Neutralizing anti-influenza a antibodies and uses thereof

An antibody or binding fragment thereof according to according to any one of the preceding claims, wherein the antibody or fragment thereof includes a set of six CDRs:

• HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 in which the set of six CDRs is selected from the group consisting of:
• (a) HCDR1 of SEQ ID NO.:
• 3, HCDR2 of SEQ ID NO.:
• 4, HCDR3 of SEQ ID NO.:
• 5, LCDR1 of SEQ ID NO.:
• 8, LCDR2 of SEQ ID NO.:
• 9 and LCDR3 of SEQ ID NO.:
• 10;
• (b) HCDR1 of SEQ ID NO.:
• 13, HCDR2 of SEQ ID NO.:
• 14, HCDR3 of SEQ ID NO.:
• 15, LCDR1 of SEQ ID NO.:
• 18, LCDR2 of SEQ ID NO.:
• 19, LCDR3 of SEQ ID NO.:
• 20;
• (c) HCDR1 of SEQ ID NO.:
• 23, HCDR2 of SEQ ID NO.:
• 24, HCDR3 of SEQ ID NO.:
• 25, LCDR1 of SEQ ID NO.:
• 28, LCDR2 of SEQ ID NO.:
• 29 and LCDR3 of SEQ ID NO.:
• 30;
• (d) HCDR1 of SEQ ID NO.:
• 33, HCDR2 of SEQ ID NO.:
• 34, HCDR3 of SEQ ID NO.:
• 35, LCDR1 of SEQ ID NO.:
• 38, LCDR2 of SEQ ID NO.:
• 39 and LCDR3 of SEQ ID NO.:
• 40;
• (e) HCDR1 of SEQ ID NO.:
• 43, HCDR2 of SEQ ID NO.:
• 44, HCDR3 of SEQ ID NO.:
• 45, LCDR1 of SEQ ID NO.:
• 48, LCDR2 of SEQ ID NO.:
• 49 and LCDR3 of SEQ ID NO.:
• 50;
• (f) HCDR1 of SEQ ID NO.:
• 53, HCDR2 of SEQ ID NO.:
• 54, HCDR3 of SEQ ID NO.:
• 55, LCDR1 of SEQ ID NO.:
• 58, LCDR2 of SEQ ID NO.:
• 59 and LCDR3 of SEQ ID NO.:
• 60;
• (g) HCDR1 of SEQ ID NO.:
• 63, HCDR2 of SEQ ID NO.:
• 64, HCDR3 of SEQ ID NO.:
• 65, LCDR1 of SEQ ID NO.:
• 68, LCDR2 of SEQ ID NO.:
• 69 and LCDR3 of SEQ ID NO.:
• 70;
• (h) HCDR1 of SEQ ID NO.:
• 73, HCDR2 of SEQ ID NO.:
• 74, HCDR3 of SEQ ID NO.:
• 75, LCDR1 of SEQ ID NO.:
• 78, LCDR2 of SEQ ID NO.:
• 79 and LCDR3 of SEQ ID NO.:
• 80;
• (i) HCDR1 of SEQ ID NO.:
• 83, HCDR2 of SEQ ID NO.:
• 84, HCDR3 of SEQ ID NO.:
• 85, LCDR1 of SEQ ID NO.:
• 88, LCDR2 of SEQ ID NO.:
• 89, LCDR3 of SEQ ID NO.:
• 90;
• (j) HCDR1 of SEQ ID NO.:
• 93, HCDR2 of SEQ ID NO.:
• 94, HCDR3 of SEQ ID NO.:
• 95, LCDR1 of SEQ ID NO.:
• 98, LCDR2 of SEQ ID NO.:
• 99 and LCDR3 of SEQ ID NO.:
• 100;
• (k) HCDR1 of SEQ ID NO.:
• 103, HCDR2 of SEQ ID NO.:
• 104, HCDR3 of SEQ ID NO.:
• 105, LCDR1 of SEQ ID NO.:
• 108, LCDR2 of SEQ ID NO.:
• 109 and LCDR3 of SEQ ID NO.:
• 110;
• (l) HCDR1 of SEQ ID NO.:
• 113, HCDR2 of SEQ ID NO.:
• 114, HCDR3 of SEQ ID NO.:
• 115, LCDR1 of SEQ ID NO.:
• 118, LCDR2 of SEQ ID NO.:
• 119 and LCDR3 of SEQ ID NO.:
• 110;
• (m) HCDR1 of SEQ ID NO.:
• 123, HCDR2 of SEQ ID NO.:
• 124, HCDR3 of SEQ ID NO.:
• 125, LCDR1 of SEQ ID NO.:
• 128, LCDR2 of SEQ ID NO.:
• 129 and LCDR3 of SEQ ID NO.:
• 130;
• (n) HCDR1 of SEQ ID NO.:
• 133, HCDR2 of SEQ ID NO.:
• 134, HCDR3 of SEQ ID NO.:
• 135, LCDR1 of SEQ ID NO.:
• 138, LCDR2 of SEQ ID NO.:
• 139 and LCDR3 of SEQ ID NO.:
• 140;
• and
• (o) HCDR1 of SEQ ID NO.:
• 143, HCDR2 of SEQ ID NO.:
• 144, HCDR3 of SEQ ID NO.:
• 145, LCDR1 of SEQ ID NO.:
• 148, LCDR2 of SEQ ID NO.:
• 149 and LCDR3 of SEQ ID NO.:
• 150
• (p) a set of six CDRS according to any one of (a) to (o) comprising one or more amino acid substitutions, deletions or insertions;
• (q) a set of six CDRS according to any one of (a) to (p) comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 or 25 amino acid substitutions;
• (r) a set of six CDRs HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 according to any one of (a) to (q) comprising:
• (i) a HCDR1 having an amino acid sequence identical to or comprising 3 or fewer amino acid residue substitutions relative to SEQ ID NO:
• 3;
• (ii) a HCDR2 having an amino acid sequence identical to or comprising 5 or fewer amino acid residue substitutions relative to SEQ ID NO:4;
• (iii) a HCDR3 having an amino acid sequence identical to or comprising 6 or fewer amino acid residue substitutions relative to SEQ ID NO:5;
• (iv) a LCDR1 having an amino acid sequence identical to or comprising 5 or fewer amino acid residue substitutions and/or one deletion relative to SEQ ID NO:6;
• (v) a LCDR2 having an amino acid sequence identical to or comprising 5 or fewer amino acid residue substitutions relative to SEQ ID NO:7;
• and
• (vi) a LCDR3 having an amino acid sequence identical to or comprising 1 or fewer amino acid residue substitutions relative to SEQ ID NO:8;
• (s) a set of six CDRs HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 according to any one of (a) to (r) comprising:
• (i) a HCDR1 in which:
• Kabat residue 31 is S,
• Kabat residue 32 is N or Y,
• Kabat residue 33 is N, S, or R,
• Kabat residue 34 is A,
• Kabat residue 35 is V or T,
• Kabat residue 35A is W
• Kabat residue 35B is N;
• (ii) a HCDR2 in which:
• Kabat residue 50 is R,
• Kabat residue 51 is T,
• Kabat residue 52 is Y,
• Kabat residue 52A is Y,
• Kabat residue 53 is R,
• Kabat residue 54 is S,
• Kabat residue 55 is K or G,
• Kabat residue 56 is W,
• Kabat residue 57 is Y,
• Kabat residue 58 is N or Y,
• Kabat residue 59 is D,
• Kabat residue 60 is Y,
• Kabat residue 61 is A,
• Kabat residue 62 is E, V or d,
• Kabat residue 63 is S or F,
• Kabat residue 64 is V or L,
• Kabat residue 65 is K;
• (iii) a HCDR3 in which:
• Kabat residue 95 is S or G,
• Kabat residue 96 is G,
• Kabat residue 97 is H,
• Kabat residue 98 is I,
• Kabat residue 99 is T,
• Kabat residue 100 is V or E,
• Kabat residue 100A is F,
• Kabat residue 1006 is G,
• Kabat residue 100C is V or L,
• Kabat residue 100D is N,
• Kabat residue 100E is V or I,
• Kabat residue 100F is D,
• Kabat residue 1000 is A,
• Kabat residue 100F is F or Y,
• Kabat residue 101 is D,
• Kabat residue 102 is M, I or V;
• (iv) a LCDR1 in which:
• Kabat residue 24 is R,
• Kabat residue 25 is T, A or absent,
• Kabat residue 26 is S or A,
• Kabat residue 27 is Q,
• Kabat residue 28 is S or R,
• Kabat residue 29 is L,
• Kabat residue 30 is S, N or R
• Kabat residue 31 is S,
• Kabat residue 32 is Y,
• Kabat residue 33 is L, T or D,
• Kabat residue 34 is H;
• (v) a LCDR2 in which:
• Kabat residue 50 is A,
• Kabat residue 51 is A, T or S,
• Kabat residue 52 is S or T,
• Kabat residue 53 is S or T,
• Kabat residue 54 is L or R,
• Kabat residue 55 is Q, L or G,
• Kabat residue 56 is S, and,
• (vi) a LCDR3 in which:
• Kabat residue 89 is Q,
• Kabat residue 90 is Q or L,
• Kabat residue 91 is S,
• Kabat residue 92 is R, and
• Kabat residue 93 is T.

An antibody or binding fragment thereof according to any one of the preceding claims comprising a VH having at least 75% identity and/or a VL having at least 75% identity to a VH and/or VL selected from the group consisting of:

• (a) VH of SEQ ID NO.:
• 2 and VL of SEQ ID NO.:
• 7,
• (b) VH of SEQ ID NO.:
• 12 and VL of SEQ ID NO.:
• 17,
• (c) VH of SEQ ID NO.:
• 22 and VL of SEQ ID NO.:
• 27,
• (d) VH of SEQ ID NO.:
• 32 and VL of SEQ ID NO.:
• 37,
• (e) VH of SEQ ID NO.:
• 42 and VL of SEQ ID NO.:
• 47,
• (f) VH of SEQ ID NO.:
• 52 and VL of SEQ ID NO.:
• 57,
• (g) VH of SEQ ID NO.:
• 62 and VL of SEQ ID NO.:
• 67,
• (h) VH of SEQ ID NO.:
• 72 and VL of SEQ ID NO.:
• 77,
• (i) VH of SEQ ID NO.:
• 82 and VL of SEQ ID NO.:
• 87,
• (j) VH of SEQ ID NO.:
• 92 and VL of SEQ ID NO.:
• 97,
• (k) VH of SEQ ID NO.:
• 102 and VL of SEQ ID NO.:
• 107,
• (l) VH of SEQ ID NO.:
• 112 and VL of SEQ ID NO.:
• 117,
• (m) VH of SEQ ID NO.:
• 122 and VL of SEQ ID NO.:
• 127,
• (n) VH of SEQ ID NO.:
• 132 and VL of SEQ ID NO.:
• 137,
• (o) VH of SEQ ID NO.:
• 144 and VL of SEQ ID NO.:
• 147 and
• (p) VH of SEQ ID NO:
• 152 and VL of SEQ ID NO:
• 157.

An antibody or binding fragment thereof according to any one of the preceding claims comprising a VH and a VL selected from the group consisting of:

• (a) VH of SEQ ID NO.:
• 2 and VL of SEQ ID NO.:
• 7,
• (b) VH of SEQ ID NO.:
• 12 and VL of SEQ ID NO.:
• 17,
• (c) VH of SEQ ID NO.:
• 22 and VL of SEQ ID NO.:
• 27,
• (d) VH of SEQ ID NO.:
• 32 and VL of SEQ ID NO.:
• 37,
• (e) VH of SEQ ID NO.:
• 42 and VL of SEQ ID NO.:
• 47,
• (f) VH of SEQ ID NO.:
• 52 and VL of SEQ ID NO.:
• 57,
• (g) VH of SEQ ID NO.:
• 62 and VL of SEQ ID NO.:
• 67,
• (h) VH of SEQ ID NO.:
• 72 and VL of SEQ ID NO.:
• 77,
• (i) VH of SEQ ID NO.:
• 82 and VL of SEQ ID NO.:
• 87,
• (j) VH of SEQ ID NO.:
• 92 and VL of SEQ ID NO.:
• 97,
• (k) VH of SEQ ID NO.:
• 102 and VL of SEQ ID NO.:
• 107,
• (l) VH of SEQ ID NO.:
• 112 and VL of SEQ ID NO.:
• 117,
• (m) VH of SEQ ID NO.:
• 122 and VL of SEQ ID NO.:
• 127,
• (n) VH of SEQ ID NO.:
• 132 and VL of SEQ ID NO.:
• 137,
• (o) VH of SEQ ID NO.:
• 144 and VL of SEQ ID NO.:
• 147 and
• (p) VH of SEQ ID NO:
• 152 and VL of SEQ ID NO:
• 157.