Fusion Polypeptides With Metal-Hydroxide Binding for Tumor Retention

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Solution Overview

Problem

Immunomodulatory polypeptides face challenges such as dose-limiting toxicities and inefficiencies in tumor treatment, particularly when delivered intratumorally, due to systemic exposure and limited persistence at the injection site.

Innovation Solution

Development of fusion polypeptides that include an immunomodulatory polypeptide moiety conjugated with a metal-hydroxide binding polypeptide, characterized by multiple phosphorylation sites, forming a complex that enhances retention at the tumor site and reduces systemic exposure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immunomodulatory polypeptides are delivered by intratumoral injection, then anti-tumor efficacy is improved, but systemic exposure increases causing dose-limiting toxicities

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidsystemic exposure toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces metal hydroxide particles as an intermediary carrier that binds to the immunomodulatory polypeptide via the metal-hydroxide binding polypeptide moiety. This intermediary system enables localized retention at the injection site while preventing systemic distribution, thereby maintaining anti-tumor efficacy and reducing dose-limiting toxicities associated with systemic exposure

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the physicochemical parameters of the immunomodulatory polypeptide by fusing it with a metal-hydroxide binding polypeptide containing multiple phosphorylation sites. This parameter change enables strong binding to metal hydroxide particles, transforming the polypeptide from a systemically distributed agent to a locally retained therapeutic at the tumor site

Inventive Principle:

Principle #35Parameter changes

2Reliability

If immunomodulatory polypeptides are administered at high doses to improve efficacy, then anti-tumor activity increases, but toxicities increase

Engineering Contradiction:

Improveanti-tumor activityVSAvoiddose-limiting toxicities

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the therapeutic function into two distinct components: the immunomodulatory polypeptide moiety that provides anti-tumor activity and the metal-hydroxide binding polypeptide moiety that enables localized retention. This segmentation allows the therapeutic to remain at effective concentrations at the tumor site without requiring high systemic doses, thereby reducing dose-limiting toxicities while maintaining anti-tumor activity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Metal hydroxide particles serve as an intermediary delivery system that concentrates the immunomodulatory polypeptide at the injection site. This intermediary approach enables high local drug concentration for effective anti-tumor activity without proportionally increasing systemic exposure and associated toxicities

Inventive Principle:

Principle #24Intermediary (Mediator)

3Adaptability or versatility

If immunomodulatory polypeptides are delivered systemically to ensure coverage, then therapeutic reach is improved, but persistence at injection site is reduced

Engineering Contradiction:

Improvetherapeutic reachVSAvoidpersistence at injection site

Core Design Contradiction:

Adaptability or versatilityVSDuration of action of stationary object

Solution Approach 1:

Instead of relying on systemic circulation to deliver the therapeutic to the tumor, the patent inverts the approach by using metal hydroxide binding to actively retain the immunomodulatory polypeptide at the injection site. This inversion transforms the therapeutic from a systemically distributed agent with brief local persistence to a locally retained therapeutic with extended duration of action at the tumor site

Inventive Principle:

Principle #13The other way round (Inversion)

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 fusion polypeptides demonstrate improved tumor treatment efficacy through enhanced retention and reduced toxicity, either as monotherapy or in combination with other therapies, including immune modulators and chemotherapies.

Implementation Method 1

polypeptides amenable to phosphorylation can adsorb to alum much more strongly when in their phosphorylated form

Methodology Applied

Scientific EffectAdsorption: Adsorption

Implementation Method 2

the metal hydroxide can act as a particulate scaffold able to persist at the site of injection for extended periods of time

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatic Induction

Data Source

PatentUS20260035706A1Fusion polypeptides

Publication Date: 2026.02.05 ANKYRA THERAPEUTICS INC

AI summary

The present disclosure provides surprisingly useful fusion polypeptides including an immunomodulatory moiety and a metal-hydroxide binding moiety, as well as various related technologies, including methods of making and of using such fusion polypeptides.