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US 12,545,718 B2Granted
Anti-influenza B virus neuraminidase antibodies and uses thereof
AssigneeIcahn School of Medicine at Mount Sinai
InventorsFlorian Krammer, Teddy John Wohlbold, Adolfo Garcia-Sastre, Peter Palese
Life of this patent
Estimating the term…
Abstract
Provided herein are antibodies that bind to neuraminidase (NA) of different strains of influenza B virus, host cells for producing such antibodies, and kits comprising such antibodies. Also provided herein are compositions comprising antibodies that bind to NA of different strains of influenza B virus and methods of using such antibodies to diagnose, prevent or treat influenza virus disease.
Claims27
An isolated antibody that binds to an influenza B virus neuraminidase (NA), wherein the antibody comprises:
- a. (i) a variable heavy chain region complementarity determining region 1 (VHCDR1) comprising the amino acid sequence of SEQ ID NO:
- 3, (ii) a variable heavy chain region CDR2 (VHCDR2) comprising the amino acid sequence of SEQ ID NO:
- 4, (iii) a variable heavy chain region CDR3 (VHCDR3) comprising the amino acid sequence of SEQ ID NO:
- 5, (iv) a variable light chain region CDR1 (VLCDR1) comprising the amino acid sequence of SEQ ID NO:
- 6, (v) a variable light chain region CDR2 (VLCDR2) comprising the amino acid sequence of SEQ ID NO:
- 7, and (vi) a variable light chain region CDR3 (VLCDR3) comprising the amino acid sequence of SEQ ID NO:
- 8;
- b. (i) a variable heavy chain region that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 1, wherein the variable heavy chain region comprises a variable heavy chain region complementarity determining region (CDR1) comprising the amino acid sequence of SEQ ID NO:
- 3, a variable heavy chain region CDR2 comprising the amino acid sequence of SEQ ID NO:
- 4, and a variable heavy chain region CDR3 comprising the amino acid sequence of SEQ ID NO:
- 5;
- and (ii) a variable light chain region that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 2, wherein the variable light chain region comprises a variable light chain region CDR1 comprising the amino acid sequence of SEQ ID NO:
- 6, a variable light chain region CDR2 comprising the amino acid sequence of SEQ ID NO:
- 7, and a variable light chain region CDR3 comprising the amino acid sequence of SEQ ID NO:
- 8;
- c. (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO:
- 94, (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO:
- 95, (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO:
- 96, (iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO:
- 97, (v) a VLCDR2 comprising the amino acid sequence of SEQ ID NO:
- 98, and (vi) a VLCDR3 comprising the amino acid sequence of SEQ ID NO:
- 99;
- d. (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO:
- 100, (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO:
- 101, (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO:
- 102, (iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO:
- 103, (v) a VLCDR2 comprising the amino acid sequence of SEQ ID NO:
- 104, and (vi) a VLCDR3 comprising the amino acid sequence of SEQ ID NO:
- 105;
- e. (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO:
- 106, (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO:
- 107, (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO:
- 108, (iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO:
- 109, (v) a VLCDR2 comprising the amino acid sequence of SEQ ID NO:
- 110, and (vi) a VLCDR3 comprising the amino acid sequence of SEQ ID NO:
- 111;
- f. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 1, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 2;
- g. (i) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168, 169, 170, 171, 172, 173, 174 or 175, and (ii) a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178, 179, 177, 180, 181, 182, 183, or 184;
- h. (i) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178;
- (ii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 179;
- (iii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 177;
- (iv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 180;
- (v) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 169 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178;
- (vi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 169 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 179;
- (vii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 169 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 180;
- (viii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 170 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178;
- (ix) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 170 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 180;
- (x) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 171 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178;
- (xi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 171 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 179;
- (xii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 171 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 180;
- (xiii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 172 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 180;
- (xiv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 172 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 181;
- (xv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 181;
- (xvi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 182;
- (xvii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 183;
- (xviii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 168 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 184;
- (xix) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 169 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 177;
- (xx) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 169 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 181;
- (xxi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 169 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 182;
- (xxii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 169 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 183;
- (xxiii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 169 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 184;
- (xxiv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 170 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 177;
- (xxv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 170 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 179;
- (xxvi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 170 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 181;
- (xxvii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 170 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 182;
- (xxviii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 170 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 183;
- (xxix) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 170 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 184;
- (xxx) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 171 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 177;
- (xxxi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 171 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 181;
- (xxxii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 171 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 182;
- (xxxiii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 171 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 183;
- (xxxiv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 171 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 184;
- (xxxv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 172 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 177;
- (xxxvi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 172 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178;
- (xxxvii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 172 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 179;
- (xxxviii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 172 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 182;
- (xxxix) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 172 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 183;
- (xl) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 172 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 184;
- (xli) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 173 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 177;
- (xlii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 173 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178;
- (xliii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 173 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 179;
- (xliv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 173 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 180;
- (xlv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 173 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 181;
- (xlvi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 173 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 182;
- (xlvii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 173 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 183;
- (xlviii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 173 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 184;
- (xlix) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 174 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 177;
- (l) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 174 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178;
- (li) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 174 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 179;
- (lii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 174 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 180;
- (liii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 174 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 181;
- (liv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 174 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 182;
- (lv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 174 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 183;
- (lvi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 174 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 184;
- (lvii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 175 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 177;
- (lviii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 175 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 178;
- (lix) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 175 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 179;
- (lx) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 175 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 180;
- (lxi) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 175 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 181;
- (lxii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 175 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 182;
- (lxiii) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 175 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 183;
- or (lxiv) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 175 and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 184;
- i. (i) a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 185, 186, 187, 188, 189, 190, 191, 192, or 193, and (ii) a light chain comprising the amino acid sequence of SEQ ID NO:
- 194, 195, 196, 197, 198, 199, 200, 201, or 202;
- j. (i) VHCDR1 comprising the amino acid sequence of SEQ ID NO:
- 19, (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO:
- 20, (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO:
- 21, (iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO:
- 22, (v) a VLCDR2 comprising the amino acid sequence of SEQ ID NO:
- 23, and (vi) a VLCDR3 comprising the amino acid sequence of SEQ ID NO:
- 24;
- k. (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO:
- 112, (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO:
- 113, (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO:
- 114, (iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO:
- 115, (v) a VLCDR2 comprising the amino acid sequence of SEQ ID NO:
- 116, and (vi) a VLCDR3 comprising the amino acid sequence of SEQ ID NO:
- 117;
- l. (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO:
- 118, (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO:
- 119, (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO:
- 120, (iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO:
- 121, (v) a VLCDR2 comprising the amino acid sequence of SEQ ID NO:
- 122, and (vi) a VLCDR3 comprising the amino acid sequence of SEQ ID NO:
- 123;
- m. (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO:
- 124, (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO:
- 125, (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO:
- 126, (iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO:
- 127, (v) a VLCDR2 comprising the amino acid sequence of SEQ ID NO:
- 128, and (vi) a VLCDR3 comprising the amino acid sequence of SEQ ID NO:
- 129;
- n. (i) a variable heavy chain region that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 17, wherein the variable heavy chain region comprises a variable heavy chain region CDR1 comprising the amino acid sequence of SEQ ID NO:
- 19, a variable heavy chain region CDR2 comprising the amino acid sequence of SEQ ID NO:
- 20, and a variable heavy chain region CDR3 comprising the amino acid sequence of SEQ ID NO:
- 21;
- and (ii) a variable light chain region that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 18, wherein the variable light chain region comprises a variable light chain region CDR1 comprising the amino acid sequence of SEQ ID NO:
- 22, a variable light chain region CDR2 comprising the amino acid sequence of SEQ ID NO:
- 23, and a variable light chain region CDR3 comprising the amino acid sequence of SEQ ID NO:
- 24;
- o. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 17, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 18;
- p. (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO:
- 51, (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO:
- 52, (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO:
- 53, (iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO:
- 54, (v) a VLCDR2 comprising the amino acid sequence of SEQ ID NO:
- 55, and (vi) a VLCDR3 comprising the amino acid sequence of SEQ ID NO:
- 56;
- q. (i) a variable heavy chain region that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 49, wherein the variable heavy chain region comprises a variable heavy chain region CDR1 comprising the amino acid sequence of SEQ ID NO:
- 51, a variable heavy chain region CDR2 comprising the amino acid sequence of SEQ ID NO:
- 52, and a variable heavy chain region CDR3 comprising the amino acid sequence of SEQ ID NO:
- 53;
- and (ii) a variable light chain region that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 50, wherein the variable light chain region comprises a variable light chain region CDR1 comprising the amino acid sequence of SEQ ID NO:
- 54, a variable light chain region CDR2 comprising the amino acid sequence of SEQ ID NO:
- 55, and a variable light chain region CDR3 comprising the amino acid sequence of SEQ ID NO:
- 56;
- or
- r. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
- 49, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
- 50.
298 more elements
Dependencies are inferred from the claim text.