PD-1 Signal Peptide and Cell-Penetrating Peptide Synthetic Antitumor Agent

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Solution Overview

Problem

Current anti-PD-1 and anti-PD-L1 antibodies have limited effectiveness on certain tumor types and are expensive, posing a significant challenge in cancer therapy due to high costs.

Innovation Solution

A synthetic peptide combining a signal peptide sequence from PD-1 and a cell-penetrating peptide (CPP) sequence, such as polyarginine, is developed to suppress tumor cell proliferation, offering a cost-effective alternative with enhanced antitumor activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-PD-1 antibodies or anti-PD-L1 antibodies are used as immune checkpoint inhibitors, then the immunoescape mechanism can be blocked and antitumor immunoreactivity can be improved on some tumors, but the therapy becomes very expensive and has substantially no or very low effects on some types of tumor

Engineering Contradiction:
Improveantitumor immunoreactivityVSAvoidproduction cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent creates a simplified copy of the PD-1 signal peptide sequence (amino acids 1-20) combined with a cell-penetrating peptide sequence, which replicates the essential function of the full-length antibody therapy at a fraction of the cost. This synthetic peptide copy achieves antitumor activity without requiring the complex structure and production processes of full antibodies

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The synthetic peptide is designed as a short-lived, easily synthesized alternative to expensive antibodies. The peptide can be produced through simple chemical synthesis rather than complex biological manufacturing, making it a disposable, cost-effective therapeutic agent that achieves its function quickly without requiring the stability and complexity of antibody molecules

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If anti-PD-1 antibodies or anti-PD-L1 antibodies are used as immune checkpoint inhibitors, then the immunoescape mechanism can be blocked, but the therapy becomes very expensive causing unavoidable serious situations in cancer therapy

Engineering Contradiction:
Improveblocking immunoescape mechanismVSAvoidtherapeutic cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent extracts only the critical functional portion of the PD-1 protein (the signal peptide sequence at the N-terminus) and combines it with a cell-penetrating peptide. This extraction approach isolates the essential element needed for immunoescape blockade while eliminating the need for expensive full-length antibody production

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent fundamentally changes the molecular parameters from large protein antibodies (150 kDa) to small synthetic peptides (under 50 amino acids). This parameter change in molecular size, complexity, and production method dramatically reduces therapeutic cost while maintaining the ability to block the immunoescape mechanism

Inventive Principle:
Principle #35Parameter changes

3Reliability

If conventional antibodies are used for cancer therapy, then antitumor activity can be achieved on some tumors, but the high production cost creates unavoidable serious situations

Engineering Contradiction:
Improveantitumor activityVSAvoidcost-effectiveness
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The synthetic peptide creates a functional copy of the essential antitumor signaling capability using only 20 amino acids from the PD-1 signal peptide plus a cell-penetrating sequence. This minimal copy achieves comparable antitumor activity to full antibodies but at dramatically reduced production cost and increased accessibility

Inventive Principle:
Principle #26Copying

Data Source

PatentEP3604345B1Antitumor peptide having PD-1 signal sequence and utilization thereof
Publication Date: 2023.05.10 TOAGOSEI CO LTD

AI summary

Provide is an artificially synthesized antitumor peptide that may suppress proliferation of tumor cells. The peptide provided is a synthetic peptide that contains both (1) an amino acid sequence that forms a signal peptide of a membrane protein, programmed cell death-1 (PD-1), or a modified amino acid sequence thereof in which 1, 2 or 3 amino acid residues deleted from, substituted in or added to the above amino acid sequence; and (2) an amino acid sequence that serves as a cell penetrating peptide (CPP), and wherein the synthetic peptide comprises a total of 100 or fewer amino acid residues.