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US 11,608,372 B2Granted
Recombinant human antibodies for therapy and prevention of polyomavirus-related diseases
AssigneesNeurimmune Holding AG, University of Zurich
InventorsJan Grimm, Roland Martin, Benoit Combaluzier, Ivan Jelcic
Life of this patent
Estimating the term…
Abstract
Provided are novel human-derived antibodies specifically recognizing polyomavirus polypeptides, preferably capable of binding to polyomaviruses of the type of JC virus (JCV) and/or BK virus (BKV) as well as methods related thereto. Furthermore, assays and kits related to antibodies specific for polyomaviruses, polyomavirus VP1 and or polyomavirus VP1 Virus-Like Particles (VLPs), preferably of the type of JCV and/or BKV, are disclosed. The human-derived antibodies as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for polyomavirus targeted immunotherapy and diagnostics.
Claims24
A monoclonal antibody or an antigen binding fragment thereof which is capable of binding to a polyomavirus and/or an antigen thereof, wherein the polyomavirus is JC virus (JCV) or BK virus (BKV), and wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and the VL comprise six complementarity determining regions (CDRs), wherein the VH comprises VH-CDR1-3 and the VL comprises VL-CDR1-3, wherein:
- (1) the VH-CDR1-3 and VL-CDR1-3 are selected from the group consisting of:
- (a) VH-CDR1:
- positions 26-36 of SEQ ID NO:
- 110,
- VH-CDR2:
- positions 51-66 of SEQ ID NO:
- 110,
- VH-CDR3:
- positions 99-116 of SEQ ID NO:
- 110,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 112,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 112, and
- VL-CDR3:
- positions 89-97 of SEQ ID NO:
- 112;
- (b) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 6,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 6,
- VH-CDR3:
- positions 99-106 of SEQ ID NO:
- 6,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 8,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 8, and
- VL-CDR3:
- positions 91-100 of SEQ ID NO:
- 8;
- (c) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 10,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 10,
- VH-CDR3:
- positions 99-110 of SEQ ID NO:
- 10,
- VL-CDR1:
- positions 23-34 of SEQ ID NO:
- 12,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 12, and
- VL-CDR3:
- positions 94-106 of SEQ ID NO:
- 12;
- (d) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 14,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 14,
- VH-CDR3:
- positions 99-109 of SEQ ID NO:
- 14,
- VL-CDR1:
- positions 23-35 of SEQ ID NO:
- 16,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 16, and
- VL-CDR3:
- positions 90-100 of SEQ ID NO:
- 16;
- (e) VH-CDR1:
- positions 26-36 of SEQ ID NO:
- 18,
- VH-CDR2:
- positions 51-66 of SEQ ID NO:
- 18,
- VH-CDR3:
- positions 99-108 of SEQ ID NO:
- 18,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 20,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 20, and
- VL-CDR3:
- positions 91-100 of SEQ ID NO:
- 20;
- (f) VH-CDR1:
- positions 26-36 of SEQ ID NO:
- 22,
- VH-CDR2:
- positions 51-66 of SEQ ID NO:
- 22,
- VH-CDR3:
- positions 99-113 of SEQ ID NO:
- 22,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 24,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 24, and
- VL-CDR3:
- positions 91-100 of SEQ ID NO:
- 24;
- (g) VH-CDR1:
- positions 26-36 of SEQ ID NO:
- 26,
- VH-CDR2:
- positions 51-66 of SEQ ID NO:
- 26,
- VH-CDR3:
- positions 99-114 of SEQ ID NO:
- 26,
- VL-CDR1:
- positions 24-35 of SEQ ID NO:
- 28,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 28, and
- VL-CDR3:
- positions 90-99 of SEQ ID NO:
- 28;
- (h) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 30,
- VH-CDR2:
- positions 50-65 of SEQ ID NO:
- 30,
- VH-CDR3:
- positions 98-113 of SEQ ID NO:
- 30,
- VL-CDR1:
- positions 24-35 of SEQ ID NO:
- 32,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 32, and
- VL-CDR3:
- positions 90-101 of SEQ ID NO:
- 32;
- (i) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 34,
- VH-CDR2:
- positions 50-65 of SEQ ID NO:
- 34,
- VH-CDR3:
- positions 98-102 of SEQ ID NO:
- 34,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 36,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 36, and
- VL-CDR3:
- positions 89-99 of SEQ ID NO:
- 36;
- (j) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 38,
- VH-CDR2:
- positions 50-68 of SEQ ID NO:
- 38,
- VH-CDR3:
- positions 101-105 of SEQ ID NO:
- 38,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 40,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 40, and
- VL-CDR3:
- positions 89-98 of SEQ ID NO:
- 40;
- (k) VH-CDR1:
- positions 26-37 of SEQ ID NO:
- 42,
- VH-CDR2:
- positions 52-67 of SEQ ID NO:
- 42,
- VH-CDR3:
- positions 100-115 of SEQ ID NO:
- 42,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 44,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 44, and
- VL-CDR3:
- positions 89-98 of SEQ ID NO:
- 44;
- (l) VH-CDR1:
- positions 26-36 of SEQ ID NO:
- 46,
- VH-CDR2:
- positions 51-66 of SEQ ID NO:
- 46,
- VH-CDR3:
- positions 99-107 of SEQ ID NO:
- 46,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 48,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 48, and
- VL-CDR3:
- positions 91-100 of SEQ ID NO:
- 48;
- (m) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 50,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 50,
- VH-CDR3:
- positions 99-118 of SEQ ID NO:
- 50,
- VL-CDR1:
- positions 23-35 of SEQ ID NO:
- 52,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 52, and
- VL-CDR3:
- positions 92-100 of SEQ ID NO:
- 52;
- (n) VH-CDR1:
- positions 26-36 of SEQ ID NO:
- 54,
- VH-CDR2:
- positions 51-66 of SEQ ID NO:
- 54,
- VH-CDR3:
- positions 99-114 of SEQ ID NO:
- 54,
- VL-CDR1:
- positions 24-35 of SEQ ID NO:
- 56,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 56, and
- VL-CDR3:
- positions 90-99 of SEQ ID NO:
- 56;
- (o) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 58,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 58,
- VH-CDR3:
- positions 99-112 of SEQ ID NO:
- 58,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 60,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 60, and
- VL-CDR3:
- positions 89-97 of SEQ ID NO:
- 60;
- (p) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 62,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 62,
- VH-CDR3:
- positions 99-109 of SEQ ID NO:
- 62,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 64,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 64, and
- VL-CDR3:
- positions 91-102 of SEQ ID NO:
- 64;
- (q) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 66,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 66,
- VH-CDR3:
- positions 99-110 of SEQ ID NO:
- 66,
- VL-CDR1:
- positions 24-40 of SEQ ID NO:
- 68,
- VL-CDR2:
- positions 56-62 of SEQ ID NO:
- 68, and
- VL-CDR3:
- positions 95-103 of SEQ ID NO:
- 68;
- (r) VH-CDR1:
- positions 26-33 of SEQ ID NO:
- 70,
- VH-CDR2:
- positions 50-65 of SEQ ID NO:
- 70,
- VH-CDR3:
- positions 98-110 of SEQ ID NO:
- 70,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 72,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 72, and
- VL-CDR3:
- positions 89-97 of SEQ ID NO:
- 72;
- (s) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 74,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 74,
- VH-CDR3:
- positions 99-116 of SEQ ID NO:
- 74,
- VL-CDR1:
- positions 24-39 of SEQ ID NO:
- 76,
- VL-CDR2:
- positions 55-61 of SEQ ID NO:
- 76, and
- VL-CDR3:
- positions 94-101 of SEQ ID NO:
- 76;
- (t) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 78,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 78,
- VH-CDR3:
- positions 99-112 of SEQ ID NO:
- 78,
- VL-CDR1:
- positions 23-35 of SEQ ID NO:
- 80,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 80, and
- VL-CDR3:
- positions 90-100 of SEQ ID NO:
- 80;
- (u) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 82,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 82,
- VH-CDR3:
- positions 99-115 of SEQ ID NO:
- 82,
- VL-CDR1:
- positions 23-33 of SEQ ID NO:
- 84,
- VL-CDR2:
- positions 49-55 of SEQ ID NO:
- 84, and
- VL-CDR3:
- positions 88-99 of SEQ ID NO:
- 84;
- (v) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 90,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 90,
- VH-CDR3:
- positions 99-112 of SEQ ID NO:
- 90,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 92,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 92, and
- VL-CDR3:
- positions 89-97 of SEQ ID NO:
- 92;
- (w) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 94,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 94,
- VH-CDR3:
- positions 99-117 of SEQ ID NO:
- 94,
- VL-CDR1:
- positions 24-35 of SEQ ID NO:
- 96,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 96, and
- VL-CDR3:
- positions 90-97 of SEQ ID NO:
- 96;
- (x) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 98,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 98,
- VH-CDR3:
- positions 99-115 of SEQ ID NO:
- 98,
- VL-CDR1:
- positions 23-33 of SEQ ID NO:
- 100,
- VL-CDR2:
- positions 49-55 of SEQ ID NO:
- 100, and
- VL-CDR3:
- positions 88-99 of SEQ ID NO:
- 100;
- (y) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 102,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 102,
- VH-CDR3:
- positions 99-110 of SEQ ID NO:
- 102,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 104,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 104, and
- VL-CDR3:
- positions 91-101 of SEQ ID NO:
- 104;
- (z) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 106,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 106,
- VH-CDR3:
- positions 99-107 of SEQ ID NO:
- 106,
- VL-CDR1:
- positions 23-35 of SEQ ID NO:
- 108,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 108, and
- VL-CDR3:
- positions 90-100 of SEQ ID NO:
- 108;
- (a2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 2,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 2,
- VH-CDR3:
- positions 99-113 of SEQ ID NO:
- 2,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 4,
- VL-CDR2:
- positions 50-57 of SEQ ID NO:
- 4, and
- VL-CDR3:
- positions 89-97 of SEQ ID NO:
- 4;
- (b2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 114,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 114,
- VH-CDR3:
- positions 99-112 of SEQ ID NO:
- 114,
- VL-CDR1:
- positions 23-35 of SEQ ID NO:
- 116,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 116, and
- VL-CDR3:
- positions 90-100 of SEQ ID NO:
- 116;
- (c2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 118,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 118,
- VH-CDR3:
- positions 99-113 of SEQ ID NO:
- 118,
- VL-CDR1:
- positions 24-35 of SEQ ID NO:
- 120,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 120, and
- VL-CDR3:
- positions 90-98 of SEQ ID NO:
- 120;
- (d2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 122,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 122,
- VH-CDR3:
- positions 99-107 of SEQ ID NO:
- 122,
- VL-CDR1:
- positions 23-35 of SEQ ID NO:
- 124,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 124, and
- VL-CDR3:
- positions 90-100 of SEQ ID NO:
- 124;
- (e2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 126,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 126,
- VH-CDR3:
- positions 99-110 of SEQ ID NO:
- 126,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 128,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 128, and
- VL-CDR3:
- positions 91-101 of SEQ ID NO:
- 128;
- (f2) VH-CDR1:
- positions 26-36 of SEQ ID NO:
- 130,
- VH-CDR2:
- positions 51-66 of SEQ ID NO:
- 130,
- VH-CDR3:
- positions 99-116 of SEQ ID NO:
- 130,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 132,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 132, and
- VL-CDR3:
- positions 89-97 of SEQ ID NO:
- 132;
- (g2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 134,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 134,
- VH-CDR3:
- positions 99-109 of SEQ ID NO:
- 134,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 136,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 136, and
- VL-CDR3:
- positions 91-100 of SEQ ID NO:
- 136;
- (h2) VH-CDR1:
- positions 26-37 of SEQ ID NO:
- 138,
- VH-CDR2:
- positions 52-67 of SEQ ID NO:
- 138,
- VH-CDR3:
- positions 100-117 of SEQ ID NO:
- 138,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 140,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 140, and
- VL-CDR3:
- positions 89-97 of SEQ ID NO:
- 140;
- (i2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 142,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 142,
- VH-CDR3:
- positions 99-112 of SEQ ID NO:
- 142,
- VL-CDR1:
- positions 23-35 of SEQ ID NO:
- 144,
- VL-CDR2:
- positions 51-57 of SEQ ID NO:
- 144, and
- VL-CDR3:
- positions 90-100 of SEQ ID NO:
- 144;
- (j2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 146,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 146,
- VH-CDR3:
- positions 99-110 of SEQ ID NO:
- 146,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 148,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 148, and
- VL-CDR3:
- positions 91-101 of SEQ ID NO:
- 148;
- (k2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 150,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 150,
- VH-CDR3:
- positions 99-113 of SEQ ID NO:
- 150,
- VL-CDR1:
- positions 23-36 of SEQ ID NO:
- 152,
- VL-CDR2:
- positions 52-58 of SEQ ID NO:
- 152, and
- VL-CDR3:
- positions 91-100 of SEQ ID NO:
- 152;
- (l2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 154,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 154,
- VH-CDR3:
- positions 99-110 of SEQ ID NO:
- 154,
- VL-CDR1:
- positions 24-39 of SEQ ID NO:
- 156,
- VL-CDR2:
- positions 55-61 of SEQ ID NO:
- 156, and
- VL-CDR3:
- positions 94-102 of SEQ ID NO:
- 156;
- (m2) VH-CDR1:
- positions 26-37 of SEQ ID NO:
- 158,
- VH-CDR2:
- positions 52-67 of SEQ ID NO:
- 158,
- VH-CDR3:
- positions 100-118 of SEQ ID NO:
- 158,
- VL-CDR1:
- positions 24-34 of SEQ ID NO:
- 160,
- VL-CDR2:
- positions 50-56 of SEQ ID NO:
- 160, and
- VL-CDR3:
- positions 89-97 of SEQ ID NO:
- 160;
- (n2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 162,
- VH-CDR2:
- positions 50-65 of SEQ ID NO:
- 162,
- VH-CDR3:
- positions 98-109 of SEQ ID NO:
- 162,
- VL-CDR1:
- positions 24-39 of SEQ ID NO:
- 164,
- VL-CDR2:
- positions 55-61 of SEQ ID NO:
- 164, and
- VL-CDR3:
- positions 94-102 of SEQ ID NO:
- 164;
- and
- (o2) VH-CDR1:
- positions 26-35 of SEQ ID NO:
- 166,
- VH-CDR2:
- positions 50-66 of SEQ ID NO:
- 166,
- VH-CDR3:
- positions 99-109 of SEQ ID NO:
- 166,
- VL-CDR1:
- positions 23-33 of SEQ ID NO:
- 168,
- VL-CDR2:
- positions 49-55 of SEQ ID NO:
- 168, and
- VL-CDR3:
- positions 88-98 of SEQ ID NO:
- 168;
- wherein the antibody or antigen binding fragment thereof comprises a heterologous polypeptide which is heterologous to at least one of the six CDRs, and wherein the remainder of the antibody or antigen binding fragment thereof is fused at its N- or C-terminus to the heterologous polypeptide;
- or
- (2) the VH-CDR1-3 and VL-CDR1-3 are identical to a group of six CDRs listed in any one of (a) to (o2) from (1), except for one conservative amino acid substitution in one of the six CDRs.
740 more elements
A monoclonal antibody or an antigen binding fragment thereof which is capable of binding to a polyomavirus and/or an antigen thereof, wherein the polyomavirus is JC virus (JCV) or BK virus (BKV), wherein the antibody or antigen binding fragment thereof comprises a VH and a VL, wherein the amino acid sequences of the VH and VL are selected from the group consisting of:
- (a) SEQ ID NO:
- 110 and SEQ ID NO:
- 112;
- (b) SEQ ID NO:
- 6 and SEQ ID NO:
- 8;
- (c) SEQ ID NO:
- 10 and SEQ ID NO:
- 12;
- (d) SEQ ID NO:
- 14 and SEQ ID NO:
- 16;
- (e) SEQ ID NO:
- 18 and SEQ ID NO:
- 20;
- (f) SEQ ID NO:
- 22 and SEQ ID NO:
- 24;
- (g) SEQ ID NO:
- 26 and SEQ ID NO:
- 28;
- (h) SEQ ID NO:
- 30 and SEQ ID NO:
- 32;
- (i) SEQ ID NO:
- 34 and SEQ ID NO:
- 36;
- (j) SEQ ID NO:
- 38 and SEQ ID NO:
- 40;
- (k) SEQ ID NO:
- 42 and SEQ ID NO:
- 44;
- (l) SEQ ID NO:
- 46 and SEQ ID NO:
- 48;
- (m) SEQ ID NO:
- 50 and SEQ ID NO:
- 52;
- (n) SEQ ID NO:
- 54 and SEQ ID NO:
- 56;
- (o) SEQ ID NO:
- 58 and SEQ ID NO:
- 60;
- (p) SEQ ID NO:
- 62 and SEQ ID NO:
- 64;
- (q) SEQ ID NO:
- 66 and SEQ ID NO:
- 68;
- (r) SEQ ID NO:
- 70 and SEQ ID NO:
- 72;
- (s) SEQ ID NO:
- 74 and SEQ ID NO:
- 76;
- (t) SEQ ID NO:
- 78 and SEQ ID NO:
- 80;
- (u) SEQ ID NO:
- 82 and SEQ ID NO:
- 84;
- (v) SEQ ID NO:
- 90 and SEQ ID NO:
- 92;
- (w) SEQ ID NO:
- 94 and SEQ ID NO:
- 96;
- (x) SEQ ID NO:
- 98 and SEQ ID NO:
- 100;
- (y) SEQ ID NO:
- 102 and SEQ ID NO:
- 104;
- (z) SEQ ID NO:
- 106 and SEQ ID NO:
- 108;
- (a2) SEQ ID NO:
- 2 and SEQ ID NO:
- 4;
- (b2) SEQ ID NO:
- 114 and SEQ ID NO:
- 116;
- (c2) SEQ ID NO:
- 118 and SEQ ID NO:
- 120;
- (d2) SEQ ID NO:
- 122 and SEQ ID NO:
- 124;
- (e2) SEQ ID NO:
- 126 and SEQ ID NO:
- 128;
- (f2) SEQ ID NO:
- 130 and SEQ ID NO:
- 132;
- (g2) SEQ ID NO:
- 134 and SEQ ID NO:
- 136;
- (h2) SEQ ID NO:
- 138 and SEQ ID NO:
- 140;
- (i2) SEQ ID NO:
- 142 and SEQ ID NO:
- 144;
- (j2) SEQ ID NO:
- 146 and SEQ ID NO:
- 148;
- (k2) SEQ ID NO:
- 150 and SEQ ID NO:
- 152;
- (12) SEQ ID NO:
- 154 and SEQ ID NO:
- 156;
- (m2) SEQ ID NO:
- 158 and SEQ ID NO:
- 160;
- (n2) SEQ ID NO:
- 162 and SEQ ID NO:
- 164;
- and
- (o2) SEQ ID NO:
- 166 and SEQ ID NO:
- 168,
- wherein the antibody or antigen binding fragment thereof comprises a heterologous polypeptide which is heterologous to the VH and/or VL, and wherein the remainder of the antibody or antigen binding fragment thereof is fused at its N- or C-terminus to the heterologous polypeptide.
122 more elements
Dependencies are inferred from the claim text.