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-11168128-B2
Publication Date
2021-11-09
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 provides an isolated antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable domain (VH) and a light chain variable domain (VL) with defined complementarity determining region amino acid sequences set forth in SEQ ID NO. numbers. The antibody or fragment is capable of binding to a SARS-CoV-2 surface glycoprotein (S) expressed on a cell surface of a host cell and/or on a SARS-CoV-2 virion.
A further definition specifies an antibody whose VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113 and whose VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:168. The disclosure also defines heavy chain and light chain sequence components using specified CH1-CH3 and CL sequence regions.
The document describes functional profiles including neutralization of SARS-CoV-2 infection and inhibition of interactions between SARS-CoV-2 and human DC-SIGN, L-SIGN, and SIGLEC-1, as well as ACE2 blocking. It also discloses Fc polypeptides and Fc mutations that enhance binding to FcRn and/or FcγR, including MLNS and GAALIE-related Fc alterations.
Claims Coverage
The consolidated content includes four independent claim families. Across these independent claims, the main inventive features are sequence-defined isolated antibodies or antigen-binding fragments defined by VH/VL CDR sequences or by VH/VL full variable domain sequences, with additional claims specifying CH1-CH3 and CL regions and FcRn/FcγR-enhancing Fc mutation sets; the CDR-based claim explicitly requires binding to SARS-CoV-2 surface glycoprotein (S).
Defined CDR sequences for SARS-CoV-2 S binding
An isolated antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable domain (VH) that comprises CDRH1 amino acid sequence set forth in SEQ ID NO.:106, CDRH2 amino acid sequence set forth in SEQ ID NO.:121, and CDRH3 amino acid sequence set forth in SEQ ID NO.:108, and a light chain variable domain (VL) that comprises CDRL1 amino acid sequence set forth in SEQ ID NO.:169, CDRL2 amino acid sequence set forth in SEQ ID NO.:170, and CDRL3 amino acid sequence set forth in SEQ ID NO.:171, wherein the antibody or antigen-binding fragment is capable of binding to a SARS-CoV-2 surface glycoprotein (S) expressed on a cell surface of a host cell, on a SARS-CoV-2 virion, or both.
VH and VL defined by full variable-domain sequences
An isolated antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), 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.
Heavy-chain and light-chain sequence composition with CH1-CH3 and CL
An isolated antibody that comprises a heavy chain comprising 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.
Alternative CH1-CH3 sequence with the same VH/VL
An isolated antibody that comprises a heavy chain comprising 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.
Overall, the claim set provides sequence-specific coverage at the CDR level and at the VH/VL or heavy-chain/light-chain region-composition level, with binding to SARS-CoV-2 surface glycoprotein (S) explicitly required in the CDR-based independent claim. The coverage also includes FcRn/FcγR-enhancing mutation sets.
Stated Advantages
Enables binding to SARS-CoV-2 surface glycoprotein (S) expressed on a cell surface of a host cell, on a SARS-CoV-2 virion, or both.
Enables neutralizing SARS-CoV-2 infection in vitro, in vivo (animal), and/or in humans.
Inhibits SARS-CoV-2 interactions with human DC-SIGN, L-SIGN, SIGLEC-1, or any combination of these.
Enhances binding to FcRn and/or FcγR compared with a reference Fc polypeptide lacking the mutations.
Provides capability to bind SARS-CoV-2 variants and/or viruses containing specified substitution mutations relative to SEQ ID NO.:165.
Documented Applications
Use of the antibody or antigen-binding fragment in relation to SARS-CoV-2 binding to a cell surface of a host cell and/or to a SARS-CoV-2 virion.
Neutralization of SARS-CoV-2 infection in vitro, in vivo (animal), and/or humans.
Inhibition of SARS-CoV-2 interactions with human DC-SIGN, L-SIGN, SIGLEC-1, or any combination of these.
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