Anti-canine CD16 Polypeptides Enhance ADCC

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Solution Overview

Problem

Current technologies face challenges in effectively targeting and eliminating cancer cells or infected cells expressing specific antigens, due to limitations in the affinity and stability of Fcγ receptors like CD16A on natural killer cells.

Innovation Solution

Development of anti-canine CD16 and CD64 polypeptides, as well as multispecific compounds that include these polypeptides linked to additional functional domains, to enhance the affinity and stability of immune cell interactions with target cells, thereby improving antibody-dependent cellular cytotoxicity (ADCC).

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional Fcγ receptors like CD16A are used on natural killer cells, then the system can recognize target cells, but the affinity and stability of the interaction is insufficient for effective cancer cell elimination

Engineering Contradiction:

Improveaffinity and stability of immune cell interactionsVSAvoidkilling of tumor cells or infected cells

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent modifies the Fcγ receptor by introducing point mutations (e.g., L212F, L212Y, L212W substitutions) to change the binding parameters and increase affinity for IgG Fc regions. This parameter change in the receptor structure directly improves the stability of immune cell interactions while maintaining the killing function

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite Fcγ receptor structures by combining mutated receptor subunits (e.g., CD16A variants with improved affinity) with signaling domains (CD3ζ, FcRγ). This composite structure achieves both high affinity binding and effective signal transduction for tumor cell killing

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If the affinity of Fcγ receptors is increased through mutations, then the stability of interactions improves, but the complexity of the receptor structure increases

Engineering Contradiction:

Improvestability of Fcγ receptor interactionsVSAvoidcomplexity of receptor structure

Core Design Contradiction:

Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent applies local quality changes by introducing specific point mutations only in the IgG-binding region (e.g., residues 212-216) of the Fcγ receptor while leaving the rest of the structure intact. This localized modification improves stability without requiring complete structural redesign, thus limiting the increase in overall complexity

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS12269887B2Anti-canine CD16 polypeptides, anti-canine CD64 polypeptides, compositions including same, and methods of using

Publication Date: 2025.04.08 REGENTS OF THE UNIVERSITY OF MINNESOTA

AI summary

An anti-canine CD16 polypeptide generally includes a CDR region of SEQ ID NO:5, a CDR region of SEQ ID NO:9, or a functional variant of either CDR region. An anti-canine CD64 polypeptide generally includes a CDR region of SEQ ID NO:13, a CDR region of SEQ ID NO:17, or a functional variant of either CDR region. The anti-canine CD16 polypeptide and anti-canine CD64 polypeptide may be incorporated into a therapeutic compound, a multispecific compound, a targeted imaging compound, or a capture assay device.