Ultrastable Antibody Ionic Liquids via Water Extraction

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Solution Overview

Problem

Current biological materials, such as proteins and antibodies, are unstable and have short shelf-lives due to the detrimental effects of water, which requires constant refrigeration for storage and handling, and are not feasible in areas without access to refrigeration equipment.

Innovation Solution

The development of ultra-stable, water-free protein ionic liquids is achieved by cationizing proteins, purifying them, titrating with biologically-compatible counter anions, dialyzing to remove excess polymer, and lyophilizing to create a stable, heat-resistant liquid that maintains biological recognition activity without refrigeration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If water is present in antibody solutions to maintain biological activity, then binding affinity and antigen recognition are preserved, but hydrolysis, oxidation, and thermal denaturation increase leading to short shelf-lives

Engineering Contradiction:
Improvebiological activityVSAvoidshelf-life
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent removes water from antibody solutions to eliminate the harmful effects of water (hydrolysis, oxidation, thermal denaturation) while preserving the antibody's biological activity. This is achieved through lyophilization and formulation in non-aqueous environments, extracting the harmful water component while retaining the functional antibody.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent creates composite antibody formulations by combining antibodies with protective excipients and non-aqueous matrices. These composite materials provide a stable environment that prevents degradation while maintaining biological activity, resolving the contradiction between water-dependent functionality and water-induced degradation.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If refrigeration is used to extend antibody shelf-life and prevent degradation, then stability is improved, but the need for refrigeration infrastructure and energy consumption increase

Engineering Contradiction:
Improveantibody stabilityVSAvoidrefrigeration energy
Core Design Contradiction:
Stability of the object's compositionVSUse of energy by stationary object

Solution Approach 1:

The patent extracts water from the antibody solution to eliminate the need for refrigeration. By removing water, the primary medium that enables thermal degradation and chemical reactions, the antibody becomes stable at ambient temperatures without requiring energy-intensive cold storage infrastructure.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the physical and chemical parameters of the antibody formulation by transitioning from aqueous to non-aqueous environments. This parameter change fundamentally alters the degradation kinetics, allowing stable storage at higher temperatures without refrigeration, thereby eliminating energy consumption for cooling.

Inventive Principle:
Principle #35Parameter changes

3Loss of energy

If antibodies are stored at ambient temperature without refrigeration, then energy consumption is reduced, but hydrolysis and thermal denaturation occur rapidly leading to short half-lives

Engineering Contradiction:
Improverefrigeration energyVSAvoidantibody half-life
Core Design Contradiction:
Loss of energyVSDuration of action of stationary object

Solution Approach 1:

The patent removes water from the system to prevent water-mediated degradation pathways (hydrolysis, oxidation) that would otherwise rapidly decompose antibodies at ambient temperatures. This extraction enables long shelf-life without refrigeration.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies preliminary protective measures during formulation, such as adding stabilizing excipients and optimizing pH buffers, to preemptively counteract thermal and chemical degradation before storage. This preliminary anti-action allows the antibody to resist degradation mechanisms at ambient temperatures.

Inventive Principle:
Principle #9Preliminary anti-action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The resulting protein ionic liquids are stable at extreme temperatures, exhibit prolonged shelf-lives, and do not require refrigeration, making them suitable for use in various applications, including diagnostics and therapeutics, while reducing the need for refrigeration infrastructure.

Implementation Method 1

titrating the cationized proteins with a corresponding biologically-compatible counter anionic polymer to create at least one antibody cation/anion pair

Methodology Applied
Scientific EffectIon pairing: Ion Repulsion/Attraction

Implementation Method 2

lyophilizing the at least one protein cation/anion pair to remove most of the water, forming a lyophilized solid

Methodology Applied
Scientific EffectFreeze drying: Freeze Drying

Data Source

PatentUS11058770B1Ultrastable antibody ionic liquids
Publication Date: 2021.07.13 THE GOVERNMENT OF THE UNITED STATES AS REPRESENTED BY THE SECRETARY OF THE AIR FORCE
  • US11058770B1 patent drawing
  • US11058770B1 patent drawing
  • US11058770B1 patent drawing

AI summary

A stable protein ionic liquid, comprising an anti-hemoglobin cation/anion pair. The anti-hemoglobin cation/anion pair may be an anionic polymer of poly(ethylene glycol) 4-nonylphenyl 3-sulfopropyl ether. The anti-hemoglobin cation/anion pair may further comprise a cationized anti-hemoglobin antibody, single-chain antibodies from camelids, antibody fragments, polyclonal Anti-horse spleen ferritin antibodies, monoclonal Anti-Flag antibodies, monoclonal Anti-HRP2 to Plasmodium falciparum, polyclonal Anti-neuropeptide Y, polyclonal Anti-human troponin, isotypes of antibodies, or combinations of multiple antibodies.