1392
`no.10
`snug
`(m; 1 ———————— 5m: P38620000
`7;: pxocsmvxwus as THE
`WATIONAL ACADEMY op
`
`MAY 15, 1992
`
`VOLUME 89
`NUMBER 10
`
`
`
`Proceedingsi
`
`OF THE
`
`National Academy
`of Sciences
`
`OF THE UNITED STATES OF AMERICA
`
`Pfizer Ex. 1008
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`

`

`Proceedings
`OF THE
`
`National Academy
`of Sciences
`
`OF THE UNITED STATES OF AMERICA
`
`Officers
`of the
`Academy
`
`Editorial Board
`ofth
`Proceedings
`
`FRANK PRESS, President
`JAMEs D. EBERT, Vice President
`PETER H. RAVEN, Home Secretary
`JAMES B. WYNGAARDEN, Foreign Secretary
`ELKAN R. BLOUT, Treasurer
`
`ROBERT H. ABELES
`MICHAEL J. CHAMBERLIN
`IGOR B. DAWID
`RONALD L. GRAHAM
`
`LAWRENCE BOGORAD, Chairman
`GORDON G. HAMMEs
`ERIC R. KANDEL
`PHILIP W. MAJERUS
`HERBERT A. SIMON
`
`MAXINE F. SINGER
`HAROLD VARMUS
`SIIERMAN M. WEISSMAN
`
`Senior Contributing
`Editors:
`
`MICIIAEL T. CLEGG, ERIC R. KANDEL, ARNO G. MOTULSKY, PAUL R. SCHIMMEL,
`CHARLES F. STEVENS, IRVING L. WEISSMAN
`
`Contributing Editors:
`
`MAX COOPER, HERMAN N. EISEN, LEROY HOOD, WILLIAM E. PAUI.
`
`Consulting Editors:
`
`RAYMOND L. ERIKSON, JOSEPH L. GOLDSTEIN, DAVID J. L. LUCK, PHILIP W. MAIERUS,
`DAVID D. SABATINI, ALLAN C. SPRADLING, SHERMAN I. WEISSMAN
`
`Managing Editor:
`Senior Associate Editor:
`Associate Editors:
`
`FRANCES R. ZWANZIG
`GARY T. COCKS
`CAY BUTLER, JOHN M. MALLOY, MARILYN J. MASON, JANET L. MORGAN, T. PEARSON,
`DOROTHY P. SMITH, COLENE RUCII WALDEN
`Asszstant Managing Editor: JOANNE D'AMJCO
`.Semor Production Editor:
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`Production Editors:
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`This mate-rialwas-eoniad
`
`Pfizer Ex. 1008
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`

`

`
`
`Proceedings
`
`OF THE
`
`National Academy
`of Sciences
`
`OF THE UNITED STATES OF AMERICA
`
`
`pp. 4221—4780
`Volume 89, Number 10
`May 15, 1992
`
`
`Table of Contents
`
`CONDENSED INFORMATION FOR CONTRIBUTORS
`
`AUTHOR INDEX
`
`Physical Sciences
`
`CHEMISTRY
`
`On the structure of the nickel/iron/sulfur center of the carbon monoxide
`dehydrogenase from Rhodoxpirillmn rubrum: An x-ray absorption
`spectroscopy study
`
`Semisynthetic combinatorial antibody libraries: A chemical solution to the
`diversity problem
`
`Identification of highest-affinity ligands by affinity selection from equimolar
`peptide mixtures generated by robotic synthesis
`
`Grace 0. Tan, Scott A. Ensign, Stefano
`Ciurli, Michael J. Scott, Britt Hedman,
`Richard H. Holm, Paul W. Ludden, Z.
`Richard Korszun, Philip J. Stephens,
`and Keith 0. Hodgson
`Carlos F. Barbas 111,.1. D. Bain,
`Denis M. Hoekstra,
`and Richard A. Lerner
`Ronald N. Zuckermann, Janice M. Kerr,
`Michael A. Siani. Steven C. Banville,
`and Daniel V. Santi
`
`xi—xiii
`
`4427—4431
`
`4457—4461
`
`4505—4509
`
`MATHEMATICS
`
`Approximating Markov chains
`
`Steven M. Pincus
`
`4432—4436
`
`iii
`
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`

`

`Contents
`
`Biological Sciences
`
`BIOCHEMISTRY
`
`MELAS mutation in mtDNA binding site for transcription termination
`factor causes defects in protein synthesis and in respiration but no
`change in levels of upstream and downstream mature transcripts
`
`Alternative usage of initiation codons in mRNA encoding the
`cAMP-responsive~element modulator generates regulators with
`opposite functions
`
`Phosphorylation sites in the amino-terminal region of mouse p53
`Transformation and transactivation suppressor activity of the c-Jun leucine
`zipper fused to a bacterial repressor
`
`Functional domains in Fok I restriction endonuclease
`
`The FixL protein of Rhizobium mclilati can be separated into a
`heme-binding oxygen-sensing domain and a functional C-terminal
`kinase domain
`
`Cloning of the low-affinity murine granulocyte—macrophage
`colony-stimulating factor receptor and reconstitution of a high-affinity
`receptor complex
`
`Direct association of pp40/lKBfi with rel/NF-KB transcription factors: Role
`of ankyrin repeats in the inhibition of DNA binding activity
`
`A 33-kDa polypeptide with homology to the laminin receptor: Component
`of translation machinery
`
`Crystal structure of an engineered subtilisin inhibitor complexed with
`bovine trypsin
`
`A gene homologous to chloroplast carbonic anhydrase (icfA) is essential to
`photosynthetic carbon dioxide fixation by Synec/zococcus PCC7942
`Efficiency of binding the retinoblastoma protein correlates with the
`transforming capacity of the E7 oncoproteins of the
`human papillomaviruses
`
`Long-term 'agonist exposure induces upregulation of fig-adrenergic receptor
`expresston Via multiple CAMP response elements
`
`lnducltlitlm of apoptosis by wild-type p53 in a human colon tumor-derived
`ce
`tne
`
`Peptidyl-prolyl cis—trans isomerase improves the efficiency of protein
`disulfide isomerase as a catalyst of protein folding
`Methods for the large-scale synthesis of psoralen furan-side monoadducts
`and diadducts
`
`Excretion of putrescine by the putreseine—ornithine antiporter encoded by
`the poIE gene of Escherichia coli
`
`Cloning of the yeast FAS3 gene and primary structure of yeast
`acetyl-CoA carboxylase
`
`The Escherichia coli chromosome contains specific. unmethylated dam and
`11cm sites
`
`Modification of histidine residues in proteins by reaction
`with 4<hydroxynonenal
`
`Adenovirus EIA, simian virus 40 tumor antigen, and human papillomavirus
`E7 protein share the capacity to disrupt the interaction between
`transcription factor E2F and the retinoblastoma gene product
`
`iv
`
`A. Chomyn, A. Martinuzzi, M. Yoneda,
`A. Daga, O. Hurko, D. Johns, S. T.
`Lai, l. Nonaka, C. Angelini,
`and G. Attardi
`
`Veronique Delmas, Brid M. Laoide.
`Denis Masquilier, Rolf P. de Groot,
`Nicholas S. Foulkes, and Paolo
`Sassone-Corsi
`
`Yeong Wang and Walter Eckhart
`Michele Granger—Schnarr, Enrico
`Benusiglio, Manfred Schnarr,
`and Paolo Sassone-Corsi
`
`Lin Li, Louisa P. Wu, and Srinivasan
`Chandrasegran
`Ellen K. Monson, Michael Weinstein,
`Gary S. Ditta, and Donald R. llelinski
`
`Linda S. Park, Unja Martin,
`Rick Sorensen, Sean Luhr,
`Philip J. Morrissey. David Cosman,
`and Alf Larsen
`
`Jun—ichiro lnoue, Lawrence D. Kerr.
`Dana Rashid, Nathan Davis,
`Henry R. Bose, Jr.,
`and Inder M. Verma
`
`Dorothy Auth and George Brawerman
`
`Yasuo Takeuchi, Takamasa Nonaka,
`Kazuo T. Nakamura, Shuichi Kojima,
`Kin—ichiro Miura, and Yuklo Mitsui
`
`Hideya Fukuzawa, Eiji Suzuki, Yutaka
`Komukai, and Shigetoh Miyachi
`Donald V. Heck, Carole L. Yee,
`Peter M. Howley, and Karl Manger
`
`Ronald F. Thomas, Brian D. Holt.
`Debra A. Schwinn,
`and Stephen B. Liggett
`P. Shaw, R. Bovey, S. Tardy, R. Sahli,
`B. Sordat, and J. Costa
`E. Ralf Schénbrunner and Franz
`X. Schmid
`
`H. Peter Spielmann, Srinivas S. Sastry,
`and John E. Hearst
`
`Keiko Kashiwagi, Saku Miyamoto,
`Fumihiro Suzuki, Hiroshi Kobayashi,
`and Kazuei Igarashi
`Walid Al-Feel,
`Subrahmanyam S. Chirala,
`and Salih .l. Wakil
`
`Steven Ringquist
`and Cassandra L. Smith
`
`Koji Uchida and E. R. Stadtman
`
`Srikumar Chellappan. Virginia B. Kraus,
`Burkhard Kroger, Karl Munger,
`Peter M. Howley, William C. Phelps,
`and Joseph R. Nevins
`
`4221—4225
`
`4226—4230
`
`4231—4235
`4236—4239
`
`4275—4279
`
`4280-4284
`
`4295—4299
`
`4333—4337
`
`4368—4372
`
`4407—4411
`
`4437—4441
`
`4442—4445
`
`4490-4494
`
`4495—4499
`
`4510—45 1}
`
`4514—45 18
`
`45294533
`
`4534—4538
`
`4539—4543
`
`4544—4548
`
`4549—4553
`
`A_“
`
`PfizerEX.1008
`
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`
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`

`

`Contents
`
`Modulation of the RNA-binding activity of a regulatory protein by iron in
`vitro: Switching between enzymatic and genetic function?
`
`Molecular cloning of epididymal and seminal vesicular transcripts encoding
`a semenogelin-related protein
`Amino acid substitutions in the sixth transmembrane domain of
`P-glycoprotein alter multidrug resistance
`Cleavage behavior of calieheamicin 71 and calicheamicin T
`
`Endoproteolytic processing of a farnesylated peptide in vitro
`
`Expression cloning of a rat brain somatostatin receptor cDNA
`
`Polar zipper sequence in the high-affinity hemoglobin of Ascaris suum:
`Amino acid sequence and structural interpretation
`
`Excision of TnIO from the donor site during transposition occurs by flush
`double—strand cleavages at the transposon termini
`
`Fatty acids activate a chimera of the clofibric acid-activated receptor and
`the glucocorticoid receptor
`
`Coupling of dual signaling pathways: Epidermal growth factor action
`involves the estrogen receptor
`
`In vitro replication of adeno-associated virus DNA
`Mutations in the catalytic subunit of cAMP-dependent protein kinase result
`in unregulated biological activity
`
`Observing the 1H NMR signal of the myoglobin Val-E11 in myocardium:
`An index of cellular oxygenation
`
`Mechanism of human methyl-directed DNA methyltransfcrase and the
`fidelity of cytosine methylation
`
`Behavior of a cloned murine interferon (1/[3 receptor expressed in
`homospecific or heterospecific background
`
`An efficient method for generating proteins with altered enzymatic
`properties: Application to B-lactamase (Correction)
`Prohormone processing in Xenopus oocytes: Characterization of cleavage
`signals and cleavage enzymes (Correction)
`Molecular cloning of a calmodulin-depcndcnt protein phosphatase from
`murine testis: Identification of a developmentally expressed nonneural
`isoenzyme (Correction)
`
`BIOPHYSICS
`
`Anne Constable, Sabine Quick,
`Nicola K. Gray, and
`Matthias W. Hentze
`
`Hans Lilja and Ake Lundwall
`
`Scott E. Devine, Victor Ling,
`and Peter W. Melera
`
`Suzanne Walker, Raphael Landovitz,
`Wei Dong Ding, George A. Ellestad,
`and Daniel Kahne
`
`Matthew N. Ashby, David S. King,
`and Jasper Rine
`Franz—Werner Kluxen, Christian Bruns,
`and Hermann Lubbert
`
`Ivo De Baere, Lu Liu, Luc Moens,
`Jos Van Beeumen, Constant Gielens,
`Jean Richelle, Clive Trotman,
`John Finch, Mark Gerstein,
`and Max Perutz
`
`Howard W. Benjamin and
`Nancy Kleckner
`Martin Gottlicher, Eva Widmark, Qiao
`Li, and Jan—Ake Gustafsson
`Diane M. lgnarfl'rowbridge,
`Karen G. Nelson, Mark C. Bidwell,
`Sylvia W. Curtis, Todd F. Washburn,
`John A. McLachlan,
`and Kenneth S. Korach
`
`G. Hong, P. Ward, and K. I. Berns
`Stephanie A. Orcllana
`and G. Stanley McKnight
`Ulrike Kreutzer, Dong S. Wang,
`and Thomas Jue
`
`Steven S. Smith, Bruce E. Kaplan,
`Lawrence C. Sewers,
`and Edward M. Newman
`
`Gilles Uze, Georges Lutfalla,
`Marie-Therese Bandu,
`Dominique Proudhon,
`and Knud E. Mogensen
`
`Arnold R. Oliphant and Kevin Struhl
`
`Judith Komer, Jay Chun, Laura
`O’Bryan, and Richard Axel
`Taro Muramatsu, Polavarapu Rathna
`Girl, Susumu Higuchi, and
`Randall L. Kincaid
`
`Complete 15N and 1II NMR assignments for the amino-terminal domain of
`the phage 434 repressor in the urea-unfolded form
`Environment affects amino acid preference for secondary structure
`
`Conformational switching at cytochrome a during steady-state turnover of
`cytochrome c oxidase (Correction)
`
`Dario Neri, Gerhard Wider, and Kurt
`Wiithrich
`
`Lingxiu Zhong
`and W. Curtis Johnson, Jr.
`
`Robert A. Copeland
`
`CELL BIOLOGY
`
`Pasteurella mnltocida toxin is a potent inducer of anchorage-independent
`cell growth
`
`Theresa E. Higgins, Anne C. Murphy,
`James M. Staddon, Alistair J. Lax,
`and Enrique Rozengurt
`
`4554—4558
`
`4559-4563
`
`4564—4568
`
`4608—4612
`
`4613—4617
`
`4618—4622
`
`4638—4642
`
`4648—4652
`
`4653-4657
`
`4658—4662
`
`4673 -4677
`4726—4730
`
`4731—4733
`
`4744—4748
`
`4774-4778
`
`4779
`
`4779
`
`4779
`
`4397—4401
`
`4462—4465
`
`4779
`
`4240—4244
`
`Pfizer Ex. 1008
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`

`

`4245—4249
`
`4260—4264
`
`4290—4294
`
`4319—4323
`
`4338—4342
`
`4466—4470
`
`4683—4687
`
`4688—4692
`
`4693—4697
`
`4734—4738
`
`.,
`
`J 8
`
`4749—475
`4754—475
`
`4519—4523
`
`4569—4572
`
`4573—4577
`
`42504254
`
`4300—4303
`4324—4328
`
`4343—4347
`
`4471—4475
`
`4476—4480
`
`4500—4504
`
`4578—4582
`
`Contents
`
`Extension growth of the water mold Achlya: Interplay of turgor and
`wall strength
`Ontogeny of the secretory immune system: Maturation of a functional
`polymeric immunoglobulin receptor regulated by gene expression
`
`Nuclear transloeation of viral Jun but not of cellular Jun is cell
`cycle dependent
`Golgi retention ofa trans-Golgi membrane protein, galactosyltransferase,
`requires cysteine and histidine residues within the membrane-
`anchoring domain
`
`SNCI. a yeast homolog of the synaptic vesicle-associated membrane
`protein/synaptobrevin gene family: Genetic interactions with the RAS
`and CAP genes
`Yeast actin filaments display ATP-dependent sliding movement over
`surfaces coated with rabbit muscle myosin
`Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts
`Thymosin 34 (Fx peptide) is a potent regulator of actin polymerization in
`living cells
`
`Expression of interleukin 1-inducible genes and production of interleukin 1
`by aging human fibroblasts
`
`1a,25-Dihydroxyvitamin DJ regulates the transcription of carbonic
`anhydrase ii mRNA in avian myelomonocytes
`Primary structure and expression ofa gamete lytic enzyme in
`Chlamydomonas reinhardrii: Similarity of functional domains to
`matrix metalloproteases
`
`Endoplasmic reticulum resident protein of 90 kilodaltons associates with
`the T— and B-cell antigen receptors and major histocompatibility
`complex antigens during their assembly
`Proteins on exocytic vesicles mediate calcium-triggered fusion
`Tumor necrosis factor a is an autocrine growth regulator during
`macrophage differentiation
`
`Nicholas P. Money and Franklin
`M. Harold
`
`Sandra Huling, George R. Fournier,
`Anna Fercn, Anan Chuntharapai,
`and Albert L. Jones
`
`Kazuhiro Chida and Peter K. Vogt
`
`Daisuke Aoki, Ni Lee, Naoto
`Yamaguchi, Craig Dubois,
`and Michiko N. Fukuda
`
`Jeffrey E. Gerst, Linda Rodgers,
`Michael Riggs, and Michael Wigier
`
`Stephen J. Kron, David G. Drubin,
`David Botstein, and James A. Spudich
`Nikolai M. Soldatov
`
`Mitchell C. Sanders, Allan L. Goldstein,
`and Yu-Li Wang
`S. Kumar, A. J. T. Millis,
`and C. Baglioni
`Abderrahim Lomri and Roland Baron
`
`Tetsu Kinoshita, Hideya Fukuzawa,
`Tomoo Shimada, 'I'atsuaki Saito,
`and Yoshihiro Matsuda
`
`Frans Hochstenbach. Violaine David,
`Simon Watkins,
`and Michael B. Brenner
`
`Steven S. Vogel and Joshua Zimmerberg
`Alice L. Witsell
`and Lawrence B. Schook
`
`DEVELOPMENTAL BIOLOGY
`
`Production of germ-line chimeras in zebrafish by cell transplants from
`genetically pigmented to albino embryos
`Id gene expression and its suppression by 1,25-dihydroxyvitamin D3 in rat
`osteoblastic osteosarcoma cells
`
`Evidence that Mos protein may not act directly on cyclin
`
`Shuo Lin, Wilbur Long, Jin Chen,
`and Nancy Hopkins
`Nanako Kawaguchi, Hector F. DeLuca,
`and Masaki Noda
`
`Weilong Xu. Katherine J. Ladner,
`and L. Dennis Smith
`
`GENETICS
`
`Leucme—responsive regulatory protein controls the expression of both the
`pup and fan pili operons in Escherichia coli
`
`Selection-induced mutations occur in yeast
`Two mutations in the B-globin polyadenylylation signal reveal extended
`transcripts and new RNA polyadenylylation sites
`
`Urate-null rosy mutants 0f Dros‘Op/zila melmmgastcr are hypersensitive to
`oxygen stress
`
`Generation of mice carrying a mutant apolipoprotein E gene inactivated by
`gene targeting in embryonic stem cells
`
`Organization and evolution of the human epidermal keratinocyte
`transglutaminase I gene
`
`Genetic identification of the DNA binding domain of Escherichia culi
`LexA protein
`
`Sequence organization of the Balbiani ring 2.1 gene in Chironomus tcnltms
`
`vi
`
`Bruce A. Braaten, Jill V. Platko,
`Marjan W. van der Woude,
`Bert H. Simons, Frits K. de Graaf,
`Joseph M. Calvo, and David A. Low
`Barry G. Hall
`Deborah Rund, Carol Dowling, Khamis
`Najjar, Eliezer A. Rachmilewitz, Haig
`H. Kazazian, Jr., and Ariella
`Oppenheim
`Arthur J. Hilliker, Brenda Duyf, David
`Evans, and John P. Phillips
`Jorge A. Piedrahita, Sunny H. Zhang,
`John R. Hagaman, Paula M. Oliver,
`and Nobuyo Maeda
`R. R. Polakowska, T. Eickbush,
`V. Falciano. F. Razvi,
`and L. A. Goldsmith
`Andrew T. Thliveris and David
`W. Mount
`Lars Wieslander and Gabrielle Paulsson
`
`PfizerEX.1008
`
`Page 6 of 14
`
`Pfizer Ex. 1008
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`
`

`

`Contents
`
`Mutational spectrometry: A general approach for hot-spot point mutations
`in selectable genes
`Dodeca satellite: A conserved G+C~rich satellite from the centromeric
`heterochromatin of Drowphila melanogaster
`
`Finding errors in DNA sequences
`
`IMMUNOLOGY
`
`Selective manipulation of the human T-cell receptor repertoire expressed
`by thymocytes in organ culture
`Humanization of an anti-p185HERZ antibody for human cancer therapy
`
`Heat shock protein HspéO-reactivc 76 cells: A large, diversified
`T—lymphocyte subset with highly focused specificity
`
`Evidence for a functional receptor for cyclosporin A on the surface
`of lymphocytes
`
`Natural human antibodies to 'y interferon interfere with the
`immunomodulating activity of the lymphokine
`
`Human growth hormone promotes engraftment of murine or human T cells
`in severe combined immunodeficient mice
`
`ya T-ccll receptor repertoire in acute multiple sclerosis lesions
`
`A vaccine carrier derived from Neisseria meningitidis with mitogenic
`activity for lymphocytes
`
`How cytotoxic T cells manage to discriminate nonself from self at the
`nonapeptide level
`
`Quantitation of reversible binding by particle counting: Hapten—antibody
`interaction as a model system
`
`Characterization of a single—chain T-cell receptor expressed in
`Escherichia coli
`
`Phouthone Keohavong and
`William G. Thilly
`José P. Abad, Mar Carmena,
`Sigrid Baars, Robert D. C. Saunders,
`David M. Glover, Paloma Ludefia,
`Carlos Sentis, Chris Tyler-Smith,
`and Alfredo Villasante
`Janos Posfai and Richard J. Roberts
`
`Matthias Merkenschlager and Amanda
`G. Fisher
`
`Paul Carter, Len Presta, Cornelia M.
`Gorman, John B. B. Ridgway,
`Dennis Henner, Wai Lee T. Wong,
`Ann M. Rowland, Claire Kotts,
`Monique E. Carver,
`and H. Michael Shepard
`Rebecca L. O’Brien, Yang-Xin Fu,
`Robin Cranfill, Angela Dallas,
`Christina Ellis, Christopher Reardon,
`Julie Lang, Simon R. Carding,
`Ralph Kubo, and Willi Born
`Nicholas A. Cacalano, B.—X. Chen,
`W. Louis Cleveland,
`and Bernard F. Erlanger
`Adolfo Turano, Andrea Balsari,
`Elisabetta Viani, Santo Landolfo,
`Lorenzo Zanoni, Franco Gargiulo,
`and Arnaldo Caruso
`
`William J. Murphy, Scott K. Durum,
`and Dan L. Longo
`
`Kai W. Wucherpfennig, Jia Newcombe,
`Hong Li, Christine Keddy,
`M. Louise Cuzner,
`and David A. Hafler
`
`Margaret A. Liu, Arthur Friedman,
`Allen 1. Cliff, Joseph Tai,
`Douglas Martinez, R. Randall Deck,
`Joseph T. C. Shieh,
`Timothy D. Jenkins, John J. Donnelly,
`and Linda A. Hawe
`Susumu Ohno
`
`Y. K. Sykulev, D. A. Sherman,
`R. J. Cohen, and H. N. Eisen
`William F. Soo Hoo, Michael J. Lacy,
`Lisa K. Denzin, Edward W. Voss, Jr.,
`Karl D. Hardman, and
`David M. Kranz
`
`4623—4627
`
`4663-4667
`
`4698—4702
`
`4255 —4259
`
`4285—4289
`
`4348—4352
`
`4353—4357
`
`4447—4451
`
`4481—4485
`
`45 88—4592
`
`4633—4637
`
`4643—4647
`
`4703—4707
`
`4759—4763
`
`MEDICAL SCIENCES
`
`Design of a long-acting follitropin agonist by fusing the C-terminal sequence
`of the chorionic gonadotropin [3 subunit to the follitropin B subunit
`
`Amplified and rearranged epidermal growth factor receptor genes in human
`glioblastomas reveal deletions of sequences encoding portions of the N-
`and/or C-terminal tails
`Saturable binding of halothane to rat brain synaptosomes
`
`Immunostimulatory human urinary protein
`
`Fuad A. Fares, Nobuhiko Suganuma,
`Keiji Nishimori, Philip S. LaPolt,
`Aaron J. W. Hsueh, and Irving Boime
`A. Jonas Ekstrand, Noriaki Sugawa, C.
`David James, and V. Peter Collins
`
`Essam A. El-Maghrabi, Roderic G.
`Eckenhoff, and Henry Shuman
`Elisabeth Fontan, Helene
`Saklani-Jusforgues, and Robert
`M. Fauve
`
`4304—4308
`
`4309—4313
`
`4329—4332
`
`4358—4362
`
`vii
`
`Pfizer Ex. 1008
`
`Page 7 of 14
`
`Pfizer Ex. 1008
`Page 7 of 14
`
`

`

`Contents
`
`2’,5’-Bis-0-(tert-butyldimethylsilyl)-3'-spiro-S"-(4”-amino-l",2"-oxathiole-2”,
`2”-dioxide)pyrimidine (TSAO) nucleoside analogues: Highly selective
`inhibitors of human immunodeficiency virus type I that are targeted at
`the viral reverse transcriptase
`
`Germ-line mutations of the APC gene in 53 familial adenomatous
`polyposis patients
`
`Detection of acute hepatitis C virus infection by ELISA using a synthetic
`peptide comprising a structural epitope
`
`Surfactant-induced sealing of electropermeabilized skeletal muscle
`membranes in viva
`
`Characterization ofa type II collagen gene (COLZAI) mutation identified in
`cultured chondmcytes from human hypochondrogenesis
`
`Integration of gene maps: Chromosome 1
`
`Molecular cloning and characterization of the human cardiac Nat/Ca2+
`exchanger eDNA
`
`Jan Balzarini, Maria—Jesus Perez-Perez,
`Ana San-Felix. Dominique Schols,
`Carlo-Federico Perno, Anne-Mieke
`Vandamme, Maria-Jose Camarasa, and
`Erik De Clercq
`Yasuo Miyoshi, Hiroshi Ando, Hiroki
`Nagase, Isamu Nishisho, Akira Horii,
`Yoshio Miki, Takesada Mori, Joji
`Utsunomiya, Shozo Baba, Gloria
`Petersen, Stanley R. Hamilton,
`Kenneth W. Kinzler, Bert Vogelstein,
`and Yusuke Nakamura
`
`Girish J. Kotwal, Bahige M. Baroudy,
`I. Ken Kuramoto, Frances F.
`McDonald, Gilbert M. Schiff, Paul V.
`Holland, and Jerome B. Zeldis
`
`Raphael C. Lee, L. Philip River,
`Fu-shih Pan, Li Ji, and Robert
`L. Wollmann
`
`William A. Horton, Mirta A. Machado,
`Jeffrey Ellard, Dianna Campbell,
`James Bartley, Francesco Ramirez,
`Emilia Vitale, and Brendan Lee
`
`A. Collins, B. J. Keats, N. Dracopoli,
`D. C. Shields, and N. E. Morton
`
`Issei Komuro, Kathleen E. Wenninger,
`Kenneth D. Philipson, and
`Seigo Izumo
`
`MICROBIOLOGY
`
`Reduced transcription of the ferredoxin gene in metronidazole-resistant
`Trichomonas vaginalis
`
`Doris V. K. Quon, Christine E.
`d‘Oliveira, and Patricia J. Johnson
`
`NEUROBIOLOGY
`
`Three additional inositol l,4,5»trisphosphate receptors: Molecular cloning
`and differential localization in brain and peripheral tissues
`
`Differential expression of c-Fos and Zif268 in rat striatum after haloperidol,
`clozapine, and amphetamine
`
`Development of antibodies against the rat brain somatostatin receptor
`
`Homosynaptic long-term depression in area CA1 of hippocampus and
`effects of N-methyl-d-aspartate receptor blockade
`Immortal rat hippocampal cell lines exhibit neuronal and glial lineages and
`neurotrophin gene expression
`
`Primary structure of high molecular weight tau present in the peripheral
`nervous system
`
`A leucine»to-proline mutation in the putative first transmembrane domain of
`the 22-kDa peripheral myelin protein in the trembler-J mouse
`
`Cloning of the rat gene encoding choline acetyltransferase, a cholinergic
`neuron-specific marker
`
`Retinal degeneration is rescued in transgenic rd mice by expression of the
`cGMP phosphodiesterase fl subunit
`
`viii
`
`Christopher A. Ross, Sonye K. Danoff,
`Michael J. Sehell, Solomon H. Snyder,
`and Axel Ullrich
`
`T. V. Nguyen, B. E. Kosot‘sky, R.
`Birnbaum, B. M. Cohen, and
`S. E. Hyman
`
`Magali Theveniau, Stephanie
`Rens-Domiano, Susan F. Law,
`Genevieve Rougon, and Terry Reisine
`Serena M. Dudek and Mark F. Bear
`
`Eva M. Eves, Marcy S. Tucker, John D.
`Roback, Martha Downen, Marsha Rich
`Rosner, and Bruce H. Wainer
`
`Dominique Couchie, Carmelo Mavilia,
`Irene S. Georgieff, Ronald K. H.
`Licm, Michael L. Shelanski, and
`Jacques Nunez
`Ueli Suter, John J. Moskow,
`Andrew A. Welcher, G. Jackson
`Snipes, Bela Kosaras, Richard L.
`Sidman, Arthur M. Buchberg.
`and Eric M. Shooter
`
`Mounou Hahn, Soonjung L. Hahn,
`Donna M. Stone, and Tong H. Joh
`
`Janis Lem, John G. Flannery, Tiansen
`Li, Meredithe L. Applebury, Debora
`B. Farber, and Melvin 1. Simon
`
`4392—4396
`
`445 2—4456
`
`4486—4489
`
`4524—4528
`
`4583—4587
`
`4598—4602
`
`4769—4773
`
`4402—4406
`
`4265—4269
`
`4270—4274
`
`43I4~4318
`
`4363—4367
`
`4373—4377
`
`4378—4381
`
`4382—4386
`
`4387—4391
`
`4422—4426
`
`Pfizer Ex. 1008
`
`Page 8 of 14
`
`Pfizer Ex. 1008
`Page 8 of 14
`
`

`

`Contents
`
`Evolution off the vasopressin/oxytocin superfamily: Characterization of a
`cDNA encoding a vasopressin-related precursor, preproconopressin,
`from the mollusc Lymnaea stagnalis
`
`p
`g
`Re ion-s ecific expression of a K'“ channel ene in brain
`
`Estrogen receptors colocalize with low—affinity nerve growth factor
`receptors in cholinergic neurons of the basal forebrain
`
`Actions of dopamine and dopaminergic drugs on cloned serotonin receptors
`expressed in Xena/ms oocytes
`Neural-specific expression, genomic structure, and chromosomal
`localization of the gene encoding the zinc-finger transcription
`factor NGFI-C
`
`Oscillations in the insect brain: Do they correspond to the cortical y—waves
`of vertebrates?
`
`Ronald E. van Kesteren, August B.
`Smit, Roeiand W. Dirks, Nico D. de
`With. Wijnand P. M. Geraerts,
`and loos Joosse
`
`B. Rudy, C. Kentros, M. Weiser,
`D. Fruhling, P. Serodio,
`E. Vega-Saenz de Miera,
`M. H. Ellisman, J. A. Pollock,
`and H. Baker
`
`C. Dominique Toran»Allerand,
`Rajesh C. Miranda, Wayne D. L.
`Bentham, Farida Sohrabji, Theodore J.
`Brown, Richard B. Hochberg, and
`Neil J. MacLusky
`R. M. Woodward, M. M. Panicker,
`and R. Miledi
`
`Seth D. Crosby, Rosalie Ann Veile,
`Helen Donis-Keller, Jay M. Baraban,
`Ratan V. Bhat, Kelli S. Simburger,
`and Jeffrey Milbrandt
`K. Kirschfeld
`
`PHARMACOLOGY
`
`Demonstration of nuclear compartmentalization of glutathione
`in hepatocytes
`
`Giorgio Bellomo, Mariapia Vairetti,
`Lucianna Stivala, Francesca Mirabelli,
`Plinio Richelmi, and Sten Orrenius
`
`PHYSIOLOGY
`
`Modulation of L-type calcium channels by sodium ions
`
`C. William Balke and W. Gil Wier
`
`PLANT BIOLOGY
`
`Induction by fungal elicitor of S-adenosyl-L-methionine synthetase and
`S-adenosyl-L—homocysteine hydrolase mRNAs in cultured cells and
`leaves of Petroselinum crispmn
`
`Petra Kawalleck, Gunnar Plesch, Klaus
`Hahlbrock, and lmre E. Somssich
`
`Light-induced phosphorylation of a membrane protein plays an early role in
`signal transduction for phototropism in Arabidopsis Ihaliana
`
`Philippe Raymond, Timothy W. Short,
`Winslow R. Briggs, and Kenneth L.
`Poff
`
`POPULATION BIOLOGY
`
`Embryonic development period and the prevalence of avian blood parasites
`
`Robert E. Ricklefs
`
`4593—4597
`
`4603—4607
`
`4668—4672
`
`4708—4712
`
`4739—4743
`
`4764—4768
`
`44 12—44 16
`
`4417—4421
`
`4713—4717
`
`4718—4721
`
`4722—4725
`
`ix
`
`Pfizer Ex. 1008
`
`Page 9 of 14
`
`Pfizer Ex. 1008
`Page 9 of 14
`
`

`

`Prac. Natl. Acad. Sci. USA
`Vol. 89, pp. 4285—4289, May 199?.
`Immunology
`
`Humanization of an anti-p185HERZ antibody for human
`cancer therapy
`(antibody engineering/site-ilirected IIIutagenesis/c-erbB-Z/neu)
`
`PAUL CARTER*, LEN PRESTA*, CORNELIA M. GORMANi, JOHN B. B. RlDGWAYl, DENNIS HENNER‘l',
`WAt LEE T. WONG‘i, ANN M. ROWLANDi, CLAIRE Korrsi, MONIQUE E. CARVERi,
`AND H. MICHAEL SHEPARD§
`
`Departments of *Protein Engineering. TCell Genetics. iMedicinal and Analytical Chemistry. and §Ccll Biology, Genentech lnc., 460 Point San Bruno
`Boulevard, South San Francisco, CA 94080
`
`Communicated by Hilary Koprowski, January 16, 1992 (receivedfor review February 15, [99])
`
`The murine monoclonal antibody mumAb4DS,
`ABSTRACT
`directed against human epidermal growth factor receptor 2
`(plSSHEm), specifically inhibits proliferation of human tumor
`cells overexpressing plBSHERZ. However,
`the efficacy of
`mumAb4DS in human cancer therapy is likely to be limited by a
`human anti-mouse antibody response and lack of effector func-
`tions. A “humanized” antibody, lIumAb4D5-l, containing only
`the antigen binding loops from mumAb4D5 and human variable
`region framework residues plus IgGl constant domains was
`constructed. Light- and heavy-chain variable regions were simul-
`taneously humanized in one step by “gene conversion mutagen-
`csis” using Sll-mer and 361-mer preassembled oligonucleotides,
`respectively. The lIumAb4D5-l variant does not block the pro-
`liferation of human breast carcinoma SK-BR-3 cells, which
`overexpress plSSHERz, despite tight antigen binding (Kd = 25
`nM). One of seven additional humanized variants designed by
`molecular modeling (humAb4D5-8) binds the p18SHER2 antigen
`250-fold and 3-fold more tightly than humAb4D5-1 and
`mumAb4D5, respectively. In addition, humAb4D5-8 has potency
`comparable to the murine antibody in blocking SK-BR-3 cell
`proliferation. Furthermore, humAb4D5-8 is much more efficient
`in supporting antibody-dependent cellular cytotoxicity against
`SK—BR-3 cells than mumAb4D5, but it does not efficiently kill
`WI-38 cells, which express pl85"ER2 at lower levels.
`
`The protooncogene HERZ encodes a protein tyrosine kinase
`(p18SHERZ)
`that
`is homologous to the human epidermal
`growth factor receptor (1—3). Amplification and/or overex-
`prcssion of IIER2 is associated with multiple human malig-
`nancies and appears to be integrally involved in progression
`of 25—30% of human breast and ovarian cancers (4, 5).
`Furthermore, the extent of amplification is inversely corre-
`lated with the observed median patient survival time (5). The
`murine monoclonal antibody mumAb4D5 (6), directed
`against the extracellular domain (ECD) of p185llER2, specif-
`ically inhibits the growth of tumor cell lines overcxpressing
`p185HERZ in monolayer culture or in soft agar (7, 8).
`mumAb4D5 also has the potential of enhancing tumor cell
`sensitivity to tumor necrosis factor (7, 9). Thus, mumAb4D5
`has potential for clinical intervention in carcinomas involving
`the overexpression of plSSHERZ.
`A major limitation in the clinical use of rodent mAbs is an
`anti-globulin response during therapy (10, 11). A partial
`solution to this problem is to construct chimeric antibodies by
`coupling the rodent antigen-binding variable (V) domains to
`human constant (C) domains (12—14). The isotypc of the
`human C domains may be varied to tailor the chimeric
`antibody for participation in antibody—dependent cellular
`
`The publication costs ot‘this article were defrayed in part by page charge
`payment. This article must therefore be hereby marked “advertisement"
`in accordance with 18 U.S.C. §1734 solely to indicate this fact.
`
`cytotoxicity (ADCC) and complement—dependent cytotoxic-
`ity (CDC) (15). Such chimeric antibody molecules are still
`230% rodent in sequence and are capable of eliciting a
`significant anti-globulin response.
`Winter and coworkers (16—18) pioneered the “humaniza—
`tion” of antibody V domains by transplanting the comple-
`mentarity determining regions (CDRs), which are the hyper-
`variable loops involved in antigen binding, from rodent
`antibodies into human V domains. The validity of this ap-
`proach is supported by the clinical efficacy of a humanized
`antibody specific for the CAMPATH-l antigen with two
`non-Hodgkin lymphoma patients, one of whom had previ-
`ously developed an anti-globulin response to the parental rat
`antibody (17, 19). In some cases, transplanting hypervariable
`loops from rodent antibodies into human frameworks is
`sufficient to transfer high antigen binding aff