X-BODY

PRESENTATIONS & PUBS

Presentations and Posters

Generation and Optimization of Fully Human VH Domain Antibodies and IgG Using dsDNA Display with Deep Sequence Hit Analysis
CHI's PEGS Conference 2012
Tuesday, May 1, 3:05-3:35pm, Boston, MA
Yan Chen, MD/Ph.D. Senior VP of R&D Phage and Yeast Display

Discovery & Optimization of XB 2202, a Potent, Stable, Soluble Anti-RTK VH Domain Implicated in Angiogenesis, by dsDNA Display and Deep Sequencing
Presentation at CHI PepTalk
January 11-12th, 2012

Discovery & Optimization of XB 2202, a Potent, Stable, Soluble Anti-RTK VH Domain Implicated in Angiogenesis, by dsDNA Display and Deep Sequencing
Presentation and Poster at IBC Antibody Engineering Conference
December 5th 2011 at 1:15PM, San Diego, CA
We describe a platform for generating and optimizing hMABs under mammalian folding conditions by dsDNA display of fully human libraries. Sequencing of thousands of hits provides an early read on the function, affinity and specificity of lead candidates. We have affinity matured these VH domains using a rapid framework optimization that maintains their fully human character. A novel VL pairing method has been used to construct fully human scFv and IgG with the biological functional activity that was predicted by deep sequencing. 

Production and Purification of Soluble VH Domains Derived from a Naïve Human VH library
Presentation: PEGS
May 9-13 2011, Boston, MA
We have established a robust high throughput E. coli expression platform to produce soluble VH domains identified from a naïve human VH library for binding and affinity screening. A single-step purification yields highly pure, monomeric and stable proteins for rapid lead characterization and selection. Extrinsic and intrinsic factors that may contribute to the solubility of these VH antibody fragments will be discussed.

Csaba Pazmany, Richard Wagner and Yan Chen

Discovery and Characterization of hMAB Targeting an RTK Implicated in Metastasis by Live Cell Screening and Interrogation of Fully Human Libraries with Deep Sequencing
Presentation: PEGS
May 9-13 2011, Boston, MA
We describe a novel platform for rapid generation of hMABs that employs interrogation of fully human libraries by deep sequencing. This human library captures the full naïve antibody repertoire and can be screened for binding to targets on living cells. Sequencing of thousands of hits provide an early read on the function, affinity and specificity of lead candidates. Label-free metastasis assays and 384 well affinity determinations in complex fluids are deployed in the screening process.

Yan Chen, Csaba Pazmany, Pascale Richalet, Steve Shamah, Robert Bruccoleri, Rachel Rennard and Richard Wagner.

BIT Life Sciences International Conference of Antibodies
Rapid Generation and Screening of Fully Human Monoclonal Antibodies and Antibody Fragments Using a Novel Platform
Yan Chen, MD/Ph.D. Vice President, X-BODY BioSciences, Inc., USA
March 24, 2011, 15:50-16:15, Beijing, China

Predicting Antibody Binding Properties by Interrogation of Fully Human Libraries with Deep Sequencing
Poster at PepTalk: Antibodies of the 21st Century
January 12-13th, 2011, San Diego, CA
We describe an integrated scalable platform for the discovery and rapid generation of hMABs and/or antibody fragments. A large fully human library of antibody VH and VL domains was generated. High affinity binding domains to targets of interest are selected against live cell or purified targets using a novel display technology. Following deep sequence analysis of the selected pools, hundreds of selective binding molecules are identified in the population. VH and VL domains have been combined to form scFv and biologically active full IgG. The platform is capable of identifying rare soluble VH domains with high affinity and selectivity.

Predicting Antibody Binding Properties by Interrogation of Fully Human Libraries with Deep Sequencing
Presentation: PepTalk
Wednesday, January 12, 2011, at 2:35pm San Diego, CA
We employ X-BODY's Protein Chain Reaction™ method for rapid cell-free generation of hMABs under mammalian folding conditions. Our human VH and VL libraries capture the natural antibody repertoire and can be screened for binding to targets on living cells. We present data showing that sequencing of thousands of hits can provide an early read on the function and specificity of lead candidates.

Presenter: Tod Woolf, Ph.D. Authors: Yan Chen, Csaba Pazmany, Pascale Richalet, Steve Shamah, Robert Bruccoleri, Rachel Rennard and Richard Wagner.

Rapid Generation of hMABs Using a Novel Integrated Platform
Poster at IBC Antibody Engineering Conference
December 5-9th 2010, San Diego,CA
We describe an integrated scalable platform for the discovery and rapid generation of hMABs and/or antibody fragments. An ultra-large fully human library of antibody VH and VL domains was generated. High affinity binding domains to targets of interest are selected using a novel display technology. Following deep sequence analysis of the selected pools, hundreds of selective binding molecules are identified in the population. Next, binding affinity is ranked using an ultra high throughput label-free SRU Biosystems BIND® system in a 384 or 1536 well plate format. VH and VL domains can be combined to form scFv or full IgG. The platform is capable of identifying rare soluble V domains with high affinity and selectivity.

Yan Chen1, Csaba Pazmany1, Pascale Richalet2, Steve Shamah1,2, Alexander Litovchick1, Robert Bruccoleri, Rachel Rennard1 and Richard Wagner1,2.

Discovery and Characterization of hMAB Targeting an RTK Implicated in Metastasis by Live Cell Screening and Interrogation of Fully Human Libraries with Deep Sequencing
Presentation at IBC Antibody Engineering Conference
December 6th 2010, San Diego, CA.
We describe a novel platform for rapid generation of hMABs that employs interrogation of fully human libraries by deep sequencing. This human library captures the full naïve antibody repertoire and can be screened for binding to targets on living cells. Sequencing of thousands of hits provide an early read on the function, affinity and specificity of lead candidates. Label-free metastasis assays and 384 well affinity determinations in complex fluids are deployed in the screening process.

Yan Chen, Csaba Pazmany, Pascale Richalet, Steve Shamah, Robert Bruccoleri, Rachel Rennard and Richard Wagner.

Publications

Members of X-BODY’s team have developed platform technologies that have been employed throughout the pharmaceutical industry

Chen Y* (co-first author), Getmanova EV (first author), Bloom L, Gokemeijer J, Shamah S*, Warikoo V, Wang J, Sun L. Antagonists to human and mouse vascular endothelial growth factor receptor 2 generated by directed protein evolution in vitro. Chemical Biology 2006, 13 (5), 549-556. Adnexus, acquired by BMS.

Parker MH, Chen Y*, Danehy F, Dufu K, Ekstrom J, Getmanova E, Gokemeijer J, Xu L, and Lipovsek D. Antibody mimics based on human fibronectin type three domain engineered for thermostability and high affinity binding to vascular endothelial growth factor receptor two. Protein Engineering Design & Selection. 2005, 18(9), 435-444. Adnexus, acquired by BMS.

Design, synthesis and selection of DNA-encoded small-molecule libraries Matthew A Clark*, Raksha A Acharya, Christopher C Arico-Muendel, Svetlana L Belyanskaya, Dennis R Benjamin, Neil R Carlson, Paolo A Centrella, Cynthia H Chiu, Steffen P Creaser, John W Cuozzo, Christopher P Davie, Yun Ding, G Joseph Franklin, Kurt D Franzen, Malcolm L Gefter, Steven P Hale, Nils J V Hansen, David I Israel, Jinwei Jiang, Malcolm J Kavarana, Michael S Kelley, Christopher S Kollmann, Fan Li1, Kenneth Lind, Sibongile Mataruse, Patricia F Medeiros, Jeffrey A Messer, Paul Myers, Heather O’Keefe, Matthew C Oliff, Cecil E Rise, Alexander L Satz, Steven R Skinner, Jennifer L Svendsen, Lujia Tang, Kurt van Vloten, Richard W Wagner, Gang Yao, Baoguang Zhao & Barry A Morgan Nature Chemical biology. 2009, 5:9; 647-654. Praecis, acquired by GSK.

Antisense gene inhibition by oligonucleotides containing C-5 propyne pyrimidines RW Wagner, MD Matteucci, JG Lewis, AJ Gutierrez, C Moulds, and BC Froehler Science. 1993, 260(5113):1510-1513. Gilead Sciences, technology acquired by Isis Pharmaceuticals.

Salomon W, Bulock K, Lapierre J, Pavco P, Woolf T & Kamens J (2010) Modified dsRNAs that are not processed by Dicer maintain potency and are incorporated into the RISC. Nucleic Acids Research. 2010, 38(11):3771-9. RXi Pharmaceuticals.

Hough SR, Wiederholt KA, Burrier AC, Woolf TM, & Taylor MF Why RNAi makes sense. Nature Biotechnology. 2003, 20:4. Sequitur, acquired by Invitrogen.

Woolf TM, Chase JM, Stinchcomb D (1995) Toward the therapeutic editing of mutated RNA sequences. Proceedings of the National Academy of Science, 92(18):8298-302 RPI, now SIRNA-Merck.