ChemAxon UGM, Budapest

20/05/2015

SureChEMBL: Open Patent Data

George Papadatos, PhD

ChEMBL Group, EMBL-EBI

georgep@ebi.ac.uk

EMBL-EBI Resources Genes, genomes & variation

ArrayExpress Expression Atlas PRIDE

InterPro Pfam UniProt

ChEMBL ChEBI

Literature &

ontologies

Europe PubMed Central

Gene Ontology

Experimental Factor

OntologyMolecular structures

Protein Data Bank in Europe

Electron Microscopy Data Bank

European Nucleotide

Archive

1000 Genomes

Gene, protein & metabolite expression

Protein sequences, families & motifs

Chemical biology

Reactions, interactions &

pathways

IntAct Reactome MetaboLights

SystemsBioModels

Enzyme Portal

BioSamples

Ensembl

Ensembl Genomes

European Genome-phenome Archive

Metagenomics portal

Bioactivity data

Compound

Assay/T

arg

et

>Thrombin

MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLE

RECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGT

NYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYT

TDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVT

THGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGY

CDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLF

EKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDR

WVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWR

ENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTA

NVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGG

PFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE

3. Insight, tools and resources for translational drug discovery

2. Organization, integration, curation and standardization of pharmacology data

1. Scientific facts

Ki = 4.5nM

APTT = 11 min.

ChEMBL: Data for drug discovery

Why looking at patent documents?

• Patent filing and searching

• Legal, financial and commercial incentives & interests

• Prior art, novelty, freedom to operate searches

• Competitive intelligence

• Unprecedented wealth of knowledge

• Most of knowledge will never be disclosed anywhere else

• Average lag of 2-3 years between patent document and journal

publication disclosure for chemistry

From SureChem to SureChEMBL

• Digital Science/Macmillan donated SureChem to EMBL-

EBI

• SureChem: commercial patent chemistry mining product

• Wellcome Trust funds further development

• EMBL-EBI provides an on-going, live service

• Full functionality freely available to everyone

• Query, view and export chemistry from patents

• Complemented with biological annotations

SureChEMBL data processing

WO

EPApplications& Granted

USApplications

& granted

JPAbstracts

Patent

OfficesChemistry Database

SureChEMBL System

Patent PDFs

(service)Application

Users

API

Database

Entity Recognition

SureChem IP

1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenylsulfonyl]-4-

methylpiperazine

Image to Structure(one method)

Name to Structure (five methods)

OCR

Processed patents(service)

SureChEMBL data processing

WO

EPApplications& Granted

USApplications

& granted

JPAbstracts

Patent

OfficesChemistry Database

SureChEMBL System

Patent PDFs

(service)Application

Users

API

Database

Entity Recognition

SureChem IP

1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenylsulfonyl]-4-

methylpiperazine

Image to Structure(one method)

Name to Structure (five methods)

OCR

Processed patents(service)

Homepage

Help

Search by keyword and meta-data

Search by chemical structure(sketch

compound)

Search by SMILES, MOL,

SMARTS, name

Search by patent numberFilter by authority

(US, EP, WO and JP)

Filter by document section (title, claims, abstract,

description and images)

Chemical search type

(substructure, similarity, identical) Filter

by date

Filter by MW

www.surechembl.org

Data growth

• ~80K novel compounds every month

• ~800K novel compounds since EBI took over

• 2–7 days for a published patent to be chemically annotated and

searchable in SureChEMBL

Cumulative growth of SureChEMBL compounds

Co

mp

ou

nd

co

un

t

Time

EMBL-EBI chemistry resources

RDF and REST API interfaces

REST API Interface - https://www.ebi.ac.uk/unichem/

Atlas

Ligand induced

transcript response

750

PDBe

Ligand structures

fromprotein

complexes

15K

ChEBI

Nomenclature of primary and

secondary metabolites.

Chemical Ontology

24K

SureChEMBL

Chemicalstructures

from patent literature

16M

ChEMBL

Bioactivity data from literature

and depositions

1.5M

UniChem – InChI-based chemical resolver (full + relaxed ‘lenses’) >90M

3rd Party Data

ZINC, PubChem, ThomsonPharma DOTF, IUPHAR,

DrugBank, KEGG, NIH NCC,

eMolecules, FDA SRS, PharmGKB,

Selleck, ….

~65M

Data access & exports

• Full compound repository

• FTP download, SDF and CSV format

• Updates quarterly

• Full compound-patent map

• FTP download, flat file

• Updates quarterly

• Data feed client

• Creates a local replica database of SureChEMBL

• Updates daily

Compound-patent map

• Flat file with

• Compound, global frequency, document, section, section frequency, publication date

• Back file

• 187,958,584 unique patent-compound pairs

• 14,076,090 unique compound IDs

• 3,585,233 EP, JP, WO and US patent docs

• 1960-2014

• Quarterly incremental updates

• Q1 2015 is also now available on the FTP

http://chembl.blogspot.co.uk/2015/03/the-surechembl-map-file-is-out.html

Data feed client

http://vartree.blogspot.co.uk/2015/01/how-to-create-your-own-replica-of.html

Use cases with SureChEMBL

• Chemoinformatics

• Chemistry landscape for a particular biological target/disease

• Novel chemistry & scaffolds

• MDS, MCS and R-group analysis for a particular patent family claimed

chemistry

• (Negative) novelty checking with UniChem

• Competitive intelligence

• Reporting

• Patent alerts

• Per target/disease/company

Bioactivity data extraction? Compounds

Target/Assay

Bioactivity

Markush structure extraction?

-alkyl

-aryl

-heteroaryl

-heterocyclyl

-cycloalkyl

….

Biological annotations

Bioannotations soon to be integrated into SureChEMBL interface –

using SciBite’s Termite text mining engine

US

-9012636-B

2

Future steps

• OpenPHACTS ENSO

• Biological tagging of targets, genes, indications and diseases

• Development of integrated use-cases

• Combine chemistry & biology from patents, literature, pathways, etc.

• OpenPHACTS API

• Accessible via KNIME nodes

• Further improvements/added value

• Data quality and accuracy

• Target and compound relevance score

Acknowledgements

ChEMBL team:

• John Overington

• Anne Hersey

• Anna Gaulton

• Mark Davies

• Nathan Dedman

• Michal Nowotka

Collaborators:

• James Siddle

• Richard Koks

• Lee Harland

• Kevin Clark

Support:

surechembl-help@ebi.ac.uk

Webinar:

http://www.ebi.ac.uk/training/online/course/surechembl-accessing-chemical-patent-data-webinar

Technology partners

ChemAxon UGM, Budapest

20/05/2015

SureChEMBL: Open Patent Data

George Papadatos, PhD

ChEMBL Group, EMBL-EBI

georgep@ebi.ac.uk

Back-up slides

• Connectivity match on single components - UniChem

ChEMBL-SureChEMBL compound overlap

21.4%SureChEMBL

ChEMBL

1.5M

16M

Too granular? Try scaffolds instead

Level 1 scaffold overlap

57%SureChEMBLChEMBL

61K

298K

Level 1 scaffold overlap

57%SureChEMBLChEMBL

61K

298K

Can we have everything?

Cost

TimeQuality

Common sources of errors

• Small, poor quality images

• OCR errors in names (OCR done by IFI). There is an OCR correction

step, but cannot fix all errors

-> ‘2,6-Difluoro-Λ/-{1 -r(4-iodo-2-methylphenyl)methvn-1 H-pyrazol-3-

vDbenzamide’

• Reliability better for US patents due to inclusion of mol files