Antibody molecules to dengue virus and uses thereof
Inventors
Robinson, Luke • Shriver, Zachary • Myette, James R. • Babcock, Gregory • Viswanathan, Karthik
Assignees
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Publication Number
US-11059883-B2
Publication Date
2021-07-13
Expiration Date
Abstract
Antibody molecules that specifically bind to dengue virus are disclosed. In certain embodiments, the antibody molecule bind to dengue virus serotypes DV-1, DV-2, DV-3, and DV-4. The antibody molecules can be used to treat, prevent, and/or diagnose dengue virus.
Core Innovation
The disclosed subject matter provides isolated, recombinant, and humanized antibody molecules directed to dengue virus EDIII, including antibodies that bind dengue virus serotypes DV-1 through DV-4. The core antibody concept targets a conserved “A” beta-strand of EDIII, and the disclosure includes monoclonal antibodies defined in terms of heavy chain and light chain variable region segments.
The antibody molecules are characterized by specified CDR1, CDR2, and CDR3 amino-acid sequences in the heavy chain immunoglobulin variable region segment and the light chain variable region segment. The disclosure provides specific VH and VL CDR sequences, including DVYMS, RIDPENGDTKYDPKLQG, and GWEGFAY for the heavy chain CDRs, and RASENVDKYGNSFMH, RASELQW, and QRSNEVPWT for the light chain CDRs, together with alternative CDR definitions including Kabat-defined CDRs and Chothia-defined CDRs.
The disclosure also provides functional property ranges for binding and neutralization, including EDIII binding with K_D values less than about 100 nM and representative values down to about 10 nM. The sequence definitions are linked to antibody molecules used to target dengue virus EDIII through specified heavy-chain and light-chain CDR amino-acid sequences and SEQ ID-defined variable regions, and the invention further includes pharmaceutical compositions, nucleic acids encoding the antibodies, expression vectors and host cells, and kit formulations.
Claims Coverage
The document includes two independent claims, each centered on treating dengue virus infection by administering an isolated antibody molecule. Across the independent claims, the inventive coverage focuses on specific heavy-chain and light-chain CDR amino-acid sequences and specific VH and VL amino-acid sequences defined by SEQ ID NO: 1 and SEQ ID NO: 2.
Specific CDR-defined heavy and light variable regions for treating dengue virus
An isolated antibody molecule for treating dengue virus in an effective amount, comprising a heavy chain variable region segment with CDR1 comprising DVYMS (SEQ ID NO: 3), CDR2 comprising RIDPENGDTKYDPKLQG (SEQ ID NO: 4), and CDR3 comprising GWEGFAY (SEQ ID NO: 5), and a light chain variable region segment with CDR1 comprising RASENVDKYGNSFMH (SEQ ID NO: 6), CDR2 comprising RASELQW (SEQ ID NO: 7), and CDR3 comprising QRSNEVPWT (SEQ ID NO: 8).
Specific VH and VL sequence-defined antibody for treating dengue virus infection
A method of treating a dengue virus infection by administering an effective amount of an isolated antibody molecule comprising the VH amino acid sequence of SEQ ID NO: 1 and the VL amino acid sequence of SEQ ID NO: 2.
Overall claim coverage in the provided material targets dengue virus treatment via administration of isolated antibody molecules defined by either explicit heavy-chain and light-chain CDR amino-acid sequences or explicit VH and VL amino-acid sequences identified by SEQ ID NO: 1 and SEQ ID NO: 2.
Stated Advantages
Improved affinity versus reference antibodies A11/4E5A and 4E11.
Improved neutralization potency versus reference antibodies A11/4E5A and 4E11, including improved IC50 in focus reduction neutralization tests.
EDIII binding with K_D values less than about 100 nM, including representative values down to about 10 nM.
Documented Applications
Treating dengue virus and preventing dengue, using the disclosed antibody molecules.
Diagnosing dengue by detecting antibody-antigen complexes after contacting a sample with an antibody and detecting the complex.
Pharmaceutical compositions and kit formulations comprising the antibody molecules.
Methods involving treatment and optional combination with antiviral agents and administration routes including parenteral or intravenous [procedural detail omitted for safety].
Treating dengue virus by administering an isolated antibody molecule in an amount effective to treat the virus.
Treating a dengue virus infection by administering an effective amount of an isolated antibody molecule comprising SEQ ID NO: 1 (VH) and SEQ ID NO: 2 (VL).
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