Multimeric Protein Complexes as Synthetic Antibody Substitutes

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Solution Overview

Problem

Current monoclonal antibody-based prophylactics and therapeutics for SARS-CoV-2 and its mutational descendants are costly, unstable, and not easily adaptable for large-scale production, posing challenges for urgent care providers and military personnel, and risk triggering unwanted viral responses such as antibody-dependent enhancement or autoimmune reactions.

Innovation Solution

Development of a multimeric protein complex as a synthetic antibody substitute, composed of a modified symmetric multimeric protein complex with a pathogen binding domain, expressed in prokaryotic cells, which can be mass-produced at low cost and adapted to emerging viral threats, utilizing a modular structure of monomeric proteins, beta solenoid domains, and pathogen binding domains to match the symmetry and geometry of viral envelope proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monoclonal antibodies are used for viral neutralization, then neutralization effectiveness is achieved, but production cost increases and scalability decreases

Engineering Contradiction:
Improveneutralization effectivenessVSAvoidproduction cost and scalability
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent creates simplified copies of antibody functionality using synthetic multimeric proteins that replicate the essential binding and neutralization functions without requiring complex mammalian cell culture systems. The synthetic proteins copy the antigen-binding capability while eliminating the expensive production infrastructure needs.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent employs synthetic proteins that can be produced more cheaply and discarded if needed, rather than investing in expensive monoclonal antibody production chains. The simplified protein structures allow for lower-cost production methods while maintaining functional effectiveness.

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

2Reliability

If monoclonal antibodies are used for prophylaxis, then viral neutralization is achieved, but environmental stability decreases

Engineering Contradiction:
Improveviral neutralizationVSAvoidenvironmental stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent modifies protein parameters by using synthetic amino acid sequences and multimeric structures that enhance environmental stability. The designed proteins have optimized structural parameters including disulfide bonds and compact folding that resist denaturation under various environmental conditions while maintaining antigen binding capability.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If monoclonal antibodies are used for treatment, then viral infection is neutralized, but adaptability to viral mutations decreases

Engineering Contradiction:
Improveviral infection neutralizationVSAvoidadaptability to viral mutations
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the antibody function into separate modular components: a stable synthetic protein scaffold and interchangeable antigen-binding domains. This segmentation allows the binding domains to be rapidly swapped or modified to match different viral variants while the stable scaffold provides consistent structural support and production advantages.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a dynamic system where the antigen-binding components can be quickly updated in response to viral mutations, while the core protein structure remains stable. This dynamic adaptability allows the treatment approach to evolve with emerging variants without requiring complete redesign of the production system.

Inventive Principle:
Principle #15Dynamics

4Reliability

If monoclonal antibodies are administered intravenously, then therapeutic effect is achieved, but production complexity increases

Engineering Contradiction:
Improvetherapeutic effectVSAvoidproduction complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts only the essential functional elements needed for viral neutralization, removing the complex glycosylation patterns, heavy chain-light chain associations, and other complicated features of natural antibodies. This extraction results in simplified proteins that are easier to produce while retaining therapeutic effectiveness.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentUS20230382977A1Multimeric protein complexes as antibody substitutes for neutralization of viral pathogens in prophylactic and therapeutic applications
Publication Date: 2023.11.30 PROTEIN ARCHITECTS CORP
  • US20230382977A1 patent drawing
  • US20230382977A1 patent drawing
  • US20230382977A1 patent drawing

AI summary

The present patent consists of an engineered multimeric protein complex as antibody substitute composed of human proteins, with an m-fold symmetry, with each m-fold element containing a modified monomeric protein derived from a symmetric human multimeric protein complex fused to a module containing n fused, modified human beta solenoid proteins (mBSP), and that fused to a human derived pathogen binding domain (PBD), as well as a separate antibody substitute composed of P human PBD complexes. The invention may find application in prophylactic and therapeutic treatments for viral infections, especially for COVID19 by neutralizing the SARS-CoV-2 virus.