Cambridge Healthtech Institute's Fourteenth Annual

Recombinant Protein Therapeutics

( 重组蛋白质疗法 )

Fusion Proteins & Beyond

2018年1月8日 - 9日


Cambridge Healthtech Institute's Fourteenth Annual Recombinant Protein Therapeutics conference once again profiles the varying designs of therapeutic fusion proteins in differing stages of development, and investigates the challenges and benefits associated with these promising therapies. By combining modular building blocks that can reach targets not accessible to antibodies, Fusion Protein Therapeutics possess advantages over antibody-based therapies; their customizable functionality translates into lower patient dosing, reduced production costs, and improved product homogeneity. This conference will disclose how these molecules are being engineered to form more efficacious therapeutics that offer specificity with enhanced stability and longer half-life. Case studies from international experts will be presented covering R&D through clinical data.

Final Agenda


7:30 am Registration and Morning Coffee

Creating Efficacious Protein Therapeutics

9:00 Welcome by Conference Organizer

Mary Ruberry, Senior Conference Director, Cambridge Healthtech Institute

9:05 Chairperson's Opening Remarks

Stefan Schmidt, Ph.D., MBA, CSO, Development and Innovation, Rentschler Biotechnology


9:10 Fusion Proteins: An Intro to the Field and Selected Case Studies from Roche's Research & Early Development Pipeline

Stefan Weigand, Ph.D., Head, Large Molecule Research, Roche Innovation Center, Roche Pharma Research & Early Development (pRED)

This talk will introduce the concept of fusion proteins, provide an overview on which fusion proteins are on the market, how they compare to classical antibodies in the same field, and look at general trends for fusion proteins from development pipelines of biotech and big pharma. In the second part, I will provide examples from Roche's pipeline how to discover, design, develop, and deliver differentiated, multi-functional therapeutics that allow for tailored solutions for the biological problem at hand.

9:50 Making Proteins "Druggable": Fc Fusion Proteins as a Therapeutic Class

Steven Chamow, Ph.D., Principal Consultant, Chamow & Associates, Inc.

Immunoglobulin G has substantial in vivo stability due to its binding to the neonatal Fc receptor (FcRn) which is responsible for IgG recycling. By creating an Fc fusion, a protein with a short in vivo half-life can be transformed into a stable therapeutic product. This technology has been applied broadly and there are now 6 FDA approved products from this therapeutic class. Their structures and properties will be reviewed.

10:20 Networking Coffee Break

next-gen engineering

10:45 Generating Ion Channel Blocking Antibodies by Fusing Cysteine-Knot Miniproteins into Peripheral CDR Loops

John McCafferty, Ph.D., CEO, Antibody Engineering, IONTAS, Ltd.

Cysteine-knot miniproteins (knottins) have potential as therapeutic agents to block proteases and ion channels involved in cancer, autoimmunity and pain, but suffer from manufacturing difficulties, short half-lives, and a lack of specificity. Using X-ray crystallography and biochemical assays, we have demonstrated that functional knottins can be inserted into peripheral antibody CDRs via short linkers. Thus, the resulting "KnotbodyTM" retains the advantage of blocking activity from the knottin while enjoying the extended half-life and additional specificity conferred by the antibody molecule.

11:15 High-Resolution Mass Spectrometry Confirms the Presence of a Hydroxyproline (Hyp) Post-Translational Modification in the GGGGP Linker of an Fc-Fusion Protein

Chris Spahr, Senior Scientist, Therapeutic Discovery, Discovery Attribute Sciences, Amgen, Inc.

(G4P)n protein linkers were proposed to replace the commonly used (G4S)n linkers recently found to carry heterogeneous xylose-containing O-glycosylation. Using high-resolution mass spectrometry (HR-MS) and MSn, we demonstrated the presence of an unexpected hydroxylation of a prolyl residue (Hyp) in a (G4P) linker. Further efforts in determining whether the modification is 3-hydroxyproline (3-Hyp) or 4-hydroxyproline (4-Hyp) will be discussed.

11:45 Turning Affibody Molecules into Efficient Peptide Binders by Dimerization

John Lofblom, Ph.D., Associate Professor, Protein Technology, Biotechnology, KTH Royal Institute of Technology

Affibody molecules are small three-helical affinity proteins. Generating binders for the amyloid β peptide yielded variants with 300-pM affinity, and with unique mode of binding, sequestering the peptide in a tunnel-like cavity. Similar binders for other peptides have been engineered, involving structural rearrangements of both affibody and peptide upon binding, indicating that it is well suited for such molecular recognitions. This presentation will include unpublished preclinical data for the Aβ binder.

12:15 pm Veltis® Engineered Albumins and Their Potential for Improved Therapeutic Performance

Helen_RawsthorneHelen Rawsthorne, Ph.D., Senior Research Scientist, Molecular Biology and Fermentation, Albumedix

The natural properties of albumin have ensured its use for decades in enhancing the pharmacokinetic and pharmacodynamic properties of drug candidates. We have designed rationally engineered albumins to enhance these properties. A half-life of more than double that seen for native sequence albumin is obtainable for therapeutic candidates associated with Veltis® albumins engineered for increased FcRn binding affinity. Newly developed thio-engineered albumins with additional free thiol groups allow further options for multi-valent site-specific drug loading.

12:45 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

Improving Therapeutic Properties and Manufacturing

2:00 Chairperson's Remarks

John McCafferty, Ph.D., CEO, Antibody Engineering,


2:05 Design, Structure and Manufacturability: Lessons Learned from Fusion Proteins

Stefan Schmidt, Ph.D., MBA, CSO, Development and Innovation, Rentschler Biotechnology

Next-generation therapeutic proteins are typically human designed molecules with no counterpart in living organisms. As they have not been selected in a natural evolution process, they can suffer from low expression, mis-assembly and mis-folding, disulfide scrambling, a tendency to aggregate, and sensitivity to protease degradation. In this presentation, I will show examples from our portfolio and the literature demonstrating how to avoid these product-related impurities by smart fusion protein design and strategies to eliminate these impurities in efficient bioprocesses.

2:35 Advanced Bi- and Multi-Specific Antibody Derivatives and Fusion Proteins for Targeted Therapy: From Molecular Design to Therapeutic Application

Ulrich Brinkmann, Ph.D., Expert Scientist, Scientific Director, Roche Pharma Research & Early Development, Roche Innovation Center Munich

3:05 Sponsored Presentation (Opportunity Available)

3:20 BuzZ Sessions with Refreshments

Join your peers and colleagues for interactive roundtable discussions.


4:30 Synergistic Inhibition of R5 HIV-1 by the Fusion Protein (FLSC) IgG1 Fc and CCR5 Antagonist Maraviroc in Primary Cells: Implications for Effective Prevention and Treatment

Olga S. Latinovic, Ph.D., Assistant Professor and Head, Lab for Imaging Studies of Pathogens & Cell Interactions and IHV Imaging Facility, Institute of Human Virology and Microbiology and Immunology, University of Maryland School of Medicine

We had previously shown that (FLSC) IgG1, a fusion protein containing gp120BAL and CD4, specifically binds cellular coreceptor CCR5, preventing HIV entry in primary cells. We reported that treatment with the CCR5 antagonist Maraviroc increased exposure of the (FLSC) IgG1 binding sites on CCR5. We demonstrated that (FLSC) IgG1 strongly synergizes with Maraviroc inhibiting HIV. This finding suggests that this combinatorial treatment has potential merit. Future in vivo studies are warranted.

5:00 Protein Engineering to Further Improve Clotting Factor-Fc Fusions and Create Novel FVIIIa Mimetic Bispecific Antibodies

Robert Peters, Ph.D., Senior Vice President, Research, Bioverativ, Inc.

Further protein engineering was performed on clotting factor-Fc fusions with a goal to further improve protection from bleeds provided by a prophylaxis regimen, and to potentially enable subcutaneous administration, while preserving the biology of the coagulation system. Considerations and the path to creation of rFVIIIFc-VWF-XTEN and rFIX(R338L) Fc-XTEN fusion proteins will be presented, as well as antibody screening methods used to generate a true FVIIIa mimetic bispecific (FIXa/FX) antibody.

5:30 Designed Ankyrin Repeat Protein as Inhibitors of Clostridium Difficile Toxin B

Zhilei Chen, Ph.D., Associate Professor, Microbial Pathogenesis and Immunology, Texas A&M College of Medicine

Using phage-panning combined with high-throughput in vitro functional screening, we recently engineered several designed ankyrin repeat protein (DARPin) with picomolar neutralization potency against C. difficile TcdB, which is 100-1000-fold more potent than bezlotoxumab. These anti-toxin DARPins were found to effectively protect mice against TcdB-associated mortality. Cryo-electromicroscopy studies revealed that binding of one of these DARPins induced significant conformational change of TcdB, likely rendering it unable to associate with the target receptor.

6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing

7:15 Close of Day


8:00 am Registration and Morning Coffee


8:30 Chairperson's Remarks

Robert Peters, Ph.D., Senior Vice President, Research, Bioverativ, Inc.

8:35 Combinatorial Protein Engineering of Proteolytically Resistant Mesotrypsin Inhibitors as Candidates for Cancer Therapy

Niv Papo, Ph.D., Group Leader and Assistant Professor, Biotechnology Engineering, Ben-Gurion University

Our study describes a rapid methodology for identifying mutations that convert the human amyloid precursor protein Kunitz protease inhibitor domain (APPI), a natural substrate of the oncogenic protease mesotrypsin, into a proteolytically stable high affinity inhibitor of mesotrypsin. We demonstrated that APPIM17G/I18F/F34V acts as a functional inhibitor in cell-based models of mesotrypsin-dependent prostate cancer cellular invasiveness. Additionally, by solving the crystal structure of the complex, we uncovered new insights into the structural and mechanistic basis for improved binding and proteolytic resistance.

9:05 Redefinition of ErbB2/3 Tumor Targeting: Novel Platform for Development of Truly Efficient Anti-ErbB Bispecific and Biparatopic Agents

Rastislav Tamaskovic, Ph.D., Senior Scientist, Biochemistry, University of Zurich

We built a new platform for RTK fingerprinting of tumors under therapy, for identification of points of fragility in oncogene-addicted tumors with the developed acquired resistance, and for the design of prospective therapeutic leads in a variety of bispecific formats. This novel approach heralds the next generation of ErbB targeting vehicles with beneficial properties owing to maximization of drug potency and minimization of the risk of side and off-target effects associated with the current drug formats.

9:35 Sponsored Presentation (Opportunity Available)

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 HERA: Engineering Next Generation TNFR-SF Agonists for Cancer Immunotherapy

Oliver Hill, Ph.D., Vice President, Molecular Biology/Protein Engineering, Apogenix AG

The HERA technology platform developed by Apogenix is based on trivalent but single-chain molecular mimics of the TNF-SF receptor binding domains (scTNFSF-RBDs) fused to a dimerization scaffold. These hexavalent fusion proteins are true agonists and their biological activity is, in contrast to agonistic anti-TNFR-SF antibodies, independent of secondary Fc-receptor based crosslinking events. We will present the molecular engineering concept and report on in vitro and in vivo activities of HERA-CD40L, HERA-CD27L, HERA-GITRL and HERA-CD137L.

11:30 Improving Enzyme-Based Therapy of Acute Lymphoblastic Leukemia: Molecular Design of Human L-Asparaginases

Manfred Konrad, Ph.D., Research Director, Enzyme Biochemistry, Max Planck Institute for Biophysical Chemistry

Acute lymphoblastic leukemia (ALL), the most common cancer in children, is a genetically heterogenous disease. We designed and engineered human enzyme homologues displaying the clinically established enzyme drug L-asparaginase (L-ASNase) activity with the aim of identifying catalytically efficient variants to substitute for the bacterial enzymes. Furthermore, to increase the serum half-life of the enzymes, we generated biocompatible microcapsules as carriers, thus enhancing serum stability and preventing exposure of the protein to the immune system.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Session Break

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Close of Recombinant Protein Therapeutics Conference

* 活动内容有可能不事先告知作更动及调整。