Velvizhi Ranganathan Heine,

Ph.D.

**** ***** *****, #**, *** Diego, CA 92122

Email: accogr@r.postjobfree.com; Tel:

617-***-****

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Summary:

. Over 18 years of diverse experience in biomedical research in

academics and industry.

. 14 years of industry experience with leading roles in executing and

directing the development and qualification of a

variety of binding and cell-based bioassays in support of in-

process, release and stability testing of drug products.

. Method development experience for a variety of biopharmaceutical

products including monoclonal antibodies

recombinant proteins, biosimilars and blood coagulation factors

and vaccines.

. Extensive experience in the quantification and characterization of

process related impurities from different host cell

systems.

. Identification and evaluation of new technologies to assess the

biological activity of biotherapeutic drug candidates.

. Experience in managing Scientists and Research Associates.

. Several years of regulatory experience from Analytical development by

supporting filings and responding to different

agencies (FDA, EMEA, Korean, etc). Author and reviewer of

several regulatory filings including IND and 4 BLA filings.

. Several years of CMC experience by supporting both clinical and

commercial programs.

. Seven years of experience in routine lab maintenance, travel budgeting

and capital planning and managed

laboratory budgeting.

. 5 years of industry experience in GMP environment required to operate

a quality control bioassay laboratory.

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Professional Experience:

Gilead Sciences, Oceanside, California

Senior Scientist - Potency Assay Group, Analytical Development

June 2013-January 2014

. Lead potency assay group in the bioassay development for: monoclonal

antibody based drug product, recombinant fusion protein vaccine, and

Bi-specific antibodies; Present potency assay approaches for various

clinical programs to the senior management.

. Developed bioassay strategies and worked on the assay development for

several drug product based bio therapeutics; Enzyme-inhibition

bioassay, kd binding assay, development of immunoassay including

western blot analysis for the quantitation of recombinant fusion

protein present in mammalian host cells (vaccine therapeutic),potency

assay development for two bi-specific antibodies.

. Worked with research team in the identification and selection of

robust assays for transfer into development. Responsible for

qualifying and maintaining all critical custom reagents used in

potency assays.

. Planned experimental design for new bioassay development and

optimization; discussed with CROs in implementing development work if

needed, review experimental results and provided technical guidance

for CROs

. Oversee potency and impurity assays for GMP lot release and stability

including data review and approval

. Supported all technical troubleshooting for both internal testing and

CRO labs.

. Authored/reviewed development summary reports, memos and author

Regulatory submissions.

. Provided bioassay support to various CMC teams

. Managed of direct reports

Biogen Idec, Cambridge, Massachusetts

Senior Scientist - Bioassay, Analytical Development

August 2009-May 2013

Scientist II- Bioassay, Analytical Development

October-2006-July 2009

Scientist I, Bioassay & Assay Technology, Bio analytical QC

July 2002-October 2006

Bioassay Development /Qualification for Clinical and Commercial

Programs

. Developed binding and cell-based functional potency assays for various

biologics and recombinant fusion protein

using different assay platforms (ELISA, DELFIA, ECL-MSD, TR-

FRET, reporter gene, cell-signaling based assays).

. Developed and qualified both chromogenic and aPTT coagulation assays

using a blood coagulation analyzer.

. Experience in FcRn assays for blood coagulation factors

. Developed and qualified peptide binding assay for anti-peptide

antibody

. Established in-house capability of assessing Antibody dependent

cellular phagocytosis (ADCP) for anti-peptide antibody

. Experience in developing bioassays for Biosimilars molecules

. Verification of the cellular expression of ligand/receptor as targets

for drug product based bio-therapeutics by FACS analysis

. Experience in assay qualification: LOQ, Accuracy, Precision and

Linearity

. Managed critical reagent qualification after labeling with different

labels (biotin and sulfo-tag)

. Extensive experience in troubleshooting and developing strategies to

address assay acceptance criteria.

. Experience in the optimization of sample preparation for activity

assays.

. Managed both internal and external assay transfers.

. Strong experience in providing technical guidance to QC after assay

transfer.

. Assessment of method robustness for several late stage clinical

programs prior to BLA filing.

. Excellent understanding of current industry best practices and

regulatory guidance for potency assays

. Author and reviewer of method development reports and protocols.

. Strong experience in potency data analysis using: Excel, Softmax,

Parallel Line Analysis (PLA), StatLIA, Image quant software programs.

Process related impurities for Clinical /Commercial Programs:

. Managed the characterization and demonstration of clearance of process

related impurities in several clinical and commercial products.

. Experience in development and qualification of process related

impurity assays for different host cell systems such as NS/0, HEK and

CHO:

. Designed strategies for the preparation of host cell protein (HCP)

antigen, generation, purification and characterization of anti-HCP

antibodies.

. Experience in interacting with contract manufacturers to generate

different anti-HCP antibodies.

. Extensive experience in the characterization of the anti-HCP

antibodies.

. Developed and qualified several assay formats for the quantitation of

HCP (ELISA/ECL-MSD platform)

. Extensive experience in cross-over studies between old and newly

developed assays to confirm assay performance and suitability.

. Developed assay acceptance criteria and guidelines for the

quantitation of host cell protein assays.

. Extensive experience in troubleshooting host cell protein assays with

special focus on non-dilutional linearity observed in process

intermediates.

. Extensive experience in comparing the host cell protein profiles of

products derived from different host cell line modifications (1D and

2D-DIGE analysis).

. Author and reviewer of process related impurity sections of several

regulatory filings.

. Experience in working with FDA or European regulatory authorities in

response to process related impurity questions.

. Authored characterization and method development reports for different

process related impurities.

. Managed all host cell protein reagents inventory.

Evaluation of New Technologies:

. Evaluated several new technologies for the bioassay development

and established first cell-based reporter gene assay for

antibody drug product.

. Evaluated several instruments for bioassay automation and

established automated pipetting station in the bioassay lab to

reduce assay variability of cell-based assays.

. Established in-house Two Dimensional Differential in Gel

Electrophoresis (2D-DIGE) and 2D-DIGE Western blot capability to

support HCP characterization.

Project Management:

. Supervised direct reports from junior research associates to

Scientist II level with experience in performance goal setting

and performance assessment.

. Continuous involvement in training and mentoring (technical and

developmental) team members.

. Efficient project management skills: Met timelines and used

effective communication to achieve set goals.

. Managed routine maintenance of bioassay lab, group travel, capital

planning and managed bioassay laboratory budgeting for 7 years.

. Collaborated with inter- and intra-departmental scientists

including Analytical Development, Cell culture, Process

Biochemistry, Protein Formulation, Quality Control, Research and

Manufacturing.

. CMC Team member of various Clinical and Commercial projects

. Managed and provided support for several regulatory filings of

early and late stage products and also responding to different

regulatory agencies questions.

. Author and reviewer of regulatory filings including 4 BLA

filings and provided support for commercial products.

GMP Experience:

. Developed and qualified: a. End-point PCR for Mycoplasma detection in

cell culture.

. b. Whole Blood Assay for testing pyrogenicity in biotherapeutical

products. c. Q-RT-PCR assay for the Quantitation of CHO-Endogenous

Retroviral burden in bulk harvest. d. End -point ELISA for the

detection of 1-3 beta D-Glucans by Glucatell Assay.

. Implemented reagent qualification guidelines and stability trending

programs for different clinical products.

. Experience in sample testing, reviewing and approving data for

product release under GMP and regulatory compliance.

. Supervised assay transfers between development and Quality labs.

. Familiarity with manufacturing processes and application of GMP, use

of ICH and FDA guidelines.

. Experience in IQ/OQ/PQ protocols and reports for new lab

instrumentation.

. Experience in handling deviations/OOSs and managed QC bioassay

and manufacturing-related investigations.

Academic Experience:

. Postdoctoral Fellow, Center for Blood Research, Harvard Medical

School, Boston.

Mechanism of regulation and functional analysis of DNA repair

and genome stability pathways in

human chromosomal disorders; mechanism of telomere extension

and chromosome stability.

. Postdoctoral Fellow, Beth Israel Medical Center, Harvard Institutes of

Medicine, Boston.

Mechanism of regulation of transcription factor, AML-1 in

normal hematopoiesis and leukemia.

Postdoctoral Fellow, The James Brown Cancer Center, University of

Louisville, KY.

Role of pro and anti-apoptotic proteins in the regulation of

Apoptosis; mechanism of drug-

resistance in breast cancer.

Education:

Education

Ph.D Biochemistry, Cancer Institute, Chennai, India

M.S. Medical Microbiology, University of Madras, India

B.S. Chemistry, University of Madras, India

Scientific Capabilities:

Molecular Biology: Nucleic acid extraction, Cloning techniques, in

vitro transcription, PCR: real time, Q-PCR and RT-PCR using Taqman

chemistry and ABI 7700 and 7900 sequence detection systems, in gel

hybridization for telomere measurements, Site-directed mutagenesis,

DNA-Protein Interactions- gel shift assays. Cell -Based Assays:

Whole blood assay and Glucatell assay to test pyrogens; primary

and general cell culture, transfection, reporter assays, gene

expression systems, exposure and survival analysis of cells to

different DNA damaging agents, DNA repair experiments, cell

fractionation techniques, cell cycle analysis, FACS, ICA, IF,ELISA

Protein Chemistry: Recombinant protein expression (bacterial),

protein-protein interactions: IP, mutant analysis by deletion or

site-directed mutagenesis using both yeast two-hybrid screens and

GST -pull down experiments, yeast two hybrid system- subcloning,

transformation and screening libraries. Biochemical/Analytical

Methods: 1 and 2D SDS-PAGE electrophoresis, IEF, in vitro

translation, iodination of proteins, immunoblotting, sub-cellular

localization of proteins.

Enzyme assays: peroxidase, caspase, phosphorylation, Kinase and

telomerase assays. Generation of Antibodies: hybridomas and

polyclonal antibodies.

Awards:

Won the "Best Overall Study" award for a project investigation study

at Biogen Idec, Cambridge, MA

Presentations/Workshops:

. Evaluation of FVIII activity method robustness for a late stage

clinical program, CASSS Bioassays 2013, March 4-6, Rockville, Maryland

(Poster)

. Strategies for Potency Assessment for Biotherapeutic Antibodies,

BioAnalytical Summit, Baltimore, MD 22-24 March 2012 (Talk)

. Cross-over study between Two Immunoassays for Quantitation of NS/0

derived Residual Host Cell Proteins: Enzyme-linked immunosorbent assay

(ELISA) and Electrochemiluminescence based Meso Scale Discovery (MSD)

Method, May 18-20, 2011, San Francisco, CA (Poster)

. To select not to select: Cell-based potency assays, CASSS Bioassays

2010, (FDA-Biotech industry collaborative conference), November 1-2,

2010, Bethesda, Maryland (Talk)

. Phase-based Approach in the Development of Potency Assays for a

Monoclonal Antibody Protein Therapeutic, IIR cell based conference,

October 3-6, 2008 San Francisco, CA (Talk)

. Requirement of ATM for the phosphorylation of Nijmegen Breakage

Syndrome protein in a DNA damage response. International Workshop on

Nijmegen Breakage Syndrome, Czestochowa, Poland, 8-11, June 2000.

(Talk)

. Requirement of ATM for the phosphorylation of Nijmegen Breakage

Syndrome protein in a DNA damage response. Cold Spring Harbor

Symposium On "Biological Responses to DNA Damage" May 31-June 5, 2000.

(Poster)

. IBC conference on: Bioassay Development and Validation, Boston, 2005

. IBC conference on: Bioassay Development and Validation, Maryland, 2003

Publications

1. Luke F. Peterson, Anita Boyapati, Velvizhi Ranganathan, Atsushi

Iwama, Daniel G.Tenen, Schickwann Tsai, and Dong-Er Zhang The

Hematopoietic Transcription Factor AML1 (RUNX1) Is Negatively

Regulated by the Cell Cycle Protein Cyclin D3 Mol. Cell. Biol. 25:

102**-*****, 2005.

2. Nakanishi, K., Taniguchi, T., Ranganathan, V., New, H.V., Moreau,

L.A., Stotsky, M., Mathew, C.G., Kastan, M.B., Weaver, D.T and Andrea,

A.D. Interaction of FANCD2 and NBS1 in the DNA damage response. Nature

cell biology 4, 913-920, 2002.

3. Ranganathan, V., Heine, W.F., Ciccone, D.N., Rudolph, K, L., Wu,

X., Chang, S., Hai, H., Ahearn, I.M., Livingston, D.M., Resnick, I.,

Rosen, F., Seemanova, E., Jarolim, P., DePinho, R.A and Weaver, D.T.

Rescue of a Telomere Length Defect of Nijmegen Breakage Syndrome Cells

Requires NBS and Telomerase Catalytic Subunit. Current Biology 11, 962-

966, 2001.

4. Clark, B.J., Ranganathan, V and Combs, R. Steroidogenic acute

regulatory protein expression is dependent upon post-translational

effects of cAMP-dependent protein kinase A.

Molecular and Cellular Endocrinology 173, 183-192, 2001.

5. Clark B.J., Ranganathan, V and Combs R. Post-translational

regulation of steroidogenic acute regulatory protein by cAMP-dependent

protein kinase A. Molecular and Cellular Endocrinology 173, 183-192,

2001.

6. Wu, X., Ranganathan, V., Weisman, D.S., Heine,W.F., Ciccone,

D.N.,O'Neill, T.B., Crick, K.B., Lane, W., Livingston, D.M and Weaver,

D.T. ATM Phosphorylation of Nijmegen breakage syndrome protein is

required in a DNA damage response. Nature 405, 477-482, 2000.

7. Murphy, K.M., Ranganathan, V., Farnsworth, M.L., Kavallaris, M and

Lock, R.B. Bcl-2 inhibits Bax translocation from cytosol to

mitochondria during drug-induced apoptosis of human tumor cells. Cell

death and Differentiation 7, 102-111, 2000.

8. Ranganathan.V., Nihar.R.J and Prabir K.De. Hormonal effects on

Hamster lacirmal gland female-specific major 20 kDa secretory protein

and its immunological similarity with submandibular gland major male-

specific proteins. J.Steroid Biochem. Mol. Biol 70, 151-158, 1999.

9. Elliot, M.J., Murphy, K.M., Stribinskiene, L., Ranganathan, V.,

Sturges, E., Farnsworth, M.L and Lock, R.B. Bcl-2 inhibits early

apoptotic events and reveals post-mitotic multinucleation without

affecting cell cycle arrest in human epithelial tumor cells exposed to

etoposide. Cancer Chemotherapy and Pharmacology 44, 1-11, 1999.

10. Prabir K. De and Ranganathan, V. Hormonal influences on Syrian

hamster lacrimal gland: Marked repression of a major 20 kDa secretory

protein by estrogens, androgens and thyroid hormones. Lacrimal Gland,

Tear Film and Dry Eye Syndromes 2 by Plenum Press, Advances in

Experimental Medicine and Biology Series, 85-88, 1998.

11. Ranganathan,V and Prabir K. De. Western Blot of Proteins from

Coomassie stained gels. Analytical Biochemistry 234, 102-104, 1996.

12. Meenakshi, A., Ranganathan. V, Veenu Manoharan and Udayachander,

M. Enzyme Immunoassay of estrogen receptors in human breast cancer.

Med. Science Res 24, 463-466, 1996.

13. Ranganathan, V and Prabir K. De. Androgens and estrogens markedly

inhibit the expression of 20 kDa major protein in Hamster exorbital

lacrimal gland. Biochemical and Biophysical Research Communications 8,

412-417, 1995.

14. Udayachander, M., Meenakshi, A., Harikrishnan, R, Padma S and

Ranganathan. V. Immunoscintigraphy of MCF-7 rat mammary tumor

xenograft using Monoclonal Antibody. Indian Journal of Biochemistry

and Biophysics 31, 31-37, 1994.

15. Udayachander, M., Meenakshi, A., Padma.S. and Ranganathan, V.

Monoclonal antibodies in the Study of Breast Cancer. Hematology

Reviews 7, 55-62, 1993.

References: Available upon request

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