High affinity human antibodies to human cytomegalovirus (CMV) gB protein
Antibodies to human Cytomegalovirus (CMV) gB protein have been isolated from human B cells. The affinities of these antibodies are higher than the best previously reported antibodies. Since high affinity is critical to prevention of virus transfer across the placenta, the invention antibodies are useful as therapeutic and prophylactic agents to prevent or ameliorate effects on the fetus of CMV infection during pregnancy.
1. An isolated monoclonal antibody (mAb) or immunoreactive fragment thereof wherein:
(a) the heavy chain comprises the CDR1, CDR2 and CDR3 regions of the variable region of MAB4A2 (SEQ ID NO:2); or
(b) comprises the CDR1, CDR2 and CDR3 regions of the heavy chain variable region of MAB19B10 (SEQ ID NO:6); or
(c) comprises the CDR1, CDR2 and CDR3 regions of the heavy chain variable region of MAB313 (SEQ ID NO:13); or
(d) comprises the CDR1, CDR2 and CDR3 regions of the heavy chain variable region of MAB338 (SEQ ID NO:20); or
(e) comprises the CDR1, CDR2 and CDR3 regions of the heavy chain variable region of MAB345 (SEQ ID NO:22).
2. The mAb of claim 1 that is in the form of a complete antibody.
3. The mAb of claim 1 that is a bi-specific antibody.
4. The antibody of claim 1 wherein the light chain
in (a) comprises the CDR1, CDR2 and CDR3 regions of light chain variable region of MAB4A2 (SEQ ID NO:4); and
in (b) comprises the CDR1, CDR2 and CDR3 regions of light chain variable region of MAB19B10 (SEQ ID NO:8); and
in (c) comprises the CDR1, CDR2 and CDR3 regions of light chain variable region of MAB313 (SEQ ID NO:27); and
in (d) comprises the CDR1, CDR2 and CDR3 regions of light chain variable region of MAB338 (SEQ ID NO:34); and
in (e) comprises the CDR1, CDR2 and CDR3 regions of light chain variable region of MAB345 (SEQ ID NO:36).
5. The monoclonal antibody MAB345 (ATCC deposit number PTA-121705) or an immunoreactive fragment thereof.
6. A pharmaceutical composition that comprises the monoclonal antibody or fragment of claim 1 , along with a pharmaceutically acceptable excipient.
7. The pharmaceutical composition of claim 6 that further contains an additional pharmaceutical agent, along with a pharmaceutically acceptable excipient.
8. The mAb or fragment of claim 1 wherein
(a) the heavy chain variable region comprises that of MAB4A2 (SEQ ID NO:2); or
(b) the heavy chain variable region comprises that of MAB19B10 (SEQ ID NO:6); or
(c) the heavy chain variable region comprises that of MAB313 (SEQ ID NO:13); or
(d) the heavy chain variable region comprises that of MAB338 (SEQ ID NO:20); or
(e) the heavy chain variable region comprises that of MAB345 (SEQ ID NO:22).
9. The mAb or fragment of claim 8 wherein
in (a) the light chain variable region comprises that of MAB4A2 (SEQ ID NO:4); and
in (b) the light chain variable region comprises that of MAB19B10 (SEQ ID NO:8); and
in (c) the light chain variable region comprises that of MAB313 (SEQ ID NO:27); and
in (d) the light chain variable region comprises that of MAB338 (SEQ ID NO:34); and
in (e) the light chain variable region comprises that of MAB345 (SEQ ID NO:36).
10. A pharmaceutical composition that comprises the monoclonal antibody or fragment of claim 8 , along with a pharmaceutically acceptable excipient.