FORM 2 THE PATENTS ACT 1970 (39 of 1970) AND The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) 1. TITLE OF THE INVENTION: "IMPROVEMENTS IN THE METHOD FOR THE TREATMENT OR PROPHYLAXIS OF THROMBOSIS OR EMBOLISM" 2. APPLICANT : (a) NAME: IPCA LABORATORIES LTD. (b) NATIONALITY: Indian Company incorporated under the Companies Act, 1956 (c) ADDRESS: 48, Kandivali Industrial Estate, Charkop, Kandivali (West), Mumbai-400067, Maharashtra, India 3. PREAMBLE TO THE DESCRIPTION: The following specification particularly describes the invention and the manner in which it is to be performed. Technical field of invention. [0001] The present invention relates to a method of ameliorating the drawbacks of antiplatelet drug named Clopidogrel. The method of the present invention comprises administration of an oxo-metabolite of clopidogrel or its derivative of the formula II in its free or pharmaceutically acceptable salt form for alleviating the symptoms of thrombosis or embolism by inhibiting blood platelet aggregation. Background of the invention. [0002] Conditions resulting from thrombotic or thromboembolic events are the leading causes of illness and death in adults in western civilization. Intravascular thrombosis and embolism are common clinical manifestations of many diseases. Unregulated activation of the hemostatic system has the potential to cause thrombosis and embolism, which can reduce blood flow to critical organs like the brain and myocardium. Certain patient groups have been identified that are particularly prone to thrombosis and embolism. These include patients (1) immobilized after surgery, (2) with chronic congestive heart failure, (3) with atherosclerotic vascular disease, (4) with malignancy, or (5) who are pregnant. The majority of "thrombosis prone" individuals have no identifiable hemostatic disorder, although there are certain groups of individuals having inherited or acquired "hypercoaguable" or "prethrombotic" conditions predisposing them to recurrent thrombosis (Harrison's Principles of Internal Medicine, 12th ed. McGraw Hill) [0003] Effective primary hemostasis requires three critical events: platelet adhesion, granule release, and platelet aggregation. Within a few seconds of injury, platelets adhere to collagen fibrils in vascular subendothelium. This interaction is facilitated by von Willebrands factor, an adhesive glycoprotein which allows platelets to remain attached to the vessel wall despite the high shear forces generated within the vascular lumen. Von Willebrand's factor accomplishes this task by forming a link between platelet receptor sites and subendothelial collagen fibrils. [0004] As the primary hemostatic plug is being formed, plasma coagulation proteins are activated to initiate secondary hemostasis. There is little difference between hemostatic plugs, which are a physiological response to injury, and pathologic thrombi. Thrombosis is often described as coagulation which has occurred in the wrong place or at the wrong time. Hemostatic plugs or thrombi that form in veins where blood flow is slow are richly endowed with fibrin and trapped red blood cells and contain relatively few platelets. These thrombi often form in leg veins and can break off and embolize to the pulmonary circulation. Conversely, clots that form in arteries under conditions of high flow are predominantly composed of platelets and have little fibrin. These arterial thrombi may readily dislodge from the arterial wall and embolize to distant sites to cause temporary or permanent ischemia. This is particularly common in the cerebral and retinal circulation and may lead to transient neurologic disfunction (transient ischemic attacks) including temporary monocular blindness (amaurosis fugax) or strokes. In addition, there is increasing evidence that most myocardial infarctions are due to thrombi which form within atherosclerotic coronary arteries. (The preceding discussion is taken primarily from Harrison's Principles of Internal Medicine, 12th ed., McGraw Hill.) [0005] Extracellular nucleotides and their receptors of platelets are important components of the cardiovascular system and are involved in functions like platelet activation and the control of vascular tone. Adenosine diphosphate (ADP) and Adenosine Triphosphate (ATP) are playing crucial roles in the physiological process of haemostasis and in the development and extension of arterial thrombosis (2). By itself ADP is a weak agonist of platelet aggregation inducing only reversible responses as compared to strong agonists such as thrombin or collagen. However, due to its presence in large amounts in the platelet dense granules and its release upon activation at sites of vascular injury, ADP is an important so-called secondary agonist which amplifies most of the platelet responses and contributes to the stabilization of the thrombus. The receptors for extracellular nucleotides belong to the P2 family which consists of two classes of membrane receptors: P2X ligand-gated cation channels (P2X1-7) and Glycoprotein-coupled P2Y receptors (P2Y 1,2,4,6,11,12,13,14). Each of these receptors has a specific function during platelet activation and aggregation, which naturally has implications for their involvement in thrombosis. [0006] Since ADP and ATP play a crucial role in platelet activation, their receptors are potential targets for antithrombotic drugs. The ATP-gated cation channel P2X1 and the 3 two G protein-coupled ADP receptors, P2Y1 and P2Y12, selectively contribute to platelet aggregation and formation of a thrombus. Owing to its central role in the growth and stabilization of a thrombus, the P2Y12 receptor is an established target of antithrombotic drugs mainly the thienopyridine class of compounds like Ticlopidine, clopidogrel, prasugrel etc... [0007] The mainstay of antiplatelet therapy for patients with acute coronary syndromes (ACS), including those undergoing early percutaneous coronary intervention (PCI) and stents implantation is administration of a combination of Aspirin and clopidogrel. Aspirin inhibits platelet thomboxane A2 production and platelet activation, and reduces the risk of recurrent ischemic events in patients at high risk of vascular events by 22% (absolute risk reduction (ARR) about 2%) at the expense of an increase in the odds of major bleeding events by about 60% (Absolute risk increase (ARJ) about 0.5%. Clopidorgel inhibits ADP induced platelet activation by blocking the platelet receptor P2Y12, which is when combined with Aspirin therapy in patients with ACS, it reduces the risk of recurrent ischemic events by a further 20% (ARR about 2.1%), in which the major bleeding events are not increased statistically from aspirin monotherapy. [0008] Clopidogrel (Formula 1), chemically named as "' (+)-(5)-methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4//)-yl)acetate", is currently considered to be the gold standard in the inhibition of blood platelet aggregation. Clopidogrel is marketed as its hydrogen sulphate, hydrochloride, and benzene sulphonate salts. It is widely used for controlling the ischemic events and other cardiovascular disorders efficiently for last 12 years or more. COOCH3 cCCO Formula I: Clopidogrel [0009] However, clopidogrel has several potential limitations. First, the onset of action is delayed, requiring a long time after administration before manifest its activity. A therapeutically significant level of 50% inhibition of ADP induced platelet aggregation, as measured by light transmission aggregometry (LTA) (5u.M ADP ex-vivo) not being reached until 4-6 hours after administration of a loading dose of 300 mg clopidogrel and until 2 hours by doubling the dose to 600 mg. Secondly, there is a dose ceiling effect, as tripling the dosing from regular dose of 300 mg to 900 mg produces only 60% inhibition of ADP induced platelet aggregation (at 5 uM ADP), and fails to produce 50% inhibition of piatelet aggregation induced by 20uM of ADP (ex vivo). Third, most common, almost all clinical trials of clopidogrel reveal that therapeutic level of platelet inhibition is not achieved in a majority of patients because of large inter-individual variability tin response to clopidogrel treatment. These patient population is referred as non-responders or poor responder to clopidogrel, and non-responders are about 14% among Chinese population and 3-4% among whites. The overall poor responders are close to 23% of overall patient population, and variation of inhibitory activity is reported in about 45% of total patient population. It is also been reported that ultrarapid metabolism of clopidogrel due to a different phenotype of CYP isoform in about 4%-18% patients leads to higher bleeding epsodes, with higher platelet aggregation. Considering these facts and data from clinical trials, FDA had put up a boxed warning in the label of Clopidogrel about the ineffectiveness of clopidogrel in certain class of patients and suggested screening of patients for genotyping to understand poor responders of clopidogrel before choosing clopidogrel as therapeutic option. [0010] Thienopyridines are prodrugs that are converted in vivo to pharmacologically active metabolites. The differences in the inhibitory activity of clopidogrel originates from the difference in the activity of liver enzymes that metabolizes clopidogrel and the differences in yielding the active metabolite. Upon ingestion of clopidogrel, it undergoes a series of metabolic reactions to produce active and inactive metabolites involving mainly the CYP 450 mediated steps as well as by action of hepatic human carboxy] esteratse (hCE). About 85-92% of the clopidogrel is hydrolyzed by hCE to its corresponding acid metabolite (Formula IV) which is the main circulating metabolite detected soon after administration of clopidogrel. Second is the oxidative conversion of 5 clopidogrel into its thiolactone metabolite (herein also referred as oxo-clopidogrel, Formula II), which is also pharmaceutical^ inactive for inhibition of thrombus formation. Oxidation step is mainly assisted by different CYPs (for example CYP1A2, CYP2B6 and CYP2C19). The third step is a second oxidative hydrolysis leading to formation of active metabolite from the thiolactone by CYP2B6, CYP2C9, CYP2C19 and CYP3A4 isoforms. This process also accompanied by parallel action of carboxylase enzyme on the thiolactone metabolite and hydrolyze it to its inactive acid form (Formula V) as shown in figure 1, which also accounts about 50% of the total oxo-clopidogrel formed in the metabolic process. In effect, only about 4-7% of the active metabolite of clopidogrel are generated in the metabolic process to reach the active site to bind with the receptor P2Y12 in order inhibit ADP mediated thrombus formation. The properties of different CYPs such as CYP2C9 and CYP2B6 as well as CYP2C19 are differing from subjects to subjects due the CYP polymorphism and some alleles are non-reactive to clopidogrel to metabolize clopidogrel to yield therapeutically required concentration of clopidogrel active metabolite and thus clopidogrel fails to produce clinically significant effect in those patients. In the group of patients, where the clopidogrel concentration does not reach the therapeutic levels, they are about 3.5 times at risk of stroke or cardiac ischemia while treatment with Clopidogrel. Therefore FDA warns of screening the CYP alleles genotyping for early identification of non-responders or poor metabolizers, and requests to switch these class of patients to drugs like Prasugrel which can produce greater platelet inhibition, but at the expense of major life threatening bleeding episodes. Moreover, these CYPs are inhibited by various external factors such as drugs, (for example, PPIs, verapamil, statins, protease inhibitors etc.), foods (such as Orange, grape-Juice, green tea), environmental factors etc. , which can alter the concentration of active metabolite of cloidogrel to a great extent, leading to significant variability in platelet response. Figure 1. Metabolic pathway of clopidogrel. COOCH, COOCH3 H0QC COOCH^ =- CYP CYP r"-'98%. [0043] 83.85 g of (S)-thiolactone compound of formula II obtained above was dissolved in 120 ml of isopropenyl acetate and mixed with 7.8 g of p-toJuene sulfonic acid. The mixture is heated to 90 °C under stirring for 6 hours. The reaction mass then cooled to about 20 °C and 20 ml of water was added to the mixture. The mixture is then basified by addition of saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. Ethyl acetate layer is further washed twice with water and distilled under vacuum to remove ethyl acetate. The residue obtained was dissolved in acetone and HCI gas was passed into the solution under cooling. The obtained precipitate was filtered, recrystallized from acetone to get hydrochloride salt of acetyl derivative. Optical purity > 99.5% PHARMACOLOGY AND TOXICOLOGY [0044] The pharmacological and toxicological results which are reported below demonstrate the properties of the derivatives of the invention both from the point of view of toxicity and tolerance, and from the point of view of their activities, particularly inhibition of platelet and thrombotic aggregation. TOXICOLOGICAL STUDY [0045] The compounds of the invention demonstrate excellent tolerance and low toxicity. In addition, the tests carried out on the acute, chronic, subchronic and delayed toxicities in different species of animals, have not demonstrated any local or general reaction, disturbance or anomaly in the biochemical, macroscopic or microscopic examinations carried out during these experiments. PHARMACOLOGICAL STUDY [0046] The platelet aggregation inhibiting activity and the toxicity of these new compounds were compared to those of the clopidogrel as described in the French Pat. No. 82,12599 (Publication No. 2 530 247). [0047] The platelet aggregation inhibiting activities and the antithrombotic activities of the compounds were studied in the rat by standard methods. 1. Measurement of platelet aggregation with ADP [0048] The activity on the aggregation of plates induced by ADP or collagen was determined ex-vivo. [0049] The products dissolved in ethanol (200 mg/ml) and diluted in water containing gum arabic (5%-wt/v) were administered by the oral route to groups of five female rats of the CD-COBS strain, weighing 250-300 g, in amounts of 10 ml of suspension per kilogram two hours before blood samples were taken. [0050] The blood samples were taken from animals anesthetized with diethyl ether by puncture of the abdominal aorta and placed over a 3.8% aqueous solution of sodium citrate (1 vol/9 volumes of blood). The platelet-rich plasma was then isolated by centrifugation at 200 g for 10 minutes. [0051] Aggregation is induced by the addition of 2 ul of aggregating solution to 400 ul of platelet-rich plasma. The aggregating solutions used were: a 500 uM aqueous solution of ADP (final concentration 2.5 u.M). [0052] The aggregation of the platelets was monitored as described in the method by G. V. R. Born in Nature 194, p. 927 (1967) using a Coultronics ® aggregometer at a temperature of 37 °C. and agitation of 900 rpm. [0053] For aggregation with ADP, the aggregometer generates a curve representing a platelet aggregation as measured by a change in optical density. The height of this curve is defined as the height of aggregation. The percentage of aggregation is the relation between the aggregation height measured and the height corresponding to 100% aggregation x 100. The percentage of inhibition is determined by the relation: Control aggregation height -produced aggregation height X100 Control aggregation height [0054] The results obtained for the aggregation with ADP are shown in Table I; they demonstrate that activity of the molecule. Table 1. Product Dose mg/kg Qty of base administered % aggregation* % inhibition p** Control 103±3 Clopidogrel bi sulphate 12.5 9.613 19±4 82 0.001 25 19.225 11±1 89 0.001 Control 94±I Thio lactone 2.5 2.5 4±2 95 0.001 *height, Mean of results ± standard deviation **Students test 2. Anti-thrombotic activity [0055] The antithrombotic activity has also been studied in the test of venous thrombosis on a screw thread described by Kumada T, et al. in Thromb. Res 18 p. 189 (1980). [0056] Female rats of the same type as those previously described, in groups of 10 animals, were anesthetized with diethyl ether and their vena cava was isolated after abdominal incision. [0057] A metallic screw thread 21 mm long consisting of a dentist's drill, marketed by Dyna (France) size No. 30, was introduced into the lumen of this vein just below the renal bifurcation descending towards the iliac veins, without damaging the wall; 19 to 20 mm of the length of the screw thread are implanted and the remaining 1 mm protrudes through the closed stomach into the exterior. [0058] The thrombi formed rapidly and five hours later, under pentobarbital anesthesia, the abdomen is reopened and ligatures are placed above and below the screw thread which is withdrawn after longitudinal incision of the vein and the isolated thrombus is weighed. [0059] The results which are presented in Table II show that thiolactone of Formula II is superior to clopidogrel. Table II Product Dose mg/kg Qty of base administered Weight of thrombus *(mg) % inhibition p** Control 3.9±0.3 Clopidogrel bisulphate 10 7.69 1.26±0.19 67 0.001 20 15.38 1.20±0.13 69 0.001 control 4.18±0.31 Thiolactone 12.5 12.5 1.18±0.18 76 0.001 *Mean of results ± standard deviation; ** Students test We claim, 1. A method of treatment or prophylaxis of thrombosis or embolisms in human in need of such treatment wherein said method achieves an effect greater or equivalent to administration of a dose of clopidogrel consisting essentially of administering an amount of (S)-oxo-metabolite of clopidogrel or its derivatives or a pharmaceutically acceptable salt wherein said amount is substantially lower than dose of clopidogrel and alleviating the side effects associated with inactive clopidogrel acid rtietabolite of Formula IV. 2. A rnethod of treatment or prophylaxis of thrombosis or embolisms comprising administering a patient in need of such treatment an amount of the (S)-oxo-metabolite of clopidogrel or its derivatives or a pharmaceutically acceptable salt such that it releases active metabolite of clopidogrel at a concentration greater than or equivalent to . administration of a dose of clopidogrel wherein said amount is substantially lower than the dose of clopidogrel and alleviating the side effects associated with inactive clopidogrel acid metabolite of Formula IV. 3. A method as claimed in claim 1 or 2, wherein the onset of action is reduced at least by 50% than treatment of clopidogrel. 4. A method as claimed in claim 1 or 2, wherein the dose of oxo-metabolite or its derivative of formula II is 20 to 40 mg in relation to 300 mg clopidogrel. 5. A method as claimed in claim 1 or 2, wherein the dose of oxo-metabolite or its derivative of formula II is 35 to 70 mg in relation to 600 mg clopidogrel. 6. A method as claimed in claim 1 or 2, wherein the dose of oxo-metabolite or its derivative of formula II is 50 to 100 mg in relation to 900 mg clopidogrel. 7. A method as claimed in claim I or 2, wherein the dose of oxo-metabofite or its derivative of formula II is 5 to 12 mg in relation to 75 mg clopidogrel. 8. A method as claimed in claim 1 or 2, wherein the dose of oxo-metabolite or its derivative of formula II is 6 to 20 mg in relation to 150 mg clopidogrel. 9. A method as claimed in claim 1 or 2, wherein 30-60 mg oxo-clopidogrel or its derivative of Formula IIA produce greater than 50% inhibition of ADP induced human blood platelet aggregation at a first loading dose. 10. A method as claimed in claim 1 or 2, wherein 6-15 mg oxo-clopidogrel or its derivative of Formula 11A produce greater than 50% inhibition of ADP induced human blood platelet aggregation during a maintenance therapy after a loading dose. 11. A method according to claim 1 to 10, wherein the method further comprise administering one or more anti-platelet agent selected from Aspirin, Cilostazol and dipyridamole. 12. A fixed dose composition of (S)-oxo-clopidogrel or its derivative of Formula HA characterized in that said composition comprising a dose selected from 5-25 mg of oxo- clopidogrel or its derivative of Formula IIA. 13. A fixed dose composition according to claim 12, wherein the dose of oxo-clopidogrel or its derivative of Formula IIA is 5-15 mg. 14. A fixed dose composition according to claim 12 to 13, wherein the method further comprise administering one or more anti-platelet agent selected from Aspirin, Cilostazole and dipyridamole. 15. An improved method for delivering of active clopidogrel metabolite in vivo for the treatment or prophylaxis of thrombosis or embolisms in human in need of such treatment wherein the improvement consisting essentially of administering an amount of (S)-oxo-metabolite of clopidogrel or its derivatives or a pharmaceutical ly acceptable salt, wherein said amount is substantially lower than dose of clopidogrel and wherein said method achieves an effect greater or equivalent to administration of a dose of clopidogrel and alleviating the side effects associated with inactive clopidogrel acid metabolite of Formula IV. 16. A method as claimed in claim 15, wherein the onset of action is reduced at least by 50% than treatment of clopidogrel. 17. A method as claimed in claim 15, wherein the dose of oxo-metabolite or its derivative of formula II is 20 to 40 mg in relation to 300 mg clopidogrel. 18. A method as claimed in claim 15, wherein the dose of oxo-metabolite or its derivative of formula II is 35 to 70 mg in relation to 600 mg clopidogrel. 19. A method as claimed in claim 15, wherein the dose of oxo-metabolite or its derivative of formula II is 50 to 100 mg in relation to 900 mg clopidogrel. 20. A method as claimed in claim 15, wherein the dose of oxo-metabolite or its derivative of formula II is 5 to 12 mg in relation to 75 mg clopidogrel. 25 21. A method as claimed in claim 15, wherein the dose of oxo-metabolite or its derivative of formula II is 6 to 20 mg in relation to 150 mg clopidogrel. 22. A method as claimed in claim 15, wherein 30-60 mg oxo-clopidogrel or its derivative of Formula IIA produce greater than 50% inhibition of ADP induced human blood platelet aggregation at a first loading dose, 23. A method as claimed in claim 15, wherein 6-15 mg oxo-clopidogrel or its derivative of Formula IIA produce greater than 50% inhibition of ADP induced human blood platelet aggregation during a maintenance therapy after a loading dose. 24. A method for minimizing inter individual platelet reactivity variability and metabolic loading in the treatment or prophylaxis of thrombosis or embolisms with administration of a dose of clopidogrel comprising administering (S)-oxo-cIopidogrel metabolite or its derivatives or a pharmaceutically acceptable salt. 25. A method according to claim 24, wherein the inter-individual variability due to CYP450 isofoms and its polymorphic manifestations. 26. A method according to claim 24, wherein the CYP450 isofoms is CYP2C19*2 allele or CYP2C19* 17 allele. 27. A method according to claim 24, wherein the inter-individual variability due to P-glycoprotein efflux transports. 28. A method according to claim 24 to 27, wherein the method further comprise administering one or more anti-platelet agent selected from Aspirin, Cilostazole and dipyridamole. 29. A method for the treatment or prophylaxis of thrombosis or embolisms comprising administration of (S)-oxo-clopidogrel metabolite or its derivatives or a pharmaceutically acceptable salt and a proton pump inhibitor. 30. A medicament or a kit containing (S)-oxo-clopidogrel metabolite or its derivatives or a pharmaceutically acceptable salt and a proton pump inhibitor.