Consensus Prostate Antigen Nucleic Acid Vaccine Design

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Solution Overview

Problem

There is a need for effective nucleic acid constructs that encode prostate cancer antigens and compositions to induce immune responses against prostate cancer, as existing DNA vaccines face challenges in immunogenicity, particularly in larger animals.

Innovation Solution

The development of nucleic acid molecules encoding consensus prostate proteins, including PSA, PSMA, STEAP, and PSCA, which are 98% homologous to specific sequences, or their immunogenic fragments, to enhance immune response induction and break immune tolerance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional DNA vaccines are used, then safety and stability are improved, but immunogenicity deteriorates in larger animals

Engineering Contradiction:

Improvesafety and stabilityVSAvoiddecreased immunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by optimizing codon usage in the DNA vaccine sequence to match host cell preferences, thereby improving translation efficiency and protein expression levels. This resolves the contradiction by modifying the nucleotide sequence parameters while maintaining the same antigenic protein, thus enhancing immunogenicity without compromising safety or stability of the DNA vaccine platform

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite immunogen structure by fusing multiple prostate cancer antigen sequences (PSA, PSMA, STEAP, PSCA) into a single chimeric protein construct. This composite approach elicits broader immune responses against multiple tumor-associated antigens simultaneously, overcoming the limited immunogenicity of single-antigen DNA vaccines while maintaining the safety profile of the DNA platform

Inventive Principle:

Principle #40Composite materials

2Object-affected harmful factors

If consensus protein sequences with high homology are used, then immunogenicity is improved, but manufacturing complexity increases

Engineering Contradiction:

ImproveimmunogenicityVSAvoidmanufacturing complexity

Core Design Contradiction:

Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent merges multiple antigen-encoding sequences into a single DNA construct that expresses a fusion protein containing epitopes from PSA, PSMA, STEAP, and PSCA. This consolidation simplifies manufacturing by requiring only one transfection step and one protein expression system, while still delivering high immunogenicity through the diverse consensus sequences from multiple prostate cancer antigens

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20250101399A1Consensus Prostate Antigens, Nucleic Acid Molecule Encoding The Same And Vaccine And Uses Comprising The Same

Publication Date: 2025.03.27 INOVIO PHARMACEUTICALS INC

AI summary

Provided herein are consensus amino acid sequences of prostate antigens that are capable of breaking tolerance in a targeted species, including PSA, PSMA, STEAP and PSCA antigens. Also provided are nucleic acid sequences that encode one or more consensus amino acid sequences of prostate antigens PSA, PSMA, STEAP and PSCA, as well as genetic constructs/vectors and vaccines expressing the sequences. Also provided herein are methods for generating an autoimmune response against prostate cancer cells by administering one or more of the vaccines, proteins, and/or nucleic acid sequences that are provided.