US2008014202A1PendingUtilityA1

Multifunctional monoclonal antibodies directed to peptidoglycan of gram-positive bacteria

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Assignee: BIOSYNEXUS INCPriority: Dec 21, 2001Filed: Dec 19, 2006Published: Jan 17, 2008
Est. expiryDec 21, 2021(expired)· nominal 20-yr term from priority
Inventors:Richard F. SchumanJohn Kokai-KunSimon FosterJeffrey R. StinsonGerald W. Fischer
A61K 39/00C07K 2317/24A61K 2039/505C07K 2317/77C07K 2319/30C07K 16/1271C07K 16/1275C07K 16/1278
62
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Claims

Abstract

The present invention encompasses protective monoclonal antibodies that bind to peptidoglycan of Gram-positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro and block nasal colonization by Gram-positive bacteria in vivo. The invention also provides human, humanized and chimeric antibodies. The invention also sets forth the heavy chain and light chain variable regions of an antibody within the invention.

Claims

exact text as granted — not AI-modified
1 . A method for treating a patient comprising, 
 administering a therapeutically effective amount of a composition comprising at least one MAb that binds to peptidoglycan (PepG) of Gram-positive bacteria; wherein said administration results in therapeutically beneficial outcome.    
     
     
         2 . The method of  claim 1 , wherein the therapeutically beneficial outcome comprises a discernable reduction in the number of Gram-positive bacteria in the nares of a colonized patient.  
     
     
         3 . The method of  claim 1 , wherein the therapeutically beneficial outcome comprises a discernable reduction in the likelihood of future nasal colonization.  
     
     
         4 . The method of  claim 1 , wherein the therapeutically beneficial outcome comprises a discernable reduction in the number of Gram-positive bacteria in an infected patient.  
     
     
         5 . The method of  claim 1 , wherein the therapeutically beneficial outcome comprises a discernable reduction in the likelihood of future infection.  
     
     
         6 . The method of  claim 1 , wherein the therapeutically beneficial outcome comprises a discernable reduction in the likelihood of nosocomial infection.  
     
     
         7 . The method of  claim 1 , wherein the composition comprises at least one MAb that enhances the opsonophagocytic killing of Gram-positive bacteria by at least 50%.  
     
     
         8 . The method of  claim 1 , wherein the composition comprises at least one MAb that binds PepG of Gram-positive bacteria at a level at least two-fold greater than background in an ELISA.  
     
     
         9 . The method of  claim 1 , wherein the composition comprises a pharmaceutically acceptable carrier.  
     
     
         10 . The method of  claim 1 , wherein the composition comprises at least one MAb that binds to lipoteichoic acid (LTA) of Gram-positive bacteria.  
     
     
         11 . The method of  claim 1 , wherein the composition comprises at least one MAb that blocks colonization by Gram-positive bacteria upon instillation into the nares of a patient.  
     
     
         12 . The method of  claim 1 , wherein the composition comprises at least one MAb that specifically binds PepG of a Gram-positive bacteria selected from  Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Bacillus subtilis, Bacillus megaterium, Enterococcus faecalis , and  Listeria monocytogenes.    
     
     
         13 . The method of  claim 1 , wherein the composition comprises at least one MAb that specifically binds PepG of  Staphylococcus aureus.    
     
     
         14 . The method of  claim 1 , wherein the composition comprises at least one MAb that specifically binds PepG of  Staphylococcus epidermidis.    
     
     
         15 . The method of  claim 1 , wherein the composition comprises at least one MAb that specifically binds PepG of  Staphylococcus aureus  and  Staphylococcus epidermidis.    
     
     
         16 . The method of  claim 1 , wherein the composition comprises at least one MAb that specifically binds PepG of  Bacillus subtilis.    
     
     
         17 . The method of  claim 1 , wherein the composition comprises at least one MAb selected from MAb-11-232.3, MAb-11-248.2, MAb-11-569.3, MAb-11-232.3 IE9, MAb-99-110FC12 IE4, A130, and M130.  
     
     
         18 . The method of  claim 1 , wherein the composition comprises at least one MAb comprising a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1.  
     
     
         19 . The method of  claim 1 , wherein the composition comprises at least one MAb comprising a light chain variable region having at least 80% identity with the amino acid sequence set forth in SEQ ID NO: 1.  
     
     
         20 . The method of  claim 1 , wherein the composition comprises at least one MAb comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 3.  
     
     
         21 . The method of  claim 1 , wherein the composition comprises at least one MAb comprising a heavy chain variable region having at least 80% identity with the amino acid sequence set forth in SEQ ID NO: 3.  
     
     
         22 . The method of  claim 1 , wherein the composition comprises at least one MAb selected from chimeric, humanized, and human MAbs.  
     
     
         23 . The method of  claim 1 , wherein the composition comprises at least one MAb comprising a modified Fc portion, wherein said modification reduces nonspecific binding of the MAb via the Fc portion.  
     
     
         24 . The method of  claim 1 , wherein the composition comprises at least one MAb selected from a Fab, Fab′, F(ab′) 2 , Fv, SFv, and scFv.  
     
     
         25 . The method of  claim 1 , wherein the composition further comprises at least one antistaphylococcal drug.  
     
     
         26 . The method of  claim 1 , wherein the patient is selected from a hospitalized infant, a premature infant, a burn victim, an elderly patient, an immunocompromised patient, an immununosuppressed patient, a patient undergoing an invasive procedure, and a health care worker.  
     
     
         27 . The method of  claim 1 , wherein the protective monoclonal antibody is administered by a route selected from intravenous, intraperitoneal, intracorporeal injection, intra-articular, intraventricular, intrathecal, intramuscular, subcutaneous, intranasal, intravaginal, and oral.  
     
     
         28 . A composition comprising, a therapeutically effective amount of at least one MAb that binds to peptidoglycan (PepG) of Gram-positive bacteria; wherein said MAb provides a therapeutically beneficial outcome upon administration to a patient.  
     
     
         29 . The composition of  claim 28 , wherein administration reduces the number of Gram-positive bacteria in a patient.  
     
     
         30 . The composition of  claim 28 , wherein at least one MAb binds PepG of Gram-positive bacteria at a level at least two-fold greater than background in an ELISA.  
     
     
         31 . The composition of  claim 28 , wherein at least one MAb enhances opsonophagocytic of Gram-positive bacteria by at least 50%.  
     
     
         32 . The composition of  claim 28 , further comprising a pharmaceutically acceptable carrier.  
     
     
         33 . The composition of  claim 28 , further comprising at least one MAb that binds to lipoteichoic acid (LTA) of Gram-positive bacteria.  
     
     
         34 . The composition of  claim 28 , wherein at least one MAb blocks colonization by Gram-positive bacteria upon instillation into the nares of a patient.  
     
     
         35 . The composition of  claim 28 , wherein at least one MAb specifically binds PepG of a Gram-positive bacteria selected from  Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Bacillus subtilis, Bacillus megaterium, Enterococcus faecalis , and  Listeria monocytogenes.    
     
     
         36 . The composition of  claim 28 , wherein at least one MAb specifically binds PepG of  Staphylococcus aureus.    
     
     
         37 . The composition of  claim 28 , wherein at least one MAb specifically binds PepG of  Staphylococcus epidermidis.    
     
     
         38 . The composition of  claim 28 , wherein at least one MAb specifically binds PepG of  Staphylococcus aureus  and  Staphylococcus epidermidis.    
     
     
         39 . The composition of  claim 28 , wherein at least one MAb specifically binds PepG of  Bacillus subtilis.    
     
     
         40 . The composition of  claim 28 , wherein at least one MAb is selected from MAb-11-232.3, MAb-11-248.2, MAb-11-569.3, MAb-11-232.3 IE9, MAb-99-110FC12 IE4, A130, and M130.  
     
     
         41 . The composition of  claim 28 , wherein at least one MAb comprises a light chain variable region comprising the amino acid sequence set forth in (SEQ ID NO: 1).  
     
     
         42 . The composition of  claim 28 , wherein at least one MAb comprises a light chain variable region having at least 80% identity with the amino acid sequence set forth in (SEQ ID NO: 1).  
     
     
         43 . The composition of  claim 28 , wherein at least one MAb comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 3.  
     
     
         44 . The composition of  claim 28 , wherein at least one MAb comprises a heavy chain variable region having at least 80% identity with the amino acid sequence set forth in (SEQ ID NO: 3).  
     
     
         45 . The composition of  claim 28 , wherein at least one MAb is selected from chimeric, humanized, and human MAbs.  
     
     
         46 . The composition of  claim 28 , wherein at least one MAb comprises a modified Fc portion, wherein said modification reduces nonspecific binding of the MAb via the Fc portion.  
     
     
         47 . The composition of  claim 28 , wherein at least one MAb is selected from a Fab, Fab′, F(ab′) 2 , Fv, SFv, and scFv.  
     
     
         48 . The composition of  claim 28 , further comprising at least one antistaphylococcal drug.  
     
     
         49 . A hybridoma cell line deposited at the ATCC under accession no. PTA-2492.  
     
     
         50 . A hybridoma cell line deposited at the ATCC under accession no. PTA-3659.  
     
     
         51 . A vaccine comprising at least one purified PepG, peptides, fragments and epitopes thereof, in a pharmaceutically acceptable carrier.  
     
     
         52 . A method for treating a patient comprising, 
 administering a therapeutically effective amount of the vaccine of  claim 51.

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