US2022340651A1PendingUtilityA1

Anti cancer combination therapy

Assignee: BOEHRINGER INGELHEIM INTPriority: Jun 2, 2017Filed: Nov 8, 2021Published: Oct 27, 2022
Est. expiryJun 2, 2037(~10.9 yrs left)· nominal 20-yr term from priority
C07K 16/22A61K 39/39558A61K 2039/507C07K 2317/569C07K 2317/31A61K 2039/505A61P 35/00A61K 31/502C07K 2317/76C07K 16/18C07K 2317/24A61K 2300/00C07K 16/3023A61K 39/39541C07K 16/2818C07K 2317/565C07K 2317/22
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Claims

Abstract

The invention relates to the combined use of certain bispecific, VEGF and Ang2 binding molecules with PD1 antagonists for the treatment of cancer. It further relates to pharmaceutical compositions and kits comprising such binding molecules and antagonists.

Claims

exact text as granted — not AI-modified
1 . A pharmaceutical composition for the treatment of solid tumor cancer comprising
 a) a Compound A and   b) a Compound B   wherein Compound A is a binding molecule comprising
 a VEGF-binding immunoglobulin single variable domain, 
 a serum albumin binding immunoglobulin single variable domain, and 
 an Ang2-binding immunoglobulin single variable domain 
 wherein
 said VEGF-binding immunoglobulin single variable domain has the following CDR sequences: 
 
   
       
         
           
                 
                 
               
                     
                   CDR1: 
                 
                     
                   (SEQ ID NO: 1) 
                 
                     
                   SYSMG, 
                 
                     
                     
                 
                     
                   CDR2: 
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   AISKGGYKYDAVSLEG, 
                 
                     
                     
                 
                     
                   CDR3: 
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   SRAYGSSRLRLADTYEY; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         said serum albumin binding immunoglobulin single variable domain has the following CDR sequences: 
       
       
         
           
                 
                 
               
                     
                   CDR1: 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   SFGMS, 
                 
                     
                     
                 
                     
                   CDR2: 
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   SISGSGSDTLYADSVKG, 
                 
                     
                     
                 
                     
                   CDR3: 
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   GGSLSR; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         said Ang2-binding immunoglobulin single variable domain has the following CDR sequences: 
       
       
         
           
                 
                 
               
                     
                   CDR1: 
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   DYAIG, 
                 
                     
                     
                 
                     
                   CDR2: 
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   AIRSSGGSTYYADSVKG, 
                 
                     
                     
                 
                     
                   CDR3: 
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   VPAGRLRYGEQWYPIYEYDA; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and
 wherein each single variable domain is separated by a linker peptide; and 
 wherein Compound B is a PD-1 antagonist selected from the group consisting of pembrolizumab, nivolumab, pidilizumab, PD1-1 (HC/LC; SEQ ID NO: 14, 15), PD1-2 (HC/LC; SEQ ID NO: 16, 17), PD1-3 (HC/LC; SEQ ID NO: 18, 19), PD1-4 (HC/LC; SEQ ID NO: 20, 21), and PD1-5 (HC/LC; SEQ ID NO: 22, 23). 
 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein said immunoglobulin single variable domains of Compound A are VHH domains. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein Compound A has the amino acid sequence according to SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , further comprising one or more pharmaceutically acceptable carriers, excipients and/or vehicles. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the solid tumor cancer is lung cancer. 
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein the solid tumor cancer is non-small cell lung cancer (NSCLC). 
     
     
         7 . A kit comprising
 a) a first pharmaceutical composition comprising Compound A and   b) a second pharmaceutical composition comprising Compound B,   wherein Compound A is a binding molecule comprising
 a VEGF-binding immunoglobulin single variable domain, 
 a serum albumin binding immunoglobulin single variable domain, and 
 an Ang2-binding immunoglobulin single variable domain 
 wherein
 said VEGF-binding immunoglobulin single variable domain has the following CDR sequences: 
 
   
       
         
           
                 
                 
               
                     
                   CDR1: 
                 
                     
                   (SEQ ID NO: 1) 
                 
                     
                   SYSMG, 
                 
                     
                     
                 
                     
                   CDR2: 
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   AISKGGYKYDAVSLEG, 
                 
                     
                     
                 
                     
                   CDR3: 
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   SRAYGSSRLRLADTYEY; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         said serum albumin binding immunoglobulin single variable domain has the following CDR sequences: 
       
       
         
           
                 
                 
               
                     
                   CDR1: 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   SFGMS, 
                 
                     
                     
                 
                     
                   CDR2: 
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   SISGSGSDTLYADSVKG, 
                 
                     
                     
                 
                     
                   CDR3: 
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   GGSLSR; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         said Ang2-binding immunoglobulin single variable domain has the following CDR sequences: 
       
       
         
           
                 
                 
               
                     
                   CDR1: 
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   DYAIG, 
                 
                     
                     
                 
                     
                   CDR2: 
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   AIRSSGGSTYYADSVKG, 
                 
                     
                     
                 
                     
                   CDR3: 
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   VPAGRLRYGEQWYPIYEYDA; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and
 wherein each single variable domain is separated by a linker peptide; and 
 wherein Compound B is a PD-1 antagonist selected from the group consisting of pembrolizumab, nivolumab, pidilizumab, PD1-1 (HC/LC; SEQ ID NO: 14, 15), PD1-2 (HC/LC; SEQ ID NO: 16, 17), PD1-3 (HC/LC; SEQ ID NO: 18, 19), PD1-4 (HC/LC; SEQ ID NO: 20, 21), and PD1-5 (HC/LC; SEQ ID NO: 22, 23). 
 
     
     
         8 . The kit according to  claim 7 , wherein said immunoglobulin single variable domains of Compound A are VHH domains. 
     
     
         9 . The kit according to  claim 7 , wherein Compound A has the amino acid sequence according to SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13. 
     
     
         10 . The kit according to  claim 7 , further comprising a package insert comprising readable instructions for simultaneous, concurrent, sequential, successive, alternate or separate administration to a patient in the treatment of solid tumor cancer. 
     
     
         11 . The kit according to  claim 10 , wherein the solid tumor cancer is lung cancer. 
     
     
         12 . The kit according to  claim 11 , wherein the solid tumor cancer is non-small cell lung cancer (NSCLC).

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