Markush Structure Usability in Patent and Combinatorial Chemistry: New Approaches and Software Tools. Wei Deng (David)

Transcription

1 Markush Structure Usability in Patent and Combinatorial Chemistry: New Approaches and Software Tools Wei Deng (David)

2 Chemical Space in Patents Exemplified structures Chemical space: Indexed by different organizations OCR and OSR extraction ChemAxon s Document to Structure Chemical space described in the specification (including background of the invention) Markush structures Chemical space: >> 10 3 Search systems: CAS STN Questel MMS ChemAxon (New) Chemical space described in the claim Exemplified compounds 2

3 Flexible Markush Structures copied from part of WO

4 ChemAxon - Thomson Reuters Markush project history 1987 Thomson Scientific (Derwent) starts indexing Markush structures (in collaboration with Questel & INPI) 1998 INPI & Derwent Markush databases merge to form MMS (Merged Markush Service) 2000 ChemAxon launches first version of JChem Base 2005 Chemaxon starts working on Markush technology 2008 Markush search & enumeration first release in JChem Markush DARC file format support in JChem Full MMS searchable with JChem

5 Markush User Community Markush user community IP experts / patent searchers / Information scientists Patent lawyers / Patent agents Medicinal chemists Computational chemists/cheminformaticians Goal Bring Markush search to a wider community

6 Summary Markush Creation Sketching Import from Thomson Reuters Markush enumeration Markush search Full patent Markush database search on Amazon EC2 Other Markush-related analysis 6

7 MARKUSH CREATION 7

8 Markush Structure Features I Atom lists, bond lists Position variation bond Link nodes and repeating units R-groups Multiple attachment points Up to thousands of R-group definitions Nested to any depth

9 Markush Structure Features II Homology groups (MMS: superatoms, CAS: generic definition) (properties) Easy to understand graphical representation All supported in MRV file

10 Import from Thomson Reuters 10

11 MARKUSH ENUMERATION 11

12 Markush Enumeration Functionality: Full Sequential Random Calculate library size Scaffold alignment and coloring Markush code Homology group enumeration Post filter

13 Markush Structure Reduction Query Substructure hit visualization Scaffold only Scaffold + relevant R-groups Scaffold + all R-group with relevant R-group colored Hit alignment Hit colouring Structure cleaning Result in original Markush Reduced result

14 Re-designed Markush Enumeration Interface Markush reduction according to the hit (expand core to contain substructure query) Query aligned and colored in enumerated structures Post-filtering (e.g. drug-like) and structure export for customized study Improved enumeration speed 14

15 MARKUSH SEARCH 15

16 Search in Instant JChem Search in both exemplified and Markush structures Various search options: Substructure or full Broad translation Stereochemistry, tautomer Atom/bond matching Text search in all fields Multiple search results can be creatively combined Flexible visualization functions to display result with scripting feasibility Integrated with new interfaces for navigation and enumeration Other search options include JChem Cartridge, JChem SharePoint, and API 16

17 Additional Markush Query Features I on Atoms Query atom any, metal, hetero... Atom topology (ring, chain) Stereochemistry (E/Z, tetrahedral) Aromatic, aliphatic atoms Substitution count Block substitution (s*) H count Explicit H full support Ring bond count Isolate ring on atoms (rb*)

18 Additional Markush Query Features II on Bonds Bond topology (chain/ring) and other... Equal homology translation Broad translation switchable Simple R-group queries

19 Improved R-group Hit Visualization Integrated with Markush Viewer

20 Markush Viewer

21 Multiple Queries: Overlap Analysis 21

22 Multiple Queries: Overlap Analysis 22

23 Search the Full Patent Database Complete patent database from Thomson Reuters dated back to 1987 VMN (Markush structures) DCR (Exemplified structures) DWPI text (non-structural information) Data stored in Amazon Cloud with Powerful virtual machine, secure connection and confidential search Useful new features: Export exemplified structures Retrieve patent document Enumerate Markush structures and output result Notation Batch search of multiple queries Constantly improving search performance 23

24 New Interface, New Buttons, New Features All information in one place 24

25 Export Exemplified Structures 25

26 Retrieve Patent Document 26

27 Add Notes 27

28 Notation Overview 28

29 Batch Search of Multiple Queries 29

30 Batch Search of Multiple Queries 30

31 OTHER MARKUSH-RELATED ANALYSIS 31

32 Other Features R-group decomposition in molecule tables Creation of Markush structure from selected rows.

33 Future Work Improve search speed and accuracy Additional query variations Better visualization Integration with Document to Structure to extract chemical information from patent documents Collaboration with Linguamatics 33

34 Acknowledgements JChem base, Markush and IJC Helpers - JChem WS, Cartridge, Core & Marvin, Marketing Steve Hajkowski Brian Larner Don Walter Gez Cross Tony Ferns Tim Miller

35 Hunting for Hidden Treasures A CINF Symposium regarding chemical information in patents and other documents ACS meeting in Philadelphia, August 19-23, Current speakers from Content providers Software providers Pharmaceutical researchers 35