Antibody to Epstein Barr virus and uses thereof
A recombinant, humanized antibody or antibody fragment that is capable of at least partly preventing or inhibiting Epstein Barr Virus gp350 binding to a human cell. The antibody may be useful for passively immunizing humans against Epstein Barr Virus and/or treating or preventing Epstein Barr Virus-associated diseases, disorders or conditions. The antibody or antibody fragment may also be used to detect Epstein Barr Virus.
1 . A recombinant, human or humanized antibody or antibody fragment that is capable of at least partly reducing or inhibiting Epstein Barr Virus (EBV) gp350 binding to a human cell, which comprises six complementarity determining regions (CDR)s comprising a HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 selected from:
Clone
CDR
SEQ ID NO:
B8
HCDR1
1 (Chothia), 37 (AbM), 73
(Kabat), 109
HCDR2
2 (Chothia), 38 (AbM), 74
(Kabat), 110
HCDR3
3 (Chothia), 39 (AbM), 75
(Kabat), 111
LCDR1
19 (Chothia), 55 (AbM), 91
(Kabat), 127
LCDR2
20 (Chothia), 56 (AbM), 92
(Kabat), 128
LCDR3
21 (Chothia), 57 (AbM), 93
(Kabat), 129; or
A11
HCDR1
4 (Chothia), 40 (AbM), 76
(Kabat), 112
HCDR2
5 (Chothia), 41 (AbM), 77
(Kabat), 113
HCDR3
6 (Chothia), 42 (AbM), 78
(Kabat), 114
LCDR1
22 (Chothia), 58 (AbM), 94
(Kabat), 130
LCDR2
23 (Chothia), 59 (AbM), 95
(Kabat), 131
LCDR3
24 (Chothia), 60 (AbM), 96
(Kabat), 132 (Contact)
E10
HCDR1
7 (Chothia), 43 (AbM), 79
(Kabat), 115 (Contact)
HCDR2
8 (Chothia), 44 (AbM), 80
(Kabat), 116 (Contact)
HCDR3
9 (Chothia), 45 (AbM), 81
(Kabat), 117 (Contact)
LCDR1
25 (Chothia), 61 (AbM), 97
(Kabat), 133 (Contact)
LCDR2
26 (Chothia), 62 (AbM), 98
(Kabat), 134 (Contact)
LCDR3
27 (Chothia), 63 (AbM), 99
(Kabat), 135 (Contact)
B7
HCDR1
10 (Chothia), 46 (AbM), 82
(Kabat), 118 (Contact)
HCDR2
11 (Chothia), 47 (AbM), 83
(Kabat), 119 (Contact)
HCDR3
12 (Chothia), 48 (AbM), 84
(Kabat), 120 (Contact)
LCDR1
28 (Chothia), 64 (AbM), 100
(Kabat), 136 (Contact)
LCDR2
29 (Chothia), 65 (AbM), 101
(Kabat), 137 (Contact)
LCDR3
30 (Chothia), 66 (AbM), 102
(Kabat), 138 (Contact)
D7
HCDR1
13 (Chothia), 49 (AbM), 85
(Kabat), 121 (Contact)
HCDR2
14 (Chothia), 50 (AbM), 86
(Kabat), 122 (Contact)
HCDR3
15 (Chothia), 51 (AbM), 87
(Kabat), 123 (Contact)
LCDR1
31 (Chothia), 67 (AbM), 103
(Kabat), 139 (Contact)
LCDR2
32 (Chothia), 68 (AbM), 104
(Kabat), 140 (Contact)
LCDR3
33 (Chothia), 69 (AbM), 105
(Kabat), 141 (Contact)
C10
HCDR1
16 (Chothia), 52 (AbM), 88
(Kabat), 124 (Contact)
HCDR2
17 (Chothia), 53 (AbM), 89
(Kabat), 125 (Contact)
HCDR3
18 (Chothia), 54 (AbM), 90
(Kabat), 126 (Contact)
LCDR1
34 (Chothia), 70 (AbM), 106
(Kabat), 142 (Contact)
LCDR2
35 (Chothia), 71 (AbM), 107
(Kabat), 143 (Contact)
LCDR3
36 (Chothia), 72 (AbM), 108,
144 (Contact).
2 . The recombinant human or humanized antibody or antibody fragment of claim 1 , produced by phage display wherein the phage comprise one or more nucleotide sequences of human origin encoding one or more amino acid sequence of the human or humanized antibody or antibody fragment.
3 . The recombinant human or humanized antibody or antibody fragment of claim 1 , which comprises, consists essentially of or consists of an amino acid sequence set forth in any one of SEQ ID NOS: 145-156, or an amino acid sequence at least 90% identical thereto.
4 . The recombinant, human or humanized antibody or antibody fragment of claim 1 , further comprising a human IgG1 constant region amino acid sequence.
5 . An antibody or antibody fragment comprising a heavy chain (VH) variable region sequence and a light chain (VL) variable region sequence selected from:
Clone
Chain
SEQ ID NO:
B8
VH
145
VL
151
A11
VH
146
VL
152
E10
VH
147
VL
153
B7
VH
148
VL
154
D7
VH
149
VL
155
C10
VH
150
VL
156
wherein the VH variable region sequence according to any one of SEQ ID NOs: 145-150 has an amino acid sequence at least 90% identical thereto, and wherein the light chain (VL) variable region sequence according to any one of SEQ ID NOS: 151-156 or an amino acid sequence at least 90% identical thereto; wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 animo acid sequences are selected from:
Clone
CDR
SEQ ID NO:
B8
HCDR1
1 (Chothia), 37 (AbM), 73
(Kabat), 109
HCDR2
2 (Chothia), 38 (AbM), 74
(Kabat), 110
HCDR3
3 (Chothia), 39 (AbM), 75
(Kabat), 111
LCDR1
19 (Chothia), 55 (AbM), 91
(Kabat), 127
LCDR2
20 (Chothia), 56 (AbM), 92
(Kabat), 128
LCDR3
21 (Chothia), 57 (AbM), 93
(Kabat), 129; or
A11
HCDR1
4 (Chothia), 40 (AbM), 76
(Kabat), 112
HCDR2
5 (Chothia), 41 (AbM), 77
(Kabat), 113
HCDR3
6 (Chothia), 42 (AbM), 78
(Kabat), 114
LCDR1
22 (Chothia), 58 (AbM), 94
(Kabat), 130
LCDR2
23 (Chothia), 59 (AbM), 95
(Kabat), 131
LCDR3
24 (Chothia), 60 (AbM), 96
(Kabat), 132 (Contact)
E10
HCDR1
7 (Chothia), 43 (AbM), 79
(Kabat), 115 (Contact)
HCDR2
8 (Chothia), 44 (AbM), 80
(Kabat), 116 (Contact)
HCDR3
9 (Chothia), 45 (AbM), 81
(Kabat), 117 (Contact)
LCDR1
25 (Chothia), 61 (AbM), 97
(Kabat), 133 (Contact)
LCDR2
26 (Chothia), 62 (AbM), 98
(Kabat), 134 (Contact)
LCDR3
27 (Chothia), 63 (AbM), 99
(Kabat), 135 (Contact)
B7
HCDR1
10 (Chothia), 46 (AbM), 82
(Kabat), 118 (Contact)
HCDR2
11 (Chothia), 47 (AbM), 83
(Kabat), 119 (Contact)
HCDR3
12 (Chothia), 48 (AbM), 84
(Kabat), 120 (Contact)
LCDR1
28 (Chothia), 64 (AbM), 100
(Kabat), 136 (Contact)
LCDR2
29 (Chothia), 65 (AbM), 101
(Kabat), 137 (Contact)
LCDR3
30 (Chothia), 66 (AbM), 102
(Kabat), 138 (Contact)
D7
HCDR1
13 (Chothia), 49 (AbM), 85
(Kabat), 121 (Contact)
HCDR2
14 (Chothia), 50 (AbM), 86
(Kabat), 122 (Contact)
HCDR3
15 (Chothia), 51 (AbM), 87
(Kabat), 123 (Contact)
LCDR1
31 (Chothia), 67 (AbM), 103
(Kabat), 139 (Contact)
LCDR2
32 (Chothia), 68 (AbM), 104
(Kabat), 140 (Contact)
LCDR3
33 (Chothia), 69 (AbM), 105
(Kabat), 141 (Contact)
C10
HCDR1
16 (Chothia), 52 (AbM), 88
(Kabat), 124 (Contact)
HCDR2
17 (Chothia), 53 (AbM), 89
(Kabat), 125 (Contact)
HCDR3
18 (Chothia), 54 (AbM), 90
(Kabat), 126 (Contact)
LCDR1
34 (Chothia), 70 (AbM), 106
(Kabat), 142 (Contact)
LCDR2
35 (Chothia), 71 (AbM), 107
(Kabat), 143 (Contact)
LCDR3
36 (Chothia), 72 (AbM), 108,
144 (Contact).
6 . The antibody or antibody fragment of claim 5 , wherein the VH sequence consists essentially of or consists of an amino acid sequence set forth in any one of SEQ ID NOS: 145-150, and the VL sequence consists essentially of or consists of an amino acid sequence set forth in any one of SEQ ID NOS: 151-156.
7 . The antibody or antibody fragment of claim 5 , produced by phage display wherein the phage comprise one or more nucleotide sequences of human origin encoding one or more amino acid sequences of the human or humanized antibody or antibody fragment.
8 . The antibody or antibody fragment according to claim 5 , which is capable of at least partly preventing or inhibiting EBV gp350 binding to a human cell.
9 . An isolated nucleic acid encoding a recombinant, human or humanized antibody or antibody fragment according to claim 1 .
10 . A genetic construct comprising the isolated nucleic acid of claim 9 .
11 . A host cell comprising the genetic construct of claim 10 .
12 . A composition comprising a recombinant, human or humanized antibody or antibody fragment according to claim 1 , and a pharmaceutically acceptable carrier diluent or excipient.
13 . A method of treating an EBV infection in a human, said method including the step of administering a composition comprising a recombinant, human or humanized antibody or antibody fragment according to claim 1 to the human to thereby treat an EBV infection in the human.
14 . A method of at least partly inhibiting EBV gp350 binding to a human cell, said method including the step of administering a recombinant, human humanized antibody or antibody fragment according to claim 1 to the human to thereby at least partly inhibit EBV gp350 binding to a human cell.
15 . A method of detecting EBVgp350 or a cell expressing EBVgp350, said method including the step of forming a complex between a recombinant, human or humanized antibody or antibody fragment according to claim 1 and EBV gp350 to thereby detect EBVgp350 or the cell expressing EBVgp350, wherein the antibody or antibody fragment is labeled.