PEG Linker Conjugates for Antigen-Specific Immune Response

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a need for expanded uses, compositions, and delivery options for immune response modifier (IRM) compounds, which are useful in treating various diseases and conditions but require innovative formulations to enhance their therapeutic potential.

Innovation Solution

The development of new conjugates that combine an immune response modifier with an antigen using specific linkers, such as those represented by certain formulas, to induce cytokine biosynthesis and modulate the immune response, allowing for effective administration and improved antigen-specific immunological memory.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If IRM compounds are administered alone, then they can stimulate immune system mechanisms, but they lack antigen-specific targeting and delivery efficiency

Engineering Contradiction:

Improveimmune response modulationVSAvoiddelivery efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent combines the immune response modifier (IRM) with the antigen into a single conjugate molecule. This merging allows the IRM to be delivered specifically to antigen-presenting cells along with its target antigen, thereby improving delivery efficiency while maintaining reliable immune response modulation through the IRM's stimulation of Toll-like receptors and cytokine production.

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If IRM compounds are conjugated to antigens, then antigen-specific immune response is enhanced, but the conjugation process may denature the antigen

Engineering Contradiction:

Improveantigen-specific immune responseVSAvoidantigen structure

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent employs a linker molecule as an intermediary between the IRM and the antigen. This linker facilitates the conjugation process while protecting the antigen from denaturation. The linker provides a controlled attachment mechanism that maintains antigen structural integrity and stability, yet still allows the conjugate to elicit a strong antigen-specific immune response through proper antigen presentation.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If complex conjugates are developed to improve therapeutic potential, then treatment efficacy increases, but formulation and delivery complexity increases

Engineering Contradiction:

Improvetreatment efficacyVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the conjugate into distinct functional modules: the immune response modifier portion, the linker portion, and the antigen portion. This segmentation allows each component to be optimized independently for its specific function while simplifying the overall formulation and delivery process. The modular structure enables controlled conjugation and facilitates manufacturing without excessive complexity.

Inventive Principle:

Principle #1Segmentation

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 conjugates induce cytokine biosynthesis, effectively treating viral diseases and tumors, and serve as potent vaccine adjuvants by enhancing the immune response to antigens, while being stable and easily deliverable without denaturing the antigens, with the ability to monitor formation using UV spectroscopy.

Implementation Method 1

the immune response modifier is covalently attached to the linker at * through a hydrazone functional group

Methodology Applied

Scientific EffectCondensation reaction:

Implementation Method 2

the antigen is covalently attached to the linker at ** through an amide, disulfide, urea, thiourea, carbamate, or a carbon-sulfur or carbon-nitrogen bond alpha to an amide or sulfone

Methodology Applied

Scientific EffectPeptide bond formation: Chemical Bonding

Implementation Method 3

with the ability to monitor formation using UV spectroscopy

Methodology Applied

Scientific EffectAbsorption spectroscopy: Absorption Spectroscopy

Data Source

PatentUS10723731B2Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom

Publication Date: 2020.07.28 SOLVENTUM INTELLECTUAL PROPERTIES CO

AI summary

Conjugates of an immune response modifier, a linker, and an antigen are disclosed. The linker is represented by formula:wherein A is CH or N, p is in a range from 1 to 50, R″ is a bond or -alkylene-O—, R′ is alkylene that is optionally interrupted or terminated with one or more amide or ether groups, and E is an amine- or thiol-reactive group. Pharmaceutical compositions containing the compound or the conjugate, methods of making a conjugate, and methods of use of the compounds or conjugates as immunomodulators for inducing cytokine biosynthesis in an animal and for vaccinating an animal are also disclosed. An antigen modified by the linker is also disclosed.