Anti-Laminin4 Antibodies Targeting LG4-5 Modules

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Solution Overview

Problem

Conventional chemotherapies for cancer lack specificity, leading to inadequate drug dosages due to side effects, and current treatments are ineffective in targeting cancer cells expressing laminin α4 and its binding partners.

Innovation Solution

Development of antibodies that specifically bind to the LG4-5 modules of laminin α4, inhibiting its binding to heparan sulfate proteoglycans and MCAM, and selectively targeting cancer cells, such as melanoma cells, while competing with antibodies like 15F7, 6C12, and 13G10, and being humanized, chimeric, or veneered to reduce immunogenicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional chemotherapies are used to treat cancer, then cancer cells can be eliminated, but side effects occur due to lack of specificity

Engineering Contradiction:
Improvecancer cell elimination efficacyVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the cancer treatment approach by targeting a specific molecular marker (laminin α4) that is differentially expressed between cancer cells and normal cells. This segmentation allows the antibody to selectively bind to cancer cells expressing laminin α4, thereby eliminating cancer cells while sparing normal cells and reducing side effects.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The antibody serves as an intermediary that specifically recognizes and binds to laminin α4 on cancer cell surfaces. This intermediary mechanism enables selective delivery of therapeutic effects to cancer cells expressing the target antigen, avoiding non-specific toxicity to normal tissues.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If higher dosages of chemotherapy are administered to overcome side effects, then cancer cell elimination improves, but toxicity increases

Engineering Contradiction:
Improvecancer cell elimination efficacyVSAvoiddrug toxicity
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The therapy segments the population of cells by targeting only those that express laminin α4. This allows effective cancer cell elimination at lower dosages because the antibody is concentrated on the target cells rather than being distributed systemically, thereby reducing overall drug toxicity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the parameter of drug delivery from non-specific systemic distribution to specific target-cell concentration. By altering how the drug is delivered and distributed in the body, effective dosages can be achieved at the tumor site while maintaining lower overall dosages that reduce systemic toxicity.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If antibodies targeting laminin α4 are developed, then cancer cell specificity improves, but development complexity increases

Engineering Contradiction:
Improvecancer cell binding specificityVSAvoidantibody development complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts the specific binding capability from a complex antibody development process by identifying and isolating the key target (laminin α4). By focusing on this single well-defined target with known expression patterns in cancer, the development complexity is managed while achieving high binding specificity.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If antibodies inhibit laminin α4 binding to heparan sulfate proteoglycans, then cancer cell adhesion is reduced, but normal physiological functions may be affected

Engineering Contradiction:
Improvecancer cell adhesion inhibitionVSAvoidphysiological function disruption
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The antibody exerts its adhesion-inhibiting effect locally at the cancer cell surface where laminin α4 is overexpressed. By targeting this specific location and context, the antibody disrupts cancer cell adhesion without significantly affecting normal physiological functions that occur in tissues with normal laminin α4 expression levels.

Inventive Principle:
Principle #3Local quality

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

These antibodies effectively inhibit laminin α4-mediated cancer cell adhesion and angiogenesis, providing a targeted approach for cancer treatment with reduced side effects and improved efficacy.

Implementation Method 1

antibodies that specifically binds to an epitope within the LG4-5 modules of the G domain of laminin α4

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentUS10059761B2Anti-Laminin4 antibodies specific for LG4-5
Publication Date: 2018.08.28 PROTHENA BIOSCI LTD
  • US10059761B2 patent drawing
  • US10059761B2 patent drawing
  • US10059761B2 patent drawing

AI summary

The invention provides antibodies that specifically bind to the LG4-5 modules of the G domain of laminin α4. The antibodies can preferentially stain cancer or tumor cells or tissue. The antibodies can be used for detecting cancer, evaluating the efficacy of a cancer therapy, treating cancer, and treating obesity or obesity-related diseases, among other applications.