Antibodies against SARS-CoV-2 and methods of using the same
Inventors
Corti, Davide • Fink, Katja • Beltramello, Martina • Cameroni, Elisabetta • PINTO, Dora • Snell, Gyorgy • LEMPP, Florian A. • Telenti, Amalio
Assignees
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Publication Number
US-11479599-B2
Publication Date
2022-10-25
Expiration Date
Abstract
The instant disclosure provides antibodies and antigen-binding fragments thereof that can bind to a SARS-CoV-2 antigen and, in certain embodiments, are capable of neutralizing a SARS-CoV-2 infection. Also provided are polynucleotides that encode an antibody or antigen-binding fragment, vectors and host cells that comprise a polynucleotide, pharmaceutical compositions, and methods of using the presently disclosed antibodies, antigen-binding fragments, polynucleotides, vectors, host cells, and compositions to treat or diagnose a SARS-CoV-2 infection.
Core Innovation
The invention relates to SARS-CoV-2 neutralizing antibodies and antigen-binding fragments that bind the SARS-CoV-2 spike (S) glycoprotein, including the RBD and RBM. The antibodies are defined by complementarity determining region amino acid sequences set forth in SEQ ID NOs, including SEQ ID NO.:106, 121, 108, and 169, 170, 171, and are characterized by binding affinity and neutralization potency against SARS-CoV-2 S and/or RBD.
The described antibodies target the ACE2 receptor binding motif and inhibit SARS-CoV-2 interactions with human DC-SIGN, human L-SIGN, and/or human SIGLEC-1. The document also states cross-reactivity with SARS-CoV and activity against multiple SARS-CoV-2 variants.
The patent additionally covers associated polynucleotides, vectors, host cells, and engineered antibody formats including IgG, Fab, Fab’, scFv, scFab, F(ab')2, monospecific or multispecific formats, including bispecific and multi-domain arrangements. It describes Fc region concepts, including FcRn and FcγR affinity-enhancing mutations, and provides embodiments for diagnosis and treatment by administering an effective amount of a SARS-CoV-2 neutralizing antibody or antigen-binding fragment defined by the specified variable-region sequences.
Claims Coverage
The partial content provides four independent claims. Across these claims, the inventive features primarily involve administering SARS-CoV-2 neutralizing antibodies or antigen-binding fragments to treat infection, with sequence-defined VH/VL and, in some claims, CH1-CH3 and CL using specific SEQ ID NOs.
Treating SARS-CoV-2 infection with specified CDR-defined neutralizing antibody or antigen-binding fragment
Administering to the subject an effective amount of a SARS-CoV-2 neutralizing antibody or antigen-binding fragment comprising a heavy chain variable domain with CDRH1 in SEQ ID NO.:106, CDRH2 in SEQ ID NO.:121, and CDRH3 in SEQ ID NO.:108, and a light chain variable domain with CDRL1 in SEQ ID NO.:169, CDRL2 in SEQ ID NO.:170, and CDRL3 in SEQ ID NO.:171.
Treating SARS-CoV-2 infection with SEQ ID NO.:113 VH and SEQ ID NO.:168 VL antibody or antigen-binding fragment
Administering to the subject an effective amount of a SARS-CoV-2 neutralizing antibody or antigen-binding fragment comprising a heavy chain variable domain and a light chain variable domain, wherein the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113 and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:168.
Treating SARS-CoV-2 infection with antibody having SEQ ID NO.:113 VH and SEQ ID NO.:173 CH1-CH3 plus SEQ ID NO.:168 VL and SEQ ID NO.:174 CL
Administering to the subject an effective amount of a SARS-CoV-2 neutralizing antibody comprising a heavy chain with a VH that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113 and a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:173, and a light chain comprising a VL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:168 and a CL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:174.
Treating SARS-CoV-2 infection with antibody having SEQ ID NO.:113 VH and SEQ ID NO.:175 CH1-CH3 plus SEQ ID NO.:168 VL and SEQ ID NO.:174 CL
Administering to the subject an effective amount of a SARS-CoV-2 neutralizing antibody comprising a heavy chain with a VH that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113 and a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:175, and a light chain comprising a VL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:168 and a CL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:174.
Across the independent claims in the provided partial content, the claim coverage focuses on treating SARS-CoV-2 infection by administering an effective amount of a neutralizing antibody or antigen-binding fragment defined by specific sequence requirements, including CDR-defined VH/VL and, in other independent claims, full-length heavy- and light-chain components including VH, CH1-CH3, VL, and CL sequences.
Stated Advantages
Neutralization of SARS-CoV-2 infection.
Inhibition of SARS-CoV-2 interactions with human DC-SIGN, human L-SIGN, and/or human SIGLEC-1.
Cross-reactivity with SARS-CoV.
Activity against multiple SARS-CoV-2 variants.
Engineered Fc polypeptide mutations increase binding to FcRn and/or FcγR compared with a reference Fc polypeptide without those mutations.
Documented Applications
Treatment of SARS-CoV-2 infection in a subject using a SARS-CoV-2 neutralizing antibody or antigen-binding fragment.
An in vitro SARS-CoV-2 diagnostic assay by detecting antigen–antibody complexes in a blood sample.
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