New Software Developments on

Chemical Information Extraction from Patent

Documents and Markush Structure Analysis

Wei Deng (David)

PIUG Meeting

May 2nd, 2012

Denver CO

ChemAxon’s Naming Technology

• Name to structure

– IUPAC, traditional and common names

– A library of existing drugs

– Support CAS Registry number

– Homology group: alkyl, aryl …

– Future: Biological names

• Structure to Name

– IUPAC Name, traditional names

• Accuracy and coverage constantly improving

• Also available from command-line

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ChemAxon’s “Document to Structure”

• Extract chemical information from documents – Names: powered by the Naming Technology

– Also import smiles, InChI, CAS number …

– Images: OSRA

– Returns structure and their location in the document

• Works with scanned PDF since 5.8 (Feb 2012)

– Great for patent mining

• OCR and syntax correction constantly developed

– 3-rnethyl-l-me- thoxynaphthalene

– 3-methyl-1-methoxynaphthalene

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From Document to Structures

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Non-searchable patent (50 pages) Structure (text + image) + location

Search by Structure or Text

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Non-searchable PDF is now Searchable

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ChemAxon’s “Document to Structure”

• New Features in 5.9 (Mar 2012)

– MS Office document: doc, docx, ppt, pptx, xls, xlsx, odt …

– Embedded structure objects (ChemDraw, Symyx, Marvin

…)

– Progressively display result

– Speed improvement

– Instant JChem Integration; Simplfied API

• Currently in development for 5.10 (May

2012) – Image-to-structure “Confidence”

– Fragment groups integration with Markush generation

– Biologic names

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Free Online Service Chemicalize.org

• Extract chemical information from web pages and documents

• Interactively display all structures and their predicted properties

• Search all structures extracted

• Gather links of interest to chemists for post processing (search,

analysis, reporting, fun…)

• Recently reviewed on Journal of Chemical Information and

Modeling

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Webpage - chemicalized

• All chemical names are highlighted with dotted line

• Mouse over a name pops up the structure image

• Click on the image will direct to the data page

• Links are “respected”

• Customizable report layout for calculation results. Users can move, open, close, expand calculation boxes and this is remembered on the next visit

Data Page: Extensive Predicted Properties

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• All structures are summarized above the chemicalized page

• Click on a structure to highlight all occurrences. Click again to

navigate to the next occurrence

• All structures can be downloaded as MRV or SDF (useful with

online patent full text)

Webpage - chemicalized

PDF File - chemicalized

Aspirin: query highlighted in results

Searching Chemicalize.org – Structure Search

• Aspirin; web page hits - “show” related structures

• Autosuggest while typing

Searching Chemicalize.org – Keyword Search

Everything is Published

• Recent viewed

– Webpages

– Structures

– Documents

– Searched queries (structure and keyword)

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Availability and Customization

• Source code available

• Minor changes required on example codes

for customization, such as

– Import extracted structures to other databases

– Post-process filtering according to properties

– Batch process of multiple documents

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MARKUSH TECHNOLOGY

UPDATE

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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 5.0

2010 Markush DARC file format support in JChem 5.3

2011 Full MMS searchable with JChem 5.5-5.8

Search the Full Patent Database

• Complete patent database from Thomson Reuters (Markush +

exemplified + non-structural information, dated back to 1987)

• Data internally hosted or on Amazon Cloud

• 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

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New Interface, New Buttons, New Features

• All information in one place

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Export Exemplified Structures

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Retrieve Patent Document

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Add Notes

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Notation Overview

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Search in Instant JChem

• Search in both exemplified and

Markush structures

• Various structure search options:

– Substructure or full

– Broad translation

– Stereochemistry, tautomer

– Atom/bond matching

• Text search (including dates)

• Multiple search results can be

creatively combined

• Flexible visualization functions to

display result with scripting feasibility

• Integrated with new interfaces for

navigation and enumeration

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Improved R-group Hit Visualization

Integrated with Markush Viewer

• Substructure hit visualization

– Scaffold only

– Scaffold + relevant R-groups

– Scaffold + all R-group with relevant R-group

colored

Query

Result in original Markush

Reduced result

Hit Expansion

Hit alignment

Hit colouring

Structure cleaning

Batch Search of Multiple Queries

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Batch Search of Multiple Queries

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OTHER MARKUSH-RELATED

ANALYSIS

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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

Markush Structure Features I

Homology groups (“Superatoms”, “Generic definitions”)

(properties)

Easy to understand

graphical representation

All supported in MRV file

Markush Structure Features II

Markush Viewer

Markush Enumeration

Functionality: Full

Sequential

Random

Calculate library size

Scaffold alignment

and coloring

Markush code

Homology group enumeration

Post filter

Re-designed Markush Enumeration Interface

• Markush reduction (hit expansion) according to query

• Query aligned and colored in enumerated structures

• Post-filtering and structure export

• Improved enumeration speed

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Other Features

• R-group decomposition in molecule tables

• Creation of Markush structure from selected rows.

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

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Hunting for Hidden Treasures

• A CINF Symposium regarding “chemical

information in patents and other documents”

• ACS meeting in Philadelphia, August 19-23,

2012.

• Current speakers from

– Content providers

– Software providers

– Pharmaceutical users

• One opening slot on Markush structure

analysis

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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

Backup Slides

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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

Import from Thomson Reuters

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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*)

Additional Markush Query Features I

on Atoms

Additional Markush Query Features II

Bond topology (chain/ring)

Equal homology translation

Broad translation switchable

Simple R-group queries

on Bonds

and other ...

Multiple Queries: Overlap Analysis

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Multiple Queries: Overlap Analysis

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