1. 1 MARPAT Basics (Markush Structures)

2. 2 Where did the term Markush come from? In 1923 Dr Eugene A Markush filed a patent application in the United States concerning a method of preparing pyrazoline dyes that could be used for wool or silk. Claim 1 of this application read: …coupling with a halogen substituted pyrazolone a diazotizated unsulphonated material selected from a group consisting of aniline, homologues of aniline and halogen substitution products of aniline. The claim was challenged as being too unspecific. On appeal the US Commissioner of Patents ruled on the propriety of such claims. The patent was granted in 1924 as US 1,506,316. Introduction

3. 3 Markush Structures Markush structures in patents condense an entire set of implied substances into a single representation using real atoms and R groups. R1 = alkyl of 1-6 carbon atoms or alkenyl of 2-6 carbon atoms R2 = alkyl of 1-6 carbon atoms R3 and R4 = H or alkyl of 1-6 carbon atoms R2 R1 R3 R4 Introduction

4. 4 not indexed Prophetic substances, e.g., those encompassed by the Markush structures in patent claims, are not indexed in CAPLUS and REGISTRY (if missing).

5. 5 Introduction not indexed Prophetic substances, e.g., those encompassed by the Markush structures in patent claims, are not indexed in CAPLUS with RNs, even if they are indexed in REGISTRY.

6. 6 Introduction But any patent containing Markush structures has examples correlated to the Markush structures.

7. 7 R R’ R = pyridyl ring (isolated/embedded) R' = carbon chain of any length No additional fusion on the polycyclic ring Additional substitution allowed at all open sites What has been reported on compounds with the following structural characteristics? Introduction

8. 8 => fil reg => Uploading C:\Program.. => d Introduction

9. 9 => l1 full FULL SEARCH INITIATED 04:51:57 FULL SCREEN SEARCH COMPLETED - 100.0% PROCESSED 4 ITERATIONS SEARCH TIME: 00.00.01 L3 0 SEA SSS FUL L1 => fil marpat Introduction

10. 10 => l3 full FULL SEARCH INITIATED 04:52:43 FULL SCREEN SEARCH COMPLETED - 100.0% PROCESSED 139 ITERATIONS SEARCH TIME: 00.00.02 L5 3 SEA SSS FUL L1 Introduction

11. 11 MARPAT Overview

12. 12 The MARPAT database – produced by CAS and available only on STN, – contains structural representations of the Markush structures that appear in patent claims. A Markush structure condenses a set of implied substances into a single representation. Only Markush structures are searchable in MARPAT.Only Markush structures are searchable in MARPAT. MARPAT Overview

13. 13 The same types of structure queries can be searched in REGISTRY and MARPAT. MARPAT queries may contain: –Specific atoms and shortcuts –Variable groups –G-groups –Specific bonds –Unspecified bonds –Isolated rings –Ring/chain nodes –Not ring/chain bonds MARPAT Overview

14. 14 In Marpat are available the following structure searches:  SSS CSS  Sample Full Range Subset MARPAT Overview

15. 15 Search Scope Iterations Answers Minutes Online SAMPLE 2,000 50 5 Subset SAMPLE 2,000 50 5 Online FULL 100,000 100,000 30 Subset FULL 100,000 100,000 30 BATCH FULL 150,000 150,000 180 Online RANGE 100,000 100,000 30 Subset RANGE 100,000 100,000 30 BATCH RANGE 150,000 150,000 180 MARPAT Overview

16. 16 MARPAT Overview Years of CoverageCurrently 1988+ ; When addition is complete, 1961+ Update FrequencyWeekly Markush StructuresOver 640,000 Markush structures in MARPAT Over 27M small molecule structures in REGISTRY Source of Data50 patent-granting authorities Patent Records247,000 (in MARPAT) 5.1M (in CA) Bibliographic DataDisplayable; Searchable in CAPLUS SDI availabilityYes

17. 17 MARPAT Enhacements Approximately 40,000 Markush structures derived from Institute National de la Propriete Industrielle (INPI) data have been added to MARPAT from the pre-1988 time period. Additional records back to the early 1960s will continue to be added during 2006. Record may include structures from disclosure MARPAT does not have File Segments, but each INPI Markush structure includes the following note: “Record may include structures from disclosure.”

18. 18 MARPAT Enhacements => fil marpat Record may include structures from disclosure => Record may include structures from disclosure L1 40359 RECORD MAY INCLUDE STRUCTURES FROM DISCLOSURE (RECORD(W)MAY(W)INCLUDE(W)STRUCTURES(1W)DISCLOSURE) => sel l1 1-10000 an L2 SEL L1 1-10000 AN : 10047 TERMS => fil hcaplus => l2/dn L5 10047 L2/DN

19. 19 MARPAT Enhacements => l5 and polymers/cc L6 293 L5 AND POLYMERS/CC TI Preparation of amides from nitriles and amines TI Olefinic benzocyclobutene polymers and processes for their preparation TI N-tert-alkyl-n-sec-alkyl secondary amine compounds TI N-substituted carbamoyl lactams TI Catalysts for the polymerization of olefins

20. 20 MARPAT Enhacements => l5 and alloys/cc L7 46 L5 AND ALLOYS/CC TI Benzoylalamine as corrosion inhibitor for aqueous systems TI Dicyclopentadiene dicarboxylic acid salts as corrosion inhibitors TI Copper etching process and solution TI Alkaline cleaning bath for aluminum

21. 21 MARPAT Enhacements => d l1 1, 40359 an AN 2003:785279 HCAPLUS DN 139:283282 Correction of: 104:177615 Correction of: 104:177615 AN 1912:8178 CAPLUS DN 6:8178 OREF 6:1274g-i

22. 22 MARPAT Enhacements 1CI 1907 v1 6CI 1957 V51 1908 v2 1958 V52 1909 v3 1959 V53 1910 v4 1960 V54 1961 V55 1911 v5 1961 V55............................... 4CI 1937 v31 1938 v32 12CI 1987 V106 and V107 1939 v33 1988 V108 and V109 1989 V110 and V111 1940 v34 1989 V110 and V111

23. 23 MARPAT Overview

24. 24 All MARPAT records are also in CAplus.All MARPAT records are also in CAplus. They have the same Accession Number (DN). CAplus information can be displayed in MARPAT. MARPAT Overview

25. 25 AN 133:290336 MARPAT TI Coordination compounds with ligands of a nitrogen heterocycle and Organic electroluminescent device using these complexes IN Kim, Kong-Kyeom; Son, Se-Hwan; Kim, Ok-Hee; Yoon, Seok-Hee; Bae, Jae-Soon; Lee, Youn-Gu; Kim, Hyo-Seok PA LG Chemical, Ltd., S. Korea SO PCT Int. Appl., 47 pp. CODEN: PIXXD2 DT Patent LA English IC ICM C07F001-00 ICS C07F003-00; C09K011-06; H05B033-14 CC 78-7 (Inorganic Chemicals and Reactions) Section cross-reference(s): 28, 73 o o o BIB information. MARPAT Overview /DN in CAPlus

26. 26 o o o FAN.CNT 1 PI PATENT NO. KIND DATE APPLICATION NO. DATE ------------- ---- ---- --------------- ----- PI WO 2000058315 A1 20001005 WO 2000-KR289 20000330 W: CA, CN, JP RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE PRAI KR 1999-11160 19990331 AB Disclosed are new coordination compds. having light-emitting and electron-transporting o o o ST zinc benzothiazole deriv complex prepn electroluminescent device IT Electroluminescent devices (zinc benzothiazole deriv. complex as electron- transporting material for) IT 7429-90-5D, Aluminum, complexes with nitrogen- contg. heterocycles o o o (continued on next page) Caplus subject and CAS RN indexing. CAplus abstract. BIB information includes patent family members. MARPAT Overview

27. 27 IT 103-72-0, Phenyl isothiocyanate 105-53-3, Diethyl malonate 122-39-4, Diphenylamine, reactions 557-34-6, Zinc acetate 1076-38-6, 4-Hydroxycoumarin 1677-46-9 RL: RCT (Reactant) (reactant for prepn. of zinc benzothiazole deriv. complexes as electron-transporting material for electroluminescent devices) RE.CNT 6 RE (1) Chen, C; US 6020078 A 2000 CAPLUS (2) Lg Chemical Ltd; WO 9837736 A1 1998 CAPLUS (3) Lg Chemical Ltd; WO 9963023 A1 1999 CAPLUS (4) Sanyo Electric Co Ltd; EP 0743809 A2 1996 CAPLUS (5) Shinko Electric Industries Co Ltd; EP 0801518 A2 1997 CAPLUS (6) Xerox Corporation; EP 0862353 A2 1998 CAPLUS o o o Citations from the patent. MARPAT Overview not searchable RNs, not searchable.

28. 28 MSTR 1 G1 = 7 / (SC 26 / 40 / 57 / 74 / 95 / 104 / 113 / 122 / 131) (continued on next page) Markush structure from the patent claims. MARPAT Overview

29. 29 G2 = CH2 (SO) / O / S / Se / 8 G3 = alkyl (SO) / aryl (SO) G4 = R G5 = 15 / (SC 140 / 153 / 166 / 182 / 195 / 211 / 227 / 253 / 265 / 277 / 289 / 301 / 314) o o o G6 = O / S / 20 G7 = R G8 = R / (SC Li / Be / Zn / Mg / Ga / In / Al) MPL: claim 1 NTE: as complex with G8 MARPAT Overview

30. 30 Searching both MARPAT and REGISTRY enhances substructure search recall of the patent literature by retrieving both –Specific compound –Specific compound matches, from REGISTRY –Prophetic compound –Prophetic compound matches, from MARPAT Techniques for conducting a substructure search in MARPAT are similar to those used in REGISTRY. MARPAT Overview

31. 31 Specific Substances, from a patent, are indexed in Registry, and in CAPlus, with a RN. MARPAT Overview For patent documents, the following substances are indexed with a RN.

32. 32  From examples  From tables (disclosure)  From claims when a Markush structure is exactly structure is exactly defined (1980 only) defined (1980 only) MARPAT Overview

33. 33 CAS RN 191411-58-2 Compound indexed from Example 1 MARPAT Overview

34. 34 CAS RN 191411-86-6 Compound indexed from Claim 4 MARPAT Overview

35. 35 AN 127:62046 MARPAT TI Preparation of arylthioalkyl- and arylthioalkenylphosphonic acids and derivatives as herbicides IT 191411-58-2P 191411-61-7P 191411-63-9P 191411-65-1P 191411-67-3P 191411-69-5P 191411-71-9P 191411-73-1P 191411-74-2P 191411-75-3P 191411-76-4P 191411-77-5P 191411-78-6P 191411-79-7P 191411-80-0P 191411-81-1P 191411-82-2P 191411-83-3P 191411-84-4P 191411-85-5P 191411-86-6P 191411-87-7P 191411-88-8P 191411-89-9P 191411-90-2P 191411-91-3P 191411-92-4P 191411-93-5P 191411-94-6P 191411-95-7P 191411-96-8P 191411-97-9P 191411-98-0P 191411-99-1P 191412-00-7P RL: AGR (Agricultural use); SPN (Synthetic preparation); BIOL (Biological study); PREP (Preparation); USES (Uses) (prepn. as herbicide) CAS RN 191411-58-2 from Example 1 CAS RN 191411-86-6 from Claim 4 MARPAT Overview

36. 36 PropheticProphetic substances, e.g., those represented by Markush structures in patent claims, are not generally indexed in CAplus. ONLYMarkush structures provide structure-searchable access (ONLY) to the substances covered by patent claims and disclosures, such as the prophetic substances. Only patents with Markush structures are indexed in Marpat MARPAT Overview

37. 37 Each specific compound generated based on the Markush variables is not indexed in CAplus. MARPAT Overview

38. 38 MSTR 1 G1 = H / F / Cl / Br / I G2 = NH2 / OH / alkylcarbonyloxy / OCHO /OCOPh G3 = S / S(O) / SO2 MARPAT Overview

39. 39 G5 = OH / 26 / 32 G6 = alkyl / 28 G8 = alkali metal atom / NH3 / R G4 = CH2CH2CH2CH2 / 13-9 16-11 / 17-9 20-11 / 21-9 24-11 MARPAT Overview

40. 40 Consider searching both REGISTRY and MARPAT when –It is important to comprehensively search all structural possibilities covered in patent claims –REGISTRY searches turn up no hits –It is important to cover "incompletely defined" compounds (/ IDS) that might not match your query specifications in REGISTRY MARPAT Overview

41. 41 Search Question: What has been reported on compounds with the following structural characteristics? 4R1 = pyridyl ring (isolated/embedded) 4R2 = carbon chain of any length 4No additional fusion on the polycyclic ring 4Additional substitution allowed at all open sites MARPAT Overview

42. 42 MARPAT Overview

43. 43 chain nodes : 20 21 ring nodes : 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 chain bonds : 2-21 3-20 ring bonds : 1-2 1-6 2-3 3-4 4-5 5-6 5-7 6-9 7-8 7-10 8-9 8-13 10-11 11-12 12-13 14-15 14-19 15-16 16-17 17-18 18-19 exact/norm bonds : 2-21 3-20 5-6 5-7 6-9 7-8 7-10 8-9 8-13 10-11 11-12 12-13 exact bonds : 1-2 1-6 2-3 3-4 4-5 normalized bonds : 14-15 14-19 15-16 16-17 17-18 18-19 Match level : 1:Atom 2:Atom 3:Atom 4:Atom 5:Atom 6:Atom 7:Atom 8:Atom 9:Atom 10:Atom 11:Atom 12:Atom 13:Atom 14:Atom 15:Atom 16:Atom 17:Atom 18:Atom 19:Atom 20:CLASS 21:CLASS 22:CLASS MARPAT Overview

44. 44 => FILE REGISTRY => Uploading mar1.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR (continued on next page) MARPAT Overview

45. 45 => S L1 SSS SAM L2 0 SEA SSS SAM L1 => S L1 SSS FULL L3 0 SEA SSS FUL L1 The REGISTRY search turns up no substances. MARPAT Overview

46. 46 "No hits" in REGISTRY means that no substances represented by the structure query were indexed in CAplus from 1967-present (or in CAOLD from the 1957-1966 Molecular Formula Indexes). The substance of interest could be encompassed in the prophetic substances covered by the Markush structure in a patent claim. MARPAT Overview

47. 47 => FILE MARPAT => S L3 SSS SAM SAMPLE SEARCH INITIATED 13:55:20 FILE 'MARPAT' SAMPLE SCREEN SEARCH COMPLETED - 7 TO ITERATE 100.0% PROCESSED 7 ITERATIONS 0 ANSWERS SEARCH TIME: 00.00.03 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 7 TO 299 PROJECTED ANSWERS: 0 TO 0 L5 0 SEA SSS SAM L1 (continued on next page) Searching MARPAT for prophetic substance matches Use a SAMPLE search in MARPAT to verify the search will run to completion. MARPAT Overview

48. 48 => S L3 SSS FULL FULL SEARCH INITIATED 13:54:52 FILE 'MARPAT' FULL SCREEN SEARCH COMPLETED - 89 TO ITERATE 100.0% PROCESSED 89 ITERATIONS 3 ANSWERS SEARCH TIME: 00.00.09 L4 3 SEA SSS FUL L1 => D 1-3 BIB ABS L6 ANSWER 1 OF 3 MARPAT COPYRIGHT 2000 ACS AN 127:293247 MARPAT TI Preparation of pyrrolopyrazines as GABAa receptor ligands IN Blum, Charles; Hutchison, Alan PA Neurogen Corp., USA o o o The MARPAT search retrieves 3 patents. HELPFUL HINT:Search the L-number resulting from the REGISTRY substructure search to take advantage of a lower, “extended” search fee in MARPAT. HELPFUL HINT: Search the L-number resulting from the REGISTRY substructure search to take advantage of a lower, “extended” search fee in MARPAT. For additional information on file-specific charges see HELP COST in the file. MARPAT Overview

49. 49 L6 ANSWER 2 OF 3 MARPAT COPYRIGHT 2000 ACS AN 126:199581 MARPAT TI aryl substituted pyrrolopyrazines as a new class of GABA brain Receptor ligands IN Blum, Charles; Hutchison, Alan PA Neurogen Corporation, USA SO U.S., 16 pp. Cont.-in-part of U.S. 5,286,860. CODEN: USXXAM o o o L6 ANSWER 3 OF 3 MARPAT COPYRIGHT 2000 ACS AN 120:245160 MARPAT TI Preparation of indolopyrazines and related compounds as brain GABAa agonists, antagonists, or inverse agonists IN Blum, Charles; Hutchison, Alan PA Neurogen Corp., USA SO U.S., 17 pp. o o o (continued on next page) MARPAT Overview

50. 50 o o o FAN.CNT 3 PATENT NO. KIND DATE APPLICATION NO. DATE --------------- ---- -------- --------------- -------- PI US 5286860 A 19940215 US 92-975409 19921112 WO 9411374 A1 19940526 WO 93-US10870 19931110 W: AT, AU, BB, BG, BR, BY, CA, CH, CZ, DE, DK, ES, FI, GB, HU, JP, KP, KR, KZ, LK, LU, MG, MN, MW, NL, NO, NZ, PL, RO, RU, SD, SE, SK, UA, US, VN RW: AT, BE, CH, DE, DK, ES, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE, BF, BJ, CF, CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG AU 9455526 A1 19940608 AU 94-55526 19931110 US 5606059 A 19970225 US 95-436252 19950512 US 5668283 A 19970916 US 95-486595 19950607 o o o MARPAT Overview

51. 51 Formats showing structures: CASLINK

52. 52 => d an fhit AN 127:293247 MARPAT MSTR 2A G1 = Ph (SO (1-2) G2) / thienyl (SO (1-2) G2) / pyridyl (SO (1-2) G2) MARPAT Overview

53. 53 G3 = 14-3 15-1 / 74-3 75-1 MARPAT Overview

54. 54 G4 = (0-2) CH2 G5 = H / alkyl G6 = 19 / C(O) / 22............. MARPAT Overview

55. 55 REGISTRY and MARPAT, Retrieval Differences: In REGISTRY, only specific substituents are present in the database compounds. Substructures match against specific substituents. In MARPAT, substructures may match against –Specific substituents: H, CF3, CN, etc. –Generic substituents: X, HY, alkoxycarbonyl, etc. MARPAT Overview

56. 56 Answers in each database are different: –Answers in REGISTRY are compounds. The bibliographic references and abstracts associated with each compound (from patents and journals) are available in CAplus. –Answers in MARPAT are references to patents. MARPAT Overview REGISTRY and MARPAT, Retrieval Differences:

57. 57 IDS/CI Retrieval in MARPAT of incompletely defined substances (IDS/CI)

58. 58 Incompletely defined substances are assigned CAS RNs in REGISTRY when all of the atoms in the structure are defined and the only uncertainty is one or more of the following: Attachment position for a substituent Site of saturation/unsaturation Site of esterification/etherification Branching of an alkyl group substructure search Generally it is not possible to anticipate and allow for all of these possibilities in a structure query for REGISTRY. As a result, some potentially interesting substances may be missed in a substructure search in REGISTRY. Incompletely defined substances

59. 59 MARPAT can effectively encompass an incompletely defined portion of the molecule in the Markush structure with its ability to support:  Variable attachment points for substituents G-group lists of substituent possibilities Incompletely defined substances

60. 60 Find all non-polymeric glycerides containing oleic and/or stearic fatty acid. Show as Marpat can find some patents,due to IDS compound, not retrieved by structure search. Incompletely defined substances

61. 61 Incompletely defined substances => fil marpat L1 STRUCTURE UPLOADED => l1 FULL FILE PROJECTIONS: ONLINE **INCOMPLETE** BATCH **INCOMPLETE**

62. 62 Incompletely defined substances => fil reg => c h o/elf(p)21-57/c(p)4-6/o not (pms/ci or rsd/fa) L3 17741 C H O/ELF(P)21-57/C(P)4-6/O NOT.... => fil hcaplus => l3 and marpat/os L4 2860 L3 AND MARPAT/OS => fil marpat => l4 L5 2860 L4 => l1 full subset=l5 (Patents in Marpat) L7 870 SEA SUB=L5 SSS FUL L1 (Patents in Marpat)

63. 63 Incompletely defined substances => fil reg => l1 full subset=l3 L9 1517 SEA SUB=L3 SSS FUL L1 => l3 and (propan? or glycer?)/cns(l)(octadecen? or oleic? or octadecan? or stear?) L10 1330 L3 AND (PROPAN? OR GLYCER?)/CNS(L).. => l10 and ids/ci L11 909 L10 AND IDS/CI => l11 not l9 (Extra IDS compounds from L12 885 L11 NOT L9 (Extra IDS compounds from dictionary) dictionary)

64. 64 Incompletely defined substances => fil hcaplus => l9 and p/dt (Patents from structure) L13 1805 L9 AND P/DT (Patents from structure) => l11 and p/dt (Patents from extra IDS) L14 6344 L11 AND P/DT(Patents from extra IDS) => l14 not l13 (Patents only from extra IDS) L15 5906 L14 NOT L13 (Patents only from extra IDS) => l7 (Patents from Marpat) L16 870 L7 (Patents from Marpat) => l15 and l16 (Patents, only extra IDS, L17 234 L15 AND L16 (Patents, only extra IDS, retrieved by Marpat) retrieved by Marpat)

65. 65 Incompletely defined substances RN 25496-72-4 HCAPLUS CN 9-Octadecenoic acid (9Z)-, monoester with 1,2,3- propanetriol CM 1 CRN 112-80-1 CMF C18 H34 O2 Double bond geometry as shown. CM 2 CRN 56-81-5 CMF C3 H8 O3

66. 66 Locate information on substances with the following structural characteristics? Any substitution at all open sites Hy = heterocycle containing exactly 3 N and no O, S, or P All rings are isolated/embedded -SO3H groups attached at any position on the benzene rings Cl N ON N NO Hy N S O O O S O O O Incompletely defined substances

67. 67 => 5/nrrs(s)c18n2o2/rf(p)cnrs>=3(p)c6/ea(p)3 n/rel and cl>=3(p)s>=2(p)o>=8(p)n>=8 L1 509 5/NRRS(S)C18N2O2/RF... => l1 and ids/ci 234090 IDS/CI L2 160 L1 AND IDS/CI Incompletely defined substances

68. 68 Incompletely defined substances

69. => FILE REGISTRY L3 STRUCTURE UPLOADED => D L3 => l3 full L4 115 SEA SSS FUL L3 Incompletely defined substances

70. => fil marpat => l4 full L5 51 SEA SSS FUL L3 Incompletely defined substances

71. => fil caplus => d his (FILE 'HOME' ENTERED AT 06:29:23 ON 08 MAR 2004) FILE 'REGISTRY' ENTERED AT 06:29:41 ON 08 MAR 2004 L1 505 5/NRRS(S)C18N2O2/RF(P)CNRS>=3(P)C6/EA(P)3 N/REL AND CL>=3(P)S>= L2 L2 160 L1 AND IDS/CI L3 STRUCTURE UPLOADED L4 115 L3 FULL FILE 'MARPAT' ENTERED AT 06:32:31 ON 08 MAR 2004 L5 51 L4 FULL

72. 72 Incompletely defined substances => l2 and p/dt L6 21 L2 AND P/DT (Reg. IDS/CAPlus) => l4 and p/dt L7 28 L4 AND P/DT (Reg. Str./CAPlus) => l5 L8 51 L5 (Marpat)

73. 73 Incompletely defined substances => l6 and l7 L9 3 L6 AND L7 => l6 not l9 L10 18 L6 NOT L9 => l10 and l5 51 L5 L11 2 L10 AND L5 (IDS structures recovered in MARPAT)

74. 74 CASLINK

75. 75 The CASLINK tool provides one-step searching of both the –Specific substances –Specific substances in REGISTRY –Prophetic substances –Prophetic substances in MARPAT CASLINK also retrieves the references to the specific substances from CAplus and eliminates any duplicate hits between CAplus and MARPAT. CASLINK

76. 76 Search Question: Locate references on the following substances: 4R1 = Any non-hydrogen substituent ring or chain 4R2 = any ring or chain carbon atom 4No additional fusion on the ring 4Additional substitution allowed at all open sites CASLINK

77. 77 1Enter the CASLINK cluster of files => FILE CASLINK FILE 'REGISTRY' ENTERED FILE 'MARPAT' ENTERED FILE 'CAPLUS' ENTERED Predefined command sequences will be executed in REGISTRY, MARPAT, MARPATPREV, and CAPLUS. 2Perform the upload => Uploading mar1.str L1 STRUCTURE UPLOADED CASLINK

78. 78 3Verify the structure online => D L1 L1 HAS NO ANSWERS L1 STR CASLINK

79. 79 Run a SAMPLE search => S L1 SSS SAM PROJECTED ITERATIONS: 4669 TO 6691 PROJECTED ANSWERS: 68 TO 532 L2 15 SEA SSS SAM L1 CASLINK

80. 80 S L2 SSS SAM FILE=MARPAT FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 9195 TO 11845 PROJECTED ANSWERS: 3 TO 164 L3 3 SEA SSS SAM L1 CASLINK

81. 81 Each answer from REGISTRY is a specific compound that matches the structure query. Each answer from MARPAT is a document record (patent) in which the Markush structure contains fragments that matchs the structure query. D SCAN is used to determine if the REGISTRY and MARPAT answers are on target. D SCAN content is file-specific. CASLINK

82. 82 => D SCAN L2 L2 15 ANSWERS REGISTRY COPYRIGHT 2000 ACS IN 3-Pyrrolidinecarboxylic acid, 4-ethenyl-2-oxo- 1-(phenylmethyl)-, Methyl ester, (3R,4R)-rel- (9CI) MF C15 H17 N O3 Relative stereochemistry. HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 (continued on next page) Note: Substance identification information from REGISTRY. CASLINK

83. 83 => D SCAN L3 MSTR 1 G5 = CHO G6 = 22 MPL: claim 1 STE: diastereoisomers and mixtures HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 CASLINK

84. 84 When a FULL structure search is requested in CASLINK, STN: 1Runs FULL structure searches in REGISTRY, MARPAT 2Searches the REGISTRY answers in Caplus 3Removes duplicate * 3Removes duplicate * answers between CAplus and MARPAT and creates a single answer set CASLINK

85. 85 => S L1 SSS FULL S L1 SSS FUL FILE=REGISTRY L4 411 SEA SSS FUL L1 S L4 SSS FUL FILE=MARPAT L5 54 SEA SSS FUL L1 S L4 FILE=CAPLUS L7 161 FILE CAPLUS CASLINK

86. 86 (this dup rem is useless) DUP REM L5 L7 (this dup rem is useless) PROCESSING COMPLETED FOR L5 PROCESSING COMPLETED FOR L7 L8 209 DUP REM L6 L5 L7 (6 DUPLICATES REMOVED) ANSWERS '1-54' FROM FILE MARPAT ANSWERS '55-209' FROM FILE CAPLUS CASLINK

87. 87 Illustration: FQHIT vs. FHIT in MARPAT With FQHIT display format, only the portions of the Markush structure that caused it to be a "hit" are displayed. The format is useful to nGet a general idea of the context in which a structure hit nDetermine if a structure query is too broad nDisplay large numbers of MARPAT hits CASLINK

88. 88 Step 6: Display Results => D 5 FQHIT L8 ANSWER 5 OF 209 MARPAT COPYRIGHT 2000 ACS DUPLICATE 6 MSTR 1 G7 = alkoxycarbonyl (SO (1-) G8) G11 = O MPL: claim 1

89. 89 Illustration: FQHIT vs. FHIT in MARPAT With FHIT display format, all G-group definitions are shown. It is useful when you need to see the entire context in which a structure hit. CASLINK

90. 90 => D 5 FHIT L8 ANSWER 5 OF 209 MARPAT COPYRIGHT 2000 ACS DUPLICATE 6 MSTR 1 G1 = H / X / CF3 / CN / Me / 13 / 16 / SMe / 20 / SO2Me / 23 / 30 / (SC Cl) G2 = 13 / 18 / CF3 G3 = Me / COPh G4 = H / Me G5 = pyridyl (SO (1-) G6) G6 = X / CF3 G7alkoxycarbonyl (SO (1-) G8) G7 = X / CN / CO2H / alkoxycarbonyl (SO (1-) G8) / cycloalkyloxycarbonyl (SO (1-) G13) / (SC Cl / CO2Et) / (EX 54 / 43) (continued on next page) The parts that caused the answer to be a "hit" are highlighted. CASLINK

91. 91 G8 = X / CF3 / Ph / cycloalkyl G9 = alkyl (SO (1-) cyclopropyl) / cycloalkyl (SO (1-) Me) / alkenyl / (SC Et / CH=CH2) / (EX 48) G10 = H / X / (SC F) G11O G11 = O / S G12 = H / X / (SC Cl) G13 = X / CF3 / Ph / alkyl MPL: claim 1 The parts that caused the answer to be a "hit" are highlighted. Helpful Hint: Helpful Hint: Markush displays can be very complicated. Option Option: Consider displaying the associated CAplus abstract. Many contain structural summaries of the claimed substances. CASLINK

92. 92 Markush displays in MARPAT consist of Base structure G-groups defining the variability in the structure CASLINK

93. 93 CASLINK

94. 94 Levels in Marpat

95. 95 Search Question: Locate references discussing compounds with the following structure: R1 = heterocyclic ring with at least one =O attached R2, R3 = any type of carbon chain (substituted or unsubstituted) The oxygen-containing ring may be isolated or embedded in a larger ring system Any substitution at all open sites All of the atoms in the structure, except for the benzopyran ring, may match real atoms or generic groups in Markush structures. The benzopyran ring may match only real atoms. Levels in Marpat

96. 96 Hy Hy=O Ak (conn. = any) Ring Isolated Connectivity: any Class Atom Levels in Marpat

97. 97 Match Levels may be changed on a single node or a group of nodes. To change match level of a single node 1Right click on the node. A pop-up menu appears. Select Markush Attributes Levels in Marpat

98. 98 Match Levels may be changed on a single node or a group of nodes. To change match level of a single node 2The Markush Attributes dialog box appears. Do the following: –Click the radio button associated with the Match Level of interest. –Click OK. Levels in Marpat

99. 99 To change match level on multiple nodes all at once, 1Highlight the nodes using the highlighting tool. Levels in Marpat

100. 100 To change match level on multiple nodes all at once, 2From the Query Def pull-down menu, select Markush Attributes. An alert dialog box appears. Click OK. The Markush Attributes dialog box appears. Do the following: a Click the radio button associated with the Match Level of interest. b Click OK. Levels in Marpat By default STN Express assign the level CLASS to all chains, and level ATOM to all rings. But you can (must) change it.

101. 101 Verifying Match Levels Assignments 1From the Query Def pull-down menu, select Query Verification. 2The Query Verification dialog box appears. aClick the Select radio button. bClick in the match level box. cClick OK. Levels in Marpat

102. 102 Verifying Match Levels Assignments 3A Query Verification pop-up dialog appears and Match Levels for all atoms display. Click OK. (You can better verify clicking on the Q button) Levels in Marpat

103. 103 => FILE CASLINK => Uploading mar2.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR CLASS match level on: Cl, Ak, O, Hy ATOM match level on: All atoms in the benzopyran ring. Levels in Marpat

104. 104 => S L1 SSS SAM S L1 SSS SAM FILE=REGISTRY o o o L2 0 SEA SSS SAM L1 o o o S L2 SSS SAM FILE=MARPAT o o o L3 4 SEA SSS SAM L1 o o o => D SCAN L3 FQHIT Levels in Marpat

105. 105 L3 4 ANSWERS MARPAT COPYRIGHT 2000 ACS MSTR 1A G1 = 11 G2 = alkyl G3 = alkyl G7 = Hy (SO) o o o HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 Note that FQHIT shows only the fragments that caused the structure to hit. For example, the complete definition of G6 is not shown - only the part that caused the answer to be a hit (G7) is shown. Levels in Marpat

106. 106 => S L1 SSS FULL S L1 SSS FUL FILE=REGISTRY o o o L4 6 SEA SSS FUL L1 o o o S L4 SSS FUL FILE=MARPAT o o o L5 42 SEA SSS FUL L1 o o o S L4 FILE=CAPLUS L7 14 FILE CAPLUS o o o L8 51 DUP REM L6 L5 L7 (5 DUPLICATES REMOVED) ANSWERS '1-42' FROM FILE MARPAT ANSWERS '43-51' FROM FILE CAPLUS Levels in Marpat

107. 107 => D 1 BIB ABS FQHIT L8 ANSWER 1 OF 51 MARPAT COPYRIGHT 2000 ACS DUPLICATE 1 AN 121:255814 MSTR 1 G1 = X G3 = alkyl MPL: claim Answers from MARPAT. Levels in Marpat

108. 108 Levels in Marpat => D 45 51 BIB ABS HITSTR L8 ANSWER 45 OF 51 CAPLUS COPYRIGHT 2000 ACS AN 1988:112204 CAPLUS DN 108:112204 Answers from CAplus/REGISTRY.

109. 109 Search REGISTRY/CAplus and MARPAT to locate references discussing substances with the following structure R1 = nitrogen in a ring or chain R1 = nitrogen in a ring or chain R2 = anything, including hydrogen R3,R4 = alkyl chain Nitrogen-containing ring may be isolated or embedded in a larger ring system Any substitution is allowed at all open sites Consider Class the rings and Atoms the chains Display the final answer set using the following formats: For MARPAT answers use BIB ABS FQHIT For CAplus answers use BIB ABS HITSTR Skills Practice

110. 110 => fil reg => Uploading C:\STNEXP\Queries\19a.str L1 STRUCTURE UPLOADED

111. 111 => l1 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 1864 TO 3216 PROJECTED ANSWERS: 8 TO 329 L2 8 SEA SSS SAM L1 => d scan

112. 112 => l1 full L4 170 SEA SSS FUL L1 => fil caplus => l4 L5 1132 L4

113. 113 => d l5 bib abs hitstr L5 ANSWER 1 OF 1132 CAPLUS COPYRIGHT 2006 ACS on STN AN 2006:151208 CAPLUS Full-textFull-text TI Transnasal composition having immediate action and high absorbability.......... AB Disclosed is a powdery composition for transnasal administration which contains a nonpeptidic nonproteinaceous drug and crystalline cellulose masses having a specific mesh-size as a carrier therefor. This composition can exert an immediate action of the drug and a high absorbability. For example, morphine hydrochloride 65 mg and Avicel PH-F20 (crystalline cellulose) 135 mg were blended and nasally administered to monkeys for the determination of pharmacokinetic parameters of morphine.

114. 114 IT 103628-46-2, Sumatriptan RN 103628-46-2 CAPLUS CN 1H-Indole-5-methanesulfonamide, 3-[2- (dimethylamino)ethyl]-N-methyl- (9CI) (CA INDEX NAME)

115. 115 => fil marpat => l4 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 16297 TO 19783 PROJECTED ANSWERS: 2 TO 125 L7 2 SEA SSS SAM L1 => d scan

116. 116 L7 2 ANSWERS MARPAT COPYRIGHT 2006 ACS on STN............ TI Preparation of indole derivatives as antagonists of gonadotropin releasing hormone......................... MSTR 1

117. 117 => l4 full L9 63 SEA SSS FUL L1 => d bib abs fqhit L10 ANSWER 1 OF 44 MARPAT COPYRIGHT 2006 ACS on STN AN 143:341070 MARPAT Full-textFull-text TI Synergistic broad-spectrum microbicide compositions containing sulfamoyl compounds and dipeptides or basic copper chloride.............. GI

118. 118 AB The microbicide compns. contain (A) sulfamoyl compds. I [R1, R2 = C1-4 alkyl; R1R2 may form C4-6 alkylene; Y = H, halo, C1-8 alkyl, C1-6 alkoxy, C1-10 alkylthio, C1-6 haloalkyl, C1-6 haloalkylthio, (un)substituted benzylthio, (un)substituted Ph, (un)substituted benzyl; R3-R8 = H, C1-8 alkyl, C3-8 cycloalkyl, C2-8 alkenyl, C5-8 cycloalkenyl, C2-8 alkynyl, C1-8 alkoxy, etc.] and/or their agrochem. acceptable salts and (B) dipeptides II (R1 = iso-Pr, Ph; R2 = Me; R3 = Ph substituted with R4 at the 4-position, 2-benzothiazolyl which may be substituted with R5; R4, R5 = F, Cl, Me, Et, MeO, cyano) or (C) basic copper chloride (copper oxychloride) (III). Concomitant application of 1-(N,N- dimethylsulfamoyl)- 3-(3-bromo-6-fluoro-2-methylindol-1-yl)sulfonyl-1,2,4-triazole (at 0.625 g/ha) and Me (  )-RS-[3- (N-isopropoxycarbonyl-S-valinyl)amino]-3-(4- chlorophenyl)propanoate (at 2.5 g/ha) showed  80% control of disease caused by Phytophthora infestans in potato. G5 = alkyl (substd. by G7) G7 = dialkylamino / dialkylaminosulfonyl

119. 119 Precision Tools

120. 120 Techniques for modifying structure queries for Markush searching are available. These structure drawing tools will either expand or reduce the number of answers retrieved in MARPAT file. Precision Tools

121. 121 Match level (limited, unlimited) Generic definitions (Generic Groups) Element count (Generic Groups) Precision Tools

122. 122 Each atom in a query structure is assigned a default Match Level. Match Level controls how query atoms match specific atoms and generic groups in the MARPAT database. Three Match Level options are possible Match Level is ignored in REGISTRY Precision Tools

123. 123 Match Level Markush structures include both real atoms and generic nodes, both of which may be matched against the real atoms and generic nodes (Ak, Cb, Hy,Cy) of the search query. Match levelMatch level determines the degree to which query nodes match with nodes in the candidate answers. Changing the degree of matching will increase or decrease the number of answers retrieved. Precision Tools

124. 124 Match Level There are three match levels: Atom Class Class Any Any Precision Tools

125. 125 Match Level Atom Match level atom is the most restrictive match level. It retrieves the most precise set of answers: Specific atoms in the query match only specific atoms in candidate answers. Generic groups in the query match only specific atoms in candidate answers. Precision Tools

126. 126 Precision Tools Match Level Atom

127. 127 Match Level Atom Precision Tools

128. 128 Match Level Class Match level class causes more answers to be retrieved than match level atom: Specific atoms in the query match specific atoms and “generic nodes” in candidate answers. Generic groups in the query match specific atoms and generic groups in candidate answers. HINT:the Class level is the most important level and you HINT: the Class level is the most important level and you should always run searches in Marpat at this level should always run searches in Marpat at this level Precision Tools

129. 129 Precision Tools Match Level Class

130. 130 Precision Tools Match Level Class

131. 131 Match Level Any Match level any is the least restrictive match level option. In addition to specific atoms and generic nodes, candidate answers also include R-nodes. R-nodes are indefinite substituents described with text terms such as Organic group Group to form ring Anion Protecting group Precision Tools

132. 132 Precision Tools Match Level Any

133. 133 Match Level Any Precision Tools

134. 134 Precision Tools Match Level Any

135. 135 Generic Groups In Marpat all pieces of structures (in query, or in the file) are also converted in Generic Groups Precision Tools

136. 136 Ak Hy X Cy Precision Tools

137. 137 In Marpat then, to the above structure is associated, in any case, the following string: Ak*-Hy*(or Cy*)-X* * Indicates that are generated Generic Groups and not original Generic Groups Precision Tools

138. 138 In searches at atom level the query does not match generated generic groups or original generic groups, but only specific atoms or groups (i.e. phenyl, ethyl, etc.) but never query generated generic groups match file generated generic groups In searches at class level the query matches also generated generic groups or original generic groups, but never query generated generic groups match file generated generic groups Precision Tools

139. 139 O || C=C-C-O-Ak-X G1 O | || CH2=C-C-O-CH2-Cl G1 = H / Me Hit (atom) O || CH2=CH-CH2-C-O-Ak-Br No Hit O || G2-C-O-G1 G1 = alkyl (SO X) / Ph G2 = alkenyl / loweralkyl Hit (class) Q* || Ak*-Q*-Ak-X O || Ak-C-O-Ak-Br Hit (class) Precision Tools QUERY FILE

140. 140 QUERY CH CH N CH Ak CH 2 CH 2 NH2 M.le All Class M.le All Atom Yes No Precision Tools FILE

141. 141 QUERY CH CH N CH Me CH 2 CH 2 NH2 M.le All Class M.le All Atom Yes Precision Tools FILE

142. 142 QUERY CH CH N CH Ak Ak NH2 M.le All Class M.le All Atom Yes No Precision Tools FILE

143. 143 QUERY CH CH N CH Ak Ak CH 2 NH2 M.le All Class M.le All Atom Yes No Precision Tools FILE

144. 144 QUERY CH CH N CH Ak CH 2 CH 2 NH2 M.le All Class M.le All Atom No Ak Precision Tools FILE

145. 145 QUERY CH CH N CH R CH 2 CH 2 NH2 M.le All Class M.le All Atom No FILE

146. 146 QUERY M.le All Class M.le All Atom Yes No Et - Hy - Ak - NH2 FILE

147. 147 QUERY M.le All Class M.le All Atom Yes No Ak - Hy - Ak - NH2 Precision Tools FILE

148. 148 QUERY M.le All Class M.le All Atom No Ak - Cb - Ak - NH2 Precision Tools FILE

149. 149 QUERY M.le All Class M.le All Atom Yes No Ak - Cy - Ak - NH2 Precision Tools FILE

150. 150 Default Match Level in STN Express Structure queries automatically include default match level assignment. This assignment is only taken into account when searching MARPAT or MARPATprev. The default settings for match levels are Atom Atom, for ring atoms and the ring generic groups Cy, Cb, and Hy Class Class, for chain atoms and the chain generic group Ak Hint: change this default, in Preferences, and put all atoms at class level Precision Tools

151. 151 Match Level Assumptions in STN Express Precision Tools

152. 152 Precision Tools Tips for setting ATOM Match Levels

153. 153 Tips for setting CLASS Match Levels Change Match Level for all ring atoms to CLASS. Precision Tools

154. 154 Change Match Level to CLASS. Precision Tools Tips for setting CLASS Match Levels

155. 155 Tips for setting CLASS Match Levels Precision Tools Change Match Level to CLASS. Rest of ring atoms are ATOM.

156. 156 G1 substituents Change Match Level for the G1 substituents to ANY to also match R which might be defined as an “electron withdrawing group.” Precision Tools Tips for setting ANY Match Levels

157. 157 Precision Tools Tips for setting ANY Match Levels

158. 158 1 Use MARPAT to locate patents on compounds with the following structure: R1, R3, R4, R5 = an alkyl chain of any length with no substitutions R2 = any ring system with no substitutions Nitrogen-containing ring is not isolated All the ring systems may match real atom rings or generic groups The -CH2-Si-CH2-Si- chain may match only real atoms The alkyl groups may match real atoms or generic groups (follows in the next slide) Skills Practice

159. 159 1 Use MARPAT to locate patents on compounds with the following structure: R1, R3, R4, R5 = an alkyl chain of any length with no substitutions R2 = any ring system with no substitutions Nitrogen-containing ring is not isolated All the ring systems may match only real atom rings The -CH2-Si-CH2-Si- chain may match only real atoms The alkyl groups may match only real atoms (Look at the differences between the results in this search and the previous one) Skills Practice

160. 160 => fil marpat => Uploading C:\Program Files\stnexp\Queries\19a.str L1 STRUCTURE UPLOADED isolated ring systems isolated ring systems : containing 1 : Connectivity Connectivity : 10:1 E exact RC ring/chain 11:1 E exact RC ring/chain 12:1 E exact RC ring/chain 13:1 E exact RC ring/chain 14:1 E exact RC ring/chain Match level Match level : 1:CLASS 2:CLASS 3:CLASS 4:CLASS 5:CLASS 6:Atom 7:Atom 8:Atom 9:Atom 10:CLASS 11:CLASS 12:CLASS 13:CLASS 14:CLASS

161. 161 => l1 full L3 1 SEA SSS FUL L1 => d l3 fhit L3 ANSWER 1 OF 1 MARPAT COPYRIGHT 2003 ACS MSTR 1 G1 = loweralkyl / CH=CH2 / CH2CH=CH2 / CH2Ph / Ph (SO) /20 / biphenylyl

162. 162 => Uploading C:\Program Files\stnexp\Queries\19abis.str L4 STRUCTURE UPLOADED Match level Match level : 1:Atom 2:Atom 3:Atom 4:Atom 5:Atom 6:Atom 7:Atom 8:Atom 9:Atom 10:Atom 11:Atom 12:Atom 13:Atom 14:Atom

163. 163 => l4 full L5 1 SEA SSS FUL L4 => d l5 fhit L5 ANSWER 1 OF 1 MARPAT COPYRIGHT 2003 ACS MSTR 1 G1 = loweralkyl / CH=CH2 / CH2CH=CH2 / CH2Ph / Ph (SO) /20 / biphenylyl

164. 164 Run two searches in Marpat on the previous structure. R1 = unsubstituted carbon chain (Level: atom, class) R2 = O, S, or N,no other substitutions on this atom (Level: atom) R3 = Any type of ring system (Level: atom, class) R4 = Nitrogen in a chain (Level: atom) The nitrogen-containing ring is isolated. Look at the differences Skills Practice

165. 165 L1 STRUCTURE UPLOADED Ak, Cy Class

166. 166 G7 = alkyl (SO) Ak G41 = 13 / aryl (SO (1-) G28) / Cy cycloalkyl (SO (1-) G28) / cycloalkenyl (SO (1-) G28) / Hy (SO (1-) G28) Ak, Cy Class

167. 167 Ak, Cy Atom

168. 168 G3 = / (SC NHCH2Ph) Cy G40 = / Bu-i Ak Ak, Cy Atom

169. 169 Suggestions: Start always a structure search in Marpat with all nodes at Class Level and save it (results in Lx); then, if necessary, run a subset structure search on Lx, changing some nodes at Atom Level. Remember that if you draw in your query a specific group (i.e. pyridine), also at Class Level (Limited), you find only Generic Groups which encompass your designed group (i.e. … a heterocycle with N …) not other Generic Groups. In order to get the best results it is a general rule to run a structure search, in Marpat, on a set previously created either from Registry eiher from CAPlus.

170. 170 Skills Practice Find patents on cytomegalovirus, and Markush structures that match the structure query:

171. 171 => fil caplus => (cytomegalovir? or cmv? or cytamegalo?(s)virus) and p/dt L1 2433 (CYTOMEGALOVIR? OR CMV? OR....... => sel rn SmartSELECT INITIATED TERM LIMIT EXCEEDED: 1458 ANSWERS PROCESSED L2 SEL L1 1- RN : 50359 TERMS => sel l1 rn 1459- SmartSELECT INITIATED L3 SEL L1 1459- RN : 12961 TERMS

172. 172 => fil reg => l2 or l3 L6 61198 L4 OR L5 => Uploading C:\Program Files\stnexp\Queries\virus.str => d L7 HAS NO ANSWERS L7 STR

173. 173 => l7 full subset=l6 FULL SUBSET SEARCH INITIATED 10:15:52 FULL SUBSET SCREEN SEARCH COMPLETED - 30485 TO ITERATE 100.0% PROCESSED 30485 ITERATIONS 85 ANSWERS SEARCH TIME: 00.00.03 L8 85 SEA SUB=L6 SSS FUL L7

174. 174 FILE 'CAPLUS' ENTERED AT.... L1 L1 2433 (CYTOMEGALOVIR?......... L2 SEL L1 1- RN : 50359 TERMS L3 SEL L1 1459- RN : 12961 TERMS FILE 'REGISTRY' ENTERED AT 10:10:05 ON 27 OCT 2003 L4 50359 S L2 L5 12961 S L3 L6 61198 S L4 OR L5 L7 STRUCTURE UPLOADED L8 L8 85 L7 FULL SUB=L6

175. 175 => fil caplus => l8 and l1 11188 L8 L9 15 L8 AND L1 => d hitstr

176. 176 FILE 'CAPLUS' ENTERED AT 10:04:43 ON 27 OCT 2003 L1 L1 2433 (CYTOMEGALOVIR? OR CMV? OR..... L2 SEL L1 1- RN : 50359 TERMS L3 SEL L1 1459- RN : 12961 TERMS FILE 'REGISTRY' ENTERED AT 10:10:05 ON 27 OCT 2003 L4 50359 S L2 L5 12961 S L3 L6 61198 S L4 OR L5 L7 STRUCTURE UPLOADED L8 L8 85 L7 FULL SUB=L6 FILE 'CAPLUS' ENTERED AT 10:16:17 ON 27 OCT 2003 L9 15 L8 AND L1

177. 177 => fil marpat => l1 L10 325 L1 => l8 full subset=l10 FULL SUBSET SEARCH INITIATED 10:19:16 FULL SUBSET SCREEN SEARCH COMPLETED - 278 TO ITERATE 100.0% PROCESSED 278 ITERATIONS 34 ANSWERS SEARCH TIME: 00.00.02 L11 34 SEA SUB=L10 SSS FUL L7

178. 178 FILE 'CAPLUS' ENTERED AT 10:04:43 ON 27 OCT 2003 L1 L1 2433 (CYTOMEGALOVIR? OR CMV? OR..... L2 SEL L1 1- RN : 50359 TERMS L3 SEL L1 1459- RN : 12961 TERMS FILE 'REGISTRY' ENTERED AT 10:10:05 ON 27 OCT 2003 L4 50359 S L2 L5 12961 S L3 L6 61198 S L4 OR L5 L7 STRUCTURE UPLOADED L8 85 L7 FULL SUB=L6 FILE 'CAPLUS' ENTERED AT 10:16:17 ON 27 OCT 2003 L9 L9 15 L8 AND L1 FILE 'MARPAT' ENTERED AT 10:17:40 ON 27 OCT 2003 L10 325 L1 L11 L11 34 L8 FULL SUB=L10

179. 179 => file caplus => l11 L12 34 L11 => l12 not l9 L13 31 L12 NOT L9 => sel l13 rn SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details L14 SEL L13 1- RN : 2630 TERMS

180. 180 => fil reg => l14 L15 2630 L14 => l7 full subset=l15 FULL SUBSET SEARCH INITIATED 10:26:22 FULL SUBSET SCREEN SEARCH COMPLETED - 2444 TO ITERATE 100.0% PROCESSED 2444 ITERATIONS 0 ANSWERS SEARCH TIME: 00.00.01 L16 0 SEA SUB=L15 SSS FUL L7

181. 181 FILE 'CAPLUS' ENTERED AT 10:16:17 ON 27 OCT 2003 L9 L9 15 L8 AND L1 FILE 'MARPAT' ENTERED AT 10:17:40 ON 27 OCT 2003 L10 325 L1 L11 L11 34 L8 FULL SUB=L10 FILE 'CAPLUS' ENTERED AT 10:19:35 ON 27 OCT 2003 L12 34 L11 L13 L13 31 L12 NOT L9 L14 SEL L13 1- RN : 2630 TERMS FILE 'REGISTRY' ENTERED AT 10:25:22 ON 27 OCT 2003 L15 2630 L14 L16 0 L7 FULL SUB=L15

182. 182 => fil marpat => l9 L17 12 L9 => l11 not l17 L18 31 L11 NOT L17 => d fhit

183. 183 alkyl (SO (1-3) G3) G2 = alkyl (SO (1-3) G3) / (SC Me / Et / 129 / 139 / 144 / 148 / 154 / 161) morpholino G3 = OH / NH2 / 37 / morpholino /

184. 184 Generic Groups

185. 185 they are always involved Generic Groups are very important in Marpat because, at level Class, they are always involved (generated or original) Generic Groups

186. 186 AkAny carbon chain (only first atom need be carbon); any bond value allowed CyAny cyclic group HyAny cyclic group with one (1) or more non-carbon atoms CbAny cyclic group with all carbon atoms Generic Groups

187. 187 Generic Groups

188. 188 Generic Groups Ak Cy Hy Cb Remember that you can use the Element Count: Minimum, Maximum, Exact, Range to estabilish the number of atoms

189. 189 Generic Text Shortcuts Ak-based Ak is a chain of 1 or more carbons, linear or branched, saturated or unsaturated AlkanoylAlkyl -C(O)-, H - C(O) - AlkenylAk with one or more double bonds, no triple bonds, and two or more carbons, Ak - An unsaturated monovalent radical chain of two or more carbons, branched or linear, containing one or more carbon-to-carbon double bonds, but no triple bonds Formed by the removal of one hydrogen from the corresponding alkene, e.g., CH3 - CH = CH - CH2 - Generic Groups

190. 190 Alkenylene An unsaturated divalent hydrocarbon chain radical of at least two carbon atoms containing one or more double bonds, but no triple bonds Formed by the removal of two hydrogens from the parent branched or linear alkene, e.g., - CH = CH - Alkenylenedioxy- O - alkenylene - O - Alkoxyalkyl - O - also called alkyloxy and alkoxyl Generic Text Shortcuts Ak-based Generic Groups - Ak -

191. 191 AlkylAk with all bonds single exact A totally saturated monovalent radical chain, branched or linear Formed from an alkane by removal of one hydrogen, e.g., Me-, Et-, t-Bu- Alkylene- alkyl - A divalent saturated hydrocarbon radical Formed by the removal of two hydrogens from the branched or linear parent alkane, e.g., - CH2 - Generic Text Shortcuts Ak-based Generic Groups

192. 192 Alkylidenealkyl = A divalent alkyl radical that is attached to the parent by a double bond or two (2) single bonds from the same carbon, e.g., = CH - CH2 - CH3 AlkynylAk with no double bonds, one (1) or more triple bonds, and two (2) or more carbons, Ak An unsaturated monovalent radical chain of two (2) or more carbons, branched or linear, containing one or more carbon-to-carbon triple bonds, but no double bonds Formed by the removal of one hydrogen from the corresponding alkyne, e.g., Generic Text Shortcuts Ak-based Generic Groups

193. 193 LowerAny of the “alk” terms may be preceded by the term “lower” which implies a total carbon count one (1) to six (6) carbons for alkanes; 2-6 carbons for alkenes and alkynes. This term is used only when no carbon count is given in the patent LoweralkylAk with all bonds single exact and one (1) to six (6) carbons PerhaloalkylAlkyl with all hydrogens replaced by halogen atoms Generic Text Shortcuts Ak-based Generic Groups

194. 194 Cb is any monocyclic or polycyclic group containing all carbon atoms with any bond values between atoms. Hy is any monocyclic or polycyclic group containing one or more non-carbon atoms with any bond values between the atoms. Generic Text Shortcuts Cb/Hy-based Generic Groups

195. 195 ArylCb with one or more aromatic rings, six (6) or more normalized bonds, and one (1) or more six (6)-membered rings Arylene- aryl - A divalent aromatic radical Formed by the removal of two (2) hydrogens from two different carbon atoms on the aromatic molecule, e.g., phenylene Generic Text Shortcuts Cb/Hy-based Generic Groups

196. 196 Cycloalkenyl Cb with one (1) or more double bonds and no triple bonds An unsaturated monovalent monocyclic or polycyclic radical containing one (1) or more carbon-to-carbon double bonds Formed by the removal of one (1) hydrogen from the corresponding cycloalkene, e.g., cyclopentadienyl, cyclohexenyl CycloalkylCb with all bonds single exact A saturated monovalent alicyclic radical Formed by the removal of one (1) hydrogen from the corresponding cycloalkane, e.g., cyclopropyl, decahydronaphthyl Generic Text Shortcuts Cb/Hy-based Generic Groups

197. 197 HeteroarylHy with one (1) or more aromatic rings with six (6) or more normalized bonds and one (1) or more six (6)-membered rings Hy with one (1) or more aromatic rings and two (2) or more double bonds and one (1) or more five (5)-membered rings A monovalent radical derived from an aromatic molecule that contains at least one (1) heteroatom. Formed by removal of one (1) hydrogen from the pyridyl, benzopyranyl Generic Text Shortcuts Cb/Hy-based Generic Groups

198. 198 AcylCarbonyl bonded to Ak (which may have R’s on it), at the carbonyl carbon Carbonyl bonded to R, at the carbonyl carbon Formyl AralkylAlkyl bonded to one-to-three (1-3) aryls, HydrocarbylAk Cb bonded to Ak Generic Text Shortcuts Hybrids Generic Groups

199. 199 MARPAT Codes

200. 200 Structure Displays MSTR Display label for the Markush Structure Example:MSTR 4 Translation:This is the 4th Markush structure in the document MARPAT Codes

201. 201 VAR G# Defines the alternatives for a G# Example:VAR G1 = O / S / 16 / NULL Translation: G1 is O or S or node 16 or G1 is a direct bond Node sixteen (16) appears in the structure diagram portion of the display Structure Displays MARPAT Codes

202. 202 REP G#= Defines a REPeating group and the number of times it repeats Example:REP G3 = (0-7) CH2 Translation:CH2 repeats (0-7) times Structure Displays MARPAT Codes

203. 203 CVA The Conditional Variable statement, currently ignored at search time Example:VAR G1 = H / OH / X VAR G2 = NO2 / Me / Et CVA = If G1 = OH, THEN G2 = Me Translation: If G1 is the OH alternative, then G2 must be Me and not NO2 or Et. Searched as G1 = H, OH, X and G2 = NO2, Me, Et (STN Express) as VAR G1 = H / OH / X and VAR G2 = NO2 / Me / Et Structure Displays MARPAT Codes

204. 204 DER DERivative information that cannot be structured Searched as single words in the Basic Index (default) Example:DER: or salts or metal complexes Structure Displays MARPAT Codes

205. 205 NTE General NoTEs Searched as single words in the Basic Index (default) Example:NTE: substitution restricted Structure Displays MARPAT Codes

206. 206 MPL Location of the Markush structure in the patent Searched as single words in the Basic Index (default) Example:MPL: claim 1 Structure Displays MARPAT Codes

207. 207 STE STEreochemistry Searched as single words in the Basic Index (default) Example:STE: 41,42-cis Structure Displays MARPAT Codes

208. 208 Generic Group Attributes AN, AR, BD, CH, DC,EC, FA, RC, RS, TX – Found in following the generic group they modify – The marked attributes are searched as Generic Definitions (STN Express queries) or Generic Group Categories (STR command queries) – All others are ignored while searching MARPAT Codes Structure Displays

209. 209 MARPAT Codes Structure Displays

210. 210 MARPAT Codes Structure Displays

211. 211 Precision Qualifiers - EX and SC Found in parentheses at the end of the variable definition Additional alternatives for the G-group MARPAT Codes

212. 212 EX Alternatives are found in the EXamples (in the disclosure) Example:VAR G1 = R /(EX Cl/ Br / I) Translation:Cl, Br and I are alternatives for G1 and were found in the disclosure. VAR denotes variability G1 is the tag on the variable group Precision Qualifiers MARPAT Codes

213. 213 SC Alternatives are Specifically Claimed Example:VAR G3 = H / alkyl / alkoxy / (SC Me / OMe) Translation:Methyl and methoxy are alternatives for G3 and are specifically claimed Precision Qualifiers MARPAT Codes

214. 214 Substitution Qualifiers - SO and SR Found in parentheses immediately after the group they modify In the current implementation, SO and SR are both searched as SO; i.e., as if the substituent were present on the group any number of times, including zero MARPAT Codes

215. 215 Substitution Qualifiers SO Alternative is Substituted Optionally by this group Example:VAR G1 = Ph (SO 5X) / alkoxycarbonyl (SO CO2H) Translation:Phenyl is substituted with zero (0) to five (5) halogens Alkoxycarbonyl is substituted with zero (0) or more carboxy groups MARPAT Codes

216. 216 SR Alternative has Substitution Required by one (1) or more of this group Currently searched as SO Example:VAR G1 = Ph (SR 5X) / alkoxycarbonyl (SR CO2H) Translation:Phenyl is substituted with one (1) to five (5) halogens Alkoxycarbonyl is substituted with one (1) or more carboxy groups Currently searched as zero (0) to five (5) halogens and zero (0) or more carboxy groups Substitution Qualifiers MARPAT Codes

217. 217 Occurrence Counts Occurrence Counts are found in front of the alternative they modify Used to limit the substitution by specifying how many times an alternative is present The occurrence counts are not currently searchable MARPAT Codes

218. 218 (n) Alternative occurs exactly “n” times Example:VAR G1 = (1) X / Me Translation:Exactly one (1) of the G1’s is X Searched as G1 = X,Me (STN Express); VAR G1=X/Me (STR command) Occurrence Counts MARPAT Codes

219. 219 (n-) Alternative occurs “n” or more times Example:VAR G3 = (2-) H / loweralkyl / X Translation:Two (2) or more of the G3’s are H Searched as G3 = H, Ak, X (STN Express); VAR G3= H / Ak, X Me (STR command) Occurrence Counts MARPAT Codes

220. 220 (-n) Alternative occurs zero (0) to “n” times Example:VAR G6 = (-1) H / alkyl / CH2Ph Translation: Zero (0) or one (1) of the G6’s are H Searched as G6 = H, Ak, CH2Ph (STN Express); VAR G6 = H / Ak, CH2Ph (STR command) Occurrence Counts MARPAT Codes

221. 221 (m-n) Alternative occurs “m” to “n” times Example:VAR G2 = X / CF3 / Ph (SO (1-2) G3) Translation: The phenyl (Ph) is optionally substituted by one (1) or two (2) of the variable G3’s Searched as the phenyl (Ph) substituted by zero (0) to five (5) G3’s Occurrence Counts MARPAT Codes