Nucleic acid encoding optimized immunogenic peptide that targets follicle stimulating hormone receptor

Inventors

Weiner, David • PERALES PUCHALT, Alfredo • Yan, Jian • SLAGER, Anna Maria

Assignees

University of Pennsylvania • The Wistar Institute • Inovio Pharmaceuticals Inc

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Publication Number

US-11865166-B2

Patent

Publication Date

2024-01-09

Expiration Date


Abstract

Provided herein is an immunogenic composition comprising a synthetic consensus antigen to Follicle Stimulating Hormone Receptor (FSHR) protein which is abundant in many ovarian cancer sub-types. Also disclosed herein is a method of treating a tumor associated pathology in a subject in need thereof, by administering the immunogenic composition to the subject.

Core Innovation

The invention features optimized consensus FSHR-encoding nucleic acids and immunogenic compositions comprising an isolated nucleic acid molecule encoding a peptide with a specified FSHR amino acid sequence. The nucleic acid molecule can be DNA or RNA, with embodiments comprising sequences with or without an IgE leader designed to break tolerance to native FSHR. These compositions elicit antitumor cellular and humoral responses against FSHR detected in ovarian cancer samples.

Consensus FSHR vaccination stimulates CD4 and CD8 T-cell responses—including IFN̂, TNF̂, and IL-2 production—and generates stronger immune responses than native FSHR. In mouse ovarian tumor models, the vaccination delays tumor progression, reduces tumor-associated signal, and increases survival compared to pVax controls. Because the background section is absent from the provided disclosure, the specific technical problem is not explicitly described in the patent.

Claims Coverage

The claims define two independent claims identifying two inventive features directed to an immunogenic composition and an isolated nucleic acid molecule.

Immunogenic composition comprising an isolated nucleic acid molecule

Claim 1 covers an immunogenic composition comprising an isolated nucleic acid molecule encoding a peptide comprising the amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, or 12. Dependent claims define DNA or RNA forms, sequence identity to listed nucleotide sequences, linkage to a start codon, an IgE leader sequence, or a stop codon, and composition formats including an expression vector, viral particle, pharmaceutically acceptable excipient, or adjuvant.

Isolated nucleic acid molecule encoding a peptide

Claim 9 covers an isolated nucleic acid molecule encoding a peptide comprising the amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, or 12. Dependent claims specify DNA or RNA forms, sequence identity to listed nucleotide sequences, and linkage to a start codon, an IgE leader sequence, or a stop codon.

The claims cover the peptide-encoding nucleic acid both within an immunogenic composition and as an isolated nucleic acid molecule, with dependent claims establishing specific molecular forms, sequence identity, regulatory linkages, and formulation components.

Stated Advantages

Consensus FSHR vaccination stimulates CD4 and CD8 T-cell and antibody responses, inducing stronger IFN̂ and overall immune responses than native FSHR.

In FSHR-positive ovarian tumor models, consensus FSHR vaccination delays tumor progression, reduces tumor-associated signal, and increases survival compared with pVax controls.

Documented Applications

The immunogenic compositions and FSHR-encoding nucleic acids are documented for eliciting antitumor immunity in mouse tumor models of FSHR-positive ovarian cancer.

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