US2018292391A1PendingUtilityA1

Gram-positive bacteria specific binding compounds

66
Assignee: GENENTECH INCPriority: Jul 15, 2009Filed: Feb 20, 2018Published: Oct 11, 2018
Est. expiryJul 15, 2029(~3 yrs left)· nominal 20-yr term from priority
A61P 31/04A61P 37/04A61P 37/06A61P 31/00C07K 2317/52C07K 2317/56C07K 16/1271C07K 2317/21G01N 2469/10C07K 2317/565C07K 2317/567G01N 33/6854C07K 16/1278G01N 33/6893G01N 2800/26G01N 33/5091A61K 39/395A61K 47/42A61K 38/18C07K 14/475C07K 16/28C07K 16/22A61K 39/00A61K 48/00C07K 16/12
66
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Claims

Abstract

The present invention provides improved binding compounds capable of specifically binding Gram-positive bacteria. Binding compounds are provided that are fully human, enabling therapeutic applications in human individuals.

Claims

exact text as granted — not AI-modified
1 - 43 . (canceled) 
     
     
         44 . A method for isolating  S. aureus  and/or  S. epidermidis  bacteria comprising contacting a sample with an antibody or functional part thereof, wherein the antibody or functional part thereof comprises a heavy chain variable domain and a light chain variable domain comprising:
 (a) a heavy chain CDR1 sequence RFAMS (SEQ ID NO:1), and   (b) a heavy chain CDR2 sequence SINNGNNPYYARSVQY (SEQ ID NO:2) or SINSGNNPYYARSVQY (SEQ ID NO:60), and   (c) a heavy chain CDR3 sequence DHPSSGWPTFDS (SEQ ID NO:3), and   (d) a light chain CDR1 sequence RASENVGDWLA (SEQ ID NO:4), and   (e) a light chain CDR2 sequence KTSILES (SEQ ID NO:5), and   (f) a light chain CDR3 sequence QHYXRFPYT (SEQ ID NO:6),   wherein X is I or M.   
     
     
         45 . The method of  claim 44 , wherein X in SEQ ID NO:6 is I. 
     
     
         46 . The method of  claim 44 , wherein X in SEQ ID NO:6 is M. 
     
     
         47 . The method of  claim 44 , wherein the heavy chain variable domain amino acid sequence comprises: 
       
         
           
                 
               
                   (SEQ ID NO: 7) 
                 
                 
               
                   EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INNGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         48 . The method of  claim 44 , wherein the heavy chain variable domain amino acid sequence comprises: 
       
         
           
                 
               
                   (SEQ ID NO: 9) 
                 
                 
               
                   EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INNGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         49 . The method of  claim 44 , wherein the heavy chain variable domain amino acid sequence comprises: 
       
         
           
                 
               
                   (SEQ ID NO: 62) 
                 
                 
               
                   EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INSGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         50 . The method of  claim 44 , wherein the light chain variable domain amino acid sequence comprises: 
       
         
           
                 
               
                   (SEQ ID NO: 8) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKLEIKRTV, wherein X is Ior M. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         51 . The method of  claim 50 , wherein X in SEQ ID NO:8 is I. 
     
     
         52 . The method of  claim 44 , wherein the light chain variable domain amino acid sequence comprises: 
       
         
           
                 
               
                   (SEQ ID NO: 10) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKLEIKRA, wherein X is I or M. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         53 . The method of  claim 52 , wherein X in SEQ ID NO:10 is M. 
     
     
         54 . The method of  claim 44 , wherein the light chain variable domain amino acid sequence comprises: 
       
         
           
                 
               
                   (SEQ ID NO: 11) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKVEIKRTV, wherein X is I or M. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         55 . The method of  claim 54 , wherein X in SEQ ID NO:11 is M. 
     
     
         56 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 7) 
                 
                 
               
                   EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INNGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS; 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 11) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKVEIKRTV, wherein X is I or M. 
                 
                     
                 
             
                
               
            
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         57 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 9) 
                 
                 
               
                   EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INNGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS; 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 8) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKLEIKRTV, wherein X is I or M. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         58 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 7) 
                 
                 
               
                   EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INNGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS; 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 8) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKLEIKRTV, wherein X is I or M. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         59 . The method of  claim 58 , wherein X in SEQ ID NO:8 is I. 
     
     
         60 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 7) 
                 
                 
               
                   EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INNGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS; 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 10) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKLEIKRA, wherein X is I or M. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         61 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 9) 
                 
                 
               
                   EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INNGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS; 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 10) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKLEIKRA, wherein X is I or M. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         62 . The method of  claim 61 , wherein X in SEQ ID NO:10 is M. 
     
     
         63 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 9) 
                 
                 
               
                   EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INNGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS; 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 11) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKVEIKRTV, wherein X is I or M. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         64 . The method of  claim 63 , wherein X in SEQ ID NO:11 is M. 
     
     
         65 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 62) 
                 
                 
               
                   EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INSGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 11) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKVEIKRTV, 
                 
                   wherein X is Ior M. 
                 
             
                
               
            
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         66 . The method of  claim 65 , wherein X in SEQ ID NO:11 is M. 
     
     
         67 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 62) 
                 
                 
               
                   EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INSGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 10) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKLEIKRA, 
                 
                   wherein X is I orM. 
                 
             
                
               
            
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         68 . The method of  claim 44 , wherein
 (a) the heavy chain variable domain amino acid sequence comprises   
       
         
           
                 
               
                   (SEQ ID NO: 62) 
                 
                 
               
                   EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVAS 
                 
                     
                 
                   INSGNNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHP 
                 
                     
                 
                   SSGWPTFDSWGPGTLVTVSS 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) the light chain variable domain amino acid sequence comprises 
 
       
         
           
                 
               
                   (SEQ ID NO: 8) 
                 
                 
               
                   DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYK 
                 
                     
                 
                   TSILESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQ 
                 
                     
                 
                   GTKLEIKRTV, 
                 
                   wherein X is Ior M. 
                 
             
                
               
            
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         69 . The method of  claim 65 , wherein the antibody or functional part thereof further comprises a light chain constant domain comprising the amino acid sequence of: 
       
         
           
                 
               
                   (SEQ ID NO: 65) 
                 
                 
               
                   AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQ 
                 
                     
                 
                   ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN 
                 
                     
                 
                   RGEC. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         70 . The method of  claim 65 , wherein the antibody or functional part thereof further comprises a heavy chain constant domain comprising the amino acid sequence of: 
       
         
           
                 
               
                   (SEQ ID NO: 66) 
                 
                 
               
                   CSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV 
                 
                     
                 
                   HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP 
                 
                     
                 
                   KSCDKTHTCP. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         71 . The method of  claim 65 , wherein the antibody or functional part thereof further comprises
 (a) a heavy chain constant domain comprising the amino acid sequence of:   
       
         
           
                 
               
                   (SEQ ID NO: 66) 
                 
                 
               
                   CSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV 
                 
                     
                 
                   HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP 
                 
                     
                 
                   KSCDKTHTCP 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) a light chain constant domain comprising the amino acid sequence of: 
 
       
         
           
                 
               
                   (SEQ ID NO: 65) 
                 
                 
               
                   AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQ 
                 
                     
                 
                   ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN 
                 
                     
                 
                   RGEC. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         72 . The method of  claim 65 , wherein the antibody or functional part thereof further comprises
 (a) a heavy chain constant domain comprising the sequence of:   
       
         
           
                 
               
                   (SEQ ID NO: 66) 
                 
                 
               
                   CSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV 
                 
                     
                 
                   HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP 
                 
                     
                 
                   KSCDKTHTCP 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and
 (b) a light chain constant domain comprising the sequence of: 
 
       
         
           
                 
               
                   (SEQ ID NO: 64) 
                 
                 
               
                   AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQ 
                 
                     
                 
                   ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN 
                 
                     
                 
                   RGEC. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         73 . The method of  claim 65 , wherein the antibody or functional part thereof further comprises
 (a) a heavy chain constant domain comprising the sequence of:   
       
         
           
                 
               
                   (SEQ ID NO: 63) 
                 
                 
               
                   ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV 
                 
                     
                 
                   HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP 
                 
                     
                 
                   KSCDKTHTCP 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and;
 (b) a light chain constant domain comprising the sequence of: 
 
       
         
           
                 
               
                   (SEQ ID NO: 65) 
                 
                 
               
                   AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQ 
                 
                     
                 
                   ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN 
                 
                     
                 
                   RGEC. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         74 . The method of  claim 65 , wherein the antibody or functional part thereof further comprises
 (a) a heavy chain constant domain comprising the sequence of:   
       
         
           
                 
               
                   (SEQ ID NO: 63) 
                 
                 
               
                   ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV 
                 
                     
                 
                   HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP 
                 
                     
                 
                   KSCDKTHTCP 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and;
 (b) a light chain constant domain comprising the sequence of: 
 
       
         
           
                 
               
                   (SEQ ID NO: 64) 
                 
                 
               
                   AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQ 
                 
                     
                 
                   ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN 
                 
                     
                 
                   RGEC. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         75 . The method of  claim 44 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:56 and a light chain comprising the amino acid sequence of SEQ ID NO:58. 
     
     
         76 . The method of  claim 44 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:55 and a light chain comprising the amino acid sequence of SEQ ID NO:57.

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