Optimized synthetic consensus immunogenic compositions targeting fibroblast activation protein
Inventors
Weiner, David • DUPERRET, Elizabeth
Assignees
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Publication Number
US-12697298-B2
Publication Date
2026-08-04
Expiration Date
Abstract
Provided herein is an immunogenic composition comprising a synthetic consensus FAP antigen. Also disclosed herein is a method of treating or preventing a tumor associated pathology in a subject in need thereof, by administering the immunogenic composition to the subject.
Core Innovation
The invention relates to optimized synthetic consensus immunogenic FAP compositions. These compositions include nucleic acids encoding FAP polypeptides based on SEQ ID-based identity/fragment criteria, and corresponding peptide embodiments. The nucleic acids are described as having a single polypeptide with an amino acid sequence such as SEQ ID NO:4.
The nucleic acid constructs are described as operably linked to regulatory elements, including a start codon, an IgE leader sequence, and a stop codon. The disclosed designs also contemplate optional expression vector, viral particle, and immunogenic composition formats for delivery of the FAP-encoding material.
The disclosed immunogenic compositions are stated to be used for inducing immune responses and for treatment and/or prevention of tumor-associated pathologies, including tumor growth, metastasis, and angiogenesis. Mechanistic/experimental support described in the partial content includes enhanced IFN-gamma and TNF-alpha T-cell responses and changes in tumor microenvironment features such as reduced tumor FAP/hyaluronan and macrophage infiltration with increased CD8+ infiltration.
Claims Coverage
The provided independent claims cover two core inventive subject matters: an isolated nucleic acid encoding a specific FAP polypeptide sequence, and an isolated peptide consisting of that FAP sequence, optionally formulated as an immunogenic pharmaceutical composition. The inventive features across these claims focus on exact sequence identity (SEQ ID NO:4) and, for the nucleic acids, operable regulatory architecture including an IgE leader.
Isolated nucleic acid encoding an FAP polypeptide of SEQ ID NO:4
An isolated nucleic acid molecule encoding a single polypeptide, wherein the single polypeptide comprises the amino acid sequence of SEQ ID NO:4.
DNA or RNA encoding SEQ ID NO:4 polypeptide
A nucleic acid molecule wherein the nucleic acid molecule is selected from DNA and RNA, encoding a single polypeptide comprising the amino acid sequence of SEQ ID NO:4.
Operable linkage to start codon, IgE leader sequence, and stop codon
A nucleic acid molecule wherein the encoded polypeptide is operably linked to regulatory sequences including a start codon, an IgE leader sequence, and a stop codon.
Isolated peptide consisting of SEQ ID NO:4
An isolated peptide consisting of the amino acid sequence of SEQ ID NO:4.
Immunogenic pharmaceutical composition with pharmaceutically acceptable excipient
An immunogenic pharmaceutical composition comprising the peptide together with a pharmaceutically acceptable excipient.
Overall, the claim set centers on sequence-defined FAP constructs using SEQ ID NO:4, with nucleic-acid embodiments limited to DNA/RNA and further requiring operable regulatory elements including an IgE leader sequence. The peptide embodiment is confined to an isolated peptide consisting of SEQ ID NO:4, with an optional immunogenic pharmaceutical formulation including a pharmaceutically acceptable excipient.
Stated Advantages
Enhanced IFN-gamma and TNF-alpha T-cell responses are described in the partial content.
Reduction of tumor FAP/hyaluronan and macrophage infiltration is described in the partial content.
Increased CD8+ infiltration is described in the partial content.
Treatment and/or prevention of tumor-associated pathologies including tumor growth, metastasis, and angiogenesis is described in the partial content.
Documented Applications
Inducing immune responses, including humoral and T-cell responses, as described in the partial content.
Treatment and/or prevention of tumor-associated pathologies including tumor growth, metastasis, and angiogenesis, as described in the partial content.
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