Engineered IL-1R-I Binding Polypeptides for Tissue Penetration

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current therapies for inflammatory, autoinflammatory, and autoimmune diseases often rely on large molecule drugs like antibodies, which have poor tissue distribution and penetration due to their size, limiting their effectiveness.

Innovation Solution

Development of engineered polypeptides with a high binding affinity for interleukin-1 receptor type-I (IL-1R-I), which can be used as therapeutic, prognostic, and diagnostic agents, overcoming the limitations of large molecule drugs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If large molecule drugs like antibodies are used to target IL-1R-I, then binding affinity for the receptor is achieved, but tissue distribution and penetration capacity deteriorate

Engineering Contradiction:

Improvebinding affinityVSAvoidtissue penetration

Core Design Contradiction:

ReliabilityVSVolume of moving object

Solution Approach 1:

The patent extracts the essential binding function from large antibody molecules by identifying and isolating the specific antigen-binding fragments (scFv, Fab, F(ab')2) that contain the complementarity-determining regions (CDRs). These extracted fragments retain the ability to bind IL-1R-I with high affinity while removing the bulky Fc regions that impede tissue penetration, thereby resolving the contradiction between binding reliability and tissue distribution

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the antibody molecule into functional domains, separating the antigen-binding variable regions from the effector Fc regions. By further dividing these into smaller units such as single-chain variable fragments (scFv) and minimal binding motifs, the invention creates progressively smaller molecular entities that maintain binding affinity while improving tissue penetration capacity

Inventive Principle:

Principle #1Segmentation

2Volume of moving object

If smaller polypeptides are used to improve tissue penetration, then tissue distribution is improved, but binding affinity may deteriorate

Engineering Contradiction:

Improvetissue penetrationVSAvoidbinding affinity

Core Design Contradiction:

Volume of moving objectVSReliability

Solution Approach 1:

The patent systematically varies the parameters of the polypeptide sequences by optimizing the length, composition, and configuration of the variable regions and CDRs. Through iterative design and selection processes, the invention identifies specific sequence parameters that maximize binding affinity within the constrained size of smaller polypeptides, thereby maintaining high reliability despite reduced molecular volume

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite polypeptide structures that combine different functional elements - such as linking sequences, stabilizing regions, and optimized CDRs - into integrated designs. These composite structures achieve enhanced binding affinity through synergistic interactions between components while maintaining the overall small size necessary for tissue penetration

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20250066451A1Il-IR-i binding polypeptide

Publication Date: 2025.02.27 SWEDISH ORPHAN BIOVITRUM AB

AI summary

The present disclosure relates to a class of engineered polypeptides having a binding affinity for interleukin-1 receptor type-I (IL-1R-I) which comprise the binding motif (BM) EX2X3X4X5X6X7EIX10X11LPNLX16RX18QYX21A FIX25X26LX28D. The present disclosure also relates to the use of such an IL-1R-I binding polypeptide as a therapeutic, prognostic and/or diagnostic agent.