Formulation and Process Development

NAZER KHALAF

Cell 508-***-****

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

P R O F I L E

Scientist with extensive experience in the biopharmaceutical industry with expertise in protein therapeutics development with skills in protein purification, pre-formulation, analytics and crystallization.

Formulation and Purification development experience has encompassed preclinical, Phase 2 & 3 and support molecular entities including enzymes, monoclonal antibodies, hormones, fusion proteins, and peptides.

Apply detailed approach and integrate new concepts and methods to solve complex technical problems.

Work effectively in team setting as well as independently to meet project goals and timelines

QUALIFICATIONS

Protein Formulation: high concentration liquid and lyophilized protein formulations/Stability Testing

Protein Purification: Down-Stream- Column Chromatography

UF/DF, TFF

Protein Crystallization- Scale up 10L (purification/ Formulation)

Protein Analytics: SEC-HPLC, RP-HPLC. IEX-HPLC, IEF, SDS-PAGE, ELISA, HIAC and western blot

Solid State Analysis: DSC, TG and XPD

PROFESSIONAL E X P E R I E N C E

Amgen:

March 2014 – May 2017

SENIOR SCIENTIST

Antibody Crystallization and Formulation experience:

A- Antibody Crystals formulation: Hypercholesterolemia treatment

Guide the team in scaling up the AB crystallization from the bench scale to 10 L batch

The crystals produced by Amgen had complication in downstream process due to crystals twinning, solved instability by introducing new formulation able to stabilize the crystals

Increased the concentration of the crystals up to 180mg/ml with viscosity 30cP

Amgen submitted provisional patent application

NAZER KHALAF

B- Antibody Liquid Formulation:

The current antibody formulation 160mg/ml with viscosity 70cP; increased the concentration up 240mg/ml with viscosity 30cP by introducing new excipient.

The new excipient used to increase the concentration of 4 antibodies more than 200mg/ml with viscosity 25-35cP.

Amgen filed patent application

C- Preventing antibody precipitation after sub-Q injection: Bone loss treatment

Reformulated to prevent from precipitating in the Sub-Q space

Increased the concentration from 60mg/ml up to 120mg/ml target concentration

Purification experience:

A-Antibody: Replacing Protein-A as capturing step:

Applied crystallization procedure directly to cell media to crystallize the target protein; crystallized Ab with yield of 75% and purity same as Ab processed through Protein-A and two polishing steps

B-Fusion protein: Inflammation Treatment

This fusion protein is prone to self-association resulting in visible aggregation after 1st polishing column, using filtration to remove visible particles final yield around 55%

Introduced an excipient to sample before loading on the polishing column and the all buffers resulting in preventing the visible particles and reducing the number particles between 1.5-50um by 30 % and increasing the yield up to 75%

ProCrysta Biologix

2009-Apr 2014

Senior Scientist

Involved in establishing a start-up contract company located in Natick, MA

Participated in establishing business relationship between ProCrysta and Althea Technology located in San Diego, CA to get potential client for both companies

NAZER KHALAF

Altus Pharmaceuticals

1993- Sep 2009

Senior Scientist-2008-2009

Staff Scientist- 2005-2007

Scientist-1998-2004

Associate Scientist-1993-1997

As one of the early founding scientist (3rd Scientist), conceived, developed, and led scientific research programs around metabolic disease, protein formulation and delivery; These resulted in product launches, IND filing, creation of platform through crystallization and crosslinked crystals, intellectual property, patents and publication for Altus.

Received “Creative Scientist” award in Jan 2004

Developed a novel sustained release formulation for human growth hormone that was successful in Phases 1 & 2 clinical trials beyond which the program was licensed to Genentech; technology easily adaptable to new and many existing protein drugs; technology provided for an expanded product pipeline and created significant intellectual property value and business partnerships; led all aspects of work including analytical method development from start of project to preclinical work in 2 species.

Developed an oral formulation of the enzyme phenylalanine hydroxylase for use in the treatment of phenylketonuria (PKU). Demonstrated preliminary proof of efficacy in mouse model. Utilized Cross-Linked Crystals technology to minimize activity loss due to stomach acid and proteolysis enzymes

Formulated the nerve agent destroying enzyme organophosphorus anhydrolase (OPAA) as a topical skin protectant. This was funded based upon an original research proposal submitted to the Department of Defense

Developed high concentration monoclonal antibody formulations of rituxan, herceptin, REMICADE and other proprietary customer proteins enabling subcutaneous drug delivery instead of intravenous mode

Formulated several enzymes as stable enzyme biocatalyst products for use in chiral resolutions of esters, alcohols and acids in both aqueous and organic solvent media. These products were available commercially.

University of Massachusetts Medical School

Research Associate

EDUCATION

B.S in Chemistry, Worcester State University, Worcester, MA

Nazer Khalaf

PATENTS (13)

Nazer K. Khalaf. Methods using cross-linked protein crystals formulation as catalysts in organic solvents. 6042824, Mar. 28, 2000

Nazer K. Khalaf. Cross-linked protein crystals formulation and their use as catalysts in organic solvent. 5932212, Aug. 3, 1999

Nazer Khalaf and Chandrika P. Govardhan Complexes of Protein Crystals and Ionic Polymers; WO 200-***-****

Alexey L. Margollin, Nazer K. Khalaf, Nancy L. St. Clair, Scott L. Rakestraw, Bhima C. Shenoy. Stabilized Protein Crystals, Formulations comprising them and Methods of making them. US 6541606 B2. Apr. 1, 2003

Alexey L. Margollin, Nazer K. Khalaf, Nancy L. St. Clair, Scott L. Rakestraw, bhaji C. Shenoy. Stabilized Protein Crystals, Formulations comprising them and Methods of making them. US 7351798 B2. Apr. 1, 2008

Chandrika Govardhan, Nazer Khalaf. Daptomycin and related analogs in crystalline form. 0111311 A1, Aug 15, 2002 EP 1383794, Dec.5. 2002

Alexi L. Margolin., Rose A. Persichetti., Nancy L. St. Clair., Nazer K. Khalaf. Controlled Dissolution Cross Linked Protein Crystals. US6140475. May.18, 2006

Ernest H. Braue, Jr., Stephen T. Hosbon., Chandrika, Govardhan. Nazer, Khalaf. Active Topical Skin Protectants containing OPAA Enzyme and CLECs. US6410604B1. June.25, 2002

Alexey L. Margolin, Rose A. Persichatti, Nancy L. St. Clair, Nazer K. Khalaf. Controlled Dissolution Cross Linked Protein crystals. US 6140475. Oct. 31, 2000

Chandrika P. Govardhan, Ben P. Simeone and Nazer Khalaf: Human Growth Hormone Crystals and methods for preparing them; WO2004060310

Yakovlevsky, Krill, Cheatline, Mikhail, Khalaf, Nazer, Govardhan, Chandrika P., Jung, Chu W. Spherical protein particles and methods for preparation and use as in drug delivery systems and diagnostic agents. WO 03/000014. Jan. 03, 2003

Keith, Dennis., Govardhan, Chandrika., Khalaf, Nazer. Methods for preparing purified daptomycin.; WO 02/056829A2 July25, 2002

Ernest H. Braue, Jr., Stephen T. Hobson, Chandrika Govardhan, Nazer Khalaf.; Active Topical skin protectants containing OPAA Enzyme and CLECs.; US 6410604B1.; Jun. 25, 2002

Patents Application

Nazer Khalaf, Saraswathi Mandapati, Reena J, Patel Crystalline antibody formulation, WO201601927 A1; Jan. 21, 2016

Nazer Khalaf

PUBLICATIONS

1.Novel and Long-Acting Crystal Formulation of Human Growth Hormone., Pharmaceutical Research (2005), 22(9), 1461-70 C Govardhan, N Khalaf, C. Jung, B Simeone A. Higbie, S. Qu, L. Chemmalil, S Pechenov, S Basu, & A Margolin,

2.A novel and efficacious, once-per-week crystalline depot formulation of human growth hormone., C Govardhan, N Khalaf, B Simeone, C. Jung, A. Higbie, L. Chemmalil, S Pechenov, S Basu, & A Margolin., Transactions of the 31st Annual meeting of the Controlled Release Society (2004)

3.Influence of lid conformation on lipase enantioselectivity. Overbeeke, P.L.A; Govardhan, C.; Khalaf, N.; Jongejan. J. A; Heijnen. J.J.; J. of Molecular Catalysis B Enzymatic. (2000); 10 (4); Page 385-393.

4.Cross-Linked Enzyme Crystals as Highly Active Catalyst in Organic Solvents. Khalaf, N.; Govardhan, C. P.; Lalonde, J. J.; Persichetti, R. A.; Wang, X. -F.; Margolin, A. L. Journal of American Chemical Society. (1996); 118; Number 23; Page.5494-5495.

5.Candida rugosa lipase: Enantioselectivity enhancements in organic solvents. Persichetti, Rose A.; Lalonde, Jim J.; Govardhan, Chandrika P.; Khalaf, Nazer K.; Margolin, Alexey. L.; Tetrahedron Letters (1996), 37, 6507-10

6.Cross-Linked Crystals of Candida rugosa Lipase: highly Efficient Catalysts for the Resolution of Chiral Esters. Lalonde, J. J.; Govardhan, C.; Khalaf, N.; Martinez, A.G. Journal of American Chemical Society. (1995): 117; Number 26; Page 6845-52

7.Cross-Linked Crystals of subtilisin: Versatile Catalysts of Organic Synthesis. Wang, Y.F; Yakovelevsky, K.; Khalaf, N.; Zhang, B. Annals-New York Academy of Science. 1996; Vol 799. Page 777-7783.

8.Principle of large scale crystallization. Jim J, Lalonde, Chandrika Govardhan, Nazer Khalaf, AldoG. Martinez, Kalevi Visuri, Alexey Margolin., 1995 J. Am. Chem. Soc. 117, pp. 6845-6852.

9.Activation of insulin –sensitive protein kinases by non-hydrolyzable GTP analogue in perminabilized 3T3-L1 adipocytes. Klarlund, J.K.; Khalaf, N.; Kotma, L.; Czech, M.P. Experimental and clinical Endocrinology. 1993; Vol 101; Number Sup/2; Page 155-157.

10.An Insulin-stimulated kemptied kinase purified from rat liver is deactivated by phosphatase 2A. KLarlund, J. K, Jaspers, S, R.; Khalaf, N.; Bradford, A. p.; Miller, T.B, Czech, M.P J. Biol.Chem.; 1991. Vol 266; Issue 7; Page 4052-4055.

11.An Insulin-sensitive cytosolic protein kinase accounts for the regulation of ATP Citrate-lyase phophorylation. Yu, K.T; Benjemin, W.B; Ramakrishna, S.; Khalaf, N, Czech, M.P.; Biochem. J. 1990; Vol 268; Issue3; Page 539-545.

12.Insulin stimulates the tyrosine phosphorylation of a 160,000 glycoprotein in rat adipocytes plasma membranes. Yu, K.T.; Khalaf, N.; Czech, M.P. J. Bio. Chem. 1987; Vol 262; Issue 16; Page 7865-7873.

13.Insulin stimulates a novel Mn+2 dependent cytosolic serine kinase in rat adipocytes. Yu, K.T.; Khalaf, N.; Czech, M.P. J.Biol. Chem 1987; Vol 262; Isuue 34; Page 6507-6510.

14.Insulin stimulates a membrane-bound serine kinase that may be phosphorylated on tyrosine. Yu, K.T.; Khalaf, N.; Czech, M.P. Proc. Natl. acad. Sci. USA. 1984; Vol 84; Issue 12; Page 3972-3976.

Contact this candidate