Anti-hK2 Radioconjugates for Prostate Cancer Targeting

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Solution Overview

Problem

Current therapies for prostate cancer, particularly those targeting kallikrein-related peptidase 2 (hK2), face challenges in terms of efficacy and specificity, with a need for next-generation treatments that offer improved therapeutic and diagnostic options.

Innovation Solution

Development of anti-hK2 radioconjugates comprising an antigen binding domain conjugated with a chelator that binds radiometals, such as 225Ac or 64Cu, to create immunoconjugates with a shorter half-life, enhancing targeting specificity and therapeutic efficacy while minimizing bone marrow toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If full-length antibody is used in radioconjugate, then circulating half-life is extended (10-21 days), but bone marrow toxicity increases and targeting specificity decreases

Engineering Contradiction:

Improvecirculating half-lifeVSAvoidbone marrow toxicity

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent segments the full-length antibody into smaller antigen binding domains (Fab, scFv, or nanobodies) that retain hK2 binding specificity but lack the Fc region. This segmentation reduces molecular size and circulating half-life to 2-12 hours, minimizing bone marrow exposure and toxicity while maintaining tumor targeting capability through the preserved antigen binding domain

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention extracts and removes the Fc region from the full-length antibody structure, keeping only the antigen binding domain (VH, VL, or derived fragments). This extraction eliminates FcRn-mediated recycling that would otherwise extend half-life, thereby reducing systemic circulation time and bone marrow toxicity while preserving specific binding to hK2 in prostate cancer cells

Inventive Principle:

Principle #2Taking out (Extraction)

2Duration of action of moving object

If full-length antibody is used in radioconjugate, then circulating half-life is extended, but targeting specificity to hK2 decreases

Engineering Contradiction:

Improvecirculating half-lifeVSAvoidtargeting specificity

Core Design Contradiction:

Duration of action of moving objectVSMeasurement precision

Solution Approach 1:

The patent applies local quality by concentrating the therapeutic payload and radioisotope exclusively at the target site (hK2-expressing prostate cancer cells) using small antigen binding domains. The shortened half-life ensures rapid clearance from circulation, reducing off-target effects, while the localized binding to hK2 maintains high targeting specificity through optimized antigen binding domain structure and affinity

Inventive Principle:

Principle #3Local quality

3Object-affected harmful factors

If antigen binding domain with shorter half-life is used, then bone marrow toxicity is reduced and targeting specificity is improved, but therapeutic efficacy may be compromised

Engineering Contradiction:

Improvebone marrow toxicityVSAvoidtherapeutic efficacy

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The invention changes the pharmacokinetic parameters of the radioconjugate by using small antigen binding domains with half-lives of 2-12 hours instead of full-length antibodies. This parameter change optimizes the therapeutic window by concentrating the radioactive payload at the tumor site during the brief circulation period, then rapidly clearing from the system to minimize bone marrow exposure, thereby maintaining therapeutic efficacy while reducing toxicity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite immunoconjugates by combining the antigen binding domain (VH, VL, Fab, scFv, or nanobody) with radiometals (e.g., 225Ac, 177Lu, 64Cu) and chelators. This composite structure integrates targeting specificity, radioactive therapy, and controlled pharmacokinetics into a single molecule, achieving both reduced bone marrow toxicity and maintained therapeutic efficacy through optimized radionuclide selection and conjugation chemistry

Inventive Principle:

Principle #40Composite materials

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 anti-hK2 radioconjugates demonstrate improved safety and efficacy in targeting hK2-expressing prostate cancer cells, offering a more effective treatment and diagnostic tool with reduced side effects.

Implementation Method 1

an antigen binding domain conjugated with a chelator that binds radiometals

Methodology Applied

Scientific EffectChelation:

Implementation Method 2

radioconjugates comprising an antigen binding domain conjugated with a chelator that binds radiometals for therapeutic use or imaging

Methodology Applied

Scientific EffectRadioactive decay: Radioactive Decay

Data Source

PatentUS20250099635A1Iimmunoconjugates comprising kallikrein related peptidase 2 antigen binding domains and their uses

Publication Date: 2025.03.27 JANSSEN BIOTECH INC

AI summary

Provided herein are immunoconjugates, such as radioimmunoconjugates, comprising a therapeutic moiety conjugated to an antibody or antigen binding domain with binding specificity for hK2. In certain embodiments, the hK2-specific immunoconjugate demonstrates a short half-life. Also provided herein are methods of using the immunoconjugates for selectively targeting cancer cells and for treating diseases such as prostate cancer.