1

The challenges related to

in-depth analysis of patent molecular spaces

in support of drug discovery projects

Zhengwei Peng

09/26/2014, 2014 ChemAxon UGM, Boston

2

Outline

• Quick introduction

• Need for in-depth analysis of patent molecular space

• Current state, major challenges, and the desired future state

• Potential implications for the wider community

• Pharma scientists

• Pharma patent attorneys

• Patent offices

• Patent content providers

• A pipe dream

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Claimed chemical space by a chemical patent

The size of a patent Markush claim space could be large (1012 – 1030).

However commercial solutions do exist to encode Markush claims into

searchable form(s) and perform structure searches (SSS and Exact)

against these vast virtual compound spaces.

Exemplified

Molecules

Broadest Claim

Encode into

computer-

searchable

format(s)

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A sample patent Markush claim

core

R1

R2

R3

R4

R5

CAS & TR are the two dominant

Markush content providers.

100-500 analysts are required to

encode published chemical

patents Time, $$ cost of

subscription for customers

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The importance of in-depth patent analysis

ViagraLevitra

The need for a

good defenseThe power of a

good analysis

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Major questions asked by project chemists

• Is my lead compound patentable, and do we have freedom to operate?• This requires comprehensive prior art search (CAS/TR Databases)

• Patent attorneys provide the analysis and opinion on patentability and FTO

• What is the competitive landscape in this area (disease, protein target, and

compound)?• literature and patent searches done by project members & expert searchers

• I want an in-depth analysis on patents or patent applications pertinent to my

project • exemplified molecules

• assay data associated with SAR

• patent Markush claim(s)

• I want an in-depth analysis of the strength of my draft patent application • Does the draft Markush claim cover all the exemplified molecules?

• Did I provide sufficient information to cover all embodiments of the invention?

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The current state, challenges,

and the desired future states

Search &

browse tool

Internal

patent store

Selective

download &

encoding

anytime needed

Markush

patent

content

Expert

Search tool

Search

expert

Patent

attorney

New

patents and

patent

applications

Encoding &

publish ~

monthly

(time & $)

• Time delay by the content provider

• No direct access to expert search tool for project chemists

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Tools and workflow to enable project teams to

perform in-depth analysis of patent Markush

Internal

patent

store

Patent

files

(xml/pdf)

Selective

patents

relevant to a

discovery

project

(10-100 per

project)

Curation

GUI tool

Manual

review &

edit to

ensure high

quality

Doc 2 Str

extraction

Auto

structure

recognition

& extraction

• Search

• Enumerate

• Compare

Search &

browse tool

Markush

patent

content

API

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An early prototype by ChemAxon

D2S: Chemical terms inside

patent doc are recognized

and converted to live

molecular structures

Molecular structures can be

dragged and dropped to

construct the searchable

patent Markush object

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Implications for the wider community

Curation

GUI tool

Markush

search &

analysis

tool

1) Patent preparation stage

2) Patent

approval

stage

3) Patent publication stage

4) Content

distribution

stage

Patent

attorney

Patent

Office

Win-Win:

• Tool potentially useful for patent attorney to prepare and prosecute

patent applications.

• Faster/cheaper content publication (good for content providers as

well as content users)

• Timely data access by scientists

• Higher efficiency & lower cost Benefit society in general…

Objections heard so far:

• Naïve, a pipe dream…

• The need for obfuscation is always here..

• Migrating from legacy formats to the new one is hard & costly..

• ..

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Summary

• To better serve drug discovery projects, in-depth analysis of patent

molecular spaces in a timely manner is highly desirable to

• understand the implication of newly published external patents and

patent applications on the project

• assist the project chemist to understand the scope of the published

art to help identify productive areas

• ChemAxon’s suite of tools (D2S, Chem-Curator, Patent Markush Search

Platform, etc.) are well positioned as the potential solution for the

wider community

• a newer & better (?) search engine one can license

• content neutral

• once adopted by the wider community as a standard, it has the

potential to solve a long standing challenge and yield significant

benefit to the drug discovery community.

• Pharma companies have an active role in shaping the future

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Acknowledgements

• ChemAxon collaborators• Tim Dudgeon, David Deng, Doug Drake, and Arpad Figyelmesi

• Merck colleagues• Chris Brofft and Wendy Cornell (MRL-IT)

• Kenrick Vidale (Legal-IP Group)

• Michael Altman and Nicolas Zorn (MRL-SC)

• Chris Waller, Frank Brown, and Emma Parmee (Management sponsorship

and support)

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Supplemental material

Backup slides

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References

• Lynch et al., (1996) The Sheffield Generic Structures Project: a retrospective review. J. Chem. Inf.

Comput. Sci., 36, 930-936.

• The MARPAT patent Markush searching system of CAS: Ebe et a;., (1991) The Chemical Abstracts Service

generic chemical (Markush) structure storage and retrieval capabilities. J. Chem. Inf. Comput. Sci. 31, 31-36.

(CAS web link: http://www.cas.org )

• The Merged Markush Service (MMS) of Thomson Reuters: Benichou et al. (1997) Handling genericity in

chemical structures using the Markush DARC software. J. Chem. Inf. Comput. Sci. 37, 43-53.

• The ChemAxon Markush search technology enables structure searches (SSS and Exact) into vast patent

Markush spaces: http://www.chemaxon.com/products/Markush-ip/

• ChemAxon Instant J-Chem interfaces with the MMS search service form Thomson-Reuters. This provides a

more interactive and user-friendly GUI to the existing STN search user interface offered by Thomson

Reuters. TR Markush patent content was converted to ChemAxon readable format automatically => 80%

concordance in search results between two search engines.

• ChemProspector (http://infochem.de/news/projectdisplay.shtml?chemprospector.shtml), a project funded by

the German government to build software to automatically extract the core and R Groups from chemical

patents and store them in a searchable database. Conclusion: it is very hard to automatically construct high-

quality Markush space definition based on the diverse ways patent claim sections were crafted.

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• Also SciFinder now interfaces with the CAS’ MARPAT search service.

• Barnard et al.,(2009) Towards in-house searching of Markush structures from patents. World Patent Inf. 31,

97-103.

• Downs & Barnard, (2011) Chemical patents information systems, Wiley Interdiscip. Rev.: Comput. Sci. 1,

727-741.

• Cosgrove et al. from Astra Zeneca, (2012) A System for Encoding and Searching Markush Structures, J.

Chem. Inf. Model, 52, 1936-1947.

References