NOBEX Issued Two Significant U.S. Patents For Small, PEG-based Polymers

NOBEX Corporation, a drug product innovation and development company specializing in medicinal chemistry-based drug delivery, today announced that it has been granted two new U.S. patents covering its polyethylene glycol (PEG) and related "micro-alkylPEGylation" technology. NOBEX focuses its efforts on the technology covered in these new patents to enable the conversion of injectible-only drugs into oral drugs. With its global co-development partner Biocon, NOBEX is developing an oral insulin product, a convenient tablet dose, for patients with diabetes.

As more peptide hormones are identified as potential drugs, particularly those for chronic diseases of metabolism and the cardiovascular system, oral delivery in tablet form is the ideal method to achieve patient convenience and compliance as well as provide new medical benefits in some cases. The two new patents described below can enable or enhance the delivery of both peptide-based and small organic molecules by oral delivery but also by other routes of administration including injection, pulmonary and transdermal delivery.

U.S. Patent No. 6,815,530, entitled "Substantially monodispersed mixtures of polymers having polyethylene glycol moieties" covers small molecular-weight (up to several hundred Daltons) PEG polymers in which substantially all of the PEG molecules have the same molecular weight. The patent covers such monodispersed PEG polymers as individual compositions of matter, as well as in combination with other components such as the alkyl and fatty acid compounds that NOBEX uses in its proprietary micro-alkylPEGylation technology for drug modification.

U.S. Patent No. 6,835,802, entitled "Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties" covers synthetic methods for producing the monodispersed PEG and micro-alkylPEG ("oligomer") compositions.

"The proprietary technology developed by NOBEX enables the synthesis of small, pure molecular weight polymers themselves and the resultant polymer-drug molecules, an advance that imparts superior chemical and biological properties to the polymer-drug molecules," said Christopher H. Price, Ph.D., President & CEO of NOBEX. "In addition to providing significant new patent coverage for the NOBEX product pipeline, we believe that the technology will be of licensing interest to other companies using PEG-based polymers to modify their therapeutic molecules. We have observed that even a single ethylene glycol unit difference in a pure polymer-modified drug can yield significantly different biological performance. Furthermore, a polymer-modified drug of single molecular weight simplifies manufacturing and chemical analyses and can also extend the patent lives of covered compounds."

"NOBEX's focus is on the oral delivery opportunities of our amphiphilic oligomer technology, however, one can envision many other uses which may capitalize on the unique properties it provides," commented Nnochiri Ekwuribe, Ph.D., Vice President of Chemistry Innovation for NOBEX. "Companies seeking to develop uses of the micro-alkylPEG polymers to exploit their solubility and ionic and nonionic surfactant properties (e.g., in pharmaceutical formulations, prepared foods, skin products) will find value in this technology. Their small, monodispersed molecular structure and chemical properties may also be useful in areas such as nanotechnology."

For NOBEX, the modification of peptide drugs for oral delivery is accomplished by chemically coupling the small, pure oligomers covered by the new patents (and other patents in the NOBEX portfolio) to the peptide at one or more selected sites, creating a new, pure single molecular entity. The oligomers are "amphiphilic", that is, they have a highly water-soluble portion (the PEG polymer) on one end and a highly lipid-soluble portion on the other end of a single structure. The balance of water and lipid solubility provided by the different polymers changes the chemical and biological properties of the drug. The results are improvements in characteristics such as increased shelf stability, resistance to enzymes, absorption into the body from the GI tract, and lengthened circulation time in the blood.

PEG polymers are well established in the biopharmaceutical industry for modifying the pharmacology of large protein drug molecules that are administered by injection. Large molecular weight (several 1,000 Daltons) PEG polymers are attached to the protein drug in random fashion and at variable numbers of sites on each molecule. This approach provides well-documented benefits to the pharmacokinetics and bioactivity of the PEG-modified drug administered by injection. However, PEG-modified proteins are not suited for delivery by the oral route of administration due to their very large size.