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`Case 1:18-cv-00924-CFC-SRF Document3 Filed 06/21/18 Page 1 of 636 PagelD #: 69
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`EXHIBIT A
`EXHIBIT A
`
`

`

`(12) United States Patent
`Cabilly et al.
`
`US006331415B1
`US 6,331,415 B1
`Dec. 18, 2001
`
`(10) Patent N0.:
`(45) Date of Patent:
`
`(54) METHODS OF PRODUCING
`IMMUNOGLOBULINS, VECTORS AND
`TRANSFORMED HOST CELLS FOR USE
`THEREIN
`
`(75) Inventors: Shmuel Cabilly, Monrovia; Herbert L.
`Heyneker, Burlingame; William E.
`Holmes, Paci?ca; Arthur D. Riggs, La
`Verne; Ronald B. Wetzel, San
`Francisco, all of CA (US)
`
`(73) Assignee: Genentech, Inc., South San Francisco,
`CA (Us)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`(21) Appl. No.: 07/205,419
`(22) Filed:
`Jun. 10, 1988
`
`Related US. Application Data
`
`(63) Continuation of application No. 06/483,457, ?led on Apr. 8,
`1983, now Pat. No. 4,816,567.
`
`(51) Int. C1.7 ......................... .. C12N 15/13; C12N 15/00;
`C12N 15/63
`
`(52) us. Cl. ..................... .. 435/69.6; 435/69.1; 435/697;
`435/701; 435/7021; 435/71.1; 435/712;
`435/320; 435/2521; 435/252.3; 435/252.33;
`435/254.11; 435/2542; 435/254.21; 435/455;
`435/471; 435/483; 435/485
`
`(58) Field of Search ................................ .. 435/691, 69.7,
`435/711, 70.1, 71.2, 320, 261, 252.1, 252.3,
`81, 55, 56, 69.6, 252.33, 254.21, 483
`References Cited
`U.S. PATENT DOCUMENTS
`
`(56)
`
`12/1979 Davis et al. .
`4,179,337
`12/1980 Cohen .
`4,237,224
`7/1982 Gilbert et al..
`4,338,397
`8/1982 Goeddel et al. .
`4,342,832
`9/1983 Hartley et al. .
`4,403,036
`4/1984 Paulus .
`4,444,878
`4/1985 Parks et al. .
`4,510,244
`4/1985 Jones et al. .
`4,512,922
`5/1985 Mark et al. .
`4,518,584
`2/1987 Moore et al. .
`4,642,334
`11/1987 Itakura et al. .
`4,704,362
`3/1989 Boss et al. .
`4,816,397
`3/1989 Cabilly et al..
`4,816,567
`7/1993 Winter.
`5,225,539
`8/1996 Page.
`5,545,403
`8/1996 Page.
`5,545,404
`8/1996 Page.
`5,545,405
`FOREIGN PATENT DOCUMENTS
`
`Case 1:18-cv-00924-CFC-SRF Document 3 Filed 06/21/18 Page 2 of 636 PageID #: 70
`
`194982
`12417/83
`B-26429/84
`46556/85
`65981/86
`0037723
`
`2/1983 (AU) .
`9/1983 (AU) .
`10/1984 (AU) .
`3/1986 (AU) .
`5/1987 (AU) .
`10/1981 (EP) .
`
`37723
`041313
`041767
`41313
`41767
`044722
`055945
`57107
`0068763
`68763
`0057107
`0073656
`075444
`73656
`75444
`A-073656
`088994
`88994
`093619
`0120694
`0125023
`194276
`196864
`234592
`255694
`324162
`550400
`08235
`62 201 581
`WO 86/01533
`
`10/1981 (EP).
`12/1981 (EP).
`12/1981 (EP).
`12/1981 (EP).
`12/1981 (EP).
`1/1982 (EP).
`7/1982 (EP).
`8/1982 (EP).
`1/1983 (EP).
`1/1983 (EP).
`3/1983 (EP).
`3/1983 (EP).
`3/1983 (EP).
`3/1983 (EP).
`3/1983 (EP).
`3/1983 (EP).
`9/1983 (EP).
`9/1983 (EP).
`11/1983 (EP).
`10/1984 (EP).
`11/1984 (EP).
`9/1986 (EP).
`10/1986 (EP).
`9/1987 (EP).
`2/1988 (EP).
`7/1989 (EP).
`7/1993 (EP).
`3/1987 (GB).
`9/1987 (JP).
`3/1986 (WO).
`
`OTHER PUBLICATIONS
`
`Dolby et al. Proc. Natl. Acad. Sci. 77(10):6027—6031
`(1980).
`Rice et al. Proc. Natl. Acad. Sci. 77:7862—7865 (1982).
`Accolla et al. Proc. Natl. Acad. Sci. 77(1):563—566 (1980).
`Raso et al. Cancer Res. 41:2073—2078 (1981).
`Nisonoff et al. Arch. Biochem. Biophys. 93:460—462 (1960).
`Glennie et al. Nature 295:712—714 (1982).
`Eisen Immunology Harper & RoW, Publishers, pp. 415 and
`428—436 (1974).
`HoZumi et al. Nuc. Acids. Res. 5(6):1779—1799 (1978).
`WetZel et al. Gene 16:63—71 (1981).
`Williams et al. Science 215:687—689 (1982).
`Falkner et al. Nature 298:286—288 (1982).
`Boss et al. Gene Expressions—Proc. Cetus—UCLA Sympo
`sium pp. 513—522, Mar. 26—Apr. 1, 1983.
`
`(List continued on neXt page.)
`
`Primary Examiner—Phillip Gambel
`(74) Attorney, Agent, or Firm—Burns, Doane, SWecker &
`Mathis, LLP
`(57)
`
`ABSTRACT
`
`The invention relates to processes for producing an immu
`noglobulin or an immunologically functional immunoglo
`bulin fragment containing at least the variable domains of
`the immunoglobulin heavy and light chains. The processes
`can use one or more vectors Which produce both the heavy
`and light chains or fragments thereof in a single cell. The
`invention also relates to the vectors used to produce the
`immunoglobulin or fragment, and to cells transformed With
`the vectors.
`
`36 Claims, 19 Drawing Sheets
`
`

`

`US 6,331,415 B1
`Page 2
`
`OTHER PUBLICATIONS
`
`Amster et al. NucleicAcid Research 8(9):2055—2065 (1980).
`DeBoer et al., Rodriguez et al.
`Promoters 462—481
`(1982).
`Gough Tibs 6(8):203—205 (Aug., 1981).
`Morrison J. of Immunology 123(2):793—800 (Aug., 1979).
`Kohler Proc. Natl. Acad. Sci. 77(4):2197—2199(Apr., 1980).
`Roberts Promoters 452—461 (1982).
`Kemp et al. Proc. Natl. Acad. Sci. 78(7):4520—4524 (Jul.,
`1981).
`Valle et al. Nature 300:71—74 (Nov. 4, 1982).
`Microbiology 3rd edition, Harper Int. Ed. 338—379 (1980).
`Hitzeman et al. Science 219:620—625 (1983).
`Mercereau—Puijalon et al. in Expression of Eukaryotic Viral
`and Cellular Genes, Pettersson et al. (ED) 295—303 (1981)
`Academic Press.
`295—303 (1981) Academic Pr.
`Pettersson et al.
`Keshet et al. Nucleic Acids Res. 9(1):19—30 (1981).
`Taniguchi et al. Proc. Natl. Acad. Sci. 77(9):5230—5233
`(1980).
`Ohsuye et al. Nucleic Acids Res. 11(5):1283—1295 (1983).
`Kadonaga et al. J. Biol. Chem. 259(4):2149—2154 (1984).
`Maniatis Molecular Cloning p. 433 (Sep., 1985).
`FujisaWa et al. NucleicAcids Res. 11(11):3581—3591 (1983).
`Roberts Promoters Structures and Function Rodriguez, R.
`L.
`452—461 (1982).
`Adams et al. Biochemistry 19:2711—2719 (1980).
`Haley et al. DNA 1:155—162 (1982).
`Gough et al. Biochemistry 19:2702—2710 (1980).
`Iserentant et a1. Gene 9:1—12 (1980).
`Seidman et al. Nature 271:582—585 (1978).
`Stevens et al. J. Mol. Biol. 78:517—525 (1973).
`Deacon et al. Biochem. Soc. Trans. 4:818—820 (1976).
`Colman et al. Cell 17:517—526 (1979).
`Valle et al. Nature 291:338—340 (1981).
`Colman et al. J. Mol. Biol. 160:459—474 (Sep., 1982).
`CoWan et al. J. Mol. Biol. 90:691—701 (1974).
`Morrison et al. J. Immunol. 114:655—659 (1975).
`Mosmann et al. J. Immunol. 115:955—962 (1975).
`Levy et al. Proc. Nat. Acad. Sci. 75:2411—2415 (1978).
`Robertson et al. Nature 287:390—392 (1980).
`Mosmann et al. Cell 20:283—292 (1980).
`Wilde et al. Eur. J. Immunol. 10:462—467 (1980).
`Ochi et al. Nature 302:340—342 (Mar. 24, 1983).
`Kemp et al. in Nagley et al., Ed., Manipulation and Expres
`sion of Genes in Eukaryotes Proceedings of an International
`Conference, 12th International Congress of Biochemistry, in
`Australia Aug. 9—13, 1982 (1983).
`Picard et al. Proc. Nat. Acad. Sci. 80:417—421 (Jan., 1983).
`Oi et al. Proc. Nat. Acad. Sci. 80:825—829 (Feb., 1983).
`HaWley et al. Proc. Nat. Acad. Sci. 79:7425—7429 (Dec.,
`1982).
`Boss et al. Immunology Today 6(1):12—13 (1985).
`LeWin, Ed. Genes 3rd Edition, 359—360 (1987).
`Skerra et al. Science 240:1038—1040 (1988).
`Kohler et al. Eur. J. Immunol. 6:292—295 (1976).
`Adair et al., “Engineering Antibodies for Therapy” Immu
`nological Reviews 130:5—40 (1992).
`Adelman et al., “In Vitro Deletional Mutagenesis for Bac
`terial Production of the 20,000—Dalton Form of Human
`Pituitary GroWth Hormone” DNA 2(3):183—193 (1983).
`Adetugbo, K., “Spontaneous Somatic Mutations” Journal of
`Biological Chemistry 253(17):6076—6080 (1978).
`
`Case 1:18-cv-00924-CFC-SRF Document 3 Filed 06/21/18 Page 3 of 636 PageID #: 71
`
`Alt et al., “Activity of Multiple Light Chain Genes in Murine
`Myeloma Cells Producing a Single, Functional Light Chain”
`Cell 21:1—12 (Aug. 1980).
`Alt et al., “Joining of immunoglobulin heavy chain gene
`segments: Implications from a chromosome With evidence
`of three D—JH fusions” Proc. Natl. Acad. Sci. USA
`79:4118—4122 (Jul. 1982).
`Alt et al., “Multiple Immunoglobulin Heavy—Chain Gene
`Transcripts in Abelson Murine Leukemia Virus—Trans
`formed Lymphoid Cell Lines” Molecular & Cellular Biol
`ogy 2(4):386—400 (Apr. 1982).
`Alt et al., “Organization and Reorganization of Immunoglo
`bulin Genes in A—MuLV—Transformed Cells: Rearrange
`ment of Heavy but Not Light Chain Genes” Cell 27:381—390
`(Dec. 1981).
`Altenburger et al., “Functional and non—functional joining in
`immunoglobulin light chain genes of a mouse myeloma”
`Nature 287:603—607 (Oct. 16, 1980).
`Amzel and Poljak, “Three—dimensional structure of immu
`noglobulins” Ann. Rev. Biochem. 48:961—997 (1979).
`Astaldi et al., “Increase of hybridoma formation by human
`lymphocytes after stimulation in vitro; effect of antigen,
`endothelial cells, and PWM” J. Immunol. 128(6):2539—2542
`(1982).
`August, “Monoclonal Antibodies—I: Discussion” Cell
`Fusion: Gene Transfer and Transformation, Beers et al. pp.
`345—351 (1984).
`Barnett—Foster and Painter, “The interaction of the Facb
`fragment of rabbit anti—sheep red cell IgG With guinea pig
`macrophages, and human monocytes and granulocytes”
`Molecular Immunology 19(2):247—252 (1982).
`Bernard and Gough, “Nucleotide sequence of immunoglo
`bulin heavy chain joining segments betWeen translocated VH
`and u constant region genes” Proc. Natl. Acad. Sci. USA
`77(6):3630—3634 (1980).
`Bernard et al., “Plasmacytomas With more than one immu
`noglobulin K mRNA: Implications for allelic exclusion”
`Proc. Natl. Acad. Sci. USA 78(9):5812—5816 (Sep. 1981).
`Bernstein et al., “Monoclonal Antibody Therapy of Mouse
`Leukemia” Monoclonal Antibodies, Kennett et al., Plenum
`Press pp. 275—291 (1980).
`Better and HorWitz, “Expression of engineered antibodies
`and antibody fragments in microorganisms” Methods in
`Enzymology 178:476—496 (1989).
`Better et al., “Escherichia coli secretion of an active chi
`meric antibody fragment” Science 240:1041—1043 (1988).
`Bevan et al,. “Biosynthesis of immunoglobulins” Progress
`In Biophysics and Molecular Biology, Butler and Noble,
`Pergamon Press pp. 133—162 (1972).
`Birshtein et al., “Effects of immunoglobulin structure on Fc
`receptor binding: a mouse myeloma variant immunoglobu
`lin With a y2b—y2a hybrid heavy chain having a complete y2a
`Fc region fails to bind a y2a Fc receptors on mouse mac
`rophages” J. Immunol. 129(2):610—614 (1982).
`Blythman et al., “Immunotoxins: hybrid molecules of mon
`clonal antibodies and a toxin subunit speci?cally kill tumour
`cells” Nature 290:145—146 (1981).
`Bobrzecka et al., “The method of controlled rearrangement
`of protein disulphides and its use for synthesis of chimeric
`immunoglobulin G” Immunology Letters 2:151—155 (1980).
`Bock et al., “Cloning and expression of the cDNA for human
`antithrombin III” NucleicAcids Research 10(24):8113—8125
`(1982).
`
`

`

`US 6,331,415 B1
`Page 3
`
`Bock et al., “HybridiZation—selected translation of Bombyx
`mori high—cysteine chorion proteins in Xenopus laevis
`oocytes” Proc. Natl. Acad. Sci. USA 79:1032—1036 (1982).
`Boss et al., “Assembly of functional antibodies from immu
`noglobulin heavy and light chains synthesised in E. coli”
`Nucleic Acids Research 12(9):3791—3806 (1984).
`Boss et al., “Production of immunoglobulin molecules in
`Escherichia coli” J. Cell. Biochem. (Abstract Only) Supple
`ment 7A:140 (0364) (1983).
`BothWell et al., “Dual expression of 9» genes in the
`MOPC—315 plasmacytoma” Nature 290:65—67 (1981).
`BothWell et al., “Heavy chain variable region contribution to
`the NP” family of antibodies: somatic mutation evident in a
`y2a variable region” Cell 24:625—637 (1981).
`BothWell et al., “Somatic variants of murine immunoglobu
`lin 0t light chains” Nature 298:380—382 (Jul. 22, 1982).
`Boulianne et al., “Production of functional chimaeric mouse/
`human antibody” Nature 312:643—646 (Dec. 13, 1984).
`Boulianne et al., “The production of chimeric mouse/human
`antibodies” Abstracts of papers presented at the meeting on
`Cellular and Molecular Biology of Neoplasia (Abstract
`only) pp. #25 (1983).
`Boyd et al., “Human monoclonal antibodies—production
`and potential” Trends in Biotechnology 2(3):70—77 (1984).
`Boyden, Alan, “Homology and Analogy” Science
`164:455—456 (Apr. 1969).
`Boylston et al., “Production of human IgM anti—D in tissue
`culture by EB—virus—transformed lymphocytes” Scand. J.
`Immunol. 12:355—358 (1980).
`Bruggemann et al., “Immunoglobulin V region variants in
`hybridoma cells. I. Isolation of a variant With altered idio
`typic and antigen binding speci?city” EMBO Journal
`1(5):629—634 (1982).
`Buchner et al., “Renaturation, puri?cation and characteriZa
`tion of recombinant Fab—fragments produced in Escherichia
`coli” Bio/Technology 9:157—162 (1991).
`BurroWs et al., “Evidence that murine pre—B cells synthesiZe
`0 heavy chains but no light chains” Nature 280:838—841
`(Aug. 30, 1979).
`Cabilly et al., “Generation of Antibody Activity from Immu
`noglobulin Polypeptide Chains Produced in Escherichia
`coli” Proc. Natl. Acad. Sci. USA 81:3273—3277 (1984).
`Chang et al., “Construction and characteriZation of ampli
`?able multicopy DNA cloning vehicles derived from the
`P15A cryptic miniplasmid” J. Bacteriol. 134(3):1141—1156
`(1978).
`Cheng et al., “Effect of deglycosylation on the binding and
`immunoreactivity of human thyroxine—binding globulin”
`Journal of Biological Chemistry 254(18):8830—8835 (Sep.
`25, 1979).
`Choi et al., “RNA splicing generates a variant light chain
`from an aberrantly rearranged K gene” Nature 286:776—779
`(Aug. 21, 1980).
`Cof?no and Laskov, “Immunoglobulin production: method
`for quantitatively detecting variant myeloma cells” Science
`167:186—188 (1970).
`Cof?no et al., “Suppression of Immunoglobulin Synthesis
`by Cellular Hybridization” Nature New Biology 231:87—90
`(May 19, 1971).
`Cook and Scharff, “Antigen—binding mutants of mouse
`myeloma cells”
`Proc.
`Natl.
`Acad.
`Sci.
`USA
`7(12):5687—5691 (1977).
`
`Case 1:18-cv-00924-CFC-SRF Document 3 Filed 06/21/18 Page 4 of 636 PageID #: 72
`
`Cook et al., “Somatic mutation in a cultured mouse
`myeloma cell affects antigen binding” Proc. Natl. Acad. Sci.
`USA 79:1240—1244 (1982).
`Cotton and Milstein, “Fusion of tWo immunoglobulin—pro
`ducing myeloma cells” Nature 244:42—43 (Jul. 6, 1973).
`CreWs et al., “A Single VH Gene Segment Encodes the
`Immune Response to Phosphorylcholine: Somatic Mutation
`Is Correlated With the Class of the Antibody” Cell 25 :59—66
`(1981).
`Croce et al., “Production of human hybridomas secreting
`antibodies to measles virus” Nature 288:488—489 (1980).
`Dangl et al., “Segmental ?exibility and complement ?xation
`of genetically engineered chimeric human, rabbit and mouse
`antibodies” The EMBO Journal 7(7):1989—1994 (1988).
`Dangl, “Rapid isolation of cloned isotype sWitch variants
`using ?uorescence activated cell sorting” Cytometry
`2(6):395—401 (1982).
`De BernardeZ—Clark and Georgiou, “Inclusion bodies and
`recovery of proteins from the aggregated state” Protein
`Refolding Chapter 1:1—20 (1991).
`De Boer et al., “Construction of a Tandem trp—lac Promoter
`and a Hybrid trp—lac Promoter for Ef?cient and Controlled
`Expression of the Human GroWth hormone Gene in Escheri
`chia coli ” Promoters, Structure and Function (Praeger Pub
`lishers, R. RodrigueZ and M. Chamberline, eds.) pp.
`462—481 (1982).
`Dildrop et al., “Immunoglobulin V region variants in hybri
`doma cells. II. Recombination betWeen V genes” EMBO
`Journal 1(5):635—640 (1982).
`Dover, Gabby, “Nonhomologous VieWs of a Terminology
`Muddle” Cell 51:515—516 (Nov. 20, 1987).
`Duyvesteyn and De Waard, “A neW sequence—speci?c endo
`nuclease from a thermophilic cyanobacterium, mastigocla
`dus laminosus” FEBS Letters 111(2):423—426 (1980).
`Duyvesteyn et al., “Sequence—speci?c endonucleases in
`strains of anabaena and nostoc” Arch. Microbiol.
`134:276—281 (1983).
`Early and Hood, “Mouse immunoglobulin genes” Genetic
`Engineering, Principles and Methods, SetloW and Hol
`laender, NY. and London, UK:Plenum Press vol. 3:157—188
`(1981).
`Early et al., “Allelic Exclusion and Nonproductive Immu
`noglobulin Gene Rearrangements” Cell 24:1—3 (Apr. 1981).
`Early et al., “An immunoglobulin heavy chain variable
`region gene is generated from three segments of DNA: VH
`D and JH” Cell 19:981—992 (1980).
`Edelman, G., “Antibody structure and molecular immunol
`ogy”Annals of the New YorkAcademy of Sciences 190:5—25
`(1971).
`EdWards et al., “A human—human hybridoma system based
`on a fast—groWing mutant of the ARH—77 plasma cell
`leukemia—derived line” European J. Immunol. 12:641—648
`(1982).
`Ellison et al., “Linkage and sequence homology of tWo
`human immunoglobulin gamma heavy chain constant region
`genes” Proc. Natl. Acad. Sci. USA 79:1984—1988 (Mar.
`1982).
`Ellison et al., “Nucleotide sequence of a human immuno
`globulin CY4 gene” DNA 1(1):11—18 (1981).
`Ellison et al., “The nucleotide sequence of a human immu
`noglobulin
`CY1
`gene”
`Nucleic Acids Research
`10(13):4071—4079 (1982).
`
`

`

`US 6,331,415 B1
`Page 4
`
`Eshhar et al., “Induction of secretion of IgM from cells of
`the B cell line 38C—13 by somatic cell hybridization” J.
`Immunol. 122(6):2430—2434 (1979).
`Feiss et al., “Separate sites for binding and nicking of
`bacteriophage A DNA by terminase” Proc. Natl. Acad. Sci.
`USA 80:955—959 (1983).
`Fiers et al., “Complete Nucleotide Sequence of SV40 DNA”
`Nature 273:113—120 (May 11, 1978).
`Gillies et al., “A tissue—speci?c transcription enhancer ele
`ment is located in the major intron of a rearranged immu
`noglobulin heavy chain gene” Cell 33:717—728 (1983).
`Gillies et al., “Antigen Binding and Biological Activities of
`Engineered Mutant Chimeric Antibodies With Human
`Tumor Speci?cities” Hum. Antibod. Hybridomas 1(1):47—54
`(1990).
`Givol et al., “Diversity of germ—line immunoglobulin VH
`genes” Nature 292:426—430 (1981).
`GluZman, Yakov, “SV40—Transformed Simian Cells Sup
`port the Replication of Early SV40 Mutants” Cell
`23:175—182 (Jan. 1981).
`Goldsby et al., “Hybrid cell lines With T—cell characteris
`tics” Nature 267:707—708 (Jun. 23, 1977).
`Graham and van der Eb, “A NeW Technique for the Assay of
`Infectivity of Human Adenovirus 5 DN ” Virology
`52:456—467 (1973).
`GritZ and Davies, “Plasmid—encoded hygromycin B resis
`tance: the sequence of hygromycin B phosphotransferase
`gene and its expression in Escherichia coli and Saccharo
`myces cerevisiae” Gene 25:179—188 (1983).
`Gupta et al., “General Orientation of Human Lymphocyte
`Subpopulations” Clinical Immunobiol., Bach and Good,
`Academic Press vol. 4:1—18 (1980).
`Hedin et al., “Speci?cities and Binding Properties of Eight
`Monoclonal Antibodies Against Carcinoembryonic Anti
`gen” Molecular Immunology 19:1641—1648 (1982).
`Herlyn et al., “Inhibition of GroWth of Colorectal Carcinoma
`in Nude Mice by Monoclonal Antibody” Cancer Research
`40:717—721 (Mar. 1980).
`HerZenberg et al., “Hybridoma Variants Affecting Isotype,
`Antigen Binding, and Idiotype” Biotechnology in Diagnos
`tics, KoproWski et al. vol. 21:3—16 (1985).
`Hieter et al., “Cloned human and mouse kappa immunoglo
`bulin constant and J region genes conserve homology in
`functional segments” Cell 22(Part 1):197—207 (1980).
`Honjo et al., “Cloning and complete nucleotide sequence of
`mouse immunoglobulin Y1 Chain Gene” Cell 18:559—568
`(1979).
`Honjo et al., “Rearrangements of Immunoglobulin Genes
`during Differentiation and Evolution” Immunological Rev.
`59:33—67 (1981).
`Hood et al., “Antibodies” Immunology, Forkner and Moore,
`PhilippineszThe Benjamin/Cummings Publishing Co., Inc.,
`Chapter 3, pp. 199—221 (1978).
`HorWitZ et al., “Secretion of functional antibody and Fab
`fragment from yeast cells” Proc. Natl. Acad. Sci. USA
`85:8678—8682 (1988).
`Houghton et al., “Detection of cell surface and intracellular
`antigens by human monoclonal antibodies” Journal of
`Experimental Medicine 158:53—65 (1983).
`HoWard et al., “A Rapid Method for the Detection of
`Antibodies to Cell Surface Antigens: A Solid Phase Radio
`immunoassay Using Cell Membranes” Journal of Immuno
`logical Methods 38:75—84 (1980).
`
`Case 1:18-cv-00924-CFC-SRF Document 3 Filed 06/21/18 Page 5 of 636 PageID #: 73
`
`HoWard et al., “Long—term culture of normal mouse B
`lymphocytes” Proc. Natl. Acad. Sci. USA 78(9):5788—5792
`(Sep. 1981).
`Hughes and Murray, “The nucleotide sequences recogniZed
`by endonucleases AvaI and AvaII from Anabaena variabi
`lis” Biochemical Journal 185:65—75 (1980).
`Hunkapiller et al., “The groWing immunoglobulin gene
`superfamily” Nature 323:15—16 (1986).
`“Immunoglobulin molecules and genes” Microbiology
`Including Immunology and Molecular Genetics, Third edi
`tion, Harper International Edition vol. Chapter 17:338—379.
`Inouye et al., “Signal Sequence of Alkaline Phosphatase of
`Escherichia coli” J. Bacteriol. 149:434 (1982).
`Isenman et al., “The structure and function of immunoglo
`bulin domains” J. Immunol. 114(6):1726—1929 (1975).
`Itakura and Riggs, “Chemical DNA synthesis and recombi
`nant DNA studies” Science 209:1401—1405 (1980).
`Jaton et al., “Conformational changes induced in a homo
`geneous anti—type III pneumococcal antibody by oligosac
`charides of increasing siZe” Biochemistry 14(24):5312—5315
`(1975).
`Johnson et al., “The Complete V Domain Amino Acid
`Sequences of TWo Myeloma Inulin—Binding Proteins” J our
`nal of Immunology 128:302—307 (1982).
`Jones, P.T. et al., “Replacing the Complementarity—deter
`mining Regions in a Human Antibody With Those From a
`Mouse” Nature 321:522—525 (May 29, 1986).
`Kabat, E., “Activation of the complement system and its
`effect on cells” Structural Concepts in Immunology and
`Immunochemistry, Second edition, Holt, Rinehart and Win
`ston vol. Chapter 13:413—435 (1976).
`Kaivarainen et al., “Hapten—induced changes in pig anti
`—Dansyl antibodies revealed by EPR spectra of spin—la
`belled antibodies” Immunol. Letters 3:5—11 (1981).
`Kalderon et al., “Deletion loop mutagenesis: a novel method
`for the construction of point mutations using deletion
`mutants” Nucl. Acids Res. 10:5161—5168 (1982).
`Keshet et al, “Cloning of bovine groWth hormone gene and
`its expression in bacteria” Nucleic Acids Research 9:19—30
`(1981).
`Kipps et al., “Allotype SWitch Variants in Cultured Mono
`clonal Producing Hybridomas” Journal of Cellular Bio
`chemistry (abstract only) pp. 163 (—1984).
`Kitai et al., “Extracellular production of human immuno
`globulin G FC region” Microbiol. Biotechnol. 28(1):52—56
`(1988).
`Klein et al., “Expression of biological effector functions by
`immunoglobulin G molecules lacking the hinge region”
`Proc. Natl. Acad. Sci. USA 78(1):524—528 (1981).
`Kohl and Moore, “Human antibody—dependent cellular
`cytotoxicity and natural killer cytotoxicity to herpes simplex
`virus—infected autologous and allogeneic cells” Immunology
`48:187—193 (1983).
`Kohler et al., “Derivation of Speci?c Antibody—producing
`Tissue Culture and Tumor Lines by Cell Fusion” European
`Journal ofImmunology 6:511—519 (1976).
`Kohler, G. and Milstein, C., “Continuous Cultures of Fused
`Cells Secreting Antibody of Prede?ned Speci?city” Nature
`256:495—497 (Aug. 7, 1975).
`KoniecZny et al., “The combination of IgM subunits and
`proteolytic IgG fragments by controlled formation of inter
`chain disulphides” Haematologia 14(1):95—99 (1981).
`
`

`

`US 6,331,415 B1
`Page 5
`
`Koskimies, S., “Human lymphoblastoid cell line producing
`speci?c antibody against Rh—antigen D” Scand. J. Immunol.
`11:73—77 (1980).
`Kuehl, W.M., “Light chain fragments: aberrant expression of
`immunoglobulin genes” TIBS pp. 206—208 (Aug. 1981).
`Kupchik et al., “Monoclonal Antibodies to Carcinoembry
`onic Antigen Produced by Somatic Cell Fusion” Cancer
`Research 41:3306—3310 (Sep. 1981).
`KWan, “TWo Kappa Immunoglobulin Genes Are Expressed
`in the Myeloma S107” Cell 26:57—66 (Oct. 1981).
`Larson et al., “Saccharomyces cerevisiae actin—Escherichia
`coli lacZ gene fusions: synthetic—oligonucleotide—mediated
`deletion of the 309 base pair intervening sequence in the
`actin gene” Gene 22:31—39 (1983).
`Laskov and Scharff, “Synthesis, assembly, and secretion of
`gamma globulin by mouse myeloma cells” Journal of
`Experimental Medicine 131(3):515—541 (1970).
`Laskov et al., “Induction of ampli?ed synthesis and secre
`tion of IgM by fusion of murine B Lymphoma With myeloma
`cells” Proc. Natl. Acad. Sci. USA 76(2):915—919 (Feb.
`1979).
`Lau and Doolittle, “Aqu I: a more easily puri?ed isoschi
`Zomer of AVA I” FEBS Letters 121(2):200—202 (1980).
`Leder, P., “The genetics of antibody diversity” Scienti?c
`America 246:72—83 (1982).
`Lee et al., “Characterization of the Gene Encoding Heat—
`Stable Toxin II and Preliminary Molecule Epidemiological
`Studies of Enterotoxigenic Escherichia coli Heat—Stable
`Toxin II Producers” Infection and Immunity 42:264—268
`(Oct. 1983).
`LetherbarroW et al., “Effector functions of a monoclonal
`aglycosylated mouse IgGZa:binding and activation of
`complement component C1 and interaction With human
`monocyte Fc receptor” Molec. Immunol. 22(4):407—415
`(1985).
`Levy and Miller, “Tumor therapy With monoclonal antibod
`ies” Fed. Proc. 42:2650—2656 (1983).
`LeWin, Roger, “When Does Homology Mean Something
`Else?” Science 237:1570 (1987).
`Liu et al., “Chimeric mouse—human IgG1 antibody that can
`mediate lysis of cancer cells” Proc. Natl. Acad. Sci. USA
`84:3439—3443 (May 1987).
`Liu, Pinghui V., “Pseudomonas Toxins” J. Infect. Dis.
`130:S94—S99 (1974).
`Maniatis et al. Molecular Cloning: A Laboratory Manual,
`1st edition, NeW York: Cold Spring Harbor Lab Press, Chap
`ter 12, pps. selected pages (1982).
`Maniatis, T., “Recombinant DNA procedures in the study of
`eukaryotic genes” Cell Biol. 3:563—608 (1980).
`Margulies et al., “Regulation of immunoglobulin expression
`in mouse myeloma cells” Immunoglobulin Expression pp.
`781—791 (1977).
`Margulies et al., “Somatic Cell HybridiZation of Mouse
`Myeloma” Cell 8:405—415 (Jul. 1976).
`Martinis et al., “Monoclonal antibodies With dual antigen
`speci?city” Oncology pp. 311—316.
`Mather et al., “Transcriptional regulation of immunoglobu
`lin V genes” Nucleic Acids Research 9(24):6855—6867
`(1981).
`Matsuuchi and Morrison, “Antigen binding variants of
`mouse plasmacytoma J558” Fed. Proc. (Abstract only)
`37:1763 (2703) (1978).
`
`Case 1:18-cv-00924-CFC-SRF Document 3 Filed 06/21/18 Page 6 of 636 PageID #: 74
`
`Max et al., “Variation in the Crossover Point of Kappa
`Immunoglobulin Gene V—J Recombination: Evidence from
`a Cryptic Gene” Cell 21:793—799 (Oct. 1980).
`McCutchan et al., “Enhancement of the Infectivity of Simian
`Virus 40 Deoxyribonucleic Acid With Diethylaminoethyl—
`Dextran” J. Natl. Cancer Institute 41:351—356 (1968).
`Melchers, F., “Biosynthesis of the carbohydrate portion of
`immunoglobulin radiochemical and chemical analysis of the
`carbohydrate moieties of tWo myeloma proteins puri?ed
`from different subcellular fractions of plasma cells” Bio
`chemistry 10(4):653—659 (1971).
`MertZ et al., “Defective Simian Virus 40 Genomes: Isolation
`and GroWth of Individual Clones” Virology 62:112—124
`(1974).
`Messing et al., “A System for Shotgun DNA Sequencing”
`Nucleic Acids Research 9(2):309—321 (1981).
`Milstein et al., “Clonal Variants of Myeloma Cells” Progress
`in Immunology II 1:157—168 (1974).
`Mohit and Fan, “Hybrid Cell Line from a Cloned Immuno
`globulin—Producing Mouse Myeloma and a Nonproducing
`Mouse Lymphoma” Science 171:75—77 (Jan. 8, 1971).
`Morrison and Scharff, “Mutational events in mouse
`myeloma cells” Critical Reviews in Immunology 3(1):1—22
`(1981).
`Morrison et al., “Chimeric Human Antibody Molecules:
`Mouse Antigen—binding Domains With Human Constant
`Region Domains” Proc. Natl. Acad. Sci. USA 81:6851—6855
`(Nov. 1984).
`Morrison et al., “Genetically Engineered Antibody Mol
`ecules” Adv. Immunol. 44:65—92 (1989).
`Morrison et al., “Transfectomas Provide Antibodies With
`Novel Structures and Functions”Antibodies: Structure, Syn
`thesis, Function, and Immunologic Intervention in Disease,
`SZentivanyi et al. pp. 167—178 (1987).
`Morrison et al., “Transfer and expression of immunoglobu
`lin genes”AnnualReview ofImmunology 2:239—256 (1984).
`Morrison, S. L., “Transfectomas Provide Novel Chimeric
`Antibodies” Science 229:1202—1207 (Sep. 20, 1985).
`Movva et al., “Amino Acid Sequence of the Signal Peptide
`of ompA Protein, a Major Outer Membrane Protein of
`Escherichia coli” The Journal of Biological Chemistry
`255:27—29 (Jan. 10, 1980).
`Nakabayashi et al., “The transforming function of bovine
`papillomavirus DNA” Proc. Natl. Acad. Sci. USA
`80:5832—5836 (1983).
`Neuberger et al., “A hapten—speci?c chimaeric IgE antibody
`With human physiological effector function” Nature
`314:268—270 (Mar. 21, 1985).
`Neuberger et al., “Recombinant Antibodies Possessing
`Novel Effector Functions” Nature 312:604—608 (Dec. 13,
`1984).
`Neuberger, “SWitch from hapten—speci?c immunoglobulin
`M to immunoglobulin D secretion in a hybrid mouse cell
`line” Proc. Natl. Acad. Sci. USA 78(2):1138—1142 (1981).
`Ochi et al., “Functional immunoglobulin M production after
`transfection of cloned immunoglobulin heavy and light
`chain genes into lymphoid cells” Proc. Natl. Acad. Sci. USA
`80:6351—6355 (1983).
`Oi et al., “Correlation betWeen segmental ?exibility and
`effector function of antibodies” Nature 307:136—140 (1984).
`Oi et al., “Hybridoma Antibody—Producing SWitch Variants:
`A Variant Lacking the CH1 Domain” Cell Fusion: Gene
`Transfer and Transformation, R.F. Beers, Jr. and EG Bas
`sett, Raven Press, NeW York pp. 281—287 (1984).
`
`

`

`US 6,331,415 B1
`Page 6
`
`Oi et al., “Localization of Murine Igh—1“ Allotypic Deter
`minants by Using a Panel of Mouse Myeloma Variant
`Immunoglobulins”
`Journal
`of
`Immunology
`130(4):1967—1969 (Apr. 1983).
`Oi et al., “Lymphocyte membrane IgG and secreted IgG are
`structurally and allotypically distinct” Journal of Experi
`mental Medicine 151:1260—1274 (1980).
`Olsson and Kaplan, “Human—human hybridomas producing
`monoclonal antibodies of prede?ned antigenic speci?city”
`Proc. Natl. Acad. Sci. USA 77(9):5429—5431 (1980).
`Orna Zemel—Dreasen et al., “Secretion and processing of an
`immunoglobulin light chain in Escherichia coli” Gene
`27(3):315—322 (1984).
`OWens and Young, “The genetic engineering of monoclonal
`antibodies” J. Immunol. Methods 168:149—165 (1994).
`Palva et al., “Secretion of interferon by bacillus subtilis”
`Gene 22:229—235 (1983).
`Parham et al., “Isolation of Heavy Chain Class SWitch
`Variants of a Monoclonal Anti—DC1 Hybridoma Cell Line:
`Effective Conversion of Noncytotoxic IgG1 Antibodies to
`Cytotoxic IgG2 Antibodies” Human Immunology 8:141—151
`(1983).
`Peden and Nathans, “Local mutagenesis Within deletion
`loops of DNA heteroduplexes” Proc. Natl. Acad. Sci. USA
`79:7214—7217 (1982).
`Periman, “IgG Synthesis in Hybrid Cells from an Anti
`body—producing Mouse Myeloma and an L Cell Substrain”
`Nature 228:1086—1087 (Dec. 12, 1970).
`Perry et al., “Transcription of mouse K chain genes: impli
`cations for allelic exclusion” Proc. Natl. Acad. Sci. USA
`77(4):1937—1941 (1980).
`Picken et al., “Nucleotide sequence of the gene for heat
`—stable enterotoxin II of Escherichia coli” Infection and
`Immunity 42(1):269—275 (1983).
`Plaut et al., “Immunoglobulin M: Fixation of human
`complement by the Fc Fragment” Science 176:55—56
`(1972).
`Ponte et al., “Transcription of immunoglobulin heavy—chain
`sequences from the excluded allele” Nature 291:594—596
`(1981).
`Raghunathan et al., “Abstract P—D2—01—In?uence of vari
`able domain glycosylation on antigen binding:crystal struc
`ture of anti—GnRH Fab frament” Prog. Biophy & Mol. Biol.
`65(5):143—(1996).
`Raschke et al., “Assembly and secretion of pentameric IgM
`in a fusion betWeen a nonsecreting B cell lymphoma and an
`IgG—secreting plasmacytoma” Proc. Natl. Acad. Sci. USA
`76(7):3469—3473 (1979).
`Rechavi et al., “Evolutionary aspects of immunoglobulin
`heavy chain variable region (VH gene subgroups” Proc.
`Natl. Acad. Sci. USA 80:855—859 (1983).
`Reeck et al., ‘“Homology’ in Proteins and Nucleic Acids: A
`Terminology Muddle and a Way out of it” Cell 50 (Aug. 28,
`1987).
`Reth et al., “Analysis of the repertoire of anti—NP antibodies
`in C57BL/6 mice by cell fusion” European Journal of
`Immunology 8:393—400 (1978).
`Rice et al, “Measurement of transient cDNA expression in
`mammalian cells using ?oW cytometric cell analysis and
`sorting” Cytometry 12:221—233 (1991).
`Riley et al., “Induction of light chain expression in a pre—B
`cell line by fusion to myeloma cells” Nature 289:804—806
`(1981).
`
`Case 1:18-cv-00924-CFC-SRF Document 3 Filed 06/21/18 Page 7 of 636 PageID #: 75
`
`Robins et al., “Regulated Expression of Human GroWth
`Hormone Genes in Mouse Cells” Cell 29:623—631 (1982).
`RoiZes, “A neW speci?c endonuclease from Anabaena vari
`abilis” FEBS Letters 104(1):39—44 (1979).
`Rouger and Goossens, “Human Monoclonal antibodies
`against human red blood cells” Therapeutic Monoclonal
`Antibodies, Borrebaeck and Larrick, M Stockton

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