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Yashraj Biotechnology Limited C-232 TTC Industrial Area, Pawane MIDC, Navi Mumbai 400705, India Website: www.yashraj.com Email: info@yashraj.com Telephone: +91 22 62166800

YBL NEWSLETTER

YBL: An Innovation Driven Biotech

ADVISORY BOARD Shri Arvind Bhanushali Shri Bharat T. Dagha Dr. G. Padmanaban Dr. Paresh Bhanushali

EDITORIAL BOARD

Chief Editor Dr. Chander P. Puri

Members

Dr. Shweta Bhatt Dr. Anuj Kumar Gupta Dr. Kunal Shukla Mrs. Prerana Rathod Dr. G. Subrahmanyam Dr. Mukesh M Tripathi

I N S I D E T H I S I S S U E

YBL: An innovation driven biotech…… Editorial…… Micro-RNAs: A diagnostic look…… Growth factors in stem cell biology…… Indigenization of technologies............

Diagnosing a disease is the beginning of clinical practice. Misdiagnosis can be lethal.

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Yashraj Biotechnology Limited (YBL), based in Mumbai, India, is the leader in the global marketplace and among the top biotechnology firms in the world manufacturing and marketing various native, recombinant and cell derived antigens; and polyclonal and monoclonal antibodies. The Company also undertakes OEM assignments for protein purification and R&D for diagnostic biomarkers using nationwide regulatory approved network of sourcing of human biological materials and product development. YBL’s major strength lies in its unique and vast network for sourcing biomedical fluids; including but not limited to urine, plasma, seminal fluid, placenta, ascetic fluid, pleural fluid etc. from a wide-range of national and international hospitals and healthcare providers. YBL endeavors to provide improved in vitro diagnostic methods which can be used under resource constraint situations.

YBL’s product portfolios span across varied disease segments such as Cancer, Cardiovascular, Neurological, Autoimmune disorders, Inflammation etc. with antigens of highest purity developed using latest and most cutting edge technologies. The highest standards of quality and unwavering commitment towards healthcare innovation, has enabled YBL to capture some of the biggest market segments for various biomarker antigens it develops.

YBL, a UL registered, and ISO 13485:2003 and ISO 9001:2008 certified company, drives procurement of human biomedical waste, production and supply chain as well as product integrity through rigorous examinations and follow-up surveillance so that safety and quality are non-negotiable.

Recently, YBL has committed itself to penetrating the niche area of drug development and to create disease specific model systems for preclinical testing of drugs and pharmacological compounds on pluripotent stem cells. YBL has state-of-the-art cell culture and stem cell facility and a fully equipped animal facility to undertake this ambitious program and several collaborators in top institutions across the globe. Through this program YBL plans to contribute to new drug discovery and clinical development programs, personalized medicine for patients and stem cell and tissue banking.

YBL encourages and facilitates the creation, discovery, dissemination and application of new knowledge through its network of technology labs, and academic alliance initiatives. R & D and product development is approved by the Department of Science and Industrial Research, Ministry of Science and Technology, Government of India.

By using the human biomedical waste for development of new diagnostics, YBL is not only resolving the problem of waste management but is creating wealth which is being geared towards improving the health.

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Yashraj Biotechnology Ltd.

A17976

Editorial

Dr.Chander P. Puri, PhD, FNASc, FAMS

Group Director Yashraj Group of Companies

In Vitro Diagnostics for Healthcare

In vitro diagnostic (IVD) tests for healthcare have become indispensable for clinical practice as the test results provide information about predisposition of disease, early and correct diagnosis of illness, and help evaluate the response to treatment. Appropriate testing allows early-stage interventions, reducing late-stage healthcare expenditure. Today the professional diagnostic labs offer more than 2000 different test parameters for the diagnosis of more than 700 medical indications. It is therefore not surprising that the diagnostic tests influence 60-70 percent of clinical decision making. It is on account of this that the Indian in vitro diagnostic market which was around Rs. 37.7 billion rupees during 2014-15, increased to 61.7 billion during 2017-18 and is expected to continue growing at 15-20 percent annually. The increase over the last few years and the projected increase are influenced by increased life expectancy at birth, high incidence of lifestyle disorders, emerging insurance sector, growing economy, greater awareness and expanding healthcare sector even in the rural areas. There are multiple segments in the IVD market like Biochemistry, Immunoassays, Microbiology, Hematology, with almost 70 percent of market share however, the molecular diagnostic product market is also expanding rapidly as they possess higher precision and allow for speedy detection of infectious diseases and genetic disorders at an early stage of development. It is therefore essential that the diagnostic methods not only provide accurate information but are also cost effective particularly for those people who contribute over 80% of healthcare expenditure out of their own pocket. YBL’s endeavors in that direction are highly commendable.

A Successful Week at Medica 2017

YBL recently exhibited its product range at MEDICA 2017 held in Dusseldorf and met with several potential customers. The show was very successful and YBL thanks all those who had visited, appreciated and encouraged us.

Meet Us at CACLP 2018

Please visit us during CACLP Expo at Chongqing, China from 18th to 20th March 2018, at Booth No. N5-B150. We will be happy to answer your queries and discuss potential collaborations and business proposals.

Please contact: Mr. LAX, Vice President Marketing, Yashraj Biotechnology Ltd.

Email: laxminarayan@yashrajbio.com; Skype ID: lax2602; Website: www.yashraj.com

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YBL invites suggestions for collaborative research, specific antigen, antibody requirements and business proposals from pioneers in diagnostic industry, scientific community, particularly young entrepreneurs.

Micro-RNAs: A Diagnostic Tool

Dr.Mukesh Mani Tripathi, PhD

Vice President Yashraj Biotechnology GmbH

New Age Molecular Diagnostics

There are growing and emerging evidences about the potential applications of micro-RNAs in early detection of the diseases. In the recent years, wide range of studies implicated, up regulation and down regulation of micro-RNAs as a hallmark of disease initiation and progression. The most recent studies performed by Li. Q et al suggest that serum miR-542-3p levels could be a potential non-invasive blood biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients. The authors clearly demonstrate that the serum levels of miR-542-3p are higher in patients with osteosarcoma compared with the control groups.

https://www.ncbi.nlm.nih.gov/pubmed/29103020

During the course of predevelopment stage and establishment of micro-RNA as a reliable diagnostic tool, one could very well envisage, the specific antibody based detection and enrichment of these known micro-RNA complexes from the native sources and hence further characterization and understanding of these invaluable tools.

YBL as a known leader in processing wide range of biomedical fluids e.g. Human serum, plasma, cancer fluid, blood cells, could play a significant role in scaling up these naturally existing micro-RNA complexes, we believe this could be of immense use in the diagnostic field and for the researchers world-wide.

List of micro RNAs controlling various physiological activities are summarized in the below list from Bertoli G, Cava C, Castiglioni I. MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer. Theranostics 2015; 5(10):1122-1143.

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In the recent years, wide range of studies implicated, up regulation and down regulation of micro-RNAs as a hallmark of disease initiation and progression.

With micro-RNAs becoming invaluable clinical biomarker, biomedical fluid, could potentially be an important source for purification of diverse range of micro-RNAs and further molecular characterization.

Growth Factors in Stem Cell Biology

Dr.Shweta Bhatt, PhD

Chief Scientific Officer Yashraj Biotechnology Limited

Tools for Preclinical Drug Discovery

Regenerative medicine shows promise for repair of damaged tissues and organs, deliver safer and more efficient drugs, better disease models, and cures for numerous devastating diseases. Growth factors, being naturally occurring regulatory molecules which bind receptors on the cell surface, provide biochemical cues for stem cell differentiation and are used to develop novel strategies to treat human diseases by investigating cellular processes controlling development, aging, and tissue regeneration. They stimulate cell and tissue function through influencing cellular differentiation by changing their biochemical activity and cellular growth patterns, and regulating their rate of proliferation. Though structurally they are peptide-like hormones, growth factors are not limited to defined tissues and act on target tissues in both diffusible and non-diffusible manners, regulating a variety of cellular events including cell migration, survival, adhesion, proliferation and differentiation.

iPSC Differentiation into Progenitor Cells Through Growth Factor Mediated Induction

Yashraj Biotechnology Ltd., owing to years of experience and technical expertise in the area of protein purification has committed itself to the development and large scale production of cell-culture safe “Peptide Growth Factors”, such as bFGF, EGF, HGF, VEGF, BMP4, Activin A, Wnt3a amongst others, which will be used in vitro for research and development activities for better elucidation of signalling pathways underlying various diseases. The R&D initiatives will pave way for the possible therapeutic use of these growth factors in the treatment of human diseases.

Modulation of growth factors at the injury site is one of the strategies to stimulate tissue regeneration.

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The global stem cells market valued at $5.23 billion in 2016 is expected to reach $13.73 billion by 2025, expanding at a CAGR of 10.5% from 2017 to 2025.

http://www.businesswire.com

Some of the clinically-approved growth factors include:

Platelet-derived growth factor-BB (PDGF-BB) – for diabetic neuropathic ulcers and periodontal defects

Bone morphogenetic factor-2 (BMP2) – tissue regeneration at sites of tibia fracture

Bone morphogenetic factor-7 (BMP7) – tissue regeneration for tibia

Cell therapy / Organ transplantation: Stem cell treatment could put an end to inefficient disease treatments and lack of donors for organ transplants. Embryonic pluripotent stem cells have the ability to differentiate into three germ layers (endoderm, mesoderm, and ectoderm) and unlimited capacity for self-renewal. The ethical issues around the use of embryonic stem cells led to the introduction of induced pluripotent stem cells or iPSCs. iPSCs are adult cells reprogrammed with the transfection of specific set of transcription factors - Oct3/4, Sox2, Klf4 and c-Myc. In the presence of growth factors, iPSCs differentiate into majority of the progenitor cells required for development. Therefore, the role of growth factors in differentiation of iPSCs provides an avenue for creating an unlimited supply of embryonic-like stem cells, bypassing the current ethical issues. Also, iPS cells allow for personalized medicine as both the nuclear and the mitochondrial DNA match the donor. Using iPS cells would also not require any immune suppression during transplant, making them a superior choice over donor embryonic stem cells for therapeutic uses.

Therefore, thorough understanding of signalling pathways controlling the fate of pluripotent stem cells, which is influenced by both physical (attachment factors) and biochemical cues (growth factors), will enable their successful differentiation into specialized cells that make up all the tissues in the body. This will enable subsequent use of stem cells in cell-based therapies, drug development, and disease modeling.

References

Tada, S., Kitajima, T., and Ito, Y. (2012) Design and synthesis of binding growth factors. Int. J. Mol. Sci. 13, 6053–6072.

Hajimiri, M., Shahverdi, S., Kamalinia, G., and Dinarvand, R. (2015) Growth factor conjugation: strategies and applications. J. Biomed. Mater. Res. A 103, 819–838.

Mao, A. S., and Mooney, D. J. (2015) Regenerative medicine: Current therapies and future directions. Proc. Natl. Acad. Sci. U. S. A. 112, 14452–14459.

Clevers, H. (2016) Modeling Development and Disease with Organoids. Cell 165, 1586–1597.

Yu, J., and Thomson, J. A. (2008) Pluripotent stem cell lines. Genes Dev. 22, 1987–1997.

Takahashi, K., and Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676.

Yin, P. T., Han, E., and Lee, K.-B. (2016) Engineering Stem Cells for Biomedical Applications. Adv. Healthc. Mater. 5, 10–55.

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Key Market Segments of Stem Cell Industry:

1. Stem Cell Banking

2. Toxicology and Drug Discovery

3. Stem Cell Therapeutics

4. Stem Cell Derivatives – antigens, growth factors, cytokines etc.

Growth factors are mainly used in the treatment of chronic diseases such as anemia, renal disorders, cancer etc. For instance, Erythropoietin, used in the stimulation of Red Blood Cells is used to treat anemia; Granulocyte Macrophage Colony Stimulating Factor is involved in the stimulation of White Blood Cells in cancer patients.

Indigenization of Technologies

Dr.Paresh Bhanushali, PhD

Director, Technical Yashraj Biotechnology Limited

Protein Purification & Characterization

Yashraj Biotechnology Ltd. is engaged in manufacturing and distribution of purified human proteins for in vitro diagnostic industry and research entities. With intensive R&D efforts YBL has developed indigenous technologies to purify antigens, most over 98% purity, from human biomedical fluids. The antigens are available to scientists for their research programmes as well to diagnostic industry.

The new native antigens under development include: Transferrin, Alpha-2-Macroglobulin, Azurocidin and Calprotectin. Recombinant antigens under development are Myoglobin, Procalcitonin and HBcAg. YBL’s state-of-the-art monoclonal antibody development facility has undertaken development of Anti-CEA, Anti-CA 125, and Anti HbA1c antibodies through cell culture using Bioreactor.

Some other products which are almost ready to be offered to the potential customers include: rTroponin I, rTroponin T, rProcalcitonin, and Azurocidin. YBL also undertakes OEM manufacturing of the antigens from our customers.

Trusted Partner For Sourcing of Antigens

Native Recombinant Cardiac: CRP D-Dimer

Cardiac: FABP3

Infection: HBsAg-Ay HBsAg-Ad

Infection: SLO Defensin Beta 2

Cancer: CA 15-3 CA 19-9 CA 72-4 CA 125 CEA AFP PSA PSA-ACT KFLC (K-free Light Chain) LFLC (L-free Light Chain) HE-4

Inflammation:

SAA TNF

Renal: A1M B2M CysC NGAL

Renal: NGAL

Autoimmune: MPO

Tumor: NSE

Others: sTfr PAPP-A Ferritin RBP Azurocidin

Others: Alpha-Synuclein CKMM S100A8 Prolactin S100A9 SHBG

We solicit your views and suggestions, as well as business-related enquiries:

Mr. Bharat T. Dagha Director International Business Development Yashraj Biotechnology Ltd E-mail: bharat@yashrajbio.com Tel: +91 9930602951

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