Development Project

Kaliappanadar Nellaiappan

***, ******* ******, *********, **

Tel: 781-***-**** (Home) 617-***-**** (Cell); e-mail: ***********@***.***

CAREER OBJECTIVE

A responsible and challenging R&D position where multi-disciplinary experience and knowledge in analytical chemistry, drug discovery and preclinical formulation development on hydrophobic small molecules and biologics are utilized for the discovery of value added pharmaceutical ingredients and products.

SUMMARY

Expertise, leadership and motivation to carry out the formulation development of small therapeutic molecule. Broad background in biochemistry, with specific training and expertise in key research areas on drug delivery system especially on formulation development of hydrophobic small molecule and biologics. As a development Scientist in Massachusetts Biologic laboratory, research on vaccine development and formulation were carried out. As a formulation scientist in Formatech for the last 10 years, expanded research and gathered a broad knowledge and brought new technology on the solubilization and stabilization of hydrophobic water insoluble small molecules, micelle formulation, emulsion formulation, micro emulsion formulation, liposomal formulation, and nano- and micro- encapsulation and formulation development of proteins though Stability Fingerprinting resulting in 10 patents on drug delivery system. Strong knowledge on lyophilization based on thermal property of lead formulation. Expertise in analytical method development including HPLC for pharmaceuticals and stability evaluation. Strong understanding of medicinal and analytical chemistry. Goal oriented, versatile team player with effective communication skills and demonstrated achievements.

EXPERIENCE

Staff Scientist II, Formatech, Inc., Andover, MA 2001 – September 2011

Responsible for preclinical formulation development of drug molecules (proteins, peptides and small molecules) including liquids and lyophilized forms.

Experience on solubilization of challenging hydrophobic small molecule utilizing Pka, micelle formulation, emulsion formulation, micro emulsion formulation, liposomal formulation, and nano- and micro- encapsulation resulting in 10 patents on drug delivery system (Docetaxel, Lapachone, Propofol, cyclosporin, colchicines, paclitaxel etc)

Studied Toxicity, PK, and efficacy of reformulated small molecule.

Rapid and efficient lyophilization process development

Developed methods for assaying various final product ingredients of proprietary nanoparticle; proprietary technology based on fatty acid micelle and natural liposome developed by me resulting 10 patents

Developed sensitive simple ELSD RP-HPLC method for the analysis of residual heat transfer fluid recovered from swabs and products after lyophilization

Characterization of formulations with the stability indicating tools including HPLC, MDSC, Intrinsic fluorescence, fluorescence in presence of dye etc.

Directly interacted with the patent examiners in Washington and clarified his questions

Actively involved in PreIND meeting with FDA in Washington

Responsible for development of Miradocetaxel. IND to be filed.

Lyophilization cycle development based on the thermal and excipient property

Experienced in aseptic formulation fill for toxicology evaluations.

Technology transfer from non-GMP research and development laboratory to GMP manufacturing facility.

Method transfer/development and qualification to support formulation development and stability fingerprinting.

Proficient in analytical techniques including UV, HPLC, SDS-PAGE, CGE, RALS, IF, EF, MDSC, KF, and osmolality.

Both non-GMP accelerated stability evaluation and GMP stability evaluation.

Preparation of standard operating procedures (SOP).

Wrote Technical report to clients for each project.

Clients teleconference on every two weeks to update the status of the project and discuss the on coming research plan

Developed project management skills.

Supervised 3 Research Associates and 1 scientist (Ph.D)

Research and Development Scientist II, Massachusetts Biologic Laboratories, Boston, MA 1997 – 2001

Designed, optimized and implemented protein purification strategies.

Developed, improved, and validated assays for vaccine, hyper-immunoglobulins, and albumin products.

Vaccine and formulation development.

Responsible for reviewing and reporting of the analysis of dose formulations for pre-clinical studies under GLP guidelines.

Novel method of extraction of STX-1 and STX-2 antigen

Novel method of toxoiding the bacterial antigens

Novel analytical method was established for the residual solvent used to inactivate viruses for biologic. Many pharmaceutical companies benefited.

Supervised 2 research associates.

Research Associate, Boston University School Of Medicine, Boston, MA. 1994 – 1997

Purification of lysyl oxidase the enzyme involved in fibrosis. Studied active-site mechanism-based inhibition by small molecules to prevent fibrosis (See my patent#(Wo/1996/040746))

Post Doctoral Research Fellow, University Of Massachusetts, Boston, MA 1992-1994

Purification of enzyme systems involved in cuticle synthesis of insects: phenoloxidase, quinone isomerase, dopachrome isomerase. Studied small molecules on inhibition of enzymes associated with cuticle.

EDUCATION

B.Sc., Biology, Madurai University

M.Sc., Biology, University of Madras

Ph.D., Bio chemistry, University of Madras

Other Experience and Professional Memberships

2008- Member, American Association of Pharmaceutical Society

2009- Reviewer for AAPS publications

2009- Reviewer for the Journal “Chemico-Biological Interactions”

Honors

Madras University, India PhD. Gold Medallists on outstanding thesis on “Biochemistry of Parasites” Madras

Oxford University, UK Royal Society Bursary award, Oxford University, Oxford, UK

SELECTED PUBLICATIONS

Patents:

1. Augustine,J, Nellaiappan, K, Isaacs, I and Isaacs,B (2008). Methods of enhancing solubility of compounds, U.S. Patent # 7,345,093

2. Augustine,J, Nellaiappan, K, Isaacs, I and Isaacs,B (2010). Methods of enhancing solubility of agents, U.S. Patent # 7,659,310

3. Augustine,J, Nellaiappan, K, Isaacs, I and Isaacs,B (2010). Pharmaceutical compositions of hydrophobic compounds, U.S. Patent # 7,687,458

4. Augustine,J, Nellaiappan, K, Isaacs, I and Isaacs,B (2005). Methods of enhancing solubility in water of hydrophobic compounds by micellar dispersions Application # (WO/2005/105041) International Application # PCT US2005/014611

5. Javeri, I, Nellaiappan, K and Dixit, B. (2011) Methods for the Preparation of Liposomes. U.S. Patent Application # 201********

6. Javeri, I, and Nellaiappan, K (2011) Methods for the Preparation of Liposomes Comprising Docetaxel. U.S. Patent Application # 201********

7. Javeri, I, and Nellaiappan, K. (2011) Methods for the Administration of Drugs Using Liposomes. U.S. Patent Application # 201********

8. Javeri, I, and Nellaiappan, K (2011) Methods for the Preparation of Liposomes Comprising Docetaxel. U.S. Patent Application # 201********

9. Javeri, I, and Nellaiappan, K (2011) Methods for the Preparation of Liposomes Comprising Docetaxel. Pub # WO/2011/038073 Internation Application No: PCT/US2010/049924

10. Javeri, I, and Nellaiappan, K (2011): METHODS FOR THE PREPARATION OF LIPOSOMES. Pub # WO/2011/038068 Internation Application No: PCT/US2010/ 049923

11. Nellaiappan, K, Bernstine E.G, Kagan H.M and Apstein C.S. (1996). Lysyl oxidase Inhibitors Pub. # (Wo/1996/040746) International Application # PCT/US1096/009102

Selected Peer-reviewed Publications (Selected from 39 peer-reviewed publications)

1. K. Nellaiappan, G. Nicklas, S. Yao and D. Malliaros 2001. Validation of a simple and sensitive gas chromatographic method for the analysis of tri-n-butyl phosphate from virally inactivated human immunoglobulin. J. Chromatography B 757: 181-189.

2. K. Nellaiappan, G. Govindan, S. Thorne, and I. Javeri 2010. A simple and sensitive ELSD RP-HPLC method for the analysis of residual heat transfer fluid recovered from swabs and products after lyophilization. AAPS Annual Meeting and Exposition, New Orleans, November 14-18-2010.

3. B. Dixit, K. Nellaiappan, P.Condon, B. Isaacs and I Isaacs 2009. Development of a rapid and efficient lyophilization process. Second Annual Lyophilization, May 12-14 2009.

4. K. Nellaiappan, B. Isaacs, and I. Isaacs 2009 NMR-2057: A Novel Lyophilized Paclitaxel Formulation with Improved Efficacy, Safety and Product Stability AAPS. Annual Meeting and Exposition, Los Angeles, CA November 7-12-2009.

5. K. Nellaiappan, A. Risitano, G. Liu, G. Nicklas and H. M. Kagan. 2000. Fully processed lysyl oxidase catalyst translocates from the extracellular space into nuclei of aortic smooth-muscle cells. Journal of Cellular Biochemistry 79(4): 576-582.

6. K. Nellaiappan and H. M. Kagan 1999. Proteins secreted by vascular smooth muscle cells as substrates of lysyl oxidase. Connective Tissue Research 40(2): 123-129.

7. W. Li, K. Nellaiappan, T. Strasmeir, K. Thomas and H. M. Kagan 1997. Localization and activity of lysyl oxidase within nuclei of fibrogenic cells. Proc Natl Acad Sci USA. 94(24): 128**-*****.

8. G. Liu, K. Nellaiappan and H. M. Kagan 1997. Irreversible inhibition of lysyl oxidase by homocysteine thiolactone and its selenium and oxygen analogues. Implications for homocystinuria. J Biol Chem 272(51): 323**-*****.

9. M. Sugumaran and K. Nellaiappan 2000. Characterization of a new phenoloxidase inhibitor from the cuticle of Manduca sexta. Biochem Biophys Res Commun 268(2): 379-83.

10. M. Sugumaran, K. Nellaiappan, and K. Valivittan 2000. A new mechanism for the control of phenoloxidase activity: inhibition and complex formation with quinone isomerase. Arch Biochem Biophys 379(2): 252-260.

11. M. Sugumaran, K. Nellaiappan, C. Amaratunga, S. Cardinale, and T. Scott 2000. Insect melanogenesis. III. Metabolon formation in the melanogenic pathway-regulation of phenoloxidase activity by endogenous dopachrome isomerase (decarboxylating) from Manduca sexta. Arch Biochem Biophys 378(2): 393-403.

12. K. Nellaiappan and M. Sugumaran 1996. On the presence of prophenoloxidase in the hemolymph of horse shoe crab, Limulus. Comparative Biochemistry and Physiology B 113: 163-168.

13. M. Sugumaran, K. Nellaiappan, T. Scott, and C. Amarathunga 1995. Complex formation between mushroom tyrosinase and Manduca sexta dopachrome isomerase. Pigment and Cell Research 8: 180-186.

14. K. Nellaiappan, and A. Vinayakam 1993. A method for demonstrating prophenol oxidase after electrophoresis. Biotechnic and Histochemistry 68: 193-195.

15. K. Nellaiappan, G. Nicklas and M. Sugumaran 1994. Detection of dopachrome isomerase activity on gels. Analytical Biochemistry 220: 122-128.

16. K. Nellaiappan, G. Nicklas and M. Sugumaran 1994. The ontogeny of dopachrome isomerase isozyme patterns in the tobacco horn worm Manduca sexta. Biochemical and Biophysical Research Communications 200: 1072-1078.

17. M. Sugumaran and K. Nellaiappan 1991. Lysolecithin-a potent activator of prophenoloxidase from the hemolymph of the lobster, Homarus americanus. Biochemical and Biophysical Research Communications, 176: 1371-1376.

18. M. Sugumaran and K. Nellaiappan 1990. On the latency and nature of phenol oxidase present in the left colleterial gland of the cockroach Periplaneta americana. Archives of Insect Biochemistry 15: 165-181.

39 publications in print; complete list available upon request

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