Engineered SARS-CoV-2 Spike Polypeptides for Stable Diagnostics

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Solution Overview

Problem

Current methods for producing stable and reliable viral proteins for COVID-19 testing and diagnostics face challenges due to the instability and low yield of SARS-CoV-2 spike ectodomain proteins, which limits the effectiveness of COVID-19 diagnostic assays and vaccine-induced immune response detection.

Innovation Solution

Engineered SARS-CoV-2 spike ectodomain polypeptides with mutations such as D614G and R682A, R683G, and R685G are developed to enhance stability and resistance to furin cleavage, increasing production yield and purity, allowing for improved diagnostic methods and immune response detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If SARS-CoV-2 spike ectodomain proteins are produced using conventional methods, then the proteins can be obtained for diagnostic use, but the proteins exhibit instability and low production yield

Engineering Contradiction:

Improveproduction yieldVSAvoidprotein stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by introducing specific amino acid mutations (D614G, R682A, R683G, R685G) in the spike ectodomain protein sequence. These mutations modify the protein's physical and chemical properties to enhance stability and resistance to furin cleavage, directly resolving the contradiction between productivity and stability by changing the molecular parameters of the protein itself

Inventive Principle:

Principle #35Parameter changes

2Reliability

If the spike ectodomain protein is engineered with mutations to enhance stability, then production yield and purity increase, but the protein structure is modified

Engineering Contradiction:

Improvediagnostic reliabilityVSAvoidprotein structure

Core Design Contradiction:

ReliabilityVSShape

Solution Approach 1:

The patent applies local quality by introducing mutations at specific localized positions (D614G, R682A, R683G, R685G) within the spike ectodomain rather than globally altering the entire protein structure. This allows the protein to maintain its overall functional structure while achieving enhanced stability and diagnostic reliability at specific critical regions

Inventive Principle:

Principle #3Local quality

3Ease of manufacture

If conventional spike protein production methods are used, then the process is simple, but the yield is low and the protein is susceptible to furin cleavage

Engineering Contradiction:

Improveproduction simplicityVSAvoidproduction yield

Core Design Contradiction:

Ease of manufactureVSProductivity

Solution Approach 1:

The patent modifies the furin cleavage motif sequence parameters (R682A, R683G, R685G mutations) to prevent furin-mediated cleavage. This simple sequence change maintains ease of manufacture while dramatically improving productivity by stabilizing the protein and preventing degradation, eliminating the need for complex production protocols

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20220324918A1SARS-CoV-2 SPIKE ECTODOMAIN POLYPEPTIDES AND COMPOSITIONS AND METHODS THEREOF

Publication Date: 2022.10.13 REGENTS OF THE UNIVERSITY OF MINNESOTA

AI summary

The present disclosure provides engineered SARS-CoV-2 spike ectodomain polypeptides and cells for producing such a polypeptide, as well as compositions and methods thereof.