Optimized nucleic acid antibody constructs encoding anti-respiratory syncytial virus (RSV) antibodies
Inventors
Weiner, David • Guibinga, Ghiabe • COOCH, Neil • Reed, Charles
Assignees
Wistar Institute of Anatomy and Biology • Inovio Pharmaceuticals Inc
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Publication Number
US-12054537-B2
Publication Date
2024-08-06
Expiration Date
Abstract
Disclosed herein are compositions comprising structurally modified DNA encoded antibodies (DMAbs), methods of structurally modifying DMAbs, and methods of using structurally modified DMAbs.
Core Innovation
The document describes recombinant nucleic acid sequence constructs that encode synthetic structurally modified DMAbs having anti-RSV activity. The nucleic acid molecules include at least one nucleotide sequence encoding an anti-RSV DMAb amino acid sequence selected from SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, and SEQ ID NO:119, and are suitable for in vivo expression and antigen binding.
The DMAbs are generated using structurally modified components that include CDR/frame/hinge/scaffold modifications and modeling approaches. It describes modification formats such as full graft, partial graft, scaffold modification, and scFv-Fc conversion, with linker concepts including a (G4S) linker (SEQ ID NO:53) and a Whitlow linker (SEQ ID NO:109).
Multiple nucleic acid construct arrangements are described for assembling the antibody components within recombinant constructs, including separate heavy- and light-chain vectors linked to a leader sequence or signal peptide, and a single construct that includes heavy and light sequences, with optional protease cleavage site and/or linker sequence and promoter/leader configurations. Construct architecture and expression elements include promoter, intron, transcription termination region, initiation codon, termination codon, polyadenylation signal, leader sequences, signal peptides, plasmids, expression vectors, circular or linear cassettes, bidirectional expression vectors, viral vectors including retrovirus, adenovirus, AAV, herpes virus, and lentivirus, and RNA transcripts.
Claims Coverage
The claim set covers nucleic acid compositions encoding structurally modified anti-RSV DMAbs with specified SEQ ID amino-acid selections, and extends to treating RSV infection by administering such compositions. Across the independent claims, the core inventive focus centers on the defined anti-RSV structurally modified DMAb sequence set and the nucleic acid/construct context.
Nucleic acid encoding structurally modified anti-rsv dmAb sequence set
A composition comprising a nucleic acid molecule comprising at least one nucleotide sequence encoding a structurally modified anti-RSV DMAb, wherein the anti-RSV DMAb comprises an amino acid sequence selected from the group consisting of SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, and SEQ ID NO:119.
Multiple encoded structurally modified anti-rsv dmAbs in one nucleic acid molecule
The composition includes a nucleic acid molecule containing at least two nucleotide sequences, each encoding a structurally modified DMAb.
Defined nucleotide sequence encodings for the anti-rsv dmAb
The composition includes a nucleic acid molecule whose nucleotide sequence is selected from SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, or SEQ ID NO:118.
Nucleic acid molecule includes an expression vector
The composition is characterized such that the nucleic acid molecule includes an expression vector.
Rsv treatment by administering nucleic acid composition
A method for treating an RSV infection by administering at least one composition comprising a nucleic acid molecule that encodes a structurally modified anti-RSV DMAb with an amino acid sequence selected from SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, and SEQ ID NO:119 to a subject in need.
Claim coverage is centered on a nucleic acid molecule encoding structurally modified anti-RSV DMAbs with amino acid sequences selected from defined SEQ IDs, and it extends to dependent embodiments specifying additional nucleotide-sequence content, specific nucleotide SEQ IDs, inclusion of an expression vector, and treating RSV infection by administration to a subject in need.
Stated Advantages
Optimizing antibody expression and antigen binding in vivo.
Documented Applications
Use in connection with antigen targeting for RSV antigens, including RSV F protein (prefusion/postfusion), RSV G protein, and RSV proteins including NS1/NS2/N/P/M/SH/M2-1/M2-2/L, for generating synthetic structurally modified DMAbs.
In vivo DNA vaccine concepts involving delivery and expression of nucleic acid constructs to generate synthetic antibodies.
Treating RSV infection by administering a nucleic-acid-encoded structurally modified anti-RSV DMAb composition to a subject who needs the treatment.
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