PHARMACEUTICAL PATENTING IN INDIA - BREAKING MYTHS
GLOCHEM INDUSTRIES LTD. VS. CADILA HEALTHCARE LTD.
Glochem Industries Ltd. [hereinafter referred to as Glochem] filed a pre-grant opposition against the grant of the patent application filed by Cadila Healthcare Ltd. [hereinafter referred to as Cadila/ the Applicant], titled “crystalline clopidogrel besylate and process for preparation thereof”. Said opposition was disposed of in January 2009 and all the grounds taken up by Glochem i.e. anticipation by prior publication, anticipation by prior claiming, anticipation by prior use, lack of inventive step, non-patentable subject matter, insufficiency of disclosure were rejected by the Controller. Particularly, the Controller intensively debated the ground under Section 3(d) of the Act taken up by the Opponent.
The Controller while adjudicating the pre-grant opposition took note of the contents of the complete specification of the application along with further data submitted by the Applicant during the course of the pleadings. The Controller held that:
“The claims 1 to 3 of the alleged invention are directed to Crystalline Clopidogrel besylate. The besylate salt of Crystalline Clopidogrel is pure, free flowing, easy to handle and chemically stable (nor hygroscopic) which can be utilized on an Industrial scale (pages 2, 3 & 5 of Complete Specification). To support this and also to meet the requirements of Section 3(d) of Patents Act, 1970 the applicants with their reply statement, have submitted the Stability study data sheet of bisulphate (Enclosure 5 & 9) and besylate (Enclosure 6); along with Stability and Comparative Pharmaceutical characterization Report of solvated (toluene and diozane) and Crystalline Clopidogrel besylate (Enclosures 13 & 14).
The stability study data for the Clopidogrel bisulphate salt reveals that there is increase in the concentration of the inactive metabolite which in the long term reduces the efficacy of bisulphate salt by reduction of therapeutic dose (Enclosure 5). Further in tablets of bisulphate salt there is an increase in acid impurities (Enclosure 9). Whereas the Crystalline Clopidogrel besylate of present invention surprisingly is not detected with inactive metabolite for over six months in any of the three batches (Enclosure 6). Hence, the Crystelline Clopidogrel Besylate of instant invention is advantageous in terms of increased shelf life of the Clopidogrel bisulphate salt.
The stability report given in the Enclosure 13 shows that the Crystalline Clopidogrel besylate of instant invention is more free flowing and stable even after two month period in comparison to the solvated (toluene and dioxane) forms of Crystalline Clopidogrel besylate (cited by the opponent).
The comparative Pharmaceutical Properties data provided in Enclosure 14 shows that the solvated (toluene and dioxane) forms of Crystalline Clopidogrel besylate are more cardiotoxic compared to the Crystalline Clopidogrel besylate of present invention. The Crystalline cop besylate is non-toxic till 50 uM concentration, whereas the toluene solvated form showed toxicity at 5uM and dioxane solvated form showed toxicity at 25uM. Hence it shows that the Crystalline Clopidogrel besylate is better and advantageous in matters of toxicity in comparison to solvated forms.
In view of the advantageous effects of Crystalline Clopidogrel besylate of instant invention over the known clopidogrel bisulphate and also over the solvated forms of Clopidogrel besylate in different characterization aspects, it can be held that the Crystalline Clopidogrel besylate of present invention compound is patentable and cannot be rejected under Section 3(d) of the Patents Act, 1970”.
The Controller took note of the contents of the complete specification, submissions made during the pleadings and the further evidence/ research data submitted by the Applicant, and accordingly observed that the test of patentability laid down by Section 3(d) of the Act had been sufficiently met by the application.
In light of the same, the Controller rejected the opposition.