Antibodies and methods for the diagnosis and treatment of Epstein Barr virus infection

Patent metadata

Field	Value
Publication number	US-11236151-B2
Application number	US-201816608386-A
Country	US
Kind code	B2
Filing date	Apr 25, 2018
Priority date	Apr 25, 2017
Publication date	Feb 1, 2022
Grant date	Feb 1, 2022

Abstract

Antibodies and compositions of matter useful for the detection, diagnosis and treatment of Epstein Barr Virus infection in mammals, and to methods of using those compositions of matter for the same. Also disclosed are proteins, referred to as anti-gp350 antibody probes, and anti-gp350 B-cell probes, that maintain the epitope structure of the CR2-binding region of gp350, but do not bind CR2.

First claim

What is claimed is:

1. An isolated antibody that binds Epstein Barr Virus (EBV) gp350 protein, comprising a variable heavy (VH) domain and a variable light (VL) domain, wherein:
(a) the VH domain comprises the complementarity determining region 1 (CDR1), CDR2 and CDR3 sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10, respectively;
(b) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20, respectively;
(c) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30, respectively;
(d) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 33, SEQ ID NO: 34 and SEQ ID NO: 35, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 38, SEQ ID NO: 39 and SEQ ID NO: 40, respectively;
(e) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 43, SEQ ID NO: 44 and SEQ ID NO: 45, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 48, SEQ ID NO: 49 and SEQ ID NO: 50, respectively;
(f) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 163, SEQ ID NO: 164 and SEQ ID NO: 165, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 168, SEQ ID NO: 169 and SEQ ID NO: 170, respectively, wherein the antibody is an engineered antibody;
(g) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 173, SEQ ID NO: 174 and SEQ ID NO: 175, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 178, SEQ ID NO: 179 and SEQ ID NO: 180, respectively, wherein the antibody is an engineered antibody;
(h) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 183, SEQ ID NO: 184 and SEQ ID NO: 185, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 188, SEQ ID NO: 189 and SEQ ID NO: 190, respectively, wherein the antibody is an engineered antibody;
(i) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 193, SEQ ID NO: 194 and SEQ ID NO: 195, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 198, SEQ ID NO: 199 and SEQ ID NO: 200, respectively, wherein the antibody is an engineered antibody;
(j) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 203, SEQ ID NO: 204 and SEQ ID NO: 205, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 208, SEQ ID NO: 209 and SEQ ID NO: 210, respectively, wherein the antibody is an engineered antibody;
(k) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 213, SEQ ID NO: 214 and SEQ ID NO: 215, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 218, SEQ ID NO: 219 and SEQ ID NO: 220, respectively, wherein the antibody is an engineered antibody;
(l) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 223, SEQ ID NO: 224 and SEQ ID NO: 225, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 228, SEQ ID NO: 229 and SEQ ID NO: 230, respectively, wherein the antibody is an engineered antibody;
(m) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 233, SEQ ID NO: 234 and SEQ ID NO: 235, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 238, SEQ ID NO: 239 and SEQ ID NO: 240, respectively, wherein the antibody is an engineered antibody;
(n) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 243, SEQ ID NO: 244 and SEQ ID NO: 245, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 248, SEQ ID NO: 249 and SEQ ID NO: 250, respectively, wherein the antibody is an engineered antibody;
(o) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 253, SEQ ID NO: 254 and SEQ ID NO: 255, respectively, and the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 258, SEQ ID NO: 259 and SEQ ID NO: 260, respectively, wherein the antibody is an engineered antibody;
(p) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 263, SEQ ID NO: 264 and SEQ ID NO: 265, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 268, SEQ ID NO: 269 and SEQ ID NO: 270, respectively, wherein the antibody is an engineered antibody;
(q) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 273, SEQ ID NO: 274 and SEQ ID NO: 275, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 278, SEQ ID NO: 279 and SEQ ID NO: 280, respectively, wherein the antibody is an engineered antibody;
(r) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 283, SEQ ID NO: 284 and SEQ ID NO: 285, respectively, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 288, SEQ ID NO: 289 and SEQ ID NO: 290, respectively, wherein the antibody is an engineered antibody.

2. The isolated antibody of claim 1 , wherein the isolated antibody is selected from the group consisting of:
(a) an isolated antibody (B03) comprising the VH domain sequence of SEQ ID NO:1 and the VL domain sequence of SEQ ID NO:6;
(b) an isolated antibody (E04) comprising the VH domain sequence of SEQ ID NO:11 and the VL domain sequence of SEQ ID NO:16;
(c) an isolated antibody (D09) comprising the VH domain sequence of SEQ ID NO:21 and the VL domain sequence of SEQ ID NO:26;
(d) an isolated antibody (C02) comprising the VH domain sequence of SEQ ID NO:31 and the VL domain sequence of SEQ ID NO:36;
(e) an isolated antibody (H02) comprising the VH domain sequence of SEQ ID NO:41 and the VL domain sequence of SEQ ID NO:46;
(f) an isolated antibody comprising the VH domain sequence of SEQ ID NO:161 and the VL domain sequence of SEQ ID NO:166;
(g) an isolated antibody comprising the VH domain sequence of SEQ ID NO:171 and the VL domain sequence of SEQ ID NO:176;
(h) an isolated antibody comprising the VH domain sequence of SEQ ID NO:181 and the VL domain sequence of SEQ ID NO:186;
(i) an isolated antibody comprising the VH domain sequence of SEQ ID NO:191 and the VL domain sequence of SEQ ID NO:196;
(j) an isolated antibody comprising the VH domain sequence of SEQ ID NO:201 and the VL domain sequence of SEQ ID NO:206;
(k) an isolated antibody comprising the VH domain sequence of SEQ ID NO:211 and the VL domain sequence of SEQ ID NO:216;
(l) an isolated antibody comprising the VH domain sequence of SEQ ID NO:221 and the VL domain sequence of SEQ ID NO:226;
(m) an isolated antibody comprising the VH domain sequence of SEQ ID NO:231 and the VL domain sequence of SEQ ID NO:236;
(n) an isolated antibody comprising the VH domain sequence of SEQ ID NO:241 and the VL domain sequence of SEQ ID NO:246;
(o) an isolated antibody comprising the VH domain sequence of SEQ ID NO:251 and the VL domain sequence of SEQ ID NO:256;
(p) an isolated antibody comprising the VH domain sequence of SEQ ID NO:261 and the VL domain sequence of SEQ ID NO:266;
(q) an isolated antibody comprising the VH domain sequence of SEQ ID NO:271 and the VL domain sequence of SEQ ID NO:276; and,
(r) an isolated antibody comprising the VH domain sequence of SEQ ID NO:281 and the VL domain sequence of SEQ ID NO:286.

3. The isolated antibody of claim 1 , wherein the isolated antibody is a

Assignees

• The Usa As Represented By The Sec Dep Of Health And Human Services
• Henry M Jackson Found Advancement Military Medicine Inc
• Us Health

Inventors

• Bu Wei
• Kanekiyo Masaru
• Joyce Michael Gordon
• Cohen Jeffrey I

Classifications

• A61P31/22

  for herpes viruses · CPC title

• C07K14/05

  Epstein-Barr virus · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title