Recombinant Vector Sustains BMP-7 for Renal Failure

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Solution Overview

Problem

Current treatments for acute and chronic renal failure in mammals are inadequate, with high mortality rates and no effective methods to prevent or reverse kidney structural alterations, and the short half-life of Bone Morphogenetic Protein-7 (BMP-7) requires frequent and costly injections, making it impractical for veterinary medicine.

Innovation Solution

A recombinant plasmid vector is developed for intramuscular delivery, encoding a codon-optimized BMP-7 polypeptide linked to a promoter, allowing for sustained expression and production of BMP-7 in mammals to prevent or treat renal failure, reducing mortality and morbidity by maintaining therapeutic plasma concentrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If recombinant BMP-7 protein is administered by injection, then therapeutic effect is achieved, but frequent injections are required due to short half-life

Engineering Contradiction:
Improvetherapeutic effectVSAvoidhalf-life
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The BMP-7 gene is introduced into the subject's cells in advance through viral vector delivery, enabling the cells to produce BMP-7 protein continuously. This preliminary genetic modification eliminates the need for repeated protein injections by establishing endogenous production capability before the therapeutic effect is needed.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The subject's own cells are engineered to serve as factories for producing BMP-7 protein. Once the gene is delivered, the subject's cellular machinery automatically synthesizes the therapeutic protein, making the system self-sustaining without requiring external administration of the protein.

Inventive Principle:
Principle #25Self-service

2Reliability

If recombinant BMP-7 protein is administered by frequent injections, then therapeutic plasma concentrations are maintained, but treatment cost increases

Engineering Contradiction:
Improvetherapeutic plasma concentrationsVSAvoidtreatment cost
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The subject's own cells are engineered to serve as factories for producing BMP-7 protein. Once the gene is delivered, the subject's cellular machinery automatically synthesizes the therapeutic protein, making the system self-sustaining without requiring external administration of the protein.

Inventive Principle:
Principle #25Self-service

3Duration of action of moving object

If BMP-7 gene is delivered to achieve sustained expression, then injection frequency is reduced, but delivery method complexity increases

Engineering Contradiction:
Improveexpression durationVSAvoiddelivery method
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

A viral vector serves as an intermediary carrier to deliver the BMP-7 gene into the subject's cells. The viral vector naturally infects cells and delivers genetic material, providing an efficient delivery mechanism that bypasses the complexity of direct gene injection or other non-viral delivery methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP3536704B1Gene therapy for renal failure
Publication Date: 2021.08.25 BOEHRINGER INGELHEIM ANIMAL HEALTH USA INC
  • EP3536704B1 patent drawingFigure 1
  • EP3536704B1 patent drawingFigure 2
  • EP3536704B1 patent drawingFigure 3~4

AI summary

The present invention relates to recombinant vectors expressing the BMP-7 polypeptide in host cells and to pharmaceutical compositions comprising such recombinant vectors. The invention also encompasses methods for prevention and/or treatment of both acute and chronic renal failure in mammals, advantageously in dogs and cats, by administration of the recombinant vectors and pharmaceutical compositions of the invention.