One of the major obstacles in bringing a potentially promising new drug to market is to deliver that drug to tissues where it is needed with minimal toxicity to other parts of the body. GlyTag LLC has developed a novel drug targeting system that increases a drug’s therapeutic efficacy while reducing its toxicity to non-targeted cells and tissues. The GlyTag system takes advantage of one of nature’s own methods of targeting growth factors to specific cells in the body through unique cell surface heparan-sulfate molecules. A “GlyTag” is a polypeptide sequence specifically designed to target recombinant proteins or other macromolecules to specific cells in the body.

Proof-of-Concept:
Thus far we have demonstrated:

1. GlyTags confer heparin-binding properties – We can successfully fuse GlyTags to polypeptide drugs, thereby conferring unique heparin- binding properties to those drugs;

2. Enhanced drug activity – Fusion of a GlyTag to a recombinant protein drug produces a significant enhancement in its biological activities due to specific, low-affinity heparin binding that significantly lowers the dose required to achieve the desired effect.  This targeting effect leads to reduced toxicity to non-targeted tissues;
3. Less frequent dosing is required – As is true for most heparin-binding growth factors, GlyTag fusion proteins become quite stable as they accumulate on cell surfaces and become protected from proteolysis.  GlyTag fusion proteins thus require less frequent dosing;
4. Pre-clinical success of lead drug – We are completing pre-clinical testing on a prototype GlyTag fusion protein for treating breast cancer.  To date, this drug has out-performed the same drug without a GlyTag.

Tissue Specificity:

Our initial efforts have been focused on targeting GlyTag fusion proteins to specific cells within the nervous system and to breast cancer cells.  However, there is mounting evidence that each cell type expresses its own, unique composition of heparin molecules on its surface that enables the cells to concentrate specific heparin-binding growth and differentiation factors on their surface.  We are, therefore, expanding our platform technology to create a large repertoire of cell-specific and tissue-specific GlyTags that could be used in the treatment of a wide variety of human diseases.

Applicability:

At present, we do not foresee limitations on the protein or other macromolecule that can be fused to a GlyTag.  Initially, we have focused our technology on the targeting and activity enhancement of both agonists such as growth factors, as well as antagonist proteins. Additionally, we are developing strategies to utilize GlyTag technology for various forms of gene therapy and small drug delivery.

Scalability of Process:

GlyTag fusion proteins can be prepared on a small scale for the initial in vitro proof of concept studies and can easily be scaled up using standard recombinant protein production methods (mammalian cell culture) for in vivo animal studies, FDA clinical trials, and production quantities.