Binding molecules against SARS-coronavirus and uses thereof

Abstract

Described are binding molecules that specifically bind to SARS-CoV, nucleic acid molecules encoding the binding molecules, compositions comprising the binding molecules, and methods of identifying or producing the binding molecules. The binding molecules are capable of specifically binding to SARS-CoV, and can be used in the diagnosis, prophylaxis, and/or treatment of a condition resulting from SAR.

1 . An binding molecule, which is recombinantly or synthetically produced and/or isolated, and is capable of specifically binding to a SARS-CoV and having SARS-CoV neutralizing activity. 
     
     
         2 . The binding molecule of  claim 1 , which is a human binding molecule. 
     
     
         3 . The binding molecule of  claim 1  comprising a variable heavy chain comprising an amino acid sequence selected from the group of amino acid sequences consisting of SEQ ID NO:23, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:315, and SEQ ID NO:447. 
     
     
         4 . The binding molecule of  claim 3  comprising a variable heavy chain comprising an amino acid sequence selected from the group of amino acid sequences consisting of SEQ ID NO:23, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:315, SEQ ID NO:447, and an amino acid sequence that is at least 95% homologous to one of said amino acid sequences. 
     
     
         5 . A binding molecule, which is recombinantly or synthetically produced and/or isolated, and is capable of specifically binding to amino acid residues 11-19 of the N protein of SARS-CoV. 
     
     
         6 . The binding molecule of  claim 5 , wherein the binding molecule comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO:86. 
     
     
         7 . An immunoconjugate comprising an isolated binding molecule able to specifically bind to a Severe Acute Respiratory Syndrome Coronavirus (SARS-Co-V) and having SARS-CoV neutralizing activity, wherein said immunoconjugate further comprises at least one tag. 
     
     
         8 . A nucleic acid molecule encoding the binding molecule of  claim 1 . 
     
     
         9 . A vector comprising at least one nucleic acid molecule of  claim 8 . 
     
     
         10 . A host cell comprising at least one vector of  claim 9 . 
     
     
         11 . A method of producing a binding molecule able to specifically bind Severe Acute Respiratory Syndrome Coronavirus (SARS-Co-V), wherein the method comprises:
 a) culturing the host cell of  claim 10  under conditions conducive to the expression of the binding molecule, and   b) recovering the expressed binding molecule   so as to produce a binding molecule able to specifically bind SARS-Co-V.   
     
     
         12 . A composition comprising the isolated binding molecule of  claim 1 . 
     
     
         13 . A composition comprising the nucleic acid molecule of  claim 8 . 
     
     
         14 . A pharmaceutical composition for the treatment of Severe Acute Respiratory Syndrome Coronavirus (SARS-Co-V), the pharmaceutical composition comprising:
 the binding molecule of  claim 1 , and   a pharmaceutically acceptable excipient.   
     
     
         15 . A method of identifying a binding molecule able to specifically bind to a Severe Acute Respiratory Syndrome Coronavirus (SARS-Co-V) or a nucleic acid molecule encoding a binding molecule specifically binding to a SARS-CoV, said method comprising:
 a) contacting a phage library of binding molecules with a SARS-CoV or a fragment thereof;   b) selecting at least once for a phage binding to the SARS-CoV or the fragment thereof; and   c) separating and recovering the phage binding to the SARS-CoV or the fragment thereof from the phage library.   
     
     
         16 . The method according to  claim 15 , further comprising:
 isolating, from the recovered phage, the binding molecule and/or the nucleic acid molecule encoding the binding molecule   so as to obtain a binding molecule specifically binding to a SARS-Co-V or a nucleic acid molecule encoding a binding molecule specifically binding to a SARS-CoV.   
     
     
         17 . A phage library of binding molecules, wherein the phage library is prepared from RNA isolated from cells obtained from a subject that has been vaccinated or exposed to a SARS-CoV. 
     
     
         18 . A method of detecting a Severe Acute Respiratory Syndrome Coronavirus (SARS-Co-V) in a sample, said method comprising:
 contacting a sample with a diagnostically effective amount of the binding molecule of  claim 1 , and   determining whether the binding molecule specifically binds to a molecule of the sample.   
     
     
         19 . A method of screening a binding molecule or a functional variant of a binding molecule for specific binding to the same epitope of a Severe Acute Respiratory Syndrome Coronavirus (SARS-Co-V) as the epitope bound by the binding molecule of  claim 1 , wherein the method comprises:
 a) contacting the binding molecule to be screened with the same epitope of a SARS-CoV as the epitope bound by the binding molecule and   b) measuring if the binding molecule to be screened is able to compete for specifically binding to the SARS-CoV with the binding molecule.   
     
     
         20 . A process of identifying a binding molecule having neutralizing activity against Severe Acute Respiratory Syndrome Coronavirus (SARS-Co-V), wherein said method comprises:
 a) contacting a collection of binding molecules on the surface of replicable genetic packages with SARS-CoV under conditions conducive to binding, wherein the neutralizing activity of the binding molecule inactivates the SARS-CoV;   b) separating and recovering binding molecules that bind to SARS-CoV from binding molecules that do not bind;   c) isolating at least one recovered binding molecule; and,   d) verifying if the binding molecule isolated has neutralizing activity against SARS-CoV.   
     
     
         21 . A binding molecule produced by the process of  claim 20 , the binding molecule having neutralizing activity against the SARS-CoV.