markush claims: representation, search, analysis and construction - where are we and how to go...

MARKUSH CLAIMS: REPRESENTATION,

SEARCH, ANALYSIS & CONSTRUCTION

Árpád Figyelmesi

27th ICIC International Conference for the Information Community

Nice 2015

Where Are We and How to Go Forward?

OVERVIEW

History and current state of Markush claims

Origins

Dr. Eugene A. Markush

1888 Budapest, Hungary

1968 New York, USA

US1506316A

”The process for manufacture of

dyes…”colorantshistory.org

Importance

• Between 1994 and 2013

• 3,704,996 US patent

• 468,262 with Markush claims

• Every eighth patent contains

Markush claims

Joseph J. Mallon, 2014

The real value in Patents not in Drugs…

You Need Good Markush Technology

or

Lot of manual work (with unavoidable mistakes)

Drug Discovery workflow

Find relevant

documents

Analyze prior art

and invent

something new

Create your

own Patents

Variation types

• Substituent variation

• Position variation

• Frequency variation

• Homology variation

• Variation inside variation (nested)

• Additional logical constraints

Patent Markush

• Nested R-groups

• Homologies

• Additional logical constraints

Combinatorial Library

• No nested R-groups

• No Homologies, Repeating

units and Position variation

Markush types

Markush chemical space size

Zhengwei Peng, 2014

Existing databases

Thomson Markush database (MMS)

2.4 million patents

1.6 million Markush structures

2 million specific compounds

CAS Markush database (MARPAT)

0.5 million patent

1 million Markush structures

REPRESENTATION

Markush representation techniques and challenges

● R-groups

● Atom lists

● Bond list

● Position variations

● Repeating units

● Homology groups

Markush Representation

US5948793A

Claimed structure represented

with multiple structures

Workarounds

CONSTRUCTION

Sketching and automatic generation of Markush structures

General structure editors

Markush Editor

R-group definitions

Tree view Scaffold

Structure checker

Nesting view & Preview

Markush Composer

Automatic Markush generation from compound list

DOCUMENT CURATION

Extracting Markush structures from Patents

Representing Covered Chemical Space

● Document processing (XML,

PDF, HTML)

● Name to structure

● NLP technologies

● OSR (CLiDE & OSRA)

Automatic Markush extraction

ChemProspektor

InfoChem

Theseus research project founded

by the Federal Ministry of

Economics and Technology

Dr. Josef Eiblmaier, ACS National Meeting, Philadelphia, August 19 - 22, 2012

ChemCurator Markush extraction view

Markush editor

Example structures

Annotated document

Selected structures

Structure checker

MARKUSH SEARCH & ANALYSIS

Understanding covered chemical space and comparison

Markush Search & Hit Visualization

● Substructure

● Full structure

● (Similarity)

● Hit visualization

● Non-Hit visualization

Markush Enumeration

• Full enumeration

• Random enumeration

• Partial enumeration

• Library size calculation

• Biased enumeration

• (Property distribution

characterization)

Markush Overlap

Overlapping chemical space

calculation

Results:

● Percentage of overlap

● Overlapping Markush

Benefits:

● No enumeration

● No size limitations

SUMMARY

Summary

• Important breakthroughs in Markush technology– Search & hit visualization

– Comparison

– Construction

– Curation

• Active development in challenging areas– Similarity search

– Characterization

THANK YOUÁrpád Figyelmesi

afigyelmesi@chemaxon.com

27th ICIC International Conference for the Information Community

Nice 2015