INTERNATIONAL SEARCH REPORT r--------------) Inte onal Application No PCT/US 00/05195 A. CLASSIFICATION OF SUBJECT MATTER IPC 7 C07D271/113 C07D413/04 C07D307/64 C07D239/38 C07D213/70 C07D487/04 C07D311/16 A61K31/4402 A61K31/4406 A61K31/44 A61P19/02 A61P35/04 A61P9/00 C07D319/04 C07D339/08 According to Intemational Patent Classification (IPC) or to both national classification and IPC B. FIELDS SEARCHED Minimum documentation searched (classification system followed by classification symbols) Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Electronic data base consulted during the international search (name of data base and, where practical, search terms used) C. DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. P, A DE B ET AL:"The next generation of MMP 1-16 inhibitors: design and synthesis" ANN. N. Y. ACAD. SCI. (ANYAA9,00778923); 1999; VOL. 878 (INHIBITION OF MATRIX METALLOPROTEINASES); PP. 40-60, XP000916382 Procter & Gamble Pharmaceuticals; Mason; 45040-8006; OH; USA (US) the whole document -/- El Further documents are listed in the continuation of box C. p3 Patent family members are listed in annex. LJ LJ ° Special categories of cited "T"later document published after the international filing date "A"document or pnonty date and not in conflict with the application but A-document defmlng the general state of the art which IS notconsidered to be of particular relevance invention invention E"eäriier document but published on or after the international"XS document of particular relevance; the claimed invention filing date cannot be considered novel or cannot be considered to "L"document which may throw doubts on priority claim (s) or involve an inventive step when the document is taken alone which is cited to establish the publication date of another"Y"document of particular relevance ; the claimed invention citation or other special reason (as specified) cannot be considered to involve an inventive step when the "0"document referring to an oral disclosure, use, exhibition or document is combined with one or more other such docu- other means ments, such combination being obvious to a person skilled "P"document published prior to the international filing date but in the art. later than the priority date claimed"&'document member of the same patent family Date of the actual completion of the international search Date of mailing of the international search report 15 September 2000 28. 09. 00 Name and mailing address of the ISA Authorized officer European Patent Office, P. B. 5818 Patentlaan 2 NL-2280 HV Rijswijk Tel. (+31-70) 340-2040, Tx. 31 651 epo nl Fax: (+31-70) 340-3016 ScrutonEvans, I INTERNATIONAL SEARCH REPORT inti tonal Application No PCT/US 00/05195 A. CLASSIFICATION OF SUBJECT MATTER IPC 7// (C07D487/04, 239: 00,235: 00) According to international Patent Classification (IPC) or to both national classification and IPC B. FIELDS SEARCHED Minimum documentation searched (classification system followed by classification symbols) Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Electronic data base consulte during the international search (name of data base and, where practical, search terms used) C. DOCUMENTS CONSIDERED TO BE RELEVANT Category ° Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. P, A CHENG M ET AL:"Design, Synthesis, and 1-16 Biological Evaluation of Matrix Metalloproteinase Inhibitors Derived from a Modified Proline Scaffold" J. MED. CHEM. (JMCMAR, 00222623); 1999; VOL. 42 (26); PP. 5426-5436, XP000919157 Procter and Gamble Pharmaceuticals; Mason; 45040; OH; USA (US) the whole document Further documents are listed in the continuation of box C. Patent family members are listed in annex. i ° Special categories of cited documents: "T'later document published after the intemational filing date kA-document defining the general state of the art which is not or pnonty date and not in conflict with the application but considered to be of particular relevance cited to understand the principle or theory underlying the invention E document but published on or after the international ^X"document of particular relevance ; the claimed invention filing date cannot be considered novel or cannot be considered to "L"document which may throw doubts on priority claim (s) or involve an inventive step when the document is taken alone which is cited to establish the publication date of another citation or other special reason (as specified) cannot be considered to involve an inventive step when the "O"document referring to an oral disclosure, use, exhibition or document is combined with one or more other such docu- other means ments, such combination being obvious to a person skilled "P"document published prior to the international filing date but in the art. later than the priority date claimed"&'document member of the same patent family Date of the actual completion of the international search Date of mailing of the international search report 15 September 2000 28. 09, 0ja Name and mailing address of the ISA Authorized officer European Patent Office, P. B. 5818 Patentlaan 2 NL-2280 HV Rijswijk Tel. (+31-70) 340-2040, Tx. 31 651 epo nl, Scruton-Evans, I Far : (+31-70) 340-3016 bcruucn-Lvans, i Int¢., lational application No. INTERNATIONAL SEARCH REPORT PCT/US 00/05195 Box I Observations where certain claims were found unsearchable (Continuation of item 1 of first sheet) This International Search Report has not been established in respect of certain claims under Article 17 (2) (a) for the following reasons: 1. IXI Claims Nos.: because they relate to subject matter not required to be searched by this Authority, namely: Although claims 14-16 are directed to a method of treatment of the human/animal body, the search has been carried out and based on the alleged effects of the compound/composition. 2. Claims Nos.: 1-11 (partly) because they relate to parts of the International Application that do not comply with the prescribed requirements to such an extent that no meaningful International Search can be carried out, specifically: see FURTHER INFORMATION sheet PCT/ISA/210 3. j Claims Nos.: because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4 (a). Box 11 Observations where unity of invention is lacking (Continuation of item 2 of first sheet) This International Searching Authority found multiple inventions in this international application, as follows: 1. As ai ! required additional search fees were timely paid by the applicant, this International Search Report covers all searchable claims. 2. As all searchable claims could be searched without effort justifying an additional fee, this Authority did not invite payment of any additional fee. 3. As only some of the required additional search fees were timely paid by the applicant, this International Search Report covers only those claims for which fees were paid, specifically claims Nos.: 4. No required additional search fees were timely paid by the applicant. Consequently, this International Search Report is restricted to the invention first mentioned in the claims ; it is covered by claims Nos.: Remark on Protest The additional search fees were accompanied by the applicant's protest. 12 No protest accompanied the payment of additional search fees.

FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 Continuation of Box 1. 2 Claims Nos.: 1-11 (partly) Present claims 1-11 relate to an extremely large number of possible compounds Support within the meaning of Article 6 PCT and/or disclosure within the meaning of Article 5 PCT is to be found, however, for only a very small proportion of the compounds claimed. In the present case, the claims so lack support, and the application so lacks disclosure, that a meaningful search over the whole of the claimed scope is impossible.

Consequently, the search has been carried out for those parts of the claims which appear to be supported and disclosed, namely those parts relating to the compounds wherein W is CH=CH and X is OH, with J as OH or R15 and R13 together as a cyclic C (X) (X) derivative (as in examples 68-72) i. e. all of the examples and closely related homologous compounds.

The applicant's attention is drawn to the fact that claims, or parts of claims, relating to inventions in respect of which no international search report has been established need not be the subject of an international preliminary examination (Rule 66.1 (e) PCT). The applicant is advised that the EPO policy when acting as an International Preliminary Examining Authority is normally not to carry out a preliminary examination on matter which has not been searched. This is the case irrespective of whether or not the claims are amended following receipt of the search report or during any Chapter II procedure. INTERNATIONAL SEARCH REPORT r, , r------- Int. ional Application No ntormation on patentfamiy members pCT/US 00/05195 Patent document Publication Patent family Publication cited in search report date member (s) date WO 9906340 A 11-02-1999 AU 8237698 A 22-02-1999 EP 1009737 A 21-06-2000 NO 20000464 A 30-03-2000 ZA 9806835 A 01-02-1999 WO 9808822 A 05-03-1998 AU 3985897 A 19-03-1998 BR 9713186 A 03-11-1999 CN 1228771 A 15-09-1999 CZ 9900628 A 14-07-1999 EP 0927168 A 07-07-1999 NO 990838 A 28-04-1999 PL 331838 A 02-08-1999 SK 24999 A 14-02-2000