Amino acid sequences for therapeutic and prophylactic use against diseases due to
The invention relates to monoclonal antibodies capable of recognizing and neutralizing epitopes from the ligand domain, the translocation domain or the catalytic domain of the enterotoxin (toxin A) and cytotoxin (toxin B) from Clostridium difficile , as well as their production and therapeutic and prophylactic applications to diseases caused by said toxins.
1. An isolated peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO. 14 and SEQ ID) NO. 16 and encoded by nucleic acid sequences identified by SEQ ID NO's: 13 and 15 respectively.
2. The isolated peptide of claim 1 , wherein said peptide is capable of forming a variable or hypervariable antigen-binding domain (region) of an antibody that specifically binds Clostridium difficile toxin A.
3. The isolated peptide of claim 1 , wherein said peptide is capable of neutralizing the biological activity of Clostridium difficile toxin A.
4. An isolated antibody or chimeric antibody fragment comprising a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 14 and SEQ ID NO. 16 wherein said peptide specifically binds Clostridium difficile toxin A.
5. The antibody or chimeric antibody fragment of claim 4 , wherein said antibody or antibody fragment is a chimeric antibody or fragment thereof comprising a human antibody constant region.
6. The chimeric antibody fragment of claim 5 , wherein said fragment is Fab.
7. An isolated peptide comprising an amino acid sequence identified by SEQ ID NO's: 14 and 16 encoded by a nucleic acid sequence identified by SEQ ID NO. 13 and SEQ ID NO. 15, respectively and, wherein said peptide specifically binds Clostridium difficile toxin A.
8. A pharmaceutical composition comprising:
a peptide comprising an amino acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO. 13 and SEQ ID No. 15; and
a pharmaceutically acceptable carrier.
9. A method of neutralizing the biological activity of Clostridium difficile toxin A, said method comprising contacting said toxin with a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO. 14 and SEQ ID NO. 16.
10. A method of treating or preventing a Clostridium difficile disease, comprising
administering to a subject in need thereof an effective amount of a composition comprising an isolated peptide comprising an amino acid sequence identified by SEQ ID NO's: 14 and 16 wherein said peptide specifically binds Clostridium difficile toxin A, thereby,
treating or preventing a Clostridium difficile disease.
11. The method of claim 10 , wherein said composition is administered parenterally.
12. The method of claim 10 , wherein said composition is administered perorally.