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US 2026/0266820 A1Published application
Human antibodies targeting zika virus ns1, ns1 polypeptides and uses thereof
AssigneeIcahn School of Medicine at Mount Sinai
InventorsMark BAILEY, Peter PALESE, Gene TAN
Life of this patent
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Abstract
In one aspect, provided herein are antibodies that bind to Zika virus non-structural protein 1 (NS1) and compositions comprising the same. In a specific embodiment, such antibodies or compositions thereof may be used to passively immunize a subject against Zika virus. In another embodiment, such antibodies or compositions thereof may be used to diagnose a Zika virus infection. In another aspect, provided herein are recombinant NS1 polypeptides and compositions comprising the same that may be used to immunize a subject against Zika virus disease.
Claims34
A recombinant monoclonal antibody that specifically binds to a Zika virus NS1, wherein the antibody comprises:
- I. (a) (1) a variable heavy chain region (VH) complementarity determining region (CDR)1 comprising the amino acid sequence GFTVSSNY (SEQ ID NO:143), (2) a VH CDR2 comprising the amino acid sequence IYSGGST (SEQ ID NO:144), (3) a VH CDR3 comprising the amino acid sequence ARDRRGFDY (SEQ ID NO:145), ARWGGKRGGAFDI (SEQ ID NO:
- 146), ARLIAAAGDY (SEQ ID NO:147), or ARGPVQLERRPLGAFDI (SEQ ID NO:148), (4) a variable light chain region (VL) CDR1 comprising the amino acid sequence QSISSX, X is Y or H (SEQ ID NO:134), (5) a VL CDR2 comprising the amino acid sequence X1X2S, X1 is A or Q, X2 is A or D (SEQ ID NO:135), and (6) a VL CDR3 comprising the amino acid sequence QQX1YSTPX2T, X1 is T or S, X2 is L, Y, or W (SEQ ID NO:136);
- or
- (b) (1) a VH antibody binding region (ABR)1 comprising the amino acid sequence FTVSSNYMS (SEQ ID NO:149), (2) a VH ABR2 comprising the amino acid sequence WVSVIYSGGSTYYA (SEQ ID NO:150), (3) a VH ABR3 comprising the amino acid sequence ARDRRGFDY (SEQ ID NO:151), ARWGGKRGGAFDI (SEQ ID NO:152), ARLIAAAGDY (SEQ ID NO:153), or ARGPVQLERRPLGAFDI (SEQ ID NO:154), (4) a VL ABR1 comprising the amino acid sequence QSISSXILN, X1 is Y or H (SEQ ID NO:
- 137), (5) a VL ABR2 comprising the amino acid sequence XILIYAASSLQS, X1 is F or L (SEQ ID NO:138), and (6) a VL ABR3 comprising the amino acid sequence QQX1YSTPX2, X1 is T or S, X2 is L, Y or W (SEQ ID NO:139);
- II. (a) (1) a VH CDR1 comprising the amino acid sequence GFTVSSNY (SEQ ID NO:
- 17), (2) a VH CDR2 comprising the amino acid sequence IYSGGST (SEQ ID NO:
- 18), (3) a VH CDR3 comprising the amino acid sequence ARDRRGFDY (SEQ ID NO:
- 19), (4) a VL CDR1 comprising the amino acid sequence QSISSY (SEQ ID NO:
- 20), (5) a VL CDR2 comprising the amino acid sequence AAS (SEQ ID NO:
- 21), and (6) a VL CDR3 comprising the amino acid sequence QQTYSTPLT (SEQ ID NO:22);
- (b) (1) a VH CDR1 comprising the amino acid sequence GFTVSSNY (SEQ ID NO:
- 45), (2) a VH CDR2 comprising the amino acid sequence IYSGGST (SEQ ID NO:
- 46), (3) a VH CDR3 comprising the amino acid sequence ARWGGKRGGAFDI (SEQ ID NO:47), (4) a VL CDR1 comprising the amino acid sequence QSISSH (SEQ ID NO:
- 48), (5) a VL CDR 2 comprising the amino acid sequence AAS (SEQ ID NO:49), and (6) a VL CDR3 comprising the amino acid sequence QQSYSTPYT (SEQ ID NO:
- 50);
- (c) (1) a VH CDR1 comprising the amino acid sequence GFTVSSNY (SEQ ID NO:
- 73), (2) a VH CDR2 comprising the amino acid sequence IYSGGST (SEQ ID NO:
- 74), (3) a VH CDR3 comprising the amino acid sequence ARLIAAAGDY (SEQ ID NO:
- 75), (4) a VL CDR1 comprising the amino acid sequence QSISSY (SEQ ID NO:76), (5) a VL CDR2 comprising the amino acid sequence AAS (SEQ ID NO:77), and (6) a VL CDR3 comprising the amino acid sequence QQSYSTPWT (SEQ ID NO:78);
- (d) (1) a VH CDR1 comprising the amino acid sequence GFTVSSNY (SEQ ID NO:
- 101), (2) a VH CDR2 comprising the amino acid sequence IYSGGST (SEQ ID NO:
- 102), (3) a VH CDR3 comprising the amino acid sequence ARGPVQLERRPLGAFDI (SEQ ID NO:103), (4) a VL CDR1 comprising the amino acid sequence KLGDKY (SEQ ID NO:
- 104), (5) a VL CDR2 comprising the amino acid sequence QDS (SEQ ID NO:
- 105), and (6) a VL CDR3 comprising the amino acid sequence QAWDSSTVV (SEQ ID NO:106);
- III (a) (1) a VH antibody binding region (ABR)1 comprising the amino acid sequence FTVSSNYMS (SEQ ID NO:31), (2) a VH ABR2 comprising the amino acid sequence WVSVIYSGGSTYYA (SEQ ID NO:
- 32), (3) a VH ABR3 comprising the amino acid sequence ARDRRGFDY (SEQ ID NO:33), (4) a VL ABR1 comprising the amino acid sequence QSISSYLN (SEQ ID NO:34), (5) a VL ABR2 comprising the amino acid sequence LLIYAASSLQS (SEQ ID NO:
- 35), and (6) a VL ABR3 comprising the amino acid sequence QQTYSTPL (SEQ ID NO:
- 36);
- (b) (1) a VH ABR1 comprising the amino acid sequence FTVSSNYMS (SEQ ID NO:
- 59), (2) a VH ABR2 comprising the amino acid sequence WVSVIYSGGSTYYA (SEQ ID NO:
- 60), (3) a VH ABR3 comprising the amino acid sequence ARWGGKRGGAFDI (SEQ ID NO:61), (4) a VL ABR1 comprising the amino acid sequence QSISSHLN (SEQ ID NO:
- 62), (5) a VL ABR2 comprising the amino acid sequence FLIYAASSLQS (SEQ ID NO:
- 63), and (6) a VL ABR3 comprising the amino acid sequence QQSYSTPY (SEQ ID NO:64);
- (c) (1) a VH ABR1 comprising the amino acid sequence FTVSSNYMS (SEQ ID NO:
- 87), (2) a VH ABR2 comprising the amino acid sequence WVSVIYSGGSTYYA (SEQ ID NO:88), (3) a VH ABR3 comprising the amino acid sequence ARLIAAAGDY (SEQ ID NO:89), (4) a VL ABR1 comprising the amino acid sequence QSISSYLN (SEQ ID NO:
- 90), (5) a VL ABR2 comprising the amino acid sequence LLIYAASSLQS (SEQ ID NO:
- 91), and (6) a VL ABR3 comprising the amino acid sequence QQSYSTPW (SEQ ID NO:
- 92);
- or
- (d) (1) a VH ABR1 comprising the amino acid sequence FTVSSNYMS (SEQ ID NO:115), (2) a VH ABR2 comprising the amino acid sequence WVSVIYSGGSTYYA (SEQ ID NO:116), (3) a VH ABR3 comprising the amino acid sequence ARGPVQLERRPLGAFDI (SEQ ID NO:117), (4) a VL ABR1 comprising the amino acid sequence KLGDKYAC (SEQ ID NO:118), (5) a VL ABR2 comprising the amino acid sequence LVIYQDSKRPS (SEQ ID NO:119), and (6) a VL ABR3 comprising the amino acid sequence QAWDSSTV (SEQ ID NO:120);
- or
- IV. (a) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 9 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 10;
- (b) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 11 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 12;
- (c) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 13 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 14;
- (d) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 15 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 16;
- (e) a VH that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 9 and a VL that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 10;
- (f) a VH that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 11 and a VL that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 12;
- (g) a VH that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 13 and a VL that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 14;
- or
- (h) a VH is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 15 and a VL is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 16.
64 more elements
-14. (canceled)
(canceled)
(canceled)
(canceled)
(canceled)
A recombinant NS1 polypeptide comprising the amino acid sequence of a Zika virus NS1 and the amino acid sequence of a fragment of a Zika virus envelope protein, wherein the amino acid sequence of the fragment of the Zika virus envelope protein is at the N-terminus of the amino acid sequence of the Zika virus NS1.
-33. (canceled)
(canceled)
(canceled)
(canceled)
(canceled)
-45. (canceled)
-49. (canceled)
A recombinant monoclonal antibody that specifically binds to a Zika virus NS1, wherein the antibody comprises:
- (i) (a) a variable heavy chain region (VH) and human IgG1 constant regions encoded by the pFUESss-CHIg-hIgG1 vector, wherein the VH comprises the amino acid sequence encoded by the cDNA sequence of SEQ ID NO:
- 1;
- and
- (b) a variable light chain region (VL) and human kappa constant regions encoded by the pFUESss-CLIg-hK vector, wherein the VL comprises the amino acid sequence encoded by the cDNA sequence of SEQ ID NO:
- 2;
- (ii) (a) a variable heavy chain region (VH) and human IgG1 constant regions encoded by the pFUESss-CHIg-hIgG1 vector, wherein the VH comprises the amino acid sequence encoded by the cDNA sequence of SEQ ID NO:
- 3;
- and
- (b) a variable light chain region (VL) and human kappa constant regions encoded by the pFUESss-CLIg-hl2 vector, wherein the VL comprises the amino acid sequence encoded by the cDNA sequence of SEQ ID NO:
- 4;
- (iii) (a) a variable heavy chain region (VH) and human IgG1 constant regions encoded by the pFUESss-CHIg-hIgG1 vector, wherein the VH comprises the amino acid sequence encoded by the cDNA sequence of SEQ ID NO:
- 5;
- and
- (b) a variable light chain region (VL) and human kappa constant regions encoded by the pFUESss-CLIg-hK vector, wherein the VL comprises the amino acid sequence encoded by the cDNA sequence of SEQ ID NO:
- 6;
- or
- (iv) (a) a variable heavy chain region (VH) and human IgG1 constant regions encoded by the pFUESss-CHIg-hIgG1 vector, wherein the VH comprises the amino acid sequence encoded by the cDNA sequence of SEQ ID NO:
- 7;
- and
- (b) a variable light chain region (VL) and human lambda constant regions encoded by the pFUESss-CLIg-hK vector, wherein the VL comprises the amino acid sequence encoded by the cDNA sequence of SEQ ID NO:
- 8.
18 more elements
An expression vector comprising:
- (a) pFUESss-CHIg-hIgG1 vector containing the cDNA sequence of SEQ ID NO:
- 1;
- (b) pFUESss-CLIg-hK vector containing the cDNA sequence of SEQ ID NO:
- 2;
- (c) pFUESss-CHIg-hIgG1 vector containing the cDNA sequence of SEQ ID NO:
- 3;
- (d) pFUESss-CLIg-hl2 vector containing the cDNA sequence of SEQ ID NO:
- 4;
- (e) pFUESss-CHIg-hIgG1 vector containing the cDNA sequence of SEQ ID NO:
- 5;
- (f) pFUESss-CLIg-hK vector containing the cDNA sequence of SEQ ID NO:
- 6;
- (g) pFUESss-CHIg-hIgG1 vector containing the cDNA sequence of SEQ ID NO:
- 7;
- or
- (h) pFUESss-CLIg-hK vector containing the cDNA sequence of SEQ ID NO:
- 8.
14 more elements
HEK 293F cells expressing:
- (i) (a) pFUESss-CHIg-hIgG1 vector containing the cDNA sequence of SEQ ID NO:
- 1;
- and
- (b) pFUESss-CLIg-hK vector containing the cDNA sequence of SEQ ID NO:
- 2;
- (ii) (a) pFUESss-CHIg-hIgG1 vector containing the cDNA sequence of SEQ ID NO:
- 3;
- and
- (b) pFUESss-CLIg-hl2 vector containing the cDNA sequence of SEQ ID NO:
- 4;
- (iii) (a) pFUESss-CHIg-hIgG1 vector containing the cDNA sequence of SEQ ID NO:
- 5;
- and
- (b) pFUESss-CLIg-hK vector containing the cDNA sequence of SEQ ID NO:
- 6;
- or
- (iv) (a) pFUESss-CHIg-hIgG1 vector containing the cDNA sequence of SEQ ID NO:
- 7;
- and
- (b) pFUESss-CLIg-hK vector containing the cDNA sequence of SEQ ID NO:
- 8.
18 more elements
Dependencies are inferred from the claim text.