Presentation is loading. Please wait.

Presentation is loading. Please wait.

1 Bioscience and Pharmaceutical Databases. 2 In Searching these databases it is very often request to run a search in many databases (multifile searches).

Similar presentations


Presentation on theme: "1 Bioscience and Pharmaceutical Databases. 2 In Searching these databases it is very often request to run a search in many databases (multifile searches)."— Presentation transcript:

1 1 Bioscience and Pharmaceutical Databases

2 2 In Searching these databases it is very often request to run a search in many databases (multifile searches). Bioscience and Pharmaceutical Databases

3 3 Multifile Searching Multifile searching can be conducted by searching several files: –Simultaneously, using one query (a "universal strategy") –Sequentially, using file-specific queries ("file-specific strategies")

4 4 Multifile Searching Simultaneous multifile searching with a universal strategy is typically used when: –The search strategy is based on natural language terms –Searching standard bibliographic information

5 5 Universal Strategy (Natural Language) Using one query to search several files simultaneously will produce a good, general answer set. A number of search techniques and STN tools are available for identifying search terms and developing comprehensive, file-independent queries. Multifile Searching

6 6 Substance Searching Multifile Searching

7 7 Search Question: Find references to the possible medical application of nifedipine to prevent premature labor. Universal Strategy Development Multifile Searching

8 8 => FILE REGISTRY => E NIFEDIPINE/CN 5 E1 1 NIFECR10SI15TI/CN E2 1 NIFECR12MO/CN E3 1 --> NIFEDIPINE/CN E4 1 NIFEDIPINE DEHYDROGENASE/CN E5 1 NIFEDIPINE N-OXIDASE/CN => S E3 L1 1 NIFEDIPINE/CN => SEL CHEM E6 THROUGH E27 ASSIGNED The EXPAND list can be varied from 5 to 25 terms. SELECT CHEM is used to extract the chemical name and CAS RN terms from the REGISTRY record and transform them into E-numbered terms which are searchable in the Basic Index. Identify Substance Search Terms Multifile Searching

9 9 => D SEL E6 1 ADALAT/BI E7 1 BAY 1040/BI E8 1 BAY-A 1040/BI E9 1 CORDAFEN/BI E10 1 CORDAFLEX/BI E11 1 CORINFAR/BI o o o E17 1 NIPHEDIPINE/BI E18 1 PROCARDIA XL/BI E19 1 PROCARDIA/BI E20 1 TN 873R/BI E /BI E /BI o o o E (2-NITROPHENYL)-2,6-DIMETHYL- 3,5-DICARBOMETHOXY-1,4DIHYDROPYRIDINE/BI Note: Many chemical names have been used in the literature to denote this substance. Identify Substance Search Terms Multifile Searching

10 10 => QUE E6-E27 L2 QUERY CREATED The QUERY command is used to build a search query for later use. Identify Substance Search Terms Multifile Searching

11 11 => s E6 E8-E10 E20 E25 Questions: write the string for searching E6,E8,E9,E10,E20,E25 using Smartselect write the same search => s L2

12 12 => S /CRN OR L1 => SELECT CHEM Question: It may be desirable to include salt and mixture forms of the substance:

13 13 A free-text, "universal query" can be developed using terminology drawn from MeSH thesaurus entries. This query can be re-searched in the Basic Index of any file. To develop a free-text strategy using controlled terminology from an online thesaurus: 1 EXPAND to identify thesaurus terminology (MeSH terms) for the main concepts. 2 EXPAND the MeSH term to identify additional relevant terminology. 3 Create a relevant search query. Identify Substance Search Terms Multifile Searching

14 14 => FILE MEDLINE => E PREMATURE LABOR/CT ADDITIONAL TERMS AVAILABLE BY USING "PREMATURE LABOR+XUSE/CT" E# FREQUENCY AT TERM E PREMATURE INFANT/CT E PREMATURE INFANTS/CT E > PREMATURE LABOR/CT E PREMATURE MENOPAUSE/CT E PREMATURE MENOPAUSES/CT o o o => E E30+ALL E > Premature Labor/CT E USE Labor, Premature/CT ******END*** E30 is NOT a MeSH term, as indicated by 0 answers and 2 associated terms. Optional pathway to identify MeSH terminology: => E PREMATURE LABOR+XUSE/CT E1 0 --> Premature Labor/CT E USE Labor, Premature/CT Identify Substance Search Terms Multifile Searching

15 15 => E E41+ALL E42 0 BT3 C Diseases/CT E43 0 BT2 Female Genital Diseases and Pregnancy Complications/CT E BT1 Pregnancy Complications/CT E > Labor, Premature/CT E MN C /CT DC an INDEX MEDICUS major descriptor o o o E47 0 UF Birth, Premature/CT E48 0 UF Births, Premature/CT E49 0 UF Premature Birth/CT E50 0 UF Premature Births/CT E51 0 UF Premature Labor/CT E RT Infant, Premature/CT E RT Tocolytic Agents/CT ******END*** The code at E46 is called the "MeSH Tree Number" (MN). Searching on an MN retrieves narrower terms (NT) associated with MeSH headings. (Here there are no narrower terms so the postings at E45 and E46 are the same.) Identify Substance Search Terms Multifile Searching

16 16 => QUE (EARLY OR PREMATURE OR PRE MATURE) (S) (BIRTH# OR LABOR# OR LABOUR# OR PARTURIT?) OR TOCOLYTIC L3 QUE (EARLY OR PREMATURE OR PRE MATURE) (S) (BIRTH# OR LABOR# OR LABOUR# OR PARTURIT?) OR TOCOLYTIC Identify Substance Search Terms Multifile Searching

17 17 Universal Search => FILE MEDLINE EMBASE BIOSIS HCAPLUS => SET POSTINGS OFF; SET MSTEPS ON SET COMMAND COMPLETED => S L2 AND L3 L4 105 FILE MEDLINE L5 189 FILE EMBASE L6 71 FILE BIOSIS L7 33 FILE HCAPLUS TOTAL FOR ALL FILES L8 398 L2 AND L3 SET POSTINGS OFF to suppress intermediate postings. SET MSTEPS ON to create answer sets in each file, as well as the merged set. Multifile Searching

18 18 => DUP REM L8 PROCESSING COMPLETED FOR L8 L9 260 DUP REM L8 (138 DUPLICATES REMOVED) Post-processing option: Relevance ranking: => FOCUS L9 L FOCUS L9 1- => D TI 1-5 L10 ANSWER 1 OF 260 HCAPLUS COPYRIGHT 2000 ACS TI A comparative study of nifedipine and isoxsuprine hydrochloride in the management of preterm labor L10 ANSWER 2 OF 260 HCAPLUS COPYRIGHT 2000 ACS TI Use of thiazolidinediones derivatives for preventing ocytocin Mediated actions such as uterine contractions in premature labour or lactation o o o The answers in L9 are arranged in reverse chronological order. Universal Search Multifile Searching

19 19 File-Specific Strategy (Thesaurus) Using file-specific indexes and features generally results in answer sets of the best precision. Developing file-specific strategies requires knowledge of the file structure and indexing and more time in query formation and search execution. A number of STN tools are available for efficiently navigating the content of file-specific indexes. Multifile Searching

20 20 File-Specific Strategy Development File-specific approaches generally incorporate file-specific indexes for precise searching. Search Question: Find human studies published since 1995 on the toxicity of halothane to the liver. Multifile Searching

21 21 Develop MEDLINE Strategy Identify controlled terminology for halothane: MeSH subheadings provide easy access to various types of studies related to a substance when a chemical name is known: e.g., adverse effect studies and toxicity studies. These subheadings are accessible in EXPAND listings in the CT index. Multifile Searching

22 22 Helpful Hint The alphabetical facets for arranging MeSH can be viewed using => HELP TREE check tags check tags ALL categories of MeSH are searchable in the CT field, including major and minor descriptors, geographicals, and check tags. A complete list of check tags can be viewed using => HELP CTAG Multifile Searching

23 23 Multifile Searching => HELP TREE A Anatomy B Organisms C Diseases D Chemicals and Drugs E Analytical, Diagnostic and Therapeutic Technics and Equipment F Psychiatry and Psychology G Biological Sciences H Physical Sciences I Anthropology, Education, Sociology and Social Phenomena J Technology, Industry, Agriculture K Humanities L Information Sciences M Named Groups N Health Care Z Geographicals

24 24 Multifile Searching => HELP CTAG Check Tags are special use descriptors that do not represent subject matter per se but that reflect parameters or aspects of subject content. Special efforts in indexing assures that these will be included or "checked" each time they appear as aspects in an item being indexed. The following list of descriptors must be entered by an indexer for every journal article citation to which they apply: ANIMAL CASE REPORT COMPARATIVE STUDY ENGLISH ABSTRACT FEMALE HUMAN IN VITRO MALE PREGNANCY SUPPORT, NON-U.S. GOV'T SUPPORT, U.S. GOV'T, NON-P.H.S. SUPPORT, U.S. GOV'T, P.H.S.

25 25 Develop MEDLINE Strategy => FILE MEDLINE => E HALOTHANE/CT ADDITIONAL TERMS AVAILABLE BY USING "HALOTHANE+XUSE/CT" E# FREQUENCY AT TERM E HALOSPOR/CT E HALOTESTIN/CT E > HALOTHANE/CT E41 34 HALOTHANE: AA, ANALOGS & DERIVATIVES/CT E HALOTHANE: AD, ADMINISTRATION & DOSAGE/CT E HALOTHANE: AE, ADVERSE EFFECTS/CT o o o Multifile Searching

26 26 o o o E62 49 HALOTHANE: PO, POISONING/CT E63 1 HALOTHANE: PY, PATHOGENICITY/CT E64 7 HALOTHANE: RE, RADIATION EFFECTS/CT E65 7 HALOTHANE: ST, STANDARDS/CT E HALOTHANE: TO, TOXICITY/CT E HALOTHANE: TU, THERAPEUTIC USE/CT E68 23 HALOTHANE: UR, URINE/CT o o o A subheading indicates "toxicity" studies of halothane. => S E66 L# 413 "HALOTHANE: TO, TOXICITY"/CT Develop MEDLINE Strategy Multifile Searching

27 27 MeSH subheadings help focus search results. => HELP PREEXPLOSION Subheading Pre-Explosions You can now search subheadings with the narrower hierarchy included automatically in the MEDLINE File without specifying them separately. For example, S KANAMYCIN/CT(L)(AE OR TO OR PO)/CT can be searched as => S KANAMYCIN/CT(L)AE./CT. In order to use this pre-explosion feature, a period (.) must be placed after the two-letter code subheading. The pre-exploded subheading hierarchy is as follows. adverse effects (AE) poisoning (PO) toxicity (TO) analysis (AN) blood (BL) cerebrospinal fluid (CF) isolation & purification (IP) urine (UR) o o o Develop MEDLINE Strategy Multifile Searching

28 28 Halothane strategy => S HALOTHANE/CT (L) AE./CT HALOTHANE/CT AE./CT L HALOTHANE/CT (L) AE./CT The heading "adverse effects" includes "toxicity", as well as the related heading "poisoning". Using related headings results in broader retrieval. Develop MEDLINE Strategy Multifile Searching

29 29 Identify controlled terminology for liver => E LIVER/CT E# FREQUENCY AT TERM E1 0 2 LIVEDO RETICULARIS/CT E2 0 2 LIVEDO RETICULARIS, SYSTEMIC INVOLVEMENT/CT E > LIVER/CT E LIVER ABSCESS/CT E LIVER ABSCESS, AMEBIC/CT o o o Develop MEDLINE Strategy Multifile Searching

30 30 => E E3+ALL E1 0 BT2 A Anatomy/CT E BT1 Digestive System/CT E > Liver/CT E MN A3.620./CT o o o E5 0 UF Effect, Hepatic/CT E6 0 UF Effects, Hepatic/CT E7 0 UF Hepatic Effect/CT E8 0 UF Hepatic Effects/CT E9 0 UF Livers/CT E NT1 Bile Ducts, Intrahepatic/CT E NT2 Bile Canaliculi/CT E RT Hepatectomy/CT ******END*** Note the difference in answers for the term at E3 versus E4. E4 (the MN) includes the answers for the narrower terms (E10-E11). Develop MEDLINE Strategy Multifile Searching

31 31 Exploding the MeSH heading: The MeSH term, plus all associated narrower terms, can be automatically searched. This is another example of "exploding" a MeSH term. => S LIVER+MN/CT L LIVER+MN/CT (2 TERMS ) Develop MEDLINE Strategy Multifile Searching

32 32 Identify Controlled terminology for organ headings In many cases, especially when searching for organ headings, such as liver, additional MeSH headings are required for a comprehensive strategy. The relationship code +KT opens up associated Keyword Terms to help locate heading candidates containing the input term. Develop MEDLINE Strategy Multifile Searching

33 33 => E LIVER+KT/CT E > Liver/CT E2 0 KT Abscess, Liver/CT E3 0 KT Abscess, Liver, Amebic/CT E4 0 KT Abscesses, Liver/CT o o o E24 0 KT Cancers, Liver/CT E25 0 KT Circulation, Liver/CT E26 0 KT Cirrhoses, Liver/CT o o o E91 0 KT Liver Disease, Parasitic/CT E KT Liver Diseases/CT o o o E119 0 KT Liver Neoplasm/CT E120 0 KT Liver Neoplasm, Experimental/CT E KT Liver Neoplasms/CT o o o Several relevant terms are identified. Develop MEDLINE Strategy Multifile Searching

34 34 MeSH entry for liver disease => E LIVER DISEASES/CT E# FREQUENCY AT TERM E1 0 2 LIVER DISEASE, ALCOHOLIC/CT E2 0 2 LIVER DISEASE, PARASITIC/CT E > LIVER DISEASES/CT E LIVER DISEASES, ALCOHOLIC/CT E5 396 LIVER DISEASES, ALCOHOLIC: BL, BLOOD/CT o o o Develop MEDLINE Strategy Multifile Searching

35 35 => E E3+ALL E1 0 BT2 C Diseases/CT E BT1 Digestive System Diseases/CT E > Liver Diseases/CT E MN C6.552./CT o o o E NT2 Alagille Syndrome/CT E NT2 Liver Cirrhosis, Biliary/CT E NT1 Fatty Liver/CT E NT2 Fatty Liver, Alcoholic/CT E NT2 Reye Syndrome/CT E25 10 NT1 Focal Nodular Hyperplasia/CT o o o Some of the same headings are listed in the NTs of this MeSH record. As well, new headings are noted. Develop MEDLINE Strategy Multifile Searching

36 36 Liver concept strategy The MeSH heading "liver diseases" is "exploded" when searched. The heading "liver diseases" is searched, as well as all narrower terms associated with the heading. => S LIVER DISEASES+NT/CT (L) CI/CT LIVER DISEASES+NT/CT (58 TERMS) CI/CT L LIVER DISEASES+NT/CT (L) CI/CT Results are made more precise by including the subheading "chemically induced“ CI. Develop MEDLINE Strategy Multifile Searching

37 37 MEDLINE answer set => D HIS FILE 'MEDLINE' ENTERED E HALOTHANE/CT L S HALOTHANE/CT (L) AE./CT E LIVER/CT E E3+ALL L S LIVER+MN/CT E LIVER+KT/CT E LIVER DISEASES/CT E E3+ALL L S LIVER DISEASES+NT/CT (L) CI/CT => S L1 AND L2 L4 522 L1 AND L2 => S L1 AND L3 L5 219 L1 AND L3 => S L4 OR L5 L6 657 L4 OR L5 Develop MEDLINE Strategy Multifile Searching

38 38 Refine results The LIMIT feature provides an easy way to narrow answers by frequently requested parameters. => S L6/HUMAN L7 459 L6/HUMAN => S L7 AND /PY /PY L8 17 L7 AND /PY Develop MEDLINE Strategy Multifile Searching

39 39 The EMBASE file contains an online thesaurus (EMTREE) in the controlled term (CT) index. It is searched in a manner similar to MEDLINE. Identify controlled terminology for halothane => FILE EMBASE => E HALOTHANE/CT E# FREQUENCY AT TERM E1 0 2 HALOTEX/CT E2 0 2 HALOTHAN/CT E > HALOTHANE/CT E4 93 HALOTHANE ANESTHESIA/CT E5 1 HALOTHANE BP/CT o o o Develop EMBASE Strategy Multifile Searching

40 40 => E E3+ALL E > halothane/CT HNTE Creation date 01 JUL 19: 79 RN RN E2 0 UF 1 bromo 1 chloro 2,2,2 trifluoroethane/CT E3 0 UF 1,1,1 trifluoro 2 bromo 2 chloroethane/CT E4 0 UF 1,1,1 trifluoro 2 haloethane/CT E5 0 UF 1,1,1 trifluoro 2,2 bromochloroethane/CT E6 0 UF 2 bromo 2 chloro 1,1,1 trifluoroethane/CT E7 0 UF 2 chloro 2 bromo 1,1,1 trifluoroethane/CT E8 0 UF bromochlorotrifluorethane/CT o o o E14 0 UF halothan/CT E15 0 UF halothane metabolite/CT E16 0 UF halthane/CT E17 0 UF narcotan/CT E18 0 UF phthorothane/CT E RMN D /CT E RMN D /CT E RMN D /CT ******END*** UF (Use For) are synonyms that are automatically referenced to the preferred name. RMN are associated EMTREE codes. RMN are not automatically searched when the EMTREE term is exploded. Explode the desired RMN (e.g. => E E19+ALL) to identify the heading. E19 is “inhalation anesthetic agent”. Develop EMBASE Strategy Multifile Searching

41 41 => HELP LTERMS Link terms are concept modifiers (subheadings) added, where appropriate, by the EMBASE database producer to EMTREE terms. Over the years, link terms have been added to EMBASE records to enhance In 1988, two searchers' ability to retrieve precise drug information. In 1988, two link term groups were introduced: drug links and disease links link term groups were introduced: drug links and disease links. Drug links may be added only to EMTREE drug terms (facet D) and disease links may be added only to EMTREE terms for diseases (facet C). See HELP TREE for further details on facets D and C. Each link term is additionally represented by a 2-letter code. Following is the list of DRUG and DISEASE links. DRUG LINKS CODE DISEASE LINKS CODE adverse drug reaction AE complication CO clinical trial CT congenital disorder CN o o o drug therapy DT rehabilitation RH drug toxicity TO side effect SI endogenous compound EC surgery SU o o o There are two categories of link terms - those applied to drugs and those applied to diseases. Develop EMBASE Strategy Multifile Searching

42 42 Multifile Searching => help tree EMTREE Classifications (facets) are as follows: A Anatomical concepts A1 body regions C Physical diseases, disorders and abnormalities C1 general aspects of disease D Chemicals and drugs D1 general and inorganic chemicals Develop EMBASE Strategy

43 43 Halothane strategy => S HALOTHANE/CT (L) (AE OR TO)/CT HALOTHANE/CT AE/CT TO/CT L HALOTHANE/CT (L) (AE OR TO)/CT Multiple link term codes can be searched. Develop EMBASE Strategy Multifile Searching

44 44 Identify controlled terminology for liver => E LIVER/CT E# FREQUENCY AT TERM E1 4 LIVEDO: DT, DRUG THERAPY/CT E2 2 LIVEDOID/CT E > LIVER/CT E4 0 2 LIVER ABCESS/CT E LIVER ABSCESS/CT o o o Develop EMBASE Strategy Multifile Searching

45 45 Controlled terminology for organs => E LIVER+KT/CT E > liver/CT E KT alcohol liver cirrhosis/CT E KT alcohol liver disease/CT E4 426 KT artificial liver/CT E5 361 KT cholesterol liver level/CT E KT chronic liver disease/CT E7 264 KT cod liver oil/CT E KT dose liver function relation/CT E9 664 KT drug liver level/CT o o o E KT liver cytosol/CT E KT liver development/CT E KT liver disease/CT E KT liver dysfunction/CT o o o Develop EMBASE Strategy Multifile Searching

46 46 EMTREE entry for liver disease => E LIVER DISEASE/CT E# FREQUENCY AT TERM E1 30 LIVER DENERVATION/CT E LIVER DEVELOPMENT/CT E > LIVER DISEASE/CT E4 0 2 LIVER DISEASE,ALCOHOL/CT E5 0 2 LIVER DISEASE,CHRONIC/CT o o o Develop EMBASE Strategy Multifile Searching

47 47 Develop EMBASE Strategy Multifile Searching => e e3+all E BT1 hepatobiliary disease/CT E > liver disease/CT E MN C /CT E25 0 UF liver illness/CT E NXT Budd Chiari syndrome/CT E NT1 Hepatitis/CT E NT2 virus hepatitis/CT E NT1 alcohol liver disease/CT ********* END*** => e17+nt L "LIVER DISEASE"+NT/CT (42 TERMS) => e17+nxt RELATIONSHIP 'NXT' IGNORED NOT A VALID RELATIONSHIP CODE FOR FIELD 'CT' L "LIVER DISEASE"+NXT/CT (1 TERM) => e18 L C /CT

48 48 Liver concept strategy Through EXPAND, unique headings are noted in both "liver" and "liver disease+KT"; therefore, both concepts are incorporated into the strategy. => S LIVER DISEASE+NT/CT OR LIVER+KT/CT LIVER DISEASE+NT/CT (39 TERMS) LIVER+KT/CT (102 TERMS) L LIVER DISEASE+NT/CT OR LIVER+KT/CT => S L10 (L) SI/CT SI/CT L L10 (L) SI/CT Results are made more precise by including the link term "side effects ". Develop EMBASE Strategy Multifile Searching

49 49 => D HIS o o o FILE 'EMBASE' ENTERED E HALOTHANE/CN E E3+ALL E HALOTHANE/CT E E3+ALL L S HALOTHANE/CT (L) (AE OR TO)/CT E LIVER/CT E LIVER+KT/CT E LIVER DISEASE/CT E E3+ALL L S LIVER DISEASE+NT/CT OR LIVER+KT/CT L S L10 (L) SI/CT => S L9 AND L11 L L9 AND L11 Develop EMBASE Strategy Multifile Searching

50 50 Refine results EMBASE also offers the LIMIT feature. => S L12/HUMAN L L12/HUMAN => S L13 AND /PY /PY L L13 AND /PY Develop EMBASE Strategy Multifile Searching

51 51 Keyword searching in the newer segment (1993-) of the BIOSIS file is optimally conducted in the Basic Index. This Eliminates the need to look up controlled terminology Requires development of a search query taking into account as many synonyms as practical to capture relevant answers Develop BIOSIS Strategy Multifile Searching

52 52 Identify controlled terminology for halothane => FILE REGISTRY => S HALOTHANE/CN L15 1 HALOTHANE/CN => SEL CHEM E1 THROUGH E15 ASSIGNED => QUE E1-E15 L16 QUE ("(.+-.)-HALOTHANE"/BI OR ANESTAN/BI OR FLUKTAN/BI OR FLUOTHANE/BI OR "FREON 123B1"/BI OR FTOROTAN/BI OR HALAN/BI OR HALOTHANE/BI OR o o o Develop EMBASE Strategy Multifile Searching

53 53 Identify controlled terminology for liver Terminology drawn from the MEDLINE thesaurus will be used in the Basic Index search of BIOSIS. => FILE BIOSIS => S LIVER OR ?HEPAT? OR BILIARY LIVER ?HEPAT? BILIARY L LIVER OR ?HEPAT? OR BILIARY Develop EMBASE Strategy Multifile Searching

54 54 Identify controlled terminology for toxicity A set of search terms encompassing the toxicity concept can be created using Natural language Concept codes in the CC index Natural language set => QUE TOXIC? OR ?CANCER? OR ATROPH? OR DISEASE# OR DYSFUNCTION# OR FAILURE# OR NEOPLASM OR ?CARCIN? OR ?TUMOR? L18 QUE TOXIC? OR ?CANCER? OR ATROPH? OR DISEASE# OR DYSFUNCTION# OR FAILURE# OR NEOPLASM OR ?CARCIN? OR ?TUMOR? Develop EMBASE Strategy Multifile Searching

55 55 Concept code set CC terms are for records before The keywords selected above will be necessary for 1999-forward records. => E TOXIC/CC E TEMPERATURE: ITS MEASUREMENT, EFFECTS AND REGULATION THERM OTHERAPY/CC o o o E TOXICOLOGY - PHARMACOLOGICAL TOXICOLOGY/CC o o o => QUE E8 L19 QUE "TOXICOLOGY - PHARMACOLOGICAL TOXICOLOGY"/CC Develop EMBASE Strategy Multifile Searching

56 56 => E NEOPLASM/CC E MUSCLE - PATHOLOGY/CC E MUSCLE - PHYSIOLOGY AND BIOCHEMISTRY/CC E3 0 --> NEOPLASM/CC E NEOPLASMS AND NEOPLASTIC AGENTS - BIOCHEMISTRY/CC E NEOPLASMS AND NEOPLASTIC AGENTS - BLOOD AND RETICULOENDOTHE LIAL NEOPLASMS/CC E NEOPLASMS AND NEOPLASTIC AGENTS - CARCINOGENS AND CARCINOGE NESIS/CC o o o => QUE E6 L20 QUE "NEOPLASMS AND NEOPLASTIC AGENTS - CARCINOGENS AND CARCINOGENESIS"/CC Develop EMBASE Strategy Multifile Searching

57 57 => D HIS o o o FILE 'REGISTRY' ENTERED L15 1 S HALOTHANE/CN SEL CHEM L16 QUE E1-E15 FILE 'BIOSIS' ENTERED L S LIVER OR ?HEPAT? OR BILIARY L18 QUE TOXIC? OR ?CANCER? OR ATROPH? OR DISEASE# OR DYSFUNCTION# E TOXIC/CC L19 QUE E8 E NEOPLASM/CC L20 QUE E6 => S L16 AND L17 AND (L18 OR L19 OR L20) L L16 AND L17 AND (L18 OR L19 OR L20) Develop EMBASE Strategy Multifile Searching

58 58 Refine results: BIOSIS also offers the LIMIT feature => S L21/HUMAN AND /PY 527 L21/HUMAN /PY L22 63 L21/HUMAN AND /PY Develop EMBASE Strategy Multifile Searching

59 59 CAS provides file pricing options for the CAplus file. The HCAplus version of the file has no search term fees. It is used here due to the large number of search terms. Identify controlled terminology for halothane The CAS RN is the optimum substance search term in CAplus. Identify controlled terminology for: liver and human and toxicity. CAS Lexicon and PSS Search are very good tool CAS Roles: CAS Roles help focus and refine substance search results. Develop HCAplus Strategy Multifile Searching

60 60 In this search there are four main concepts:  Halothane  Liver  Toxicity  Human Develop HCAplus Strategy Multifile Searching

61 61 Identify controlled terminology for liver and toxicity For liver search terms the Lexicon can be used in HCAplus. For toxicity search terms the CATOX.PSS File can be used in HCAplus. Keyword searching is generally performed in the Basic Index of the HCAplus file. For added precision, some concepts can be searched in (L) proximity. Develop HCAplus Strategy Multifile Searching

62 62 => fil reg => HALOTHANE/CN L1 1 HALOTHANE/CN => sel chem SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details L2 SEL L1 1- CHEM : 23 TERMS Develop HCAplus Strategy Multifile Searching

63 63 => fil hcaplus => l1/adv 7065 L ADV/RL L3 477 L1/ADV (L1 (L) ADV/RL) => e liver/ct E# FREQUENCY AT TERM E1 0 1 LIVED/CT E2 0 1 LIVENS/CT E > LIVER/CT Develop HCAplus Strategy Multifile Searching

64 64 => e e3+all E BT3 Body, anatomical/CT E14 0 BT2 Organ systems (non-CA heading)/CT E BT1 Digestive tract/CT E > Liver/CT => E16-E61/bi or ?HEPAT? OR BILIAR? L (LIVER/BI OR "LIVER EP Develop HCAplus Strategy Multifile Searching

65 65 Develop HCAplus Strategy Multifile Searching => This Predefined Search L5 QUE TOXICOLOGY/SC,SX OR 59/SC, => d his FILE 'REGISTRY' ENTERED AT 03:55:56 ON 16 MAR 2003 L1 1 HALOTHANE/CN L2 SEL L1 1- CHEM : 23 TERMS FILE 'HCAPLUS' ENTERED AT 03:57:14 ON 16 MAR 2003 L3 477 L1/ADV E LIVER/CT E E3+ALL L E16-E61/BI OR ?HEPAT? OR BILIAR? L5 QUERY TOXICOLOGY/SC,SX

66 66 Develop HCAplus Strategy Multifile Searching => l2(l)l5 L L6(L)L5 => (l3 or l7)(l)l4 L8 473 (L3 OR L7)(L)L4

67 67 Develop HCAplus Strategy Multifile Searching => expand human/ct E# FREQUENCY AT TERM E HULZ 70C/CT E HUMACITE/CT E > HUMAN/CT => e e64+all E79 19 BT1 Homo/CT E > Human/CT

68 68 Develop HCAplus Strategy Multifile Searching => e80-e82/bi or MAN OR WOMAN OR CHILD OR PATIENT OR BOY OR GIRL OR VOLUNTEER L (HUMAN/BI OR "HOMO SAPIENS"/BI OR "HUMAN GROUPS"/BI) OR MAN OR WOMAN OR CHILD OR PATIENT OR BOY OR GIRL OR VOLUNTEER => d his FILE 'REGISTRY' ENTERED AT 03:55:56 ON 16 MAR 2003 L1 1 HALOTHANE/CN L2 SEL L1 1- CHEM : 23 TERMS FILE 'HCAPLUS' ENTERED AT 03:57:14 ON 16 MAR 2003 L3 477 L1/ADV E LIVER/CT E E3+ALL L E16-E61/BI OR ?HEPAT? OR BILIAR? L5 QUERY TOXICOLOGY/SC,SX OR 59/SC, L S L2 L S L6(L)L5 L8 473 (L3 OR L7)(L)L4 EXPAND HUMAN/CT E E64+ALL L E80-E82/BI OR MAN OR WOM!N OR

69 69 Develop HCAplus Strategy Multifile Searching => l8(l)l9 L26 83 L8(L)L9 => l10 and /py /PY L27 18 L26 AND /PY

70 70 Combine Results into One Unique Set => DUP REM L8 L14 L22 L27 FILE 'MEDLINE' ENTERED FILE 'EMBASE' ENTERED FILE 'BIOSIS' ENTERED FILE 'HCAPLUS' ENTERED PROCESSING COMPLETED FOR L8 PROCESSING COMPLETED FOR L14 PROCESSING COMPLETED FOR L22 PROCESSING COMPLETED FOR L27 L DUP REM L8 L14 L22 L27 (39 DUPLICATES REMOVED) Multifile Searching

71 71 => D TI FROM EACH L28 ANSWER 2 OF 165 MEDLINE TI Hepatotoxicity following desflurane anesthesia [letter]. L28 ANSWER 1 OF 165 EMBASE COPYRIGHT 2000 ELSEVIER SCI. B.V. TI Alternative strategies in the treatment of bronchial asthma. L28 ANSWER 3 OF 165 BIOSIS COPYRIGHT 2000 BIOSIS TI Hemodynamic changes in patients with Alagille's syndrome during orthotopic liver transplantation. L28 ANSWER 24 OF 165 CAPLUS COPYRIGHT 2000 ACS TI Does general anesthesia affect sinusoidal liver cells as measured by.beta.-N-acetyl hexosaminidase serum activity level? Combine Results into One Unique Set Multifile Searching

72 72 Biomolecule Search Strategies

73 73 Overview of search techniques

74 74 Searching methods Name, Dictionary, Structures searching Specific Code Match (SCM) searching Similarity (homology) searching

75 75 CAS Index names –All substances are given standardised names (plus common names), available in Registry Bioscience file cluster –60 databases with bioscience content –Searchable simultaneously –STNindex can be used to investigate Name Searching

76 76 Biosequence records in REGISTRY contain nomenclature which can be used to find sequences of interest. REGISTRY records may contain Systematic names Derivative names based on a known peptide Biological names, with biological function, source organism, and gene/strain/clone designation Trade names Common names GenBank accession numbers Name Searching

77 77 RN REGISTRY CN Somatotropin (human) (9CI) (CA INDEX NAME) OTHER NAMES: CN 3: PN: WO SEQID: 1 claimed protein CN Bio-Tropin CN CB 311 CN Corpormon CN Crescormon CN Genotropin CN Growth hormone (human pituitary) CN Human growth hormone o o o CN PN: US TABLE: 5 claimed protein CN Saizen CN SJ 0011 CN Somatogen CN Somatotropin (human) CN Somatropin CN SR FS PROTEIN SEQUENCE SQL 191 (continued on next page) Name Searching

78 78 NTE type location description bridge Cys-53 - Cys-165 disulfide bridge bridge Cys Cys-189 disulfide bridge SEQ 1 FPTIPLSRLF DNAMLRAHRL HQLAFDTYQE FEEAYIPKEQ KYSFLQNPQT 51 SLCFSESIPT PSNREETQQK SNLELLRISL LLIQSWLEPV QFLRSVFANS 101 LVYGASDSNV YDLLKDLEEG IQTLMGRLED GSPRTGQIFK QTYSKFDTNS 151 HNDDALLKNY GLLYCFRKDM DKVETFLRIV QCRSVEGSCG F DR MF Unspecified CI MAN LC STN Files: ADISINSIGHT, AGRICOLA, ANABSTR, BIOBUSINESS, BIOSIS, BIOTECHNO, CA, CANCERLIT, CAPLUS, CASREACT, CBNB, CEN, CHEMCATS, CHEMLIST, CIN, CSCHEM, DDFU, o o o 1017 REFERENCES IN FILE CA (1967 TO DATE) 89 REFERENCES TO NON-SPECIFIC DERIVATIVES IN FILE CA 1019 REFERENCES IN FILE CAPLUS (1967 TO DATE) Name Searching

79 79 CAS assigns names to protein and nucleic acid sequences according to the following guidelines: Name Searching

80 80 CAS assigns names to protein and nucleic acid sequences according to the following guidelines: Name Searching

81 81 Some classes of biosequences, e.g., enolase (an enzyme), have a CAS RN with a preferred CA Index Name. Other classes of biosequences do not have CA Index Name. They are indexed in the Registry file as headings in the controlled term field. In these cases, the sequence name is based on the CA-preferred controlled term. The CA Lexicon is a good resource to verify the CA-preferred controlled term. Name Searching

82 82 => fil reg => e spectrin/cn E186 1 SPECTRIM RM 903, POLYMER... E187 1 SPECTRIM RM 903,.... E > SPECTRIN/CN => fil caplus => e spectrin/ct E# FREQUENCY AT TERM E SPECTRIM HT 75/CT E SPECTRIM HT 95/CT E > SPECTRIN/CT => e e200+all E > Spectrin/CT HN Valid heading.... E NEW Spectrins/CT ********* END*** Name Searching

83 83 => fil reg => e spectrins/cn E219 1 SPECTRIN-LIKE PROTEIN.... E220 1 SPECTRINASE/CN E > SPECTRINS/CN L13 ANSWER 1 OF 1 REGISTRY COPYRIGHT 2002 ACS Spectrins CN Spectrins (CA INDEX NAME) OTHER NAMES: CN Proteins, specific or class, spectrins CN Proteins, spectrins CN Spectrins, dimers CN Tektins A Name Searching

84 84 Biosequence name searching has many applications. It can be used to find specific sequences, as well as to refine subsequence searches. Three techniques will be highlighted: Chemical name searching for specific, precisely defined biosequence names, such as trade names and common names Controlled term searching for certain classes of proteins Combination strategies - combining sequence searching with controlled term or name fragment searching Name Searching

85 85 The REGISTRY file is very useful for finding sequences for very specific proteins or nucleic acids. Access to the biosequence records is possible using Common names Trade names Systematic names In almost all cases, it is necessary to identify first the preferred CA Index Name of the biosequence. Name Searching

86 86 Search Question: Find the sequence and references to human enolase. Name Searching

87 87 => FILE REGISTRY => E ENOLASE/CN E1 1 ENOL-LUTEOVIS/CN E2 1 ENOL-PYRUVYL 3-SHIKIMYL ETHER/CN E3 1 --> ENOLASE/CN E4 1 ENOLASE (2-PHOSPHO-D-GLYCERATE HYDROYLASE) ARABIDOPSIS THAL IANA GENE AT2G29560)/CN o o o => S E3 L1 1 ENOLASE/CN Name Searching

88 88 => D L1 ANSWER 1 OF 1 REGISTRY COPYRIGHT 2001 ACS RN REGISTRY CN Hydratase, phosphoenolpyruvate (9CI)(CA INDEX NAME) OTHER NAMES: CN Antigens CN 2-Phosphoglycerate dehydratase CN 2-Phosphoglycerate enolase o o o CN Antigens, TLA-a (thermolabile antigen a) CN E.C CN Enolase CN Phosphoenolpyruvate hydratase CN Phosphoglycerohydratase CN Phosphopyruvate hydratase CN TLA-a antigens MF Unspecified CI MAN (continued on next page) This is not a sequence record. We know this because there is no FS (file segment) entry. The CA Index Name is the first name in the record. Name Searching

89 89 => S HYDRATASE (L) PHOSPHOENOLPYRUVATE 766 HYDRATASE 510 PHOSPHOENOLPYRUVATE L2 126 HYDRATASE (L) PHOSPHOENOLPYRUVATE => S L2 AND PS/FS PS/FS L3 67 L2 AND PS/FS (L) proximity is used to ensure that both name fragments appear in the same name. Name Searching

90 90 => D SCAN L3 L3 67 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Hydratase, phosphoenolpyruvate (Schistosoma japonicum clone C30 reduced) (9CI) SQL 434 MF Unspecified CI MAN *** STRUCTURE DIAGRAM IS NOT AVAILABLE *** *** USE 'SQD' OR 'SQIDE' FORMATS TO DISPLAY SEQUENCE *** HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 (continued on next page) This enolase is from Schistosoma. Name Searching

91 91 Organism names used in the sequence descriptor are CA-preferred names. For example, the term cattle is preferred, not ox, bovine, or cow. The CA Lexicon is a good resource to identify CA-preferred names for organisms. => FILE CAPLUS => E COW/CT E# FREQUENCY AT TERM E1 0 2 COVISIL 9760/CT E2 0 2 COVULCANIZATION/CT E > COW/CT o o o => E E3+ALL E1 0 --> Cow/CT E USE Cattle/CT ********* END*** => FILE REGISTRY => S L3 AND CATTLE Name Searching

92 92 => e human/ct E# FREQUENCY AT TERM E1 0 2 HULZ 70C/CT E2 0 2 HUMACITE/CT E > HUMAN/CT..... Name Searching

93 93 => e e3+ all E BT6 Eukaryote (Eukaryotae)/CT E BT5 Metazoan (Metazoa)/CT E BT4 Vertebrate (Vertebrata)/CT E BT3 Mammal (Mammalia)/CT E BT2 Primate/CT E18 16 BT1 Homo/CT E > Human/CT HN Valid heading during volume 136 (2002) to present Name Searching

94 94 => S L3 AND HUMAN HUMAN 1 HUMANS HUMAN (HUMAN OR HUMANS) L4 4 L3 AND HUMAN Name Searching

95 95 => D SCAN IN L4 4 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Hydratase, phosphoenolpyruvate (human isoenzyme.alpha.) (9CI) HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):3 L4 4 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Hydratase, phosphoenolpyruvate (human isoenzyme.alpha.) (9CI) L4 4 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Hydratase, phosphoenolpyruvate (human clone B.21.beta.-subunit reduced) (9CI) L4 4 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Hydratase, phosphoenolpyruvate (human lung clone HLE1.alpha.-isoform reduced) (9CI) ALL ANSWERS HAVE BEEN SCANNED Name Searching

96 96 => D SQIDE 1-4 L4 ANSWER 1 OF 4 REGISTRY COPYRIGHT 2001 ACS RN REGISTRY CN Hydratase, phosphoenolpyruvate (human isoenzyme.alpha.) (9CI) (CA INDEX NAME) FS PROTEIN SEQUENCE SQL 57 SEQ 1 GLELLKTAIG KAGYTDKVVI GMDVAASEFF RSGKYDLDFK SPDDPSRYIS 51 PDQLADL MF C280 H437 N69 O89 S CI MAN SR CA LC STN Files: CA, CAPLUS 1 REFERENCES IN FILE CA (1967 TO DATE) 1 REFERENCES IN FILE CAPLUS (1967 TO DATE) Name Searching

97 97 => FILE CAPLUS => S L4 L5 5 L4 => D TI SO 1-5 L5 ANSWER 1 OF 5 CAPLUS COPYRIGHT 2001 ACS TI Identification of an epitope of.alpha.-enolase (a candidate plasminogen receptor) by phage display SO Thromb. Haemostasis (1997), 78(3), CODEN: THHADQ; ISSN: L5 ANSWER 2 OF 5 CAPLUS COPYRIGHT 2001 ACS TI An expression profile of active genes in human colonic mucosa SO DNA Res. (1994), 1(1), CODEN: DARSE8; ISSN: Name Searching

98 98 p. 52 Search Question: Find the sequence and references for rat differentiation-retarding factor, which is associated with leukemia. Name Searching

99 99 In order to determine that this class of biosequences is not indexed by CAS RN, a likely first step is to conduct a REGISTRY search. In this case, the closest name match is to a different class of proteins. => FILE REGISTRY => E DIFFERENTIATION-RETARDING FACTOR/CN E1 1 DIFFERENTIATION-INDUCING FACTOR 3/CN E2 1 DIFFERENTIATION-INDUCING-FACTOR DECHLORINASE/CN E3 0 --> DIFFERENTIATION-RETARDING FACTOR/CN E4 1 DIFFERENTIATION-STIMULATING FACTOR RECEPTOR (MOUSE STRAIN o o o Name Searching

100 100 => E DIFFERENTIATION RETARDING FACTOR/CN E1 1 DIFFERENTIATION FACTOR P48 (MYCOPLASMA FERMENTANS CLONE SMP RECURSOR)/CN E2 1 DIFFERENTIATION FACTOR, MONOCYTES/MACROPHAGE (HUMAN TCO-1 CELL)/CN E3 0 --> DIFFERENTIATION RETARDING FACTOR/CN E4 1 DIFFERENTIATION REVERSAL FACTOR/CN o o o Name Searching

101 101 => FILE CAPLUS => E DIFFERENTIATION RETARDING FACTOR/CT 5 E# FREQUENCY AT TERM E1 0 2 DIFFERENTIATION ANTIGENS/CT E DIFFERENTIATION INDUCERS/CT E3 0 --> DIFFERENTIATION RETARDING FACTOR/CT E4 0 3 DIFFERENTIATION, ADIPOCYTE/CT E5 0 2 DIFFERENTIATION, MAGMA/CT The term is tested with and without the internal hyphen. Name Searching

102 102 => E DIFFERENTIATION-RETARDING FACTOR/CT 5 E# FREQUENCY AT TERM E1 0 2 DIFFERENTIATION-REGULATED TRANSCRIPTION FACTOR 1 RNA FORMATION FACTORS/CT E2 0 1 DIFFERENTIATION-RETARDING/CT E > DIFFERENTIATION-RETARDING FACTOR/CT E4 0 1 DIFFERENTIATION-STIMULATING/CT E5 0 1 DIFFERIN/CT => E E3+ALL E1 0 --> Differentiation-retarding factor/CT E2 684 USE Leukemia inhibitory factor/CT ********* END*** Name Searching

103 103 => FILE REGISTRY => E E2/CN 5 E1 1 LEUKEMIA CELL DIFFERENTIATION FACTOR (HUMAN CLONE FDH7/FDE KILODALTON PRECURSOR)/CN E2 1 LEUKEMIA INHBITORY FACTOR RECEPTOR (RAT LIVER SUBUNIT.ALPHA.)/CN E3 0 --> LEUKEMIA INHIBITORY FACTOR/CN E4 1 LEUKEMIA INHIBITORY FACTOR (121- TRYPTOPHAN,135-ISOLEUCINE,197- VALINE) (RAT PRECURSOR)/CN E5 1 LEUKEMIA INHIBITORY FACTOR (CATTLE)/CN EXPAND is used to verify the controlled term in the Chemical Name index. Name Searching

104 104 => S LEUKEMIA (W) INHIBITORY (W) FACTOR 2235 LEUKEMIA 673 INHIBITORY FACTOR 157 FACTORS FACTOR (FACTOR OR FACTORS) L2 73 LEUKEMIA (W) INHIBITORY (W) FACTOR Name segments are searched in the Basic Index of REGISTRY. Name Searching

105 105 => S L2 AND PS/FS PS/FS L3 50 L2 AND PS/FS => S L3 AND (RAT OR RATTUS) RAT 4 RATS RAT (RAT OR RATS) RATTUS L4 3 L3 AND (RAT OR RATTUS) The organism name was obtained using the CA Lexicon. PS = Protein Sequences, FS = File Segment Name Searching

106 106 => D SQIDE 1-3 L4 ANSWER 1 OF 3 REGISTRY COPYRIGHT 2001 ACS RN REGISTRY CN Leukemia inhibitory factor [121-tryptophan,135- isoleucine,197-valine] (rat precursor) (9CI) (CA INDEX NAME) OTHER NAMES: CN Cholinergic neuronal differentiation factor [121- tryptophan,135-isoleucine,197-valine] (rat precursor) FS PROTEIN SEQUENCE SQL 202 SEQ 1 MKVLAAGIVP LLLILHWKHG AGSPLPITPV NATCAIRHPC HGNLMNQIKS 51 QLAQLNGSAN ALFISYYTAQ GEPFPNNVDK LCAPNMTDFP PFHANGTEKT 101 KLVELYRMVA YLGASLTNIT WDQKNLNPTA VSLQIKLNAT TDVMRGLLSN 151 VLCRLCNKYH VGHVDVPCVP DNSSKEAFQR KKLGCQLLGT YKQVISVVVQ 201 AF MF Unspecified CI MAN SR CA (continued on next slide) Name Searching

107 107 => FILE CAPLUS => S L4 L5 3 L4 => D TI SO 1-3 L5 ANSWER 1 OF 3 CAPLUS COPYRIGHT 2001 ACS TI Stimulation of nerve growth and/or vitality by cholinergic neuronal differentiation factor SO U.S., 6 pp., Cont.-in-part of U.S. Ser. No. 451,635, abandoned. CODEN: USXXAM L5 ANSWER 2 OF 3 CAPLUS COPYRIGHT 2001 ACS TI Asparagine-linked glycosylation of the rat leukemia inhibitory factor expressed by simian COS7 cells SO Biosci., Biotechnol., Biochem. (1998), 62(7), CODEN: BBBIEJ; ISSN: o o o Name Searching

108 108 Within the substance-based files, biomolecule name (or descriptive) information appears in the following fields. The Basic Index (/BI) of these files includes the single words appearing in these descriptive fields and usually represents the best search field. Name Searching

109 109 Each record in REGISTRY, DGENE, and GENBANK represents one substance. To retrieve literature indexed to these substances, the following strategies are recommended : Name Searching

110 110

111 111 Search Question: Retrieve journal and patent literature describing FSH-like receptors.

112 112 Important Search Concepts: Major concepts — must be present for relevance FSH receptors Follicle-stimulating hormone receptors GPCR or G-protein coupled receptors (may be too broad, depending on client needs) Minor concepts — may be used for refinement Agonist Antagonist Antibody Ligand

113 113 Online thesauri such as the CA Lexicon in CAplus or MeSH in MEDLINE may provide information on a class of biomolecules. Explore FSH receptors in the CA Lexicon: => FILE HCAPLUS => SET EXPAND CONTINUOUS => SET ABBREV ON; SET PLURALS ON (continued on next slide)

114 114 => E FSH RECEPTORS/CT E# FREQUENCY AT TERM E1 0 1 FSE/CT E2 0 1 FSH/CT E > FSH RECEPTORS/CT E4 0 1 FSH-FORMING/CT E5 0 2 FSH-FORMING CELL ANTERIOR LOBE PITUITARY GLAND/CT E6 0 1 FSH-PRODUCING/CT E7 0 2 FSH-PRODUCING CELL ANTERIOR LOBE PITUITARY GLAND/CT E8 0 1 FSH-SECRETING/CT E9 0 2 FSH-SECRETING CELL ANTERIOR LOBE PITUITARY GLAND/CT E FSL/CT E FSL 300/CT E FSM/CT (continued on next slide)

115 115 => E E3+ALL E BT3 Proteins/CT E BT2 Receptors/CT E BT1 G protein-coupled receptors/CT E BT4 Proteins/CT E BT3 Receptors/CT E BT2 G protein-coupled receptors/CT E BT4 Proteins/CT E BT3 Receptors/CT E BT2 Protein receptors/CT E BT1 Gonadotropin receptors/CT E BT3 Proteins/CT E BT2 Receptors/CT E BT1 Protein receptors/CT E > FSH receptors/CT HN Valid heading during volume 126 (1997) to present. E27 OLD Receptors (L) FSH/CT E28 UF Follitropin receptors/CT ********* END*** FSH Receptors has been a valid controlled term since Its use will result in precise search results. If broader retrieval is desired, terms such as the following can be used: Protein receptors Gonadotropin receptors G protein-coupled receptors

116 116 Search for indexed records: => S E26+PFT L1 915 "FSH RECEPTORS"+PFT/CT (3 TERMS) The PFT relationship code is used to search for OLD, NEW and UF terms.

117 117 Search for non-indexed records: => S FSHR OR (FOLLICLE STIMULAT? OR FSH OR FOLLITROPIN) (3A) RECEPTOR L FSHR OR (FOLLICLE STIMULAT? OR FSH OR FOLLITROPIN) (3A) RECEPTOR => S L2 NOT L1 L3 738 L2 NOT L1 (continued on next page) (3A) proximity ensures that search terms are closely associated with one another, in either order.

118 118 => S L2 AND NONINDEXED/FS NONINDEXED/FS L4 32 L2 AND NONINDEXED/FS => D SCAN L4 32 ANSWERS HCAPLUS COPYRIGHT 2002 ACS CC 3 (Biochemical Genetics) TI Stability of human follicle-stimulating hormone receptor mRNA in stably transfected cells HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1 L4 32 ANSWERS HCAPLUS COPYRIGHT 2002 ACS CC 3 (Biochemical Genetics) TI Stage-dependent expression of androgen receptor and FSH receptor in adult rat testis ST androgen receptor cellular localization expression pattern; FSH receptor testis testosterone spermatogenesis HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 (continued on next slide) Some of these records will be of marginal interest. But some, especially those from the non-indexed portion of the file may be very relevant. The File Segment index (/FS) clearly differentiates records that are indexed from those that are not.

119 119 => S L1 OR L4 L5 947 L1 OR L4 => S L5 AND PY> PY>1999 L6 172 L5 AND PY>1999

120 120 ANALYZE the answer set for highly posted terms: => ANALYZE L6 1- CT IC NCL L7 ANALYZE L6 1- CT IC NCL : 889 TERMS CT = controlled terminology IC = international patent class NCL = US national patent class

121 121 => D CT TOP20 DOC L7 ANALYZE L6 1- CT IC NCL : 889 TERMS TERM # # OCC # DOC % DOC CT IC NCL FSH RECEPTORS OVARY GONADOTROPIN RECEPTORS SIGNAL TRANSDUCTION, BIOLOGICAL GENE, ANIMAL TESTIS CELL PROLIFERATION MRNA MUTATION STRUCTURE-ACTIVITY RELATIONSHIP FERTILITY PROTEIN MOTIFS THYROTROPIN RECEPTORS PROTEINS, SPECIFIC OR CLASS (continued on next slide) The display code TOP20 shows the top 20 controlled indexing terms from the answer set. Results confirm that the majority of retrieved records do have FSH Receptors as a controlled term.

122 122 => D IC DGT2 L7 ANALYZE L6 1- CT IC NCL : 889 TERMS TERM # # OCC # DOC % DOC CT IC NCL C12N C12Q C12N C07K C07K A61K A61K C12N The top international patent classes appearing on 3 or more patent documents. The display code DGT2 shows answers with document counts >2. Any number may be used here. In the File PATIPC verify the IC meanings.

123 123 IC summary:

124 124 Expand search to include “receptor” IC classes: => S (C07K /IC OR C07K014-72/IC) AND (FSH OR FOLLICLE STIMULAT? OR FOLLITROPIN) L8 11 (C07K /IC OR C07K014-72/IC) AND (FSH OR FOLLICLE STIMULAT? OR FOLLITROPIN) Expand search to include “FSH” IC class: => S A61K038-24/IC AND RECEPTOR L9 15 A61K038-24/IC AND RECEPTOR => S (L8 OR L9) AND PY> PY>1999 L10 20 (L8 OR L9) AND PY>1999

125 125 Isolate unique records: => S L10 NOT L6 L11 11 L10 NOT L6 11 additional patent records of possible interest. Combine results: => S L6 OR L11 L L6 OR L11

126 126 Test exact matches on biomolecule names: => FILE REGISTRY => E FSH RECEPTORS/CN E165 1 FSH RECEPTOR (SHEEP CLONE S3352A 670- AMINO ACID RESIDUE ISOFORM PRECURSOR)/CN E166 1 FSH RECEPTOR (THALARCTOS MARITIMUS)/CN E > FSH RECEPTORS/CN E168 1 FSH-BI/CN E169 1 FSH-BINDING INHIBITOR/CN E170 1 FSH-P/CN E171 1 FSH-RELEASING FACTOR/CN E172 1 FSH-RELEASING HORMONE/CN E173 1 FSH-RH/CN E174 1 FSH36/CN E175 1 FSI1/CN E176 1 FSJ-III/CN

127 127 => E FOLLITROPIN E FOLLISTATIN/BI E178 1 FOLLISTREL/BI E > FOLLITROPIN/BI E180 1 FOLLORMON/BI E181 6 FOLLOWING/BI E182 1 FOLLTROPIN/BI E183 1 FOLLUTEIN/BI E184 1 FOLNIT/BI E185 1 FOLOBUS/BI E186 1 FOLOGE/BI E187 1 FOLOGENON/BI E188 6 FOLONE/BI

128 128 => E FSH E189 1 FSGSH/BI E190 2 FSGTP1/BI E > FSH/BI E192 4 FSH.BETA./BI E193 3 FSH05/BI E194 1 FSH1/BI E195 1 FSH15W6/BI E196 2 FSH16/BI E197 1 FSH2/BI E198 2 FSH22/BI E199 8 FSH23/BI E200 2 FSH24/BI

129 129 => S FSHR OR (FSH OR FOLLITROPIN OR FOLLICLE STIMULAT?) (L) RECEPTOR L FSHR OR (FSH OR FOLLITROPIN OR FOLLICLE STIMULAT?) (L) RECEPTOR Note: (L) proximity is used to ensure that name segments appear in the same name.

130 130 => FILE HCAPLUS => s l13 and py> L PY>1999 L14 15 L13 AND PY>1999

131 131 Combining results of text- and substance-based searches: => S L14 OR L12 L L14 OR L12 Isolating unique records from the substance search: => S L14 NOT L12 L16 3 L18 NOT L15

132 132 The DGENE file, from Derwent, includes records for individual sequences indexed from the patent records that are also added to the WPINDEX record. Each sequence record provides more detail about the sequence itself, whereas the WPINDEX file includes more information about the invention. Extending the search to DGENE

133 133 The sequence information is indexed into three fields in DGENE:

134 134 Conducting a free-text name segment search: => FILE DGENE => S (FSHR OR (FSH OR FOLLITROPIN OR FOLLICLE STIMULAT?) (L) RECEPTOR)/FEAT, KW, DESC L (FSHR OR (FSH OR FOLLITROPIN OR FOLLICLE STIMULAT?) (L) RECEPTOR)/FEAT,KW,DESC => D TRIAL 1-2 L17 ANSWER 1 OF 117 DGENE COPYRIGHT 2002 DERWENT INFORMATION LTD AN AAM47959 Protein DGENE TI New polynucleotide, useful for treating Alzheimer's disease, Parkinson's disease, Huntington's chorea, diabetes and tumours, comprises isolated polynucleotide encoding human follicle stimulating hormone-like G- protein coupled receptor - DESC Lymnaea stagnalis GPCR GRL101 precursor protein SEQ ID NO 3. (continued on next page)

135 135 => FILE WPINDEX => TRANSFER L17 PN ENTER ANSWER NUMBERS, RANGES (1-), OR ?:1- L18 TRANSFER L17 1- PN : 12 TERMS L19 12 L18 => S L19 AND PY.B> PY.B>1999 (PY.B>1999) L20 3 L19 AND PY.B>1999 The TRANSFER command selected 12 PN terms. This implies that the 117 sequences were described in 12 patents.

136 136 Dictionary searching Find polypeptides like Consupren used in drugs delivery

137 137 => consupren/cn L1 1 CONSUPREN/CN => d Dictionary searching

138 138 => ps/fs and ratc>=30(s)c n/relf(s)nrrs=1 and c h n o/elf PS/FS RATC>= C N/RELF NRRS= RATC>=30(S)C N/RELF(S)NRRS= C H N O /ELF L PS/FS AND RATC>=30(S)C N/RELF(S)NRRS=1 AND C H N O/ELF => fil caplus Dictionary searching

139 139 => l1(l)drug(1a)deliv? L DRUG DRUGS DRUG (DRUG OR DRUGS) DELIV? L2 28 L1(L)DRUG(1A)DELIV? => d hitstr Dictionary searching

140 140 Dictionary searching

141 141 Monitoring Drug Developments

142 142 Are there pharmaceuticals, containing the following piece of structure, under phase tests? The ring system is isolated. Who are the owners of the patents? Monitoring Drug Developments

143 143 Monitoring Drug Developments => fil reg => c3o-c6-c6-c8/ea and c16o/rf and rps/ci 7467 C3O-C6-C6-C8/EA C16O/RF RPS/CI L1 1 C3O-C6-C6-C8/EA AND C16O/RF AND RPS/CI => d rsd L1 ANSWER 1 OF 1 REGISTRY COPYRIGHT 2003 ACS Ring System Data Elemental | Elemental | Size of |Ring System| Ring | RID Analysis | Sequence |the Rings| Formula |Identifier|Occurrence EA | ES | SZ | RF | RID | Count ============+============+=========+===========+==========+========== C3O-C6-C6-C8|OC3-C6-C6-C8| |C16O | |1 => /rid L /RID

144 144 Monitoring Drug Developments => fil medline => e phase/ct E# FREQUENCY AT TERM E1 100 PHARYNX: VI, VIROLOGY/CT E2 0 2 PHARYNXS/CT E > PHASE/CT E4 0 1 PHASE 1/CT E5 0 2 PHASE 1 CLINICAL TRIALS/CT E6 0 1 PHASE 2/CT E7 0 2 PHASE 2 CLINICAL TRIALS/CT => e e7+all E > Phase 2 Clinical Trials/CT E USE Clinical Trials, Phase II/CT

145 145 Monitoring Drug Developments => l2 and (clinical trials, phase I)/ct L3 93 L2 AND (CLINICAL TRIALS, PHASE I)/CT => sel hit rn SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details NO TERMS MATCH REQUESTED CRITERIA => sel rn SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details L4 SEL L3 1- RN : 57 TERMS

146 146 Monitoring Drug Developments => l2 and (clinical trials, phase II)/ct 6967 L (CLINICAL TRIALS, PHASE II)/CT (9 TERMS) ('CLINICAL TRIALS, PHASE II'+XUSE/CT) L5 186 L2 AND (CLINICAL TRIALS, PHASE II)/CT => sel rn SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details L6 SEL L5 1- RN : 65 TERMS

147 147 Monitoring Drug Developments => l2 and (clinical trials, phase III)/ct 6967 L (CLINICAL TRIALS, PHASE III)/CT (9 TERMS) ('CLINICAL TRIALS, PHASE III'+XUSE/CT) L7 88 L2 AND (CLINICAL TRIALS, PHASE III)/CT => sel rn SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details L8 SEL L7 1- RN : 38 TERMS

148 148 Monitoring Drug Developments => l2 and (clinical trials, phase IV)/ct 6967 L2 59 (CLINICAL TRIALS, PHASE IV)/CT (9 TERMS) ('CLINICAL TRIALS, PHASE IV'+XUSE/CT) L9 0 L2 AND (CLINICAL TRIALS, PHASE IV)/CT

149 149 Monitoring Drug Developments => fil reg => d his FILE 'REGISTRY' ENTERED AT 05:20:49 ON 24 MAR 2003 L1 1 C3O-C6-C6-C8/EA AND C16O/RF AND RPS/CI L /RID FILE 'MEDLINE' ENTERED AT 05:24:28 ON 24 MAR 2003 L3 93 L2 AND (CLINICAL TRIALS, PHASE I)/CT L4 SEL L3 1- RN : 57 TERMS L5 186 L2 AND (CLINICAL TRIALS, PHASE II)/CT L6 SEL L5 1- RN : 65 TERMS L7 88 L2 AND (CLINICAL TRIALS, PHASE III)/CT L8 SEL L7 1- RN : 38 TERMS L9 0 L2 AND (CLINICAL TRIALS, PHASE IV)/CT

150 150 Monitoring Drug Developments => l4 and l2 L11 2 L10 AND L2

151 151 Monitoring Drug Developments => l6 and l2 L13 2 L12 AND L2 => l8 and l2 L15 2 L14 AND L2 => l11 or l13 or l15 L16 2 L11 OR L13 OR L15

152 152 Monitoring Drug Developments => fil embase => e phase/ct E# FREQUENCY AT TERM E16 3 PHASCOLOPSIS GOULDII/CT E17 2 PHASCOLOSOMINE/CT E > PHASE/CT E PHASE 1 CLINICAL STUDY/CT E PHASE 1 CLINICAL TRIAL/CT E PHASE 1 STUDY/CT E PHASE 1 TRIAL/CT E PHASE 2 CLINICAL STUDY/CT E PHASE 2 CLINICAL TRIAL/CT E PHASE 2 STUDY/CT E PHASE 2 TRIAL/CT E PHASE 3 CLINICAL TRIAL/CT => e e19+all E > phase 1 clinical study/CT E USE phase 1 clinical trial/CT ********* END***

153 153 Monitoring Drug Developments => l2 and e20+all L "PHASE 1 CLINICAL TRIAL"+ALL/CT (11 TERMS) L L2 AND "PHASE 1 CLINICAL TRIAL"+ALL/CT => sel l17 hit rn SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details L19 SEL L17 1- RN HIT : 4 TERMS

154 154 Monitoring Drug Developments => l2 and e24+all L "PHASE 2 CLINICAL TRIAL"+ALL/CT (11 TERMS) L L2 AND "PHASE 2 CLINICAL TRIAL"+ALL/CT => sel hit rn SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details L21 SEL L20 1- RN HIT : 4 TERMS

155 155 Monitoring Drug Developments => fil reg => l19 or l21 L24 4 L22 OR L23

156 156 Monitoring Drug Developments

157 157 ADISINSIGHT –Drugs in active R&D - initial report to market launch –Bibliographic references and Lehman Bros PharmaPipeline Data –ADIS R&D Insight Monitoring Drug Developments

158 158 DRUGUPDATES –Drugs in active R&D –Biotechnological products, mixtures, new formulations –IMSworld R&D Focus Monitoring Drug Developments

159 159 PHAR –Pharmaceutical products under development in world’s major markets –Discontinued drugs –PharmaProjects Monitoring Drug Developments

160 160 CAS RN’s Chemical names Combination of CAS RN’s and chemical names Monitoring Drug Developments Searching with:

161 161 Locate information on the development of an antimigraine drug, related to Sumatriptan, named Nomig Monitoring Drug Developments

162 162 Identify relevant substance terms from the REGISTRY File Conduct a multifile search of the substance terms Display results Monitoring Drug Developments

163 163 Complete chemical name search –Expand or Search in /CN Search key name fragments and analyze results –Search in /CNS Monitoring Drug Developments

164 164 => FILE REGISTRY => E NOMIG/CN 5 E1 1 NOMIFENSINE MALEATE/CN E2 1 NOMIFENSINE N-GLUCURONIDE/CN E3 0 --> NOMIG/CN E4 1 NOMILEN/CN E5 1 NOMILIN/CN NOMIG is not indexed in REGISTRY Monitoring Drug Developments

165 165 => S ?TRIPTAN?/CNS L1 25 ?TRIPTAN?/CNS CNS supports left handed truncation Monitoring Drug Developments CNS is also available, with left handed truncation, in ADISINSIGHT and DRUGUPDATES

166 166 Monitoring Drug Developments => sel name SmartSELECT INITIATED New TRANSFER and ANALYZE Commands Now Available See HELP TRANSFER and HELP ANALYZE for Details L2 SEL L1 1- NAME : 98 TERMS => d 1-98 ans L2 SEL L1 1- NAME : 98 TERMS TERM # # OCC # DOC % DOC NAME ZOLMITRIPTAN (ANS: 18) ZOMIG (ANS: 18) ,2,3-TRIMETHYLBUTANE ********* END OF L2 ***

167 167 => D L1 18 IDE L1 ANSWER 14 OF 21 REGISTRY COPYRIGHT 1999 ACS RN REGISTRY CN 2-Oxazolidinone, 4-[[3-[2-(dimethylamino)ethyl]-1H- indol-5-yl]methyl]-,(4S)- (9CI) (CA INDEX NAME) O O O CN 311C90 CN BW 311C90 CN Zolmitriptan CN Zomig FS STEREOSEARCH MF C16 H21 N3 O2 CI COM SR CA (continued) Monitoring Drug Developments

168 168 LC STN Files: ADISINSIGHT, BIOBUSINESS, BIOSIS, CA, CANCERLIT, CAPLUS,CASREACT, CIN, DDFU, DRUGNL, DRUGPAT, DRUGU, DRUGUPDATES, EMBASE, IPA, MEDLINE, MRCK*, PHAR, PROMT, TOXLINE, TOXLIT, USAN, USPATFULL (*File contains numerically searchable property data) Absolute stereochemistry. 77 REFERENCES IN FILE CA (1967 TO DATE) 1 REFERENCES TO NON-SPECIFIC DERIVATIVES IN FILE CA 77 REFERENCES IN FILE CAPLUS (1967 TO DATE) Monitoring Drug Developments

169 169 Synonyms from REGISTRY File may useful when CAS RN’s are not indexed SELECT CHEM creates an E-numbered list of search terms Also available in USAN, MRCK Monitoring Drug Developments

170 170 => SEL CHEM L1 18 E13 THROUGH E18 ASSIGNED => D SEL E13-E18 E13 1 (S)-4-((3-(2-(DIMETHYLAMINO)ETHYL) -1H-INDOL-5-YL)METHYL)-2- OXAZOLIDINONE/BI E14 1 BW 311C90/BI E15 1 ZOLMITRIPTAN/BI E16 1 ZOMIG/BI E /BI E C90/BI Monitoring Drug Developments

171 171 => FILE ADISINSIGHT DRUGUPDATES PHAR => SET MSTEPS ON => S E17 L3 1 FILE ADISINSIGHT L4 1 FILE DRUGUPDATES L5 1 FILE PHAR TOTAL FOR ALL FILES L /BI Monitoring Drug Developments

172 172 => FILE ADISINSIGHT DRUGUPDATES PHAR => S E14-E16,E18/CN L7 1 FILE ADISINSIGHT L8 1 FILE DRUGUPDATES L9 1 FILE PHAR TOTAL FOR ALL FILES L10 3 ("BW 311C90"/BI OR ZOLMITRIPTAN/BI OR ZOMIG/BI OR 311C90/BI) Monitoring Drug Developments

173 173 Often preferable to use the ALL format HELP FORMAT, HELP DFIELDS HELP COST Substantial subscriber discounts are available Monitoring Drug Developments

174 174 ADISINSIGHT Record => D L6 ALL 1-3 L6 ANSWER 1 OF 3 ADISINSIGHT COPYRIGHT 1999 (ADIS) AN 1998:2524 ADISINSIGHT SO Adis R&D Insight DN CDAT Aug 12, 1999 CN Zolmitriptan CN 311C; 311C90 CN S-4((3-(2-(Dimethylamino)ethyl)-1H-indol-5-yl) methyl)- 2-oxazolidinone CN Zomig; Zomigon MF C16 H21 N3 O2 RN STR Absolute stereochemistry. Monitoring Drug Developments

175 175 CC EPHMRA ATC CODE: N2C Anti-Migraine Preparations CC WHO ATC CODE: N02C-C Selective serotonin 1 receptor agonists HDP Launched DSTA Launched, Argentina, Migraine Launched, Bulgaria, Migraine Launched, Denmark, Migraine Launched, Finland, Migraine Launched, France, Migraine Launched, Germany, Migraine o o o ORIGINATOR: Burroughs Wellcome (United Kingdom) PARENT: Glaxo Wellcome LICENSEE: AstraZeneca OTHER: Cephalon ADISINSIGHT Record Monitoring Drug Developments

176 176 TX TEXT Introduction: o o o TX EVALUATION: Migraine 59 (PO). TX COMMERCIAL SUMMARY: Migraine acute treatment / 5HT-1 agonist Company Region Launch Date Peak Sales Patent Exp ASTRAZENECA Jap 2002 $50m 2012 ASTRAZENECA US Mar-1998 $300m 2012 ASTRAZENECA ex US,Jap Mar-1997 $220m Jun Copyright (C) Lehman Brothers International. ADISINSIGHT Record Monitoring Drug Developments

177 177 TX PHARMACOLOGY OVERVIEW: Pharmacodynamics: Antimigraine activity Mechanism of action: Serotonin 1D receptor agonists Serotonin 1 receptor agonists Serotonin receptor agonists TX CLINICAL OVERVIEW o o o TX THERAPEUTIC TRIALS o o o RDAT RNTE 12 Aug 1999 Sales forecasts reviewed by Lehman Bro 23 Jun 1999 A study in patients with cluster headache has been added to the therapeutic trials field ADISINSIGHT Record Monitoring Drug Developments

178 178 RE 1. Dixon R, Gillotin C, et al. The pharmacokinetics and effects on blood pressure of multiple doses of the novel anti-migraine drug zolmitriptan (311C90) in healthy volunteers. British Journal of Clinical Pharmacology. 43: , Mar (English) o o o ADISINSIGHT Record Monitoring Drug Developments

179 179 DRUGUPDATES Record L6 ANSWER 2 OF 3 DRUGUPDATES COPY 1999 IMSWORLD AN 93:3223 DRUGUPDATES SO R&D Focus, (26 Apr 1999) CN zolmitriptan RE pINN CN 311C90; BW 311C90 CN ZOMIG CN (4S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol- 5-yl]methyl]-2-oxazolidinone RN STR Absolute stereochemistry. Monitoring Drug Developments

180 180 RN Der: (4S), zolmitriptan (4S), monohydrochloride (4S), monobenzoate (4S), maleate (1:1) (4S), cpd with succinic acid(1:1) (4R), monohydrochloride no stereo, monohydrochloride no stereo no stereo, monoacetate CC N2C Antimigraine Preparations CT Indication: migraine Pharmacology: 5HT agonist; 5HT1Dalpha agonist; 5HT1Dbeta agonist; 5HT1B agonist HDP Marketed (80) DRUGUPDATES Record Monitoring Drug Developments

181 181 LI UPDATE: Zeneca merger with Astra. AstraZeneca has launched the 5HT1D agonist zolmitriptan (ZOMIG) in France for the treatment of migraine. o o o DSTA Type | Status |Stage| Region =======+==========+=====+==================== Highest|Marketed |80 | Phase | | | Phase |Marketed | |United States Phase |Marketed | |United Kingdom o o o DRUGUPDATES Record Monitoring Drug Developments

182 182 CO Type | Company | Nationality | Region ==========+==============+==============+============ Originator|Glaxo Wellcome|United Kingdom| Licensee |AstraZeneca |United Kingdom|Worldwide Other |Cephalon |United States |UK Assignee |Wellcome | | DRUGUPDATES Record Monitoring Drug Developments

183 183 TX Patent Summary: Product: WO 91/ , priority GB , designating 25 states. Equivalents identified in nine countries. Commercial Summary: AstraZeneca (previously o o o Scientific Summary: Zolmitriptan o o o RDAT: APR 1999 RNTE: Zeneca merger with Astra. DEC 1998 Cephalon to copromote in the UK. JUN 1998 Marketed, France. APR 1998 Phase II, Japan. o o o JAN 1992 Preclinical, UK. JUN 1990 Priority product patent AB 10th MTIS, 5-8th September In a o o o DRUGUPDATES Record Monitoring Drug Developments

184 184 IDETAB –Based on CAS RN CCTAB –Based on Therapeutic Classification COTAB –Based on Company Name DRUGUPDATES Tabular Display Monitoring Drug Developments

185 185 L6 ANSWER 3 OF 3 PHAR COPYRIGHT 1999 PJB AN 94 PHAR DN CN zolmitriptan CN 311C CN 311C90 CN AscoTop CN BW-311C90 CN Zomig CN Zomigon CN 2-Oxazolidinone,4-((3-(2-(dimethylamino)ethyl)- 1H-indol-5-yl)methyl)-,(S)- (CAS) RN STA Active PHAR Record Monitoring Drug Developments

186 186 CO Type |Company Name(Country) |Develop Status ==========+===========================+============== Originator|AstraZeneca(United Kingdom)|Launched SO Pharmaprojects. PJB Publications Ltd., TX Zolmitriptan (311C90) is a dual action 5-HT1D/1B receptor agonist originally synthesized by Glaxo Wellcome (GW), but o o o PHAR Record Monitoring Drug Developments

187 187 MARKETING GW signed a memorandum with AstraZeneca to divest zolmitriptan to the latter, in accordance with the US FTC consent order regarding the GW o o o CLINICAL It is in Phase III trials as a nasal spray, o o o ADDITIONAL CLINICAL INFORMATION POST MARKETING o o o DSTA WORLD: LAUNCHED Australia: Launched 1997 Austria: Launched 1997 PHAR Record Monitoring Drug Developments

188 188 CC N8A ANTIMIGRAINE CT INDICATION: MIGRAINE ORGM CH-SY (CHEMICAL SYNTHESIS, SYNTHETIC) RTE A-PO (ALIMENTARY, PO); R-NA (RESPIRATORY, TRANSNASAL) RDAT RNTE ##NEW PRODUCT ##Compound identified Pharmaprojects No ##Status changed Phase II Clinical Trial o o o PHAR Record Monitoring Drug Developments

189 189 PHCD 5HT-1-D-AG; Receptor, Hormonal, 5 Hydroxytryptamine 1D agonist; 5HT1D receptor agonist; Serotonin 1D receptor agonist; R-H-5HT-1-D-AG. PHCD 5HT-1-B-AG; Receptor, Hormonal, 5 Hydroxytryptamine 1B agonist; 5HT1B receptor agonist; Serotonin 1B receptor agonist; R-H-5HT-1-B-AG. PHCD R; R-AG; R-H; R-H-AG; R-H-5HT; R-H-5HT-AG; R-H-5HT-1; R-H-5HT-1-AG; R-H-5HT-1-D; R-H-5HT-1-D-AG; H; H-AG; H-5HT; H-5HT-AG; H-5HT-1; H-5HT-1-AG; H-5HT-1-D; H-5HT-1-D-AG; 5HT; 5HT-AG; 5HT-1; 5HT-1-AG; o o o LN Therapy (CC)|Pharmacology (PHCD) |Status (DSTC) ============+=====================+============= N8A |5HT-1-D-AG 5HT-1-B-AG|L PHAR Record Monitoring Drug Developments

190 190 NRAT 4:Novelty Rating - Leading compound of this type for this therapy MRAT 2:Market Size - Therapeutic category market $ million worldwide SRAT E:Development Speed - Development completed TRAT N:Total Rating - Overall rating not available PHAR Record Monitoring Drug Developments

191 191 What other unlaunched products are in U.S. clinical trials in the anti-migraine therapeutic area? Who are the companies associated with this development? Monitoring Drug Developments

192 192 => INDEX ADISINSIGHT DRUGUPDATES PHAR => SET DETAIL ON => E N2C/CC E# FILE FREQUENCY TERM o o o E > N2C/CC ADISINSIGHT 76 N2C/CC DRUGUPDATES 71 N2C/CC PHAR 0 N2C/CC E4 DRUGUPDATES 71 N2C ANTIMIGRAINE PREPARATIONS/CC E5 ADISINSIGHT 76 N2C ANTI MIGRAINE PREPARATIONS/CC o o o Monitoring Drug Developments

193 193 => E N8A/CC E# FILE FREQUENCY TERM E13 ADISINSIGHT 65 N7X ALL OTHER CNS DRUGS/CC E14 PHAR 157 N8/CC E > N8A/CC ADISINSIGHT 0 N8A/CC DRUGUPDATES 0 N8A/CC PHAR 157 N8A/CC E16 PHAR 157 N8A ANTIMIGRAINE/CC E17 PHAR 162 N9/CC Monitoring Drug Developments

194 194 => E ANTIMIGRAINE/CC E# FILE FREQUENCY TERM o o o ADISINSIGHT 127 ANTIMETABOLITES/CC DRUGUPDATES 53 ANTIMETABOLITES/CC E >ANTIMIGRAINE/CC ADISINSIGHT 76 ANTIMIGRAINE/CC DRUGUPDATES 71 ANTIMIGRAINE/CC PHAR 157 ANTIMIGRAINE/CC E28 90 ANTIMIGRAINE PREPARATIONS/CC ADISINSIGHT 19 ANTIMIGRAINE PREPARATIONS/CC DRUGUPDATES 71 ANTIMIGRAINE PREPARATIONS/CC Monitoring Drug Developments

195 195 => S E3 OR E15 FILE 'ADISINSIGHT' 76 N2C/CC 0 N8A/CC 76 N2C/CC OR N8A/CC FILE 'DRUGUPDATES' 71 N2C/CC 0 N8A/CC 71 N2C/CC OR N8A/CC FILE 'PHAR' 0 N2C/CC 157 N8A/CC 157 N2C/CC OR N8A/CC L15 QUE N2C/CC OR N8A/CC Monitoring Drug Developments

196 196 => S (ANTIMIGRAINE OR ANTI MIGRAINE)/CC FILE 'ADISINSIGHT' o o o 76 ANTI MIGRAINE/CC ((ANTI(S)MIGRAINE)/CC) 76 (ANTIMIGRAINE OR ANTI MIGRAINE)/CC FILE 'DRUGUPDATES' o o o (("ANTI"(S)"MIGRAINE")/CC) 71 (ANTIMIGRAINE OR ANTI MIGRAINE)/CC FILE 'PHAR' 157 ANTIMIGRAINE/CC 0 ANTI MIGRAINE/CC 157 (ANTIMIGRAINE OR ANTI MIGRAINE)/CC L16 QUE (ANTIMIGRAINE OR ANTI MIGRAINE)/CC Monitoring Drug Developments

197 197 => E PHASE/DSTA E# FILE FREQUENCY TERM o o o E >PHASE/DSTA ADISINSIGHT 0 PHASE/DSTA DRUGUPDATES 0 PHASE/DSTA PHAR 5655 PHASE/DSTA E PHASE I/DSTA ADISINSIGHT 1060 PHASE I/DSTA DRUGUPDATES 1064 PHASE I/DSTA E53 PHAR 2212 PHASE I CLINICAL TRIAL/DSTA Monitoring Drug Developments

198 198 => E CLINICAL/DSTA E# FILE FREQUENCY TERM E61 DRUGUPDATES 51 CL/DSTA E62 ADISINSIGHT 2 CLAUDICATION/DSTA E >CLINICAL/DSTA ADISINSIGHT 0 CLINICAL/DSTA DRUGUPDATES 0 CLINICAL/DSTA PHAR 6213 CLINICAL/DSTA E64 ADISINSIGHT 547 CLINICAL (PHASE UNKNOWN)/DSTA E65 PHAR 782 CLINICAL TRIAL/DSTA E66 DRUGUPDATES 78 CLINICALS/DSTA Monitoring Drug Developments

199 199 => E MIGRAINE/CT E# FILE FREQUENCY TERM o o o E74 DRUGUPDATES 21 MICROTUBULE ASSEMBLY PROMOTER/CT E > MIGRAINE/CT ADISINSIGHT 79 MIGRAINE/CT DRUGUPDATES 72 MIGRAINE/CT PHAR 80 MIGRAINE/CT E76 DRUGUPDATES 1 MINERALOCORTICOID ANTAGONIST/CT In ADISINSIGHT the indication may be linked to DSTA Monitoring Drug Developments

200 200 ADISINSIGHT –Links indication to development phase PHAR –Supports a STATUS field DRUGUPDATES –Uses “marketed” instead of “launched” Monitoring Drug Developments

201 201 => FILE ADISINSIGHT => S L15 OR L16 76 N2C/CC (N2C/CC) 0 N8A/CC (N8A/CC) 46 ANTIMIGRAINE/CC (ANTIMIGRAINE/CC) o o o ((ANTI(S)MIGRAINE)/CC) L18 76 L15 OR L16 L15 = CC by code L16 = CC by text terms Monitoring Drug Developments

202 202 => S ((PHASE? OR CLINICAL?) (L) UNITED STATES (L) MIGRAINE)/DSTA NOT (LAUNCHED (L) UNITED STATES)/DSTA o o o 12 ((PHASE? OR CLINICAL?)(L) UNITED STATES(L)MIGRAINE)/DSTA 738 LAUNCHED/DSTA 6114 UNITED STATES/DSTA 337 (LAUNCHED(L)UNITED STATES)/DSTA L19 10 ((PHASE? OR CLINICAL?)(L)UNITED STATES (L)MIGRAINE)/DSTA NOT (LAUNCHED(L)UNITED STATES)/DSTA => S L18 AND L19 L20 9 L18 AND L19 Monitoring Drug Developments

203 203 => FILE PHAR => S L15 OR L16 0 N2C/CC 157 N8A/CC 157 ANTIMIGRAINE/CC 0 ANTI MIGRAINE/CC L L15 OR L16 L15 = CC by code L16 = CC by text terms Monitoring Drug Developments

204 204 => S ((PHASE? OR CLINICAL?)(L)UNITED STATES)/DSTA AND ACTIVE/STA 5655 PHASE?/DSTA 6213 CLINICAL?/DSTA UNITED STATES/DSTA 2871 ((PHASE? OR CLINICAL?)(L)UNITED STATES)/DSTA 6634 ACTIVE/STA L ((PHASE? OR CLINICAL?)(L)UNITED STATES)/DSTA AND ACTIVE/STA => S L21 AND L22 L23 13 L21 AND L22 Monitoring Drug Developments

205 205 => FILE DRUGUPDATES => S L15 OR L16 71 N2C/CC 0 N8A/CC 71 ANTIMIGRAINE/CC 3427 "ANTI"/CC 0 "MIGRAINE"/CC 0 ANTI MIGRAINE/CC (("ANTI"(S)"MIGRAINE")/CC) L24 71 L15 OR L16 L15 = CC by code L16 = CC by text terms Monitoring Drug Developments

206 206 => S ((PHASE? OR CLINICAL?)(L)UNITED STATES)/DSTA NOT (MARKETED (L) UNITED STATES)/DSTA 2723 PHASE?/DSTA 78 CLINICAL?/DSTA 7511 UNITED STATES/DSTA 1496 ((PHASE? OR CLINICAL?)(L)UNITED STATES)/DSTA ZZZ MARKETED/DSTA 7511 UNITED STATES/DSTA ZZZ (MARKETED(L)UNITED STATES)/DSTA L ((PHASE? OR CLINICAL?)(L)UNITED STATES)/DSTA NOT (MARKETED(L)UNITED STATES)/DSTA => S L24 AND L25 L26 10 L24 AND L25 Monitoring Drug Developments

207 207 DUPLICATE –Usually used to remove duplicates –DUP REMOVE is not available in all files –However DUPLICATE IDE (identify) may still be used to “merge” and arrange answer sets Monitoring Drug Developments

208 208 => SET DUPORDER FILE => DUP IDE L20 L23 L26 DUPLICATE IS NOT AVAILABLE IN 'ADISINSIGHT, PHAR,DRUGUPDATES'. ANSWERS FROM THESE FILES WILL BE CONSIDERED UNIQUE L27 32 DUP IDE L20 L23 L26 (INCLUDES 0 SETS OF DUPs) ANSWERS '1-9' FROM FILE ADISINSIGHT ANSWERS '10-22' FROM FILE PHAR ANSWERS '23-32' FROM FILE DRUGUPDATES DUPORDER FILE arranges answers by file Monitoring Drug Developments

209 209 Recall the question: Who are the companies associated with this development? Monitoring Drug Developments

210 210 ALL format provides detailed information about each drug product For quick analysis of information use: –Tabular display formats for DRUGUPDATES IDETAB, CCTAB, COTAB –Or, ANALYZE for an analysis and display of data Monitoring Drug Developments

211 211 => SET NOTICE DISPLAY 100 => D L COTAB THE EST COST FOR THIS REQUEST IS U.S. DOLLARS DO YOU WANT TO CONTINUE WITH THIS REQUEST? (Y)/N: Y L27 File DRUGUPDATES COPYRIGHT 1999 IMSWORLD ANS|Company |Compound |Class |High Phase| Type ===+========+===========+======+==========+========= O O O 24|Lilly |lanepitant;|R3C; |Phase II |Originator | |LY |N2C | | |Lilly | | | |Assignee O O O DRUGUPDATES COTAB Monitoring Drug Developments

212 212 => ANALYZE L27 1- CN TN CC CT CO L28 ANALYZE L27 1- CN TN CC CT CO : 304 TERMS => D CN 1- DOC ANS L28 ANALYZE L27 1- CN TN CC CT CO : 304 TERMS TERM # # OCC # DOC % DOC CN TN CC CT CO PINN/CN (ANS: 24,30,31) ALMOTRIPTAN/CN (ANS: 6,20,30) o o o LANEPITANT/CN (ANS: 18,24) o o o ANALYZE up to 5 fields at a time Monitoring Drug Developments

213 213 => D CO DOC 1- ANS L28 ANALYZE L27 1- CN TN CC CT CO : 304 TERMS TERM # # OCC # DOC % DOC CN TN CC CT CO LILLY/CO (ANS: 17,18,24,26,28,32) PHARMACIA & UPJOHN/CO (ANS: 6,12,20,21,30) SEPRACOR/CO (ANS: 4,17,26,28) FERRER/CO (ANS: 7,22,31) ALMIRALL-PRODESFARMA/CO (ANS: 6,20) o o o Monitoring Drug Developments

214 214 SYNTHLINE

215 215 Synthline – Drug Synthesis Database Syntheses for drugs from 1984 Chemical Information Bibliografic References ( patents ) SYNTHLINE

216 216 => fil reg => nalorex 0 NALOREX L1 0 NALOREX SYNTHLINE

217 217 => fil synthline FILE 'SYNTHLINE' FILE COVERS 1984 TO 15 Mar 2002 ( /ED) => e nalorex SYNTHLINE

218 218 E13 1 NALMEFENE/BI E14 1 NALMETRENE/BI E > NALOREX/BI E16 35 NALPHA/BI E17 1 NALTREL/BI o o o o o o o o o o SYNTHLINE

219 219 => nalorex/pro L3 1 NALOREX/PRO => d all SYNTHLINE

220 220 L3 ANSWER 1 OF 1 SYNTHLINE COPYRIGHT 2002 PROUS SCIENCE AN 2000:864 SYNTHLINE DN CN Naltrexone hydrochloride; EN- Nalorex 1639A; Antaxone; Celupan; Nalorex; SYNTHLINE

221 221 RN RN (free base) MF C20 H23 N O4. Cl H MW SYNTHLINE

222 222 CC Treatment of Alcohol Dependency; Treatment of Opioid Dependency; Treatment of Substance Dependency HDP Launched-1984 CO DuPont Pharmaceuticals Co.; Zambon Group SpA; F. Hoffmann-La Roche AG; DrugAbuse Sciences, Inc.; Alkermes, Inc. SYNTHLINE

223 223 STRUCTURE: SYNTHLINE

224 224 TX Compound can be prepared in two different ways both starting from 14-hydroxydihydronormorphinone (I): 1) By reaction of (I) with cyclopropylmethyl bromide (C) in DMF at 70 C. 2) Product (I) is ketalized with ethylene glycol (A) by means of p-toluenesulfonic acid giving the cyclic ketal (II), m.p C; this in turn, is treated with cyclopropyl carbonyl chloride (B) in a mixture of methylene chloride and triethylamine yielding the N,O-dicyclopropylcarbonyl derivative (III), mp C. Compound (III) is reduced with LiAlH4, in refluxing THF yielding the ethylene ketal of naltrexone (IV), m.p C, which is finally hydrolyzed with aqueous HCl at 100 C. SYNTHLINE

225 225 SYNTHLINE

226 226 TI Naltrexone AU Castaner, J.; Roberts, P.J. SO Drugs Fut (1977), 2(1), 45 TI 14-Hydroxydihydronormorphinone derivatives IN Blumberg, H.; et al PI US TI Verfahren zur Herstellung von N-substituierten 14-Hydroxydidronormorphinen IN Blumberg, H.; et al PI CH ; DE ; DE ; GB TI Derives de 14-hydroxydihydronormorphinones IN Anon PI FR 6358 SYNTHLINE

227 227 RCT (A) RN CN Polyethylene glycol; Ethylene glycol MF C2 H6 O2 MW CO AccuStandard; Acros Organics; Aldrich; SYNTHLINE

228 228 RCT (B) RN CN Cyclopropanecarboxylic acid chloride; cyclopropanecarbonyl chloride MF C4 H5 Cl O MW CO Acros Organics; Aldrich; Alfa Aesar; SYNTHLINE

229 229 DRUGPAT

230 230  Covers 56 Countries  Updated Monthly  Sources: British Patent Office  Producer: IMS DRUGPAT

231 231 Find patent information on Deracyn DRUGPAT

232 232 => deracyn/cn L1 47 DERACYN/CN => d 1-47 cotab DRUGPAT

233 233 L1 File DRUGPAT COPYRIGHT 2002 IMSWORLD ANS| Patent Assignee | Compound |Patent No. ===+========================+==========+=========== 1|Upjohn (USA) |adinazolam|DE |Upjohn (USA) |adinazolam|US |Upjohn (USA) |adinazolam|US |Ciba Geigy (Switzerland)|adinazolam|SU |Ciba Geigy (Switzerland)|adinazolam|GB |Ciba Geigy (Switzerland)|adinazolam|CH |Ciba Geigy (Switzerland)|adinazolam|CH |Takeda (Japan) |adinazolam|YU |Takeda (Japan) |adinazolam|DE |Takeda (Japan) |adinazolam|GB

234 234 For what therapeutic classes does Glaxo hold patents in the United Kingdom? DRUGPAT

235 235 => glaxo?/pa and gb/pc 4144 GLAXO?/PA 1212 GB/PC L2 57 GLAXO?/PA AND GB/PC => sel cc SmartSELECT INITIATED L3 SEL L2 1- CC : 25 TERMS => d 1-25 DRUGPAT

236 236 TERM # # OCC # DOC % DOC CC J1D CEPHALOSPORINS R3A ANTIASTHMATIC, B2-STIMULANTS A2B1 ANTIULCERANTS, HISTAMINE H2 ANTAGONISTS N2C1 ANTIMIGRAINE TRIPTANS R7X ALL OTHER RESPIRATORY SYSTEM PRODUCTS R3D ANTIASTHMATIC, CORTICOIDS A4A ANTIEMETICS D7A PLAIN TOPICAL CORTICOSTEROIDS A16A OTHER ALIMENTARY TRACT PRODUCTS A2B9 ALL OTHER ANTIULCERANTS N6D NOOTROPICS N7E DRUGS USED IN ALCOHOL DEPENDENCE S1 OPHTHALMOLOGICALS B1C PLATELET AGGREGATION INHIBITORS G4B9 ALL OTHER UROLOGICAL PRODUCTS J5C1 NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS R1A1 NASAL CORTICOSTEROIDS WITHOUT ANTI-INFECTIVES R3C NON-STEROIDAL RESPIRATORY ANTI-INFLAMMATORIES A3G GASTRO-INTESTINAL SENSORIMOTOR MODULATORS A7H MOTILITY INHIBITORS C8A CALCIUM ANTAGONISTS, PLAIN G4B3 ERECTILE DYSFUNCTION PRODUCTS J1C BROAD SPECTRUM PENICILLINS M1B ANTIRHEUMATIC CORTICOSTEROID COMBINATIONS N7X ALL OTHER CNS DRUGS DRUGPAT

237 237 Find supplementary protection certificate (SPC) for Formoterol DRUGPAT

238 238 => formoterol L6 430 FORMOTEROL => l6 and (spc or ccp) 5596 SPC 241 SPCS 5646 SPC (SPC OR SPCS) L7 42 L6 AND SPC => d 1-37 cytab DRUGPAT

239 239 ANS| Country |Patent No. | Published | Expiry |Expiry Comments |NOTE | | | Appln. No. | Date | | ===+=============+===========+============+========+================+==== 1|Norway |NO |NO | |SPC Filed |(1) |Czech |CZ |CZ | |SPC Filed |(2) |Republic | | | | | supplementary (1) Norwegian patent is based on WO 93/ A supplementary protection certificate (SPC) protection certificate (SPC) DRUGPAT

240 240 DRUGPAT Find supplementary protection certificate (SPC) for ep26044

241 241 DRUGPAT => fil drugpat => ep26044/pn L1 11 EP26044/PN => d l1 cytab 1-11

242 242 DRUGPAT ANS| Country |Patent No. | Expiry |Expiry Comments|NOTE | | | Date | | ===+=============+===========+========+===============+==== 1|European |EP | | |(1) |Patent Office|Germany, | | | | |Federal | | | | |Republic of| | | |European |EP | | |(2) |Patent Office|United | | | | |Kingdom | | | |European |EP | | |(2) |Patent Office|Switzerland| | | |European |EP | | |(2) |Patent Office|Sweden | | | |European |EP | | |(2) |Patent Office|Netherlands| | | |European |EP | | |(2) |Patent Office|Luxembourg | | | |European |EP | | |(2) |Patent Office|Liechtenste| | | | |in | | | |European |EP | | |(2) |Patent Office|Italy | | | |European |EP | |CCP Granted |(3) |Patent Office|France | | | |European |EP | | |(2) |Patent Office|Belgium | | | |European |EP | | |(4) |Patent Office|Austria | | |

243 243 DRUGPAT (3) A complementary protection certificate (certificat complementaire de protection-CCP) has been granted in France citing European patent expires The certificate comes into force on expiry of the cited patent and expires on 4 June on 4 June The certificate covers the AUGMENTIN powder for injection composition of amoxicillin sodium equivalent to 1 g amoxicillin with potassium clavulanate equivalent to 200 mg clavulanic acid. EP B also has product claims to clavulanic acid t-butylamine salt acetone solvate.

244 244 DRUGPAT => fil inpadoc => ep26044/pn L5 1 EP26044/PN => d ls

245 245 DRUGPAT L5 ANSWER 1 OF 1 INPADOC COPYRIGHT 2003 EPO LEGAL STATUS AN INPADOC UPLS EPAA A PRIORITY (PATENT APPLICATION) GB A EPAE A EP-APPLICATION EP A EPAK + DESIGNATED CONTRACTING STATES: AT BE CH DE FR GB IT LU NL SE EPA1 + PUBLICATION OF APPLICATION WITH SEARCH REPORT EP17P + REQUEST FOR EXAMINATION FILED EPRAP1 APPLICANT REASSIGNMENT (CORRECTION)

246 246 DRUGPAT EPREG REFERENCE TO A NATIONAL CODE FRCC FR: SUPPLEMENTARY CERTIFICATE OF PROTECTION LAID OPEN TO THE PUBLIC (LAW OF 25 JUNE 1990) 92C0136, EPMEDD + IT: SPC for pharmaceutical products: granted CCP 170, ; BEECHAM GROUP PLC * CCP 171, ; BEECHAM GROUP PLC

247 247 Conjugates/adducts/carriers/vehicles are used to deliver a target molecule The conjugate might be made up of a number of different pieces CAS indexes the chemistry of the conjugate based on what is revealed about it in the publication Conjugates AB A review. Different anticancer drugs, farmorubicin, doxorubicin, paclitaxel and cis-platin were conjugated through a Gly-Phe-Leu-Gly tetrapeptide side chain to a water-sol. synthetic polymeric carrier based on N-(2-hydroxypropyl)methacryalmide (HPMA)....

248 248 Possibility 1 If the entire conjugate is described and completely characterized (and there are actual bonds that connect the pieces together) Then CAS does this: –assigns RNs for the completely characterized substance in REGISTRY –uses descriptive text in CAPLUS to describe the utility of such substances

249 249 Possibility 1 - sample carrier (monomeric)peptide linkerdrug IT P P P P RL: SPN (Synthetic preparation); THU (Therapeutic use); BIOL (Biological study); PREP (Preparation); USES (Uses) (anthracycline polymeric conjugates, their preparation, and their use as antitumor agents)

250 250 CM 2 CRN ( ) CMF C7 H14 N2 O. Cl H CM 3 CRN CMF C7 H13 N O2 Possibility 1 - sample carrier (polymeric) drug IT DP, reaction products with succinimidyl maleimidomethylcyclohexanecarboxylate and fluorescein-amino acid derivs. RL: BSU (Biological study, unclassified); SPN (Synthetic preparation); THU (Therapeutic use); BIOL (Biological study); PREP (Preparation); USES (Uses) (prepn. of polymer-Tat peptide conjugates for intracellular drug delivery to human ovarian carcinoma cells) CM 1 CRN CMF C50 H59 N5 O16 peptide linker

251 251 One query has the entire conjugate described The broadest search will have –the pieces unattached –only a monomeric unit –a simple amide fragment to suggest a peptide linkage Structure search

252 252 Possibility 2 If (only) some part of the conjugate is described and completely characterized Then CAS does this: –assigns RNs for the part that is known –uses descriptive text in CAPLUS to describe what the rest of the conjugate is like

253 253 RN REGISTRY CN 2-Propenamide, N-(2-hydroxypropyl)-2-methyl-, homopolymer (9CI) (CA INDEX NAME) OTHER NAMES: CN N-(2-Hydroxypropyl)methacrylamide homopolymer CN N-(2-Hydroxypropyl)methacrylamide polymer CN Poly[N-(2-hydroxypropyl)methacrylamide] CM 1 CRN CMF C7 H13 N O2 Possibility 2 - samples IT Antitumor agents (antitumor drug delivery by conjugates with N-(2- hydroxypropyl)methacrylamide copolymers) IT , Poly(N-(2-Hydroxypropyl) methacrylamide) RL: CPS (Chemical process); PEP (Physical, engineering or chemical process); THU (Therapeutic use); BIOL (Biological study); PROC (Process); USES (Uses) (conjugated with antitumor agents; antitumor drug delivery by conjugates with N-(2-hydroxypropyl)methacrylamide copolymers) Polymer is indexed by RN Class of drugs is indexed in very broad terms

254 254 Possibility 2 - samples IT , Doxorubicin hydrochloride RL: RCT (Reactant); RACT (Reactant or reagent) (N-(2-Hydroxypropyl)methacrylamide copolymers containing doxorubicin bound by a proteolytically or hydrolytically cleavable bond) IT P, N-(2-Hydroxypropyl)methacrylamide RL: RCT (Reactant); SPN (Synthetic preparation); PREP (Preparation); RACT (Reactant or reagent) (N-(2-Hydroxypropyl)methacrylamide copolymers containing doxorubicin bound by a proteolytically or hydrolytically cleavable bond) Monomer is indexed by RN Drug is indexed by RN

255 255 Possibility 3 If little or none of the conjugate is completely characterized Then CAS does this: –uses descriptive text in CAPLUS to describe what conjugate is like

256 256 Possibility 3 - samples IT Liver, neoplasm (hepatoma, inhibitors; glycosylated/galactosylated peptide-bifunctional linker-nucleotidic monomer/polymer conjugates, compns., and methods of use) IT Antitumor agents (hepatocellular carcinoma; glycosylated/galactosylated peptide-bifunctional linker-nucleotidic monomer/polymer conjugates, compns., and methods of use) IT Antiviral agents Cytotoxic agents Drug delivery systems Hepatitis virus Human Linking agents Liver (glycosylated/galactosylated peptide-bifunctional linker-nucleotidic monomer/polymer conjugates, compns., and methods of use)

257 257 Other queries should be built (or use ‘optional substitution’ substructure search techniques) so that all combinations are covered –drug-linker (then use text in CAPLUS to add the polymer) –drug-polymer (then use text in CAPLUS to add the linker) –polymer-linker (then use text in CAPLUS to add the drug) Structure search - to be complete

258 258 Another query will have only the drug moiety –use text in CAPLUS to add the linker and polymer Another query will have only the polymer moiety –use text in CAPLUS to add the drug and linker Another query (perhaps a sequence query) will have only the linker possibilities –use text in CAPLUS to add the drug and polymer Structure search – to be complete

259 259 In CAPLUS, combine the various structure answer sets accompanied by text to account for the different scenarios L10 might be drug substructure answers OR (doxorubicin/CN or doxorubicin or other drugs or anthracycline?...) L20 might be polymer substructure answer set OR (methacrylamide? or...) L30 might be linker sequence answer set OR (?peptide? or Gly or...) S L10 AND L20 AND L30 Search to account for all scenarios

260 260 Possibility 4 If the conjugate is described by means of a Markush structure Then CAS does this: –makes a Markush structure entry in MARPAT as long as the focus is not the polymer chemistry as long as it comes from a patent 1988-present

261 261 TITLE: Camptothecin-taxoid conjugates as antimitotic and antitumor agents... DOCUMENT TYPE: Patent LANGUAGE: English FAMILY ACC. NUM. COUNT: 1 PATENT INFORMATION: PATENT NO. KIND DATE APPLICATION NO. DATE US B US WO A WO 2003-US GI AB C'-L-T where C' is a camptothecin group, L is a linking moiety, and T is a taxoid group are useful in treating cancer, including cellular differentiation, and inhibiting cellular mitosis. An example compd.... Possibility 4 – MARPAT sample

262 262 Sample claim polymer carrier – other polymers (methacrylamides and such) are also described Gly is the “linker” – might be any peptide linkage R 1 is an anthracycline drug (such as doxorubicin) connected through N


Download ppt "1 Bioscience and Pharmaceutical Databases. 2 In Searching these databases it is very often request to run a search in many databases (multifile searches)."

Similar presentations


Ads by Google