An optimized and highly versatile fully human monoclonal antibody platform. Monoclonal antibodies are powerful biological therapeutics with broad appeal for the treatment of diverse human diseases. Trianni’s new technology is designed to overcome the major barriers complicating the facile isolation of these remarkable molecules.
New technologies to generate an advanced human monoclonal antibody resource
Founded in 2010, Trianni is a company with the primary scientific mission of creating an optimized and highly versatile platform for isolating fully human monoclonal antibodies. Drawing on its expertise in immunology and genetics, the company has created advanced designs for extensively engineered genes encoding human antibodies. These genes, and the antibodies they produce, retain the capacity to function normally in mice, while crucially also permitting single-step isolation of fully human therapeutics. Trianni seeks partnerships with other companies interested in licensing its new technology for the development of their own therapeutic monoclonal antibodies.
The Trianni Mouse
Monoclonal antibodies are the most successful class of biological therapeutic currently available to clinicians. Their unique appeal lies both in their specificity (i.e., their capacity to engage disease associated molecules in a highly discriminating fashion) and their ability to marshal the might of the body’s immune system against target molecules, cells or pathogens. Today, scores of monoclonal antibodies are approved for the treatment of diverse conditions from cancer to infectious diseases, and hundreds more are at various stages of development.
The methodology for isolating monoclonal antibodies was invented in the 1970s. Numerous advances since then have spawned a broad range of alternatives to the original Nobel Prize-winning technology. Among these, the creation of transgenic mice carrying human antibody genes was of particular importance because even in its infancy this technology promised a rapid means for the isolation of therapeutic antibodies. Whereas early versions of the transgenic mice were significantly limited in many crucial respects, Trianni has used advanced molecular biological procedures to overcome these limitations and create a powerful next-generation drug discovery resource.
The Trianni Mouse, in its final form, carries extensively engineered versions of all three antibody-encoding genetic loci (Heavy, Kappa, and Lambda). The normal mouse variable and diversity/joining gene segments in these loci have been replaced by synthetic chimeric versions each comprised of human coding sequences combined with mouse regulatory genomic sequences. The Trianni loci are optimized for the expression of antibodies that are entirely human in their variable parts yet completely permissive of efficient lymphocyte development and immune responses in the mouse because they retain mouse constant domains. Fully human therapeutics can be generated from such chimeric antibodies by standard single-step cloning methodology.
Key Features of the Trianni Mouse
- Engineered versions of all three antibody genetic loci (Heavy, Kappa and Lambda)
- Novel chimeric antibody gene segments each comprised of human coding sequences combined with mouse regulatory genomic sequences
- Expression of a full repertoire of human heavy and light chain variable domains
- Multiple enhancements to antibody gene segments to improve V(D)J recombination and expression
- Retention of all mouse constant domain exons
- Two designs for the Lambda allele, both of which are fully capable of expressing Lambda light chains
- Designs allow for facile future modifications to loci
- Normal genomic [V(D)J] rearrangement in developing B cells
- Normal B cell development
- Normal immune responses
- Somatic hypermutation
Creation of the Trianni Mouse
An advanced platform for the facile isolation of fully human monoclonal antibodies
Heavy chain – Chromosome 12
Light chain – Chromosome 6 (Kappa) or 16 (Lambda)
Native Kappa Locus
Trianni Kappa Locus
(containing novel chimeric gene segments optimized for the expression of human variable domains)
- Similar humanization at the Heavy and Lambda loci
- The final Trianni Mouse expresses a full complement of human antibody variable domains
Dr. Matthias Wabl, Ph.D., Chairman and CEO.
Dr. Wabl was a cofounder and managing partner of Picobella, LLC, and a co-founder of Sagres Discovery, Inc. (now Novartis), where he served as President and as Chair, Scientific Advisory Board. He has been a member of the NIH, Small Business Innovative Research Study Section and an advisor to numerous biotechnology companies and the FDA. He is also a Professor of Microbiology and Immunology at the University of California at San Francisco (UCSF) where he has been engaged in research on the generation of antibody diversity and the basis of autoimmunity for over 20 years. He received his Ph.D. from the Max-Planck Institute in Berlin.
Dr. Nigel Killeen, D.Phil., CSO.
Before moving full-time to Trianni, Dr. Killeen was Associate Professor of Microbiology and Immunology at the University of California at San Francisco (UCSF). In addition to directing a highly active research program in T lymphocyte biology, Dr. Killeen was also the director of the UCSF Transgenic and Targeted Mutagenesis facility responsible for generating genetically engineered mice for researchers in and outside the UCSF community. Dr. Killeen received his Ph.D. from Oxford University in England; he has served as a consultant to numerous biotechnology companies and has been a permanent member of the NIH Cellular and Molecular Immunology Scientific Review Panel.
Dr. Maria Wabl, M.D., CFO.
Dr. Wabl has held positions at the Max-Planck Institute in Tübingen and at the Robert-Bosch Hospital, Stuttgart, Germany. She served as fundraiser, member of the board and president of several schools in the San Francisco Bay Area. Dr. Wabl received her M.D. from the University of Tübingen, Germany.
Alan Schwartz-Ocio, J.D., Company Counsel.
Mr. Schwartz Ocio received his J.D. from the George Washington University Law School. He is a corporate and commercial attorney specializing in intellectual property transactions, venture capital, M&A, and other aspects of corporate law. Mr. Schwartz Ocio has served as Vice President & General Counsel at Synergenics, LLC, Kestrel Solutions, Inc., and Orbital Imaging Corporation. He was also Of Counsel at DLA Piper and an associate at Piper & Marbury and Cole, Corette & Abrutyn. Mr. Schwartz Ocio received his BA in Economics and Political Science from the University of Maryland, Baltimore County.
Sally Brashears, J.D., Company Patent and Licensing Counsel.
Sally Brashears has over 18 years' experience in intellectual property law in the fields of biotechnology, genomics and biopharmacology, including preparing and prosecuting patent applications, monitoring competitor portfolios, conducting IP due diligence reviews, and drafting and negotiating license agreements, research collaboration and joint development agreements. Ms. Brashears served as the Executive Vice President of Legal Affairs at Antara Biosciences, Inc. and Benitec, Inc., as Director of Intellectual Property at Perlegen Sciences, Inc. and Clontech Laboratories, Inc., and as Senior Division Counsel at Applied Materials, Inc. Ms. Brashears graduated summa cum laude from the University of Nebraska College of Law and received her B. Sc. from Missouri Western State College.
Andreas Wabl, Vice President of Business Relations.
Mr. Wabl has been active for many years in the public and political life of Austria. His more prominent roles include serving as a Member of the Austrian Parliament for thirteen years, being chairman of the committee overseeing the audit commission of the Austrian State, and holding the position of Climate Commissioner to the Chancellor of Austria.
Please contact us at:
5980 Horton St., Suite 405
Emeryville, CA 94608 USA