| 摘要 |
The present invention provides fully human antibodies that bind to either toxin A or toxin B of Clostridium difficile, or to both toxin A and toxin B, compositions comprising the antibodies and methods of use. The antibodies of the invention are useful for neutralizing the toxins from C. difficile, thus providing a means of treating the disease and symptoms associated with a C. difficile infection, including the treatment of diarrhea, or pseudomembranous colitis caused by C. difficile. The antibodies may also prevent the severity and/or duration of the primary disease, or may prevent the number, duration, and/or the severity of recurrences, or relapses of the disease attributed to the presence of C. difficile. The antibodies of the invention may also be useful for diagnosis of an infection by C. difficile. |
| 主权项 |
1. An isolated antibody that specifically binds to Clostridium difficile toxin A or to toxin B, or that binds to, or cross reacts with, both toxin A and B, wherein:
a) the isolated antibody or antigen-binding fragment thereof that specifically binds toxin A of Clostridium difficile comprises the three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 98, 114, 130, 146 and 162; and the three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 106, 122, 138, 154 and 170; b) the isolated antibody or antigen-binding fragment thereof that specifically binds toxin B of Clostridium difficile comprises the HCDR1, HCDR2 and HCDR3 contained within a HCVR amino acid sequence selected from the group consisting of SEQ ID NOs: 178, 194, 210, 226, 242, 258, 274, 290, 306, 322, 338 and 354; and the LCDR1, LCDR2 and LCDR3 contained within a LCVR amino acid sequence selected from the group consisting of SEQ ID NOs: 186, 202, 218, 234, 250, 266, 282, 298, 314, 330, 346 and 362; and c) the isolated antibody or antigen-binding fragment that binds to, or cross reacts with both toxin A and toxin B of Clostridium difficile comprises the HCDR1, HCDR2 and HCDR3 contained within a HCVR amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 34, 50, 66 and 82; and the LCDR1, LCDR2 and LCDR3 contained within a LCVR amino acid sequence selected from the group consisting of SEQ ID NOs: 26, 42, 58, 74 and 90. |
