Science.
`v. 349, no. 6246 (Ju ly 24 2015)
`Reference Collection
`W1 SC653
`2015-08-13 13:10:39
`
`PROPERTY OF THE
`NATIONAL
`LIBRARY OF
`MEDICINE
`
`PFIZER EX. 1023
`Page 1
`
`

`

`6
`
`Toward an
`HIV vaccine
`
`INSIGHTS
`
`PERSPECTIVES
`374 FOUR LEGS TOO MANY?
`A long-bod ied foss il snake retains
`fore- and hindlimbs By S. Evans
`., REPORT P. 416
`
`376 MAKING METHANE DOWN DEEP
`Scientists find active life 2.5 km
`beneath the sea floor By.!. A. Huber
`• REPORT P. 420
`
`377 MOVING CTLA-4 FROM THE TRASH
`TO RECYCLING
`Individuals lacking a protein
`ex pressed in T cells have low CTLA-4·
`and develop auto immunity
`By D. M. Sansom.
`• flEPORT P. 4 36
`
`379 CATALYSTS BY PLATONIC DESIGN
`Sophisticated shape-controlled
`design is yielding ever more active
`nanocatalysts By P Strasser
`• REPORT P. 412
`
`380 BREAKERS AND BLOCKERS(cid:173)
`miRNAS AT WORK
`MicroRNAs med iate silencing
`through messenger RNA degradation
`and translation repression
`By E. I ZClltrralcle
`
`382 STRETCH, WRAP, AND RELAX
`TO SMARTNESS
`Carbon nanotubes wrapped around
`rubber cores create resilient conducting
`fibers By 1: Ghosh
`., REPORT P. 400
`
`384 YELLOW LIGHTS FOR EMERGING
`TECHNOLOGIES
`AJ I-or-none regulatory systems
`are not adequate for
`revolutionary innovations
`By R . A . Charo
`
`386 TOWARD AN HIV
`VACCINE: A SCIENTIFIC
`JOURNEY
`Different strategies are
`coming together to provide
`insights for an effective HIV
`vaccine By A. S. Fau.ci and
`H. D. Marston
`
`sci cnccmag.o rg SCIENCE
`
`356 IRAN NUCLEAR DEAL HOLDS
`'GOODIES' FOR SCIENTISTS
`Researchers to collaborate at
`repurposed nuclear facilities
`By R. Stone
`
`357 WEB BILLIONAIRE JOINS SEARCH
`FOR ALIEN SIGNALS
`Yuri Mil ner hopes that $100 million
`can answer one of humanity's most
`enduring questions By D. Clen;
`
`FEATURES
`358 NEW LIFE FOR OLD BONES
`After a stormy adol escence, the
`field of ancient DNA enters its
`golden era By E. Culotta
`., PODCA ST
`
`362 REVOLUTION IN HUMAN EVOLUTION
`As it smashes disciplinary boundaries,
`ancient DNA is rewriting mu ch of
`human prehistory By A . Gibbons
`
`367 LOST WORLDS FOUND
`Sugar cubes of buried soil reveal how
`ecosystems warmed after the last ice
`age By E. Pennisi
`369 Prospecting for genetic gold
`By E. Pennisi
`• BOOKS ET AL. P. 388; VIDEO
`• RESEAr~CH ART ICLE BY A. COOPER ET AL.
`10.1126/sc ience.aac4315
`
`370 BREAKING A TROPICAL TABOO
`Most ancient DNA comes from
`frigid environs. Can new methods
`sample hot and humid locales?
`By L. Wade
`
`372 PROTEIN POWER
`Paleoproteomics hustles to catch up
`with its more developed cousin
`By R. F Service
`
`This materia I w as co~ i erl
`at the NLM anrl m ay be
`Subject UCSCo~yright Laws
`
`24 JULY 2015 • VOLUME 349 • ISSUE 6246
`
`NEWS
`
`IN BRIEF
`350 Roundup of the week's news
`
`IN DEPTH
`352 SCIENTISTS PONDER AN IMPROBABLY
`ACTIVE PLUTO
`New Horizons delights researchers with
`stark vistas and perplexing puzzles
`ByE. Hand
`
`354 NEW MYSTERY FOR NATIVE
`AMERICAN ORIGINS
`Rival papers compete to explain
`surprising link to Australia and
`Melanesia By M . BalteT
`.. RESEARC H ART ICLE BY M. RAG HAVAN ET AL.
`10.ll26/scie nce.aab3884
`
`355 CHILD FIGHTS HIV TO A DRAW
`After 12 years off treatment, a young
`woman has had remarkable-and
`unexplained-control of her infection
`ByJ. Cohen
`
`346
`
`24· JULY 2015 • VOL 3·~9 I SSUE 6246
`
`PFIZER EX. 1023
`Page 2
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`

`

`A Cretaceous snake
`with limbs
`
`An autoimmunity
`mechanism
`
`BOOKSETAL.
`388 HOW TO CLONE A MAMMOTH
`By B. Shapiro, reviewed
`by A. R. Hoelzel
`~ t~EW S STORY P 369
`
`389 THE LOCK AND KEY OF
`MEDICINE
`By L. V. Mark:;, ·rev·iewed by S. Pmbalcamn
`
`LETTERS
`390 PRECISION MEDICINE:
`LOOK TO THE MICE
`By K. C. K. Lloycl et al.
`
`390 SEXISM DISCUSSION
`MISSES THE POINT
`By H. S. Young
`
`391 CHIMPANZEES DESERVE
`THEIR FREEDOM
`By S. M. Wise
`
`391 TECHNICAL COMMENT ABSTRACTS
`
`RESEARCH
`
`IN BRIEF
`392 From Science and other journals
`
`REVIEW
`395 HUMAN MICROBIOTA
`Small molecules from the
`human microbiota MS. Donia. and
`M . A . Fischbach
`REV IEW SU MMARY: FOR FULL TEXT:
`d' .cl 0 I.Or!(/10.ll26/;cll"llr.C.l25476G
`
`REPORTS
`396 APPLIED ORIGAMI
`Origami of thick panels Y. Chen et al.
`
`400 STRETCHY ELECTRONICS
`Hierarchically buckled sheath-core
`fibers for superelastic electronics,
`sensors, and muscles z. F Liu et al.
`~ PER~PECT IV E P 382
`
`392
`
`QUANTUM INFORMATION
`405 Coherent coupling between a
`ferromagnetic magnon and a
`superconducting qubit
`Y. Tabuchi et al.
`408 Coherent coupling of a single spin
`to microwave cavity photons
`J. J. Viennot et al.
`
`412 NANOCATALYSTS
`Platinum-based nanocages with
`subnanometer-thick walls and well(cid:173)
`defined, controllable facets L. Zhang et al.
`~ PERSPECTIVE P. 379
`
`416 EVOLUTION
`A four-legged snake from the Early
`Cretaceous of Gondwana
`D. M MaTtill et al.
`~ PERSPECTIV E P. 374
`
`420 DEEP BIOSPHERE
`Exploring deep microbial life in coal(cid:173)
`bearing sediment down to -2.5 km
`below the ocean floor F Inagalci et al.
`~ PERSPECTIVE P. 376
`
`424 NEURODEVELOPMENT
`Adult cortical plasticity depends on
`an early postnatal critical period
`S. D. G1·eenhill et al.
`
`INTRACELLULAR TRANSPORT
`428 PI4-P/phosphatidylserine
`countertransport at ORPS(cid:173)
`and ORP8-mediated
`ER-plasma membrane
`contacts J. Chung et al.
`432 Phosphatidylserine transport
`by ORP/Osh proteins is
`driven by phosphatidylinositol
`4·-phosphate
`J. MoseT von Filseclc et al.
`
`436 AUTOIMMUNE DISEASE
`Patients with LRBA deficiency
`show CTLA4 loss and immune
`dysregulation responsive to
`abatacept therapy B. Lo et al.
`~ PERSPECTIVE P. 377
`
`DEPARTMENTS
`349 EDITORIAL
`Rethinking graduate education
`By Alan I. Leshner
`
`446 WORKING LIFE
`Songwriting and science
`By C. Neal Stewm·t Jr.
`
`ON THE COVER
`A researcher drills
`into ancient bone to
`extract material for
`DNA analysis at the
`Max Planck Institute
`for Evolutionary
`Anthropology in
`Leipzig, Germany. As
`the newest sequencing
`methods are applied to ancient samples and
`spread to many laboratories, ancient DNA
`is poised to enter its golden age, delivering
`stunning results ranging from the evolution
`of humans to that of microbes. See page 358.
`Photo: © Jorg SingeT
`
`Science Staff
`New Products
`Science Careers
`
`... 348
`.... ... 441
`. 442
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`2-1- JULY 201 !\ • VOL 3·1·9 I SSUE (iH (i 347
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`Carlo Bcen.lkker, lerdc:n U
`Laura Machesky, CRUK IkJISOO lnst.
`Kamran Behnia, LSPC/ PJitSf!!!h
`fOf Cmcer Research
`Yasmine Belkald, NMIO.Nlif
`Anne Magurran. U ofSI.Andre~-:s
`Philip Benfey, Du~e U
`Oscar Marin. CSIC & U. Mrguellfemjnde!
`Stephen J. Oenkovlc, P.~nrr S/1/e U
`Charles Marshall. U. of Cdlrfotmd, Bt">~ielet
`May Berenb.1um. U. oflllulfJt~
`C. Robertson McC lung, OJr/mout/1 C<Hiege
`Gabriele Bergers. U of WMomu. Sd11francrsw
`Graham Medley, U. oiiVJrWlck
`Bradley Bernsteln,M,m.Y..trusel/~sG~;rlffr!llfotpl!.ll Tom Misteii. NC/
`Peer Bork, [MOL
`Yasushi Miyashlta. U. of Tokyo
`Bernard Bourdon. fcoleNormcl/eSuJJt rr-~'Urcck /yofl Mary Ann Moran, U.of CH!OI}!I.J
`Richard Morris. U. of fdmburp,/1
`Chri s Bowler, {1.'01~ NotmJicSut>IJrreure
`lan Boyd. U. of St.And1ews
`Alison Motslngcr·Relf. NCState U. (S)
`Sean Munro, MRC l ab. of Mole<:uiJ1 1l10togy
`Emily Brodsky. U of CJidowir~.S.mt<~ Cru/
`Ron Brookmcyer. U. of CJ/rlorm.1 Los Angelc~ (S)
`Thomas Murray, /lle II.1SimgsCenler
`Christian BUche!. U. 1/Jmburg fppcmlorl
`James Nelson, Stanford U. School of Mcd.
`Joseph A. Burns. Ct;tnc/1 U.
`Daniel Neumark. U. of CIJ/Jform:J. Jkr~eley
`Kitty Nijmeijer, U.of r .... -ente
`Gyorgy Buzsaki. NewYorkU.Sd!fJO/o/MC(1JW1C
`Blanche Ca1>ei. !Me U
`Pi1r Nordlund. K.1ro/rnsk:J lust.
`Mats Carlsson, U. ofO~/Q
`Helga Nowotny, [mopeJn ResecJnhM~t.M~tyBrurd
`Ben Oiken, MIT
`David Clapham, Clutdu.:f! 's 1/o:,rnt,J/ Bostoll
`David Clary, U of Oxf'Jid
`Joe Orenstein, U ot CJirfomJJ
`Joel Cohen. H!YJefellcr U., Columbu U
`Berkeley& LaYo·reru Ber~eley NJ/fi)IJJILab
`Harry Orr, U. of MmncS!J/a
`James Collins. Bo}/011 U
`Andrew Oswald. U.ol \'lam/Ck
`Robert Cook·Deegan. !Me:U.
`Steve Palumbi,Sianford U.
`Alan Cowman. WJ/Icr & [/rLJ/111/Ins/.
`Robert H. Crabtree, rate U
`Jane Parker. A-fJl Plc1nck/ns/
`Roberta Croce, VfiJf! Un•lf:rslle•l
`of P/Jrll Brt.i!drng Research
`Janet Currie, l'rmce/on U.
`Giovanni PMmigianl, O.JnJ (Jtbet G.Jncet lnst. (SJ
`Jeff l. Dangl. U. of Notlll Ctlroi111J
`Donald R. Paul. U of Te.us. Auslm
`John H. J. Petrini. Mernoti,li Siodn Kellenng
`Tom Daniel, U of Wasfungt!JII
`Cancer Center
`Frans de Waai.f."mory U
`Joshua Plotkin, U.of Pennsyfv,lma
`Stanislas Dehacne, Collfgcde Fr.u~te
`Robert Desimone, MIT
`Albert Polrnan.TO!I fnsliruleA.\101 F
`Claude Desplan, New York U
`Philippe Poulin. CNRS
`Ap Dijksterhuls, Ra!lbo!KI U. ol NrJIIIC£CII
`Jonathan Pritchard ,SitJJtfOid U.
`Dennis Di scher, U of Pwnsyl~im/J
`David Randall, GfllotJdoSt.tlaU.
`Gerald W. Dorn II. IVasiiiiiP,Iun U &llool ol Mcdrcme CoHn Renfrew, U ol Camb11dp,e
`Jennifer A. Doudna, U. of Callfomn. Ber~eley
`Felix Rey, I11Sftlul PrJ~teur
`Bruce Dunn. U. of C.lld!JI/1/J,losAngeks
`Trevor Robbins, U. of Camb11dge
`Jim Roberts, Trcd 1/utchmsou Cancet RestJrr:h Ctr
`Chri stopher Dye,l'l/10
`Todd Ehlers, U. of fuebmee11
`Barbara A. Romanowlcz, U af Cc'Jitforma.&r~or:lr:t
`David Ehrhardt. C,mlfg,e /ll}t of\Yo~5lrmglall
`Jens Rostrup·Nielsen, /1.1/dOI Topsoe
`Mike Ryan. U. of fCXJs.Auslm
`Tim Elston. U. of NortlrCawlruJ dl Clrapelllrll
`Gerhard ErU , frt ll 1/Jf)(.I lmlrlu/, Betlm
`Mitinori Saitou. l<yotoU.
`Barry Everitt , U. !Jf Cambudge
`Shimon Sakaguchi, Kyo/aU
`Ernst Fe hr. U. of l!111Cfr
`Mlquel Salmeron, Lawrence lkr~elej NJfi()(JJ/ LJb
`Anne C. Ferguson· Smith. U. of Gambndge
`JOrgen Sandkllhler. MediCiJIU. of Vlcflii,J
`Michael Feuer. I lie Ctilf£C IV,utrmgton U
`Alexander Schier,lfJrvJrtl U.
`Toren Finkel, N/11.01. N/11
`Randy Seeley. U.of CmcmnJit
`Kate Fitzgerald, U. of MaSSclCilusetl.t
`Vladimir Shalaev. PurdtieU.
`Robert Sllic/n no, Jollns llopkmsSchoolof MedKrrl'!
`Peter Fratzl, M<ix·l'lmrck Ins/.
`Elaine Fuchs, Hod.efellet U.
`Denis Simon,AfiAAH Slate U.
`0.1nlcl Geschwlnd, UCLA
`Alison Smith, .k>l1nlmws Cer1/re
`Richard Smith. U. of Nor/lr Cmoltna (S)
`And rew Gewlrth. U. of 11/motr
`John Speakman. U. of Aberdceu
`Kari·Helnz Giassmeler, IU lliiwtt~hr-.-e,e
`Ramon Gonzalez, R11.& U.
`Allan C. Spradling, C.lllll!gre lnsltlui/On
`Julia R. Greer, C,11teclt
`of WJshmgton
`Elizabeth Grove, U. of Chtc:Jgo
`Jonathan Sprent. G:~rvJfllnsl. ol ~.fe<J,c.Jf Reseau;.h
`Nicolas Gruber, [ 11 /lullclt
`Eric Steig, U. o/W,Jslungton
`Kip Guy, SI. Jude"sCfrJ/dtfm's RereJnhllosprtill
`Paula Stephan, Geotgr<~Sia/e U.,md NJIIOIIJI8urt•JU
`Tackjip Ha, u. of IIIIIJOIS elf Urbarld ClrdtnJAliJJII
`of [COIIOIWC He>Mcir
`Christian Haass, Lu!/Yrilf M.wrmlrm•s U
`Molly Stevens. fmperra/Collt-ge tondOII
`V. S. Subrahmanian, U of MJryiJnd
`Steven Hahn, fr&d JfulcllrrmmCalk:et
`Res:eiJttir Ctmlcr
`Ira Tabas. CDiumbiJ U.
`Michael Hasselmo, /kis/!ifl U
`Sarah Teichmann, Camb11dge U.
`Martin Heimann, M,u Pfa11ck ln'>t.Jena
`John Thomas, N!N/IrCJrolmJ Stale U.
`Yka Helariutta, U. afCilmtmclge
`Shubha Tole, Tatd lnsfrluteof FundJfll€/IIJI ReseJJch
`James A. Hendler, Rr:nsseiM:t l'ulylfXfm;c /n~t.
`ChrlstophcrTyler·Smlth. Thc \'ellcome 1iu~t
`Janet G. Hering, Swrss fed. Ins/. of ArJUilllc
`Sanger lnsl.
`Herbert Virgin, tvasfrmg/011 U.
`Sc~crJ>::e & Tt·cimology
`Kai·Uwe Hinrichs. U.of 81f!IIJCI'I
`Bert Vogel stein, .Jo/Jns 1/opAmr U.
`Cynthia Volkert. U. ofGOttmee"
`Kei Hirose, rokyv l11sl. o!Tecltnology
`David Hod ell, U. o!Cmnbrtdge
`Douglas Wallace. Oal/oosre U.
`David Holden, fmfJf.!liJICollep,e
`David Wallach, Werzmann Ins/. of Science
`ian Wa lmsley, U. of O.rford
`Lora Hooper, UT Soulhrte'slcm Medtca/Ctr.,ll OiJII,JS
`Raymond Huey, U. of WashiiiHIOII
`Jane· Ling Wang, U. of Cald01ma. Dims
`David A. Wardle, S .... -er.ilsh U. ofAg11c. Screncts
`Steven Jacobsen, U. o/C,J!Jfomia. Los Angelc:s
`David Waxman. fudan U.
`Kai Johnsson, [Pft Lau~111110
`Peter Jonas, Ins/. ofScrern:e& Tcclmology(ISI)Auslrw Jonathan Weissman. U. of CalrfotnrJ. Sc'Jn ftJIICr5l.O
`Chris Wikle. U. ofAfrssoutt (S)
`Matt Kaeberlein, U. of Wasf~mg/ou
`William Kaelin Jr .• Oana·(arOOt Cancer /1151.
`lan A. Wll son.Tt.eScttflpsRes./nsl.{$)
`Timothy D. Wilson, U o!Virgms,J
`Daniel Kahne, lfarvardU.
`Daniel Kammen, U. ol Caltfomia. &r~eley
`Rosemary Wyse, Johns llopkms U.
`Masashl Kawasaki, U. of Toi)'O
`Jan Zaanen. Lelden U.
`V. Narry Kim, Seoul Na/1011al U.
`Kenneth Zaret, U. of PennsylrantJSchool of Medl(..nt
`Joel Kingsolver, U. of fiCKtlr Carolma a/ Clrapel 1/r/1
`Jonathan Zehr. U. of CJIIfonua. SJnfa Cwt
`Robert Kingston,l/amid Medical Scl;oot
`l en Zon. Chr/diell·s lloSfi/IJI Bcsloo
`Etienne Koechlin. [co/cNomldlcSutlfli:UW
`Marla Zuber, MIT
`
`BOOK REVIEW BOARD
`David Bloom,l/arvrmJU., Samuel Bowring. MIT. Angela Creager, Prmcet011 U.
`Richard Shweder, U. of Cluc,J[!O. Ed Wasserman, Ot!F\mt
`
`sci encc m ag.or g SCIENCE
`
`PFIZER EX. 1023
`Page 4
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`

`

`IMMUNOLOGY
`
`The quest for a magic bullet
`Widely used in science and medicine today, monoclonal
`antibodies got off to a rocky start
`
`The Lock and Key of Medicine
`Monoclonal Antibodies and the
`Transformation of Healthcare
`Lam V Marks
`Yale University Press. 2015.
`344pp.
`
`By Sudhakaran Prabakarrut
`
`I n a cold January evening in 1975,
`
`postdoctoral fellow Georges Kohler
`brought his wife to the lab to keep
`him company as he checked on his
`latest experiment. Far from the un(cid:173)
`eventful evening he anticipated, what
`h e observed that night would transform the
`world of drug development and disease treat(cid:173)
`m ent. "I looked clown at the first two plates.
`I saw these halos .... It was the best result I
`could think of;' he recalls. The halos were
`evidence that the cells in the petri
`dish were secreting highly specific
`antibodies. Dubbed "monoclonal
`antibodies;' or Mabs, they would
`have a radical influence on both
`science and medicine in the years
`that followed .
`In her book, The Lock and Key
`of Medicine, Lara Marks presents
`a compelling, well-researched ac(cid:173)
`count of the di scovery of Mabs
`the development of Mat(cid:173)
`a nd
`based treatments and therapies.
`Th e book also narrates the chal(cid:173)
`lenges faced by Cesar Milstein
`(Kohler's postdoctoral adviser)
`and hi s collaborators, from pat(cid:173)
`enting their findin gs to raising
`money for further testing and
`scaling up production. It is an ex(cid:173)
`cellent account of all the impedi-
`ments the researchers faced in bringing
`Mabs from the bench to the market. Per(cid:173)
`sonal stories of the major players involved
`are skillfully interwoven with the narrative,
`bringing a human face to the drug cliscov-
`ery process.
`In the early 1970s, Kohler and Milstein
`were studying the variable regions of anti(cid:173)
`bodies- the proteins that recognize foreign
`molecules and tag them for destruction(cid:173)
`with the hope of understanding how diverse
`populations of antibodies are generated
`by the mammalian immune system. In the
`course of their studies, they developed a
`technique that enabled the mass production
`of antibodies designed to recognize a spe(cid:173)
`cific antigen. The technique involved fusing
`a myeloma cell with an antibody-producing
`
`The reviewer is at Science Signaling. AAAS. Washington. DC
`20005. USA. E-mail: sprabaka@aaas.org
`
`SCIENCE scicnccmag.o rg
`
`Cesar Milstein (left), Georges Kohler (right), and Niels Jerne (not pictured) were
`awarded the Nobel Prize in 1984 for their work on monoclonal antibodies.
`
`B cell taken from the spleen of an immu(cid:173)
`nized mouse. The B cell provided the immu(cid:173)
`nological specificity, whereas the myeloma
`lent immortality to the construct.
`These hybrid cells, or hybridomas as they
`were later called, became a vehicle for thou(cid:173)
`sands of other biomedical inventions. How(cid:173)
`ever, the initial reception to this breakthrough
`was lukewarm. When they tried to publish
`their results, the editors at NatuTe reportedly
`requested that the article be shortened and
`did not feature it prominently in the journal,
`and their patent application was rejected.
`
`Milstein sent samples and protocols of his
`newly created antibody-secreting cell lines to
`other research institutions and even trained
`scientists to generate their own hybridomas.
`One such scientist who benefited from this
`goodwill was Hilary Koprowski, director
`of the Wistar Institute in Philadelphia. The
`first patents for monoclonal antibodies were
`granted to Koprowski and his colleagues in
`October 1979 (for Mabs targeting influenza
`antigens) and April 1980 (for Mabs target(cid:173)
`ing tumor antigens). The "Wistar patents"
`proved controversial in the scientific com(cid:173)
`munity, because the antibodies had been cre(cid:173)
`ated using the cell lines originally supplied
`by Milstein.
`In the years that followed, there was an
`explosion in Mab research. Some were gener(cid:173)
`ated to identify different types of white blood
`cells, and several proved to be important in
`investigating HIV/AIDS. The first medical
`
`application of this technology used Mabs to
`purify inte1ierons, signaling proteins that are
`released by cells in response to the presence
`of pathogens.
`Mabs were soon being used to identify
`blood group types, an application that radi(cid:173)
`cally improved the accuracy and cost of
`blood typing. This now-routine test has since
`saved millions of lives.
`After these initial success stories, many
`clinicians and founders of biotech companies
`began to believe that Mabs were "magic bul(cid:173)
`lets" for diagnosing and curing diseases. In
`1979, Koprowski cofounded Cento(cid:173)
`cor, one of the original companies
`that exploited Mabs to diagnose
`cancer, cardiovascular disorders,
`and liver problems. The f01tunes
`of Centocor ebbed and flowed dur(cid:173)
`ing the 1980s and 1990s. It was
`acquired by Johnson & Johnson in
`1999 and is known today as Jans(cid:173)
`sen Biotech. It is one of the few
`original companies still in exis(cid:173)
`tence today.
`In 1995, edrecolomab (Panorex)(cid:173)
`a Mab developed in mice-was
`licensed by German authorities
`as an adjuvant therapy for post(cid:173)
`operative colorectal cancer.
`It
`was the first Mab-based cancer
`therapeutic to proceed to mar(cid:173)
`ket. In 1997, rituximab (Rituxan),
`a chimeric (part human and part
`mouse) Mab, was authorized by the FDA to
`treat B cell lymphoma. It was later found to
`be beneficial in the treatment of rheumatoid
`atthritis as well.
`By 2012, there were more than 30 Mab
`drugs on the market, generating more than
`$50 billion in revenue (10 of which gener(cid:173)
`ated profits exceeding $1 billion each). The
`number of Mab-based therapies (and their
`market share) will likely increase with time.
`Marks has done great justice to the
`topic, although the book would have been
`strengthened by the inclusion of additional
`illustrations and a broader discussion of the
`impact of Mabs on basic science. This book
`is in many ways a tribute to Kohler and Mil(cid:173)
`stein, which makes the timing of its publi(cid:173)
`cation (just over 40 years since that fateful
`January evening) all the more appropriate.
`
`10.1126/science.aac5603
`
`24 JULY 201 5 • VOL 349 ISS UE 6246 389
`
`PFIZER EX. 1023
`Page 5
`
`