Antibodies against SARS-CoV and methods of use thereof

• US 7,750,123 B2
• Filed: 11/24/2004
• Issued: 07/06/2010
• Est. Priority Date: 11/25/2003
• Status: Expired due to Fees

• Current Assignee: Dana-Farber Cancer Institute
• Original Assignee: Dana-Farber Cancer Institute
• Inventors: Sui, Jianhua, Marasco, Wayne
• Primary Examiner(s): Peng; Bo
• Application Number:
  US10/997,201
• Publication Number:
  US 20050249739A1
• Time in Patent Office: 2,050 Days
• Field of Search: None
• US Class Current: 530/387.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: C07K 16/10 from RNA viruses
• CPC Class Codes: C07K 16/1002 Coronaviridae
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 2770/20011 Coronaviridae

Abstract

The invention provides scFv antibodies and monoclonal antibodies that neutralize SARS-CoV. Also provided are methods of treating and/or preventing a coronavirus-related disease or disorder such as SARS. The invention also provides methods of vaccinating a patient against SARS-CoV. Also provided are methods of diagnosing coronavirus-related diseases or disorders and methods of detecting the presence of a coronavirus in a sample. The invention additionally provides methods of screening for compounds that modulate the binding of SARS-CoV and the SARS-CoV receptor ACE2 as well as for compounds useful to treat SARS-CoV-related diseases or disorders.

Claims

1. A monoclonal antibody which neutralizes SARS-CoV, wherein said monoclonal antibody binds to an epitope on the spike protein (S) of SARS-CoV consisting of amino acids 324 to 503, wherein the antibody neutralizes SARS-CoV, and wherein said monoclonal antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:

12 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO;

20.

2. A monoclonal antibody which neutralizes SARS-CoV, wherein said monoclonal antibody binds to an epitope on the spike protein (S) of SARS-CoV consisting of amino acids 324 to 503, wherein the antibody neutralizes SARS-CoV, and wherein said monoclonal antibody comprises the amino acid sequences encoded by the nucleotide sequences of SEQ ID NOs:

2, 3, 4, and 5.

3. An scFv antibody which neutralizes SARS-CoV, wherein said scFv antibody binds to an epitope on the spike protein (S) of SARS-CoV consisting of amino acids 324 to 503, wherein said scFv antibody neutralizes SARS-CoV, and wherein said scFv antibody comprises the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:

1.

4. A monoclonal antibody which neutralizes SARS-CoV, wherein said antibody has a light chain with three CDRs comprising an amino acid sequence selected from the group consisting of the amino acid sequences of RASQVRSNLA (SEQ ID NO:

37);

DASTAT (SEQ ID NO;

38); and

QQRSNWPPT (SEQ ID NO;

39), and wherein said antibody has a heavy chain with three CDRs comprising an amino acid sequence selected from the group consisting of the amino acid sequences of AH;

VYDNK (SEQ ID NO;

     35); and

RSYYL (SEQ ID NO;

36).