INTERNATIONAL SEARCH j------------------. Inte ional Application No PCT/US00/15287 A. CLASSIFICATION OF SUBJECT MATTER IPC 7 C07H1/06 C07H19/06 C07H19/16 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) IPC 7 C07H 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) EPO-Internal, WPI Data C. DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. X US 5 734 041 A (JUST GEORGE ET AL) 1,2, 31 March 1998 (1998-03-31) 9-13, 15-18 column 31, line 27-column 32, line 45 Y US 5 124 442 A (CZERNECKI STANISLAS ET 1-3, AL) 23 June 1992 (1992-06-23) 9-11, 14-18 column 5, line 50-line 53 Y US 5 824 793 A (GRYAZNOV SERGEI M ET AL) 1-3,5, 20 October 1998 (1998-10-20) 11-14, 17,18 column 21, line 21-line 17, 18 /-- Further documents are listed in the continuation of box C. Patent family members are listed in annex. LJ l'-I ° Special categories of cited documents : "A"document defining the general state of the art which is not or priority 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"eariier document but published on or after the international"X"document of particular relevance ;claimed invention considered to be of particular relevance invention ' cannot be considered novel or cannot be considered to tH! ng 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 or other to establish the publication date of another ^Y^ document of particular relevance ; the claimed invention canot bye 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 93.03.20Q1 14 November 2000 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, de Nooy, A Fax: (+31-70) 340-3016 INTERNATIONAL SEARCH REPORT Intë'onal Application No PCT/US00/15287 C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Category ° Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. Y G S LI ET AL :"Transient protection: 1-3, 5, efficient one-flask syntheses of protected 9-18 deoxynucleosides" JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, US, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, vol. 104, 1982, pages 1316-1319, XP002136167 ISSN:0002-7863 cited in the application the whole document A M. P. REDDY ET AL. :"Ultrafast cleavage 1 and deprotection of oligonucleotides synthesis and use of Cac derivatives" NUCLEOSIDES & NUCLEOTIDES, vol. 16,1997, pages 1589-1598, XP002152800 page 1593, figure 1 A B. KASDAR, A. MARKOVAC :"A new synthesis 1 of 2', 3'-dideoxycytidine" J. HETEROCYCLIC CHEM., vol. 26,1989, pages 1531-1533, XP002152801 page 1531, scheme 1 rational application No. INTERNATIONAL SEARCH REPORT PCT/US 00/15287 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.Claims Nos. : because they relate to subject matter not required to be searched by this Authority, namely: 2. Claims Nos. : 1-19 (in part), 36 (in part), 39-59 (in part) 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. 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 II 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: see additional sheet 1. As ai ! required additional search fees were timely paid by the applicant, this International Search Report covers all searchable claims. 2. j 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.: 1-19 (in part), 20-35 (in full) Remark on Protest The additional search fees were accompanied by the applicant's protest. No protest accompanied the payment of additional search fees. L-J FURTHER INFORMATION CONTINUED FROM PCT/ISA/21û This International Searching Authority found multiple (groups of) inventions in this international application, as follows: 1. Claims: 1-19 (in part), 20-35 (in full) A process for preparing an essentially pure 5'-protected deoxyribonucleoside product where the polar aprotic solvent for step a of claim 1 is an amide. 2. Claims: 1-19 (in part) A process for preparing an essentially pure 5'-protected deoxyribonucleoside product where the polar aprotic solvent for step a of claim 1 is dimethylsulfoxide or dimethylsulfone. 3. Claims: 1-19 (in part) A process for preparing an essentially pure 5'-protected deoxyribonucleoside product where the polar aprotic solvent for step a of claim 1 is hexamethylphosphate. 4. Claims: 36 (in part), 37-38 (in full), 39-59 (in part) A process for selectively protecting the exocyclic amino group of a starting deoxyribonucleoside which has an exocyclic amino group which is to be protected by acylation and at least one hydroxyl group which is to be left unprotected where the polar solvent for step a of claim 36 is a straight chain or branched Cl to C5 alcohol. 5. Claims: 36 (in part), 39-59 (in part) A process for selectively protecting the exocyclic amino group of a starting deoxyribonucleoside which has an exocyclic amino group which is to be protected by acylation and at least one hydroxyl group which is to be left unprotected where the polar solvent for step a of claim 36 is tetrahydrofuran. 6. Claims: 36 (in part), 39-59 (in part) A process for selectively protecting the exocyclic amino group of a starting deoxyribonucleoside which has an exocyclic amino group which is to be protected by acylation and at least one hydroxyl group which is to be left unprotected where the polar solvent for step a of claim 36 isacetonitrile. FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 7. Claims: 36 (in part), 39-59 (in part) A process for selectively protecting the exocyclic amino group of a starting deoxyribonucleoside which has an exocyclic amino group which is to be protected by acylation and at least one hydroxyl group which is to be left unprotected where the polar solvent for step a of claim 36 is an amide. 8. Claims: 36 (in part), 39-59 (in part) A process for selectively protecting the exocyclic amino group of a starting deoxyribonucleoside which has an exocyclic amino group which is to be protected by acylation and at least one hydroxyl group which is to be left unprotected where the polar solvent for step a of claim 36 is dimethylsulfoxide or dimethylsulfone. 9. Claims: 36 (in part), 39-59 (in part) A process for selectively protecting the exocyclic amino group of a starting deoxyribonucleoside which has an exocyclic amino group which is to be protected by acylation and at least one hydroxyl group which is to be left unprotected where the polar solvent for step a of claim 36 is hexamethylphosphate. FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 Continuation of Box 1. 2 Claims Nos.: 1-19 (in part), 36 (in part), 39-59 (in part) Although claim 1 does not explicitly indicate so, an essential and indispensable feature of this claim is that pyridine is not used as a solvent in the claimed process (see page 7, lines 19-22 of the description). According to PCT preliminary examination Guidelines III 4.3, this claim is unclear (Article 6 PCT). The lack of clarity of claim 1 is to such an extent that no meaningful search can be executed on this claim insofar as it does not contain this feature. Consequently the search on this claim (and claims dependent thereon) has been limited to processes which do not use pyridine as a solvent. Furthermore, claim 1 lacks support in the description in as far as it relates to the use of pyridine as a solvent (Article 6 PCT) and the search has been limited as mentioned above, also for this reason. Furthermore, claim 17 lacks support in the description in as far as it relates to the use of combinations of the solvents mentioned in this claim (Article 6 PCT) and the search has been limited as mentioned above. Present claims 1-19,36 and 39-59 relate to processes defined by reference to a desirable characteristic or property, namely the synthesis of protected deoxyribonucleoside derivatives avoiding the use of pyridine as a solvent. The claims cover all processes having this characteristic or property, whereas the application provides support within the meaning of Article 6 PCT and/or disclosure within the meaning of Article 5 PCT for only a very limited number of such processes. 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. Independent of the above reasoning, the claims also lack clarity (Article 6 PCT). An attempt is made to define the processes by reference to a result to be achieved. Again, this lack of clarity in the present case is such as to render a meaningful search over the whole of the claimed scope impossible. Consequently, the search has been carried out for those parts of the claims which appear to be clear, supported and disclosed, namely those parts relating to the processes for the synthesis of either 5'-protected deoxyribonucleoside derivatives (as in claim 1) using polar aprotic solvents for the step of claim la chosen from the amides, dimethylsulfoxide (DMSO), dimethylsulfone and hexamethylphosphate (HMPA), as mentioned in the description on page 13, lines 24-26, or to processes relating to the synthesis of exocyclic N-acylated deoxyribonucleoside derivatives (as in claim 36) using polar solvents for the step of claim 36a chosen from straight chain or branched Cl to C5 alcohols, tetrahydrofuran (THF), acetonitrile, amides, DMSO, dimethylsulfone and HMPA, as mentioned in the description, page 9, lines 21-22; page 10, lines 26-29; page 12, line 6. FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 The scope of the search is further limited by virtue of a lack of unity-See PCT form 206. 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 nformation on patent family members PCT/US 00/15287 Patent document Publication Patent Publication cited in search report date member (s) date US 5734041 A 31-03-1998 AU 7327596 A 07-05-1997 EP 0904275 A 31-03-1999 WO 9714710 A 24-04-1997 JP 11511480 T 05-10-1999 US 6160109 A 12-12-2000 US 5945521 A 31-08-1999 US 6031092 A 29-02-2000 US 5124442 A 23-06-1992 FR 2653771 A 03-05-1991 AT 147749 T 15-02-1997 CA 2028648 A 28-04-1991 DE 69029708 D 27-02-1997 EP 0427587 A 15-05-1991 JP 3209393 A 12-09-1991 US 5824793 A 20-10-1998 US 5684143 A 04-11-1997 US 5859233 A 12-01-1999 AU 703509 B 25-03-1999 AU 6178996 A 10-09-1997 CZ 9802629 A 12-05-1999 EP 0882059 A 09-12-1998 PL 328639 A 15-02-1999 WO 9731009 A 28-08-1997