Antibodies and methods for the diagnosis and treatment of epstein barr virus infection
AssigneesThe U.S.A., as represented by the Secretary, Department of Health and Human Services, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
InventorsWei Bu, Masaru Kanekiyo, Michael Gordon Joyce, Jeffrey I. Cohen
Life of this patent
Estimating the term…
Abstract
Antibodies and compositions of matter useful for the detection, diagnosis and treatment of Epstein Barr Virus (EBV) infection in mammals, and methods of using those compositions of matter for the detection, diagnosis and treatment of EBV infection are described. Also described 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.
Claims20
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:
- 1, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 6;
- (b) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 11, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 16;
- (c) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 21, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 26;
- (d) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 31, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 36;
- (e) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 41, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 46;
- (f) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 161, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 166, wherein the antibody is an engineered antibody;
- (g) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 171, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 176, wherein the antibody is an engineered antibody;
- (h) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 181, the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 186, wherein the antibody is an engineered antibody;
- (i) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 191, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 196, wherein the antibody is an engineered antibody;
- (j) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 201, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 206, wherein the antibody is an engineered antibody;
- (k) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 211, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 216, wherein the antibody is an engineered antibody;
- (l) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 221, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 226, wherein the antibody is an engineered antibody;
- (m) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 231, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 236, wherein the antibody is an engineered antibody;
- (n) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 241, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 246, wherein the antibody is an engineered antibody;
- (o) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 251, and the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 256, wherein the antibody is an engineered antibody;
- (p) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 261, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 266, wherein the antibody is an engineered antibody;
- (q) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 271, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 276, wherein the antibody is an engineered antibody;
- or
- (r) the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 281, and the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:
- 286, wherein the antibody is an engineered antibody.
A protein comprising a polypeptide at least 85% identical to the amino acid sequence of the complement receptor 2 (CR2)-binding region of Epstein-Barr virus (EBV) gp350 set forth as amino acid residues 2-425 of SEQ ID NO:
- 124, wherein:
- the amino acid residue corresponding to amino acid I160 of SEQ ID NO:
- 124 is substituted with arginine, serine, threonine, cysteine, proline, asparagine, glutamine, tyrosine, phenylalanine, tryptophan, glutamate, aspartate, glutamine, histidine, or lysine;
- and/or
- the amino acid corresponding to amino acid K161 of SEQ ID NO:
- 124 is substituted with methionine, leucine, isoleucine, glycine, alanine, valine, phenylalanine, tyrosine, tryptophan, lysine, arginine, histidine, glutamate, serine, or aspartate,
- wherein the protein can bind an anti-gp350 antibody, or a B-cell expressing an anti-gp350 B-cell receptor (BCR), wherein binding of the B-cell is through the BCR, and wherein binding of the protein to CR2 is substantially reduced compared to binding of wild-type gp350 to CR2.
Dependencies are inferred from the claim text.