药物传递之蛋白质治疗工学

5月 1日 (四)

1:00 - 1:30pm Registration

ENGINEERING PHARMACOLOGY OF PROTEINS:
Using Non-Native Amino Acids to Engineer Desired Properties of Biologic Drugs

1:30 Chairperson's Opening Remarks
Ho Sung Cho, Ph.D., Vice President, Technology & Process Development, Ambrx Inc.

 

KEYNOTE PRESENTATION

1:40 The Continuing Story of Inhaled Insulin John S. Patton, Ph.D., Founder and Chief Scientific Officer, Nektar Therapeutics　 After 16 years of development, the first inhaled insulin, Exubera, was approved in January 2006 for meal time use by Type 1 and Type 2 diabetics in both Europe and the US. The dry powder product was a joint effort between Inhale Therapeutics (now Nektar Therapeutics) and Pfizer. Exubera represents a large number of technical firsts, and was widely preferred over injections by diabetics who used it. In October 2007, Pfizer stopped marketing the product because of poor sales. This was the first time that a new product was pulled from the market without any safety concerns. The story of inhaled insulin continues as other companies move their products to market.

2:10 Engineering the Pharmacology of Protein Therapeutics
Ho Sung Cho, Ph.D.
The success of modern drug discovery and development programs are highly dependent on the ability to efficiently transition from activities observed in "lead' compounds to creation of therapeutically relevant entities – molecules possessing the appropriate (or competitive) efficacy, safety and pharmacological profiles. In the case of small molecule drugs, medicinal chemists are able to start from an active lead scaffold and optimize the structure-activity of candidates by drawing from an almost limitless space of chemical diversity. Unfortunately, in the case of protein leads, protein chemists are limited to the optimization that can be performed with the set of chemical groups present in the natural 20 amino acids. While there are now a few examples of commercially successful optimized or second generation protein products utilizing the natural 20 amino acids, the ability to incorporate novel amino acids (Protein Medicinal Chemistry), especially those with chemo-selective properties, provides new tools to optimize proteins such as Growth Hormone, GCSF and Ifn-alpha.

2:40 Solutions Showcase (Sponsorship Available)

3:10 Refreshment Break in the Exhibit Hall

4:00 Recombinant Protein Sequences with PEG-Like Properties for Half-Life Extension
Volker Schellenberger, Ph.D., Vice President, Drug Discovery, Amunix, Inc.
The modification of proteins with hydrophilic chemical polymers like PEG is a validated approach to improve the pharmacokinetic properties of many therapeutic proteins. However, PEGylation requires an expensive conjugation step and it typically leads to product mixtures resulting in complex clean-up and characterization protocols. We developed recombinant protein sequences (called rPEG) that share many properties of PEG polymers: large hydrodynamic radius, slow kidney filtration, low immunogenicity. These rPEG sequences can be directly fused to most drug proteins thus eliminating the need for chemical conjugation. Fusion proteins between rPEG and several protein drugs were manufactured in microbial hosts. These proteins closely mimic the properties of PEG-conjugated proteins.

4:30 Use of Hesylation to Improve Drug Characteristics, Such as Circulating Half-life and Efficacy
Peter Vorstheim, Ph.D., Senior Vice President, HESylation Technology, Fresenius Kabi Deutschland GmbH
HESylation utilises hydroxyethyl starch derivatives linked to drug substances (e.g. proteins, peptides, oligonucleotides) in order to modify the drug characteristics. This modification enables the prolongation of the circulation half-life by increasing the stability of the molecule, as well as by reducing renal clearance, resulting in an increased biological activity. Furthermore, HESylation potentially alters the immunogenicity or allergenicity. By varying different parameters, such as the molecular weight or the number of hydroxyethyl groups of HES, a wide range of HES drug conjugates can be customized. HESylation is based on the extensive expertise of Fresenius Kabi in the field of hydroxyethyl starch as the world's largest producer of HES. HES is a modified natural polymer that has been widely used in clinical practice for decades as a plasma volume expander. Consequently, it has an impressive safety record.

5:00pm End of Day