;

[0469] (j) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 21 ; a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 21 ;[0...

Claims

Claims1 . An anti-BDCA-2 (CLEC4C) antigen binding molecule comprising an IgG 1 Fc with the following substitution: M252Y / S254T / T256E.

2. An anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule has a half maximal inhibitory concentration (IC50) for inhibition of IFN secretion of less than about 2nM, and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitution: M252Y / S254T / T256E.

3. An anti-BDCA-2 (CLEC4C) antigen binding molecule, wherein the antigen binding molecule has an IC90 for inhibition of IFN secretion of less than about 20nM, and wherein the antigen binding molecule comprises an lgG1 Fc with the following substitution: M252Y / S254T / T256E.

4. The anti-BDCA-2 (CLEC4C) antigen binding molecule any preceding claim, wherein the antigen binding molecule has an equilibrium dissociation constant (KD) for BDCA-2 (CLEC4C) of less than about 2nM, a half maximal inhibitory concentration (IC50) for inhibition of IFN secretion of less than about 2nM, and an IC90 for inhibition of IFN secretion of less than about 20nM.

5. The anti-BDCA-2 (CLEC4C) antigen binding molecule of claim 4, wherein the antigen binding molecule has an equilibrium dissociation constant (KD) for BDCA-2 (CLEC4C) of less than about 0.01 nM, a half maximal inhibitory concentration (IC50) for inhibition of IFN secretion of less than about 0.5nM, and an IC90 for inhibition of IFN secretion of less than about 5nM6. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim, wherein the antigen binding molecule comprises: a VHCDR3 comprising the amino acid sequence of any one of SEQ ID NOs 48, 28, 8, 38, 58, 68 and 78; and / or a VLCDR3 comprising the amino acid sequence of any one of SEQ ID NOs 34, 24, 44, 4, 14, 54, 64 and 74.

7. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim, wherein the antigen binding molecule comprises: a VHCDR1 comprising the amino acid sequence of any one of SEQ ID NOs 46,49, 26, 29, 6, 9, 16, 19, 36, 39, 56, 59, 66, 69, 76 and 79; a VHCDR2 comprising the amino acid sequence of any one of SEQ ID NOs 47,50, 27, 30, 7, 10, 17, 20, 37, 40, 57, 60, 67, 70, 77 and 80; and a VHCDR3 comprising the amino acid sequence of any one of SEQ ID NOs 48, 28, 8, 18, 38, 58, 68 and 78; and / or a VLCDR1 comprising the amino acid sequence of any one of SEQ ID NOs 32,22, 42, 2, 12, 52, 62 and 72; a VLCDR2 comprising the amino acid sequence of any one of SEQ ID NOs 33,23, 43, 3, 13, 53, 63 and 73; and a VLCDR3 comprising the amino acid sequence of any one of SEQ ID NOs 34,24, 44, 4, 14, 54, 64 and 74.

8. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim, wherein the antigen binding molecule is selected from the group consisting of:(a) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34);(b) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising theamino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34);(c) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24);(d) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24);(e) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44);(f) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); anda light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44);(g) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 6), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 7) and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4);(h) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 9), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 10) and a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 8); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 4);(i) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14);(j) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acidsequence SSGGGNTY (SEQ ID NO: 20), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14);(k) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14);(l) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14);(m) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), a VHCDR3 comprising the amino acid HDYYDGGLYYAMDY sequence (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14);(n) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising:a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), a VHCDR3 comprising the amino acid HDYYDGGLYYAMDY sequence (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14);(o) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14);(p) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 12), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 13) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 14);(q) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24);(r) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24);(s) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), a VHCDR3 comprising the amino acid HDYYDGGLYYAMDY sequence (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24);(t) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), a VHCDR3 comprising the amino acid HDYYDGGLYYAMDY sequence (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24);(u) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising theamino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24);(v) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 22), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 23) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 24);(w) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34);(x) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34);(y) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 26), a VHCDR2 comprising the amino acid sequence YISSGGGNTYYADSVKG (SEQ ID NO: 27), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); anda light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34);(z) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 29), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 30), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 28); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34);(aa) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), a VHCDR3 comprising the amino acid HDYYDGGLYYAMDY sequence (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34);(bb) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), a VHCDR3 comprising the amino acid HDYYDGGLYYAMDY sequence (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KSSQSVDYDGDSSMN (SEQ ID NO: 32), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 33) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 34);(cc) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 16), a VHCDR2 comprising the amino acidsequence YISSGGGNTYYPDSVKG (SEQ ID NO: 17), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44);(dd) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 19), a VHCDR2 comprising the amino acid sequence SSGGGNTY (SEQ ID NO: 20), a VHCDR3 comprising the amino acid sequence HDYYDGGLYYAMDY (SEQ ID NO: 18); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44);(ee) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 36), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 37), a VHCDR3 comprising the amino acid HDYYDGGLYYAMDY sequence (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44);(ff) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 39), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 40), a VHCDR3 comprising the amino acid HDYYDGGLYYAMDY sequence (SEQ ID NO: 38); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44);(gg) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising:a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence YISSGGGQTYYPDSVKG (SEQ ID NO: 47), a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYEGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44);(hh) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 49), a VHCDR2 comprising the amino acid sequence SSGGGQTY (SEQ ID NO: 50), a VHCDR3 comprising the amino acid sequence HDYYEGGLYYAMDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSSMN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence AASTLES (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QQTNEDPPT (SEQ ID NO: 44);(ii) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTIS (SEQ ID NO: 56), a VHCDR2 comprising the amino acid sequence YISSGGDNAYYPDSVKG (SEQ ID NO: 57), a VHCDR3 comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54);(jj) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 59), a VHCDR2 comprising the amino acid sequence SSGGDN (SEQ ID NO: 60), a VHCDR3 comprising the amino acid sequence HLYYGDYFYVMDY (SEQ ID NO: 58); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDNCLH (SEQ ID NO: 52), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 53) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 54);(kk) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence SYTMS (SEQ ID NO: 66), a VHCDR2 comprising the amino acid sequence YISGVGGDTYYPDSVKG (SEQ ID NO: 67), a VHCDR3 comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64);(II) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 69), a VHCDR2 comprising the amino acid sequence SGVGGD (SEQ ID NO: 70), a VHCDR3 comprising the amino acid sequence HHYSHYFWYFDV (SEQ ID NO: 68); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDGFMN (SEQ ID NO: 62), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 63) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 64);(mm)an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence YYTMS (SEQ ID NO: 76), a VHCDR2 comprising the amino acid sequence YISSGGDNAYYPDSVRG (SEQ ID NO: 77), a VHCDR3 comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74); and(nn) an anti-BDCA-2 (CLEC4C) antigen binding molecule comprising: a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GFTFSYY (SEQ ID NO: 79), a VHCDR2 comprising the amino acid sequence SSGGDN (SEQ ID NO: 80), a VHCDR3 comprising the amino acid sequence HHYSNYFWYFDV (SEQ ID NO: 78); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYAGDSYVN (SEQ ID NO: 72), a VLCDR2 comprising theamino acid sequence AASNLES (SEQ ID NO: 73) and a VLCDR3 comprising the amino acid sequence QQSNEDPPT (SEQ ID NO: 74).

9. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim, wherein the antigen binding molecule comprises: a heavy chain variable region having at least 80% identity to the amino acid sequence selected from the group consisting of SEQ ID NO: 45, SEQ ID NO: 25, SEQ ID NO: 5, SEQ ID NO: 15, SEQ ID NO: 35, SEQ ID NO: 55, SEQ ID NO: 65 and SEQ ID NO: 75; and / or a light chain variable region having at least 80% identity to the amino acid sequence selected from the group consisting of SEQ ID NO: 31 , SEQ ID NO: 21 , SEQ ID NO: 41 , SEQ ID NO: 1 , SEQ ID NO: 11 , SEQ ID NO: 51 , SEQ ID NO: 61 and SEQ ID NO: 71.

10. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim, wherein the antigen binding molecule comprises: a heavy chain variable region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 45, SEQ ID NO: 25, SEQ ID NO: 5, SEQ ID NO: 15, SEQ ID NO: 35, SEQ ID NO: 55, SEQ ID NO: 65 and SEQ ID NO: 75; and / or a light chain variable region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 31 , SEQ ID NO: 21 , SEQ ID NO: 41 , SEQ ID NO: 1 , SEQ ID NO: 11 , SEQ ID NO: 51 , SEQ ID NO: 61 and SEQ ID NO: 71.11 . The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim, wherein the antigen binding molecule comprises: a. a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 31 , or at least the CDRs thereof; b. a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 21 , or at least the CDRs thereof;c. a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 41 , or at least the CDRs thereof; d. a VH comprising the amino acid sequence of SEQ ID NO: 5 and a VL comprising the amino acid sequence of SEQ ID NO: 1 , or at least the CDRs thereof; e. a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 11 , or at least the CDRs thereof; f. a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 11 , or at least the CDRs thereof; g. a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 11 , or at least the CDRs thereof; h. a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 11 , or at least the CDRs thereof; i. a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 21 , or at least the CDRs thereof; j. a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 21 , or at least the CDRs thereof; k. a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 21 , or at least the CDRs thereof; l. a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 31 , or at least the CDRs thereof; m. a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 31 , or at least the CDRs thereof;n. a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 31 , or at least the CDRs thereof; o. a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 41 , or at least the CDRs thereof; p. a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 41 , or at least the CDRs thereof; q. a VH comprising the amino acid sequence of SEQ ID NO: 45 and a VL comprising the amino acid sequence of SEQ ID NO: 41 , or at least the CDRs thereof; r. a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 51 , or at least the CDRs thereof; s. a VH comprising the amino acid sequence of SEQ ID NO: 65 and a VL comprising the amino acid sequence of SEQ ID NO: 61 , or at least the CDRs thereof; or t. a VH comprising the amino acid sequence of SEQ ID NO: 75 and a VL comprising the amino acid sequence of SEQ ID NO: 71 , or at least the CDRs thereof.

12. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim wherein the anti-BDCA-2 (CLEC4C) antigen binding molecule is an antibody comprising a variable region as set forth in Table 1 or Table 2, or at least the CDRs thereof.

13. The anti-BDCA-2 (CLEC4C) antibody of claim 12, wherein the antibody comprises 1 or 2 amino acid substitutions across all 6 CDR regions.

14. The anti-BDCA-2 (CLEC4C) antibody of claim 12 or claim 13, wherein the antibody comprises 1 or 2 amino acid substitutions in one or more framework regions.

15. An anti-BDCA-2 (CLEC4C) antigen binding molecule that specifically binds to BDCA-2 (CLEC4C), comprises an lgG1 Fc region with the substitution:M252Y / S254T / T256E, and competes with binding to BDCA-2 (CLEC4C) with an antigen-binding molecule of any one of claims 1 to 14.

16. An anti-BDCA-2 (CLEC4C) antigen binding molecule comprising a means for binding BDCA-2 and an lgG1 Fc with the following substitution: M252Y / S254T / T256E.

17. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim wherein the antigen binding molecule is an antibody.

18. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any one of claims 1 to 17, wherein the anti-BDCA-2 (CLEC4C) antigen binding molecule is an antibody fragment conjugated to an IgG Fc region comprising the YTE mutation.

19. The anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim, wherein the antigen binding molecule decreases the secretion of IFNa when administered in vivo or in vitro.

20. A pharmaceutical composition comprising an anti-BDCA-2 (CLEC4C) antigen binding molecule of any preceding claim and a pharmaceutically acceptable excipient.

21. An anti-BDCA-2 (CLEC4C) antigen binding molecule of any one of claims 1 to 19, or a pharmaceutical composition according to claim 20, for use in medicine.

22. An anti-BDCA-2 (CLEC4C) antigen binding molecule of any one of claims 1 to 19, or a pharmaceutical composition according to claim 20, for use in the treatment or prevention of an inflammatory disorder or disease or an autoimmune disorder or disease.

23. The anti-BDCA-2 (CLEC4C) antigen binding molecule or pharmaceutical composition or kit for use as claimed in claim 22, wherein the inflammatory or autoimmune disorder or disease is selected from the group consisting of systemic sclerosis, fibrosis (such as skin fibrosis), pemphigus vulgaris, systemic lupus erythematosus (SLE), cutaneous lupus, discoid lupus, lupus nephritis, polymyositisand dermatomyositis, psoriasis, rheumatoid arthritis, Grave’s disease, morphea, inflammatory bowel disease, morphea, type I diabetes, Sjogren's disease and Hashimoto’s disease.

24. The anti-BDCA-2 (CLEC4C) antigen binding molecule or pharmaceutical composition or kit for use as claimed in claim 22, wherein the inflammatory disease is systemic sclerosis, fibrosis (such as skin fibrosis) or pemphigus vulgaris.

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