US 11,767,358 B2 · Human antibodies to Bet v 1 and methods of use thereof

Abstract

Provided herein are antibodies that bind Fagales allergens, Fagales related allergens, birch pollen, or Bet v 1, compositions comprising the antibodies, nucleic acids encoding the antibodies, and methods of using the antibodies. According to certain embodiments, the antibodies are fully human monoclonal antibodies that bind to Bet v 1. The antibodies are useful for binding Bet v 1 in vivo, thus preventing binding of the allergen to pre-formed IgE on the surface of mast cells or basophils. In doing so, the antibodies act to prevent the release of histamine and other inflammatory mediators from mast cells and/or basophils, thus ameliorating the untoward response to the Fagales allergens in sensitized individuals.

A method of preventing or reducing mast cell degranulation or blocking basophil activation associated with natural Bet v 1, Betula pendula birch pollen extract (BPE), Betula nigra BPE, or Betula populifolia BPE sensitization, the method comprising administering to a patient in need thereof one or more human monoclonal antibodies or antigen-binding fragments thereof that bind to natural Bet v 1 or BPE, or a pharmaceutical composition comprising one or more antibodies or antigen-binding fragments thereof, wherein the one or more antibodies or antigen-binding fragments thereof comprises:

(a) a heavy chain complementarity determining region (HCDR)1 comprising the amino acid sequence of SEQ ID NO:
148;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
150;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
152;
a light chain complementarity determining region (LCDR)1 comprising the amino acid sequence of SEQ ID NO:
156;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
158;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
160;
or
(b) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
292;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
294;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
296;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
300;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
302;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
304;
or
(c) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
100;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
102;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
104;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
108;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
110;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
112;
or
(d) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
116;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
118;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
120;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
124;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
126;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
128;
or
(e) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
4;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
6;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
8;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
12:
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
14;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
16;
or
(f) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
20;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
22;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
24;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
28;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
30;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
32;
or
(g) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
36;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
38;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
40;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
44;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
46;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
48;
or
(h) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
52;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
54;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
56;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
60;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
62;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
64;
or
(i) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
68;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
70;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
72;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
76;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
78;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
80;
or
(j) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
84;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
86;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
88;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
92;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
94;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
96;
or
(k) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
132;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
134;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
136;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
140;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
142;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
144;
or
(l) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
164;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
166;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
168;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
172;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
174;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
176;
or
(m) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
180;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
182;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
184;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
188;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
190;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
192;
or
(n) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
196;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
198;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
200;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
204;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
206;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
208;
or
(o) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
212;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
214;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
216;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
220;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
222;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
224;
or
(p) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
228;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
230;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
232;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
236;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
238;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
240;
or
(q) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
244;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
246;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
248;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
252;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
254;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
256;
or
(r) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
260;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
262;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
264;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
268;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
270;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
272;
or
(s) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
276;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
278;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
280;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
268;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
270;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
272;
or
(t) an HCDR1 comprising the amino acid sequence of SEQ ID NO:
284;
an HCDR2 comprising the amino acid sequence of SEQ ID NO:
286;
an HCDR3 comprising the amino acid sequence of SEQ ID NO:
288;
an LCDR1 comprising the amino acid sequence of SEQ ID NO:
268;
an LCDR2 comprising the amino acid sequence of SEQ ID NO:
270;
and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
272.

256 more elements

Human antibodies to Bet v 1 and methods of use thereof

Life of this patent

Human antibodies to Bet v 1 and methods of use thereof

Life of this patent

Abstract

Claims40