Biologics have become an integral part of the drug development cycle within the pharmaceutical industry. But current cheminformatics toolkits are not well-suited to facilitate representation and computational interrogation of large biomolecules in the same way as for small molecules. Our Marvin suite is the product most frequently exposed to our users, and with recent releases, we aimed to continuously improve support for its application in a biopharmaceutical setting. But where these improvements are a mere extension of our classical cheminformatics tools, we have taken up development of a novel Biomolecule toolkit in parallel. It shall address the identified shortcomings in the data handling of large biomolecules with full atomic description, comparison of large biomolecules, and the exposure of distinct data views for different specialty groups of scientists. In this short presentation we will outline our future roadmap in the biological sector.

1. Biologics - From old powerhouses
to novel tools
Roland Knispel

2. * Inside BIO Industry Analysis, David Thomas, CFA, 01/17/2013
28/39 new therapeutics approved by FDA were
small molecule drugs
New drug approvals in 2012*
30% of new therapeutics approved by FDA were
Biologics

3. FASTA import
Biologics in MarvinSketch 6.0

4. Unlimited attachment points for S-groups
Biologics in MarvinSketch 6.0
1-Phospho-histidine
3-Phospho-histidine
4
3

5. • Sequence bridges, cyclizations
• Leaving groups
In progress

6. • Improved clean-up upon sequence residue
expansion
In progress

7. New tools for information management

8. At the heart of
Corporate Business Intelligence
ChemAxon Registration solution
Registration
Web Services
Web Clients
Chemist Biologist AdministratorsProject Leader
ELN Feeder
Bulk Loader
Data Provider
Interfaces
Downstream
Applications
Downstream
Data Stores
User groups
Feeder systems Consumer systems
Registrar

9. • Distinct descriptors of biological entities
• Lack of representation standards
• Highly dynamic R&D workflows
• Genealogy-dependent uniqueness
Biologics registration challenges
S126

10. • Integrated browser-based registration system
– Agnostic data model
– Mapping of workflow processes to business logic
• Data mart capabilities
• BioSketcher
• Webservice-based architecture
Long-term goals

11. • Java-based toolkit and webservices facilitating
– Standardization and canonicalization of
Bio-macromolecule representation
– DB storage and simple queries
– Duplicate checks
– Full HELM notation support
• HELM editor applet as early stage GUI
Short-term goals

12. • Externalized from
Pfizer for Pistoia
Alliance project
• Established tools in
Biotherapeuticals
R&D at Pfizer
HELM editor and notation toolkit

13. Example – HELM notation
RNA1{R(A)P.R(G)P.R(C)PS.R(U)}
|PEPTIDE1{K.K.K.G.C}
|CHEM1{PEG3}$
RNA1,CHEM1,16:R2-1:R1
|PEPTIDE1,CHEM1,5:R2-1:R2$
$
RNA1{StrandType:ss}$
Definitions of simple polymers
Connectivity of simple polymers
Annotation tags
NotationStructure
RNA1
CHEM1
PEPTIDE1
Bond[16:R2-1:R1]
Bond[5:R2-1:R2]
x

14. Stage 1: Bio-molecule toolkit
API
Biomolecule DB
HELM Notation Toolkit
HELM parser
Standardization/
Canonicalization
Duplicate check
Webservice Core
HELM
HELM
Browser
application
Feeder service
HELM Editor
*
*
* As part of Pistoia Alliance HELM project, based on Pfizer tools

15. Stage 2: Bio-molecule toolkit
AuxiliayWebservices
Sequence BLAST
Calculators
Coordinate mapping
CompReg Link Service
API
Biomolecule DB
HELM Notation Toolkit
HELM parser
Standardization/
Canonicalization
Duplicate check
Webservice Core
HELM
HELM
Browser
application
Feeder service
HELM Editor
*
*
* As part of Pistoia Alliance HELM project, based on Pfizer tools

16. IJC integration
BioCore API
JChem tables
for Biologics
ID Structure Formula Length MW EC
1
C130H190N32
O41S2
28 2921 17190
2
C155H238N44
O46S1
30 3486 12660
3
C121H196N38
O35
25 2743 5690

17. – Full HELM support
– SOAP/REST-supporting Core and DAO webservices
for Bio-molecule registration DB
– Limited performance constraints
Option for interested parties to
– Evaluate features and integration capabilities
– Engage in joint discussions for future developments
Toolkit alpha version in Summer 2013

18. Stay tuned...
Q3
Q4
Q1
Q2
Bio-molecule toolkit
Alpha version*
Bio-molecule registration
Bio-material registration
2013
2014
* Contact us to find out more
Modular
Registration
System