US2011020323A1PendingUtilityA1

Gram-positive bacteria specific binding compounds

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Assignee: BEAUMONT TIMPriority: Jul 15, 2009Filed: Jul 15, 2010Published: Jan 27, 2011
Est. expiryJul 15, 2029(~3 yrs left)· nominal 20-yr term from priority
Inventors:Tim BeaumontMark Jeroen KwakkenbosEric J. BrownJohn Hiroshi MorisakiWouter HazenbosSanjeev MariathasanKimberly KajiharaYi Xia
A61P 31/00A61P 37/04A61P 31/04A61P 37/06C07K 2317/567C07K 2317/56C07K 16/1278C07K 2317/52G01N 33/5091C07K 16/1271C07K 2317/21G01N 33/6893G01N 33/6854C07K 2317/565G01N 2469/10G01N 2800/26A61K 39/395A61K 47/42A61K 38/18C07K 14/475C07K 16/28C07K 16/22A61K 39/00A61K 48/00C07K 16/12
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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 . An antibody or functional part thereof or immunoglobulin chain or functional equivalent thereof, which comprises:
 (a) a heavy chain CDR1 sequence comprising a sequence which has at least 70% sequence identity to the sequence RFAMS (SEQ ID NO:1), and/or   (b) a heavy chain CDR2 sequence comprising a sequence which has at least 70% sequence identity to the sequence SINNGNNPYYARSVQY (SEQ ID NO:2), and/or   (c) a heavy chain CDR3 sequence comprising a sequence which has at least 70% sequence identity to the sequence DHPSSGWPTFDS (SEQ ID NO:3), and/or   (d) a light chain CDR1 sequence comprising a sequence which has at least 70% sequence identity to the sequence RASENVGDWLA (SEQ ID NO:4), and/or   (e) a light chain CDR2 sequence comprising a sequence which has at least 70% sequence identity to the sequence KTSILES (SEQ ID NO:5), and/or   (f) a light chain CDR3 sequence comprising a sequence which has at least 70% sequence identity to the sequence QHYXRFPYT(SEQ ID NO:6), wherein X is I or M.   
     
     
         2 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , having a heavy chain sequence comprising a sequence which has at least 70% sequence identity to the sequence EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYARSV QYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:7) and/or having a light chain sequence which has at least 70% sequence identity to the sequence DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRFSGS GSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRTV, wherein X is I of M (SEQ ID NO:8). 
     
     
         3 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , having a heavy chain sequence comprising a sequence which has at least 70% sequence identity to the sequence EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYARSV QYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:7) and/or having a light chain sequence which has at least 70% sequence identity to the sequence DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRFSGS GSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRA, wherein X is I of M (SEQ ID NO:10). 
     
     
         4 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , having a heavy chain sequence comprising a sequence which has at least 70% sequence identity to the sequence EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYARSV QYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:7) and/or having a light chain sequence which has at least 70% sequence identity to the sequence DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRFSGS GSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKVEIKRTV, wherein X is I of M (SEQ ID NO:11). 
     
     
         5 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , having a heavy chain sequence comprising a sequence which has at least 70% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYARS VQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:9) and/or having a light chain sequence which has at least 70% sequence identity to the sequence DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRFSGS GSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRTV, wherein X is I of M (SEQ ID NO:8). 
     
     
         6 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , having a heavy chain sequence comprising a sequence which has at least 70% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYARS VQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:9) and/or having a light chain sequence which has at least 70% sequence identity to the sequence DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRFSGS GSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRA, wherein X is I of M (SEQ ID NO:10). 
     
     
         7 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , having a heavy chain sequence comprising a sequence which has at least 70% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYARS VQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:9) and/or having a light chain sequence which has at least 70% sequence identity to the sequence DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRFSGS GSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKVEIKRTV, wherein X is I of M (SEQ ID NO:11). 
     
     
         8 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , wherein an asparagine has been replaced by another amino acid. 
     
     
         9 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 8 , wherein said asparagine is an asparagine at position 53 of the heavy chain, whereby the amino acid numbering is according to Kabat (1991). 
     
     
         10 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 9 , wherein said other amino acid is serine. 
     
     
         11 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , wherein at least one amino acid other than cysteine has been replaced with cysteine. 
     
     
         12 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 11 , wherein said at least one amino acid other than cysteine is valine at light chain position 205 and/or valine at light chain position 110, and/or alanine at heavy chain position 114, whereby the amino acid numbering is according to Kabat (1991). 
     
     
         13 . The antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 , which is a human antibody. 
     
     
         14 . An isolated antibody that binds to in vivo-grown  S. aureus.    
     
     
         15 . The antibody of  claim 14 , wherein said antibody is human. 
     
     
         16 . An antibody or functional part or immunoglobulin chain or functional equivalent capable of binding an SD-repeat dependent epitope. 
     
     
         17 . An antibody or functional part or immunoglobulin chain or functional equivalent capable of binding to  S. aureus  ClfA, ClfB, SdrC, SdrD and SdrE. 
     
     
         18 . An antibody or functional part or immunoglobulin chain or functional equivalent which is capable of competing with the antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1  for binding to a  Staphylococcus  species. 
     
     
         19 . An isolated, synthetic or recombinant nucleic acid sequence with a length of at least 15 nucleotides, or a functional equivalent thereof, encoding at least one CDR sequence of the antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 . 
     
     
         20 . An isolated, synthetic or recombinant nucleic acid sequence, or a functional equivalent thereof, comprising a sequence which has at least 70% sequence identity to a sequence selected from the group consisting of cgctttgccatgagc (SEQ ID NO:12), tcgatcaataatgggaataacccatactacgcacggtcggtacaatac (SEQ ID NO:13), gatcaccctagtagtggctggcccacctttgactcc (SEQ ID NO:14), cgggccagtgaaaacgttggtgactggttggcc (SEQ ID NO:15), aagacatctattctagaaagt (SEQ ID NO:16) and caacactatatacgtttcccgtacact (SEQ ID NO:17). 
     
     
         21 . The nucleic acid sequence or functional equivalent according to  claim 20 , wherein said nucleic acid sequence or functional equivalent comprises a sequence which has at least 70% sequence identity to at least part of a nucleotide sequence as depicted in  FIG. 1 , said part having at least 15 nucleotides and encoding at least one CDR region. 
     
     
         22 . An isolated, synthetic or recombinant nucleic acid sequence, or a functional equivalent thereof, comprising a sequence encoding an amino acid sequence which has at least 70% sequence identity to the sequence RFAMS (SEQ ID NO:1), and/or at least 70% sequence identity to the sequence SINNGNNPYYARSVQY (SEQ ID NO:2), and/or at least 70% sequence identity to the sequence DHPSSGWPTFDS (SEQ ID NO:3), and/or at least 70% sequence identity to the sequence RASENVGDWLA (SEQ ID NO:4), and/or at least 70% sequence identity to the sequence KTSILES (SEQ ID NO:5), and/or at least 70% sequence identity to the sequence QHYXRFPYT, wherein X is I or M (SEQ ID NO:6), and/or at least 70% sequence identity to the sequence EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYARSV QYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:7), and/or at least 70% sequence identity to the sequence DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRFSGS GSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRTV, wherein X is I or M (SEQ ID NO:8). 
     
     
         23 . Methods of treating and/or preventing a Gram-positive bacterium-related disorder comprising administering an effective amount of the antibody or functional part or the immunoglobulin chain or functional equivalent thereof according to  claim 1 . 
     
     
         24 . A pharmaceutical composition comprising the antibody or functional part or the immunoglobulin chain or functional equivalent thereof according to  claim 1  and a pharmaceutical acceptable carrier, diluent or excipient. 
     
     
         25 . An isolated or recombinant antibody producing cell capable of producing the antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 . 
     
     
         26 . A method for producing the antibody or functional part or immunoglobulin chain or functional equivalent according to  claim 1 . 
     
     
         27 . The method according to  claim 26 , further comprising harvesting, purifying and/or isolating the antibody or functional part or immunoglobulin chain or functional equivalent. 
     
     
         28 . A method for diagnosing a  Staphylococcus  infection comprising contacting a sample with the antibody or functional part or the immunoglobulin chain or functional equivalent thereof according to  claim 1 . 
     
     
         29 . A method for detecting  S. aureus  and/or  S. epidermidi  comprising contacting a sample with the antibody or functional part or an immunoglobulin chain or functional equivalent thereof according to  claim 1 . 
     
     
         30 . A method for isolating  S. aureus  and/or  S. epidermidis  bacteria comprising contacting a sample with the antibody or functional part or the immunoglobulin chain or functional equivalent thereof according to  claim 1 .

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