Brian Frederick
Ben Lomond, CA 95005
abmh3g@r.postjobfree.com
Summary
Highly productive, experienced medicinal synthetic chemist, proven
accomplishments in small molecule discovery and peptide conjugate discovery
and development, expertise in molecular design, synthesis and analysis of
biologically active molecules
Technical Skills
Solution and solid phase synthesis and purification of small organic
molecules, peptides and conjugates
Chromatography - column, analytical and prep HPLC, IE, SEC, LC/MS, FPLC
Spectroscopy - NMR, UV/Vis, Fluorescence, CD, IR, DLS
Professional Experience
Intradigm Corp. April 2009 -
May 2010
Scientist
Responsible for synthesis, purification and analysis of polycationic
peptides and their conjugates for evaluation in nanoparticle siRNA
formulations
. Developed conjugation strategies for site specific PEGylation
. Created numerous homing conjugates tethered through PEG to our polycation
carriers for selective tissue delivery
. Synthesized many Polycation-PEG-Lipid constructs
. Chemically modified polycation peptide carrier to alter chem/physical
properties of resulting siRNA nanoparticle
. Developed chromatographic analytical methods, HPLC, IE; utilized
colorimetric UV/fluorescent assays to follow conjugation/derivitization
reactions and evaluate product purity
. Developed fluorescent and biotinylated constructs for use as biological
research tools
. Initiated, set up and employed analytical CRO for AAA analysis
. Worked collaboratively, contributed ideas and presented original data as
part of multidisciplinary Technology Development team
Affymax, Inc., Palo Alto, CA 1999 -
March 2009
Staff Scientist, January 2004 - March 2009
First non-PhD promoted to Staff Scientist in Medicinal Chemistry group,
recognizing my independence in day to day activities, goal setting, analog
design, literature and patent reviews as well as my abilities to work
cooperatively and productively with scientists in other disciplines such as
biology, preclinical, analytical development and manufacturing
Played key role in the discovery and development of HematideTM, a PEGylated
peptide dimer currently in phase III clinical trials for the correction of
anemia
. Developed linker and PEG conjugation strategies that led to the IND
candidate and supporting patents
. Worked on the synthetic process leading to first gram scale batches used
in critical tox and IND enabling animal studies
. Studied the stability of HematideTM in a variety of conditions; proposed
and synthesized many major degradants and process impurities used for
tox. and analytical method validation
. Developed route to C14 radiolabeled HematideTM used for QWBA analysis
. Designed and synthesized many conjugates for basic research, including
fluorescent, biotinylated, discrete PEG and photoaffinity labeled analogs
. Participated in formal characterization of HematideTM, proposed new
characterization test, identified and oversaw contract labs, set up legal
agreements, designed proof-of-principle experiments
Key team member in the development of intranasal ESA
. Worked on team creating analogs of in-house ESA peptide to find minimal
size and charge for functional activity. Succeeded in reducing size of
active peptide dimer by 12 AA while minimizing charged residues
. Made numerous peptide dimer conjugates with a range of PEG sizes and
other functionalities to improve formulation and/or nasal penetration
. Developed a series of (Acyloxy) alkyl carbamate prodrugs conjugates to
mask charge for increased tight junction transport for intranasal
systemic delivery
. Developed synthetic process and delivered multigram batches of peptide
dimer for creation of WRSS and pre-IND enabling animal and toxicology
studies; wrote process description used by CMO for creation of 100 + g of
intranasal IND candidate
Worked on numerous discovery project teams optimizing peptides as
therapeutics in hematology, tissue protection, oncology and immune-mediated
disease programs
. Synthesized and delivered for biological assay hundreds of peptide
analogs, conjugates and constraints
. Proposed and synthesized numerous series of bicyclic peptides using a
variety of ring closing chemistries to restrict conformation
. Proposed and synthesized a series of antiangiogenic peptide conjugates
with RGD and cyclic NGR homing peptides coupled through a variety of
chemistries for localization to the neovasculature
. Outsourced contract work for characterization of compounds using CD, DLS
Affymax, Inc., Continued
Research Associate I-II, 1999 - 2003
. Designed, synthesized and purified small molecule libraries, including
tetramic acids, thiazolidinones, 1,4 dihydropyridines, pyrolidinetriones,
3,4-Dihydropyrimidin-2(1H)-ones, dihydropyrimidines
. Designed novel phosphotyrosine mimetics and their incorporation into
small molecule library scaffolds, for the inhibition of PTP-1B
AMM, Division of Honeywell, Santa Clara, CA
1999
Chemist
Synthesized and characterized hybrid organic/inorganic network polymers in
the development of low dielectric constant spin on glasses for semi-
conductor industry
Education
. M.S., Chemistry, April 1999
Dept. of Chemistry, University of California Santa Cruz
. B.S., Chemistry, June 1994
California Polytechnic State University, San Luis Obispo
Cum laude
Patents, Publications, Presentations and Posters
1. Frederick, Max B., Frederick, Brian, "Substantially environmental-
pollution-free cleaning method and device employing electric energy
and surface physical properties", 630****-****
2. Holmes, C. P., Yin, Q., Zemede, G., Bhandari, A., Dong, Y. S.,
Tumelty, D., Lalonde, G., Palani, B., Schatz, P. J., Wrighton, N. C.,
Dower, W. J., Frederick, B. T., Chakrabarti, A. "Erythropoietin
receptor-binding peptides, peptide derivatives, and dimers for
treatment of diseases", WO2006062685 2006.
3. Holmes, C. P., Yin, Q., Zemede, G., Bhandari, A., Dong, Y. S.,
Tumelty, D., Lalonde, G., Palani, B., Schatz, P. J., Wrighton, N. C.,
Dower, W. J., Frederick, B. T.; Chakrabarti, A. "Peptides that bind to
the erythropoietin receptor, pharmaceutical compositions, and
therapeutic use", WO2006060148 2006.
4. Hembrough, T. A., Holmes, C. P., Yin, Q., Zemede, G. H., Angell, Y.
M., Frederick, B. T., Xu, C. "Compositions and methods for inhibiting
cellular proliferation", WO2007070372 2007.
5. Hembrough, T. A., Holmes, C. P., Yin, Q., Zemede, G. H., Angell, Y.
M., Frederick, B. T., Xu, C. "Compositions and methods for inhibiting
cellular proliferation", US20070203066 2007.
6. Holmes, Christopher P., Yin, Qun, Zemede, Genet, Bhandari, Ashok,
Dong, Yaohua S., Tumelty, David, Lalonde, Guy, Frederick, Brian T.,
Chakrabarti, Anjan, Balu, Palani, Schatz, Peter J., Wrighton, Nicholas
C., Dower, William J. "NOVEL PEPTIDES THAT BIND TO THE ERYTHROPOIETIN
RECEPTOR" 200********-****
7. Holmes, Christopher P., Chakrabarti, Anjan, Frederick, Brian T., Pan,
Yijun, Dong, Yaohua S., Bhandari, Ashok. "NITROGEN-BASED LINKERS FOR
ATTACHING MODIFYING GROUPS TO POLYPEPTIDES AND OTHER MACROMOLECULES"
8. Holmes, Christopher P., Yin, Qun, Zemede, Genet, Bhandari, Ashok,
Tumelty, David, Lalonde, Guy, Balu, Palani, Schatz, Peter J., Dower,
William J., Chakrabarti, Anjan, Dong, Yaohua S., Frederick, Brian T.,
Wrighton, Nicholas C. "Novel Peptides that Bind to the Erythropoietin
Receptor" 200********-****
9. Holmes, C. P., Jones, D. G., Frederick, B. T., Dong, L.-C.
"Development of a New ortho-Nitrobenzyl Photolabile Linker for Solid
Phase Synthesis" in Peptides: Chemistry, Structure and Biology,
Proceedings of the 14th Am. Peptide Symposium, Kaumaya, P. T. P.,
Hodges, R. S. eds., Mayflower Scientific: Kingswinford, 1996, pp. 44-
45.
10. Holmes, C. P., Li, X., Pan, Y., Xu, C., Bhandari, A., Moody, C. M.,
Miguel, J. A., Ferla, S. W., DeFrancisco, M. N., Frederick, B. T.,
Zhou, S., Macher, N., Jang, L., Irvine, J. D., Grove, J. R. "Discovery
and structure-activity relationships of novel sulfonamides as potent
PTP1B inhibitors" Bioorg. Med. Chem. Lett. 2005, 15, 4336-4341.
11. Woodburn K.W., Leuther K, Fan Q, Holmes C, Frederick B., Xu C, Wehrman
T, Press R: Renal excretion is the primary route of elimination for
the erythropoiesis stimulating agent Hematide as assessed by
quantitative whole-body autoradioluminography (QWBA) in Sprague Dawley
rats [Abstract SaP333]. Presented at the ERA-EDTA Congress; June 21-
24, 2007; Barcelona, Spain
12. Holmes, C. P., Li, X., Pan, Y., Xu, C., Bhandari, A., Moody, C. M.,
Miguel, J. A., Ferla, S. W., De Francisco, M. N., Frederick, B. T.,
Zhou, S., Macher, N., Jang, L., Irvine, J. D., Grove J. R. "PTP1B
Inhibitors: Synthesis and Evaluation of Difluoro-methylenephosphonate
Bioisosteres on a Sulfonamide Scaffold" Bioorg. Med. Chem. Lett. 2008,
18, 2719-2724.
13. Y. M. Angell, A. Bhandari, A. Chakrabarti, M. N. De Francisco, A. N.
Duguay, B. T. Frederick, K. Leu, K. Leuther, X. Li, K. Penta, S.
Piplani, R. Sana, E. A. Whitehorn, P. J. Schatz, K. Yin, and C. P.
Holmes "Discovery and Optimization of a TRAIL R2 Agonist for Cancer
Therapy", Understanding Biology Using Peptides: Proceedings of the
American Peptide Symposium, 19th, San Diego, 2005.
14. Y. M. Angell, A. Bhandari, A. Chakrabarti, M. N. De Francisco, A. N.
Duguay, B. T. Frederick, K. Leu, K. Leuther, X. Li, K. Penta, S.
Piplani, R. Sana, E. A. Whitehorn, P. J. Schatz, K. Yin, and C. P.
Holmes "Update on the Discovery and Optimization of a TRAIL R2 Agonist
for Cancer Therapy", Peptides for Youth: Proceedings of the American
Peptide Symposium, 20th, Montreal, Quebec, Canada, 2007, 101 -103.
15. Daniel E. Levy, Brian Frederick, Zhongli Ding, Bing Luo, Samuel
Zalipsky. "Nanoparticle-Based Delivery of siRNA" DL invited lecture
at upcoming 240th ACS National Meeting, Boston MA, August 25, 2010
Formal references are available upon request. Please visit my LinkedIn
profile for recommendations from former colleagues.