Pistoia Alliance RSC evening event 2015: Stefan Klostermann, Roche, on the HELM Antibody Editor
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Transcript of Pistoia Alliance RSC evening event 2015: Stefan Klostermann, Roche, on the HELM Antibody Editor
![Page 1: Pistoia Alliance RSC evening event 2015: Stefan Klostermann, Roche, on the HELM Antibody Editor](https://reader035.fdocuments.net/reader035/viewer/2022062710/55a717211a28ab4f798b45ab/html5/thumbnails/1.jpg)
The HELM Antibody Editor
Stefan Klostermann, Roche pREDi
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Agenda
• Scope of the HELM Antibody Editor
• DEMO: From raw sequences to drugs
• Role of
• DEMO: Integration with HELM Editor
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HELM Antibody Editor
to handle complex antibodies
• Analysis / decomposition
• Visualization
• Manipulation
• Registration
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• Detection, analysis and annotation of all domains
• Cys-Cys bonds
– Intra-domain (Ig-like)
– Inter-domains (scFv, scFab)
– Inter-chains (HC-HC/LC)
– Alert if free Cys left
HELM Antibody Editor
Decomposition & Assembly
• Variable, hinge, constant
• V: germlines, C: isotypes
• Species ( human?)
• Mutations (Knob into hole)
• Peptides, linkers, payloads
bispecific
trispecificeffector protein
knob into hole
Xmab
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HELM Antibody EditorRegistration & Data Analysis
Registration
• Unique identifier (check)
• Full chemical structure
• Domains & annotations
• Antibody format (used modules)
• Antibody figure
• Fully automatic even startingwith just raw sequences!
Data analysis
1) SAR analysis of
• Specificities
• Antibody formats
• Linker types
• Payloads (+position)
2) Retrieval of components
21
3
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HELM Antibody Editor
Open the HELM Editor
Note: Architecture of version
released soon will be different
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HELM Antibody Editor
Start the HELM Antibody Editor
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HELM Antibody Editor
Load raw sequences
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HELM Antibody Editor
Raw sequences in FASTA format
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HELM Antibody Editor
Review sequence decomposition
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HELM Antibody Editor
Fully assembled and annotated
antibody drug molecule
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HELM Antibody Editor
Review single domains
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Role of HELM
Background
• Hierarchical Editing Language for Macromolecules
– Notation
– HELM Editor & toolkit
• Released by Pfizer to the Pistoia Alliance for public distribution
– http://openhelm.org/ Github
• Emerging new notation standard for complex biologicals
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Role of HELM
for the HELM Antibody Editor
• HELM notation used for registration
• HELM toolkit used for coding
• HELM Editor used for manipulations of domains (e.g. for ADCs)
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HELM Antibody Editor
Fully assembled and
annotated antibody
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HELM Antibody Editor
Select a single domain for editing
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HELM Editor
Edit domain in HELM Editor
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HELM Editor
Load SMCC and connect to domain
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HELM Editor
Load peptide and connect to SMCC
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Sync back from HELM Editor
to HELM Antibody Editor
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HELM Antibody Editor
Final drug molecule & further manipulations
Manually create Cys-Cys bonds
Manually delete Cys-Cys bonds
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HELM Editor
Final drug molecule
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Summary
The HELM Antibody Editor
• allows easy (usually automatic) registration of even complex antibody
formats
• ... to enable SAR analysis within and across projects
• ... and full search & retrieval of all components.
• Will be made public in the tradition of the HELM Editor
by Q1 2015 on Github.
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Acknowledgements
To the developers
Domain editor and framework (Pharma Research and Early
Development Informatics, Roche Innovation Center Penzberg, Germany)
• Pandu Raharja (Trainee)
• Stefan Zilch (BridgingIT GmbH, Mannheim)
• Marco Lanig (quattro research GmbH, Martinsried)
Domain recognition (quattro research GmbH, Martinsried, Germany)
• Anne Mund (Trainee)
• Marco Lanig
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Doing now what patients need next
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HELM Antibody Editor
Methodology
• Chop chains into domains (use BLAST against domain library)
• Annotate domains
– e.g., Vh, Ck, linkers, peptides, effector proteins
– as defined by domain library
• Detect known mutations in constant domains
– e.g. LALA, knob-in-hole
– as defined by mutation table
• Detect known multi-domain modules
– e.g. XMab, scFv, scFab
– as defined by auto-connector rule set