IPR2016-01284
`Declaration of Jackson Gibbs, Ph.D.
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________________________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________________________________
`APOTEX INC., APOTEX CORP., APOTEX PHARMACEUTICALS
`HOLDINGS INC., AND APOTEX HOLDINGS, INC.,
`Petitioners,
`v.
`OSI PHARMACEUTICALS, INC.,
`Patent Owner.
`____________________________________________
`Case IPR2016-01284
`U.S. Patent No. 6,900,221
`____________________________________________
`
`DECLARATION OF JACKSON GIBBS, PH.D.
`
`OSI 2022
`APOTEX V. OSI
`IPR2016-01284
`
`

`

`IPR2016-01284
`Declaration of Jackson Gibbs, Ph.D.
`
`TABLE OF CONTENTS
`
`Page
`I.
`BACKGROUND .............................................................................................1
`BACKGROUND AND CONTEXT OF MY RESEARCH............................3
`II.
`III. COMPENSATION..........................................................................................5
`IV. AVAILABILITY FOR CROSS EXAMINATION.........................................6
`V.
`JURAT.............................................................................................................6
`
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`

`

`IPR2016-01284
`Declaration of Jackson Gibbs, Ph.D.
`
`I, Jackson Gibbs, Ph.D., declare as follows:
`1.
`My name is Jackson Gibbs.
`
`I.
`
`BACKGROUND
`2.
`I am currently an Independent Pharmaceuticals Professional at JBG
`
`Pharma Consulting and a Network Partner at Synergy Partners R&D Solutions
`
`where I specialize in Oncology and Pharmacology R&D. I am also an Adjunct
`
`Professor in the Department of Biochemistry and Molecular Medicine at George
`
`Washington University School of Medicine and Health Sciences.
`
`3.
`
`Most recently, I worked at AstraZeneca for 6 years as Director,
`
`Licensing and Scientific Affairs, Cancer Research. I was a member of the Cancer
`
`Management Team in R&D Boston, a member of the Oncology Business
`
`Development team, and the Scientific Lead for Oncology Alliance activities with
`
`major academic Cancer Centers such as Massachusetts General Hospital and
`
`Memorial Sloan Kettering. At AstraZeneca, I helped to plan and implement the
`
`scientific strategy and evaluated licensing opportunities.
`
`4.
`
`I received my Ph.D. in Pharmacology from the University of Virginia
`
`where I trained with faculty that included future Nobel Laureates Alfred Gilman
`
`and Ferid Murad. I conducted postdoctoral studies with Edward Scolnick, a
`
`member of the National Academy of Sciences. I was at Merck for 23 years
`
`working in oncology drug discovery, and rose to the level of Senior Director,
`
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`

`IPR2016-01284
`Declaration of Jackson Gibbs, Ph.D.
`
`Cancer Research. During my career at Merck, I performed target
`
`identification/validation studies, and led multidisciplinary teams on five medicinal
`
`chemistry supported projects in the areas of signal transduction, angiogenesis, and
`
`cell cycle (three of which led to IND filings – Farnesyl transferase, VEGFR, and
`
`c-Met). I also was involved with preclinical/early clinical development (including
`
`being the co-Chair of the cross functional VEGFR Project Development team).
`
`5.
`
`I am a co-inventor of five issued U.S. patents and an author of 128
`
`research articles, book chapters, and review articles. Some of the invited review
`
`articles (published in Cell and Science) focus on the interface between basic
`
`research and drug discovery in oncology. I also have been actively involved with
`
`the external scientific community. I have made over 100 presentations at
`
`universities and meetings.
`
`6.
`
`I have been a member of several research advisory boards. For
`
`example, I have served on the Medical Affairs Committee of the Children’s Tumor
`
`Foundation (“CTF”), on the Research Advisory Board for the CTF, and as the
`
`Chair of the External Advisory Board for the CTF Preclinical Consortium.
`
`Previously, I was Chair of the Integration Panel, U.S. Army Medical Research
`
`Program for Neurofibromatosis. I have been invited and participated in setting the
`
`Scientific Strategic Vision for the CTF, the Lustgarten Foundation, and the
`
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`IPR2016-01284
`Declaration of Jackson Gibbs, Ph.D.
`
`Multiple Myeloma Research Foundation. I have also served as a member of the
`
`External Advisory Board for the Fox Chase Cancer Center.
`
`7.
`
`I was an Adjunct Professor of Pharmacology at the University of
`
`Pennsylvania School of Medicine for fifteen years. I also was a member of the
`
`American Association for Cancer Research (“AACR”) standing committee on
`
`Science Policy and Legislative Affairs and a member of the AACR Task Force on
`
`Regulatory Science and Policy.
`
`8.
`
`My complete curriculum vitae is attached hereto as Appendix 1.
`
`II.
`
`BACKGROUND AND CONTEXT OF MY RESEARCH
`9.
`I understand that Apotex has challenged the validity of patent claims
`
`from U.S. Patent No. 6,900,221 (“the ’221 Patent”) relating to a method of treating
`
`inter alia non-small cell lung cancer (“NSCLC”) with a therapeutically effective
`
`amount of erlotinib based on a combination of a patent to Schnur and a prior
`
`publication drafted by me (i.e., Exhibit 1010).
`
`10.
`
`I am the author of Exhibit 1010, Jackson B. Gibbs, Anticancer drug
`
`targets: growth factors and growth factor signaling, 105 J. Clinical Investigation 9
`
`(2000), which I will refer to as the Gibbs reference. I have been asked to provide
`
`factual background and context regarding my work at the time of the article that I
`
`drafted.
`
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`IPR2016-01284
`Declaration of Jackson Gibbs, Ph.D.
`
`11. At the time I drafted the Gibbs reference, I was investigating the
`
`general state of the field of anticancer drugs targeting growth factors; I was not
`
`working on an authoritative review of clinical literature for any particular
`
`compound, including erlotinib, or any particular cancer, including NSCLC.
`
`12.
`
`The only article I cite specifically in connection with CP-358,774 is
`
`Citation 13. Citation 13 in my article, James D. Moyer et al., Induction of
`
`Apoptosis and Cell Cycle Arrest by CP-358,774, an Inhibitor of Epidermal Growth
`
`Factor Receptor Tyrosine Kinase, 57 Cancer Research 4838 (1997) (Ex. 1016), is
`
`an article by OSI and Pfizer relating to pre-clinical studies describing anti-tumor
`
`activity in an HN5 human head and neck tumor xenograft and a DiFi human colon
`
`tumor cell line. I did not gather any information from this article about treatment
`
`of NSCLC with CP-358,774.
`
`13.
`
`In conducting my research at the time I drafted my article, I also
`
`reviewed the 1999 Proceedings of the American Society of Clinical Oncology
`
`(“ASCO”) and the 1999 Proceedings of the AACR-NCI-EORTC International
`
`Conference (“AACR”). Id. at 9 (Ex. 1010). I did not find anything in the AACR
`
`abstracts relating to CP-358,774. In the ASCO abstracts, I found two abstracts
`
`relating to CP-358,774. From these two abstracts, I learned certain information
`
`about safety, pharmacokinetic and dosing results from Phase I trials for
`
`CP-358,774, but did not identify any efficacy data for any tumor type including
`
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`IPR2016-01284
`Declaration of Jackson Gibbs, Ph.D.
`
`NSCLC. See L.L. Siu et al., Dose and Schedule-Duration Escalation of the
`
`Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase (TK) Inhibitor CP-
`
`358, 774: A Phase I and Pharmacokinetic (PK) Study, 18 ASCO Program /
`
`Proceedings 388a (1999); D.D. Karp et al., Phase I Dose Escalation Study of
`
`Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase (TK) Inhibitor CP-
`
`358,774 in Patients with Advanced Solid Tumors, 18 ASCO Program / Proceedings
`
`388a (1999).
`
`14. Based on references 12 and 13, the abstracts from the 1999 ASCO and
`
`AACR Conferences, and my own personal recollection, my research at the time of
`
`my article did not identify any information suggesting that CP-358,774 exhibited
`
`anti-tumor activity in NSCLC. I was (and still am) not aware of any published
`
`abstracts or articles describing the clinical or preclinical response of a NSCLC
`
`tumor to CP-358,774 that were available as of the time my article was published,
`
`and I reviewed no such abstracts or articles in drafting my article.
`
`III. COMPENSATION
`15.
`I am being compensated at a rate of $500/hour for the time I spend on
`
`this matter. My compensation is not dependent on and in no way affects the
`
`substance of my statements in this Declaration.
`
`16.
`
`I have no financial interest in Patent Owner. I similarly have no
`
`(cid:73)(cid:76)(cid:81)(cid:68)(cid:81)(cid:70)(cid:76)(cid:68)(cid:79)(cid:3)(cid:76)(cid:81)(cid:87)(cid:72)(cid:85)(cid:72)(cid:86)(cid:87)(cid:3)(cid:76)(cid:81)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:1932)221 patent.
`
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`

`

`Declaration of Jackson Gibbs, PhD.
`
`IPR2016-01284
`
`IV. AVAILABILITY FOR CROSS EXAMINATION
`
`17.
`
`In signing this declaration, I recognize that the declaration will be
`
`filed as evidence in a contested case before the Patent Trial and Appeal Board of
`
`the United States Patent and Trademark Office.
`
`I also recognize that I may be
`
`subject to cross examination in the case and that cross examination will take place
`
`within the United States. If cross examination is required of me, I will appear for
`
`cross examination within the United States during the time allotted for cross
`
`examination.
`
`V.
`
`JURAT
`
`18.
`
`I declare that all statements made herein of my own knowledge are
`
`true and that all statements made on information and belief are believed to be true;
`
`and further that these statements were made with the knowledge that willful false
`
`statements and the like so made are punishable by fine or imprisonment, or both,
`
`under Section 1001 of Title 18 of the United States Code.
`
`Danni/admit
`
`I"
`
`/
`
`

`

`IPR2016-01284
`Declaration of Jackson Gibbs, Ph.D.
`
`APPENDIX 1 TO
`DECLARATION OF JACKSON GIBBS, PH.D
`
`7
`
`

`

`Jackson (Jay) B. Gibbs
`117 Barberry Ct.
`Chalfont, PA 18914
`
`AREAS OF EXPERTISE
`
`General
`
`Jaygibbs2003@yahoo.com
`Jgibbs@synergymedicines.com
`Jackson_gibbs@gwu.edu
`(M) 781•244•8466
`
`(cid:120) Biochemistry and Pharmacology, Pharmaceutical R&D, Extensive experience in
`evaluating/planning/managing research and drug discovery efforts
`(cid:120) Portfolio management
`(cid:120) Evaluation of licensing opportunities
`(cid:120) External project liaison/consult – both domestic and international (Japan, Sweden),
`Served/Chaired on scientific advisory committees (academic, government, and nonprofit
`organizations)
`(cid:120) Extensive journal editorial experience
`
`Basic
`
`(cid:120) Cancer biology and genetics, Neurofibromatosis (NF1 and NF2), Signal transduction, Cell
`cycle regulation, Angiogenesis, G-proteins, Protein kinases
`
`Applied
`
`(cid:120) Target identification and validation
`(cid:120) Assay development
`(cid:120) Small molecule drug discovery (5 med-chem. supported projects; invited review articles on
`this topic in for example Ann. Rev. Pharm., Cell, J. Clin. Invest., Science)
`(cid:120) Preclinical/Clinical development issues (co-Chaired a Product Development Team through
`phase I), prepare IND filings (FTI and VEGFRi); JRC for the AZD6244 + MK-2206 phase I
`(cid:120) Plan and implement external scientific strategy (Alliances and Licensing) to fit global
`portfolio needs
`(cid:120) Manage/guide Alliances and participate/advise in Due Diligence Teams for licensing
`opportunities
`
`EMPLOYMENT HISTORY
`
`Synergy Partners R&D Solutions
`Network Partner/Consultant to the Bio-Pharmaceutical Industry
`
`JBG Pharma Consulting
`Independent Pharmaceuticals Professional
`
`ASTRAZENECA PHARMACEUTICALS, Waltham, MA
`2006-2012
`Director, Licensing and Scientific Affairs,
`Cancer Research
`
` 2014-Present
`
`2012-Present
`
`2006- 2012
`
`8
`
`

`

`JACKSON (JAY) B. GIBBS
`
`MERCK RESEARCH LABORATORIES, West Point, PA & Boston, MA
`Senior Director, Cancer Research
`1995-2005
`Director, Cancer Research
`1993-1995
`Associate Director, Cancer Research
`1990-1993
`Research Fellow
`1988-1990
`Senior Research Biochemist
`1985-1988
`Postdoctoral Scientist
`1982-1985
`
`Page Two
`
`1982 – 2005
`
`ACADEMIC EXPERIENCE
`
`GEORGE WASHINGTON UNIV. SCHOOL OF MEDICINE AND HEATH SCIENCES
`Adjunct Professor, Dept. of Biochemistry and Molecular Medicine
` 2015 - present
`
`UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE
`Adjunct Professor of Pharmacology
`Adjunct Associate Professor of Pharmacology
`
`Invited ad hoc graduate lectures (Harvard, Penn, Princeton, and Virginia)
`Invited ad hoc undergraduate lectures (Bucknell, Haverford, and Swarthmore)
`
`GEORGETOWN UNIVERSITY, Lecturer, Biochemistry
`UNIVERSITY OF VIRGINIA, Lecturer, Pharmacology
`BUCKNELL UNIVERSITY, Teaching Assistant
`
`PROFESSIONAL HONORS & SOCIETY MEMBERSHIPS
`
`2004 – 2007
`1992 – 2003
`
`1981
`1979 – 1981
`1974 – 1977
`
`Research Advisory Board, Children’s Tumor Foundation (formerly the National
`Neurofibromatosis Foundation), 1993-2015
`Scientific Review Panel, New Jersey Commission on Cancer Research, 1995-2001
`NCI Working Group - Preclinical models of cancer, 1996
`U.S. Army Grant Review Panel, Neurofibromatosis, 1997
`Corporate Relations Committee, Cancer Institute of New Jersey, 1998-2003
`Scientific organizing committee and Chair of Opening session, 2003 AACR-NCI-EORTC
`international conference, Boston
`Scientific organizing committee and Keynote Speaker, 2004 Princess Takamatsu Cancer Fund
`Symposium
`Integration Panel, U.S. Army Medical Research Programs (Neurofibromatosis and Tuberous
`Sclerosis), 2001-2006
`Chair-Elect/Chair/Chair Emeritus, Integration Panel, U.S. Army Medical Research Programs
`(Neurofibromatosis), 2003-2006
`Advisor to the Drug Discovery Initiative, Children’s Tumor Foundation, 2006-present
`External Advisory Board of the NF Consortium, Chair of the Preclinical group, 2007-2013
`AACR Princess Takamatsu Memorial Lectureship Committee, 2008
`Medical Affairs Committee reporting to the Board of Directors, Children’s Tumor Foundation,
`2009-2012
`AACR standing committee: Science Policy and Legislative Affairs, 2009-2012
`Scientific organizing committee, AACR-NCI-EORTC meeting, Berlin, 2010
`AACR Task Force on Regulatory Science and Policy, 2011-2012
`
`9
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`

`

`JACKSON (JAY) B. GIBBS
`
`Page Three
`
`Strategic Vision setting committees for the Children’s Tumor Foundation (2006, 2011),
`Lustgarten Foundation (Banbury Conference, 2008), and the Multiple Myeloma Research
`Foundation (2011, 2012)
`External Advisory Board, Fox Chase Cancer Center, 2012-2014
`
`Editorial Board
`Exp. Opin. Invest. Drugs, 1994-2001
`Exp. Rev. Anticancer Therapy, 2001-2005
`IDrugs, 1998-2010
`Int. J. Oncology, 1995-2002
`J. Biol. Chem., 1995-2000
`Molec. Cell. Biol., 1995-2000
`
`Ad Hoc Reviewer
`Biochemistry; Cancer Res.; Cell; Nature; Proc. Natl. Acad. Sci. USA; Science
`
`USPHS Predoctoral Fellowship
`American Association for Advancement of Science
`American Association for Cancer Research
`
`EDUCATION
`
`B.A., Biology/Chemistry, BUCKNELL UNIVERSITY, 1977
`Ph.D., Pharmacology (1982), UNIVERSITY OF VIRGINIA, 1981
`Advisor: Gary Brooker
`Biochemistry, GEORGETOWN UNIVERSITY, 1982
`
`PROFESSIONAL DEVELOPMENT
`
`Postdoctoral Fellowship, Merck Research Laboratories,
` Advisor: Edward Scolnick
`
`10
`
`

`

`JACKSON (JAY) B. GIBBS
`
`ADDENDUM
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`10.
`
`11.
`
`12.
`
`I. PUBLICATIONS
`
`DePaoli-Roach, A.A., Gibbs, J.B. and Roach, P.J. (1979). Calcium and calmodulin
`activation of muscle phosphorylase kinase: Effect of tryptic proteolysis. FEBS Lett.
`105:321-324.
`
`Gibbs, J.B., Hsu, C.Y., Terasaki, W.L. and Brooker, G. (1980). Calcium and microtubule
`dependence for increased ornithine decarboxylase activity stimulated by ß-adrenergic
`agonists, dibutyryl cyclic AMP or serum in a rat astrocytoma cell line. Proc. Natl. Acad.
`Sci. USA 77:995-999.
`
`Gibbs, J.B., Ellis, R.W. and Scolnick, E.M. (1984). Autophosphorylation of v-Ha-ras p21
`is modulated by amino acid residue 12. Proc. Natl. Acad. Sci. USA 81:2674-2678.
`
`Gibbs, J.B. and Brooker, G. (1984). Dissociation of RNA synthesis from the calcium
`requirement for serum-increased ornithine decarboxylase activity in rat glioma cells.
`Biochim. Biophys. Acta 801:87-98.
`
`Gibbs, J.B. and Brooker, G. (1984). Calcium dependence for increased antizyme
`inhibitory activity of ornithine decarboxylase in rat glioma cells. Biochem. Biophys.
`Acta 801:99-105.
`
`Gibbs, J.B., Sigal, I.S., Poe, M. and Scolnick, E.M. (1984). Intrinsic GTPase activity
`distinguishes normal and oncogenic ras p21 molecules. Proc. Natl. Acad. Sci. USA
`81:5704-5708.
`
`Temeles, G.L., Gibbs, J.B., D’Alonzo, J.S., Sigal, I.S. and Scolnick, E.M. (1985). Yeast and
`mammalian ras proteins have conserved biochemical properties. Nature 313:700-703.
`
`Gibbs, J.B., Sigal, I.S. and Scolnick, E.M. (1985). Biochemical properties of normal and
`oncogenic ras p21. Trends Biochem. Sci. 10:350-353.
`
`Sigal, I.S., Gibbs, J.B., D’Alonzo, J.S., Temeles, G.L., Wolanski, B.S., Socher, S.H. and
`Scolnick, E.M. (1986). Mutant ras -encoded proteins having altered nucleotide binding
`exert dominant biological effects. Proc. Natl. Acad. Sci. USA 83:952-956.
`
`Cannon, J.F., Gibbs, J.B. and Tatchell, K. (1986). Suppressors of the ras2 mutation of
`Saccharomyces cerevisiae. Genetics 113:247-264.
`
`Sigal, I.S., Gibbs, J.B., D’Alonzo, J.S. and Scolnick, E.M. (1986). Identification of effector
`residues and a neutralizing epitope of Ha-ras p21. Proc. Natl. Acad. Sci. USA 83:4725-
`4729.
`
`Bradley, M.O., Kraynak, A., Storer, R.D. and Gibbs, J.B. (1986). Experimental metastasis
`in nude mice of NIH-3T3 cells containing various ras genes. Proc. Natl. Acad. Sci. USA
`83:5277-5281.
`
`11
`
`

`

`13.
`
`14.
`
`15.
`
`16.
`
`17.
`
`18.
`
`19.
`
`20.
`
`21.
`
`22.
`
`23.
`
`24.
`
`Robinson, L.C., Gibbs. J.B., Marshall, M.S., Sigal, I.S. and Tatchell, K. (1987). CDC25: a
`component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae. Science
`235:1218-1221.
`
`Marshall, M.S., Gibbs, J.B., Scolnick, E.M. and Sigal, I.S. (1987). Regulatory function of
`the yeast RAS C-terminus. Molec. Cell. Biol., 7:2309-2315.
`
`Gibbs, J.B., Schaber, M.D., Marshall, M.S., Scolnick, E.M. and Sigal, I.S. (1987).
`Identification of guanine nucleotides bound to ras-encoded proteins in growing yeast
`cells. J. Biol. Chem. 262:10426-10429.
`
`Sigal, I.S., Smith, G.M., Jurnak, F., Marsico-Ahern, J.D., D’Alonzo, J.S., Scolnick, E.M.
`and Gibbs, J.B. (1987). Molecular approaches toward an anti-ras drug. Anti-Cancer
`Drug Design 2:107-115.
`
`Marshall, M.S., Gibbs, J.B., Scolnick, E.M. and Sigal, I.S. (1988). An adenylate cyclase
`from Saccharomyces cerevisiae that is stimulated by RAS proteins with effector
`mutations. Molec. Cell. Biol., 8:52-61.
`
`Sigal, I.S., D’Alonzo, J.S., Ahern, J.D., Marshall, M.S., Smith, G.M., Scolnick, E.M. and
`Gibbs, J.B. (1988). The ras oncogene protein as a G-protein. Adv. Second Messenger
`and Phosphoprotein Res. 21:193-200.
`
`Gibbs, J.B., Marsico-Ahern, J.D., Scolnick, E.M. and Sigal, I.S. (1988). Inhibition of yeast
`adenylate cyclase by antibodies to ras p21. Biochem. J., 252:289-292.
`
`Gibbs, J.B., Schaber, M.D., Allard, W.J., Sigal, I.S. and Scolnick, E.M., (1988). Purification
`of ras GTPase activating protein from bovine brain. Proc. Natl. Acad. Sci., USA,
`85:5026-5030.
`
`Sigal, I.S., Marshall, M.S., Schaber, M.D., Vogel, U.S., Scolnick, E.M. and Gibbs, J.B.
`(1988). Structure/Function Studies of the ras Protein. Cold Spring Harbor Symposium
`on Quantitative Biology, 53:863-869.
`
`Vogel, U.S., Dixon, R.A.F., Schaber, M.D., Diehl, R.E., Marshall, M.S., Scolnick, E.M.,
`Sigal, I.S. and Gibbs, J.B. (1988). Cloning of bovine GAP and its interaction with
`oncogenic ras p21. Nature 335:90-93.
`
`Gibbs, J.B., Vogel, U.S., Schaber, M.D., Marshall, M.S., Diehl, R.E., Scolnick, E.M., Dixon,
`R.A.F. and Sigal, I.S. (1989). Purification and molecular cloning of bovine GAP. in The
`Guanine nucleotide binding proteins: Common structural and functional properties (L.
`Bosch, B. Kraal, and A. Parmeggiani, eds) Plenum p. 191-200.
`
`Marshall, M.S., Hill, W.S., Ng, A.S., Vogel, U.S., Schaber, M.D., Scolnick, E.M., Dixon,
`R.A.F., Sigal, I.S. and Gibbs, J.B., (1989). A C-terminal domain of GAP is sufficient to
`stimulate ras p21 GTPase activity. EMBO J. 8:1105-1110.
`
`25.
`
`Sigal, I.S. and Gibbs, J.B., (1989) Oncogenes. Current Opinion in Cell Biology 6-290.
`
`12
`
`

`

`26.
`
`27.
`
`28.
`
`29.
`
`30.
`
`31.
`
`32.
`
`33.
`
`34.
`
`35.
`
`36.
`
`37.
`
`Vogel, U.S., Dixon, R.A.F., Schaber, M.D., Diehl, R.E., Marshall, M.S., Hill, W.S., Ng,
`A.S., Scolnick, E.M., Sigal, I.S. and Gibbs, J.B., (1989). Molecular biology of GAP and its
`interaction with ras p21. in ras Oncogenes (D. Spandidos, ed.) Plenum p. 303-309.
`
`Gibbs, J.B. and Marshall, M.S., (1989). The ras oncogene - an important regulatory
`element in lower eucaryotic organisms. Microbiol. Rev. 53: 171-185.
`
`Marshall, M.S., Schaber, M.D., Vogel, U.S., Hill, W.S., Ng, A.S., Scolnick, E.M., Dixon,
`R.A.F., Sigal, I.S. and Gibbs, J.B. (1989). The ras oncogene protein. in 40th Colloquium
`Mosbach, Molecular mechanisms of hormone action. Springer-Verlag, p. 85-91.
`
`Gibbs, J.B., Schaber, M.D., Schofield, T.L., Scolnick, E.M. and Sigal, I.S., (1989). Xenopus
`oocyte germinal vesicle breakdown induced by [Val12]Ras is inhibited by a cytosol-
`localized Ras mutant. Proc. Natl. Acad. Sci. USA 86: 6630-6634.
`
`Schaber, M.D., Garsky, V.M., Boylan, D., Hill, W.S., Scolnick, E.M., Marshall, M.S., Sigal,
`I.S. and Gibbs, J.B. (1989). Ras interaction with the GTPase activating protein (GAP).
`Proteins: Structure, Function, and Genetics, 6: 306-315.
`
`Molloy, C.J., Bottaro, D.P., Fleming, T.P., Marshall, M.S., Gibbs, J.B. and Aaronson,
`S.A. (1989). PDGF induction of tyrosine phosphorylation of GTPase activating protein.
`Nature 342:711-714.
`
`Gibbs, J.B., Schaber, M.D., Hill, W.S., Vogel, U.S., Scolnick, E.M., Dixon, R.A.F., Sigal, I.S.
`and Marshall, M.S. (1990). Structure-function analyses of ras and the GTPase activating
`protein. in ADP-ribosylating toxins and G-proteins: Insights into Signal Transduction.
`(J. Moss and M. Vaughn, eds) ASM, p. 381-396.
`
`Gibbs, J.B., Schaber, M.D., Garsky, V.M., Vogel, U.S., Scolnick, E.M., Dixon, R.A.F. and
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`Signal Transduction. Rockefeller University, Press. p. 78-85.
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`Tanaka, K., Nakafuku, M., Satoh, T., Marshall, M.S., Gibbs, J.B., Matsumoto, K., Kaziro,
`Y. and Toh-e, A. (1990). Saccharomyces cerevisiae genes, IRA1 and IRA2, encode
`proteins which may be functionally equivalent to mammalian GTPase activating protein
`(GAP). Cell, 60:803-807.
`
`Hata, Y., Kikuchi, A., Sasaki, T., Schaber, M.D., Gibbs, J.B. and Takai, Y. (1990).
`Inhibition of the ras p21 GTPase activating protein stimulated activity of c-Ha-ras p21
`by smg p21 having the same putative effector domain as ras p21s. J. Biol. Chem.
`265:7104-7107.
`
`Sadler, S.E., Maller, J.L. and Gibbs, J.B. (1990). Transforming ras proteins accelerate
`hormone-induced maturation and stimulate cyclic AMP phosphodiesterase in Xenopus
`oocytes. Molec. Cell. Biol. 10:1689-1696.
`
`Schaber, M.D., O’Hara, M.B., Garsky, V.M., Mosser, S.D., Bergstrom, J.D., Moores, S.L.,
`Marshall, M.S., Friedman, P.A., Dixon, R.A.F. and Gibbs, J.B. (1990). Polyisoprenylation
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`factors, and the GTPase activating protein (GAP). J. Biol. Chem. 265:20437-20442.
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`Gibbs, J.B., (1990). Toward the function of Ras: Filling in the GAPs. Cancer Cells 2:291-
`293.
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`Bouton, A.H., Kanner, S.B., Vines, R.R., Wang, H.-C.R., Gibbs, J.B. and Parsons, J.T.
`(1991). Transformation by pp60src or stimulation of cells with epidermal growth factor
`induces stable association of tyrosine-phosphorylated cellular proteins with GTPase-
`activating protein. (1991). Molec. Cell. Biol. 11:945-953.
`
`Brott, B.K., Decker, S., Shafer, J., Gibbs, J.B. and Jove, R. (1991). GTPase-activating
`protein interactions with the viral and cellular Src kinases. Proc. Natl. Acad. Sci. USA
`88:755-759.
`
`Farnsworth, C.L., Marshall, M.S., Gibbs, J.B., Stacey, D.W. and Feig, L.A. (1991).
`Preferential inhibition of the oncogenic form of RasH by mutations in the GAP
`binding/effector domain. Cell 64:625-633.
`
`Gibbs, J.B. (1991). Ras C-terminal processing enzymes - new drug targets? Cell 65:1-4.
`
`Tsai, M.-H., Roudebush, M., Dobrowolski, S., Yu, C.-L., Gibbs, J.B. and Stacey, D.W.
`(1991). Ras GTPase-activating protein physically associates with mitogenically active
`phospholipids. Molec. Cell. Biol. 11:2785-2793.
`
`Nori, M., Vogel, U.S., Gibbs, J.B. and Weber, M.J. (1991). Inhibition of v-src-induced
`transformation by a GTPase-activating protein. Molec. Cell. Biol. 11:2812-2818.
`
`Eklund, E.A., Marshall, M.S., Gibbs, J.B., Crean, C.D. and Gabig, T.G. (1991). Resolution
`of a low molecular weight G protein in neutrophil cytosol required for NADPH-oxidase
`activation and reconstitution by recombinant Krev-1 protein. J. Biol. Chem., 266:13964-
`13970.
`
`Marshall, M.S., Davis, L.J., Keys, R.D., Mosser, S.D., Hill, W.S., Scolnick, E.M. and
`Gibbs, J.B. (1991). Identification of amino acid residues required for ras p21 target
`activation. Molec. Cell. Biol., 11:3997-4004.
`
`Stacey, D.W., Feig, L.A. and Gibbs, J.B. (1991). Dominant inhibitory Ras mutants
`selectively inhibit the activity of either cellular or oncogenic Ras. Molec. Cell.
`Biol.,11:4053-4064.
`
`Moores, S.L., Schaber, M.D., Mosser, S.D., Rands, E., O’Hara, M.B., Garsky, V.M.,
`Marshall, M.S., Pompliano, D.L. and Gibbs, J.B. (1991). Sequence dependence of
`protein isoprenylation. J. Biol. Chem.,266:14603-14610.
`
`Kohl, N.E., Diehl, R.E., Schaber, M.D., Rands, E., Soderman, D.D., He, B., Moores, S.L.,
`Pompliano, D.L., Ferro-Novick, S., Powers, S., Thomas, K.A. and Gibbs, J.B., (1991).
`Structural homology among mammalian and Saccharomyces cerevisiae isoprenyl-protein
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`Dominguez, I., Marshall, M.S., Gibbs, J.B., Garcia de Herreros, A., Cornet, M.E.,
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`Role of GTPase activating protein in mitogenic signaling through phosphatidylcholine-
`hydrolyzing phospholipase C. EMBO J. 10:3215-3220.
`
`Gibbs, J.B. (1991). GAP and farnesyl-protein transferase: potential anti-Ras targets. in
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`
`Stacey, D.W., Roudebush, M., Day, R., Mosser, S.D., Gibbs, J.B. and Feig, L.A. (1991).
`Dominant inhibitory Ras mutants demonstrate the requirement for Ras activity in the
`action of tyrosine kinase oncogenes. Oncogene, 6:2297-2304.
`
`Pompliano, D.L., Rands, E., Schaber, M.D., Mosser, S.D., Anthony, N.J., and Gibbs, J.B.
`(1992). Steady state kinetic mechanism of Ras farnesyl: protein transferase.
`Biochemistry, 31:3800-3807.
`
`Park, S., Marshall, M.S., Gibbs, J.B., and Jove, R. (1992). Reconstitution of interactions
`between the Src tyrosine kinases and Ras GAP using a baculovirus expression system. J.
`Biol. Chem., 267:1612-11618.
`
`Goldschmidt-Clermont, P.J., Mendelsohn, M.E., and Gibbs, J.B. (1992). Rac and Rho in
`control. Current Biology, 2:669-671.
`
`Gibbs, J.B. (1992). Pharmacological probes of Ras function. Seminars in Cancer Biology,
`3:383-390.
`
`Gibbs, J.B. (1993). Lipid modifications of proteins in the Ras superfamily. in GTPases in
`Biology. (L. Birnbaumer & B. Dickey, eds.). Springer-Verlag, p. 335-344.
`
`Gibbs, J. B., Pompliano, D. L., Mosser, S. D., Rands, E., Lingham, R B., Singh, S. B.,
`Scolnick, E. M., Kohl, N. E., and Oliff, A. (1993). Selective inhibition of farnesyl-protein
`transferase blocks Ras processing in vivo. J. Biol. Chem. 268:7617-7620.
`
`Omer, C.A., Kral, A.M., Diehl, R.E., Prendergast, G.C., Powers, S., Allen, C.M., Gibbs,
`J.B., and Kohl, N.E. (1993). Characterization of recombinant human farnesyl-protein
`transferase: Cloning, expression, farnesyl diphosphate binding and functional
`homology with yeast prenyl-protein transferases. Biochemistry 32:5167-5176.
`
`Kohl, N.E., Mosser, S.D., deSolms, S.J., Giuliani, E.A., Pompliano, D.L., Graham, S.L.,
`Smith, R.L., Scolnick, E.M., Oliff, A., and Gibbs, J.B. (1993). Selective inhibition of ras-
`dependent transformation by a farnesyltransferase inhibitor. Science 260:1934-1937.
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`Singh, S.B., Zink, D.L., Liesch, J.M., Goetz, M.A., Jenkins, R.G., Nallin-Omstead, M.,
`Silverman, K.C., Bills, G.F., Mosley, R.T., Gibbs, J.B., Albers-Schonberg, G., and
`Lingham, R.B. (1993). Isolation and structure of chaetomellic acids A and B from
`Chaetomella acutiseta: farnesyl pyrophosphate mimic inhibitors of Ras farnesyl-protein
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`transferase: interactive binding between substrates and a preferred kinetic pathway.
`Biochemistry, 32: 8341-8347.
`
`Prendergast, G.C., and Gibbs, J.B. (1993). Pathways of Ras function: connections to the
`actin cytoskeleton. Adv. Cancer. Res. 62:19-64.
`
`Prendergast, G.C., Davide, J.P, Kral, A., Diehl, R., Gibbs, J.B., Omer, C.A., and Kohl, N.E.
`(1993). Negative growth selection against rodent fibroblasts targeted for genetic
`inhibition of farnesyl transferase. Cell Growth & Differ. 9:707-713.
`
`VanRenterghem, B., Gibbs, J.B., and Maller, J.L. (1993). Reconstitution of p21ras-
`dependent and -independent mitogen-activated protein kinase activation in a cell-free
`system. J. Biol. Chem. 268:19935-19938.
`
`Lingham, R.B., Silverman, K.C., Bills, G.F., Cascales, C., Sanchez, M., Jenkins, R.G.,
`Gartner, S.E., Martin, I., Diez, M.T., Pelaez, F., Mochales, S., Kong, Y.L., Burg, R.W.,
`Meinz, M.S., Huang, L., Nallin-Omstead, M., Mosser, S.D., Schaber, M.D., Omer, C.A.,
`Pompliano, D.L., Gibbs, J.B., and Singh, S.B. (1993). Chaetomella acutiseta produces
`chaetomellic acid A and B which are reversible inhibitors of farnesyl-protein transferase.
`Appl. Microbiol. Biotech. 40:370-374.
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`Dufresne, C., Wilson, K.E., Singh, S.B., Zink, D.L., Bergstrom, J.D., Rew, D., Polishook,
`J.D., Meinz, M., Huang, L.Y., Silverman, K.C., Lingham, R.B., Mojena, M., Cascales, C.,
`Pelaez, F. and Gibbs, J.B. (1993). Zaragozic acid-D and acid-D(2) - Potent inhibitors of
`squalene synthase and of Ras farnesyl-protein transferase. J. Natural Products 56:1923-
`1929.
`
`Zhang, F.L., Diehl, R.E., Kohl, N.E., Gibbs, J.B., Giros, B., Casey, P.J., and Omer, C.A.
`(1994). cDNA cloning and expression of rat and human protein
`geranylgeranyltransferase type-I. J. Biol. Chem. 269:3175-3180.
`
`Omer, C.A. and Gibbs, J.B. (1994). Protein prenylation in eukaryotic microorganisms:
`Genetics, biology, and biochemistry. Molec. Microbiol. 11:219-225.
`
`Prendergast, G.C. and Gibbs, J.B. (1994). Ras regulatory interactions: novel targets for
`anti-cancer intervention? BioEssays 16:187-191.
`
`Graham, S.L., deSolms, S.J., Giuliani, E.A., Kohl, N.E., Mosser, S.D., Oliff, A.I.,
`Pompliano, D.L., Rands, E., Breslin, M.J., Deana, A.A., Garsky, V.M., Scholz, T.H.,
`Gibbs, J.B., and Smith, R.L. (1994). Pseudopeptide inhibitors of Ras farnesyl-protein
`transferase. J. Med. Chem. 37:725-732.
`
`Gibbs, J.B., Oliff, A., and Kohl, N.E. (1994). Farnesyltransferase inhibitors: Ras research
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`Oliff, A., and Kohl, N.E. (1994). Farnesyl transferase inhibition causes morphological
`reversion of ras-transformed cells by a complex mechanism that involves regulation of
`the actin cytoskeleton. Molec. Cell. Biol. 14:4193-4202.
`
`Singh, S.B., Jones, E.T., Goetz, M.A., Bills, G.F., Nallin-Omstead, M., Jenkins, R.G.,
`Lingham, R.B., Silverman, K.C., and Gibbs, J.B. (1994). Fusidienol: a novel inhibitor of
`Ras farnesyl-protein transferase from Fusidium griseum. Tetrahedron Lett. 35:4693-4696.
`
`Kohl, N.E., Wilson, F.R., Mosser, S.D., Giuliani, E., deSolms, S.J., Conner, M.W.,
`Anthony, N.J., Holtz, W.J., Gomez, R.P., Lee, T.-J., Smith, R.L., Graham, S.L., Hartman,
`G.D., Gibbs, J.B., and Oliff, A. (1994). Protein farnesyltransferase inhibitors block the
`growth of ras-dependent tumors in nude mice. Proc. Natl. Acad. Sci. USA 91:9141-9145.
`
`Gibbs, J.B. and Oliff, A. (1994). Pharmaceutical research in molecular oncology. Cell 79:
`193-198.
`
`Singh,