Combination therapies using anti-pseudomonas PSL and PCRV binding molecules

Patent metadata

Field	Value
Publication number	US-10597439-B2
Application number	US-201214356500-A
Country	US
Kind code	B2
Filing date	Nov 6, 2012
Priority date	Nov 7, 2011
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Medimmune Llc
• Medimmune Ltd

Inventors

• Digiandomenico Antonio
• Warrener Paul
• Stover Charles
• Sellman Bret
• Minter Ralph
• Guillard Sandrine
• Rust Steven
• Tomich Mladen
• Venkatraman Vignesh
• Varkey Reena
• Peng Li
• Damschroder Melissa
• Chowdhury Partha
• Dimasi Nazzareno
• Fleming Ryan
• Bezabeh Binyam
• Gao Changshou
• Rainey Godfrey
• Gao Cuihua

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K16/1214 Primary

  Pseudomonadaceae (F) · CPC title