CFC1 binding molecule

Abstract

The present invention relates to a binding molecule comprising a CFC1 binding domain. The present invention also relates to antibodies comprising the binding molecule.

Description

[0001] CFC1 BINDING MOLECULE

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a binding molecule comprising a CFC1 binding domain. The present invention also relates to antibodies comprising the binding molecule.

[0004] BACKGROUND TO THE INVENTION

[0005] CFC1 is a member of the EGF-CFC protein family and can be cell-associated / membrane bound or can be extracellular and present in soluble form.

[0006] CFC1 is involved in Akt and MAPK signalling and is known to be a co-receptor that binds Nodal with ALK4 / 7 receptors, which can result in phosphorylation of SMAD 2 / 3 that in turn associates with SMAD4 and translocates to the nucleus.

[0007] It is also known that CFC1 is involved in regulation of gastrulation, mesoderm induction, and axis formation during embryonic development. Moreover, CFC1 functions as a Nodal coreceptor to establish left right asymmetry of developing organs.

[0008] CFC1 is associated with heterotaxy syndrome in humans. Mice with knock-out of CFC1 survive until birth and display severe left-right laterality defects, but do not exhibit the phenotypes associated with pre-gastrulation patterning and differentiation.

[0009] CFC1 is expressed in tumors.

[0010] There is a need for improved therapies targeting CFC1 expressing tumours and cancers, in particular for CFC1 binding molecules with advantageous properties for in vivo administration and for use as medicaments.

[0011] SUMMARY OF THE INVENTION

[0012] The present invention provides a binding molecule comprising a CFC1 binding domain.

[0013] In some embodiments, the binding molecule according to the invention binds to at least 40% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml. In some embodiments, the binding molecule according to the invention binds to at least 50%, at least 60%, at least 70%, at least 80% or at least 85% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml.

[0014] In some embodiments, the binding molecule according to the invention binds to at least 90% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml; In some embodiments, the binding molecule according to the invention binds to at least 91%, at least 92%, at least 93%, or at least 94% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml.

[0015] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0016] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 1 ,

[0017] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 2, and

[0018] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 3; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0019] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0020] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7,

[0021] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 8, and

[0022] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 9; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0023] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein: LCDR1 comprises the amino acid sequence according to SEQ ID NO: 4,

[0024] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 5, and

[0025] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 6; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0026] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0027] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 10,

[0028] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 11 , and

[0029] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0030] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0031] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 60,

[0032] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 61 , and

[0033] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 62; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0034] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0035] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64,

[0036] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 65, and

[0037] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 66; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0038] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0039] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 63, LCDR2 comprises the amino acid sequence SAS, and

[0040] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 6; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0041] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0042] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 67,

[0043] LCDR2 comprises the amino acid sequence GAS, and

[0044] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0045] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto.

[0046] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 125 or a variant having at least 80% sequence identity thereto.

[0047] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 107 or a variant having at least 80% sequence identity thereto.

[0048] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 100 or a variant having at least 80% sequence identity thereto.

[0049] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 102 or a variant having at least 80% sequence identity thereto.

[0050] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 105 or a variant having at least 80% sequence identity thereto.

[0051] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 106 or a variant having at least 80% sequence identity thereto.

[0052] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 125 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto.

[0053] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 107 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto.

[0054] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 100 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 101 or a variant having at least 80% sequence identity thereto.

[0055] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 102 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 103 or a variant having at least 80% sequence identity thereto.

[0056] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 104; and the VL domain comprises the amino acid sequence according to SEQ ID NO:

[0057] 105.

[0058] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 104; and the VL domain comprises the amino acid sequence according to SEQ ID NO:

[0059] 106.

[0060] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 125; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 108. In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 107; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 108.

[0061] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 100; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 101.

[0062] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 102; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 103.

[0063] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0064] (i)

[0065] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 13,

[0066] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 14, and

[0067] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 15; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0068] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0069] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 19,

[0070] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 20, and

[0071] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 21 ; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0072] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0073] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 25, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 26; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0074] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0075] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 30,

[0076] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 31 , and

[0077] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 32; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0078] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0079] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 36,

[0080] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 37, and

[0081] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 38; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0082] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0083] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 42,

[0084] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 43, and

[0085] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 44; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0086] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0087] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 48,

[0088] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 49, and

[0089] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 50; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0090] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0091] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 54,

[0092] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 55, and

[0093] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 56; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0094] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0095] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 158,

[0096] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 159, and

[0097] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 160; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0098] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0099] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 16,

[0100] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and

[0101] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0102] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0103] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 22,

[0104] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 23, and

[0105] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0106] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0107] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 27,

[0108] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 28, and

[0109] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0110] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0111] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 33,

[0112] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 34, and

[0113] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0114] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0115] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 39,

[0116] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 40, and

[0117] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41 ; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0118] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0119] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 45,

[0120] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 46, and

[0121] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0122] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0123] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 51 ,

[0124] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 52, and

[0125] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 53; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0126] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0127] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 57,

[0128] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 58, and

[0129] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0130] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0131] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 161 ,

[0132] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and

[0133] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0134] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0135] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 68,

[0136] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 69, and

[0137] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 70; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0138] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0139] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 72,

[0140] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 73, and

[0141] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 74; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0142] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0143] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 76,

[0144] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 77, and

[0145] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 78; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0146] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0147] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 80,

[0148] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 81 , and

[0149] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 82; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0150] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0151] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 84,

[0152] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 85, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 86; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0153] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0154] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 88,

[0155] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 89, and

[0156] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 90; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0157] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0158] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 92,

[0159] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 93, and

[0160] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 94; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0161] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0162] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 96,

[0163] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 97, and

[0164] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 98; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0165] In some embodiments, the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0166] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64,

[0167] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 163, and

[0168] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 164 optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0169] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0170] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 71 ,

[0171] LCDR2 comprises the amino acid sequence RAS, and

[0172] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0173] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0174] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 75,

[0175] LCDR2 comprises the amino acid sequence EAS, and

[0176] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0177] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0178] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 79,

[0179] LCDR2 comprises the amino acid sequence SAS, and

[0180] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0181] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0182] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 83,

[0183] LCDR2 comprises the amino acid sequence GAS, and

[0184] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0185] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0186] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 87,

[0187] LCDR2 comprises the amino acid sequence RTS, and

[0188] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41 ; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0189] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0190] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 91 ,

[0191] LCDR2 comprises the amino acid sequence YAS, and

[0192] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0193] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0194] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 95,

[0195] LCDR2 comprises the amino acid sequence DAS, and

[0196] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 53; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0197] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0198] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 99,

[0199] LCDR2 comprises the amino acid sequence AAS, and

[0200] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0201] In some embodiments, the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0202] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 165,

[0203] LCDR2 comprises the amino acid sequence RAS, and

[0204] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0205] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 109 or a variant having at least 80% sequence identity thereto.

[0206] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 111 or a variant having at least 80% sequence identity thereto.

[0207] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 113 or a variant having at least 80% sequence identity thereto.

[0208] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 115 or a variant having at least 80% sequence identity thereto.

[0209] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 117 or a variant having at least 80% sequence identity thereto.

[0210] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 119 or a variant having at least 80% sequence identity thereto.

[0211] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 121 or a variant having at least 80% sequence identity thereto.

[0212] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 123 or a variant having at least 80% sequence identity thereto. In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 166 or a variant having at least 80% sequence identity thereto.

[0213] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 109 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 110 or a variant having at least 80% sequence identity thereto.

[0214] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 111 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 112 or a variant having at least 80% sequence identity thereto.

[0215] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 113 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 114 or a variant having at least 80% sequence identity thereto.

[0216] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 115 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 116 or a variant having at least 80% sequence identity thereto.

[0217] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 117 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 118 or a variant having at least 80% sequence identity thereto.

[0218] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 119 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 120 or a variant having at least 80% sequence identity thereto.

[0219] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 121 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 122 or a variant having at least 80% sequence identity thereto. In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 123 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 124 or a variant having at least 80% sequence identity thereto.

[0220] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 166 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 167 or a variant having at least 80% sequence identity thereto.

[0221] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 109; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 110.

[0222] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 111 ; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 112.

[0223] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 113; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 114.

[0224] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 115; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 116.

[0225] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 117; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 118.

[0226] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 119; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 120. In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 121 ; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 122.

[0227] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 123; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 124.

[0228] In some embodiments, the VH domain comprises the amino acid sequence according to SEQ ID NO: 166; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 167.

[0229] In some embodiments, the binding molecule according to the invention further comprises an Fc domain.

[0230] In some embodiments, the binding molecule according to the invention comprises a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 126 or a variant having at least 80% sequence identity thereto.

[0231] In some embodiments, the binding molecule according to the invention comprises a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 127 or a variant having at least 80% sequence identity thereto.

[0232] In some embodiments, the binding molecule according to the invention comprises:

[0233] (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 126 or a variant having at least 80% sequence identity thereto; and

[0234] (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 127 or a variant having at least 80% sequence identity thereto.

[0235] In some embodiments, the binding molecule according to the invention comprises:

[0236] (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 126; and

[0237] (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 127.

[0238] In some embodiments, the binding molecule according to the invention comprises: (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 168 or a variant having at least 80% sequence identity thereto; and

[0239] (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 169 or a variant having at least 80% sequence identity thereto.

[0240] In some embodiments, the binding molecule according to the invention comprises:

[0241] (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 168; and

[0242] (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 169.

[0243] In some embodiments, the binding molecule according to the invention comprises:

[0244] (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 170 or a variant having at least 80% sequence identity thereto; and

[0245] (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 171 or a variant having at least 80% sequence identity thereto.

[0246] In some embodiments, the binding molecule according to the invention comprises:

[0247] (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 170; and

[0248] (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 171.

[0249] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 134 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 135 or a variant having at least 80% sequence identity thereto.

[0250] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 134 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 137 or a variant having at least 80% sequence identity thereto.

[0251] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 156 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 139 or a variant having at least 80% sequence identity thereto. In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 138 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 139 or a variant having at least 80% sequence identity thereto.

[0252] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 128 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 129 or a variant having at least 80% sequence identity thereto.

[0253] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 132 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 133 or a variant having at least 80% sequence identity thereto.

[0254] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 140 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 141 or a variant having at least 80% sequence identity thereto.

[0255] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 142 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 143 or a variant having at least 80% sequence identity thereto.

[0256] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 144 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 145 or a variant having at least 80% sequence identity thereto.

[0257] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 146 ora variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 147 or a variant having at least 80% sequence identity thereto. In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 148 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 149 or a variant having at least 80% sequence identity thereto.

[0258] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 150 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 151 or a variant having at least 80% sequence identity thereto.

[0259] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 152 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 153 or a variant having at least 80% sequence identity thereto.

[0260] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 154 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 155 or a variant having at least 80% sequence identity thereto.

[0261] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 172 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 173 or a variant having at least 80% sequence identity thereto.

[0262] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 174 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 175 or a variant having at least 80% sequence identity thereto.

[0263] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 134; and a light chain sequence of SEQ ID NO: 135.

[0264] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 134; and a light chain sequence of SEQ ID NO: 137. In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 156; and a light chain sequence of SEQ ID NO: 139.

[0265] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 138; and a light chain sequence of SEQ ID NO: 139.

[0266] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 128; and a light chain sequence of SEQ ID NO: 129.

[0267] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 132; and a light chain sequence of SEQ ID NO: 133.

[0268] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 140; and a light chain sequence of SEQ ID NO: 141.

[0269] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 142; and a light chain sequence of SEQ ID NO: 143.

[0270] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 144; and a light chain sequence of SEQ ID NO: 145.

[0271] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 146; and a light chain sequence of SEQ ID NO: 147.

[0272] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 148; and a light chain sequence of SEQ ID NO: 149.

[0273] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 150; and a light chain sequence of SEQ ID NO: 151.

[0274] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 152; and a light chain sequence of SEQ ID NO: 153.

[0275] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 154; and a light chain sequence of SEQ ID NO: 155. In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 172; and a light chain sequence of SEQ ID NO: 173.

[0276] In some embodiments, the binding molecule according to the invention comprises a heavy chain sequence of SEQ ID NO: 174; and a light chain sequence of SEQ ID NO: 175.

[0277] In some embodiments, the Fc domain binds to one or more Fc receptor(s).

[0278] In some embodiments, the Fc domain is capable of binding to immune cells. In some embodiments, the immune cells are cytotoxic immune cells and / or are capable of killing target cells.

[0279] In some embodiments, the Fc domain is capable of recruiting immune cells. In some embodiments, the immune cells are cytotoxic immune cells and / or are capable of killing target cells.

[0280] The present invention provides an antibody or antigen-binding fragment thereof comprising the binding molecule according to the invention.

[0281] In some embodiments, the antibody or fragment thereof is a humanized antibody or fragment thereof. In some embodiments, the antibody or fragment thereof is a chimeric antibody or fragment thereof.

[0282] In some embodiments, the antibody or fragment thereof is a monoclonal antibody or fragment thereof.

[0283] The present invention provides a polynucleotide comprising a nucleic acid sequence encoding the binding molecule according to the invention or the antibody or fragment thereof according to the invention.

[0284] In some embodiments, the nucleic acid sequence is a DNA sequence.

[0285] The present invention provides a vector which comprises a polynucleotide according to the invention. The present invention provides a cell comprising a polynucleotide according to the invention, or a vector according to the invention.

[0286] In some embodiments, the cell is capable of expressing the binding molecule according to the invention or the antibody or fragment thereof according to the invention.

[0287] The present invention provides a method for making a cell according to the invention, comprising the step of introducing a polynucleotide according to the invention, or a vector according to the invention into said cell.

[0288] The present invention provides a method for producing the binding molecule according to the invention or the antibody or fragment thereof according to the invention, wherein the method comprises the steps of:

[0289] (i) introducing a polynucleotide according to the invention, or a vector according to the invention into a cell; and

[0290] (ii) expressing the binding molecule or antibody or fragment thereof in the cell; and optionally

[0291] (iii) harvesting the binding molecule or antibody or fragment thereof from the cell or cell culture supernatant of the cell.

[0292] The present invention provides a composition which comprises the binding molecule according to the invention, or the antibody or fragment thereof according to the invention; together with a carrier, diluent or excipient.

[0293] BRIEF DESCRIPTION OF THE FIGURES

[0294] Figure 1 - (A)-(C) Binding of antibodies MAB-18-0110, MAB-18-0111 , MAB-18-0113, MAB- 18-0116, MAB-18-0117, MAB-18-0121 , MA B- 18-0127, MAB-18-0133, MAB-18-0134, MAB- 18-0136, MAB-18-0139, MAB-20-0212, MAB-20-0227, MAB-20-0271 , MAB-20-0273 and anti- CFC1 antibody control to human CFC1 ECD in a concentration range from 2,000 - 0.06 ng / ml was determined in an ELISA. The data was analyzed by non-linear regression.

[0295] Figure 2 - (A)-(F) Binding of antibodies MAB-18-0110, MAB-18-0111 , MAB-18-0113, MAB- 18-0116, MAB-18-0117, MAB-18-0121 , MAB-18-0127, MAB-18-0133, MAB-18-0134, MAB- 18-0136, MAB-18-0139, MAB-20-0212, MAB-20-0227, MAB-20-0271 , MAB-20-0273 and anti- CFC1 antibody control to human or cynomolgus CFC1 on ectopically overexpressing CHO- K1 by high content imaging. Antibodies were diluted in a concentration range from 5,000 - 0.05 ng / ml and data was analyzed by non-linear regression.

[0296] Figure 3 - The binding and specificity of anti-CFC1 recombinant antibodies to tumor cells that expressed CFC1 was measured by FACS. (A) CFC1 positive (NCI-H810_hCFC1_hi) and as a control (B) CFC1 negative (CHO-K1_hCLDN18.2-gp740_24H5_MACS-FACS) cells were incubated with dilutions of recombinant anti-CFC1 antibodies in the range of 0.1 to 1000 ng / ml.

[0297] Figure 4 - Antibody-dependent cellular cytotoxicity (ADCC). The efficacy of CFC1 -targeting recombinant antibodies was assessed by analyzing the ability to induce antibody-dependent cellular cytotoxicity (ADCC) using Jurkat ADCC effector cells (AcCELLerate) as a surrogate for immune effector cells. The CFC1-positive lung cancer transfectant NCI- H810_hCFC1_sort-high and the CFC1-negative breast cancer cell line MDA-MB-231 were used to assess specific Jurkat activation in an effector to target (E:T) ratio of 10:1 with a 3.5- fold, 10-point dilution from 3,500 to 0.044 ng / mL antibody dilution row.

[0298] DETAILED DESCRIPTION OF THE INVENTION

[0299] BINDING MOLECULE

[0300] CFC1 , also known as Cryptic protein, is a NODAL co-receptor involved in the correct establishment of the left-right axis. An illustrative amino acid sequence is the human CFC1 sequence designated as UniProt: P0CG37.

[0301] The present invention provides a binding molecule comprising a CFC1 binding domain. In other words, the binding molecule according to the invention may be capable of binding to CFC1.

[0302] It will be understood that a binding molecule is a molecule that interacts with a target (e.g., a target antigen) such that a stable association is formed. An example of a binding molecule is an antigen (or antibody-like molecule) that binds to its cognate antigen. Such binding interaction will be known in the art. The binding interaction may be non-covalent, reversible covalent or irreversible covalent.

[0303] Binding properties

[0304] Suitable assays and techniques for measuring / quantifying binding activity of the binding molecule according to the invention may include, but are not limited to, ELISA, surface plasmon resonance (SPR), quartz crystal microbalance (QCM), bioluminescence assays and flow cytometry. Other suitable techniques will be known in the art.

[0305] In particular, it will be understood that the ability of a binding molecule to bind to its cognate target may be assessed by flow cytometry, where the effectiveness of a binding molecule to bind to a cognate target expressed by a population of cells can be measured in a flow cytometry assay.

[0306] Without wishing to be bound by theory, a binding molecule may be tagged with a detectable marker and exposed to a population of cells expressing a cognate target, such that detection of the marker may provide an indicator of the ability of a binding molecule to bind to its cognate target. The detectable marker may be a fluorophore that is conjugated to the binding molecule or the detectable marker may involve the use of a second binding molecule (e.g. secondary antibody) that binds to the first binding molecule, wherein the second binding molecule comprises a detectable marker such as a fluorophore. Techniques for performing such assays will be known in the art. In particular, the use of primary antibodies and labelled secondary antibodies for flow cytometry assays will be known in the art. In a flow cytometry assay, a binding molecule may be tagged with a fluorophore and exposed to a population of cells expressing a cognate target, such that detection of fluorescence from the fluorophore may provide an indicator of the ability of a binding molecule to bind to its cognate target. Such an assay is described in Figure 3.

[0307] It will be understood that in such a flow cytometry assay, the % of cells that are positive for a fluorescence signal associated with the binding molecule may provide an indicator of the ability of a binding molecule to bind to its cognate target.

[0308] In some embodiments, the binding molecule according to the invention may bind to 1-100% of a population of cells expressing CFC1 (i.e., “CFC1 expressing cells”). In some embodiments, the binding molecule according to the invention may bind to at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of a population of CFC1 expressing cells.

[0309] Without wishing to be bound by theory, it will be understood that the % of CFC1 expressing cells that are bound by the binding molecule according to the invention may depend on the concentration of the binding molecule. As such, a titration of the binding molecules at different concentrations may provide an indicator of the effectiveness of a binding molecule to bind to its cognate target.

[0310] In some embodiments, the concentration of the binding molecule may be in the range of 0.1 to 1000 ng / ml.

[0311] In some embodiments, the concentration of the binding molecule may be 1 ng / ml. In some embodiments, the concentration of the binding molecule may be 10 ng / ml.

[0312] In some embodiments, the binding molecule according to the invention may bind to 40-100% of a population of cells expressing CFC1 (i.e. “CFC1 expressing cells”) when the concentration of the binding molecule is 1 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml. 1 In some embodiments, the binding molecule according to the invention may bind to at least 40% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml.

[0313] In some embodiments, the binding molecule according to the invention may bind to at least 50% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 60% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 70% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 80% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 85% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml.

[0314] In some embodiments, the binding molecule according to the invention may bind to 90-100% of a population of cells expressing CFC1 (i.e. “CFC1 expressing cells”) when the concentration of the binding molecule is 10 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 90%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml.

[0315] In some embodiments, the binding molecule according to the invention may bind to at least 90% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml.

[0316] In some embodiments, the binding molecule according to the invention may bind to at least 91% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 92% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 93% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml. In some embodiments, the binding molecule according to the invention may bind to at least 94% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml. Without wishing to be bound by theory, it will be understood that the % of CFC1 expressing cells that are bound by the binding molecule according to the invention may depend on the type of cell used. It will also be understood that an assay for measuring % of CFC1 expressing cells that are bound by the binding molecule according to the invention may require a comparison to a control, such as a population of cells that do not express CFC1 .

[0317] In some embodiments, the CFC1 expressing cells may be tumour cells.

[0318] In some embodiments, the CFC1 expressing cells may be the CFC1 positive cell line: NCI- H810_hCFC1_hi.

[0319] In some embodiments, the control cells may be the CFC1 negative cell line: (CHO- K1_hCLDN18.2-gp740_24H5_MACS-FACS).

[0320] It will also be understood that in a flow cytometry assay, the intensity of the fluorescence signal (i.e. mean fluorescent intensity (MFI)) may provide an indicator of the ability of a binding molecule to bind to its cognate target.

[0321] It will also be understood that a comparison between the binding molecule according to the invention and known anti-CFC1 binding molecules can be determined by measuring the MFI value obtained when the binding molecule according to the invention and known anti-CFC1 binding molecules are exposed to CFC1 expressing cells. The same can be performed using CFC1 negative cells to act as a control and to determine baseline MFI values.

[0322] It will also be understood that the MFI value may depend on the fluorophore used. In some embodiments, the fluorophore may be Allophycocyanin (APC). Other suitable fluorophore will be known in the art.

[0323] In some embodiments, an MFI between 4500 and 23400 may be measured when using the binding molecule according to the invention in a flow cytometry assay.

[0324] In some embodiments, an MFI between 4500 and 11200 may be measured when using the binding molecule according to the invention in a flow cytometry assay, wherein the binding molecule according to the invention is present at a concentration of 10 ng / ml, wherein the binding molecule according to the invention binds to CFC1 expressing cells, and wherein an APC coupled secondary antibody binds to the binding molecule according to the invention. In some embodiments, an MFI between 16400 and 23400 may be measured when using the binding molecule according to the invention in a flow cytometry assay, wherein the binding molecule according to the invention is present at a concentration of 100 ng / ml, wherein the binding molecule according to the invention binds to CFC1 expressing cells, and wherein an APC coupled secondary antibody binds to the binding molecule according to the invention.

[0325] It will be understood that EC50 is a measure of the concentration of an antibody that induces a specific response that is 50% between the maximum response and the baseline response. As such, EC50 can be used to assess the ability of an antibody to bind to a target.

[0326] Variable domain

[0327] In some embodiments, the binding molecule according to the invention may comprise a heavy chain variable (VH) domain and a light chain variable (VL) domain.

[0328] It will be understood that the VH domain and VL domain of the binding molecule according to the invention is capable of binding to CFC1 and thus the VH domain and VL domain form the CFC1 binding domain of the binding molecule according to the invention.

[0329] In other words, the CFC1 binding domain of the binding molecule according to the invention may comprise a VH domain and a VL domain.

[0330] In some embodiments, the VH domain may comprise one or more complementarity determining regions (CDRs). In some embodiments, the VH domain may comprise one, two or three CDRs. In some embodiments, the VH domain may comprise three CDRs. It will be understood that CDRs of the VH domain may be termed HCDRs. It will also be understood that each of the three CDRs of the VH domain may be termed HCDR1 , HCDR2 and HCDR3 respectively.

[0331] In some embodiments, the VL domain may comprise one or more CDRs. In some embodiments, the VL domain may comprise one, two or three CDRs. In some embodiments, the VL domain may comprise three CDRs. It will be understood that CDRs of the VL domain may be termed LCDRs. It will also be understood that each of the three CDRs of the VL domain may be termed LCDR1 , LCDR2 and LCDR3 respectively.

[0332] The terms “heavy chain variable region” or “VH” may refer to the portion of the heavy chain of an antigen-binding molecule, or antibody, that typically contains three CDRs, where each CDR is positioned between stretches of amino acids known as framework regions that form a scaffold to support the CDRs.

[0333] The terms “light chain variable region” or “VL” may refer to the fragment of the light chain of an antigen-binding domain, or antibody, that typically contains three CDRs, where each CDR is positioned between stretches of amino acids known as framework regions that form a scaffold to support the CDRs.

[0334] The terms “complementarity determining region” or “CDR” refer to a highly variable loop in the variable region which interact with a cognate antigen and is largely responsible for determining the ability of a binding molecule (e.g., an antibody) to bind to an antigen and for determining binding affinity. The CDRs within a variable region are typically numbered from the amino to the carboxy terminus, with CDR1 being closest to the amino terminus of the variable region and CDR3 being closest to the carboxy terminus of the variable region.

[0335] The CDRs may be determined according to the Kabat definition and / or the IMGT definition, both of which are well-known in the art.

[0336] In some embodiments, the binding molecule according to the invention may comprise one or more of the HCDRs 1-3 and / or LCDRs 1-3 presented in Table 1.

[0337] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0338] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 1 , HCDR2 comprises the amino acid sequence according to SEQ ID NO: 2, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 3.

[0339] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0340] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 8, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 9.

[0341] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0342] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 13, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 14, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 15.

[0343] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0344] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 19,

[0345] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 20, and

[0346] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 21.

[0347] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0348] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7,

[0349] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 25, and

[0350] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 26.

[0351] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0352] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 30,

[0353] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 31 , and

[0354] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 32.

[0355] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0356] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 36,

[0357] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 37, and

[0358] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 38.

[0359] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0360] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 42,

[0361] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 43, and

[0362] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 44.

[0363] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0364] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 48,

[0365] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 49, and

[0366] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 50. In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0367] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 54,

[0368] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 55, and

[0369] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 56.

[0370] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition, wherein:

[0371] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 158,

[0372] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 159, and

[0373] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 160.

[0374] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0375] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 4, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 5, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 6.

[0376] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0377] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 10, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 11 , and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12.

[0378] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0379] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 16, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18.

[0380] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0381] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 22, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 23, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24. In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0382] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 27,

[0383] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 28, and

[0384] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29.

[0385] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0386] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 33, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 34, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35.

[0387] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0388] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 39, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 40, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41.

[0389] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0390] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 45, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 46, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47.

[0391] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0392] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 51, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 52, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 53.

[0393] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0394] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 57,

[0395] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 58, and

[0396] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59. In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0397] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 161 , LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162.

[0398] In some embodiments, the binding molecule according to the invention may comprise the combination of HCDRs 1-3 and LCDRs 1-3 specified for each of the antibody clones presented in Table 1.

[0399] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0400] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 1 , HCDR2 comprises the amino acid sequence according to SEQ ID NO: 2, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 3, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 4, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 5, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 6.

[0401] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0402] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 8, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 9, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 10, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 11 , and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12.

[0403] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0404] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 13,

[0405] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 14,

[0406] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 15,

[0407] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 16, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18.

[0408] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0409] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 19, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 20, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 21, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 22, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 23, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24.

[0410] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0411] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 25, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 26, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 27, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 28, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29.

[0412] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0413] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 30, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 31, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 32, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 33, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 34, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35.

[0414] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0415] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 36, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 37, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 38, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 39, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 40, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41.

[0416] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0417] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 42, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 43, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 44, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 45, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 46, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47.

[0418] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0419] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 48, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 49, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 50, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 51, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 52, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 53.

[0420] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0421] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 54, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 55, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 56, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 57, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 58, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59. In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the Kabat definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the Kabat definition, wherein:

[0422] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 158, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 159, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 160, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 161, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162.

[0423] In some embodiments, the binding molecule according to the invention may comprise one or more of the HCDRs 1-3 and / or LCDRs 1-3 presented in Table 2.

[0424] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0425] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 60, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 61 , and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 62.

[0426] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0427] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 65, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 66.

[0428] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0429] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 68, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 69, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 70.

[0430] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0431] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 72, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 73, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 74. In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0432] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 76, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 77, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 78.

[0433] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0434] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 80, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 81 , and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 82.

[0435] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0436] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 84, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 85, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 86.

[0437] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0438] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 88, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 89, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 90.

[0439] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0440] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 92, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 93, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 94.

[0441] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0442] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 96, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 97, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 98. In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition, wherein:

[0443] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 163, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 164.

[0444] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0445] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 63,

[0446] LCDR2 comprises the amino acid sequence SAS, and

[0447] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 6.

[0448] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0449] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 67,

[0450] LCDR2 comprises the amino acid sequence GAS, and

[0451] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12.

[0452] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0453] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 71,

[0454] LCDR2 comprises the amino acid sequence RAS, and

[0455] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18.

[0456] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0457] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 75,

[0458] LCDR2 comprises the amino acid sequence EAS, and

[0459] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24.

[0460] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0461] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 79,

[0462] LCDR2 comprises the amino acid sequence SAS, and

[0463] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29. In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0464] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 83,

[0465] LCDR2 comprises the amino acid sequence GAS, and

[0466] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35.

[0467] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0468] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 87,

[0469] LCDR2 comprises the amino acid sequence RTS, and

[0470] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41.

[0471] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0472] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 91,

[0473] LCDR2 comprises the amino acid sequence YAS, and

[0474] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47.

[0475] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0476] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 95,

[0477] LCDR2 comprises the amino acid sequence DAS, and

[0478] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 53.

[0479] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0480] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 99,

[0481] LCDR2 comprises the amino acid sequence AAS, and

[0482] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59.

[0483] In some embodiments, the binding molecule according to the invention may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0484] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 165,

[0485] LCDR2 comprises the amino acid sequence RAS, and

[0486] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162. In some embodiments, the binding molecule according to the invention may comprise the combination of HCDRs 1-3 and LCDRs 1-3 specified for each of the antibody clones presented in Table 2.

[0487] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0488] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 60,

[0489] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 61 , HCDR3 comprises the amino acid sequence according to SEQ ID NO: 62, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 63, LCDR2 comprises the amino acid sequence SAS, and

[0490] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 6;

[0491] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0492] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64,

[0493] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 65, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 66, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 67, LCDR2 comprises the amino acid sequence GAS, and

[0494] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12.

[0495] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0496] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 68,

[0497] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 69, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 70, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 71 , LCDR2 comprises the amino acid sequence RAS, and

[0498] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18.

[0499] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein: HCDR1 comprises the amino acid sequence according to SEQ ID NO: 72, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 73, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 74, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 75,

[0500] LCDR2 comprises the amino acid sequence EAS, and

[0501] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24.

[0502] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0503] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 76,

[0504] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 77, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 78, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 79, LCDR2 comprises the amino acid sequence SAS, and

[0505] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29.

[0506] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0507] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 80,

[0508] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 81, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 82, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 83, LCDR2 comprises the amino acid sequence GAS, and

[0509] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35.

[0510] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0511] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 84,

[0512] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 85, HCDR3 comprises the amino acid sequence according to SEQ ID NO: 86, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 87, LCDR2 comprises the amino acid sequence RTS, and

[0513] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41. In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0514] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 88,

[0515] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 89,

[0516] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 90,

[0517] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 91, LCDR2 comprises the amino acid sequence YAS, and

[0518] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47.

[0519] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0520] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 92,

[0521] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 93,

[0522] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 94,

[0523] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 95, LCDR2 comprises the amino acid sequence DAS, and

[0524] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 53.

[0525] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0526] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 96,

[0527] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 97,

[0528] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 98,

[0529] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 99, LCDR2 comprises the amino acid sequence AAS, and

[0530] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59.

[0531] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising HCDRs 1-3 as defined by the IMGT definition and may comprise a VL domain comprising LCDRs 1-3 as defined by the IMGT definition, wherein:

[0532] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64,

[0533] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 163,

[0534] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 164, LCDR1 comprises the amino acid sequence according to SEQ ID NO: 165, LCDR2 comprises the amino acid sequence RAS, and

[0535] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162.

[0536] In some embodiments, one or more of the HCDRs may comprise one, two or three amino acid mutations.

[0537] In some embodiments, HCDR 1 may comprise one, two or three amino acid mutations.

[0538] In some embodiments, HCDR 2 may comprise one, two or three amino acid mutations.

[0539] In some embodiments, HCDR 3 may comprise one, two or three amino acid mutations.

[0540] In some embodiments, one or more of the LCDRs may comprise one, two or three amino acid mutations.

[0541] In some embodiments, LCDR 1 may comprise one, two or three amino acid mutations.

[0542] In some embodiments, LCDR 2 may comprise one, two or three amino acid mutations.

[0543] In some embodiments, LCDR 3 may comprise one, two or three amino acid mutations.

[0544] It will be understood that a mutation in any of the CDRs described herein may encompass a deletion of an amino acid, an insertion of an amino acid, or a substitution of an amino acid. It will also be understood that such a mutation may not prevent the binding molecule according to the invention from binding to CFC1. In other words, a binding molecule according to the invention comprising a mutation in one or more CDRs described herein may suitably maintain the capacity to bind to CFC1.

[0545] In some embodiments, the binding molecule according to the invention may comprise the combination of VH domain and VL domain specified for each of the antibody clones presented in Table 3.

[0546] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 104. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 104.

[0547] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 125 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 125. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 125.

[0548] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 107 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 107. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 107.

[0549] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 100 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 100. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 100.

[0550] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 102 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 102. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 102.

[0551] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 109 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 109. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 109. In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 111 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 111. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 111.

[0552] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 113 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 113. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 113.

[0553] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 115 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 115. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 115.

[0554] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 117 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 117. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 117.

[0555] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 119 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 119. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 119. In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 121 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 121. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 121.

[0556] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 123 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 123. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 123.

[0557] In some embodiments, the VH domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 166 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 166. In some embodiments, the VH domain may consist of the amino acid sequence according to SEQ ID NO: 166.

[0558] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 105 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 105. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 105.

[0559] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 106 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 106. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 106.

[0560] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 108. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 108.

[0561] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 101 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 101. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 101.

[0562] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 103 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 103. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 103.

[0563] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 110 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 110. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 110.

[0564] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 112 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 112. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 112.

[0565] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 114 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 114. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 114.

[0566] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 116 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 116. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 116.

[0567] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 118 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 118. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 118.

[0568] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 120 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 120. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 120.

[0569] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 122 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 122. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 122.

[0570] In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 124 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 124. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 124. In some embodiments, the VL domain of the binding molecule according to the invention may comprise the amino acid sequence according to SEQ ID NO: 167 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 167. In some embodiments, the VL domain may consist of the amino acid sequence according to SEQ ID NO: 167.

[0571] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 105 or a variant having at least 80% sequence identity thereto.

[0572] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 104; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 105.

[0573] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 106 or a variant having at least 80% sequence identity thereto.

[0574] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 104; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 106.

[0575] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 125 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto.

[0576] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 125; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 108.

[0577] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 107 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto.

[0578] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 107; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 108.

[0579] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 100 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 101 or a variant having at least 80% sequence identity thereto.

[0580] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 100; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 101.

[0581] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 102 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 103 or a variant having at least 80% sequence identity thereto.

[0582] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 102; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 103.

[0583] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 109 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 110 or a variant having at least 80% sequence identity thereto.

[0584] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 109; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 110.

[0585] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 111 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 112 or a variant having at least 80% sequence identity thereto.

[0586] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 111 ; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 112.

[0587] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 113 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 114 or a variant having at least 80% sequence identity thereto.

[0588] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 113; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 114.

[0589] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 115 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 116 or a variant having at least 80% sequence identity thereto.

[0590] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 115; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 116.

[0591] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 117 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 118 or a variant having at least 80% sequence identity thereto.

[0592] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 117; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 118.

[0593] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 119 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 120 or a variant having at least 80% sequence identity thereto.

[0594] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 119; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 120.

[0595] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 121 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 122 or a variant having at least 80% sequence identity thereto.

[0596] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 121 ; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 122.

[0597] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 123 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 124 or a variant having at least 80% sequence identity thereto.

[0598] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 123; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 124.

[0599] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 166 or a variant having at least 80% sequence identity thereto; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 167 or a variant having at least 80% sequence identity thereto.

[0600] In some embodiments, the binding molecule according to the invention may comprise a VH domain comprising the amino acid sequence according to SEQ ID NO: 166; and a VL domain comprising the amino acid sequence according to SEQ ID NO: 167.

[0601] It will be understood that a variant of a VH domain as described herein may have an equivalent function to a full length VH domain amino acid sequence as described herein and may suitably maintain the capacity to bind to CFC1 . It will be understood that a variant of a VL domain as described herein may have an equivalent function to a full length VL domain amino acid sequence as described herein and may suitably maintain the capacity to bind to CFC1 .

[0602] Fc domain

[0603] In some embodiments, the binding molecule may comprise an immunoglobulin constant region.

[0604] In some embodiments, the binding molecule according to the invention may comprise an immunoglobulin constant region and the VH domain described above and the VL domain described above.

[0605] It will be understood that a VH domain and a VL domain may together form a variable region. Thus, the binding molecule according to the invention may comprise an immunoglobulin constant region and a variable region.

[0606] In some embodiments, the immunoglobulin constant region may comprise one or more immunoglobulin constant domain(s).

[0607] In some embodiments, the immunoglobulin constant domain may be selected from the list consisting of: a constant heavy 1 (CH1) domain, a constant heavy 2 (CH2) domain, and a constant heavy 3 (CH3) domain.

[0608] It will be understood that an immunoglobulin constant region may comprise an Fc domain, such as an Fc domain as described herein.

[0609] In some embodiments, the binding molecule according to the invention may comprise an immunoglobulin constant region comprising an Fc domain. In some embodiments, the binding molecule according to the invention may comprise an immunoglobulin constant region comprising an Fc domain and the VH domain described above and the VL domain described above.

[0610] It will be understood that the Fc domain may interact with Fc receptors presented on the surface of a cell. The Fc receptors may be Fc gamma receptors. In some embodiments, the Fc domain of the binding molecule according to the invention may be capable of interacting with Fc receptors and / or be able to recruit immune cells.

[0611] In some embodiments, the Fc domain of the binding molecule according to the invention may bind to one or more Fc receptors. In some embodiments, the Fc domain of the binding molecule according to the invention may bind to one or more Fc gamma receptors.

[0612] In some embodiments, the Fc domain of the binding molecule according to the invention may be capable of binding to immune cells. In some embodiments, the Fc domain of the binding molecule according to the invention may be capable of recruiting immune cells.

[0613] In some embodiments, the immune cells may be cytotoxic immune cells. In some embodiments, the immune cells may be capable of killing target cells. In some embodiments, the cytotoxic immune cells may be selected from the list consisting of: NK cells, macrophages, neutrophils and eosinophils.

[0614] In some embodiments, the binding molecule according to the invention may comprise a heavy chain constant domain. In some embodiments, the heavy chain constant domain may be a heavy chain IgG constant domain. In some embodiments, the heavy chain IgG constant domain may be a heavy chain IgG 1 constant domain. In some embodiments, the heavy chain IgG constant domain may be a heavy chain lgG2 constant domain. In some embodiments, the heavy chain IgG constant domain may be a heavy chain lgG3 constant domain. In some embodiments, the heavy chain IgG constant domain may be a heavy chain lgG4 constant domain.

[0615] In some embodiments, the binding molecule according to the invention may comprise one or more constant domain sequence(s) presented in Table 4.

[0616] In some embodiments, the binding molecule according to the invention may comprise a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 126 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 126. In some embodiments, the heavy chain constant domain may consist of the amino acid sequence according to SEQ ID NO: 126.

[0617] In some embodiments, the binding molecule according to the invention may comprise a light chain constant domain. In some embodiments, the light chain constant domain may be a light chain kappa constant domain. In some embodiments, the light chain constant domain may be a light chain lambda constant domain.

[0618] In some embodiments, the binding molecule according to the invention may comprise a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 127 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 127. In some embodiments, the light chain constant domain may consist of the amino acid sequence according to SEQ ID NO: 127.

[0619] In some embodiments, the binding molecule according to the invention may comprise a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 126; and a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 127.

[0620] In some embodiments, the binding molecule according to the invention may comprise a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 168 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 168. In some embodiments, the heavy chain constant domain may consist of the amino acid sequence according to SEQ ID NO: 168.

[0621] In some embodiments, the binding molecule according to the invention may comprise a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 169 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 169. In some embodiments, the light chain constant domain may consist of the amino acid sequence according to SEQ ID NO: 169.

[0622] In some embodiments, the binding molecule according to the invention may comprise a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 168; and a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 169.

[0623] In some embodiments, the binding molecule according to the invention may comprise a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 170 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 170. In some embodiments, the heavy chain constant domain may consist of the amino acid sequence according to SEQ ID NO: 170.

[0624] In some embodiments, the binding molecule according to the invention may comprise a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 171 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 171. In some embodiments, the light chain constant domain may consist of the amino acid sequence according to SEQ ID NO: 171.

[0625] In some embodiments, the binding molecule according to the invention may comprise a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 170; and a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 171.

[0626] Full heavy chain and full light chain

[0627] In some embodiments, the binding molecule according to the invention may comprise the combination of the full heavy chain and full light chain specified for each of the antibody clones presented in Table 5.

[0628] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 134 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 135 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 134. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 135.

[0629] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 134; and a light chain sequence of SEQ ID NO: 135.

[0630] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 134 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 137 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 134. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 137.

[0631] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 134; and a light chain sequence of SEQ ID NO: 137.

[0632] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 156 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 139 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 156. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 139.

[0633] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 156; and a light chain sequence of SEQ ID NO: 139.

[0634] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 138 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 139 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 138. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 139.

[0635] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 138; and a light chain sequence of SEQ ID NO: 139.

[0636] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 128 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 129 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 128. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 129.

[0637] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 128; and a light chain sequence of SEQ ID NO: 129.

[0638] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 132 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 133 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 132. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 133.

[0639] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 132; and a light chain sequence of SEQ ID NO: 133.

[0640] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 140 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 141 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 140. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 141.

[0641] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 140; and a light chain sequence of SEQ ID NO: 141 .

[0642] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 142 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 143 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 142. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 143.

[0643] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 142; and a light chain sequence of SEQ ID NO: 143.

[0644] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 144 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 145 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 144. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 145.

[0645] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 144; and a light chain sequence of SEQ ID NO: 145.

[0646] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 146 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 147 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 146. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 147.

[0647] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 146; and a light chain sequence of SEQ ID NO: 147.

[0648] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 148 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 149 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 148. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 149.

[0649] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 148; and a light chain sequence of SEQ ID NO: 149.

[0650] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 150 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 151 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 150. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 151.

[0651] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 150; and a light chain sequence of SEQ ID NO: 151 .

[0652] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 152 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 153 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 152. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 153.

[0653] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 152; and a light chain sequence of SEQ ID NO: 153.

[0654] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 154 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 155 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 154. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 155.

[0655] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 154; and a light chain sequence of SEQ ID NO: 155.

[0656] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 130 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 131 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 130. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 131.

[0657] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 130; and a light chain sequence of SEQ ID NO: 131 .

[0658] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 172 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 173 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 172. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 173.

[0659] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 172; and a light chain sequence of SEQ ID NO: 173.

[0660] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 174 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 175 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 174. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 175.

[0661] In some embodiments, the binding molecule according to the invention may comprise a heavy chain sequence of SEQ ID NO: 174; and a light chain sequence of SEQ ID NO: 175.

[0662] CFC1 antigen

[0663] The present invention provides a binding molecule that binds to a CFC1 antigen.

[0664] In some embodiments, the binding molecule according to the invention may bind to a CFC1 antigen.

[0665] In some embodiments, the CFC1 antigen may be defined according to the UniProt entry: P0CG37.

[0666] In some embodiments, the CFC1 antigen may comprise an amino acid sequence according to SEQ ID NO: 157 or a variant having at least 80% sequence identity thereto. In some embodiments, the variant may have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 157. In some embodiments, the CFC1 antigen may consist of an amino acid sequence according to SEQ ID NO: 157.

[0667] ANTIBODY

[0668] The present invention provides an antibody, or antigen-binding fragment thereof, comprising the binding molecule according to the invention.

[0669] As used herein, the term “antibody” is well-known in the art and typically means a protein or polypeptide having an antigen binding site or antigen-binding domain comprising at least one CDR.

[0670] In some embodiments, the antibody may comprise 6 CDRs. It will be understood that such an antibody may be a classical antibody molecule.

[0671] In some embodiments, the antibody or fragment thereof may be a humanised antibody or fragment thereof. In some embodiments, the antibody or fragment thereof may be a chimeric antibody or fragment thereof.

[0672] In some embodiments, the antibody may be a full-length, classical antibody. In some embodiments, the antibody may be an IgG, IgM, IgD, IgE or IgA molecule.

[0673] In some embodiments, the antibody may be an IgG molecule. In some embodiments, the antibody may be an lgG1 molecule. In some embodiments, the antibody may be an lgG2 molecule. In some embodiments, the antibody may be an lgG3 molecule. In some embodiments, the antibody may be an lgG4 molecule.

[0674] In some embodiments, the antibody may be a monoclonal antibody or fragment thereof. In some embodiments, the antibody may be a humanised monoclonal antibody or fragment thereof.

[0675] Techniques for obtaining antibodies are well-known in the art. For example, antibodies may be obtained by techniques comprising immunizing an animal with a target antigen and isolating the antibody from serum.

[0676] It will be understood that an antigen-binding fragment comprises an amino acid sequence that is shorter than the full-length sequence of an antibody, but retains the biological activity (e.g., binding specificity and / or affinity) of the full-length antibody.

[0677] The term "humanised antibody" typically refers to a genetically engineered antibody generated in a non-human animal that has been engineered to reduce immunogenicity when used in a human whilst retaining antigen specificity. The humanised antibody typically contains human antibody constant domains and non-human variable domains that are modified to contain a high level of sequence homology to human variable domains.

[0678] POLYNUCLEOTIDE

[0679] The present invention provides a polynucleotide comprising a nucleic acid sequence encoding the binding molecule according to the invention or the antibody or fragment thereof according to the invention.

[0680] The present invention provides one or more polynucleotide(s) comprising a nucleic acid sequence encoding the binding molecule according to the invention or the antibody or fragment thereof according to the invention. As used herein, the terms “polynucleotide”, “nucleotide”, and “nucleic acid” are intended to be synonymous with each other. The nucleic acid sequence may be a DNA sequence. The nucleic acid sequence may be single-stranded or may be double-stranded. The nucleic acid sequence may be, for example, genomic, recombinant, or cDNA. The nucleic acid sequence may comprise synthetic nucleotides and / or modified nucleotides. These synthetic nucleotides and / or modified nucleotides may enhance the in vivo activity and / or stability of the polynucleotide.

[0681] In some embodiments, the nucleic acid sequence may be a DNA sequence. In some embodiments, the nucleic acid sequence may be a cDNA sequence.

[0682] Due to the redundancy of the genetic code, variations in nucleic acid sequences are possible that encode for the same polypeptide. These sequences are encompassed by the present invention. Therefore, multiple polynucleotides are envisaged, each with a different nucleic acid sequence but which encodes a polypeptide according to the invention or a further polypeptide as described herein. It is known in the art how to design and produce such nucleic acid sequences.

[0683] In some embodiments, the nucleic acid sequence of the polynucleotide may be codon optimised for production in the host cell of choice.

[0684] In some embodiments, the nucleic acid sequence of the polynucleotide may be operably linked to a sequence such as a control sequence, e.g., a promoter sequence, an enhancer sequence or regulatory sequence, which controls transcription and / or translation. The polynucleotide may be in the form of an expression cassette.

[0685] The polynucleotide may be suitable for expression in prokaryotic cells or in eukaryotic cells, such as mammalian cells.

[0686] Any promoter may be used in the polynucleotide, such as a strong promoter that is functional in prokaryotic cells or in eukaryotic cells. Suitable promoters will be known in the art. The promoter may be a constitutive promoter. The promoter may be a tissue specific promoter.

[0687] VECTOR

[0688] The present invention provides a vector comprising the polynucleotide according to the invention. Accordingly, the vector may comprise a polynucleotide comprising a nucleic acid sequence which encodes the binding molecule according to the invention or the antibody or fragment thereof according to the invention.

[0689] The vector may be used to introduce polynucleotide according to the invention into a cell so that the cell expresses and / or produces the binding molecule according to the invention or the antibody or fragment thereof according to the invention.

[0690] As used herein, the term “vector” may be considered interchangeable with the term “expression vector” and “expression construct”. The vector may be any vector that is suitable for introducing and / or expressing a nucleic acid sequence in a cell. The vector may comprise regulatory sequences, enhancer sequences and / or promoter sequences that promote expression of a nucleic acid sequence in a cell.

[0691] The vector according to the invention may be any agent capable of delivering a polynucleotide according to the invention to a cell and / or expressing a nucleic acid sequence of a polynucleotide according to the invention in a cell. Examples of suitable vectors include but are not limited to plasmids, cosmids, phages, viruses or artificial chromosomes.

[0692] In some embodiments, the vector may be a plasmid or a viral vector. In some embodiments, the vector may be a retroviral vector or a lentiviral vector.

[0693] The vector may be capable of transfecting or transducing a cell.

[0694] CELL AND RELATED METHODS

[0695] The present invention provides a cell comprising a polynucleotide according to the invention, or a vector according to the invention.

[0696] The polynucleotide or vector may, for example, be introduced into a cell by transduction or transfection in vitro or ex vivo.

[0697] As such, the present invention also provides a method for making a cell according to the invention comprising the step of introducing a polynucleotide according to the invention, or a vector according to the invention into said cell. In some embodiments, the polynucleotide may be introduced as described herein. In some embodiments, the cell may be capable of expressing the binding molecule according to the invention or the antibody or fragment thereof according to the invention.

[0698] In some embodiments, the cell may be capable of producing the binding molecule according to the invention or the antibody or fragment thereof according to the invention.

[0699] In some embodiments, the cell may be capable of expressing and / or producing the binding molecule according to the invention or the antibody or fragment thereof according to the invention when the cell is cultured under suitable conditions.

[0700] As such, the present invention also provides a method for producing the binding molecule according to the invention or the antibody or fragment thereof according to the invention, wherein the method comprises the steps of:

[0701] (i) introducing a polynucleotide according to the invention, or a vector according to the invention into a cell; and

[0702] (ii) expressing the binding molecule or antibody or fragment thereof in the cell.

[0703] In some embodiments of the methods according to the invention, the polynucleotide or vector may be introduced into the cell by transduction or transfection in vitro or ex vivo.

[0704] In some embodiments of the methods according to the invention, culturing the cell under suitable conditions may result in the cell expressing and / or producing the binding molecule or antibody or fragment thereof.

[0705] In some embodiments, the method for producing the binding molecule or the antibody or fragment thereof may further comprise step (iii) harvesting the binding molecule or antibody or fragment thereof from the cell or cell culture supernatant of the cell.

[0706] It will be understood that the binding molecule according to the invention or the antibody or fragment thereof according to the invention may be harvested from the cell. It will also be understood that the binding molecule according to the invention or the antibody or fragment thereof according to the invention may be harvested from supernatant of the cell, for example when the binding molecule, antibody or fragment thereof is released out of the cell into the cell culture medium that the cell is cultured in.

[0707] In some embodiments, the cell may be a prokaryotic cell or a eukaryotic cell. In some embodiments, the cell may be a bacterial cell, a fungal cell, a yeast cell, a plant cell or an animal cell.

[0708] In some embodiments, the cell may be a mammalian cell or an insect cell. In some embodiments, the cell may be a human cell.

[0709] COMPOSITION

[0710] The present invention provides a composition which comprises the binding molecule according to the invention, or the antibody or fragment thereof according to the invention; together with a carrier, diluent or excipient.

[0711] In some embodiments, the composition may comprise the binding molecule according to the invention, together with a carrier, diluent or excipient.

[0712] In some embodiments, the composition may comprise the antibody or fragment thereof according to the invention, together with a carrier, diluent or excipient.

[0713] The present invention also provides a composition which comprises the polynucleotide according to the invention, together with a carrier, diluent or excipient.

[0714] The present invention also provides a composition which comprises the vector according to the invention, together with a carrier, diluent or excipient.

[0715] In some embodiments, the composition described herein may further comprise one or more selected from this list consisting of: a adjuvant, salt, active polypeptide, compound, and component.

[0716] Compositions typically should be sterile and stable under the conditions of manufacture and storage. The composition according to the invention may be produced using current good manufacturing practices (CGMP).

[0717] The term “carrier”, as used herein, may refer to a diluent, adjuvant, excipient, or vehicle . Such carriers can be sterile liquids, such as saline solutions in water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil. A sterile saline solution is a preferred carrier. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers. Suitable excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like.

[0718] The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. The composition of the invention can be formulated as neutral or salt forms. Salts include those formed with free amino groups such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and those formed with free carboxyl groups such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine, procaine, etc.

[0719] In some embodiments, the salt may comprise a metal cation, such as a sodium salt or a potassium salt.

[0720] In some embodiments, the composition may comprise an aqueous diluent or solvent. In some embodiments, the aqueous diluent or solvent may be a phosphate buffered saline solution, such as a sterile phosphate buffered saline solution.

[0721] IDENTITY

[0722] The terms “identity” and “% sequence identity” as used herein, may refer to the proportion of amino acids (expressed in percent) of an amino acid sequence in a peptide or protein, which across the amino acid sequence, are identical to a reference sequence.

[0723] The percentage of identity is thus calculated by counting the number of aligned amino acids that are identical (a Match) between two sequences (in the amino acids sequence of the peptide or protein of the invention and in the reference sequence), dividing that number by the total number of amino acids in the aligned region and multiplying by 100.

[0724] Therefore, Percentage of Identity = (Matches divided by Length of the aligned region) multiplied by 100.

[0725] Insertions and deletions are not allowed in the calculation the percentage of identity of an amino acid sequence.

[0726] Any method of calculating percentage identity is permitted within the scope of the invention. GENERAL TERMS AND DEFINITIONS

[0727] This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of this disclosure.

[0728] The term “polypeptide” is used in the conventional sense to mean a series of amino acids, typically L-amino acids, connected one to the other, typically by peptide bonds between the a- amino and carboxyl groups of adjacent amino acids.

[0729] The term “polypeptide” is used interchangeably with the terms “amino acid sequence”, “peptide” and / or “protein”.

[0730] The term “residues” is used to refer to amino acids in an amino acid sequence.

[0731] Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, any nucleic acid sequences are written left to right in 5' to 3' orientation; amino acid sequences are written left to right in amino to carboxy orientation, respectively.

[0732] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within this disclosure. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within this disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in this disclosure.

[0733] It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0734] The terms "comprising", "comprises" and "comprised of' as used herein are synonymous with "including", "includes" or "containing", "contains", and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps. The terms "comprising", "comprises" and "comprised of also include the terms "consisting of' or “consisting essentially of”. As used herein, the term “variant” is synonymous with the term “mutant” and refers to an amino acid sequence or a nucleic acid sequence that differs in comparison to the corresponding wildtype sequence. The term “wild-type” is used to mean a protein comprising an amino acid sequence or a polynucleotide comprising an amino acid sequence, which is identical to the native protein or native polynucleotide (e.g. gene) respectively. The variant may have an equivalent function to the amino acid sequences or nucleic acid sequences described herein, but may include one or more amino acid or nucleic acid (respectively) substitutions, insertions or deletions. Amino acid substitutions, insertions and / or deletions may be considered as mutations. Nucleic acid substitutions, insertions and / or deletions may be considered as mutations.

[0735] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that such publications constitute prior art to the claims appended hereto.

[0736] SEQUENCES

[0737] The antibody clones used herein are: MAB-18-0113, MAB-18-0139, MAB-20-0212, MAB-20-0227, M AB-20-0271, MAB-18-0110, MAB-18-0111 , MAB-18-0116, MAB-18-0117, MAB-18-0121 , MAB-18-0133, MAB-18-0134, MAB-18-0136, MAB-18-0127, MAB-20-0273.

[0738] Table 1 - CDR sequences determine using Kabat numbering system

[0739]

[0740] Table 2 - CDR sequences determine using IMGT numbering system

[0741]

[0742] Table 3 - VH and VL sequences

[0743]

[0744]

[0745] Table 4 -Constant domain sequences

[0746]

[0747] Table 5 - Full heavy and light chain sequences

[0748]

[0749]

[0750]

[0751]

[0752]

[0753]

[0754]

[0755]

[0756] Table 6 - Other sequences

[0757] NUMBERED PARAGRAPHS

[0758] The present invention may be described by way of the following numbered paragraphs:

[0759] 1. A binding molecule comprising a CFC1 binding domain.

[0760] 2. The binding molecule according to paragraph 1, wherein the binding molecule:

[0761] (i) binds to at least 40% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml; optionally wherein the binding molecule binds to at least 50%, at least 60%, at least 70%, at least 80% or at least 85% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml; or

[0762] (ii) binds to at least 90% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml; optionally wherein the binding molecule binds to at least 91%, at least 92%, at least 93%, or at least 94% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml.

[0763] 3. The binding molecule according to paragraph 1 or paragraph 2, wherein the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0764] (i)

[0765] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 1,

[0766] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 2, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 3; or

[0767] (ii)

[0768] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7,

[0769] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 8, and

[0770] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 9; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0771] 4. The binding molecule according to any one of paragraphs 1-3, wherein the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0772] (i)

[0773] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 4,

[0774] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 5, and

[0775] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 6; or

[0776] (ii)

[0777] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 10,

[0778] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 11 , and

[0779] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0780] 5. The binding molecule according to paragraph 1 or paragraph 2, wherein the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0781] (i)

[0782] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 60, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 61 , and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 62; or

[0783] (ii)

[0784] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64,

[0785] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 65, and

[0786] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 66; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0787] 6. The binding molecule according to any one of paragraphs 1 , 2 or 5, wherein the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0788] (i)

[0789] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 63,

[0790] LCDR2 comprises the amino acid sequence SAS, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 6; or

[0791] (ii)

[0792] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 67,

[0793] LCDR2 comprises the amino acid sequence GAS, and

[0794] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0795] 7. The binding molecule according to any one of paragraphs 3-6, wherein the VH domain comprises

[0796] (i) the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; or

[0797] (ii) the amino acid sequence according to SEQ ID NO: 125 or a variant having at least 80% sequence identity thereto; or

[0798] (iii) the amino acid sequence according to SEQ ID NO: 107 or a variant having at least 80% sequence identity thereto; or

[0799] (iv) the amino acid sequence according to SEQ ID NO: 100 or a variant having at least 80% sequence identity thereto; or

[0800] (v) the amino acid sequence according to SEQ ID NO: 102 or a variant having at least 80% sequence identity thereto.

[0801] 8. The binding molecule according to paragraph 7, wherein:

[0802] (i) the VH domain comprises the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 105 or a variant having at least 80% sequence identity thereto; or

[0803] (ii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 106 or a variant having at least 80% sequence identity thereto; or

[0804] (iii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 125 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto; or

[0805] (iv) the VH domain comprises the amino acid sequence according to SEQ ID NO: 107 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto; or

[0806] (v) the VH domain comprises the amino acid sequence according to SEQ ID NO: 100 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 101 or a variant having at least 80% sequence identity thereto; or

[0807] (vi) the VH domain comprises the amino acid sequence according to SEQ ID NO: 102 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 103 or a variant having at least 80% sequence identity thereto.

[0808] 9. The binding molecule according to paragraph 1 , wherein the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the Kabat definition, wherein:

[0809] (i)

[0810] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 13,

[0811] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 14, and

[0812] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 15; or

[0813] (ii)

[0814] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 19,

[0815] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 20, and

[0816] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 21 ; or

[0817] (iii)

[0818] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7,

[0819] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 25, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 26; or

[0820] (iv)

[0821] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 30,

[0822] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 31 , and

[0823] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 32; or

[0824] (v)

[0825] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 36, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 37, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 38; or

[0826] (vi)

[0827] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 42,

[0828] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 43, and

[0829] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 44; or

[0830] (vii)

[0831] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 48,

[0832] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 49, and

[0833] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 50; or

[0834] (viii)

[0835] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 54,

[0836] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 55, and

[0837] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 56; or

[0838] (ix)

[0839] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 158,

[0840] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 159, and

[0841] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 160; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0842] 10. The binding molecule according to paragraph 1 or paragraph 9, wherein the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:

[0843] (i)

[0844] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 16, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18; or

[0845] (ii)

[0846] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 22,

[0847] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 23, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24; or

[0848] (iii)

[0849] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 27,

[0850] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 28, and

[0851] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29; or

[0852] (iv)

[0853] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 33,

[0854] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 34, and

[0855] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35; or

[0856] (v)

[0857] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 39,

[0858] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 40, and

[0859] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41; or

[0860] (vi)

[0861] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 45,

[0862] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 46, and

[0863] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47; or

[0864] (vii)

[0865] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 51,

[0866] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 52, and

[0867] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 53; or

[0868] (viii)

[0869] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 57,

[0870] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 58, and

[0871] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59; or

[0872] (ix)

[0873] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 161,

[0874] LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and

[0875] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0876] 11. The binding molecule according to paragraph 1 , wherein the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:

[0877] (i)

[0878] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 68,

[0879] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 69, and

[0880] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 70; or

[0881] (ii)

[0882] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 72,

[0883] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 73, and

[0884] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 74; or

[0885] (iii)

[0886] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 76,

[0887] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 77, and

[0888] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 78; or

[0889] (iv)

[0890] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 80,

[0891] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 81 , and

[0892] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 82; or

[0893] (v)

[0894] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 84,

[0895] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 85, and

[0896] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 86; or

[0897] (vi)

[0898] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 88,

[0899] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 89, and

[0900] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 90; or (vii)

[0901] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 92,

[0902] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 93, and

[0903] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 94; or

[0904] (viii)

[0905] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 96,

[0906] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 97, and

[0907] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 98; or

[0908] (ix)

[0909] HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64,

[0910] HCDR2 comprises the amino acid sequence according to SEQ ID NO: 163, and

[0911] HCDR3 comprises the amino acid sequence according to SEQ ID NO: 164; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0912] 12. The binding molecule according to paragraph 1 or paragraph 11, wherein the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:

[0913] (i)

[0914] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 71, LCDR2 comprises the amino acid sequence RAS, and

[0915] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18; or

[0916] (ii)

[0917] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 75, LCDR2 comprises the amino acid sequence EAS, and

[0918] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24; or

[0919] (iii)

[0920] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 79, LCDR2 comprises the amino acid sequence SAS, and

[0921] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29; or

[0922] (iv) LCDR1 comprises the amino acid sequence according to SEQ ID NO: 83,

[0923] LCDR2 comprises the amino acid sequence GAS, and

[0924] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35; or

[0925] (v)

[0926] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 87,

[0927] LCDR2 comprises the amino acid sequence RTS, and

[0928] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41 ; or

[0929] (vi)

[0930] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 91 ,

[0931] LCDR2 comprises the amino acid sequence YAS, and

[0932] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47; or

[0933] (vii)

[0934] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 95,

[0935] LCDR2 comprises the amino acid sequence DAS, and

[0936] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 53; or

[0937] (viii)

[0938] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 99,

[0939] LCDR2 comprises the amino acid sequence AAS, and

[0940] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59; or

[0941] (ix)

[0942] LCDR1 comprises the amino acid sequence according to SEQ ID NO: 165,

[0943] LCDR2 comprises the amino acid sequence RAS, and

[0944] LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

[0945] 13. The binding molecule according to any one of paragraphs 9-12, wherein the VH domain comprises

[0946] (i) the amino acid sequence according to SEQ ID NO: 109 or a variant having at least

[0947] 80% sequence identity thereto; or

[0948] (ii) the amino acid sequence according to SEQ ID NO: 111 or a variant having at least

[0949] 80% sequence identity thereto; or (iii) the amino acid sequence according to SEQ ID NO: 113 or a variant having at least 80% sequence identity thereto; or

[0950] (iv) the amino acid sequence according to SEQ ID NO: 115 or a variant having at least 80% sequence identity thereto; or

[0951] (v) the amino acid sequence according to SEQ ID NO: 117 or a variant having at least 80% sequence identity thereto; or

[0952] (vi) the amino acid sequence according to SEQ ID NO: 119 or a variant having at least 80% sequence identity thereto; or

[0953] (vii) the amino acid sequence according to SEQ ID NO: 121 or a variant having at least 80% sequence identity thereto; or

[0954] (viii) the amino acid sequence according to SEQ ID NO: 123 or a variant having at least 80% sequence identity thereto; or

[0955] (ix) the amino acid sequence according to SEQ ID NO: 166 or a variant having at least 80% sequence identity thereto. The binding molecule according to paragraph 13, wherein:

[0956] (i) the VH domain comprises the amino acid sequence according to SEQ ID NO: 109 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 110 or a variant having at least 80% sequence identity thereto; or

[0957] (ii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 111 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 112 or a variant having at least 80% sequence identity thereto; or

[0958] (iii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 113 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 114 or a variant having at least 80% sequence identity thereto; or

[0959] (iv) the VH domain comprises the amino acid sequence according to SEQ ID NO: 115 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 116 or a variant having at least 80% sequence identity thereto; or

[0960] (v) the VH domain comprises the amino acid sequence according to SEQ ID NO: 117 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 118 or a variant having at least 80% sequence identity thereto; or (vi) the VH domain comprises the amino acid sequence according to SEQ ID NO: 119 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 120 or a variant having at least 80% sequence identity thereto; or

[0961] (vii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 121 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 122 or a variant having at least 80% sequence identity thereto; or

[0962] (viii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 123 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 124 or a variant having at least 80% sequence identity thereto; or

[0963] (ix) the VH domain comprises the amino acid sequence according to SEQ ID NO: 166 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 167 or a variant having at least 80% sequence identity thereto.

[0964] 15. The binding molecule according to any one of paragraphs 1-14, further comprising an Fc domain.

[0965] 16. The binding molecule according to any one of paragraphs 1-15, wherein the binding molecule comprises:

[0966] (a) (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 126 or a variant having at least 80% sequence identity thereto; and / or

[0967] (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 127 or a variant having at least 80% sequence identity thereto; or

[0968] (b) (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 168 or a variant having at least 80% sequence identity thereto; and / or (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 169 or a variant having at least 80% sequence identity thereto; or

[0969] (c) (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 170 or a variant having at least 80% sequence identity thereto; and / or

[0970] (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 171 or a variant having at least 80% sequence identity thereto. 17. The binding molecule according to any one of paragraphs 1-16, wherein the binding molecule comprises:

[0971] (i) a heavy chain sequence of SEQ ID NO: 134 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 135 or a variant having at least 80% sequence identity thereto; or

[0972] (ii) a heavy chain sequence of SEQ ID NO: 134 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 137 or a variant having at least 80% sequence identity thereto; or

[0973] (iii) a heavy chain sequence of SEQ ID NO: 156 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 139 or a variant having at least 80% sequence identity thereto; or

[0974] (iv) a heavy chain sequence of SEQ ID NO: 138 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 139 or a variant having at least 80% sequence identity thereto; or

[0975] (v) a heavy chain sequence of SEQ ID NO: 128 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 129 or a variant having at least 80% sequence identity thereto; or

[0976] (vi) a heavy chain sequence of SEQ ID NO: 132 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 133 or a variant having at least 80% sequence identity thereto; or

[0977] (vii) a heavy chain sequence of SEQ ID NO: 140 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 141 or a variant having at least 80% sequence identity thereto; or

[0978] (viii) a heavy chain sequence of SEQ ID NO: 142 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 143 or a variant having at least 80% sequence identity thereto; or

[0979] (ix) a heavy chain sequence of SEQ ID NO: 144 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 145 or a variant having at least 80% sequence identity thereto; or

[0980] (x) a heavy chain sequence of SEQ ID NO: 146 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 147 or a variant having at least 80% sequence identity thereto; or

[0981] (xi) a heavy chain sequence of SEQ ID NO: 148 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 149 or a variant having at least 80% sequence identity thereto; or (xii) a heavy chain sequence of SEQ ID NO: 150 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 151 or a variant having at least 80% sequence identity thereto; or

[0982] (xiii) a heavy chain sequence of SEQ ID NO: 152 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 153 or a variant having at least 80% sequence identity thereto; or

[0983] (xiv) a heavy chain sequence of SEQ ID NO: 154 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 155 or a variant having at least 80% sequence identity thereto; or

[0984] (xv) a heavy chain sequence of SEQ ID NO: 172 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 173 or a variant having at least 80% sequence identity thereto; or

[0985] (xvi) a heavy chain sequence of SEQ ID NO: 174 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 175 or a variant having at least 80% sequence identity thereto.

[0986] 18. The binding molecule according to any one of paragraphs 15-17, wherein

[0987] (i) the Fc domain binds to one or more Fc receptor(s); and / or

[0988] (ii) the Fc domain is capable of binding to immune cells; and / or

[0989] (iii) the Fc domain is capable of recruiting immune cells; optionally wherein the immune cells of (ii) and (iii) are cytotoxic immune cells and / or are capable of killing target cells.

[0990] 19. An antibody or antigen-binding fragment thereof comprising the binding molecule according to any preceding paragraph.

[0991] 20. The antibody or fragment thereof according to paragraph 19, wherein the antibody or fragment thereof is a humanized antibody or fragment thereof, or a chimeric antibody or fragment thereof.

[0992] 21. The antibody or fragment thereof according to paragraph 19 or paragraph 20, wherein the antibody or fragment thereof is a monoclonal antibody or fragment thereof.

[0993] 22. A polynucleotide comprising a nucleic acid sequence encoding the binding molecule according to any of paragraphs 1-18 or the antibody or fragment thereof according to any one of paragraphs 19-21. 23. The polynucleotide according to paragraph 22, wherein the nucleic acid sequence is a DNA sequence.

[0994] 24. A vector which comprises a polynucleotide according to paragraph 22 or paragraph 23.

[0995] 25. A cell comprising a polynucleotide according to paragraph 22 or paragraph 23, or a vector according to paragraph 24.

[0996] 26. The cell according to paragraph 25, wherein the cell is capable of expressing the binding molecule according to any of paragraphs 1-18 or the antibody or fragment thereof according to any one of paragraphs 19-21.

[0997] 27. A method for making a cell according to paragraph 25 or paragraph 26, comprising the step of introducing a polynucleotide according to paragraph 22 or paragraph 23, or a vector according to paragraph 24 into said cell.

[0998] 28. A method for producing the binding molecule according to any of paragraphs 1-18 or the antibody or fragment thereof according to any one of paragraphs 19-21 , wherein the method comprises the steps of:

[0999] (i) introducing a polynucleotide according to paragraph 22 or paragraph 23, or a vector according to paragraph 24 into a cell; and

[1000] (ii) expressing the binding molecule or antibody or fragment thereof in the cell; and optionally

[1001] (iii) harvesting the binding molecule or antibody or fragment thereof from the cell or cell culture supernatant of the cell.

[1002] 29. A composition which comprises the binding molecule according to any of paragraphs 1-18, or the antibody or fragment thereof according to any one of paragraphs 19-21 ; together with a carrier, diluent or excipient.

[1003] The invention will now be further described by way of Examples, which are meant to serve to assist one of ordinary skill in the art in carrying out the invention and are not intended in any way to limit the scope of the invention. EXAMPLES

[1004] Example 1 : Generation of CFC1-bindinq monoclonal antibodies

[1005] To obtain CFC1 -specific monoclonal antibodies, New Zealand White rabbits were immunized with recombinant human CFC1 extracellular domain containing a C-terminal 10xHIS protein. Single B-cells were isolated by FACS from peripheral blood and cultivated to obtain monoclonal antibodies in the medium supernatant. Selected monoclonal B-cell clones were lysed in RNA extraction RLT buffer for RNA extraction, RT-PCR and Sanger sequencing of the antibody heavy and light chain variable regions. Antibody heavy and light chain V-regions were gene synthesized, cloned into pCEP4 expression plasmids upstream of hlgG1-constant domains and produced in HEK293-FreeStyle™ cells.

[1006] Example 2: Humanization of CFC1-bindinq monoclonal antibodies

[1007] VL and VH-region coding sequences of MAB-18-0113 and MAB-18-0139 antibodies were subjected to an in silico humanization procedure based on a combination of CDR grafting and antibody structure guided modifications. Five heavy chain and four light chain humanized V- regions were gene synthesized and cloned into pCEP4 expression plasmids upstream of hlgG1-constant domains. Combinations of all possible humanized antibody heavy and light chains were produced in HEK293-FreeStyle™ cells.

[1008] Example 3: human CFC1 ELISA

[1009] The specificity and binding potencies of the anti-CFC1 chimeric and humanized antibodies of the invention to human CFC1 were determined by an ELISA (Figure 1 and Table 7).

[1010] Recombinant human CFC1 ECD (R&D Systems) was coated on 384-well Nunc MaxiSorp™ flat bottom plates at a concentration of 0,6 pg / ml in PBS for 60 minutes at room temperature. After 3 washes with PBS 0.1 % Tween (wash buffer), blocking with PBS, 2% BSA, 0.05% Tween for 60 minutes at room temperature and another 3 washes, the chimeric and humanized antibodies of the invention were added in PBS, 0.5% BSA, 0.05% Tween (ELISA buffer) in concentrations ranging from 2,000 to 0.06 ng / ml and the plate was incubated for 60 minutes at room temperature. As reference antibodies, a control anti-CFC1 antibody was added in same concentration range. After 3 washes with wash buffer, horseradish peroxidase coupled anti-human-IgG (Fab’)2 fragment (AbD Serotec) was added in ELISA buffer at a dilution of 1 :5000. The plate was incubated for 60 minutes at room temperature, washed 6 times with wash buffer before TMB solution (Thermo Fisher Scientific) was added. The color reaction was stopped with HCI and the absorbance was recorded at wavelengths 450 / 620 nm using a Tecan Infinite M1000 reader. Data analysis including 4PL curve fitting and EC50 calculation were done with IDBS XLfit.

[1011] Example 4: CHO-K1 human CFC1 and CHO-K1 cynomolgus cell binding

[1012] Binding potencies of anti-CFC1 chimeric or humanized antibodies of the invention to human or cynomolgus CFC1 ectopically expressing CHO-K1 cell line were analyzed by high content imaging (Figure 2 and Table 7).

[1013] 1 ,000 CHO-K1 cells were seeded per well in black 384-well cell-culture treated plates and incubated for 2 hours at 37°C and 5% CO2. Chimeric or humanized antibodies of the invention were diluted ranging from 5,000 to 0.05 ng / ml. As reference antibodies, a control anti-CFC1 antibody was used at same concentration range. After overnight incubation at 37°C and 5% CO2, plates were washed once with PBS, 0.05% Tween 20 (cell wash buffer) and Alexa-Fluor- 448-conjugated anti-human-IgG F(ab’)2 fragment was added at a concentration of 0.8 pg / ml. Plates were incubated for 4 hours at 37°C and 5% CO2 in the dark, washed once with cell wash buffer and incubated for 10 minutes with medium containing 5pg / ml Hoechst (Invitrogen). Cell-associated immunofluorescent signals were recorded using a Celllnsight CX5 high content imager (Thermo Fisher) given as the mean spot intensity averaged over all cells. Data analysis including 4PL curve fitting and EC50 calculation were done with IDBS XLfit.

[1014] Table 7

[1015] Example 5: Binding and specificity of anti-CFC1 recombinant antibodies

[1016] The binding and specificity of anti-CFC1 recombinant antibodies to tumor cells that expressed CFC1 was measured by FACS (see Figure 3). CFC1 positive (NCI-H810_hCFC1_hi) and as a control CFC1 negative (CHO-K1_hCLDN18.2-gp740_24H5_MACS-FACS) cells were incubated with dilutions of recombinant anti-CFC1 antibodies in the range of 0.1 to 1000 ng / ml. For the detection, a Allophycocyanin (APC) coupled secondary antibody was used. The recombinant anti-CFC1 antibodies bound and thereby stained the CFC1 positive cells very efficiently while CFC1 negative target cells were not stained. When the antibodies bound the CFC1 expressing target cells an MFI between 4500 and 11200 was reached with a concentration of 10 ng / ml. The MFI increased depending on the concentration of the antibodies. With a concentration of 100 ng / ml a MFI between 16400 and 23400 was reached. Using only 1 ng / ml between 40 % and 85 % of the CFC1 expressing target cells could be stained. When the concentration of the anti-CFC1 antibodies was increased to 10 ng / ml over 94% of the CFC1 expressing target cells were stained.

[1017] The flow cytometer was a BD FACSCelesta (BD Bioscience). Flow cytometer settings: APC channel (594 nm 1633 nm) with emission peak 660 nm.

[1018] Example 6: Antibody-dependent cellular cytotoxicity (ADCC)

[1019] The efficacy of CFC1 -targeting recombinant antibodies was assessed by analysing the ability to induce antibody-dependent cellular cytotoxicity (ADCC) (see Figure 4). A Jurkat surrogate ADCC assay was conducted, using Jurkat ADCC effector cells (AcCELLerate) as a surrogate for immune effector cells. The potency of inducing ADCC was measured by the activation of Jurkat cells. The CFC1 -positive lung cancer transfectant NCI-H810_hCFC1_sort-high and the CFC1-negative breast cancer cell line MDA-MB-231 were used to assess specific Jurkat activation in an effector to target (E:T) ratio of 10:1 with a 3.5-fold, 10-point dilution from 3,500 to 0.044 ng / mL antibody dilution row. The candidates MAB-20-0212, MAB-20-0227 and MAB- 20-0271 induced a higher Jurkat activation compared to the anti-CFC1 control Ab. All publications mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described methods and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in molecular biology or related fields are intended to be within the scope of the following claims.

Claims

CLAIMS1. A binding molecule comprising a CFC1 binding domain.

2. The binding molecule according to claim 1 , wherein the binding molecule:(i) binds to at least 40% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml; optionally wherein the binding molecule binds to at least 50%, at least 60%, at least 70%, at least 80% or at least 85% of a population of CFC1 expressing cells when the concentration of the binding molecule is 1 ng / ml; or(ii) binds to at least 90% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml; optionally wherein the binding molecule binds to at least 91%, at least 92%, at least 93%, or at least 94% of a population of CFC1 expressing cells when the concentration of the binding molecule is 10 ng / ml.

3. The binding molecule according to claim 1 or claim 2, wherein(i)(a) the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1- 3 as defined by the Kabat definition, wherein:(i)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 1 ,HCDR2 comprises the amino acid sequence according to SEQ ID NO: 2, andHCDR3 comprises the amino acid sequence according to SEQ ID NO: 3; or(ii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7,HCDR2 comprises the amino acid sequence according to SEQ ID NO: 8, andHCDR3 comprises the amino acid sequence according to SEQ ID NO: 9; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences; and / or(b) the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:(i)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 4,LCDR2 comprises the amino acid sequence according to SEQ ID NO: 5, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 6; or(ii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 10,LCDR2 comprises the amino acid sequence according to SEQ ID NO: 11 , and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 12; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences; or(ii)(a) the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1-3 as defined by the IMGT definition, wherein:(i)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 60, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 61 , andHCDR3 comprises the amino acid sequence according to SEQ ID NO: 62; or(ii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64,HCDR2 comprises the amino acid sequence according to SEQ ID NO: 65, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 66; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences; and / or(b) the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:(i)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 63, LCDR2 comprises the amino acid sequence SAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 6; or(ii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 67, LCDR2 comprises the amino acid sequence GAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 12; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

4. The binding molecule according to claim 3, wherein the VH domain comprises(a)(i) the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; or(ii) the amino acid sequence according to SEQ ID NO: 125 or a variant having at least 80% sequence identity thereto; or(iii) the amino acid sequence according to SEQ ID NO: 107 or a variant having at least 80% sequence identity thereto; or(iv) the amino acid sequence according to SEQ ID NO: 100 or a variant having at least 80% sequence identity thereto; or(v) the amino acid sequence according to SEQ ID NO: 102 or a variant having at least 80% sequence identity thereto; optionally wherein(b)(i) the VH domain comprises the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 105 or a variant having at least 80% sequence identity thereto; or(ii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 104 or a variant having at least 80% sequence identity thereto; and the VL domainIllcomprises the amino acid sequence according to SEQ ID NO: 106 or a variant having at least 80% sequence identity thereto; or(iii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 125 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto; or(iv) the VH domain comprises the amino acid sequence according to SEQ ID NO: 107 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 108 or a variant having at least 80% sequence identity thereto; or(v) the VH domain comprises the amino acid sequence according to SEQ ID NO: 100 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 101 or a variant having at least 80% sequence identity thereto; or(vi) the VH domain comprises the amino acid sequence according to SEQ ID NO: 102 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 103 or a variant having at least 80% sequence identity thereto.

5. The binding molecule according to claim 1 , wherein(i)(a) the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1- 3 as defined by the Kabat definition, wherein:(i)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 13, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 14, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 15; or(ii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 19, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 20, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 21 ; or(iii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 7,HCDR2 comprises the amino acid sequence according to SEQ ID NO: 25, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 26; or(iv)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 30, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 31 , and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 32; or(v)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 36, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 37, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 38; or(vi)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 42, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 43, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 44; or(vii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 48, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 49, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 50; or(viii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 54, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 55, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 56; or(ix)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 158,HCDR2 comprises the amino acid sequence according to SEQ ID NO: 159, andHCDR3 comprises the amino acid sequence according to SEQ ID NO: 160; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences; and / orthe CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the Kabat definition, wherein:(i)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 16, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 18; or(ii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 22, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 23, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 24; or(iii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 27, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 28, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 29; or(iv)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 33, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 34, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 35; or(v)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 39,LCDR2 comprises the amino acid sequence according to SEQ ID NO: 40, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 41 ; or(vi)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 45, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 46, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 47; or(vii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 51 ,LCDR2 comprises the amino acid sequence according to SEQ ID NO: 52, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 53; or(viii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 57, LCDR2 comprises the amino acid sequence according to SEQ ID NO: 58, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 59; or(ix)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 161 , LCDR2 comprises the amino acid sequence according to SEQ ID NO: 17, and LCDR3 comprises the amino acid sequence according to SEQ ID NO: 162; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences; or(ii)(a) the CFC1 binding domain comprises a heavy chain variable (VH) domain; wherein the VH domain comprises heavy chain complementarity determining regions (HCDRs) 1- 3 as defined by the IMGT definition, wherein:(i)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 68, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 69, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 70; or(ii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 72, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 73, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 74; or(iii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 76, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 77, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 78; or(iv)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 80, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 81 , and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 82; or(v)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 84, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 85, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 86; or(vi)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 88, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 89, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 90; or(vii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 92, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 93, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 94; or(viii)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 96, HCDR2 comprises the amino acid sequence according to SEQ ID NO: 97, and HCDR3 comprises the amino acid sequence according to SEQ ID NO: 98; or(ix)HCDR1 comprises the amino acid sequence according to SEQ ID NO: 64,HCDR2 comprises the amino acid sequence according to SEQ ID NO: 163, andHCDR3 comprises the amino acid sequence according to SEQ ID NO: 164; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences; and / or(b)the CFC1 binding domain comprises a light chain variable (VL) domain; wherein the VL domain comprises light chain complementarity determining regions (LCDRs) 1-3 as defined by the IMGT definition, wherein:(i)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 71, LCDR2 comprises the amino acid sequence RAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 18; or(ii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 75, LCDR2 comprises the amino acid sequence EAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 24; or(iii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 79, LCDR2 comprises the amino acid sequence SAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 29; or(iv)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 83, LCDR2 comprises the amino acid sequence GAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 35; or(v)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 87,LCDR2 comprises the amino acid sequence RTS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 41; or(vi)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 91,LCDR2 comprises the amino acid sequence YAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 47; or(vii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 95, LCDR2 comprises the amino acid sequence DAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 53;or(viii)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 99,LCDR2 comprises the amino acid sequence AAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 59; or(ix)LCDR1 comprises the amino acid sequence according to SEQ ID NO: 165,LCDR2 comprises the amino acid sequence RAS, andLCDR3 comprises the amino acid sequence according to SEQ ID NO: 162; optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations relative to the recited sequences.

6. The binding molecule according to claim 5, wherein the VH domain comprises(a)(i) the amino acid sequence according to SEQ ID NO: 109 or a variant having at least 80% sequence identity thereto; or(ii) the amino acid sequence according to SEQ ID NO: 111 or a variant having at least 80% sequence identity thereto; or(iii) the amino acid sequence according to SEQ ID NO: 113 or a variant having at least 80% sequence identity thereto; or(iv) the amino acid sequence according to SEQ ID NO: 115 or a variant having at least 80% sequence identity thereto; or(v) the amino acid sequence according to SEQ ID NO: 117 or a variant having at least 80% sequence identity thereto; or(vi) the amino acid sequence according to SEQ ID NO: 119 or a variant having at least 80% sequence identity thereto; or(vii) the amino acid sequence according to SEQ ID NO: 121 or a variant having at least 80% sequence identity thereto; or(viii) the amino acid sequence according to SEQ ID NO: 123 or a variant having at least 80% sequence identity thereto; or(ix) the amino acid sequence according to SEQ ID NO: 166 or a variant having at least 80% sequence identity thereto; optionally wherein (b)(i) the VH domain comprises the amino acid sequence according to SEQ ID NO: 109 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 110 or a variant having at least 80% sequence identity thereto; or(ii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 111 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 112 or a variant having at least 80% sequence identity thereto; or(iii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 113 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 114 or a variant having at least 80% sequence identity thereto; or(iv) the VH domain comprises the amino acid sequence according to SEQ ID NO: 115 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 116 or a variant having at least 80% sequence identity thereto; or(v) the VH domain comprises the amino acid sequence according to SEQ ID NO: 117 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 118 or a variant having at least 80% sequence identity thereto; or(vi) the VH domain comprises the amino acid sequence according to SEQ ID NO: 119 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 120 or a variant having at least 80% sequence identity thereto; or(vii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 121 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 122 or a variant having at least 80% sequence identity thereto; or(viii) the VH domain comprises the amino acid sequence according to SEQ ID NO: 123 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 124 or a variant having at least 80% sequence identity thereto; or(ix) the VH domain comprises the amino acid sequence according to SEQ ID NO: 166 or a variant having at least 80% sequence identity thereto; and the VL domain comprises the amino acid sequence according to SEQ ID NO: 167 or a variant having at least 80% sequence identity thereto.

7. The binding molecule according to any one of claims 1-6, further comprising an Fc domain.

8. The binding molecule according to any one of claims 1-7, wherein the binding molecule comprises:(a) (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 126 or a variant having at least 80% sequence identity thereto; and / or(ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 127 or a variant having at least 80% sequence identity thereto; or(b) (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 168 or a variant having at least 80% sequence identity thereto; and / or (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 169 or a variant having at least 80% sequence identity thereto; or(c) (i) a heavy chain constant domain comprising the amino acid sequence according to SEQ ID NO: 170 or a variant having at least 80% sequence identity thereto; and / or (ii) a light chain constant domain comprising the amino acid sequence according to SEQ ID NO: 171 or a variant having at least 80% sequence identity thereto.

9. The binding molecule according to any one of claims 1-8, wherein the binding molecule comprises:(i) a heavy chain sequence of SEQ ID NO: 134 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 135 or a variant having at least 80% sequence identity thereto; or(ii) a heavy chain sequence of SEQ ID NO: 134 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 137 or a variant having at least 80% sequence identity thereto; or(iii) a heavy chain sequence of SEQ ID NO: 156 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 139 or a variant having at least 80% sequence identity thereto; or(iv) a heavy chain sequence of SEQ ID NO: 138 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 139 or a variant having at least 80% sequence identity thereto; or(v) a heavy chain sequence of SEQ ID NO: 128 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 129 or a variant having at least 80% sequence identity thereto; or(vi) a heavy chain sequence of SEQ ID NO: 132 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 133 or a variant having at least 80% sequence identity thereto; or(vii) a heavy chain sequence of SEQ ID NO: 140 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 141 or a variant having at least 80% sequence identity thereto; or(viii) a heavy chain sequence of SEQ ID NO: 142 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 143 or a variant having at least 80% sequence identity thereto; or(ix) a heavy chain sequence of SEQ ID NO: 144 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 145 or a variant having at least 80% sequence identity thereto; or(x) a heavy chain sequence of SEQ ID NO: 146 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 147 or a variant having at least 80% sequence identity thereto; or(xi) a heavy chain sequence of SEQ ID NO: 148 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 149 or a variant having at least 80% sequence identity thereto; or(xii) a heavy chain sequence of SEQ ID NO: 150 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 151 or a variant having at least 80% sequence identity thereto; or(xiii) a heavy chain sequence of SEQ ID NO: 152 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 153 or a variant having at least 80% sequence identity thereto; or(xiv) a heavy chain sequence of SEQ ID NO: 154 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 155 or a variant having at least 80% sequence identity thereto; or(xv) a heavy chain sequence of SEQ ID NO: 172 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 173 or a variant having at least 80% sequence identity thereto; or(xvi) a heavy chain sequence of SEQ ID NO: 174 or a variant having at least 80% sequence identity thereto; and a light chain sequence of SEQ ID NO: 175 or a variant having at least 80% sequence identity thereto.

10. An antibody or antigen-binding fragment thereof comprising the binding molecule according to any preceding claim.

11. A polynucleotide comprising a nucleic acid sequence encoding the binding molecule according to any of claims 1-9 or the antibody or fragment thereof according to claim 10.

12. A vector which comprises a polynucleotide according to claim 11 .

13. A cell comprising a polynucleotide according to claim 11 , or a vector according to claim 12.

14. A method for producing the binding molecule according to any of claims 1-9 or the antibody or fragment thereof according to claim 10, wherein the method comprises the steps of:(i) introducing a polynucleotide according to claim 11 , or a vector according to claim 12 into a cell; and(ii) expressing the binding molecule or antibody or fragment thereof in the cell; and optionally(iii) harvesting the binding molecule or antibody or fragment thereof from the cell or cell culture supernatant of the cell.

15. A composition which comprises the binding molecule according to any of claims 1-9, or the antibody or fragment thereof according to claim 10; together with a carrier, diluent or excipient.

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