CSIR

Innovation in drug development:

1. Innovation of novel drugs:

CSIR has made valuable contributions to the pharma industry which is reflected by the development of
several novel drugs, (13 out of the 20 new drugs developed in India since inception and one during last 5
years) which have been successfully commercialized, and are currently marketed for eg:

Drug/Product Use Licensee & year of license

α β – Arteether Antimalarial Themis Medicare Ltd., Mumbai (1997)
Centchroman Contraceptive & HLL Lifecare Ltd., Thiruvananthapuram (1990) Torrent
DUB Pharma. Ltd., Ahmedabad (1991)
Bacosides Enriched Memory Lumen Marketing Co. Chennai (2002)
Standardized Extract improvement
of Bacopa
Dalzbone Rapid Fracture Pharmanza Herbal Pvt. Ltd. Gujarat (2015)
Healing
Centimizone Anti-thyroid Unichem Lab. Ltd., Mumbai (1972)
Elubaquin Anti-relapse anti- Nicholas Piramal India Ltd., Mumbai (1999)
malarial
Centpropazine Antidepressant Merind Ltd., Mumbai (1996)
Chandonium Iodide Neuromuscular Ranbaxy Labs Ltd., New Delhi (1987) Cipla Ltd.,
blocker Mumbai (1995)
Consap Spermicidal cream HLL Lifecare Ltd., Thiruvananthapuram (2004)
Centbutindole Neuroleptic Chemosyn Pvt. Ltd., Mumbai (1987)
Centbucridine Local anaesthetic Themis Chemical Ltd., Mumbai (1987)
Gugulipid Hypolipidemic Cipla Ltd., Mumbai (1987) Nicholas Piramal India Ltd.,
Mumbai (2000)
Isaptent Cervical dilatation Unichem Lab. Ltd., Mumbai (1972)
Joint Fresh Osteoarthritis Pharmanza Herbal Private Ltd. (2018)
CDRI a CSIR institute has a rich drug pipeline in both single molecule and herbal categories that are
ready for licensing. These candidates include single molecules to treat dyslipidemia, thrombosis,
malaria, post-menopausal osteoporosis and fracture, and several standardized herbal
extracts/formulations that have hepatoprotective, cardioprotective and osteoprotective effects.

2. Development of drug processes/drug formulation:

Cost effective and innovative processes for around 25 generic drugs/drug intermediaries have been
developed. Some of the drug technologies that have been commercialized are:

 l-Ephedrine hydrochloride (broncho-dilator), dextroproxyphene hydrochloride (analgesic)

arteether (anti-malarial), amlodipine (Calcium channel blocker), Naltrexone (anti-alcoholic).

List of formulations developed by CDRI are provided below:

 Dry powder Inhalation of anti-tuberculosis drug

 Layer-by-layer nanostructures for delivery of kaempferol to bone marrow
 Self-microemulsifying delivery system for anti-malarial combination
 Combination kit for delivery of native glucagon-like peptide 1 (glp-1) fragment 7-36 for
euglycemia
 A novel oral formulation of amphotericin b to treat visceral leishmaniasis
 Vaginal film containing sapindus saponins for contraception and antimicrobial activity
 Nasal dry powder eutectic for nose-to-brain transport of zolmitriptan
 GLP-1- once a month in-situ depot for diabetes treatment
 Cyclodextrin based drug delivery systems have been developed for rifampicin to
improve its bioavailability in fixed dose combinations
 Development of plant-based adjuvants: RRL Jammu is involved in the development of
plant based molecules for use with anti-hepatitis vaccine as adjuvant replacing Al(OH)3.
DST and Bharat Biotech Ltd have extended financial support. One of the molecules, RLJ-
NE-299A is in the advanced stage of its development as an adjuvant

Development of medical technology:

1 Diagnostic kits/Probes
 PCR based diagnostic probes for tuberculosis/leishmaniasis
 Direct agglutination test for leishmaniasis
 An antigen-based ELISA diagnostic kit has been developed for allergic
bronchopulmonary Aspergillosis. It is a sensitive and specific test for early diagnosis of
the infection
 A diagnostic kit for alpha-fetoprotein for detection of fetal abnormalities has been
commercialized by Shantha Biotech
  DNA based diagnostic methods for prediction of predisposition to certain diseases:

a. Method of detection of allelic variants of Spino cerebellar ataxia 2 gene.

b. Novel primers for screening schizophrenia and a method thereof.

 A method of detecting predisposition to atopic disoders by screening for human (Stat

6) gene variants
o A method of detection of SP-A2 gene variants useful for prediction of
predisposition to pulmonary tuberculosis
o Detection of MBL gene variants useful for prediction of predisposition to
bronchial asthma with allergic rhinitis.

2 Other technologies

 Biomaterials have been prepared from reconstituted human amnion for in vitro culture of
fibroblasts, with potential application as dressings in open wounds. Chemically modified bovine
collagen, which forms a clear solution, has been used to prepare collagen shields and bandage
lenses, for use in cataract surgery. A collagen membrane has also been prepared for use in
periodontal surgery
 Technologies for Hip-joint prosthesis and artificial eyeballs transferred to a Kolkata-based
industry.
 Rights for marketing of a bio-informatics software tool, PL-HOSTFA assigned to Jalaja Tech,
Hyderabad.
 Technology for gene delivery using cationic amphiphiles.
 Seapath: A bio-informatics software tool for identifying adhesin and adhesin-like proteins useful
for developing new therapeutics
 Gene-decipher. A bio-informatics software tool for identifying protein coding DNA sequences
useful as potential drug targets.
 Comparative genomics and biology of non-coding RNA in the human genome
 Translational applications of hologenome sequencing: using nextgeneration sequencing on a
sample containing mixed population of genomes from an epidemic with appropriate processing
and enrichment
 A rapid method of enzyme linked immuno-sorbent assay (ELISA).
 Pharmacogenomics (Variable Drug response)

 A method for predicting an individual’s bronchodilatory response to a beta agonist.

 Novel allelic variant of CYP2C19 associated with drug metabolism.
Biopharma:

 Genetically engineered oral cholera vaccine, has been developed in a collaborative project of
IMTECH, NICED and IICB and based on recombinant strain of V. cholerae ‘VAL3’ is currently
under phase II clinical trials
 Streptokinase: Developed technology for first indigenous clot buster drugNatural streptokinase,
being produced by Cadila Pharma Ltd. under brand name 'STPase' and a recombinant form of
streptokinase, being produced by Shasun Chemicals & Drugs Ltd. under the brand name of
'Lupiflo' and Klotbuster', which have made India self-sufficient in terms of affordable 'clot
buster' drugs for heart attack
 Better vaccines for tuberculosis CSIR-IMTECH has proposed the use of novel vaccines called
lipidated-promiscuouspeptide vaccines. These synthetic vaccines are safer than BCG because
they do not contain infectious material. Moreover, they generate long-lasting, protective
immune responses and are not influenced by pre-existing antibodies. This type of vaccine
strategy has already proven to be successful in an animal model of tuberculosis and is being
tested in human clinical trials for other infectious diseases and cancer. Lipidated-promiscuous-
peptide vaccines have all the essential qualities that can make them successful in tuberculosis-
endemic countries. Such vaccines can impart better protection than BCG and will have a long-
reaching positive impact on millions of people
 Molecular mechanism of signal transduction and gene regulation by M.tuberculosis phop-phor
system
 Biomarker for asthma using repeat and single nucleotide polymorphisms
 Technology for oral delivery of insulin and Hepatitis B vaccine
 Stem cell research facility for regenerative medicine
 Ayurgenomics: Focusses on discovery of prediction marker(s) for preventive and personalized
medicine
 Mutational variations buffered by chemical chaperons Hidden genetic variations have the
potential to lead to the evolution of new traits. Molecular chaperones, which assist protein
folding, may conceal genetic variations in protein-coding regions. CSIR-IGIB has investigated the
potential of chemical milieu of cells to affect protein folding. It was found that osmolyte
trimethylamine N-oxide (TMAO) can buffer mutations that impose kinetic traps in the folding
pathways of two model proteins. This study has provided a new insight into understanding of an
important phenomenon.
 Nonprocessive [2 + 2]e- off-loading reductase domains from mycobacterial nonribosomal
peptide synthetases In mycobacteria, polyketide synthases and nonribosomal peptide
synthetases (NRPSs) produce complex lipidic metabolites by using a thio-template mechanism of
catalysis. CSIR-IGIB has demonstrated that the off-loading reductase (R) domain of
mycobacterial NRPSs performs two consecutive [2 + 2]e(-) reductions to release corresponding
 alcohols. The first crystal structure of an R domain from Mycobacterium tuberculosis NRPS
provides strong support to this mechanistic model. This study presents an elegant example of
the recruitment of a canonical short-chain dehydrogenase/ reductase family member as an off-
loading domain in the context of assembly-line enzymology.
 Metastases suppressor NME2 associates with telomere ends and telomerase and reduces
telomerase activity within cells
 Genome-wide analysis reveals distinct patterns of epigenetic features in long non-coding RNA
loci

 Multi-functional mini pilot scale fermentor: RRL has designed and fabricated a microprocessor
controlled 75 to 100 litre fermentor with in situ autoclaving facilities. The pilot plant has been
successfully installed and commissioned at a number of places under consultancy programme.
The total cost of the each unit is approximately Rs. 1.5 million. The plant has all the features of
an R&D pilot scale fermentor wherein distributed parameters and variables can be studied. It
can also be used as a production plant for high-value, low-volume products, even for genetically
engineered organisms
 Know-how for clones for expressing Lysostaphin, r-CGF, r-streptokinase and r-proinsulin licensed
to Bharat Biotech International, Hyderabad
 Genome-wide analysis reveals distinct patterns of epigenetic features in long non-coding RNA
loci
 Hepatitis C Virus NS5A Binds to the mRNA Cap-binding Eukaryotic Translation Initiation 4F
(eIF4F) Complex

Annexure:

CSIR biological lab list