US2018094047A1PendingUtilityA1
Anti-pre-s1 hbv antibodies
Est. expiryMay 22, 2035(~8.8 yrs left)· nominal 20-yr term from priority
C07K 2317/92C07K 2317/55C07K 2317/732C07K 16/082C07K 2317/622C07K 2317/56C07K 2317/76C07K 2317/34A61P 31/20C07K 2317/33C07K 2317/21A61K 2039/505C07K 2317/565Y02A50/30
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Claims
Abstract
Provided are human antibodies that specifically bind to HBV Pre-S1 domain ligand and inhibit HBV or HDV infection, antibodies binding to a set of amino acid residues that are critical for viral receptor engagement, and uses of these antibodies to prevent, or treat or diagnose HBV or HDV infection.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . An antibody antigen binding domain which specifically binds HBV Pre-S1, and comprises complementarity determining region (CDR) 1, CDR2 and CDR3, in a combination selected from (a)-(r) as follows, wherein the antibody (Ab), heavy chain (HC) or light chain (LC) and CDR nomenclature system (Kabat, IMGT or composite) from which the CDR combinations derive are shown in the first column, and residues in bold text are Kabat system, and residues underlined are IMGT system:
HCDRs of unique HBV Pre-S1 specific antibodies
MAbs
CDR1
CDR2
CDR3
m36-HC
GFTFD DYA
MH
G
ISWNSGSI
GYADSVKG
AK TSYGGAFDI
K: SEQ ID NO: 59,
K: SEQ ID NO: 60
K: SEQ ID NO: 61,
res. 6-10
res. 3-11
I: SEQ ID NO: 59,
I: SEQ ID NO: 60,
I: SEQ ID NO: 61
res. 1-8
res. 2-9
C: SEQ ID NO: 59
C: SEQ ID NO: 60
C: SEQ ID NO: 61
m36-LC
SGN
TSNIGSYY
AY
DNN
QRPS
ATWDDSLNGPV
K: SEQ ID NO: 62
K: SEQ ID NO: 63
K: SEQ ID NO: 64
I: SEQ ID NO: 62,
I: SEQ ID NO: 63,
I: SEQ ID NO: 64
res. 4-11
res. 1-3
C: SEQ ID NO: 62
C: SEQ ID NO: 63
C: SEQ ID NO: 64
71-HC
GYTT GYY
IH
RINPNSGGTN
AR EGRGGMDV
K: SEQ ID NO: 65,
K: SEQ ID NO: 66
K: SEQ ID NO: 67,
res. 5-9
res. 3-10
I: SEQ ID NO: 65,
I: SEQ ID NO: 66
I: SEQ ID NO: 67
res. 1-7
C: SEQ ID NO: 65
C: SEQ ID NO: 66
C: SEQ ID NO: 67
71-LC
RSSQSLLHSNGY NY
LGSNRAS
MQGLQPPIT
K: SEQ ID NO: 68,
K: SEQ ID NO: 69
K: SEQ ID NO: 70
res. 1-12
I: SEQ ID NO: 68,
I: SEQ ID NO: 69
I: SEQ ID NO: 70
res. 4-14
C: SEQ ID NO: 68
C: SEQ ID NO: 69
C: SEQ ID NO: 70
76-HC
GFTFS SYA
MH
V
ISYDGSNK
YYADSVKG
AS GAFDI
K: SEQ ID NO: 71,
K: SEQ ID NO: 72
K: SEQ ID NO: 73,
res. 6-10
res. 3-7
I: SEQ ID NO: 71,
I: SEQ ID NO: 72,
I: SEQ ID NO: 73
res. 1-8
res. 2-9
C: SEQ ID NO: 71
C: SEQ ID NO: 72
C: SEQ ID NO: 73
76-LC
RSS
HSLVYSDGNTY
LS
KVS
NRDF
MQGTHWPGT
K: SEQ ID NO: 74
K: SEQ ID NO: 75
K: SEQ ID NO: 76
I: SEQ ID NO: 74,
I: SEQ ID NO: 75,
I: SEQ ID NO: 76
res. 4-14
res. 1-3
C: SEQ ID NO: 74
C: SEQ ID NO: 75
C: SEQ ID NO: 76
T47-HC
GDSVS SNSVA
WN
R
TYYRSKWYN
DYAVSVKS
AR ADGSRGGGYDQ
K: SEQ ID NO: 77,
K: SEQ ID NO: 78
K: SEQ ID NO: 79,
res. 6-12
res. 3-13
I: SEQ ID NO: 77,
I: SEQ ID NO: 78,
I: SEQ ID NO: 79
res. 1-10
res. 2-10
C: SEQ ID NO: 77
C: SEQ ID NO: 78
C: SEQ ID NO: 79
T47-LC
KSS
QSILYRSNNKNY
LA
WAS
TRES
QQYYTTPQ
T
K: SEQ ID NO: 80
K: SEQ ID NO: 81
K: SEQ ID NO: 82
I: SEQ ID NO: 80,
I: SEQ ID NO: 81,
I: SEQ ID NO: 82,
res. 4-15
res. 1-3
res. 1-8
C: SEQ ID NO: 80
C: SEQ ID NO: 81
C: SEQ ID NO: 82
m1Q-HC
GFTFS SYA
MH
V
ISYDGSNK
YYVDSVKG
AR STYGMDV
K: SEQ ID NO: 83,
K: SEQ ID NO: 84
K: SEQ ID NO: 85,
res. 6-10
res. 3-9
I: SEQ ID NO: 83,
I: SEQ ID NO: 84,
I: SEQ ID NO: 85
res. 1-8
res. 2-9
C: SEQ ID NO: 83
C: SEQ ID NO: 84
C: SEQ ID NO: 85
m1Q-LC
RSS
QSLVHSDGNTY
LN
KVS
NRDS
MQGTHWWT
K: SEQ ID NO: 86
K: SEQ ID NO: 87
K: SEQ ID NO: 88
I: SEQ ID NO: 86,
I: SEQ ID NO: 87,
I: SEQ ID NO: 88
res. 4-14
res. 1-3
C: SEQ ID NO: 86
C: SEQ ID NO: 87
C: SEQ ID NO: 88
2H5-HC
GDSVS SKSAA
WN
R
TYYRSKWHN
DYAVS
AR GQMGALDV
K: SEQ ID NO: 89,
K: SEQ ID NO: 90
K: SEQ ID NO: 91,
res. 6-12
res. 3-10
I: SEQ ID NO: 89,
I: SEQ ID NO: 90,
I: SEQ ID NO: 91
res. 1-10
res. 3-10
C: SEQ ID NO: 89
C: SEQ ID NO: 90
C: SEQ ID NO: 91
2H5-LC
SGS
SSNIGSYY
VYWY
GNN
QRPS
QSYDSSLSGVI
K: SEQ ID NO: 92
K: SEQ ID NO: 93
K: SEQ ID NO: 94
I: SEQ ID NO: 92,
I: SEQ ID NO: 93,
I: SEQ ID NO: 94
res. 4-11
res. 1-3
C: SEQ ID NO: 92
C: SEQ ID NO: 93
C: SEQ ID NO: 94
m150-HC
GFTFS SYAMH
V
ISYDGSNK
YYADSVKG
AR LVAGRSAFDI
K: SEQ ID NO: 95,
K: SEQ ID NO: 96
K: SEQ ID NO: 97,
res. 6-10
res. 3-12
I: SEQ ID NO: 95,
I: SEQ ID NO: 96,
I: SEQ ID NO: 97
res. 1-8
res. 2-9
C: SEQ ID NO: 95
C: SEQ ID NO: 96
C: SEQ ID NO: 97
m150-LC
RAS
QSVSSN
LA
GAS
TRAT
QQYNNWPPIT
K: SEQ ID NO: 98
K: SEQ ID NO: 99
K: SEQ ID NO: 100
I: SEQ ID NO: 98,
I: SEQ ID NO: 99,
I: SEQ ID NO: 100
res. 4-9
res. 1-3
C: SEQ ID NO: 98
C: SEQ ID NO: 99
C: SEQ ID NO: 100
HCDRs of antibodies derived from 2H5 VH-chain shuffled libraries
MAbs
HCDR1
HCDR2
HCDR3
#4 VH
GDSVS SKSVT
WN
R
TYYRSKWFN
DYAVS
AR AKMGGMDV
K: SEQ ID NO: 101,
K: SEQ ID NO: 102
K: SEQ ID NO: 103,
res 6-12
res 3-10
I: SEQ ID NO: 101,
I: SEQ ID NO: 102,
I: SEQ ID NO: 103
res. 1-10
res. 2-10
C: SEQ ID NO: 101
C: SEQ ID NO: 102
C: SEQ ID NO: 103
#31 VH
GDSVS SNSAA
WN
R
TYYRSKWYN
DYAVS
TR QSWHGMEV
K: SEQ ID NO: 104,
K: SEQ ID NO: 105
K: SEQ ID NO: 106,
res 6-12
res 3-10
I: SEQ ID NO: 104,
I: SEQ ID NO: 105,
I: SEQ ID NO: 106
res. 1-10
res. 2-10
C: SEQ ID NO: 104
C: SEQ ID NO: 105
C: SEQ ID NO: 106
#32 VH
GDSVS SNSAA
WN
R
TYYRSKWYN
DYAVS
AR SIATGTDY
K: SEQ ID NO: 107,
K: SEQ ID NO: 108
K: SEQ ID NO: 109,
res 6-12
res 3-10
I: SEQ ID NO: 107,
I: SEQ ID NO: 108,
I: SEQ ID NO: 109
res. 1-10
res. 2-10
C: SEQ ID NO: 107
C: SEQ ID NO: 108
C: SEQ ID NO: 109
#69 VH
GDSVS SSRAT
WN
R
TYYRSKWFN
DYAVS
AR AKMGGMDV
K: SEQ ID NO: 110,
K: SEQ ID NO: 111
K: SEQ ID NO: 112,
res 6-12
res 3-10
I: SEQ ID NO: 110,
I: SEQ ID NO: 111,
I: SEQ ID NO: 112
res. 1-10
res. 2-10
C: SEQ ID NO: 110
C: SEQ ID NO: 111
C: SEQ ID NO: 112
A14 VH
GDSVS SNSAA
WN
R
TYYRSKWYN
DYAVS
AR GTRWGMDV
K: SEQ ID NO: 113,
K: SEQ ID NO: 114
K: SEQ ID NO: 115,
res 6-12
res 3-10
I: SEQ ID NO: 113,
I: SEQ ID NO: 114,
I: SEQ ID NO: 115
res. 1-10
res. 2-10
C: SEQ ID NO: 113
C: SEQ ID NO: 114
C: SEQ ID NO: 115
A21 VH
GDSVS SNSAA
WN
R
TYYRSKWYN
DYAVS
AR AKVYGVDV
K: SEQ ID NO: 116,
K: SEQ ID NO: 117
K: SEQ ID NO: 118,
res 6-12
res 3-10
I: SEQ ID NO: 116,
I: SEQ ID NO: 117,
I: SEQ ID NO: 118
res. 1-10
res. 2-10
C: SEQ ID NO: 116
C: SEQ ID NO: 117
C: SEQ ID NO: 118
B103 VH
GDSVS SKSAT
WN
R
TYYRSRWFN
DYAVS
AR GNMGAMDV
K: SEQ ID NO: 119,
K: SEQ ID NO: 120
K: SEQ ID NO: 121,
res 6-12
res 3-10
I: SEQ ID NO: 119,
I: SEQ ID NO: 120,
I: SEQ ID NO: 121
res. 1-10
res. 2-10
C: SEQ ID NO: 119
C: SEQ ID NO: 120
C: SEQ ID NO: 121
B129 VH
GDRVS SNRAA
WN
R
TYYRSQWYN
DYAVS
AR GTAMG - DA
K: SEQ ID NO: 122,
K: SEQ ID NO: 123
K: SEQ ID NO: 124,
res 6-12
res 3-9
I: SEQ ID NO: 122,
I: SEQ ID NO: 123,
I: SEQ ID NO: 124
res. 1-10
res. 2-10
C: SEQ ID NO: 122
C: SEQ ID NO: 123
C: SEQ ID NO: 124
B139 VH
GDSVS SNSAA
WN
R
TYYRSKWYN
DYAVS
AR QASNGFDI
K: SEQ ID NO: 125,
K: SEQ ID NO: 126
K: SEQ ID NO: 127,
res 6-12
res 3-10
I: SEQ ID NO: 125,
I: SEQ ID NO: 126,
I: SEQ ID NO: 127
res. 1-10
res. 2-10
C: SEQ ID NO: 125
C: SEQ ID NO: 126
C: SEQ ID NO: 127
B172 VH
GDSVS SNSAA
WN
R
TYYRSKWYN
DYAVS
AR QGTTGFDY
K: SEQ ID NO: 128,
K: SEQ ID NO: 129
K: SEQ ID NO: 130,
res 6-12
res 3-10
I: SEQ ID NO: 128,
I: SEQ ID NO: 129,
I: SEQ ID NO: 130
res. 1-10
res. 2-10
C: SEQ ID NO: 128
C: SEQ ID NO: 129
C: SEQ ID NO: 130
HCDRs of antibodies derived from A14 VL-chain shuffled libraries
MAbs
LCDR1
HCDR2
HCDR3
#8 VL
SGS
SSNIGNYY
VSWY
DNA
KRPS
QSYDNSLSGLV
K: SEQ ID NO: 131
K: SEQ ID NO: 132
K: SEQ ID NO: 133
I: SEQ ID NO: 131,
I: SEQ ID NO: 132,
I: SEQ ID NO: 133
res. 4-11
res. 1-3
C: SEQ ID NO: 131
C: SEQ ID NO: 132
C: SEQ ID NO: 133
#20 VL
SGT
SSNIGSKY
VYWY
TND
QRPS
QSYDSSLRAVV
K: SEQ ID NO: 134
K: SEQ ID NO: 135
K: SEQ ID NO: 136
I: SEQ ID NO: 134,
I: SEQ ID NO: 135,
I: SEQ ID NO: 136
res. 4-11
res. 1-3
C: SEQ ID NO: 134
C: SEQ ID NO: 135
C: SEQ ID NO: 136
#20-m1 VL
SGT
SSNIGSFY
VYWY
TND
QRPS
QSYDSSLRAVV
K: SEQ ID NO: 137
K: SEQ ID NO: 138
K: SEQ ID NO: 139
I: SEQ ID NO: 137,
I: SEQ ID NO: 138,
I: SEQ ID NO: 139
res. 4-11
res. 1-3
C: SEQ ID NO: 137
C: SEQ ID NO: 138
C: SEQ ID NO: 139
#20-m2 VL
SGT
SSNIGSFY
VYWY
TND
QRPS
QSYDSSLRAVV
K: SEQ ID NO: 140
K: SEQ ID NO: 141
K: SEQ ID NO: 142
I: SEQ ID NO: 140,
I: SEQ ID NO: 141,
I: SEQ ID NO: 142
res. 4-11
res. 1-3
C: SEQ ID NO: 140
C: SEQ ID NO: 141
C: SEQ ID NO: 142
#20-m3 VL
SGT
SSNIGSYY
VYWY
TND
QRPS
QSYDSSLRAVV .
K: SEQ ID NO: 143
K: SEQ ID NO: 144
K: SEQ ID NO: 145
I: SEQ ID NO: 143,
I: SEQ ID NO: 144,
I: SEQ ID NO: 145
res. 4-11
res. 1-3
C: SEQ ID NO: 143
C: SEQ ID NO: 144
C: SEQ ID NO: 145.
2 . An antibody antigen binding domain according to claim 1 comprising a heavy chain variable region (Vh) comprising a CDR1, CDR2 and CDR3 combination and a light chain variable region (Vl) comprising a CDR1, CDR2 and CDR3 combination, selected from:
m36, 71, 76, T47, m1Q, 2H5, m150; and
4, 31, 32, 69, A14, A21, B103, B129, B139, B172; and
8, 20, 20-m1, 20-m2, 20-m3.
3 . An antibody antigen binding domain according to claim 1 comprising a heavy chain variable region (Vh) or a light chain variable region (VD, selected from:
m36, 71, 76, T47, m1Q, 2H5, m150; and
4, 31, 32, 69, A14, A21, B103, B129, B139, B172; and
8, 20, 20-m1, 20-m2, 20-m3.
4 . An antibody antigen binding domain according to claim 1 comprising a heavy chain variable region (Vh) and a light chain variable region (Vl), selected from
m36, 71, 76, T47, m1Q, 2H5, m150; and
4, 31, 32, 69, A14, A21, B103, B129, B139, B172; and
8, 20, 20-m1, 20-m2, 20-m3.
5 . An antibody antigen binding domain according to any of claims 1 - 4 which specifically binds aa11-28 or aa19-25 of pre-S1.
6 . A monoclonal IgG antibody comprising an antibody antigen binding domain according to any of claims 1 - 5 .
7 . A method of using an antibody antigen binding domain according to any of claims 1 - 5 to treat HBV or HDV infection or to induce antibody-dependent cell-mediated cytotoxicity (ADCC), comprising the step of administering the domain to a person determined to have HBV or HDV infection, to have been exposed to HBV or HDV, to be at high risk for HBV or HDV exposure or infection, to be in need of Pre-S1 domain antagonism, or to be otherwise in need thereof.
9 . An expression vector encoding an antibody antigen binding domain according to any of claims 1 - 5 .
10 . A cultured cell expressing an antibody antigen binding domain according to any of claims 1 - 5 .Join the waitlist — get patent alerts
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