Combination therapies using anti-pseudomonas PSL and PCRV binding molecules
This disclosure relates to combination therapies comprising anti- Pseudomonas Psl and PcrV binding molecules and related compositions, for use in prevention and treatment of Pseudomonas infection.
1. A bispecific antibody or antigen-binding fragment thereof comprising a binding domain that binds to Pseudomonas Psl and a binding domain that binds to Pseudomonas PcrV, wherein the domain that binds to Pseudomonas Psl comprises:
a heavy chain CDR1 comprising amino acids PYYWT (SEQ ID NO:47);
a heavy chain CDR2 comprising amino acids YIHSSGYTDYNPSLKS (SEQ ID NO:48);
a heavy chain CDR3 comprising amino acids ADWDRLRALDI (SEQ ID NO:258);
a light chain CDR1 comprising amino acids RASQSIRSHLN (SEQ ID NO:50);
a light chain CDR2 comprising amino acids GASNLQS (SEQ ID NO:51); and
a light chain CDR3 comprising amino acids QQSTGAWNW (SEQ ID NO:280); and
wherein the domain that binds to Pseudomonas PcrV comprises:
a heavy chain CDR1 comprising amino acids SYAMN (SEQ ID NO:218);
a heavy chain CDR2 comprising amino acids AITMSGITAYYTDDVKG (amino acids 50-66 of SEQ ID NO:264);
a heavy chain CDR3 comprising amino acids EEFLPGTHYYYGMDV (SEQ ID NO:220);
a light chain CDR1 comprising amino acids RASQGIRNDLG (SEQ ID NO:221);
a light chain CDR2 comprising amino acids SASTLQS (SEQ ID NO:222); and
a light chain CDR3 comprising amino acids LQDYNYPWT (SEQ ID NO:223).
2. The bispecific antibody or antigen-binding fragment thereof of claim 1 , wherein the binding domain that binds to Psl comprises amino acids:
QVQLQESGPGLVKPSETLSLTCTVSGGSISPYYWTWI RQPPGKCLELIGYI HSSGYT DYNPSLKSRVTISGDTSKKQFSLKLSSVTAADTAVYYCARADWDRLRALDIWGQGTMVTVS SGGGGSGGGGSGGGGSGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSIRSHLNWYQQ KPGKAPKLLIYGASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSTGAWNWF GCGTKVEIK (SEQ ID NO:262).
3. The bispecific antibody of or antigen-binding fragment thereof claim 1 , wherein the binding domain that binds to Pseudomonas PcrV comprises:
a heavy chain variable region (VH) comprising amino acids: EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSAITMSGITAYY TDDVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEEFLPGTHYYYGMDVWGQGTTV TVSS (amino acids 1-124 OF SEQ ID NO:264); and
a light chain variable region (VL) comprising amino acids: AIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYSASTLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCLQDYNYPWTFGQGTKVEIK (amino acids 1-107 OF SEQ ID NO:263).
4. The bispecific antibody or antigen-binding fragment thereof of claim 1 , wherein the binding domain that binds to Psl comprises amino acids:
QVQLQESGPGLVKPSETLSLTCTVSGGSISPYYWTWIRQPPGKCLELIGYIHSSGYT DYNPSLKSRVTISGDTSKKQFSLKLSSVTAADTAVYYCARADWDRLRALDIWGQGTMVTVS SGGGGSGGGGSGGGGSGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSIRSHLNWYQQ KPGKAPKLLIYGASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSTGAWNWF GCGTKVEIK (SEQ ID NO:262); and
wherein the binding domain that binds to Pseudomonas PcrV comprises:
a heavy chain variable region (VH) comprising amino acids: EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSAITMSGITAYY TDDVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEEFLPGTHYYYGMDVWGQGTTV TVSS (amino acids 1-124 of SEQ ID NO:264); and
a light chain variable region (VL) comprising amino acids: AIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYSASTLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCLQDYNYPWTFGQGTKVEIK (amino acids 1-107 of SEQ ID NO:263).
5. A composition comprising the bispecific antibody or fragment thereof of claim 1 , and a pharmaceutically acceptable carrier.
6. A bispecific antibody comprising a binding domain that binds to Pseudomonas Psl and a binding domain that binds to Pseudomonas PcrV, wherein the bispecific antibody comprises a heavy chain comprising SEQ ID NO:264 and a light chain comprising SEQ ID NO:263.
7. A composition comprising the bispecific antibody or fragment thereof of claim 6 , and a pharmaceutically acceptable carrier.