Archived Content

Novel Antibody Constructs and Alternative Scaffolds

Engineering, New Targets and Lead Selection

4-5 November 2013

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Tuesday, 5 November  

07:45 Registration and Morning Coffee 

 

ENGINEERING OF BI- AND MULTI-SPECIFIC PRODUCTS 

08:30 Chairperson’s Remarks

Stefan Dübel, Ph.D., Director, Biotechnology and Bioinformatics, Institute of Biochemistry, Technische Universität Braunschweig

08:35 Anticalins: A Versatile Non-Ig Scaffold for the Design of Bifunctional Biotherapeutics

Arne SkerraArne Skerra, Ph.D., Professor, Technische Universität Munich; Co-Founder, Pieris AG, Germany

Anticalins are based on the small lipocalin scaffold (160-180 aa) that displays four hypervariable loops on a robust beta-barrel. These single-chain proteins, which can be generated against a wide variety of medically relevant targets, from small haptens to large antigens, are ideally suited for functionalization: either in a fusion protein approach (e.g. as Duocalins) or via chemical conjugation. We will present data for an anti-VEGF Anticalin tested in a Phase 1 clinical trial, for an anti-hepcidin Anticalin currently under development for the treatment of anemia, and novel strategies to couple radiometal chelators, drugs or toxins to tumor-specific Anticalins for cancer treatment or in vivo imaging.

09:05 Efficient Generation of Stable Bispecific IgG1 by Controlled Fab-Arm Exchange

Janine SchuurmanJanine Schuurman, Ph.D., Director, Strategic Research, Genmab B.V.

We will present a technology for the efficient generation of IgG1 bispecific antibodies. The platform generates antibodies with normal IgG structures, regular Fc-mediated effector functions and in vivo stability typical of IgG1 antibodies. The platform is amenable to both antibody drug discovery and development. Technical background and proof-of-concept studies will be presented.

09:35 Engineering Bispecificity into a Single Albumin-Binding Domain Aimed for Drug Targeting and in vivo Half-Life Extension

Johan NilvebrantJohan Nilvebrant, Ph.D., Post-Doctoral Researcher, Protein Technology, Royal Institute of Technology, Alba Nova University Center, Stockholm

We have engineered a 46 amino acid albumin-binding domain as a scaffold for bispecific affinity proteins. By diversification of the non-albumin binding side of this small domain, followed by display of the resulting libraries on phage or on cells, bispecific single-domain proteins with high affinities for several targets have been isolated. These molecules approach the size limit of bispecific, folded proteins and have many interesting properties for biotherapeutical applications.

AbCheck10:05 Novel Discovery Platform for Bispecifics

Molkenthin_VeraVera Molkenthin, Ph.D., Chief Scientist, AbCheck s.r.o

Wouldn’t it be nice to skip reformatting steps between antibody discovery and lead development and to address key features like folding yield and stability already during antibody discovery?  The potential of a novel recombinant antibody discovery platform allowing display and selection of complex molecules in combination with a smart bioinformatics approach for library design will be demonstrated. Besides being compatible with full-length IgG the platform holds special and unique advantages to address bispecific formats.   

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

11:15 Engineering Stable Bispecific Antibodies in the Final Therapeutic Format

Robert MabryRobert Mabry, Ph.D., Associate Director, Antibody Discovery and Bispecific Engineering, Adimab LLC

Bispecifics assembled from individual components frequently do not retain affinity and structural stability of parental antibodies. We have presented large libraries of full-length bispecific antibody formats on the surface of yeast to select for significant affinity and biophysical improvements over antibody assembly. These molecules express well in mammalian hosts, and detailed biophysical characterization demonstrates a consistent pattern of generating stable bispecifics.

11:45 F-star: Advancing Novel Bispecific Antibody Biologics in Oncology

Haijun Sun, VP, Biological Products, f-Star

F-star’s Modular Antibody Technology uses straight forward “mix-and-matching” of antibody components to create unique mAb2 bispecific antibodies and allows rapid exploration of their novel biology. An Fcab against a single target, with a site introduced in the constant region, can either be developed as a therapeutic agent or be combined with the variable regions of different existing antibodies to create a panel of bispecific antibodies. F-star’s mAb2 bispecific antibodies retain all conventional antibody properties such as Fc-mediated effector function, manufacturability, stability, and PK and can be progressed from Fcab to in vivo pharmacology testing in very short periods of time. F-star is now developing a preclinical oncology product pipeline based on this next generation biologics technology platform.

12:15 Bispecific Antibody Derivatives that Bind Cell Surface Targets and Capture Payloads

Ulrich BrinkmannUlrich Brinkmann, Ph.D., Senior Principal Scientist, Pharma Research and Early Development (pRED), Large Molecule Research, Roche Penzberg

Antibody Derivatives that bind cell surface targets and capture payloads via hapten binding moieties can be generated in various formats. Various payloads such as fluorophores, small compounds, proteins, peptides, nucleic acids or nanoparticles can be complexed with such delivery vehicles. These antibody complexes deliver payloads specifically to target cells that are recognized by the targeting moieties of the delivery vehicles.

Morphosys12:45 Luncheon Presentation: Strategies for the Directed Engineering of Antibodies

Van den Brulle_JanJan Van den Brulle, Ph.D., Director, Discovery Alliances Technologies, MorphoSys AG

The properties required for antibody candidates on their way to an approved therapeutic agent are getting more and more ambitious. We therefore have established a technology platform (arYla) to engineer antibody candidates with respect to defined properties like affinity, immunogenicity and biophysical behavior. Successfully conducted case studies will be presented.

 

ENGINEERING OF BI- AND MULTI-SPECIFIC PRODUCTS (Continued) 

14:00 Chairperson’s Remarks

Janine Schuurman, Ph.D., Director, Strategic Research, Genmab B.V.

14:05 Human Bispecific Antibodies with a Common Light Chain: Combining Superior Functionality and Developmental Reliability in the Well-Established Full Length IgG Format

Ton LogtenbergTon Logtenberg, Ph.D., CEO, Merus B.V.

A common light chain (cLC) transgenic mouse for human mAbs and CH3-engineering have been used for the efficient discovery of full length IgG human bispecific antibodies. Screening of thousands of bispecific antibodies against combinations of RTKs in cell-based assays uncovered bispecific antibodies with superior activity vis-a-vis ‘best in class’ comparators. cLC bispecific antibodies, like conventional therapeutic IgG antibodies, have attractive features: they recruit immune effector functions, have excellent stability and give high yields during manufacturing.

Icosagen14:35 Novel Hybridoma-free Technology for the Development of Recombinant Monoclonal Antibodies 

Mannik_AndresAndres Männik, Ph.D., CTO, Icosagen Cell Factory Ltd

Continuously growing need for therapeutic monoclonal antibodies forces the search of novel and efficient methods to accelerate the development process. Classical hybridoma-derived method is time consuming, laborious and not efficient way to generate monoclonal antibodies. Icosagen has developed novel hybridoma-free method for the generation of recombinant antibodies from different hosts: chickens, mice or rabbit using direct isolation of antibody variable region encoding cDNAs from a spleen or bone marrow of the immunized animal and generation of scFv antibodies. From scFv, generation of expression vectors for different subtypes and origin of antibodies in high throughput format is validated. For the production of reconstructed antibodies, mammalian stable episomal expression technology (QMCF Technology) is used.

15:05 Problem Solving Roundtable Discussions

Table 1: How to Get What You Want from Antibody Phage Display

Moderators: Stefan Dübel, Ph.D., Director, Biotechnology and Bioinformatics, Institute of Biochemistry, Technische Universität Braunschweig
Stefan Ewert, Ph.D., Senior Investigator, NIBR Biologics Center, Novartis Pharma AG

Table 2: Measures to Increase Half-Life and Stability of the Product

Moderator: Arne Skerra, Ph.D., Professor, Technische Universität Munich; Co-Founder, Pieris AG, Germany

Table 3: Engineering of Bispecific Antibodies

Moderator: Robert Mabry, Ph.D., Associate Director, Antibody Discovery and Bispecific Engineering, Adimab LLC

Table 4: Immuno-Oncology: The Next Big Thing?

Moderator: Haijun Sun, VP, Biological Products, f-Star

16:05 Refreshment Break in the Exhibit Hall with Poster Viewing


PLENARY SESSION* 

16:55 Designing Receptor Binding Proteins with Highly Potent Biological Function

Andreas PlückthunAndreas Plückthun, Ph.D., Director and Professor, Biochemistry, University of Zurich

Non-IgG molecules, unless armed with toxins or other effector units, are usually thought to be limited in the biological responses they can elicit. However, Designed Ankyrin Repeat Proteins (DARPins) are particularly versatile, because of their favorable biophysical properties, and they can be engineered into many formats. Using DARPins generated against members of the EGFR family, and a combination of x-ray crystallography, signaling studies, and in vivo experiments, it will be demonstrated how molecules could be engineered to selectively induce apoptosis in tumors, and their mechanism of action has been deduced. New intracellular sensors will be described for such studies.

17:45 Immunotherapy with BiTE® Antibodies

Luis BorgesLuis Borges, Ph.D., Scientific Director, Therapeutic Innovation Unit, Amgen, Inc.

BiTE® antibodies are potent bispecific single-chain antibodies that redirect T cells to kill tumors. They engage a tumor target and a constant region of the T cell receptor to recruit and activate polyclonal T cells to eliminate tumors. They have demonstrated potent efficacy in various preclinical tumor models and have now transitioned to clinical studies. Blinatumomab, a CD19xCD3 BiTE® antibody, is in clinical development and has shown high single-agent response rates in patients with refractory or relapsed B-ALL and B-NHL.

* For Attendees of Novel Antibody Constructs & Alternative Scaffolds and Cancer Biotherapeutics 

18:30 End of Novel Antibody Constructs and Alternative Scaffolds


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