Novel antibody molecules and nucleic acids

Abstract

An scFv peptide comprising a V H domain and a V L domain linked by an amino acid spacer is disclosed. The V H domain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 64. The V L domain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 66. The scFv peptide also comprises the substitution or deletion of an amino acid in the V H domain at the position corresponding to C 28 .

1 . An scFv peptide comprising a V H  domain and a V L  domain, wherein the V H  domain comprises the amino acid sequence set forth in SEQ ID NO:64 and the V L  domain comprises the amino acid sequence set forth in SEQ ID NO:66, and wherein the scFv peptide comprises a substitution of an amino acid in the V H  domain at the position corresponding to C 28  of SEQ ID NO:64. 
     
     
         2 . The scFv peptide according to  claim 1 , wherein the substitution of the amino acid in the V H  domain is C 28 Y. 
     
     
         3 . The scFv peptide according to  claim 1 , wherein the substitution of the amino acid in the V H  domain is C 28 S. 
     
     
         4 . The scFv peptide according to  claim 1 , wherein an amino acid spacer links the V H  domain and the V L  domain. 
     
     
         5 . An scFv peptide, comprising an amino acid sequence selected from the group consisting of SEQ ID NO:8, 10 and 14, wherein Xaa denotes an amino acid residue other than cysteine and wherein the N-terminal methionine residue may optionally be cleaved off. 
     
     
         6 . An scFv peptide comprising the amino acid sequence as set forth in SEQ ID NO:10, wherein Xaa is tyrosine or serine and wherein the N-terminal methionine residue may optionally be cleaved off. 
     
     
         7 . The scFv peptide of  claim 6 , wherein said scFv peptide is encoded by a nucleic acid sequence having (taa) 2  located at the 3′ end of said nucleic acid sequence. 
     
     
         8 . A pharmaceutical composition comprising the scFv peptide according to  claim 6  in combination with a pharmaceutically acceptable excipient, diluent or carrier. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , further comprising an antifungal agent. 
     
     
         10 . A nucleic acid molecule comprising a nucleic acid sequence encoding the scFv peptide according to  claim 1 . 
     
     
         11 . The nucleic acid molecule according to  claim 10 , further comprising the sequence (taa) n  located at the 3′ end of the sequence encoding the scFv peptide wherein n is 1 or 2. 
     
     
         12 . The nucleic acid molecule according to  claim 10 , wherein the molecule comprises a nucleic acid sequence selected from the group consisting of: SEQ ID NO:7, 9 and 13, wherein nnn denotes a codon coding for an amino acid other than a cysteine residue. 
     
     
         13 . A vector molecule comprising the nucleic acid molecule according to  claim 10 . 
     
     
         14 . A host cell comprising the vector molecule according to  claim 13 . 
     
     
         15 . A method for producing a scFv peptide, comprising culturing a host cell having incorporated therein an expression vector containing, under control of suitable transcriptional control elements, the nucleic acid molecule according to  claim 10  under conditions sufficient for expression of said peptide in the host cell thereby causing the production of said peptide and recovering the peptide produced by said host cell. 
     
     
         16 . A method of treating a fungal infection, comprising administering to a patient in need thereof an effective amount of the scFv peptide according to  claim 1 . 
     
     
         17 . The method according to  claim 16 , further comprising the step of administering to the patient an effective amount of an antifungal agent. 
     
     
         18 . The method according to  claim 17 , wherein the antifungal agent is an azole antifungal agent, a polyene antifungal agent or an echinocandin antifungal agent. 
     
     
         19 . A method of treating a fungal infection, comprising administering to a patient in need thereof an effective amount of the scFv peptide according to  claim 6 . 
     
     
         20 . The method according to  claim 19 , wherein the fungal infection is due to a  Candida, Cryptococcus, Histoplasma, Aspergillus, Torulopsis, Mucormycosis, Blastomycosis, Coccidioidomycosis  or  Paracoccidioidomycosis  organism. 
     
     
         21 . The method according to  claim 19 , further comprising administering to the patient an effective amount of at least one additional antifungal agent. 
     
     
         22 . The method according to  claim 21 , wherein the at least one additional antifungal agent is an azole antifungal agent, a polyene antifungal agent or an echinocandin antifungal agent. 
     
     
         23 . The method according to  claim 22 , wherein the at least one additional antifungal agent is an azole antifungal agent and wherein the azole antifungal agent is selected from the group consisting of: itraconazole, voriconazole isavuconazole, fluconazole, miconazole, ketoconazole, and posaconazole. 
     
     
         24 . The method according to  claim 23 , wherein the azole antifungal agent is voriconazole. 
     
     
         25 . The method according to  claim 21 , wherein the at least one additional antifungal agent is a polyene antifungal agent, and wherein said polyene antifungal agent comprises amphotericin B or a derivative thereof. 
     
     
         26 . The method according to  claim 21 , wherein the at least one additional antifungal agent is an echinocandin antifungal agent, and wherein said echinocandin antifungal agent is caspofungin.