Recombinant Polypeptide Bone Growth via Calcium Phosphate Carrier

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Solution Overview

Problem

Current recombinant polypeptides and chemical agents used for bone formation exhibit variability in osteoinductive activity, making them unreliable for therapeutic applications, and there is a need for consistent osteoinductive agents that can induce bone growth at specific sites.

Innovation Solution

A recombinant polypeptide comprising specific domains fused in various configurations, including intramolecular and intermolecular disulfide bonds, is used in conjunction with a biodegradable calcium phosphate carrier to promote bone growth, with the polypeptide being homogeneously entrained within the carrier to ensure localized bone formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If recombinant polypeptides are used for bone formation, then bone growth can be induced at predetermined sites, but osteoinductive activity is inconsistent and unreliable

Engineering Contradiction:

Improveosteoinductive activity consistencyVSAvoidpolypeptide structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The polypeptide is divided into three functional domains (first domain from BMP-2, second domain from BMP-4, third domain from BMP-7) that can be independently selected and combined. This segmentation allows optimization of osteoinductive activity while maintaining structural manageability through modular domain selection.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention creates a composite polypeptide structure combining elements from three different BMP family members (BMP-2, BMP-4, BMP-7) into a single chimeric molecule. This composite approach integrates the osteoinductive properties of multiple BMPs to achieve consistent and enhanced bone formation activity.

Inventive Principle:

Principle #40Composite materials

2Reliability

If chemical agents are used to induce bone formation, then bone growth can be promoted, but osteoinductive variability exists across different products and production lots

Engineering Contradiction:

Improveosteoinductive activity consistencyVSAvoidproduct variability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention defines specific parameter ranges for each domain (first domain: SEQ ID NO: 35 or 39; second domain: SEQ ID NO: 47 or 49; third domain: SEQ ID NO: 57 or 61) that ensure consistent osteoinductive activity. By controlling these sequence parameters and their combinations, the invention achieves reliability across production lots while maintaining the ability to adapt to different bone formation requirements.

Inventive Principle:

Principle #35Parameter changes

3Manufacturing precision

If polypeptide is released from carrier, then localized bone formation is achieved, but carrier degradation time affects treatment duration

Engineering Contradiction:

Improvelocalized bone formationVSAvoidtreatment duration

Core Design Contradiction:

Manufacturing precisionVSDuration of action of moving object

Solution Approach 1:

The polypeptide is pre-entrained within the biodegradable calcium phosphate carrier during manufacturing, ensuring precise localization at the target site before treatment begins. The carrier is designed to degrade over a predetermined time period, providing sustained polypeptide release exactly where needed, thus achieving both localization precision and controlled treatment duration.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The biodegradable calcium phosphate carrier serves as an intermediary vehicle that temporarily holds the polypeptide in a controlled manner. The carrier mediates between the polypeptide and the target bone tissue, providing localized delivery and controlling the release timeline through its degradation rate, thereby decoupling localization precision from treatment duration constraints.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 recombinant polypeptide and calcium phosphate carrier combination provides consistent and localized bone growth, effectively promoting healing of fractures and fusion of vertebrae by gradually releasing the polypeptide as the carrier degrades, ensuring confined bone formation.

Implementation Method 1

the recombinant polypeptide is capable of inducing alkaline phosphatase activity

Methodology Applied

Scientific EffectOsteoinduction:

Implementation Method 2

gradually releasing the polypeptide as the carrier degrades

Methodology Applied

Scientific EffectBiodegradation:

Implementation Method 3

the second domain comprises an intramolecular disulfide bond between the twenty-third amino acid of the second domain and the twenty-seventh amino acid of the second domain

Methodology Applied

Scientific EffectDisulfide bonding: Chemical Bonding

Data Source

PatentUS10919948B2Recombinant polypeptides, compositions, and methods thereof

Publication Date: 2021.02.16 BIOGEND THERAPEUTICS CO LTD

AI summary

The present disclosure provides recombinant polypeptides, homodimeric and heterodimeric proteins comprising the recombinant polypeptides, nucleic acid molecules encoding the recombinant polypeptides, and vectors and host cells comprising the nucleic acid molecules. The present disclosure also provides compositions comprising the recombinant polypeptides and methods of making and using the recombinant polypeptides.