Title of Invention

"A CHIMERIC MONOCLONAL ANTIBODY PIPP OF HIGH SPECIFICITY AND AFFINITY FOR BINDING TO HCG"

Abstract

The present invention relates to a set of three light and three heavy chain Complementarity Determining Regions (CDRs), and thereby a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG)useful in detecting as well as treating cancer cells making hCG, imaging metastasis hCG synthesizing tumors, delivering radiations or drugs selectively to such cancer cells sparing normal cells, lastly, preventing onset of pregnancy, and a composition thereof.

Full Text

COMPLETE SPECIFICATION CfflMERIC MONOCLONAL ANTIBODY FOR BINDING WITH HIGH AFFINITY SHiECnVELY TO hCG Field of the present Invention The f|ield of the present invention relates to a set of three light and three heavy chain Complementarity Determining Regions (CDRs), and thereby a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG) useful in detecting as well as treating cancer cells making hCG, imaging metastasis of hCG-synthesizing tumors, delivering radiations selectively to such cancer cells sparing normal cells, lastly, preventing onset of pregnancy, and a composition thereof. Background and prior art references of the Invention HCG is an oncofetal protein. It is made soon after fertilization and its presence in urine or blood is employed as criteria for diagnosis of pregnancy. All pregnancy diagnosis kits employ antibodies specific to hCG in enzyme-immuno-assay or radio-imnaunoassay based kits. As hCG plays also a crucial role in implantation of the embryo onto the uterine endometrium, antibodies against hCG have the capability of preventing the establishment of pregnancy (GP Talwar et al 1994 & 1997).These publications describe the protection offered to normally menstruating and ovulating sexjually active women against pregnancy so long as the titres of circulating antibodies against hCG are above SOng/ml. These and other previous clinical trials (I Kharat et al 1990, GP Talwar et al 1990) in women provide evidence on the safety of anti-hCG antibodies in humans in whom no other body function is disturbed except control of fertility. From these studies it is obvious mat competent antibodies can be used for preventing pregnancy without any side effects. Administration of preformed antibodies has the advantage over active immunization of assuring efficacy of protection in every woman who receives antibody of desirable characteristics in adequate dose. As is well recognized, active immunization with a vaccine does not elicit high enough antibody response in every recipient. Moreover the duration over which the antibody titres persist varies considerably from person to person. These disadvantages are overcome by delivery of proper dose of the antibody whose biological half life is predictable. There is thus scope of using this antibody as a vacation contraceptive for providing protection to women against pregnancy for 4-6 Weeks without disturbance of hormonal profiles and derangement of menstruation. (Besides pregnancy, hCG synthesis and secretion is observed in cancers. Trophoblastic cancers (choriocarcinomas) make this protein in abundance and monitoring of hCG serially provides an index of growth of such cancers. Disappearance of hCG would indicate successful surgical removal of cancerous tissues or success of chemotherapeutic treatment. Subsequent appearance of hCG in blood and urine would, on tile other hand, be indicative of relapses of such tumours (S.K Gupta et al 1982). Apart from choriocarcinomas, an observation of great interest is the unexpected Synthesis of hCG by a number of non-trophoblastic cancers. Its ectopic synthesis has been reported in lung cancers (YT Ikura 2000, MJ Szturmowicz et al 1999), uroethelial i cancer (RK lies et al 1990, R Nishimura et al 1995,), colon adenocarcinomas ( RP Kiran et al 2001, M Lundin et al 2000), pancreatic carcinoma (H Alfthan et al 1992, H faylor et al 1990), liver malignancies, neuroendocrine tumours (JM Bidart et al 1997) and in patients with poorly differentiated carcinomas (H Sumi et al 2001). Production of (3- hCG detected in non-trophoblastic tumours is usually associated with cancers of p(oor prognosis (SA Butler et al 2000, HF Acevado et al 1996,1 Marcillac et al 1992, V Ijazar et al 1995, R Hoermann et al 1992). Szturmowicz et al (1999) observed that serum 3- hCG was elevated more frequently in stage 4 patients of non- small cell lung cancer. Syrigos et al (1998) reported mat 40% of pancreatic exocrine tumours produce (J- hCG and its production is correlated with adverse survival. The survival time between P-hCG positive colorectal cancers was significantly shorter than p- hCG negative cancer patients (M Lundin et al 2001, RP Kiran et al 2001). It would thu$ be evident that this protein or its sub-units alpha and beta are made by a variety of cancers at advanced stages, which are highly aggressive and patients bearing these have short survival. More often than not, cancers at mis stage are resilient to the presently available chemotherapeutic drugs. Most tumours which start making ectopically alpha or beta (or bom) carry the subunit o^i their membranes (H. Acevado et al 1996), presumably by virtue of the presence of receptors for hCG and its subunits, which pick up the protein made by the tumour cells. In at least one tumour, the non-small cell lung cancer, the alpha subunit of hCG made un-expectedly by these cells was observed to act as growth promoter of these cells. Antibody against alpha-hCG given to nude mice along with the tumour cells prevented the establishment of die tumour implants (S.Kumar et al 1992). Antibodies given to mice* with established tumours caused necrosis of the established tumour (Kumar et al 1992). Thus antibodies competent to bind alpha or beta subunits of hCG and inactivate their bioactivity have the potential of exercising immuno-therapeutic action for preventing the dissemination of tumours whose growth is promoted by hCG or its subunits. References • AceVedo, H. F., and R. J. Hartsock. 1996. Metastatic phenotype correlates with high expression of membrane- associated complete beta-human chorionic gonadotropin in vivo. Cancer. 7:2388-99 • Altaian, H., C. Haglund, P. Roberts, and U. H. Stenman. 1992. Elevation of free beta subunit of human chorionic gonadotropin and core beta fragment of human chorionic gonadotropin in the serum and urine of patients with malignant pancreatic and biliary disease. Cancer Res. 52:4628-33. • Bidatt, J. M., E. Baudin, F. Troalen, D. Bellet, and M. Schlumberger. 1997. Eutopic and ectopic production of glycoprotein hormones alpha and beta subunits. Ann Endocrinol. 58:125-8. • Butter, S. A., M. S. Ikram, S. Mathieu, and R. K. lies. 2000. The increase in bladder carcinoma cell population induced by the free beta subunit of human chorionicgonadotrophin is a result of an anti- apoptosis effect and not cell proliferation. Br J Cancer.82:1553-6. • Choudhary, J., Bhattacharya S., and Das, C. 1992. Regulation of progesterone secretion in human syncytiotrophoblast in culture by hCG. J. Steroid Mol. Biol. 42:425-432. • Dhar, R., Karmakar, S., Sriraman, R., Talwar, G.P., Das, C. 2004. Efficacy of a recombinant chimeric anti-hCG antibody to prevent human cytotrophoblasts fusion and block progesterone synthesis. Am. J. Reprod. Immunol. 51: 358-363. • Gupta S.K, S. Ramakrishnan and G. P. Talwar. 1982. Properties and characteristics of an anti-hCG monoclonal antibody. J Biosc .4:105-113 • Hoermann, R., A. L. Gerbes, G. Spoettl, D. Jungst, and K. Mann. 1992. Imnaunoreactive human chorionic gonadotropin and its free beta subunit in serum and ascites of patients with malignant tumors. Cancer Res. 52:1520-4. • Danla,Y.,Inoue, H. Tsukuda, T. Yammoto and Y. Koboayashi.2000. Primary choriocarcinoma and human chorionic gonadoptrophin- producing giant cell carcinoma of the lung: are they independent entities ? HisiDpaihology. 36:17-25 • Hes, ft. K., and T. Chard. 1989. Enhancement of ectopic beta-human chorionic gonadotrophin expression by interferon-alpha. J Endocrinol. 123:501-7. • lies, £.. K., C. L. Lee, R. T. Oliver, and T. Chard. 1990. Composition of intact hormone and free subunits in the human chorionic gonadotrophin-like material 1 found in serum and urine of patients with carcinoma of the bladder. Clin EndOcrinol (Oxf). 33:355-64 • Kiran, R. P., R. Visvanathan, and C. G. Simpson. 2001. Choriocarcinomatous metaplasia of a metachronous adenocarcinoma of the colon. Eur J Surg Oncol. 27:436-7 • Kumar, S., G. P. Talwar, and D. K. Biswas. 1992. Necrosis and inhibition of growth of human lung tumor by anti-alpha- human chorionic gonadotropin antibody. J Natl Cancer Inst. 84:42-48 • Kharat . I., Nair, N.S., Dhall .K., Sawney,.H., Krishna,U.,1990 . Analysis of menstrual records of women immunized with anti-hCG vaccines inducing antibodies partially cross-reactive withhLH.Contraception. 41:293-9. • Lazar, V., S. G. Diez, A. Laurent, Y. Giovangrandi, F. Radvanyi, D. Chopin, J. M. Bidart, D. Bellet, and M. Vidaud. 1995. Expression of human chorionic gonadotropin bete subunit genes in superficial and invasive bladder carcinomas. Cancer Res. 55:3735-8. • Lundin, M., S. Nordling, M. Carpelan-Holmstrom, J. Louhimo, H. Alfthan, U. H. Stenman, and C. Haglund. 2000. A comparison of serum and tissue hCG beta as prognostic markers in colorectal cancer. Anticancer Res. 20:4949-51. • Lundin, M., S. Nordling, J. Lundin, H. Alfthan, U. H. Stenman, and C. Haglund. 2001. Tissue expression of human chorionic gonadotropin beta predicts outcome in colorectal cancer: a comparison with serum expression. Int J Cancer. 95:18-22. • M«rcillac, I., F. Troalen, J. M. Bidart, P. Ghillani, V. Ribrag, B. Escudier, B. Malassagne, J. P. Droz, C. Lhomme, P. Rougier, and et al. 1992. Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer Res. 52:3901-7. • Nisjiimura, R., T. Koizumi, K. Morisue, N. Yamanaka, R. Lalwani, M. Yoshimura, T. Nakagawa, K. Shii, K. Hasegawa, and S. Baba. 1995. Expression and secretion of the beta subunit of human chorionic gonadotropin by bladder carcinoma in vivo and in vitro.Cancer Res. 55:1479-84. • SM, Q.J., Lei, Z. M., Rao, C.V., Lin, J. 1993. Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts. Endocrinology 132: 1387*1395. • Sumi^ H., K. Itoh, Y. Onozawa, Y. Shigeoka, K. Kodama, K. Ishizawa, H. Fujii, H. Minami, T. Igarashi, and Y. Sasaki. 2001. Treatable subsets in cancer of unknown primary origin. Jpn J Cancer Res. 92:704-9. • Syrigos, K. N., I. Fyssas, M. M. Konstandoulakis, K. J. Harrington, S. Papadopoulos, N. Milingos, P. Peveretos, and B. C. Golematis. 1998. Beta human chorionic gonadotropin concentrations in serum of patients with pancreatic adenocarcinoma. Gut. 42:88-91. • Szturmowicz, M., J. Slodkowska, J. Zych, P. Rudzinski, A. Sakowicz, and E. Rowinska- Zakrzewska. 1999. Frequency and clinical significance of beta- subunit human chorionic gonadotropin expression in non-small cell lung cancer patients. Tumour Biol. 20:99-104. • Talwar, G. P., O. Singh, R. Pal, N. Chatterjee, P. Sahai, K. Dhall, J. Kaur, S. K. Das, S. Suri, K. Buckshee, and et al. 1994. A vaccine that prevents pregnancy in women. ProcNatl Acad Sci U S A. 91:8532-6. « Talwar, G. P., O. M. Singh, S. K. Gupta, S. E. Hasnain, R. Pal, S. S. Majumbar, S. Vrati,A. Mukhopadhay, J. Srinivasan, U. Deshmukh, S. Ganga, A. Mandokhot, and A. Gupta. 1997. The HSD-hCG vaccine prevents pregnancy in women: feasibility study of areversible safe contraceptive vaccine. Am J Reprod Immunol. 37:153-60. • Talwar G.P., Hingorani .V ., Kumar, S., Roy, S.m Banerjee.A., Shahani, S.M Krishna. 1990 Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine. Contraception. 1990 41:301-16. • ! Taylor, H., N. Heaton, P. Farrands, N. Kirkham, and M. Fletcher. 1990. Elevated human chorionic gonadotrophin levels in a patient with pancreatic carcinoma presenting with a testicular metastasis. Postgrad Med J. 66:1073-5. Objects of the Present Invention The {main object of the present invention relates to developing light chain Complementarity Determining Regions (CDRs) of an antibody reacting selectively with human chorionic gonadotropin (hCG). Another main object of the present invention relates to developing heavy chain Complementarity Determining Regions (CDRs) of an antibody reacting selectively with human chorionic gonadotropin (hCG). Yet another main object of the present invention relates to a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG). Stil| another object of the present invention relates to develop a method of detecting cancer cells making hCG in a subject in need thereof, said method comprising estimating hCG in blood and/or in urine and/or in biopsies using chimeric monoclonal antibody. Still another object of the present invention relates to develop a safe method of imaging metastasis of human chorionic gonadotropin (hCG) synthesizing tumors. Still another Object of the present invention relates to develop a method of delivering radiations selectively to cancer cells sparing normal cells. Still another object of the present invention relates to develop a method of treating cancer. Still another object of the present invention relates to develop a method of preventing onset of pregnancy in sexually active women. Still another object of the present invention relates to develop a composition Comprising chimeric monoclonal antibody PIPP, specific to human chorionic gonadotropin (hCG), and along with pharmaceutically acceptable additives. Summary of the present Invention The present invention relates to a set of three light and three heavy chain Complementarity Determining Regions (CDRs), and thereby a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG) useful in detecting as well as treating cancer cells making hCG, imaging metastasis hCG-synthesizing tumors, delivering radiations and drugs selectively to such cancer cells sparing normal cells, lastly, preventing onset of pregnancy, and a composition thereof. Detailed description of the present Invention The Unique Monoclonal Antibody This antibody was developed by immunizing BALB/c mice with highly purified beta subunit of hCG. Splenocytes from mice carrying high antibody titers reactive with both beta sub-unit of hCG and hCG were fused with NSI myeloma cells by methodologies originally described by Nobel Laureates Milstein and Kohler, which are now commonly followed for the purpose by those in the art. The hybrid cells bearing genes for perpetual replication derived from NSI tumour cells and those coding for synthesis and secretion of the particular antibody derived from a lymphocyte of the mouse immunized with beta-hCG were selected and cloned by methodologies familiar to those in the field. Briefly the principle is that, after fusion of splenocytes lacking thymidine kinase with NSI, the hybrid cells are selected for growth in medium containing hypoxanthine, aminopterin and thymidine (HAT medium). Aminopterin blocks the main biosynthetic pathways of purine and pyrimidine nucleotides and forces the cells to utilize hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and TK enzymes of the salvage pathways for nucleotide biosynthesis. Whereas neither NSI nor the splenocytes would multiply, the hybrid between these two cells carries functional genes jfor both HGPRT and TK and therefore are able to grow in HAT medium. The cells were cloned repeatedly by infinite dilution so as to obtain eventually a population in which each cell secretes the same antibody. The product is thus homogeneous for its characteristics of specificity and binding affinity with the target antigen. Properties ofPIPP Specificity: This antibody secreted by the hybridoma cells binds with beta hCG and hCG. These was no perceptible binding of this antibody to other pituitary hormones, the human growth hormone, human thyroid stimulating hormone and human follicle stimulating hormone. Its binding to human leutinizing hormone was less than 5% and functionally negligible. As hCG is not measurable in the blood and urine of males or non-pregnant females, this hormone or its sub-units are not synthesized and secreted to any appreciably detectable extent by healthy non-pregnant females nor by normal healthy males. It is on account of its literal absence in healthy non-pregnant state, and its appearance as soon as pregnancy takes place, that it is taken as a reliable criterion of diagnosis of pregnancy excluding, of course, the existence in the woman of cancers making hCG. Specificity of the anti-hCG antibody was tested by studying the reactivity of the antibody with other hormones secreted in humans such as growth hormone, follicle stimulating hormone, chorionic gonadotropin. Experimentally the binding of the antibody was determined by competitive immunoassay using radiolabelled hormones- ml-KLM, 125I-hFSH and 125I-hCG (Gupta et al, 1982). Affinity &f binding: The antibody binds with hCG with fairly high affinity. The Association constant of the antibody was of the order of 3xlO10 M1, as determined by Scatchard Plot. The affinity of the antibody to its antigen, hCG, was determined as association constant 1 (Ka) of the hCG-PIPP complex from Scatchard plot using Radioimmuneassay (RIA). Molecular Structure and Complementarity Determining Regions (CDRs) of the Unique AMbody PjPP is a monoclonal developed initially by immunizing mouse with hormone specific beta-subunit of hCG. It has subsequently been converted into a chimeric antibody in i which the constant domain of the heavy chain is the human IgGi and the constant domain of the light chain is Kappa. These are fused by genetic engineering techniques with the variable regions of the original mouse monoclonal antibody. The antigen blinding property of the monoclonal antibody is resident in the variable portion and is expressed by a set of three Complementarity Determining Regions (CDRs) in the light and by three CDRs in the heavy chain. The nucleotide and amino acid sequences of CDRs in this unique antibody in the variable light and heavy chains are as follows: Light Chain CDRs VL-CDR1 (SEQIDNo. 1) ACT GCC AGC TCA AGT GTG ACT TCC AGT TAC TTG CAC (SEQIDNo. 7) TASSSVTSSYLH VL-CDR2 (SEQIDNo. 2) AGC ACA TCC AAC CTG GCT TCT (SEQIDNo.8) S T S N L A S P&-CDR3 (SEQIDNo.3) CAC CAG TAT CAT CGT TCC CCG TAC ACG (SEQIDNo.9) HQYHRSPYT Heavy Chain CDRs VH-cnm (SEQIDNo.4) UC TAC TGG ATC ATC (SEQ ID. No. 10) N Y W I I PH-CDR2 (SEQ ID No. 5) GAG ATT AAT CCT GGT TTT GAT ACT (SEQ ID No. 11) El N P G F D T VH-CDR3 (SEQ ID No. 6) TAT GAT TAC GAC GGA AAC TGG TTC TTC GAT GTC (SEQ ID No. 12) YDYDGNWF F DV The above-denoted CDRs are flanked in this antibody by the 'Framework' residues. These are depicted in SEQ ID Nos.13, and 14 below. I Nttcteotidc SeQiicncc of Variable Powin in Light Chain showing the CDRs and SEQ ID No. 13. ATGGAAATTGTGCTGACCCAGTCTCCAGCAATCATGTCTGCATCTCTGGGG GAACGGGTCACCATGACCTGCACTGCCAGCTCAAGTGTGACTTCCAGTT ACTTGCACTGGTACCAGCAGAAGCCAGGATCCTCCCCCAAACTCTGGATTT ATAGCACATCCAACCTGGCTTCTGGAGTCCCAGCTCGCTTCACTGGCAGT GGGTCTGGGACCTCTTACTCTCTCACAATCAGCAGCATGGAGGCTGAAGAT GCTGCCACTTATTACTGCCACCAGTATCATCGTTCCCCGTACACGTTCGG AGGGGGGACCAAGCTGGAACTGAAACGG ftudeotide Sequence of Variable Domain in Heavy Chain showing the CDRs and fee Flanking Framework regions (CPUs are shown in Bold font) SEQIDNo. 14 ATGGCCGAGGTTCAGCTGCAGCAGTCTGGAGCTGAGGTTGTGAAGCCTGGG GCTTCAGTGAAGATGTCCTGCAAGGCTTCTGGCTTCACCTTCACCAACTAC •TGGATAATCTGGGTGAGGCAGAGGCCTGGACAAGGCCTTGAGTGGATTGG A|GAGATTAATCCTGGTTTTGATACTACTAACTACAGTGAGAAGTTCAAGA (XAAGGCCACACTGACTGTTGACACATCCTCCACCACAGCCTACATGCAGC TTAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTTTTGTGCAAGATATG ATLTACGACGGAAACTGGTTCTTCGATGTCTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCA In the following sequences ranging between SEQ ID Nos. 15 to 18, Normal font sequences correspond to variable region and bold font sequences correspond to constant domain IgGl (heavy chain) or kappa (light chain). SEQIDNo. 15: Nucleotide sequence in PIPP chimeric light-chain AlpGAAATTGTGCTGACCCAGTCTCCAGCAATCATGTCTGCATCTCTGGGG GAACGGGTCACCATGACCTGCACTGCCAGCTCAAGTGTGACTTCCAGTTAC i TT AGCACATCCAACCTGGCTTCTGGAGTCCCAGCTCGCTTCACTGGCAGTGGG TC^GGGACCTCTTACTCTCTCACAATCAGCAGCATGGAGGCTGAAGATGCT GCCACTTATTACTGCCACCAGTATCATCGTTCCCCGTACACGTTCGGAGGGG GGACCAAGCTGGAACTGAAACGGACTGTGGCTGCACCATCTGTATTCAT CT^CCCGCCATCTGATGAGCAGTTGAAATCTGGAGCTGCCTCTGTTGT GTCFCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA GG^GGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGA GCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCT GAGX:AAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCAC CCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGA GTGt SEQIDNo. 16: Amino add sequence in PIPP chimeric light-chain METVLTQSPAIMSASLGERVTMTCTASSSVTSSYLHWYQQKPGSSPKLWIYSTS NLASGVPARFTGSGSGTSYSLTISSMEAEDAATYYCHQYHRSPYTFGGGTKLEL KRTVAAFSVWFPFSDEQLKSGAASWCLLNNFYPREAKVQWKVDNALQSG NSC^SVTIQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS FNR^EC SEQIDNo. 17: ATGGCCGAGGTTCAGCTGCAGCAGTCTGGAGCTGAGGTTGTGAAGCCTGGG GCTTCAGTGAAGATGTCCTGCAAGGCTTCTGGCTTCACCTTCACCAACTACT GGATAATCTGGGTGAGGCAGAGGCCTGGACAAGGCCTTGAGTGGATTGGA GA0ATTAATCCTGGTTTTGATACTACTAACTACAGTGAGAAGTTCAAGACC AA(JGCCACACTGACTGTTGACACATCCTCCACCACAGCCTACATGCAGCTC AGCTAGCCTGACATCTGAGGACTCTGCGGTCTATTTTTGTGCAAGATATGATT AC(^ACGGAAACTGGTTCTTCGATGTCTGGGGCGCAGGGACCACGGTCACCG TCTCCTCAGCCTCCACTAAGGGCCCATCGGTCTTCCCCCTGGCACCCTC CT^CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAA GGJACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCT GACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC CCJAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGT GGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCC ACFCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTT C^CCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGT CACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTT CAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCC GJCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCAC C^JTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGT CtTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGC C|AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCG G|GATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGG CfrrCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCC GGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTC CTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCA GGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA SEQ ID No. 18: Amino acid sequence in PIPP chimeric heavy-chain MAEVQLQQSGAEWKPGASVKMSCKASGFTFTNYWIIWVRQRPGQGLEWIGE INPGFDTTNYSEKFKTKATLTVDTSSTTAYMQLSSLTSEDSAVYFCARYDYDG NWFFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID No. 19: Amino acid sequence corresponding to polynucleotide SEO ID No. 13, representing the CDRs and framework residues in PIPP chimeric light-chain (sequence in normal font correspond to framework residues and sequence in bold font corresponds to CDRs) MEIVLTQSPAIMSASLGERVTMTCTASSSVTSSYLHWYQQKPGSSPKLWIYSTS NLASGVPARFTGSGSGTSYSLTISSMEAEDAATYYCHQYHRSPYTFGGGTKLE LKR SEQ ID No. 20: Amino acid sequence corresponding to polvnucleotide SEO ID No. 14, representing the CDRs and framework residues in PIPP chimeric heavy-chain (sequence in normal font correspond to framework residues and sequence in bold font corresponds to CDRs) MAEVQLQQSGAEWKPGASVKMSCKASGFTFTNYWnWVRQRPGQGLEWIG EINPGFDTTNYSEKFKTKATLTVDTSSTTAYMQLSSLTSEDSAVYFCARYDYD GNWFFDVWGAGTTVTVSS Although the specificity and the affinity of binding with beta-hCG and hCG are primarily considered to be the functions of CDRs, the flanking amino acids residues have complementary roles in projecting these residues in appropriate conformation. Binding ofPIPP Selectively with Cancer Cells Discriminating Normal Healthy Cells of the Same Lineage An example will now be given of a blood cancer cell-line, which manifests binding with the PIPP antibody on the membranes with high specificity and affinity. The case in point is of MOLT-4, a human cell line developed by American Typed Culture Collection (ATCC) from a relapse patient of T-lymphoblastic leukemia. On incubation of these cells with the antibody developed by us (the PIPP), nearly all cancer cells bound the antibody on membranes, which is clearly evident by Flow Cytometry analysis (Fig. 1). The binding is authentically with hCG, proven and confirmed by competition with pure hCG (Fig. 2). An irrelevant monoclonal antibody directed at epitopes other than beta-hCG fails to bind with the cancer cells (Fig. 1). Furthermore, normal human peripheral blood white cells do not bind with the PIPP antibody, demonstrating thereby its ability to bind selectively with cancer cells, sparing normal healthy leukocytes (Fig.l). Thus, this antibody by virtue of the aforesaid property of specific location on cancer cells making hCG and non binding to normal cells has the potential to image metastasis of such tumour cells and has also the capability of delivering radiations and/ or drugs selectively to the tumour cells without affecting normal healthy cells (Fig. 3). It is thereby readily apparent that in contrast to chemotherapeutic drugs, which act not only on tumour cells but also on normal dividing cells in the body and thereby cause high toxicity and undesirable side effects, the selective homing of a high affinity antibody to the tumour cells provides an invaluable means to treat the tumour selectively without undue side-effects on other tissues of the body. Prevention of onset of pregnancy by PIPP PIPP is indeed workable and useful in preventing onset of pregnancy. Pregnancy is marked by hCG, which has an autocrine effect on formation of synctium, with enhanced synthesis of hCG and secretion of progesterone (Shi et al., 1993; Choudhary et al., 1992). To demonstrate this, the bioactivity of the PIPP was tested in differentiation of cytotrophoblasts derived from placentae (Dhar et al., 2004). Cytotrophoblast cells were isolated from placentae and maintained in culture with or without the chimeric antibody (PIPP). Progesterone secreted was quantified by ELISA. Fusion and cyto-architecture of the cells was studied by electron microscopy. Transmission electron micrographs given in Fig. 4 show that in the presence of PIPP antibody the cells retain distinctly their plasma membrane, while the control cells cultured in the absence of the antibody had no plasma membrane separating i cytotrophoblasts, a feature characteristic of syncytium formation. Fig. S shows that in presence of the antibody, the cells in culture fail to produce progesterone as compared with the control cells cultured without the antibody. Accordingly, the present invention relates to a set of three light and three heavy chain Complementarity Determining Regions (CDRs), and thereby a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic i gonadotropin (hCG) useful in detecting as well as treating cancer cells making hCG, imaging metastasis hCG-synthesizing tumors, delivering radiations or drugs selectively to such cancer cells sparing normal cells, lastly, preventing onset of pregnancy, and a composition thereof. 14 an embodiment of the present invention, wherein the invention relates to a set of 1 ti|ree light chain Complementarity Determining Regions (CDRs) VL-CDR1, VL- dDR2, and VL-CDR3 of SEQ ID Nos. 7 to 9 respectively of an antibody reacting selectively with human chorionic gonadotropin (hCG). In another embodiment of the present invention, wherein the invention relates to a set of three heavy chain Complementarity Determining Regions (CDRs) VH-CDR1, VH- CDR2, and VH-CDR3 of SEQ ID Nos. 10 to 12 respectively of an antibody reacting selectively with human chorionic gonadotropin (hCG). In yet another embodiment of the present invention, wherein the invention relates to a set of three oligonucleotides of SEQ ID Nos. 1 to 3 encoding three light chain (Complementarity Determining Regions (CDRs) VL-CDR1, VL-CDR2, and VL-CDR3 f SEQ ID Nos. 7 to 9 respectively. In still another embodiment of the present invention, wherein the invention relates to a Set of three oligonucleotides of SEQ ID Nos. 4 to 6 encoding three heavy chain Complementarity Determining Regions (CDRs) VH-CDR1, VH-CDR2, and VH-CDR3 bf SEQ ID Nos. 10 to 12 respectively. In still another embodiment of the present invention, wherein the invention relates to a polynucleotide of SEQ ID No. 13 comprising a set of three oligonucleotides of SEQ ID Nos. 1 to 3 encoding three light chain Complementarity Determining Regions (CDRs) VL-CDR1, VL-CDR2, and VL-CDR3 of SEQ ID Nos. 7 to 9 respectively, and framework residues flanking the corresponding three oligonucleotides. In still another embodiment of the present invention, wherein the invention relates to a polynucleotide of SEQ ID No. 14 comprising a set of three oligonucleotides of SEQ ID pJos. 4 to 6 encoding Ifcree heavy chain Complementarity Determining Regions (CDRs) VH-CDR1, VH-CDR2, and VH-CDR3 of SEQ ID Nos. 10 to 12 respectively, and framework residues flanking the corresponding three oligonucleotides. In still another embodiment of the present invention, wherein the invention relates to a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG), wherein said antibody comprises: o three light chain Complementarity Determining Regions (CDRs) VL-CDR1, VL-CDR2, and VL-CDR3 of SEQ ED Nos. 7 to 9 respectively, O three heavy chain Complementarity Determining Regions (CDRs) VH-CDR1, VH-CDR2, and VH-CDR3 of SEQ ID Nos. 10 to 12 respectively, o framework residues conforming to polypeptide sequences corresponding to polynucleotide sequences depicted in SEQ ID. Nos. 13, and 14, o Human IgGi as constant domain of Heavy Chain, and o Kappa as constant domain of light chain. In still another embodiment of the present invention, wherein the antibody binds to the beta-subunit of hCG. In still another embodiment of the present invention, wherein the antibody has an association constant of about 3x 1010 M'1 of binding with hCG. In still another embodiment of the present invention, wherein the invention relates to a method of detecting cancer cells making hCG in a subject in need thereof, said method comprising estimating hCG in blood and/or in urine and or in biopsies using aforementioned chimeric monoclonal antibody. In still another embodiment of the present invention, wherein the subject is a human being. In still another embodiment of the present invention, wherein the invention relates to a Safe method of imaging metastasis of human chorionic gonadotropin (hCG) synthesizing tumors in a subject in need thereof, said method comprising step of using pharmaceutically effective amount of chimeric monoclonal antibody tagged to radioisotope. In still another embodiment of the present invention, wherein the invention relates to a method of delivering radiations selectively to a cancer cells sparing normal cells in a subject in need thereof, using effective amount of chimeric monoclonal antibody, tagged to an appropriate source of radiation. In still another embodiment of the present invention, wherein the invention relates to a method of treating cancer in a subject in need thereof wherein cancer cells make hCG, said method comprising steps of administering pharmaceutically effective amount of chimeric monoclonal antibody tagged to appropriate drug, optionally along with pharmaceutically acceptable additives to the subject. In still another embodiment of the present invention, wherein the invention relates to a method of preventing onset of pregnancy in sexually active women said method comprising step of administering pharmaceutically effective amount of chimeric monoclonal antibody, optionally along with pharmaceutically acceptable additives to the subject In still another embodiment of the present invention, wherein it relates to a composition i comprising chimeric monoclonal antibody PIPP, specific to human chorionic gonadotropin (hCG), and along with pharmaceutically acceptable additives. In still another embodiment of the present invention, the PIPP binds to (3-subunit of hCG; therefore antibody binding to oc-subunit of hCG, is likely to have additive effect On PIPP mediated hCG intervention. Antibodies can be administered intramuscularly/intravenously. Antibodies can be delivered naked without attaching i any drug or radioactive material to them. Antibodies can be joined to a chemotherapy drag, radioactive particle (e.g. 13II), toxin (diphtherial toxin, pseudomonal toxin, plant toxins such as ricin A or saporin) or to cancer inhibiting compounds (such as curcumin, methotrexate), and used as delivery vehicles to take those substances directly to the cancer cells. Hie monoclonal antibody acts as a homing device, circulating in the body until it is attracted by, and attaches itself to, a cancer cell with a matching antigen. It delivers the toxic substance to where it is needed most, minimizing damage to normal cells in other parts of the body. Brief description of the accompanying drawings Fig 1 shows histograms reflecting binding of PIPP antibody on the membrane of Molt-4, a T-lymphoblastic leukemia cell line derived from a relapsed patient, as seen by flow (jsytometry. Fig 2 shows competition of binding of the antibody with Molt-4 cells by pure hCG, I further establishing binding of antibody PIPP with hCG exposed on membrane of the i cancer cells. Fig 3 shows ability of antibody PIPP to discriminate between cancer and normal cells. fig 4 Transmission electron micrographs of trophoblast cells in culture, showing a distinct plasma membrane separating the two adjoining trophoblast cells in the presence of the anti-hCG antibody PIPP. In the absence of the antibody, no plasma membrane is observed separating the cytotrophoblasts, indicating a true syncytium formation. N: nucleus; Cy: cytoplasm; PM: plasma membrane. Magnification: x2650. Fig 5: Quantitation of progesterone levels secreted by trophoblast cells in the presence r absence of PIPP. Progestrone was estimated by ELISA kit (IBL, Germany). The antibody was added to the culture medium at a dilution of 1:500 and 1:1000. The values ^re the mean ± S.D of three experiments performed in triplicate (** P PROVISIONAL SPECIFICATION A CHIMERIC MONOCLONAL ANTIBODY FOR BINDING SELECTIVELY TO hCG Field of the present Invention The field of the present invention relates to a set of three light and three heavy chain Complementarity Determining Regions (CDRs), and thereby a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG) useful in detecting as well as treating cancer cells making hCG, imaging metastasis of hCG-synthesizing tumors, delivering radiations selectively to such cancer cells sparing normal cells, lastly, preventing onset of pregnancy, and a composition thereof. Background and prior art references of the Invention HCG is an oncofetal protein. It is made soon after fertilization and its presence in urine or blood is employed as criteria for diagnosis of pregnancy. All pregnancy diagnosis kits employ antibodies specific to hCG in enzyme-immuno-assay or radio-immunoassay based kits. As hCG plays also a crucial role in implantation of the embryo onto the uterine endometrium, antibodies against hCG have the capability of preventing the establishment of pregnancy (GP Talwar et al 1994 & 1997).These publications describe the protection offered to normally menstruating and ovulating sexually active women against pregnancy so long as the titres of circulating antibodies against hCG are above 50ng/ml. These and other previous clinical trials (I Kharat et al 1990, GP Talwar et al 1990) in women provide evidence on the safety of anti-hCG antibodies in humans in whom no other body function is disturbed except control of fertility. From these studies it is obvious that competent antibodies can be used for preventing pregnancy without any side effects. Administration of preformed antibodies has the advantage over active immunization of assuring efficacy of protection in every woman who receives antibody of desirable characteristics in adequate dose. As is well recognized, active immunization with a vaccine does not elicit high enough antibody response from every recipient. Moreover the duration over which the antibody titres persist varies considerably from person to person. These disadvantages are overcome by delivery of proper dose of the antibody whose biological half life is predictable. There is thus scope of using this antibody as a vacation contraceptive for providing protection to women against pregnancy for 4-6 weeks without disturbance of hormonal profiles and derangement of menstruation. Besides pregnancy, hCG synthesis and secretion is observed in cancers. Trophoblastic cancers (choriocarcinomas) make this protein in abundance and monitoring of hCG serially provides an index of growth of such cancers. Disappearance of hCG would indicate successful surgical removal of cancerous tissues or success of chemotherapeutic treatment. Subsequent appearance of hCG in blood and urine would, on the other hand, be indicative of relapses of such tumours (S.K Gupta et al 1982). Apart from choriocarcinomas, an observation of great interest is the unexpected synthesis of hCG by a number of non-trophoblastic cancers. Its ectopic synthesis has been reported in lung cancers (YT Ikura 2000, MJ Szturmowicz et al 1999), uroethelial cancer (RK lies et al 1990, R Nishimura et al 1995,), colon adenocarcinomas ( RP Kiran et al 2001, M Lundin et al 2000), pancreatic carcinoma (H Alfthan et al 1992, H Taylor et al 1990), liver malignancies, neuroendocrine tumours (JM Bidart et al 1997) and in patients with poorly differentiated carcinomas (H Sumi et al 2001). Production of (3- hCG detected in non-trophoblastic tumours is usually associated with cancers of poor prognosis (SA Butler et al 2000, HF Acevado et al 1996, I Marcillac et al 1992, V Lazar et al 1995, R Hoermann et al 1992). Szturmowicz et al (1999) observed that serum P- hCG was elevated more frequently in stage 4 patients of non- small cell lung cancer. Syrigos et al (1998) reported that 40% of pancreatic exocrine tumours produce (3- hCG and its production is corelated with adverse survival. The survival time between p-hCG positive colorectal cancers was significantly shorter than P- hCG negative cancer patients (M Lundin et al 2001, RP Kiran et al 2001). It would thus be evident that this protein or its sub-units alpha and beta are made by a variety of cancers at advanced stages, which are highly aggressive and patients bearing these have short survival. More often than not cancers at this stage are resilient to the presently available chemotherapeutic drugs. Most tumours which start making ectopically alpha or beta (or both) carry the subunit on their membranes ( H.Acevado et al 1996), presumably by virtue of the presence of receptors for hCG and its subunits, which pick up the protein made by the tumour cells. In at least one tumour, the non-small cell lung cancer, the alpha subunit of hCG made unexpectedly by these cells was observed to act as growth promoter of these cells. Antibody against alpha-hCG given to nude mice along with the tumour cells prevented the establishment of the tumour implants (S.Kumar et al 1992). Antibodies given to mice with established tumours caused necrosis of the established tumour (Kumar et al 1992). Thus antibodies competent to bind alpha or beta subunits of hCG and inactivate their bioactivity have the potential of exercising immuno-therapeutic benefit for preventing the dissemination of tumours whose growth is promoted by hCG or its subunits. References • Acevedo, H. F., and R. J. Hartsock. 1996. Metastatic phenotype correlates with high expression of membrane- associated complete beta-human chorionic gonadotropin in vivo. Cancer. 7:2388-99 • Alfthan, H., C. Haglund, P. Roberts, and U. H. Stenman. 1992. Elevation of free beta subunit of human chorionic gonadotropin and core beta fragment of human chorionic gonadotropin in the serum and urine of patients with malignant pancreatic and biliary disease. Cancer Res. 52:4628-33. • Bidart, J. M., E. Baudin, F. Troalen, D. Bellet, and M. Schlumberger. 1997. Eutopic and ectopic production of glycoprotein hormones alpha and beta subunits. Ann Endocrinol. 58:125-8. • Butler, S. A., M. S. Ikram, S. Mathieu, and R. K. lies. 2000. The increase in bladder carcinoma cell population induced by the free beta subunit of human chorionicgonadotrophin is a result of an anti- apoptosis effect and not cell proliferation. Br J Cancer.82:1553-6. • Gupta S.K., S. Ramakrishnan and G. P. Talwar. 1982. Properties and characteristics of an anti-hCG monoclonal antibody. J Biosc .4:105-113 • Hoermann, R., A. L. Gerbes, G. Spoettl, D. Jungst, and K. Mann. 1992. Immunoreactive human chorionic gonadotropin and its free beta subunit in serum and ascites of patients with malignant tumors. Cancer Res. 52:1520-4. • Ikura,Y.,Inoue, H. Tsukuda, T. Yammoto and Y. Koboayashi.2000. Primary choriocarcinoma and human chorionic gonadoptrophin-producing giant cell carcinoma of the lung: are they independent entities ? Histopathology. 36:17-25 lies, R. K., and T. Chard. 1989. Enhancement of ectopic beta-human chorionic gonadotrophin expression by interferon-alpha. J Endocrinol. 123:501-7. lies, R. K., C. L. Lee, R. T. Oliver, and T. Chard. 1990. Composition of intact hormone and free subunits in the human chorionic gonadotrophin-like material found in serum and urine of patients with carcinoma of the bladder. Clin Endocrinol (Oxf). 33:355-64 Kiran, R. P., R. Visvanathan, and C. G. Simpson. 2001. Choriocarcinomatous metaplasia of a metachronous adenocarcinoma of the colon. Eur J Surg Oncol. 27:436-7 Kumar, S., G. P. Talwar, and D. K. Biswas. 1992. Necrosis and inhibition of growth of human lung tumor by anti-alpha- human chorionic gonadotropin antibody. J Natl Cancer Inst. 84:42-48 Kharat . I., Nair, N.S., Dhall .K., Sawney,.H., Krishna,U.,1990 . Analysis of menstrual records of women immunized with anti-hCG vaccines inducing antibodies partially cross-reactive with hLH.Contraception. 41:293-9. Lazar, V., S. G. Diez, A. Laurent, Y. Giovangrandi, F. Radvanyi, D. Chopin, J. M. Bidart, D. Bellet, and M. Vidaud. 1995. Expression of human chorionic gonadotropin beta subunit genes in superficial and invasive bladder carcinomas. Cancer Res. 55:3735-8. Lundin, M., S. Nordling, M. Carpelan-Holmstrom, J. Louhimo, H. Alfthan, U. H. Stenman, and C. Haglund. 2000. A comparison of serum and tissue hCG beta as prognostic markers in colorectal cancer. Anticancer Res. 20:4949-51. Lundin, M, S. Nordling, J. Lundin, H. Alfthan, U. H. Stenman, and C. Haglund. 2001. Tissue expression of human chorionic gonadotropin beta predicts outcome in colorectal cancer: a comparison with serum expression. Int J Cancer. 95:18-22. Marcillac, I., F. Troalen, J. M. Bidart, P. Ghillani, V. Ribrag, B. Escudier, B. Malassagne, J. P. Droz, C. Lhomme, P. Rougier, and et al. 1992. Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer Res. 52:3901-7. Nishimura, R., T. Koizumi, K. Morisue, N. Yamanaka, R. Lalwani, M. Yoshimura, T. Nakagawa, K. Shii, K. Hasegawa, and S. Baba. 1995. Expression and secretion of the beta subunit of human chorionic gonadotropin by bladder carcinoma in vivo and in vitro.Cancer Res. 55:1479-84. Sumi, H., K. Itoh, Y. Onozawa, Y. Shigeoka, K. Kodama, K. Ishizawa, H. Fujii, H. Minami, T. Igarashi, and Y. Sasaki. 2001. Treatable subsets in cancer of unknown primary origin. Jpn J Cancer Res. 92:704-9. Syrigos, K. N., I. Fyssas, M. M. Konstandoulakis, K. J. Harrington, S. Papadopoulos, N. Milingos, P. Peveretos, and B. C. Golematis. 1998. Beta human chorionic gonadotropin concentrations in serum of patients with pancreatic adenocarcinoma. Gut. 42:88-91. Szturmowicz, M, J. Slodkowska, J. Zych, P. Rudzinski, A. Sakowicz, and E. Rowinska- Zakrzewska. 1999. Frequency and clinical significance of beta-subunit human chorionic gonadotropin expression in non-small cell lung cancer patients. Tumour Biol. 20:99-104. Talwar, G. P., O. Singh, R. Pal, N. Chatterjee, P. Sahai, K. Dhall, J. Kaur, S. K. Das, S. Suri, K. Buckshee, and et al. 1994. A vaccine that prevents pregnancy in women. ProcNatl Acad Sci USA. 91:8532-6. Talwar, G. P., O. M. Singh, S. K. Gupta, S. E. Hasnain, R. Pal, S. S. Majumbar, S. Vrati,A. Mukhopadhay, J. Srinivasan, U. Deshmukh, S. Ganga, A. Mandokhot, and A. Gupta. 1997. The HSD-hCG vaccine prevents pregnancy in women: feasibility study of areversible safe contraceptive vaccine. Am J Reprod Immunol. 37:153-60. Talwar G.P., Hingorani .V ., Kumar, S., Roy, S.m Banerjee.A., Shahani, S.M Krishna. 1990 Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine. Contraception. 1990 41:301-16. Taylor, H., N. Heaton, P. Farrands, N. Kirkham, and M. Fletcher. 1990. Elevated human chorionic gonadotrophin levels in a patient with pancreatic carcinoma presenting with a testicular metastasis. Postgrad Med J. 66:1073-5. Objects of the Present Invention The main object of the present invention relates to developing light chain Complementarity Determining Regions (CDRs) of an antibody reacting selectively with human chorionic gonadotropin (hCG). Another main object of the present invention relates to developing heavy chain Complementarity Determining Regions (CDRs) of an antibody reacting selectively with human chorionic gonadotropin (hCG). Yet another main object of the present invention relates to a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG). Still another object of the present invention relates to develop a method of detecting cancer cells making hCG in a subject in need thereof, said method comprising estimating hCG in blood and/or in urine and/or in biopsies using chimeric monoclonal antibody. Still another object of the present invention relates to develop a safe method of imaging metastasis of human chorionic gonadotropin (hCG) synthesizing tumors. Still another object of the present invention relates to develop a method of delivering radiations selectively to cancer cells sparing normal cells. Still another object of the present invention relates to develop a method of treating cancer. Still another object of the present invention relates to develop a method of preventing onset of pregnancy in sexually active women. Still another object of the present invention relates to develop a composition comprising chimeric monoclonal antibody PIPP, specific to human chorionic gonadotropin (hCG), and along with pharmaceutically acceptable additives. Summary of the present Invention The present invention relates to a set of three light and three heavy chain Complementarity Determining Regions (CDRs), and thereby a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG) useful in detecting as well as treating cancer cells making hCG of hCG synthesizing tumors, imaging metastasis hCG, delivering radiations and drugs selectively to such cancer cells sparing normal cells, lastly, preventing onset of pregnancy, and a composition thereof. Detailed description of the present Invention The Unique Monoclonal Antibody This antibody was developed by immunizing BALB/c mice with highly purified beta subunit of hCG. Splenocytes from mice carrying high antibody titers reactive with both beta sub-unit of hCG and hCG were fused with SP2O myeloma cells by methodologies originally described by Nobel Laureates Milstein and Kohler, which are now commonly followed for the purpose by those in the art. The hybrid cells bearing genes for perpetual replication derived from SP2O tumour cells and those coding for synthesis and secretion of the particular antibody derived from a lymphocyte of the mouse immunized with beta-hCG were selected and cloned by methodologies familiar to those in the field. Briefly the principle is that, after fusion of splenocytes lacking thymidine kinase with SP2O, the hybrid cells are selected for growth in medium containing hypoxanthine, aminopterin and thymidine (HAT medium). Aminopterin blocks the main biosynthetic pathways of purine and pyrimidine nucleotides and forces the cells to utilize hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and TK enzymes of the salvage pathways for nucleotide biosynthesis. Whereas neither SP2O nor the splenocytes would multiply, the hybrid between these two cells carries functional genes for both HGPRT and TK and therefore are able to grow in HAT medium. The cells were cloned repeatedly by infinite dilution so as to obtain eventually a population in which each cell secretes the same antibody. The product is thus homogeneous for its characteristics of specificity and binding affinity with the target antigen. Properties ofPIPP Specificity. This antibody secreted by the hybridoma cells binds with beta hCG and hCG. There was no perceptible binding of this antibody to other pituitary hormones, the human growth hormone, human thyroid stimulating hormone and human follicle stimulating hormone. Its binding to human leutinizing hormone was less than 5% and functionally negligible. As hCG is not measurable in the blood and urine of males or non-pregnant females, this hormone or its sub-units are not synthesized and secreted to any appreciably detectable extent by healthy non-pregnant females nor by normal healthy males. It is on account of its literal absence in healthy non-pregnant state, and its appearance as soon as pregnancy takes place, that it is taken as a reliable criterion of diagnosis of pregnancy excluding, of course, the existence in the woman of cancers making hCG. Affinity of binding. The antibody binds with hCG with fairly high affinity. The Association constant of the antibody was of the order of 3xlO10 M"1, as determined by Scatchard Plot. Molecular Structure and Complementarity Determining Regions (CDRs) of the Unique Antibody PIPP is a monoclonal developed initially by immunizing mouse with hormone specific beta-subunit of hCG. It has subsequently been converted into a chimeric antibody in which the constant domain of the heavy chain is the human IgGi and the constant domain of the light chain is Kappa. These are fused by genetic engineering techniques with the variable regions of the original mouse monoclonal antibody. The antigen binding property of the monoclonal antibody is resident in the variable portion and is expressed by a set of three Complementarity Determining Regions (CDRs) in the light and by three CDRs in the heavy chain. The nucleotide and amino acid sequences of CDRs in this unique antibody in the variable light and heavy chains are as follows: Light Chain CDRs VL-CDR1 (SEQ ID No. 1) ACT GCC AGC TCA AGT GTG ACT TCC AGT TAC TTG CAC (SEQ ID No. 7) TASSSVTSSYLH VL-CDR2 (SEQ ID No. 2) AGC ACA TCC AAC CTG GCT TCT (SEQ ID No. 8) S T S N L A S VL-CDR3 (SEQ ID No. 3) CAC CAG TAT CAT CGT TCC CCG TAC ACG (SEQ ID No. 9) HQYHRSPYT Heavy Chain CDRs VH-CDR1 (SEQ ID No. 4) AAC TAC TGG ATC ATC (SEQ ID. No. 10) N Y W I I VH-CDR2 (SEQ ID No. 5) GAG ATT AAT CCT GGT TTT GAT ACT (SEQ ID No. 11) El N P G F D T VH-CDR3 (SEQ ID No. 6) TAT GAT TAC GAC GGA AAC TGG TTC TTC GAT GTC (SEQ ID No. 12) YDYDGNWFFDV The above denoted CDRs are flanked in this antibody by the 'Framework' residues. These are depicted in SEQ ID Nos.13, and 14 below. Variable Light Chain with CDRs and Flanking Residues (CDR residues are shown in Bold) SEQ ID No. 13. ATGGAAATTGTGCTGACCCAGTCTCCAGCAATCATGTCTGCATCTCTGGGGGA ACGGGTCACCATGACCTGCACTGCCAGCTCAAGTGTGACTTCCAGTTACTT GCACTGGTACCAGCAGAAGCCAGGATCCTCCCCCAAACTCTGGATTTATAGC ACATCCAACCTGGCTTCTGGAGTCCCAGCTCGCTTCACTGGCAGTGGGTCTG GGACCTCTTACTCTCTCACAATCAGCAGCATGGAGGCTGAAGATGCTGCCAC TTATTACTGCCACCAGTATCATCGTTCCCCGTACACGTTCGGAGGGGGGAC CAAGCTGGAACTGAAACGG Variable Heavy Chain showing the particular CDRs and the Framework Flanking Residues (CDR residues are shown in Bold) SEQIDNo. 14. ATGGCCGAGGTTCAGCTGCAGCAGTCTGGAGCTGAGGTTGTGAAGCCTGGGG CTTCAGTGAAGATGTCCTGCAAGGCTTCTGGCTTCACCTTCACCAACTACTG GATAATCTGGGTGAGGCAGAGGCCTGGACAAGGCCTTGAGTGGATTGGAGA GATTAATCCTGGTTTTGATACTACTAACTACAGTGAGAAGTTCAAGACCAA GGCCACACTGACTGTTGACACATCCTCCACCACAGCCTACATGCAGCTCAGC AGCCTGACATCTGAGGACTCTGCGGTCTATTTTTGTGCAAGATATGATTACG ACGGAAACTGGTTCTTCGATGTCTGGGGCCAGGGAACCCTGGTCACCGTCT CCTCA Although the specificity and the affinity of binding with beta-hCG and hCG are primarily considered to be the functions of CDRs, the flanking amino acids residues have complementary roles in projecting these residues in appropriate conformation. Binding ofPIPP Selectively with Cancer Cells Discriminating Normal Healthy Cells of the Same Lineage An example will now be given of a blood cancer cell-line, which manifests binding with the PIPP antibody on the membranes with high specificity and affinity. The case in point is of MOLT-4, a human cell line developed by American Typed Culture Collection (ATCC) from a relapse patient of T-lymphoblastic leukemia. On incubation of these cells with the antibody developed by us (the PIPP), nearly all cancer cells bound the antibody on membranes, which is clearly evident by Flow Cytometry analysis (Fig. 1). The binding is authentically with hCG, proven and confirmed by competition with pure hCG (Fig. 2). An irrelevant monoclonal antibody directed at epitopes other than beta-hCG fails to bind with the cancer cells (Fig. 1). Furthermore, normal human peripheral blood white cells do not bind with the PIPP antibody, demonstrating thereby its ability to bind selectively with cancer cells, sparing normal healthy leukocytes (Fig.l). Thus, this antibody by virtue of the aforesaid property of specific location on cancer cells making hCG and non binding to normal cells has the potential to image metastasis of such tumour cells and has also the capability of delivering radiations and/ or drugs selectively to the tumour cells without affecting normal healthy cells (Fig. 3). It is thereby readily apparent that in contrast to chemotherapeutic drugs, which act not only on tumour cells but also on normal dividing cells in the body and thereby cause high toxicity and undesirable side effects, the selective homing of a high affinity antibody to the tumour cells provides an invaluable means to treat the tumour selectively without undue side-effects on other tissues of the body. Brief description of the accompanying drawings Fig 1 shows histograms reflecting binding of PIPP antibody on the membrane of Molt-4, a T-lymphoblastic leukemia cell line derived from a relapsed patient, as seen by flow cytometry. Fig 2 shows competition of binding of the antibody with Molt-4 cells by pure hCG, further establishing binding of antibody PIPP with hCG exposed on membrane of the cancer cells. Fig 3 shows ability of antibody PIPP to discriminate between cancer and normal cells. Accordingly, the present invention relates to a set of three light and three heavy chain Complementarity Determining Regions (CDRs), and thereby a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG) useful in detecting as well as treating cancer cells making hCG of hCG-synthesizing tumors, imaging metastasis hCG, delivering radiations or drugs selectively to such cancer cells sparing normal cells, lastly, preventing onset of pregnancy, and a composition thereof. In an embodiment of the present invention, wherein the invention relates to a set of three light chain Complementarity Determining Regions (CDRs) VL-CDR1, VL-CDR2, and VL-CDR3 of SEQ ID Nos. 7 to 9 respectively of an antibody reacting selectively with human chorionic gonadotropin (hCG). In another embodiment of the present invention, wherein the invention relates to a set of three heavy chain Complementarity Determining Regions (CDRs) VH-CDR1, VH- CDR2, and VH-CDR3 of SEQ ID Nos. 10 to 12 respectively of an antibody reacting selectively with human chorionic gonadotropin (hCG). In yet another embodiment of the present invention, wherein the invention relates to a set of three oligonucleotides of SEQ ID Nos. 1 to 3 encoding three light chain Complementarity Determining Regions (CDRs) VL-CDR1, VL-CDR2, and VL-CDR3 of SEQ ID Nos. 7 to 9 respectively. In still another embodiment of the present invention, wherein the invention relates to a set of three oligonucleotides of SEQ ID Nos. 4 to 6 encoding three heavy chain Complementarity Determining Regions (CDRs) VH-CDR1, VH-CDR2, and VH-CDR3 of SEQ ID Nos. 10 to 12 respectively. In still another embodiment of the present invention, wherein the invention relates to a polynucleotide of SEQ ID No. 13 comprising a set of three oligonucleotides of SEQ ID Nos. 1 to 3 encoding three light chain Complementarity Determining Regions (CDRs) VL-CDR1, VL-CDR2, and VL-CDR3 of SEQ ID Nos. 7 to 9 respectively, and framework residues flanking the corresponding three oligonucleotides. In still another embodiment of the present invention, wherein the invention relates to a polynucleotide of SEQ ID No. 14 comprising a set of three oligonucleotides of SEQ ID Nos. 4 to 6 encoding three heavy chain Complementarity Determining Regions (CDRs) VH-CDR1, VH-CDR2, and VH-CDR3 of SEQ ID Nos. 10 to 12 respectively, and framework residues flanking the corresponding three oligonucleotides. In still another embodiment of the present invention, wherein the invention relates to a chimeric monoclonal antibody PIPP of high specificity and affinity for binding to human chorionic gonadotropin (hCG), wherein said antibody comprises: o three light chain Complementarity Determining Regions (CDRs) VL-CDR1, VL-CDR2, and VL-CDR3 of SEQ ID Nos. 7 to 9 respectively, o three heavy chain Complementarity Determining Regions (CDRs) VH-CDR1, VH-CDR2, and VH-CDR3 of SEQ ID Nos. 10 to 12 respectively, o framework residues conforming to polypeptide sequences corresponding to polynucleotide sequences depicted in SEQ ID. Nos. 13, and 14, o Human Igd as constant domain of Heavy Chain, and o Kappa as constant domain of light chain. In still another embodiment of the present invention, wherein the antibody binds to the beta-subunit of hCG. In still another embodiment of the present invention, wherein the antibody has an association constant of about 3x 1010 M"1 of binding with hCG. In still another embodiment of the present invention, wherein the invention relates to a method of detecting cancer cells making hCG in a subject in need thereof, said method comprising estimating hCG in blood and/or in urine and or in biopsies using aforementioned chimeric monoclonal antibody. In still another embodiment of the present invention, wherein the subject is a human being. In still another embodiment of the present invention, wherein the invention relates to a safe method of imaging metastasis of human chorionic gonadotropin (hCG) synthesizing tumors in a subject in need thereof, said method comprising step of using pharmaceutically effective amount of chimeric monoclonal antibody tagged to radioisotope. In still another embodiment of the present invention, wherein the invention relates to a method of delivering radiations selectively to a cancer cells sparing normal cells in a subject in need thereof, using effective amount of chimeric monoclonal antibody, tagged to an appropriate source of radiation. In still another embodiment of the present invention, wherein the invention relates to a method of treating cancer in a subject in need thereof wherein cancer cells make hCG, said method comprising steps of administering pharmaceutically effective amount of chimeric monoclonal antibody tagged to appropriate drug, optionally along with pharmaceutically acceptable additives to the subject. In still another embodiment of the present invention, wherein the invention relates to a method of preventing onset of pregnancy in sexually active women said method comprising step of administering pharmaceutically effective amount of chimeric monoclonal antibody, optionally along with pharmaceutically acceptable additives to the subject. In still another embodiment of the present invention, wherein the invention relates to a composition comprising chimeric monoclonal antibody PIPP, specific to human chorionic gonadotropin (hCG), and along with pharmaceutically acceptable additives.

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670-del-2004-drawings.pdf

670-del-2004-Form-2-(23-11-2012).pdf

670-DEL-2004-Form-3-(13-09-2013).pdf

670-del-2004-Form-5-(23-11-2012).pdf

670-del-2004-form1.pdf

670-del-2004-form2 (provisional).pdf

670-del-2004-form2.pdf

670-del-2004-form26.pdf

670-del-2004-form3.pdf

670-del-2004-form5.pdf

670-del-2004-GPA-(23-11-2012).pdf

670-del-2004-Petition-137-(10-09-2013).pdf