利用縮氨酸及蛋白質的治療方法會議 - Day 1

短期研討會 | Day 1 | Day 2 | Day 3

議程 (PDF : English)

滿足生物療法開發、設計、實施的需求是第4屆利用縮氨酸及蛋白質的治療方法會議的主要目的。

Scientific Advisors Manuel Vega, Ph.D., President & CEO, Nautilus Biotech David Szymkowski, Ph.D., Director, Biotherapeutics, Xencor Inc. Ryan Darling, Ph.D., Research Scientist, Biotechnology Discovery Research, Eli Lilly & Co. William Strohl, Ph.D., Executive Director, Biologics Research, Merck Research Labs  WP

The Peptide & Protein-Based Therapeutics meeting is bringing together experts who will present data from their work developing therapeutic peptide and protein products. 

Join the information exchange with the pioneers of therapeutics as they address:

• Seeking to understand biological properties - and mastering them 
• Improving stability, enhancing efficacy and innovating delivery systems 
• Strategies that lead to breakthroughs and success 

Monday, January 7

7:30am - 6:00 pm Registration Open

7:30am Morning Coffee

8:45 Chairperson�fs Opening Remarks

KEYNOTE PRESENTATION

9:00 Functional Screening of the Extracellular Proteome for Biotherapeutics Lewis T. (Rusty) Williams, M.D., Ph.D., Executive Chairman, FivePrime Therapeutics There are approximately 5,000 genes encoding theproteins in the extracellular space. We have produced most of these as recombinant proteins, including secreted proteins and extracellular domains of transmembrane proteins as well as peptides predicted as products of proteolytic processing. By screening this collection one-at-a-time in cell-based or in vivo assays for functions relevant to therapeutic utility, we have found candidate agonist biotherapeutics (secreted proteins) and antagonists (extracellular domains).

9:45 Screening for Chromatographic Success and Failure on Small Scale 
William Gillette, Ph.D., Senior Scientist, Protein Purification Group Leader, Protein Expression Laboratory, Advanced Technology Program, NCI/SAIC-Frederick
For proteomic and core service laboratories charged with purifying numerous proteins, a method to quickly screen the outcomes of different chromatographic approaches for multiple proteins in small-scale would be extremely useful in terms of reducing costs, increasing throughput and, more importantly, improving the success rate. Such a method must have the flexibility to interrogate multiple parameters, while also providing enough material for downstream analysis. We have approached this problem by maximizing the usefulness of samples which are generated by the expression screening groups of our lab and minimizing the amount of sample required for the purification screen. 

10:20 Coffee Break 

Featured Presentation

10:45 Functional Antibodies - Potent and Specific Signal Transduction Modulators Marc Nasoff, Ph.D., Director of Biotherapeutics, Genomics Institute of The Novartis Foundation  The therapeutic antibody field has evolved from its primary early role of developing antibodies against tumor associated antigens, to its current status of modulating therapeutically significant signal transduction pathways. Functional antibodies directed against the extra-cellular domains of receptors can mimic the actions of natural ligands that activate receptor signaling (agonists) or inhibit ligand mediated receptor activation (antagonists). Functional antibody agonists are usually more specific, have better pharmacological properties such as improved serum stability, and can be more potent than naturally occurring ligands. Functional antibodies can be used as a research tools to elucidate signal transduction pathways and as potential modulators of disease. We have developed a number of functional antibodies against a wide variety of diverse receptors using a high throughput hybridoma platform. The development and characterization of several functional antibodies will be discussed.

11:30 Transferrin Fusion Technology: Generation of Novel Peptide and Protein Therapeutics 
Graeme Bainbridge, Ph.D., Associate Research Fellow, Biotherapeutics Center of Emphasis, Pfizer Global Research and Development
The development and commercialization of peptide therapeutics has proved challenging because of short half-lives requiring frequent administration or large doses, leading to side effects, poor efficacy and high cost. BioRexis�f unique proprietary technology platform, acquired by Pfizer in Feb 2007, enables the production of superior biopharmaceuticals by genetically engineering peptide drugs into the scaffold of a variant of the human plasma protein transferrin. This engineered fusion protein significantly enhances drug half-life from minutes or hours to days. An overview of several peptide projects using this transferrin platform across several therapeutic areas will be presented.

12:15pm Close of Morning Session

12:30 Luncheon Workshop 

2:30 Chairperson�fs Remarks

2:35 The NusA Fusion Protein System: Development and Applications
Roger Harrison, Ph.D., Associate Professor, Chemical & Biological & Materials Engineering, University of Oklahoma
The NusA fusion protein system was developed using a systematic evaluation to identify E. coli proteins that have the highest potential for solubility when overexpressed. A modification of the Wilkinson-Harrison statistical discriminant analysis solubility model for predicting protein solubility after expression in E. coli was used in this evaluation. The success of using the NusA fusion protein system to solubilize a number of heterologous proteins after expression in E. coli will be discussed. Examples of the cleavage of target proteins from NusA fusion proteins and the subsequent purification of the target proteins will also be discussed. To aid researchers in predicting whether the NusA or other fusion protein system needs to be used for the expression of a desired protein in soluble form, the protein solubility model was improved further using neural network modeling of an expanded protein database. 

3:05 Thyrotropin Releasing Hormone: A Neuropeptide for the Regulation of Pancreatic Beta Cell Function 
LuGuang Luo, M.D., Ph.D., Assistant Professor, Stem Cell Center, Roger Williams Hospital
The best-characterized physiologic role of TRH is the stimulation of the pituitary-thyroid axis. However, TRH has many other effects such as the regulation of neuronal growth and controlling appetite behavior. TRH levels in the pancreas peak during the stages of late embryonic and early neonatal β cell development. The observations are consistent with a linkage of TRH to islet cell proliferation and differentiation. In this presentation, we will discuss the novel effects of TRH in pancreatic β cell function and the possibility for a future drug for normalizing blood glucose based on evidence from our preliminary studies on diabetic animal models.

3:35 IgG2m4, An Engineered IgG Isotype Lacking Effector Functionality 
William Strohl, Ph.D., Executive Director, Biologics Research, Merck Research Labs - WP
IgG was engineered to remove the ability to bind to FcgRI, FcgRII, FcgRIII and C1q. The resultant antibody, IgG istoype, behaves as designed in all assays performed. This talk will discuss how IgG2m4 has been used with several constructs.

4:05 Refreshment Break 

4:30 Using Ig-Fold Sequences and Antibody Folding Mechanisms to Engineer Improved Antibody and Antibody-Like Therapeutics 
Stephen Demarest, Ph.D., Senior Scientist, Protein Chemistry, Biogen Idec Inc.
We have investigated the folding/unfolding mechanisms of IgG variable and constant domains with the goal that this information may provide input into antibody design concepts. Additionally, we utilize multi-faceted sequence approaches for defining functionally or structurally important residues within antibody domains that can be modified to suit our design purposes. These initiatives have enabled the generation of stable and manufacturable multispecific and multivalent antibody molecules.

5:00 ReCODE PEGylation: Site Matters 
Bruce Kimmel, Ph.D., Vice President, Therapeutic Applications, Ambrx Inc.
Ambrx has developed technology called ReCODETM to incorporate novel amino acids into proteins. The first application of ReCODE directs incorporation of chemically selective conjugation points into proteins for site selective PEGylation. We have found that site of PEGylation can influence protein pharmacokinetics, potency, stability and absorption rate. Ambrx has applied ReCODE PEGylation to several proteins optimizing their medicinal properties.

5:30 Welcoming Reception in the Exhibit Hall

7:00 Close of Day