EXHIBIT B
`
`EXHIBIT B
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 253 of 1040
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 253 of 1040
`
`
`
`EXHIBIT B
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 253 of 1040
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 253 of 1040
`
`
`
`REFERENCES CONSIDERED BY DR. EDUARDO A. PADLAN
`
`Exhibit No.
`
`1001
`
`Description
`
`U.S.Pate nt N o.6 ,4 07,213 , Method for making humanized
`antibodies (file d Ju l.17, 1993 ) (issu e d Ju ne 18, 2002)
`
`1002Part I
`
`F ile H istory forU.S.Pate nt N o.6 ,4 07,213 Part I
`
`1002Part II
`
`F ile H istory forU.S.Pate nt N o.6 ,4 07,213 Part II
`
`1003
`
`1003 A
`
`1003 B
`
`1003 C
`
`1004
`
`1004 A
`
`1004 B
`
`1021
`
`1022
`
`103 0
`
`103 1
`
`D e c laration ofD r.Ed u ard oA .Pad lan in Su pport ofPe tition for
`Inter Partes Re vie w ofPate nt N o.6 ,4 07,213
`
`Curriculum Vitae ofD r.Ed u ard oA .Pad lan
`
`M ate rialsRe vie we d by D r.Ed u ard oA .Pad lan
`
`ExhibitsA -M ofD r.Ed u ard oA .Pad lan
`
`D e c laration ofProfe ssorEd ward Ball, M .D .in Su pport of
`Pe tition forInter Partes Re vie w ofPate nt N o.6 ,4 07,213
`
`Curriculum Vitae ofProfe ssorEd ward Ball, M .D .
`
`M ate rialsRe vie we d by Profe ssorEd ward Ball, M .D .
`
`H u d ziak e t al.p185HER2 Monoclonal Antibody Has
`Antiproliferative Effects In Vitro and Sensitizes Human Breast
`Tumor Cells to Tumor Necrosis Factor. M ol.C e llBiol.
`9(3 ):116 5 -1172(M arc h1989)
`
`K öhle rand M ilste in, Continuous Cultures of Fused Cells
`Secreting Antibody of Predefined Specificity. N atu re
`25 6 (5 5 17):4 95 -4 97 (A u gu st 7, 1975 )
`
`“Prote in D ataBank –C hronology”at
`https://www.nsf.gov/ne ws_su m m .jsp? c ntn_id =1006 89(ac c e sse d
`A u gu st 29, 2016 )
`
`M orrison e t al., Chimeric Human Antibody Molecules: Mouse
`Antigen-Binding Domains with Human Constant Region
`
`-1-
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 254 of 1040
`
`
`
`Exhibit No.
`
`Description
`Domains. Pro.N at’lA c ad .Sc i.81:6 85 1-6 85 5 (N ove m be r1984 ).
`
`103 3
`
`103 4
`
`104 5
`
`104 6
`
`104 7
`
`104 8
`
`104 9
`
`105 0
`
`105 1
`
`105 2
`
`Jone se t al.Replacing the Complementarity-Determining Regions
`in a Human Antibody with those from a Mouse. N atu re 3 21:5 22-
`5 25 (1986 )
`
`Qu e e n e t al.A Humanized Antibody that Binds to the Interleukin
`2 Receptor. Pro.N at’lA c ad .Sc i.86 :10029-1003 3 (1989)
`
`Slam on, D .J.e t al.Human Breast Cancer Correlation of Relapse
`and Survival with Amplification of the HER-2/neu Oncogene.
`Sc ie nc e 23 5 :177-182(1987)
`
`K rau s, M .H ., e t al.Overexpression of the EGF receptor-related
`proto-oncogene erbB-2 in human mammary tumor cell lines by
`different molecular mechanisms. The EM BOJou rnal6 (3 ):6 05 -
`6 10(1987)
`
`H u d ziak, R.M ., e t al.Increased expression of the putative
`growth factor receptor p185HER2 causes transformation and
`tumorigenesis of NIH 3T3 cells. Pro.N at’lA c ad .Sc i.84 :715 9-
`716 3 (1987)
`
`She pard , H .M .e t al.Monoclonal Antibody Therapy of Human
`Cancer: Taking the HER2 Protooncogene to the clinic. Jou rnal
`ofC linic alIm m u nology, 11(3 ):117-127 (1991).
`
`C hothia, C .e t al.Conformations of immunoglobulin
`hypervariable regions. N atu re 3 4 2(21):877-883 (D e c e m be r
`1989).
`
`Qu e e n, C ary L .:Inte rnationalPu blic ation N o.W O1990/0786 1
`(pu blishe d Ju ly 26 , 1990)
`
`Tram ontano, A .e t al.Framework Residue 71 is a Major
`Determinant of the Position and Conformation of the Second
`Hypervariable Region in the VH Domains of Immunoglobulins, J.
`M ol.Biol.215 :175 -182(1990)
`K abat, e t al.Sequences of Proteins of Immunological Interest 4th
`
`-2-
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 255 of 1040
`
`
`
`Exhibit No.
`
`105 3
`
`105 5
`
`105 7
`
`105 8
`
`105 9
`
`106 0
`
`106 1
`
`106 2
`
`106 3
`
`Description
`Ed., Tabulation and Analysis of Amino Acid and Nucleic Acid
`Sequences of Precursors, V-Regions, C-Regions, J-Chain, T-Cell
`Receptor for Antigen, T-Cell Surface Antigens (N ational
`Institu te sofH e alth, Be the sd a, M d .) (1987)
`
`W u and K abat, An analysis of the sequences of the variable
`regions of Bence Jones proteins and myeloma light chains and
`their implications for antibody complementarity. J.Exp.M e d .
`13 2:211-25 0(1970)
`K abat, e t al.Sequences of Proteins of Immunological Interest 5 th
`Ed., Tabulation and Analysis of Amino Acid and Nucleic Acid
`Sequences of Precursors, V-Regions, C-Regions, J-Chain, T-Cell
`Receptor for Antigen, T-Cell Surface Antigens (N ational
`Institu te sofH e alth, Be the sd a, M d .) (1991)
`
`Johnson and W u The Kabat database and a bioinformatics
`example, M e thod sin M ole c u larBiology 24 8:11-25 (D e c e m be r
`2003 )
`
`D avie s& M e tzge r, Structural Basics of Antibody Function,
`A nnu .Re v.Im m u nol.1:87-117 (1983 )
`
`A m it e t al.Three-Dimensional Structure of an Antigen-Antibody
`Complex at 2.8 A Resolution Sc ie nc e 23 3 :74 7-5 3 (1986 )
`
`L asc om be e t al.Three-dimensional Structure of Fab R19.9, a
`Monoclonal Murine Antibody Specific for the p-
`azobenzenearsonate group. Pro.N at’lA c ad .Sc i.86 :6 07-6 11
`(Janu ary 1989)
`
`N ovotný e t al.Molecular Anatomy of the Antibody Binding Site.
`J.Biol.C he m .25 8(23 ):14 4 3 3 -14 4 3 7 (D e c e m be r10, 1983 )
`
`L e sk 1987, Canonical structures for the hypervariable
`C hothia&
`regions of immunoglobulins.J.M ol.Biol.196 :901-917 (1987)
`
`C hothiae t al.Domain Association in Immunoglobulin
`Molecules: The Packing of Variable Domains.J.M ol.Biol.
`186 :6 5 1-6 3 (1985 )
`
`-3 -
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 256 of 1040
`
`
`
`Exhibit No.
`
`Description
`
`106 4
`
`106 5
`
`106 6
`
`106 7
`
`106 8
`
`106 9
`
`1070
`
`1071
`
`1072
`
`1073
`
`Van K roone nbu rgh& Pau we ls Human Immunological Response
`to Mouse Monoclonal Antibody Treatment or Diagnosis of
`Malignant Diseases.N u c l.M e d .C om m u n.9:919-3 0(1988)
`
`Tjand rae t al.Development of human anti-murine antibody
`(HAMA) response in patients.Im m u nol.C e ll.Biol.6 8:3 6 7-76
`(1990)
`
`L ind , e t al.Development of human antimouse antibodies
`(HAMA) after single and repeated diagnostic application of
`intact murine monoclonal antibodies. A ntibod .Im m u noc onj.
`Rad iopharm .4 (4 ):811-818 (1991)
`
`M ou ntain and A d air, Engineering Antibodies for Therapy.
`Biote c h.Ge ne t.Eng.Re v.10:1-14 2(1992)
`
`Ve rhoe ye n, M ilste in & W inte re t al.Reshaping Human
`Antibodies: Grafting an Antilysozyme Activity. Sc ie nc e
`23 9:15 3 4 -15 3 6 (M arc h25 , 1988)
`
`Rie c hm ann, e t al.Reshaping human antibodies for therapy.
`N atu re 3 3 2:3 23 -3 27 (M arc h24 , 1988)
`
`Te m pe st, e t al.Reshaping a human monoclonal antibody to
`inhibit human respiratory syncytial virus infection in vivo.
`BioTe c hnology 9:26 6 -271(M arc h1991)
`
`K u rrle , e t al.Improved monoclonal antibodies against the human
`alphabeta T-Cell receptor, their production and use. EP04 03 15 6 .
`(1990)
`
`She arm an, e t al.Construction, expression and characterization of
`humanized antibodies directed against the human a/b T cell
`receptor. J.Im m u nol.14 7(12):4 3 6 6 -4 3 73 , (D e c e m be r15 , 1991)
`
`W inte r, Gre gory Pau le t al.EP Pu blic ation N u m be r023 94 00,
`Recombinant antibodies and methods for their productions.
`Pu blishe d Se pte m be r3 0, 1987.
`
`-4 -
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 257 of 1040
`
`
`
`Exhibit No.
`
`Description
`
`1076
`
`1077
`
`1078
`
`1079
`
`1080
`
`1081
`
`1082
`
`1083
`
`1085
`
`1086
`
`L oe w, G.e t al.Engergy-Conformational Studies of B-Endorphis:
`Identification of Plausible Folded Conformers.Int.J.Qu ant.
`C he m .Qu ant.Biol.15 :5 5 -6 6 (1988)
`
`Bru c c ole rie t al.Structure of antibody hpervariable loops
`reproduced by a conformational search algorithm. N atu re
`3 3 5 (6 ):5 6 4 -5 6 8 (1988)
`
`C hothiae t al.The Predicted Structure of Immunoglobulin D1.3
`and its Comparison with the Crystal Structure. Sc ie nc e N e w
`Se rie s, 23 3 (4 76 5 ):75 5 -75 8 (A u gu st 15 , 1986 )
`
`K abat e t al., Sequences of Proteins of Immunological Interest
`Tabulation and Analysis of Amino Acid and Nucleic Acid
`Sequences of Precursors, V-Regions, C-Regions, J-Chain, T-Cell
`Receptor for Antigen, T-Cell Surface Antigens (N ational
`Institu te sofH e alth, Be the sd a, M d .) (1983 ).
`
`Be rnste in e t al.The Protein Data Bank: A Computer-based
`Archival File for Macromolecular Structures.J.M ol.Biol.
`112:5 3 5 -5 4 2(1977)
`
`She riffe t al.Three-Dimensional Structure of an Antibody-
`Antigen Complex, Proc .N at’lA c ad .Sc i.U.S.A .84 :8075 (1987)
`
`M arqu art e t al.The three-dimensional structure of antibodies.
`Im m u n.Tod ay 3 (6 ):16 0-16 6 (1982)
`
`Sau le t al.Preliminary Refinement and Structural Analysis of the
`FAB Fragment from Human Immunoglobulin NEW at 2.0
`Angstroms Resolution.J.Biol.C he m .25 3 :5 85 (1978)
`
`Satow e t al.Phosphocholine Binding Immunogloubulin Fab
`McPC306 An X-ray Diffraction Study at 2•Å.J.M ol.Biol.
`190:5 93 -6 04 (1986 )
`
`H e rron e t al.Three-Dimensional Structure of a Flourescein-Fab
`Complex Crystallized in 2-Methyl-2,4-pentanediol.Prote ins
`5 :271-280(1989)
`
`-5 -
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 258 of 1040
`
`
`
`Exhibit No.
`
`Description
`
`1087
`
`1088
`
`1089
`
`1090
`
`1091
`
`1092
`
`1097
`
`1098
`
`1099
`
`1100
`
`Pad lan e t al.Structure of an antibody-antigen complex: crystal
`structure of the HYHEL-10 FAB-lysozyme complex. Proc .N at’l
`A c ad .Sc i.86 :5 93 8-5 94 2(A u gu st 1989)
`
`K u m are t al.Regulation of phosphorylation of the c-erbB-
`2/HER2 gene product by monoclonal antibody and serum growth
`factor(s) in human mammary carcinoma cells.M ol.C e ll.Biol.
`11(2):979-986 (F e bru ary 1991)
`
`Soom roe t al.C-erbB-2 expression in different histological types
`of invasive breast carcinoma.J.C lin.Pathol.4 4 :211-14 (1991)
`
`K e nne thH .Gou ld ing, A Biologist’s Guide to
`K e ithW ilson &
`Principles and Techniques of Practical Biochemistry, §Protein
`sequencing, 170-173 (3 rd e d ., 1986 )
`
`Ed e lm an e t al.The Covalent Structure of an Entire γG
`Immunoglobulin Molecule.Proc .N at’lA c ad .Sc i6 3 :78-85
`(196 9)
`
`C apra, J.D onald and K e hoe , K .M ic hae lVariable Region
`Sequences of Five Human Immunoglobulin Heavy Chains of the
`VHIII Subgroup: Definitive Identification of Four Heavy Chain
`Hypervariable Regions.Proc .N at’lA c ad .Sc i.71:84 5 -8 (1974 )
`
`Sam brook e t al., Molecular Cloning (2d e d ., C old SpringH arbor
`L aboratory Pre ss) (1989)
`
`D au ghe rty e t al., Polymerase chain reaction facilitates the
`cloning, CDR-grafting and rapid expression of a murine
`monoclonal antibody directed against the CD18 component of
`leukocyte integrins.N u c l.A c id sRe s.19(9):24 71-24 76 (M ay
`1991).
`
`Pad lan and K abat, Modeling of Antibody Combining Sites M e th.
`Enzym ol.203 :3 (1991)).
`
`C olm an e t al., Three-dimensional structure of a complex of
`antibody with influenza virus neuraminidase, N atu re 3 26 :3 5 8
`
`-6 -
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 259 of 1040
`
`
`
`Exhibit No.
`
`Description
`
`(1987)
`
`1101
`
`1102
`
`1103
`
`1104
`
`1105
`
`1106
`
`1107
`
`1108
`
`1109
`
`1110
`
`Tu lipe t al., Crystal structures of neuraminidase-antibody
`complexes, C old SpringH arborSym p.Qu ant.Biol.4 :25 7 (1989)
`
`Be nd e re t al., Immunogenicity, efficacy and adverse events of
`adalimumab in RA patients. Rhe u m atol.Int.27:26 9-74 (2007)
`
`Brie nt, Bru c e W .and N isonoff, A lfre d Quantitative
`investigations of idiotypic antibodies. IV. Inhibition by specific
`haptens of the reaction of anti-hapten antibody with its anti-
`idiotypic antibody, JExpM e d .13 2:95 1-6 2(1970)
`
`K oprowskie t al., Human anti-idiotype antibodies in cancer
`patients: Is the modulation of the immune response beneficial for
`the patient? Proc .N at’l.A c ad .Sc i.U.S.A .81:216 (1984 )
`
`C hanhe t al., Monoclonal anti-idiotypic antibody mimics the CD4
`receptor and binds human immunodeficiency virus, Proc .N at’l.
`A c ad .Sc i.U.S.A .84 :3 891(1987)
`
`Sc hroffe t al., Human Anti-Murine Immunoglobulin Responses in
`Patients Receiving Monoclonal Antibody Therapy, C anc e rRe s.
`4 5 :879(1985 )
`
`A bd ou e t al., Network Theory in Autoimmunity. In vitro
`suppression of serum anti-DNA by anti-idiotypic antibody in
`systemic lupus erythematosus, J.C lin.Inve st.6 7:1297 (1981)
`
`H arris, L .J.e t al.The three-dimensional structure of an intact
`monoclonal antibody for canine lymphoma, N atu re 3 6 0:3 6 9-72
`(1992)
`
`Jane way, C .A .e t al., IM M UN OBIOL OGY:TH E IM M UN E SYSTEM IN
`H EA L TH & D ISEA SE (4 the d ., Garland Sc ie nc e Pu blishing, N Y,
`(1999))
`
`Potte r, M .Immunoglobulin-producing tumors and myeloma
`proteins of mice, Physiol.Re v.5 2:6 3 1-719(1972)
`
`-7 -
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 260 of 1040
`
`
`
`Exhibit No.
`
`Description
`
`1111
`
`1112
`
`1113
`
`1114
`
`1115
`
`1116
`
`1117
`
`1118
`
`1119
`
`1120
`
`K abat K .A .and W u , T.T.Attempts to locate complementarity-
`determining residues in the variable positions of light and heavy
`chains A nn.N Y A c ad .Sc i.190:3 82-93 (1971);
`
`D .R.D avie se t al.A ntibod y-antige n c om ple xe s, Ann. Rev.
`Biochem. 5 9:4 3 9-73 (1990).
`
`Eppe t al., The molecular structure of a dimer composed of the
`variable portions of the Bence Jones protein REI refined at 2.0Å
`resolution, Bioc he m .14 :4 94 3 (1975 )
`M ian, I.S.Structure, function and properties of antibody binding
`sites, J.M ol.Biol.217:13 3 -5 1(1991)
`
`Poljak e t al.The three-dimensional structure of the fab fragment
`of a human myeloma immunoglobulin at 2.0-angstrom resolution,
`Proc .N at’lA c ad .Sc i.U.S.A .71:3 4 4 0-4 (1974 )
`
`Pad lan e t al.Model building studies of antigen binding sites: The
`hapten binding site of MOPC315 C old SpringH arborSym p.
`Qu ant.Biol.4 1:6 27-3 7 (1977))
`
`Bou lianne e t al.Production of functional chimaeric
`mouse/human antibody, N atu re 3 12:6 4 3 -6 (1984 )
`
`Pad lan, E.A .A possible procedure for reducing the
`immunogenicity of antibody variable domains while preserving
`their ligand-binding properties, M ol.Im m u nol.28:4 89-98 (1991)
`
`U.S.Pate nt N o.6 ,797,4 92Method for Reducing the
`Immunogenicity of Antibody Variable Domains (ve ne e ringof
`C D 18 m onoc lonalantibod ie s) (F ile d M arc h16 , 2001)(Issu e d
`Se pte m be r28, 2004 )
`
`Pad lan, Ed u ard oA ., Choosing The Best Framework To Use In
`The ‘Humanization’ Of An Antibody by CDR-Grafting:
`Suggestions From 3-D Structural Data. The 2nd A nnu alIBC
`Inte rnationalC onfe re nc e on A ntibod y Engine e ring.Om niSan
`D ie goH ote l, San D ie go, C A .(D e c e m be r16 -18, 1991)
`
`-8 -
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 261 of 1040
`
`
`
`Exhibit No.
`
`Description
`
`1121
`
`1122
`
`1123
`
`1124
`
`1125
`
`1126
`
`1127
`
`1128
`
`1129
`
`113 0
`
`Su he t al., The galactan-binding immunoglobulin Fab J539: an
`X-ray diffraction study at 2.6-Å resolution, Prote ins1:74 (1986 )
`
`U.S.Pate nt N o.5 ,792,85 2Polynucleotides Encoding Modified
`Antibodies with Human Milk Fat Globule Specificity
`(hu m anization ofm onoc lonalantibod ie sbind ingtohu m an m ilk
`fat globu le antige n) (F ile d N ove m be r16 , 1992) (Issu e d A u gu st
`11, 1998)
`
`U.S.Pate nt N o.5 ,889,15 7 Humanized B3 Antibody Fragments,
`Fusion Proteins, and Uses Thereof (hu m anization ofm onoc lonal
`antibod ie stoL e wisϒ-re late d c arbohyd rate antige n) (F ile d
`Oc tobe r28, 1994 ) Issu e d M arc h3 0, 1999)
`
`USPate nt N o.5 ,795 ,96 5 Reshaped human antibody to human
`interleukin-6 receptor (c laim ingpriority toA pril25 , 1991)
`(Issu e d A u gu st 18, 1998)
`
`F u re y e t al.Structure of a novel Bence-Jones protein (Rhe)
`fragment at 1.6 Å resolution, J.M ol.Biol.16 7:6 6 1-92(1983 )
`
`Se gale t al.The Three-Dimensional Structure of a
`Phosphorylcholine-Binding Mouse Immunoglobulin Fab and the
`Nature of the Antigen Binding Site, Proc .N at’lA c ad .Sc i.U.S.A .
`71:4 298 (1974 )
`
`Jone s, TA Diffraction methods for biological macromolecules.
`Interactive computer graphics: FRODO, M e th.Enzym ol.
`115 :15 7-71(1985 )
`
`C o, M .e t al.Humanized antibodies for antiviral therapy, Proc .
`N at’lA c ad .Sc i.U.S.A .88:286 9-73 (1991)
`
`http://www.e xc e ltric k.c om /othe rs/history-of-e xc e l/(ac c e sse d
`A u gu st 29, 2016 )
`
`U.S.Pate nt N o.4 ,891,76 2Method and Apparatus for Tracking,
`Mapping and Recognition of Spatial Patterns (F ile d F e bru ary 9,
`1988) (Issu e d Janu ary 2, 1990)
`
`-9-
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 262 of 1040
`
`
`
`Exhibit No.
`
`113 1
`
`Description
`
`W allic k, S.e t al.Glycosylation of a VH residue of a monoclonal
`antibody against α(1-6) dextran increases its affinity for antigen,
`J. Exp. Med. 16 8:1099-109(1988)
`
`-10-
`
`PETITIONER'S EXHIBITS
`
`Exhibit 1003 Page 263 of 1040
`
`
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
