Comprehensive DWPI SM structure searching using DCR and DWPIM on STN

Comprehensive DWPI SM structure searching using DCR and DWPIM on STN Brian Larner, IP & Science, Thomson Reuters Robert Austin, Senior STN Trainer, FIZ Karlsruhe 19 May 2016

AGENDA Introduction to DWPI chemical structure indexing DCR The Derwent Chemistry Resource What is it? Search example The Derwent Markush Resource (DWPIM) What is it? Structures indexed Search example Advanced topics Substance descriptors Roles Polymers, Inorganics, Phthalocyanines & Metallocenes 2

WHAT IS CHEMICAL INDEXING? Markush structural indexing for generic structures Created for all Markush Structures that meet the criteria for being indexed Also created to cover generic disclosures described only in words (eg cleaning solution containing a 2-8C alcohol) DCR indexing for specific compounds Created for any specific compounds mentioned in the patent Some compounds may be covered in Markush structure if system limits are exceeded Fragmentation coding auto-generated from the above 3

DWPI structure databases on STN SUBX DWPIM > 1.9 M structures DWPI > 3.2 M patents DCR > 2.5 M structures REFX Each structure has a unique Markush Compound Number (MCN) or DCR number (DCR) which is used as the basis of the cross-file search. 4

CHEMICAL STRUCTURE INDEXING IN DWPI - CRITERIA To receive structural indexing a DWPI record must meet the following criteria Classified in Sections B, C and / or E From a major country* * See list on next slide 5

DWPI COUNTRY COVERAGE FOR CHEMICAL INDEXING 6

WHAT IS INDEXED Compounds claimed to be new Compounds produced by a new process Compounds having a new use Components of compositions Novel catalysts and known specific catalysts Specific reagents and starting materials in production processes (DCR only) Materials detected, detecting agents, detection media Materials recovered or purified in new ways Materials removed and removing agents 7

DERWENT CHEMISTRY RESOURCE (DCR) This is a database of specific chemical substances mentioned in patents They are also organised into families of closely related compounds as follows basic compound salts, isotopes, mixtures, isomers Substance records include structure diagrams and substance data, e.g. IUPAC-name, synonyms molecular formula, molecular weight 8

DWPI CHEMISTRY RESOURCE (DCR) The DCR numbers are associated with the relevant fragmentation codes for the substance so they can be searched in conjunction with non-structural fragmentation codes if desired They also have roles associated with them (e.g. produced, detected)so that you can limit your answers by the role of the compound 9

BENEFITS OF DWPI INDEXING - REAL EXAMPLE Search on Diclofenac or its most common synonyms (Voltarol or Voltaren) using Key words in DWPI title & abstract - Find 3530 documents Search on Diclofenac via DCR record We find 3105 records 447 of these were not found by the keyword search 10

SOME INVENTIONS FOUND ONLY BY THE KEYWORD SEARCH ARE LESS RELEVANT 11

BUT THE ONES FOUND ONLY BY DCR ARE HIGHLY RELEVANT 12

DCR COVERAGE DCR records are only created for patents that are classified in at least one of the following CPI sections B(Pharmaceuticals) C (Agrochemcals) E (General Chemistry) In addition existing DCR records are cited when the substances they relate to are mentioned in the DWPI abstracts for patents classified in Section D, F, G, J and K DCR numbers are auto-generated from the specific compound codes in polymer indexing and added to the indexing 13

DCR COVERAGE BY COMPOUND TYPE Ordinary organic compounds (eg ethanol, ibuprofen) Inorganic compounds (eg Sodium chloride, ammonia) Complexes and organometallics (eg ferrocene, Copper phthalocyanine, diethyl magnesium bromide) Peptides with 10 or less amino acids Proteins and other natural polymers with well defined names* Synthetic Polymers from a standard list of around 340 commonly occurring ones Plant, animal & microbial extracts* *these records do not contain structures 14

WHAT IS NOT COVERED Generic classes of compounds These are covered by other forms of chemical structure indexing in DWPI eg fragmentation coding Synthetic polymers other than the ones in the predefined list of around 340 These are covered by polymer indexing Any compound of ambiguous structure This could be those with ill defined ratios of ions or components Or ones with ambiguous names where we can not be sure of the correct structure 15

New STN workflow is oriented around projects 16 To create a project, click the icon. Projects allow you to: Easily return to previous work Reuse common queries Update searches with the most current information

The new STN interface puts query, history and results at your fingertips 17 Structure Editor Query Builder panel History panel Results panel

Prepare structure queries using the structure editor 18 Click OK to add the query to the structures tab of the history panel.

Search the structure query and review structures 19 Automatic Cross File Search is set ON. Click on any structure to enlarge (zoom).

Crossover with REFX and review hit structures in DWPI 20 Use the REFX operator to retrieve corresponding DWPI references (L2). Hit structures with hit highlighting are included in DWPI full view. The structure search (L1) is combined with technology terms in DWPI (L2).

DERWENT MARKUSH RESOURCE ON STN Approximately 1.9 million structures from around 780,000 patents Covers 33 patent issuing authorities (as basic patent country) Can be searched in conjunction with DCR, MARPAT and CAS REGISTRY on STN In most cases using the same structure query Gives the most comprehensive chemical structure search possible 21

TYPES OF STRUCTURES INDEXED Non-polymeric organic molecules Organometallic compounds Inorganic structures Simple inorganic molecules Extended structures such as clays, zeolites and heteropolyacids Partially defined structures Polymeric structures Only for pharmaceutical and agrochemical patents Includes peptides as well as synthetic polymers 22

MARKUSH COVERAGE IN OLDER PATENTS Prior to the introduction of DCR in 1999/2000 the policy was different Both specific and generic structures were covered by Markush structures, often as part of the same structure Some commonly occurring compounds were indexed using Derwent Compound Numbers It was the analysts choice whether to use these or combine them into a Markush These have now been converted to DCR records and can found by a DCR search But are still included in the Derwent Markush Resource 23

ORGANIC MOLECULES IN THE DERWENT MARKUSH RESOURCE Generally speaking they are indexed as shown in the Patent Counter ions are sometimes ignored (but not in the example below) Derwent Markush Resource Version In the patent 24

WHY THE CORE STRUCTURE CAN DIFFER FROM THE ONE DRAWN IN THE PATENT Indexing conventions Keto-enol tautomerism (keto form is the preferred one) Amidine normalisation (amidine/guanidine groups have normalised bonds not single and double bonds) Use of DWPI markush terminology and shortcuts Use of Superatoms terms (CHK, ARY etc.) & shortcuts (CO2, SO3 etc.) Allowing for variable attachments Replace all the parts of the structure where the attachment can be made by a variable group Allowing for exceptions mentioned in the patent For example where at least one of R1 & R2 is not H Allowing for system limits Means sometimes one structure is split into 2 or more 25

SUPERATOMS AND THEIR MEANING (ORGANIC) Superatom Definition STN query node CHK Fully saturated alkyl chain Ak CHE CHY Carbon chain containing at least one double bond (no triple bonds) Carbon chain containing at least one triple bond (optionally with double bonds) CYC Non-aromatic carbocyclic ring Cb ARY Carbocyclic ring system containing at least one benzene ring or quinoid variant HEA 5 membered ring with 2 double bonds or 6 membered ring with 3 double bonds HET Any mononuclear heterocyclic ring other than HEA HEF Fused heterocyclic ring system Hy Ak Ak Cb Hy Hy See also: DWPIM Reference Manual, Table 3, Page 18. 26

SUPERATOMS AND THEIR MEANING (INORGANIC OR NON-SPECIFIC) Superatom Definition STN query node HAL Halogen excluding At X AMX Alkali(ne earth) metal M A35 Group 3 to 5 metal M TRM Transition metal M LAN Lanthanide (excluding Lanthanum) M ACT Actinide or other trans-uranic metal M MX Unspecified metal M XX UNK Unspecified group but not hydrogen, mostly used for unspecified substituent groups Unspecified group (no longer used but may be present in some older structures) See also: DWPIM Reference Manual, Tables 4-6, Pages 19-20. 27

SUPERATOMS USED FOR DISPLAY ONLY Superatom ACY DYE PRT PEG POL Definition Acyl group (derived from any organic acid, not just carboxylic) Undefined dye chromophore Protecting group Polymer end group Polymer group Please note Derwent Superatoms will become directly searchable in a subsequent release of the Derwent Markush resource on New STN See also: DWPIM Reference Manual, Table 6, Page 20. 28

ATTRIBUTES Attributes can be applied to Superatoms to restrict the scope of the group they describe. For carbon chain Superatoms (CHK, CHE, CHY) we have the following Describing chain length LOW (1-6C), MID (7-10C) & HI (>10C) Describing chain structure STR (Straight) & BRA (Branched) For ring Superatoms we have the following Type of ring system - MON (Monocyclic) & FU (Fused) Degree of saturation SAT (Saturated) & UNS (Unsaturated) MON & FU are not applied to HEA SAT & UNS are not applied to HEA and ARY See also: DWPIM Reference Manual, Table 18, Page 62. 29

Search example 30 Search Query: 1 2 3 4 = No further substitution on Ak (Locked). 1 2 3 4 Thiophene: ML = Atom Carbocycle (Cb): ML = Atom Class Alkyl (Ak): ML = Class Heterocycle (Hy): ML = Atom Class Default settings.

STN variable query nodes retrieve DWPIM generic nodes 31 STN variable query nodes DWPIM retrieved generic nodes DWPIM generic nodes for Ak CHK CHE CHY DWPIM generic nodes for Cb ML = Class ARY CYC DWPIM generic nodes for Hy HEA HET HEF

STN node attributes retrieve DWPIM indexed attributes 32 STN node attributes, e.g. Ak ML = Class DWPIM retrieved attributes DWPIM alkyl (no limitation) CHK CHE CHY ML = Class DWPIM alkyl (low) CHK CHK LOW ML = Class DWPIM alkyl (straight) CHK CHK STR

STN variable query nodes retrieve DWPIM generic nodes 33 STN search query Typical DWPIM assembled hits 3 4 1 2 3 4 1 2 STN query nodes with Match Level Class, retrieve corresponding generic and specific nodes in DWPIM. 4 DWPIM attributes are also accessible, e.g. MON = monocyclic, FUS = Fused. 2 3 1

Prepare structure queries using the structure editor 34 Cb and Hy nodes have been set to Class match. Changes from defaults are indicated with an asterisk. This has no effect on DCR. Right click on a node to change Attributes, e.g. Match Level. Block substitution with the lock atoms tool. Click OK to add the query to the structures tab of the history panel.

Search the structure query and review structures 35 Click on a Markush compound number of interest for detailed display views (next). Assembled structures with hit highlighting. Automatic Cross File Search is set ON. Click on any structure to enlarge (zoom).

DWPIM detailed display Brief view 36 Unassembled DWPIM Markush base structure. Hit fragments are combined to form the assembled structure. Query relevant G- groups (G2, etc.). Hit fragments are highlighted.

37 Detailed display allows you to choose a preferred view Brief unassembled hit Markush base structure with complete hit G-groups related to the query Hit fragments within hit G-groups are highlighted Full unassembled hit Markush base structure with all G-groups, including those not related to the query Hit fragments within hit G-groups are highlighted

Crossover with REFX and review hit structures in DWPI 38 Use the REFX operator to retrieve corresponding DWPI references (L2). The structure search (L1) is combined with terms for antiviral in DWPI (L2).

SUBSTANCE DESCRIPTORS (FILE SEGMENTS IN MMS TERMINOLOGY) These are assigned to all Markush structures You can use them to filter your results There are three types of substance descriptor Technology related define the technology area the structure relates to Structure related - define the type of structure the Markush describes Miscellaneous identifies a Markush which contains structure which are components of a composition At least one technology related Substance Descriptor and at least one structure related Substance Descriptor is applied to each Markush 39

SUBSTANCE DESCRIPTORS RELATING TO STRUCTURE Substance Descriptor C F L M N P V W Z Definition Co-ordination complex (includes metallocenes) Any polymer not covered by P or N Oligomer (Precise definition depends on structure type) Alloy (Section B/C patents only) Natural polymer (Section B/C patents only) Polypeptide (3-10 amino acids only) Ordinary organic compound (not a salt) Extended inorganic structures (eg zeolites) Organic salt (at least one ion is organic) 1 Record derived from DCN database 7 Simple Inorganic compound See also: DWPIM Reference Manual, Table 17, Page 56

OTHER SUBSTANCE DESCRIPTORS Substance descriptor Definition A Patent is classified in CPI Section A* B E Y Patent is classified in CPI Section B and/or C Patent is classified in CPI Section E Substances indexed form part of a mixture *Patent must also have a B, C and/or E class to receive Markush indexing See also: DWPIM Reference Manual, Table 17, Page 56

POLYMER OR OLIGOMER Substance Substance descriptors BC definition E definition Oligopeptide VP 3 amino acids 3 amino acids Polypeptide P >=4 amino acids >=4 amino acids Oligosaccharide L 3-6 sugar units 3-9 sugar units Polysaccharide N >= 7 sugar units >=10 sugar units* Other oligomer L 3-8 repeat units 3-9 repeat units Other polymer F >=9 repeat units >=10 repeat units* BC definition refers to definition used when indexing pharmaceutical and agrochemical patents (Sections B and / or C) E definition refers to the definition used when indexing general chemistry patents (Section E) If a patent is classified in Section E as well as Section B and / or Section C the BC definitions are used * Not indexed unless part of a dye molecule 42

FILTER BY SUBSTANCE DESCRIPTOR 43

ROLES OF MARKUSH RECORDS Role A C D M N P Q R U X Definition Compound is analyzed or detected Catalyst Detecting agent Component of a mixture (at least 2 components have been indexed) New compound Compound is produced or purified Compound defined in terms of starting materials Removing or purifying agent New use of compound Compound is removed See also: DWPIM Reference Manual, Table 15, Page 55. 44

POLYMERS Only for Pharmaceutical (B) and agrochemical (C) patents Addition polymers are typically indexed based on the monomers with Role Q assigned Condensation polymers are typically indexed based on the Structural Repeat Unit (SRU) with Substance Descriptor F assigned (polysiloxane example)...

INORGANIC STRUCTURES Salts are drawn as discrete ions with charges added whenever they are shown or can be easily deduced More complex structures are indexed by listing each element present as a separate entity with zero valency Compounds formed entirely of non metallic elements are mostly shown with covalent bonds in much the same way as for organics 46

PHTHALOCYANINES These are drawn fully normalized The central metal atom used to be bonded to all 4 N atoms but now (since 2000) it is disconnected 47

METALLOCENES Are indexed with the cyclopentadienyl or other π bonded ligands shown disconnected from the metal atom The valency on the metal is reduced by 1 for each bond to a cyclopentadienyl ring For example Ti in titanocene dichloride is shown as 2 valent (a +2 charge would be placed on the Ti atom) 48

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Metallocene search example 50 Hint: bond values are adjusted to normalized, because cyclopentadienyl rings are indexed with normalized bonds in DWPIM. Click OK to add the query to the structures tab of the history panel.

Metallocene search example 51 Automatic Cross File Search is set ON.

Resources 52 DWPIM Reference Manual (new STN Sign In required) https://www.stn.org/help/stn/en/dwpim_manual.pdf Recorded Events http://www.stn-international.com/recorded_events.html Derwent Markush Resource (DWPIM) on STN DWPIM vs. MMS Unified Markush Search on new STN Structure Searching on new STN

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