Affinity-Matured and Humanized NRP2 Antibodies for Ligand Modulation

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Solution Overview

Problem

Current technologies lack effective antibodies that can modulate the neuropilin-2 (NRP2) axis to address a spectrum of diseases related to cellular processes such as cancer initiation, growth, metastasis, and chemoresistance, as well as muscular, vascular, neuronal, bone, and immune homeostasis, by targeting the previously unrecognized roles of tRNA synthetases like HARS in cellular stress and tissue homeostasis.

Innovation Solution

Development of affinity matured and humanized antibodies and antigen-binding fragments that specifically bind to human neuropilin-2 (NRP2) polypeptides, modulating binding interactions and downstream signaling events, including therapeutic compositions that target NRP2-associated diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibody technologies are used, then general antibody functions are available, but effective modulation of NRP2 axis for treating diseases related to cellular processes is lacking

Engineering Contradiction:

Improveeffectiveness in modulating NRP2 axisVSAvoidability to address spectrum of diseases

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by affinity-maturing antibodies to achieve higher binding affinity and specificity to NRP2. This involves optimizing antibody parameters (affinity, specificity) to effectively modulate NRP2 axis while maintaining the ability to address multiple diseases associated with NRP2 deregulation

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If affinity matured and humanized antibodies are developed, then specific binding to NRP2 is achieved, but development complexity increases

Engineering Contradiction:

Improvespecificity of binding to NRP2VSAvoidantibody development process

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses phage display technology as an intermediary system to facilitate affinity maturation and humanization processes. This intermediary platform enables systematic optimization of antibody specificity to NRP2 while managing the complexity of antibody engineering through standardized procedures

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If antibodies target NRP2 to address cellular process deregulation, then therapeutic benefits are achieved, but understanding of tRNA synthetase roles must be established first

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidknowledge of tRNA synthetase functions

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent applies preliminary action by first establishing the knowledge foundation about tRNA synthetases (particularly HARS) and their interaction with NRP2 before developing therapeutic antibodies. This preliminary research into cellular stress responses and tissue homeostasis mechanisms enables subsequent effective targeting of NRP2 for therapeutic benefit

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS12410253B2Compositions comprising anti-NRP2 antibodies

Publication Date: 2025.09.09 ATYR PHARM INC

AI summary

Provided are affinity matured and humanized antibodies and antigen-binding fragments thereof that specifically bind to human neuropilin-2 (NRP2) polypeptides, including those that modulate binding interactions between human NRP2 and at least one NRP2 ligand, and which thereby modulate subsequent NRP2-mediated downstream signaling events, including related therapeutic compositions and methods for modulating NRP2 activity and treating diseases such as NRP2-associated diseases.