Reindeer Antler BMP-4 with Heparin Binding Site

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Solution Overview

Problem

Current methods for isolating and producing bone morphogenetic proteins (BMPs), particularly BMP-4, are challenging due to high homology and similarity with other BMPs, making separation, purification, and identification difficult, and existing recombinant production methods do not fully utilize the unique properties of BMPs from species like reindeer antlers.

Innovation Solution

The development of recombinant BMP-4 from reindeer antlers with a heparin binding site, which improves expression and biological activity, and the use of specific amino acid sequences such as Pro6 and Pro21, enhancing bone and cartilage formation capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional isolation and purification methods are used for BMPs, then BMPs can be obtained from bone matrix, but the process is very time consuming and expensive due to high homology and difficulty in separation

Engineering Contradiction:
Improveproduction efficiencyVSAvoidtime for separation and purification
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent replaces traditional mechanical/chemical separation methods with molecular biological tools (recombinant DNA technology) to produce BMPs. By cloning the BMP-4 gene into expression vectors and using recombinant protein expression systems, the invention eliminates the need for time-consuming separation and purification of BMPs from bone matrix, directly producing pure recombinant BMP-4 protein.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of manufacture

If recombinant protein techniques are used to produce BMPs, then production can be achieved, but existing methods do not fully utilize the unique properties of BMPs from species like reindeer antlers

Engineering Contradiction:
Improveproduction feasibilityVSAvoidutilization of species-specific properties
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by incorporating specific amino acid sequences (Pro6 and Pro21) that are unique to reindeer antler BMP-4 into the recombinant protein structure. These localized structural features enhance the osteoinductive activity of the recombinant BMP-4, making it more effective than human BMP-4 while maintaining the benefits of recombinant production.

Inventive Principle:
Principle #3Local quality

3Manufacturing precision

If BMPs with high homology are separated and purified, then all BMP variants can be identified, but the process is very expensive and time consuming

Engineering Contradiction:
Improvepurification accuracyVSAvoidcomplexity of separation process
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent extracts only the essential BMP-4 gene sequence from the complex bone matrix environment using molecular biological techniques. By isolating and cloning the specific gene of interest rather than attempting to separate and purify multiple BMP variants from tissue, the invention simplifies the process while maintaining high precision in obtaining the desired BMP-4 protein.

Inventive Principle:
Principle #2Taking out (Extraction)

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 BMP-4 from reindeer antlers demonstrates significantly improved bone induction potency compared to human BMP-4, with enhanced expression and biological activity, making it a more effective osteoinductive agent for clinical applications.

Implementation Method 1

The development of recombinant BMP-4 from reindeer antlers with a heparin binding site, which improves expression and biological activity

Methodology Applied
Scientific EffectHeparin binding: Electrostatic Induction

Implementation Method 2

Between these cysteines there are three disulfide bonds within mature BMP monomers and one disulfide bond which combines two monomers into a biologically active BMP dimer

Methodology Applied
Scientific EffectDisulfide bonding: Chemical Bonding

Data Source

PatentEP1885750B1Bone morphogenetic protein 4 and osteogenic devices and pharmaceutical products containing thereof
Publication Date: 2011.08.17 BBS BIOACTIVE BONE SUBSTITUTES
  • EP1885750B1 patent drawingFigure 1
  • EP1885750B1 patent drawingFigure 2
  • EP1885750B1 patent drawingFigure 3

AI summary

The present invention relates to reindeer bone formation inducing protein called bone morphogenetic protein 4 (BMP-4) and nucleotide molecules encoding said proteins and host cells expressing said proteins. The present invention relates also to the use of said BMP-4 for treating disorders related to bone and cartilage formation. The present invention further relates to osteogenic devices and pharmaceutical compositions containing said proteins.