TAT-Fused AJ007 Eye Drops for Blood-Ocular Barrier Penetration
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current polypeptide drugs, such as multifunctional fusion polypeptide VI (HM-1), cannot effectively penetrate the blood-ocular barrier and require intravitreal injection, leading to serious side effects and poor patient compliance.
Innovation Solution
A fusion polypeptide AJ007 is developed by linking a cell-penetrating peptide TAT to the multifunctional fusion polypeptide VI (HM-1) to enhance its ability to penetrate through the blood-ocular barrier, combined with appropriate auxiliary materials to prepare eye drops for treating neovascular diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibody drugs are used to treat wet age-related macular degeneration, then the therapeutic effect is improved, but the side effects and patient compliance deteriorate due to intravitreal injection requirements
Solution Approach 1:
The patent uses a cell-penetrating peptide as an intermediary component to enable the therapeutic polypeptide to cross the blood-ocular barrier. This mediator allows the drug to reach the choroid and retina through systemic circulation, avoiding direct intravitreal injection while maintaining therapeutic efficacy.
Solution Approach 2:
The patent modifies the molecular structure by fusing the therapeutic polypeptide with a cell-penetrating peptide sequence, changing the physical and chemical parameters of the drug molecule to enable blood-ocular barrier penetration and improve patient compliance.
2Reliability
If antibody drugs with large molecular weights are used, then the therapeutic effect is improved, but the ability to pass through blood-ocular barrier deteriorates
Solution Approach 1:
The patent segments the drug delivery system into two functional parts: a therapeutic polypeptide component for VEGF inhibition and a cell-penetrating peptide component for barrier crossing. This segmentation allows each component to optimize its function while working together as a unified therapeutic agent.
Solution Approach 2:
The patent creates a composite polypeptide structure by fusing the therapeutic polypeptide sequence with the cell-penetrating peptide sequence, forming a single chimeric molecule that combines the therapeutic function with the barrier-penetration capability.
3Reliability
If VEGF is directly neutralized by antibody drugs, then neovascularization is inhibited, but retinal and choroidal atrophy risk increases due to VEGF nutritional effect deprivation
Solution Approach 1:
The patent applies local quality by enabling the therapeutic polypeptide to concentrate specifically at the choroid and retina sites through the cell-penetrating peptide-mediated delivery system, achieving high local efficacy while maintaining lower systemic concentrations that preserve VEGF's nutritional functions in other tissues.
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
AJ007 eye drops significantly improve the delivery of active molecules to the posterior segment of the eye, achieving therapeutic effects comparable to intravitreal injection while reducing side effects and enhancing patient compliance.
Implementation Method 1
linking a cell-penetrating peptide TAT to a front end of a multifunctional fusion polypeptide VI (HM-1) sequence that has a higher ability to inhibit neovascularization, thereby enhancing its ability to penetrate through the blood-ocular barrier or sclera to reach the posterior segment of ocular
Data Source
Figure 1~3H
Figure 4~6
Figure 7~10
AI summary
This application discloses a fusion polypeptide AJ007 and use thereof, and belongs to the technical field of ophthalmic drugs. The fusion polypeptide AJ007 is formed by linking a TAT cell-penetrating peptide to a front end of a polypeptide HM-1 molecule that inhibits neovascularization. The fusion polypeptide AJ007 is used for preparing polypeptide eye drops. By selecting a prescription of this application, the fusion polypeptide AJ007 is prepared into eye drops. When a wet age-related macular degeneration disease is prevented or treated, an administration route of the eye drops can effectively avoid the problems of various serious side effects and poor patient tolerance caused by intravitreal injection clinically, has the advantage of non-invasive treatment, and exhibits excellent efficacy of improving abnormal proliferation of choroidal neovascularization in the laser-induced wAMD mouse model, thereby having good clinical treatment potential.