KNOW-HOW FOR NATURAL STREPTOKINASE
After concerted R&D efforts of several years, IMTECH scientists could develop process technology for the first indigenous clot buster drug. This was launched in the year 2001 and ever since then has been received well by the market. As a result of the introduction of this Indian brand, the overall price of streptokinase has seen a crash-down from about Rs.3500 to about Rs.1500 per dose of 1.5 million units.
The complete technological package for the production of SK, including hyper-producer strain, fermentation, and down stream processing to prepare injectable quality British Pharmacopial grade drug (with more than 98% purity and approx. 65% overall process yield) was transferred to industry (M/S Cadila Pharma. Ltd., Ahmedabad). It has been commercialized and the product (christened ‘STPase’) produced through CSIR/IMTECH technology, is already in the market. Streptokinase was earlier not manufactured in India and was wholly imported. Therefore, the development of this indigenous, cost effective technology for large scale purification of this drug by biotechnological means is an appreciable achievement.
In summary, it is a testimony to the high standards of the natural SK technological package developed at IMTECH that the testing, implementation, scale-up, production and Regulatory Approval could be accomplished within a year of the transfer of know-how from the laboratory to the first pharmaceutical firm (Cadila Pharmaceuticals Ltd., Ahmedabad) in the year 2001.
This drug which is cheaper than the other brands based on imported technologies has been well received by the market, as is apparent from the regular royalty payments received by IMTECH.
KNOW-HOW FOR RECOMBINANT STREPTOKINASE
After the introduction of natural streptokinase in the market in the year 2001, the IMTECH team (headed by Dr. Girish Sahni) continued to work in this area and soon thereafter developed a facile process to manufacture a recombinant version of natural type streptokinase which is roughly ten times efficient as the natural SK production technology.
The technological package (recombinant clones, fermentation parameters and down-stream processing to obtain drug-quality product)) was successfully transferred in the year 2002-03 to a leading drug industrial house M/S Shasun Chemicals & Drugs Ltd., Chennai which specializes in bulk drug manufacture.
Being a recombinant DNA-derived product, besides the process scale-up, various stages of getting detailed safety clearances for both animal toxicology and human clinical trials required several years of hand-holding between Shasun and IMTECH teams. The end result is an extremely proficient process at 300-500 liter scaled levels.
The product has been launched for the Indian markets on July 10, 2009 under the brand names ‘Lupiflo’ and ‘Klotbuster’.
This technology, introduced in the market, is expected to bring down the prices significantly and make this vital life-saver drug available to even the most economically challenged consumer at affordable costs.
KNOW-HOW FOR CLOT-SPECIFIC STREPTOKINASE
A team of IMTECH scientists has designed state-of-the-art new-generation clot buster protein which shows strong promise as a ‘clot-specific’ thrombolytic drug. Although the most used thrombolytic protein, Streptokinase, has generally proven to be as efficacious in large scale field trials on myocardial infarction as its more expensive counterparts (urokinase & tissue plasminogen activator), the administration of the drug at clinically effective doses often results in rapid plasminogen activation in the blood stream, leading to the unwanted proteolytic degradation of clotting factors, causing bleeding and other serious side effects in many patients. Hence, a clot-buster drug with minimal side effects has been highly desirable. This function i.e. the ability to dissolve the pathological blood clot without plasminogen activation through the circulatory system is a highly coveted and premium property in any clot buster drug of choice. The new clot-buster drug developed at IMTECH is unique in its functions, where the engineered clot buster circulates in an inactive state without activating the blood plasminogen. However, once it encounters and binds to the pathological blood clot, it is activated and thereby generates plasmin in and around the vicinity of the clot, which, in turn, cleaves the fibrin clots without the occurrence of generalized proteolysis, as often happens during SK mediated (and other thrombolytic based) therapies.
The technology package for the new thrombolytic has been transferred to a US firm (Nostrum Pharmaceuticals Inc., USA) and primate studies have successfully been completed in Nov. 2007, validating the proof-of-concept of this molecule. Work on upscaling, animal and human testing in progress. Based on the tie-up made between Nostrum pharmaceuticals, USA, and CSIR (IMTECH), Chandigarh, the new, engineered Clot buster will be developed and commercialized both in developing countries and other markets worldwide. It is expected to be commercialized by middle of 2011.
KNOW-HOW FOR IMMUNOSUPPRESSIVE AGENT
Nostrum Pharmaceuticals, a privately-held company based in Edison, New Jersey, had obtained a worldwide license to develop and commercialize Caerulomycin A, and its proprietary derivatives and analogues (“Caerulomycin”) for their novel indication of immunosuppression. The license was obtained from Institute of Microbial Technology (“IMTECH”), Chandigarh, India, one of India’s preeminent research institutes, governed by the national government’s Council of Scientific and Industrial Research (“CSIR”).
Caerulomycin has shown remarkable promise in immunosuppression of both T-cells and B-cells in both in-vitro experiments and in rodent animal model studies. In addition, preliminary studies carried out by IMTECH also show a lack of toxicity in the rodent experiments. Based on these observations made by IMTECH’s scientists, Caerulomycin has a potential to develop into a blockbuster drug to be used to prevent organ transplant rejection and diseases such as certain autoimmune disorders where immunosuppression is the key to the mitigation of the disease symptoms.
Licensing of Caerulomycin to Nostrum is a proud achievement for IMTECH, especially for the scientific teams that developed Caerulomycin over several years of meticulous research which led to the filing of patent applications for the technology. Caerulomycin is the first small molecule being licensed by IMTECH to a foreign company, and it is a proud achievement for IMTECH and CSIR.
KNOW-HOW FOR RECOMBINANT STAPHYLOKINASE
A recombinant strain has been developed for high level intracellular production of Staphylokinase in E. coli. This agent (a biogeneric) has previously shown, promise as an improved clot-buster in clinical trials abroad.
A high-efficiency facile two step protocol for purification of staphylokinase has been developed.
The complete technological package for the production for recombinant staphylokinase has been transferred to M/S Strides Arcolab Ltd., Bangalore. The licensee is working on development of the commercial scale process with IMTECH’s advice.
ENERGY EFFICIENT ALCOHOL TECHNOLOGY
This Technology developed jointly by IMTECH and Vittal Mallya Scientific Research Foundation, Bangalore, has been licenced to a leading Indian distillery chain. The process gives about 10% alcohol using molasses having initial sugar levels of 25-30% in about 30 hours, saves 15-20% steam upon distillation; keeps net effluent load same while reducing effluent volume by about 30%.
BIOCONVERSION OF RIFAMYCIN B TO RIFAMYCIN S
This know-how provides an efficient, cost-effective enzymatic process for rifamycin B to rifamycin S in almost 100 percent yield using an IMTECH isolate. It obviates the harsh chemical treatments involving oxidative and corrosive agents.
IMTECH has licenced this know-how to two large sector Indian drug companies.
MICROBIAL PROCESS FOR D-p-HYDROXYPHENYLGLYCINE
IMTECH scientists have developed a commercially viable process for the enzymatic conversion of D-l-hydantoin to corresponding d-amino acid; i.e., D-p-hydroxyphenylglycine. This work was sponsored by a leading multinational company.KNOW-HOW FOR ALKALINE PROTEASE
Alkaline proteases have found increasing applications in detergent and leather industry. A strain of Bacillus sphaericus, isolated by IMTECH scientists showed protease activity upto 70,000 AU/litre in 100 L fermenter with a medium containing starch and soyatose.This know-how can be used for the production of a better quality enzyme for use in detergents and in leather industry for bating etc. The process is available for licensing. The advantage of IMTECH process is its thermotolerance at higher temperatures.
KNOW-HOW FOR ALPHA AMYLASE
This enzyme is used in textiles and food industry and in many other applications. IMTECH scientists have cloned and expressed in B. subtilis, alpha-amylase gene from a thermophilic strain. The know-how is available for transfer at 100 L, process scale.
KNOW-HOW FOR UROKINASE
Another enzyme to dissolve blood clots. The know-how is available for transfer.
DEVELOPMENT OF A LIVE, ORAL, RECOMBINANT VACCINE FOR CHOLERA
IMTECH in collaboration with the National Institute of Cholera & Enteric Diseases and Indian Institute of Chemical Biology, Calcutta has developed an oral recombinant cholera vaccine. This vaccine, first of its kind anywhere in the world outside USA was constructed following a novel strategy in which an avirulent strain was converted into a vaccine candidate capable of elaborating only the immunogenic B subunit of the cholera toxin using recombinant DNA technology. This candidate vaccine which has been found to give full protection in animal studies and completely safe has also been found to be completely safe toxicologically. This vaccine is undergoing phase II human volunteer studies. This vaccine has been granted patent No. 6,106,843 in the USA and is under consideration in several European countries under EPO. This project has been accorded a high priority under the Jai-Vigyan Mission Plan of the Govt. of India.
Vaxipred- A Software tool for vaccine design:
IMTECH in collaboration with bioinformatics company BioMantra, launched an immunoinformatics software tool ‘VaxiPred’ for computer aided vaccine design. This new software tool helps in the prediction of vaccine candidates from a pathogen, thus reducing time in vaccine development. VaxiPred is available to users as a subscription-based web service. This software tool is an integrated version of 14 different immunoinformatics based software programmes developed by IMTECH for discovering antigens of the disease causing pathogens.
This software tool has been licensed to National Institute for Biologicals, Noida.