D.P.S.PARMAR,TECHNICAL MEMBER (PATENTS) - (1.) THE appellant is aggrieved by the order of the respondent No.1 dated 12.01.2011 wherein he refused patent application No.924/DEL/NP/2006 relating to "3 -[(2 -(4 -(Hexyloxycarbonylamino -lmino -Methyl) -Phenylamino -Methyl) -1 -Methyl -1h -Benzimidazol -5 -Carbonyl) -Pyridine -2 -Yl -Amino] -Propionic Acid Ethyl Ester Methane Sulphonate and Use Thereof as a Medicament."
(2.) ON examination of the application following objections were mentioned: 1. Claims 1 -4 fall within the scope of such clause (d) of section 3 of Patents Act 1970 as the claimed compound is a new form of a known substance with no enhanced therapeutic efficacy. 2. Subject matter does not constitute an invention u/s 2(1)(ja) as the claims lack inventive step in view of cited documents: D1: WO03/074056 discloses the ethyl 3 -[2 -([4 -(hexyloxycarbonylamino -imino -methyl) -phenylamino] -methyl) -1 -methyl -1H -benzimidazole -5 -carbonyl) -pyridin -2 -yl -aminol -propionate methane suphonate and process of its preparation. D2: Hauel N.H. et al: "Structure -based design of novel patent nonpeptide thrombin inhibitors" Journal of Medicinal Chemistry, American Chemical Society, Washington, US, vol. 45, No.9, 2002, pages 1757 -1766. D3: Mungall D.: "BIBR -1048 Boehringer Ingelheim" in Investigational Drugs, Pharmapress, US, Vol 2002 (2002 -06), pages 905 - 907, XPOOI147306 ISSN Current Opinion 3, No.6, June 1472 -4472 discloses BIBR -1048 MS as well as results from studies with this thrombin inhibitor. D4: Caira M.R.: "Crystalline Polymorphism of Organic Compounds" Topics in Current Chemistry, Springer, Berlin, DE, Vol. 198, 1998, pages 1 63 -208. D5: WO98/37075 discloses BIBR -1048 base having a thrombin -inhibiting effect and a thrombin time prolonging activity. D6: Collins B, and Hollidge C.: "Antithrombotic Drug Market" Nature Reviews Drug Discovery, Nature Publishing Group, 2002, Vol. 2, January 2003, pages 11 -12, ISSN: 1474 -1776 reports on developmental oral anticoagulants, such as BIBR -1048 MS, which is said to be in phase II trials. D7: J.M. Stassen: Ex vivo Anticoagulant Activity of BIBR953ZW, A Novel Synthetic Direct Thrombin Inhibitor and of its Prodrug BIBR1048 MS in different animal species, Supplement to the Journal Thrombosis and Haemostasis, July 2001, ISSN: 0340 -6245 discloses oral active prodrug BIBR -1048 MS and its antithrombotic potential in vivo. D8: J. Stangier: Pharmacokinetics of BIBR 953 Z, A novel low molecular weight direct thrombin inhibitor in healthy volunteers, Supplement to the journal Thrombosis and Haemostatis, July 2001, ISSN: 0340 -6245 discloses administration of BIBR 1048 MS as oral solution to study pharmacokinetics of BIBR953Z.
(3.) THE respondent No.1 found that documents D1 -D8 disclose all the features defined in claim -1 and dependent claims 2 -4 and hence according to the respondent No.1 claimed invention is not new and lack inventive step under S.2(1)(j). He also found claims 1 -4 fall within the scope of S.3(d) and the claimed process is a mere use of known process to prepare polymorphic forms of a substance and respondent No.1 refused the grant of the patent. Aggrieved by the said order, the appellant filed this appeal. The appellant submitted that the application has been filed under PCT contained 14 claims and are reproduced below: 1. Ethyl 3 -[(2 -([4 -(Hexyloxycarbonylamino -imino -methyl) -phenylaminoJ -methylJ -1 -methy l -1H -benzimidazol -5 -carbonyl) -pyridin -2 -yl -aminoJ -propionate - methanesulfonate in crystalline form, characterised by a melting point of Tm.p. = 180 +3 C (form I) (determined by DSC; evaluation by peak maximum; heating rate: 10 C/min). 2. Ethyl3 -[(2 -([4 -(Hexyloxycarbonylamino -imino -methyl) -phenylamino] - methyl} -1 -methyl -1H -benzimidazol -5 -carbonyl) -pyridin -2 -yl -amino] - propionate - methanesulfonate in crystalline form, characterised by a melting point of Tm.p. = 190 +3 C (formII) (hemihydrate) (determined by DSC; evaluation by peak maximum; heating rate: 10 C/min). - 3. Ethyl 3 - [(2 - ([4 - (Hexyloxycarbonylamino -imino -methyl) -phenylamino] - methyl} -1 -methyl -1H -benzimidazole -5 -carbonyl) -pyridin -2 -yl -amino] -propionat e -methanesulfonate in crystalline form, characterised by a melting point of Tm.p. =120 +5 C (hemihydrate) (determined by DSC; evaluation by peak maximum; heating rate: 10 C/min). 4. Phannaceutical composition, containing the salt ethyl 3 -[(2 -([4 - (Hexyloxycarbonylamino -imino -methyl) - phenylaminoJ -methyI] -1 -methyl -1H - benzimidazol -5 -carbonyl) -pyridin -2 -yI -amino] -propionate -methanesulfonate according to one of claims 1 to 3, optionally together with one or more inert carriers and/ or diluents. 5. Use of ethyl3 -[(2 -([4 -(Hexyloxycarbonylamino imino -methyl) -phenyl -amino] - methyIJ -1 -methyl -1H -benzimidazole -5 -carbonyl) -pyridin -2 -yl -amino] - propionate - methanesulphonate according to one of claims 1 to 3 for preparing a pharmaceutical composition which is suitable for the post -operative prophylaxis of deep vein thrombosis and the prevention of stroke. 6. Process for preparing a pharmaceutical composition according to claim4, characterized in that by a non -chemical method the salt ethyl 3 -[(2 -{[4 -(Hexyloxycarbonylamino -imino -methyl) -phyenylamino] -methyl} -1 -methyl -1H - benzimidazole -4 -carbo -nyl) -proprionate -methanesulphonate according to one of claims 1 to 3 is incorporated in one or more inert carriers and/or diluents. 7. Process for preparation BIBR 1048 MS polymorph 1, characterized in that a) a solution of a slight deficiency of methanesulphonic acid in acetone is slowly added to a solution of BIBR 1048 base in acetone at a temperature of approx. 30 C to 36 C, b) the mixture is stirred for about 1 hour at a temperature of approx. 26 C to 33 C, c) the mixture is cooled to about 17 C to 23 C and stirred for a further 40 to 80 minutes at this temperature, d) the precipitated crystals of BIBR 1048 MS form1 are suction filtered and - e) the product thus obtained is dried in vacuo for at least 4 hours at a maximum of 50 C. 8. Process for preparing BIBR 1048 MS Polymorph II, characterized in that a) a solution of a slight deficiency of methanesulphonic acid in acetone is slowly added to a solution of BIBR 1048 base in acetone at a temperature of approx. 40 C to 46 C, b) the mixture is optionally inoculated with BIBR 1048 polymorph II crystals, c) it is then stirred for about 1 hour at a temperature of approx. 40 C to 46 C, d) cooled to approx. 17 C to 23 Cand stirred for a further 40to 80 minutes at this temperature, e) the precipitated crystals of BIBR MS form II are suction filtered and f) the product thus obtained is dried in vacuo for at least 4 hours at a maximum of 50 C. 9. Process for preparing BIBR 1048 MS polymorphII, characterised in that a) a suspension of BIBR 1048 MS polymorph I in acetone is heated to 45 C to 50 C for approx. 4 hours with stirring, b) optionally(i) inoculated withBIBR 1048 polymorph II crystals, or (ii) inoculated with BIBR 1048 polymorph II crystals and additionally a small amount of BIBR 1048 base is added, c) then cooled to approx. 15 C, d) the precipitated crystals of BIBR 1048 MS form II are suction filtered and e) the product thus obtained is dried in vacuofor at least 4 hours at a maximum 50 C. 10. Process for preparing BIBR 1048 MS polymorph II, characterised in that a) BIBR 1048 MS polymorph I is placed in acetone and b) optionally (i) inoculated with a small amount of BIBR 1048 polymorph II, or (ii) inoculated with BIBR 1048 polymorph II crystals and additionally a small amount of BIBR 1048 base is added, c) the mixture thus obtained is heated to 40 C to 46 C for at least one hour with stirring, d) then cooled to approx. 17 C to 23 C and stirred for a further 40 to 80 minutes at this temperature, e) the precipitated crystals of BIBR 1048 MS form II are separated off and f) the product thus obtained is dried in vacuo for at least 4 hours at a maximum 50 C. 11. Process for preparing BIBR 1048 MS hemihydrate, characterised in that a) a solution of one equivalent of methanesulphonic acid in ethyl acetate is slowly added to a solution of BIBR 1048 base in a mixture of 90% aqueous ethanol and ethyl acetate in a ratio by volume of approx, 2:5 at a temperature of approx, 35 C to 40 C, b) optionally, as the product begins to crystallize out, further ethyl acetate is added for dilution, c) the mixture is stirred for about 'another 30 minutes at approx. 35 Cto 40 C, d) then stirred for a further 30 minutes at ambient temperature, d) the precipitate of BIBR 1048 MShemihydrate is suction filtered and e) dried at approx. 40 C in the circulating air drying cupboard. 12. BIBR 1048 MS polymorph I obtainable by the process according to claim 7, 13. BIBR 1048 MS polymorph II obtainable by the process according to one of claims 8, 9 or 10. 14. BIBR 1048 MS hemihydrate obtainable by the process according to claims 11. ;