Recombinant Protein Therapeutics
Fusion Proteins & Beyond
January 21-22, 2013
Day 1 | Day 2 | Download Pipeline 3 Brochure
By combining modular building blocks, Fusion Protein Therapeutics have an advantage over antibody-based therapies resulting in a customizable functionality. Fusion protein therapeutics can also access several targets on different proteins or on the same protein with the potential to reach targets that are not accessible to antibodies. Additional advantages include lower patient dosing, reduced production costs, and improved product homogeneity. This meeting will explore the varying constructs and ‘designs’ of fusion protein therapeutics, and will discuss how they are being engineered to form more efficacious therapeutics that offer specificity with enhanced stability and longer half life. Experts will present case studies from R&D through clinical data, and will share the results they’ve achieved. Please join leaders from around the world for this in-depth discussion of the innovations being developed for the next-generation protein-based therapeutics.
SUNDAY, JANUARY 20
4:00-8:00 pm Conference Registration
MONDAY, JANUARY 21
7:30 am Conference Registration and Morning Coffee
8:55 Chairperson’s Opening Remarks
Bazbek Davletov, Ph.D., Professor & Chair, Biomedical Sciences, University of Sheffield
» KEYNOTE PRESENTATION:
9:10 Targeted Secretion Inhibitors: A Novel Therapeutic Protein Platform Affecting Cell Secretion
Keith Foster, Ph.D., FSB, Founder and CSO, Syntaxin Ltd. - Biography
Targeted Secretion Inhibitors (TSI) are novel recombinant proteins that employ unique pharmacological properties of the clostridial neurotoxins. TSI technology has broad potential for the discovery of therapeutic proteins to treat a range of diseases, and can be combined with a variety of binding scaffolds to generate targeted proteins of high specificity and potency. TSI inhibit secretion from the target cell for a prolonged period, and are in clinical development for treatment of both postherpetic neuralgia and overactive bladder.
» Featured Presentation:
9:50 Transcriptional Inhibition of Notch Signaling Using Cell Penetrating Fusion Proteins
Agamemnon Epenetos, Ph.D., Chairman, Trojan Technologies Ltd. - Biography
We have created a novel protein, consisting of the Drosophila transcription factor Antennapedia (ANTP) and the truncated version of Mastermind-like (MAML) that behaves in a dominant negative (DN) fashion and inhibits the Notch transactivation complex. A Notch activity reporter-gene assay revealed that addition of Antp-DN-Maml-1 leads to a dose dependent decrease in luminescence, corresponding to an inhibition of Notch signaling. Inhibition of Notch signaling may represent future therapeutics against cancer stem cells.
10:20 Coffee Break
10:45 Recombinant Proinsulin-Transferrin Fusion Protein as an Insulin Prodrug for the Selective Inhibition of Hepatic Glucose Production
Wei-Chiang Shen, Ph.D., John A. Biles Professor, Pharmaceutical Sciences, School of Pharmacy, University of Southern California - Biography
A slow but sustained hypoglycemic efficacy of subcutaneously injected proinsulin-transferrin fusion protein (ProINS-Tf) was observed in diabetic mice under fasting conditions. When IV administered, a lag time was observed in the hypoglycemic effect, indicating an in vivo activation of ProINS-Tf. Furthermore, it was found that the expression of liver gluconeogenic/glycogenolytic enzymes was inhibited after the fusion protein treatment. These results indicated that ProINS-Tf can potentially be developed into a long-acting hypoglycemic prodrug with the selective inhibition of hepatic glucose production.
11:15 iPEP – Interfering Peptides Targeting Protein-Protein Interactions
Katja Arndt, Ph.D., Professor, Molecular Biotechnology, Institute for Biochemistry and Biology, University of Potsdam - Biography
Protein-protein interaction surfaces are attractive yet challenging targets for disease intervention. We use rational design in combination with in vivo and in vitro selection systems to generate interfering peptides (iPEP) specifically targeting intracellular protein interaction domains. Different selection strategies, the generation of iPEPs against Jun, Fos, AF10 and Mitf as well as photoswitchable iPEPs will be discussed.
11:45 A Ligand-Receptor Fusion of Growth Hormone Generates a Long-Acting Biopharmaceutical
Ian Robert Wilkinson, Ph.D., Senior Scientist, Human Metabolism, University of Sheffield
There is a need for cytokine formulations that minimize manufacturing costs, have good pharmacokinetic profiles, are easy to administer, and are acceptable to patients. We have investigated the biological actions of a ligand-receptor fusion (LR-fusion) of GH with its extracellular domain receptor. The LR-fusion forms a reciprocal, head-to-tail dimer that provides a reservoir of inactive hormone as occurs naturally with GH and its binding protein and generates a potent long-acting agonist with exceptional pharmacokinetic properties.
12:15 pm Sponsored Presentations (Sponsorship Opportunities Available) or Lunch on Your Own
2:00 Chairperson’s Remarks
Simon Brack, Ph.D., Director, Discovery Research, Covagen AG
2:05 Antibody Fusion Proteins for Cancer Immunotherapy
Dafne Müller, Ph.D., Scientist, Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart - Biography
Cytokines of the common cytokine receptor gamma-chain family and costimulatory members of the B7- and TNF-family have shown great potential to support the generation and development of an antitumor immune response. In order to improve the efficacy of such molecules at the tumor site, we designed antibody fusion proteins for therapeutic approaches, focusing either on optimized presentation or a combined mode of action.
2:35 Protein Polymer Nanoparticles as Therapeutics
Joshua Gustafson, Ph.D., Postdoctoral Research Associate, Pharmaceutics & Pharmacology, University of Southern California
Genetic engineering can be used to generate high molecular weight, environmentally-responsive protein polymers, which can be fused directly to biopharmaceuticals. Our group studies therapeutic fusions with protein polymers that control PK, release-rate, and self-assembly of multivalent protein nanoparticles. After discussing these polymers’ biophysical behavior, I will present data related to targeted transcytosis across the lacrimal gland that produces tears, and the targeting of ligands associated with cancer.
3:05 Antibodies and ImmunoRNase Fusion Proteins Targeting CD30+ Lymphoma
Thomas Schirrmann, Ph.D., Research Group Leader and Lecturer, Biotechnology, Technische Universitaet Braunschweig - Biography
Antibody RNase fusion proteins show promise to improve the efficacy of antibody tumor therapies without the immunogenicity and/or unspecific toxicity issues associated with immunotoxins. We engineered an entirely human immunoRNase directed to CD30+ tumors by fusing a single chain (sc)Fv-Fc antibody with human RNases. The scFv-Fc-RNase protein showed binding to CD30+ lymphoma cells, ribonucleolytic activity RNase even excess of cytosolic RNase inhibitor (RI) and inhibited the growth of CD30+ lymphoma cells at low nanomolar concentrations.
3:35 Bio-Layer Interferometry (BLI): Instant Dip and ReadTM Label-Free Protein Quantitation and Binding KineticsDarick Dayne, Ph.D., Senior Product Manager, Marketing, ForteBio, A Division of Pall Life SciencesThis presentation will describe the use of label-free binding assays on the Octet and BLItz platforms for antibody therapeutic discovery and development. The Octet systems utilize a simple Dip and Read assay formatcombined with highly parallel analysis of binding interactions to rapidly screen for antibody titer, affinity ranking and cross-blocking assays with high throughput. The versatility of assay configurations allows fast and efficient screening of multiple binding interactions of biomolecules including antibodies, proteins, peptides, DNA, RNA and small organic molecules.le)
3:50 Refreshment Break
4:15 Protein Stapling Technology
Bazbek Davletov, Ph.D., Professor & Chair, Biomedical Sciences, University of Sheffield - Biography
We developed a new linking method which allows site-oriented, non-covalent, yet irreversible stapling of modified proteins at neutral pH and ambient temperature. This method is based on two distinct polypeptide linkers that self-assemble within minutes, in the presence of a short peptide staple. On-demand and irreversible combination of clostridial domains allowed us to design new neuronal blocking agents with enhanced features. We demonstrate the general versatility of this modular approach.
4:45 Apolipoprotein A-I Fusion Proteins: Beyond Liver Targeting
Pedro Berraondo López, Ph.D., Staff Scientist, Division of Gene Therapy and Hepatology, CIMA, University of Navarra - Biography
High-density lipoproteins and apolipoprotein A-Idecorated particles are ideal candidates as vehicles for liver-targeted drug delivery. The fusion of apolipoprotein A-I with therapeutic proteins and peptides allows them to benefit from the favorable pharmacokinetic properties of high-density lipoproteins. However, apolipoprotein A-I is not only a passive vector but also influences the PD properties of the fused proteins. In the case of IFN anchorage to ApoA-I reduces the hematopoietic toxicity and increases the immunostimulatory activity.
5:15 Rational Fusion Engineering Approaches for Therapeutic Use
Rachel Rennard, Senior Scientist, Merrimack Pharmaceuticals - Biography
Targeted agonists comprise a promising new class of biotherapeutics. However, these molecules are complex and present multiple design and production challenges. At Merrimack, we have developed a network biology platform where we use mechanistic models to identify optimal design parameters such as format, targeting moieties, and affinities. Rational engineering approaches are then used to construct molecules with these defined properties. An application of this approach to develop an active targeted agonist will be presented.
5:45 – 7:00 Welcome Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Day
Day 1 | Day 2 | Download Pipeline 3 Brochure