Design Development

Laxman Eltepu, PhD

*******@*****.***

858-***-**** (M) 781-***-**** (H)

STATUS : US Permanent Resident

SUMMARY

Experienced synthetic organic, medicinal chemistry and drug discovery chemist: In depth knowledge of the design and

synthesis of biologically active complex organic molecules using modern synthetic and separation techniques. Specialize in

finding innovative solutions to complex synthetic challenges.

• Expertise in multi-step asymmetric total synthesis, SAR based design and synthesis of small molecules, peptide

synthesis, and combinatorial parallel library synthesis to address medicinal chemistry issues.

• Strong background in the bio-conjugation chemistry of proteins, antibodies and polymers.

• Well versed in the design and synthesis of potential delivery vehicles for the lipid nano particle mediated delivery of

drug molecules especially in siRNA delivery.

• Multiple patents, extensive publication record and numerous professional presentations in diverse research areas.

• Able to work effectively in a team setting; excellent written and verbal communication skills.

• Proven ability to manage multiple projects effectively and meet tight deadlines in challenging situations.

• Familiarity with modern tools and analytical techniques such as automated purification systems, NMR, GC, LC-MS,

Gel electrophoresis and AAA analysis; strong computer skills.

PROFESSIONAL EXPERIENCE/SCIENTIFIC ACHIEVEMENTS

Alnylam Pharmaceuticals, Cambridge, MA Dec 2008 – Sept 2010

Scientist

• Designed and synthesized novel cationic lipids for the lipid nano particle mediated delivery of siRNA.

• Designed and synthesized small molecule building blocks with biodegradable linkers using folate-conjugated siRNA

for targeted delivery.

• Managed multi-step synthesis of potential delivery vehicles and pharmaceutical ingredients for RNAi therapeutics.

• Developed a novel re-usable copper catalyst on solid supports for the conjugation of macromolecules and

biomolecules via click chemistry.

AstraZeneca, Boston, MA 2008

Scientist

• Synthesized biologically active molecules in multi-step synthesis based on their structure activity relationship

studies, these new classes of chemically diversified compounds have been showed promising activities in their

biological studies.

• Designed and synthesized library of novel class of molecules for anti-infectives.

MediVas LLC, San Diego, USA Mar 2005-Dec 2007

Senior Staff Scientist, Bioorganic Chemistry

• Developed new technologies and ideas for exploring and expanding MediVas proprietary polymer platform.

• Prepared conjugated products of small molecules, drugs, proteins and peptides using MediVas proprietary

polymer technology to discover and generate new products in the therapeutic area.

• Implemented novel MRI project and synthesized DTPA and DOTA compounds modified with amino acids

and development new platform of Gd contrast agents using the imaging technology.

• Designed and synthesized amino acid based monomers and their polymers for water soluble and

biodegradable properties.

The Scripps Research Institute, San Diego, USA Mar 2003-Mar 2005

Postdoctoral Research Associate

Advisors: Prof. Dr. P. Wentworth Jr. and Prof.Kim D. Janda group

• Total synthesis of Beauveriolide I, inhibitors of acyl-CoA: cholesterol acyltransferase.

Laxman Eltepu, PhD Page 1 of 4

• Accomplished antibody conjugated Gd–complexes as novel contrast agents for cardiovascular imaging. These

molecular specific antibodies when conjugation with paramagnetic reagents, results in disease-specific MRI contrast

agent.

• Designed and synthesized novel contrast agents as MRI compounds.

Max-Plank Institute for Molecular Physiology, Dortmund, Germany Jan 2001-Dec 2002

Humboldt and Max-Plank Postdoctoral Research Fellow

Advisor: Prof. Dr. Herbert Waldmann

• Developed solid-phase library of chiral phosphoramidite ligands for enantioselective conjugate addition reactions.

• Designed and synthesized polymer-bound bispidine-derived diphosphine library and developed Pd catalyzed Suzuki

reactions at room temperature.

Indian Institute of Chemical Technology June 1996-Jan 2001

Hyderabad, India

Graduate Research Fellow (PhD) (CSIR)

Advisor: Dr. Ahmed Kamal

• Designed and synthesized novel piperazine-linked pyrrolo[2,1-c][1,4] benzodiazepine antitumor antibiotics and their

DNA cross-linking dimers. These newly synthesized cross-linking PBD dimers have been commercialized for further

pre-clinical studies, due to their high level DNA binding ability and anticancer activity.

• Prepared novel C2-exo-fluorounsaturated pyrrolobenzodiazepines (PBDs) as potential antitumor agents.

• Performed biological evaluation and QSAR studies of novel dimers of podophyllotoxin and its demethyl

epipodophyllotoxin as cytotoxic agents.

• Synthesized 4ß-substituted benzophenone derivatives of podophyllotoxin and 4'-O-demethyl epipodophyllotoxin as

DNA-topoisomerase II inhibitors.

• Developed novel and efficient methodologies by employing trimethylsilyl chloride and sodium iodide for the

synthesis of biologically active molecules.

PATENTS

1. Manoharan, Muthiah; Jayaraman, Muthusamy; Rajeev, Kallanthottathil G.; Eltepu, Laxman; Ansell, Steven; Chen,

Jianxin. Preparation of lipids and compositions for the delivery of therapeutics PCT Int. Appl. ( 2010), WO

2010/054401 A1 20100514.

2. Manoharan, Muthiah; Rajeev, Kallanthottathil G.; Jayaraman, Muthusamy; Butler, David; Narayanannair,

Jayaprakash K.; Maier, Martin; Eltepu, Laxman. Preparation of lipids and compositions for the delivery of

therapeutics PCT Int. Appl. (2010), WO 2010/054405 A1 20100514.

3. Manoharan, Muthiah; Rajeev, Kallanthottathil G.; Butler, David; Narayanannair, Jayaprakash K.; Jayaraman,

Muthusamy; Eltepu, Laxman. Novel lipids and compositions for the delivery of therapeutics PCT Int. Appl. (2010),

WO 2010/054406 A1 20100514.

4. Solid-support Immobilized, Reusable Cu (I) Catalyst for the preparation of oligonucleotide conjugates (Patent

Filed, Alnylam Pharmaceuticals)

5. Ahmed Kamal, Laxman Eltepu, M.Arifuddin and Ramesh Khanna. A Process for the Synthesis of New

Podophyllotoxin Dimers as Potential DNA-Topoisomerase II Inhibitors. US Patent (2002), 6,441,198.

6. Ahmed Kamal, Laxman Eltepu, M.Arifuddin and Ramesh Khanna.A Process for the Synthesis of New

Podophyllotoxin Dimers as Potential DNA-Topoisomerase II Inhibitors. Indian patent published.

7. Ahmed Kamal, Laxman Eltepu and P.S.M.M. Reddy A One-Pot Process for the Syntheis of New Podophyllotoxin

Dimers as Potential Anticancer Agents Employing TMSCl/NaI. Indian patent published.

EDUCATION

PhD, Synthetic Organic & Medicinal Chemistry 2001

Indian Institute of Chemical Technology, Hyderabad, India.

Thesis Title:"Design and synthesis of novel podophyllotoxin dimers and DNA-interactive pyrrolo[2,1-c]

[1,4]benzodiazepine antitumor antibiotics” Advisor: Dr. Ahmed Kamal.

Laxman Eltepu, PhD Page 2 of 4

MS, Organic Chemistry 1995, Osmania University (Top Rank)

BS, Chemistry and Biology 1993, Osmania University (Distinction)

AWARDS AND FELLOWSHIPS

Mar 2003 Skaggs Research Fellowship. The Scripps Research Institute, USA

Sept 2001 Alexander Von Humboldt Research Fellowship (AvH). Germany

Jan 1998 Senior Research Fellowship. Council of Scientific and Industrial Research, India

MEMBERSHIP

American Chemical Society, USA

REVIEWER

Active reviewer for the following articles: Chemical Communications; Organic and Biomolecular

Chemistry; Journal of Organic Chemistry; Organic Letters; Canadian Journal of Chemistry; Chemistry

- A European Journal; and Synthesis.

PUBLICATIONS

1. Synthesis and evaluation of bicyclicketal based cationic lipids for the delivery of siRNA via lipid nano particle based

delivery systems (Manuscript under preparation, 2010).

2. Solid-support immobilized reusable Cu (I) catalyst for bioconjugation via click reaction, (manuscript under

preparation, 2010).

3. Gomurashvili, Zaza; Zhang, Huashi; Jenkins, Turner D.; Hughes, Jonathan; Wu, Mark; Lambert, Leanne; Eltepu,

Laxman; Pabba, Chittari; Chowdari, Naidu; Vassilev, Vassil; Katsarava, Ramaz; Turnell, William G. From drug-

eluting stents to biopharmaceuticals: poly(ester amide) a versatile new bioabsorbable biopolymer. PMSE 2006, 95,

826.

4. Paul T. Nyffeler, Nicholas A. Boyle, Laxman Eltepu, Chi-Huey Wong, Albert Eeschenmoser, Richard A. Lerner and

Wentworth P. Jr., Generated dihydrogen trioxide during the thermochemical reaction between hydrogen peroxide and

ozone. Angewandte Chemie International Edition, 2004, 43, 4656.

5. Diastereo and Enantio Selective Crotylation of α-Ketoesters Using Crotyl Boronic Acid Ester Complexes. Yanping

Chen, Laxman Eltepu and Paul Wentworth, Jr, Tetrahedron Lett. 2004, 45, 8285.

6. Ahmed Kamal, P. S. M. M. Reddy, D. Rajasekhar Reddy, Laxman Eltepu, M. Deepak, M. S. Achary and H. A.

Nagarajan, DNA binding potential and cytotoxicity of newly designed pyrrolobenzodiazepine dimers linked through

a piperazine side-armed-alkane spacer Bioorg. Med. Chem. 2006, 14, 385.

7. Ahmed Kamal, Laxman Eltepu, M. Arifuddin, R. Khanna, P. S. M. M. Reddy, Tasneem Rehana, M. Arifuddin, K.

Neelima, Anand K. Kondapi, Sunanda G. Dastidar, Design and Synthesis of Novel Podophyllotoxin Dimers as DNA-

Topoisomerase II Inhibitors. Bioorg. Med. Chem. 2004, 12, 4197.

8. Ahmed Kamal, P. S. M. M. Reddy, D. Rajasekhar Reddy, Laxman Eltepu and Y. L. N. Murthy, Synthesis of

fluorounsaturated analogues of SJG-136 and their DNA-binding potential, Bioorg. Med. Chem. Lett. 2004, 14, 5699.

9. Oliver Huttenloch, Laxman Eltepu, Herbert Waldmann, Solid-Phase Development of Chiral Phosphoramidite

Ligands for Enantioselective Conjugate Addition Reactions. Chem. Eur. J. 2002, 8, 4767.

10. Oliver Huttenloch, Laxman Eltepu, Herbert Waldmann, Combinatorial Development of Chiral Phosphoramidite-

Ligands for Enantioselective Conjugate Addition Reactions. Chem. Commun. 2002, 7, 673.

11. Laxman Eltepu and Herbert Waldmann, Development of Polymer-Bound Bispidine-Derived Diphosphine Ligands

for Pd catalyzed Suzuki Reactions (under Communication).

12. Ahmed Kamal, Laxman Eltepu, P. S. M. M. Reddy, A Mild and Efficient Dethioacetalization Employing

FeCl3.6H2O: Synthesis of DNA-binding Pyrrolo[2,1-c][1,4]benzodiazepine Ring System and its Dimers. Synlett

2000, 10, 1476.

13. Ahmed Kamal, Laxman Eltepu, N. Laxman, N. V. Rao, Synthesis of Pyrrolo[2,1-c][1,4]benzodiazepines via

Reductive Cyclization of w-Azido Carbonyl Compounds by TMSI: An Efficient Preparation of Antibiotic DC-81 and

its Dimers.; Bioorg. Med. Chem. Lett. 2000, 10, 2311.

Laxman Eltepu, PhD Page 3 of 4

14. Ahmed Kamal, Laxman Eltepu, P. S. M. M. Reddy, Reductive Cyclization of w-azido/nitro Carbonyl Compounds

by Samarium Iodide: A Facile Preparation of DNA-binding Pyrrolo[2,1-c] [1,4]benzodiazepine and its Dimers.

Tetrahedron Lett. 2000, 41, 8631.

15. Ahmed Kamal, Laxman Eltepu, M. Arifuddin, An Efficient Reduction of Azides to Amines: Synthesis of DNA-

Interactive Pyrrolo[2,1-c][1,4]benzodiazepines. Tetrahedron Lett. 2000, 41, 7743.

16. Ahmed Kamal, Laxman Eltepu, N.V. Rao, A Mild and Rapid Regeneration of Alcohols from their Allylic Ethers by

Chlorotrimethylsilane/Sodium iodide. Tetrahedron Lett. 1999, 40, 371.

17. Ahmed Kamal, Laxman Eltepu, N. Laxman, N.V. Rao, Efficient One-Pot Synthesis of N-Substituted

Phthalimide/Naphthalimides from Azides and Anhydrides by Iodotrimethylsilane. Tetrahedron Lett. 1998, 39, 8733.

18. Ahmed Kamal, N.V. Rao, Laxman Eltepu, A Mild and Efficient Reduction of Azides to Amines by Employing

Chlorotrimethylsilane/Sodium iodide. Tetrahedron Lett. 1997, 38, 6945.

PRESENTATIONS AT CONFERENCES

1. Laxman Eltepu, Chang G. Peng, K. Narayanannair Jayaprakash, Takeshi Yamada, Muthusamy Jayaraman, G.

Rajeev Kallanthottathil, Muthiah Manoharan, Solid-support Immobilized, Reusable Cu (I) Catalyst for 'Click

Reactions' of Oligonucleotides with Ligands at 240th National ACS, Boston, August 24, 2010.

2. Muthusamy Jayaraman, David Butler, Laxman Eltepu, Martin A. Maier, Akin Akinc, Tom Madden, Michael Hope,

Ying Tam, Barbara Mui, Andrew Sprague, Soma De, Kallanthottathil G. Rajeev, and Muthiah Manoharan, Synthesis

And Evaluation Of Bicyclic Ketal-based Cationic Lipids For The Delivery of siRNA via Lipid Nanoparticle Delivery

Systems at 240th National ACS, Boston, August 24, 2010.

3. Gomurashvili, Zaza; Zhang, Huashi; Jenkins, Turner D.; Hughes, Jonathan; Wu, Mark; Lambert, Leanne; Eltepu,

Laxman; Pabba, Chittari; Chowdari, Naidu; Vassilev, Vassil; Katsarava, Ramaz; Turnell, William G. From drug-

eluting stents to biopharmaceuticals: poly(ester amide) a versatile new bioabsorbable biopolymer. Abstracts of

Papers, 232nd ACS National Meeting, San Francisco, CA, United States, Sept. 10-14, 2006.

4. Laxman Eltepu and Paul Wentworth Jr., Preparation of anti-atheronal antibody Gd-complexes as novel contrast

agents for cardiovascular imaging. 229 American Chemical Society National Meeting, San Diego USA, 2005.

5. Laxman Eltepu and Paul Wentworth Jr., A bifunctional polymer-supported reagent/catalyst approach for the

preparation of pure dihydrogen trioxide (HOOOH). 229 American Chemical Society National Meeting, San Diego

USA, 2005.

6. Laxman Eltepu, M.Arifuddin and Ahmed Kamal, Design and Synthesis of Novel Podophyllotoxin Dimers as

Potential DNA-Topoisomerase II Inhibitors. International Symposium on Bio-Organic Chemistry (IUPAC) Pune,

India 2000.

7. Laxman Eltepu, N.Laxman and Ahmed Kamal, A Mild and Facile Synthesis of Pyrrolo[2,1-c][1,4]benzodizepines

employing TMSCl/NaI. 2nd National Symposium in Chemistry, Hyderabad, India 2000.

8. B.S.N.Reddy, Laxman Eltepu and Ahmed Kamal, Chemo-Enzymatic synthesis of Biologically Important

Heterocycles. First National Symposium on Green Chemistry, New Delhi, India 1999.

9. B.S.P.Reddy, B.S.N.Reddy, Laxman Eltepu, M.Arifuddin and Ahmed Kamal, New methods for the conversion of

thiocarbonyl compounds to carbonyl compounds. Indo-German Symposium: Organic Synthesis-Growing Interface

with Adjacent Sciences, Hyderabad, India 1996.

REFERENCES: Available upon request.

Laxman Eltepu, PhD Page 4 of 4

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