81
`
`US 6,407,213 Bl
`
`-continued
`
`82
`
`va l Val Thr Va l Thr Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr
`215
`220
`225
`
`Cys Asn Va l Asp His Lys Pro Ser Asn Thr Ly s Val As p Lys Th r
`230
`235
`240
`
`val Glu Arg Lys cys cys val Glu cys Pro Pro cys Pro Ala Pro
`245
`250
`255
`
`Pro Val Al a Gly Pro ser val Phe Leu Phe Pro Pro Lys Pro Lys
`260
`265
`270
`
`Asp T hr Leu Met Ile Ser Ar g T hr Pro Glu Val Thr Cys Val Val
`275
`280
`285
`
`val Asp Val ser His Gl u Asp Pro Gl u Va l Gln Phe Asn Trp Tyr
`290
`295
`300
`
`Va l Asp Gly Met Glu Va l His Asn Ala Lys Thr Lys Pro Arg Glu
`305
`3 10
`315
`
`Glu Gln Phe Asn ser Thr Phe Arg Val Va l ser Val Leu Th r Val
`320
`325
`3 30
`
`Val His Gln Asp Tr p Leu ASn Gly Lys Gl u Tyr Lys cys Lys Val
`335
`340
`345
`
`Ser Asn Ly s Gly Leu Pro Al a Pro Ile Glu Ly s Thr lle Ser Ly s
`350
`355
`360
`
`Thr Lys Gly Gl n Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
`365
`370
`375
`
`Ser Ar g Glu Glu Met Thr Ly s Asn Gln Va l Se r Leu Thr Cys Leu
`380
`385
`390
`
`Va l Lys Gly Phe Tyr Pro Ser Asp I le Al a val Glu Trp Glu Ser
`395
`400
`405
`
`ASn Gly Gln Pro Glu Asn ASn Tyr Lys Thr Thr Pro Pro Met Leu
`410
`4 15
`420
`
`Asp Ser Asp Gly Se r Phe Phe Leu Ty r Ser Ly s Leu Thr Val Asp
`425
`430
`435
`
`Lys Ser Arg Trp Gln Gl n Gl y Asn Val Phe Ser Cys Ser Val Met
`440
`445
`450
`
`His Glu Ala Leu His Asn His Ty r Thr Gln Ly s Ser Leu Ser Leu
`455
`460
`465
`
`Ser Pro Gly Lys
`469
`
`(2) INFORMATION FOR S EQ ID N0:24:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 214 amino acids
`(B) TYPE: Amino Aci d
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCR IPTION : SEQ IO N0: 24 :
`
`ASp Va l Gln Met Thr Gl n Thr Th r Ser Ser Leu ser Ala ser Leu
`1
`5
`1 0
`15
`
`Gly Asp Ar g Va l Th r Ile Asn Cys Ar g Al a Se r Gln Asp Ile Asn
`25
`~
`~
`
`Asn Ty r Leu Asn Trp Tyr Gln Gln Ly s Pro Asn Gly Thr Val Ly s
`35
`40
`45
`
`Leu Leu I l e Tyr Tyr Thr Ser Th r Leu His Ser Gl y Va l Pro Ser
`w
`55
`~
`
`Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr I le
`65
`70
`75
`
`Board Ass gne
`
`BIOEPIS EX. 1095
`Page 251
`
`

`

`83
`
`US 6,407,213 Bl
`
`-continued
`
`84
`
`Ser Asn Le u Asp Gln Glu Asp Ile Ala Thr Ty r Phe Cys Gl n Gln
`H
`85
`~
`
`Gly Asn Thr Leu Pr o Pro Tbr Ph e Gly Gly Gly Thr Lys Val Glu
`95
`1 00
`1 05
`
`Ile Lys Arg Thr Val Ala Ala Pro ser Va l Phe I le Phe Pro Pro
`110
`115
`120
`
`Ser Asp Glu Gln Le u Lys Ser Gly Thr Ala Ser Va l Val Cys Le u
`125
`130
`135
`
`Leu Asn Asn Phe Tyr Pro Ar g Glu Ala Lys Val Gln Trp Lys Val
`140
`1 45
`150
`
`Asp Asn Ala Leu Gln ser Gl y Asn ser Gln Glu ser val Thr Glu
`155
`160
`165
`
`Gln Asp Ser Lys Asp Ser Thr Ty r Ser Leu Ser Ser Thr Leu Thr
`170
`175
`180
`
`Leu ser Lys Ala Asp Tyr Glu Lys His Lys va l Tyr Ala cys Glu
`185
`190
`195
`
`Val Th r His Gln Gly Leu Ser ser Pro Val Thr Lys Ser Ph e Asn
`200
`205
`210
`
`Ar g Gly Glu Cy s
`214
`
`(2) INFORMAT ION FOR SEQ ID N0:25:
`
`(i) SEQUENCE CHARACTERISTICS :
`(A) LENGTH : 233 amino acids
`(B) TYPE : Amino Aci d
`( D) TOPOLOGY : Linea r
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:25:
`
`Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Tbr Al a Thr
`1
`5
`10
`15
`
`Gl y Val His ser Asp Ile Gln Met Thr Gln ser Pro ser ser Le u
`25
`~
`~
`
`Ser Ala Ser Va l Gly Asp Ar g Val Tbr I le Thr Cys Ar g Al a Ser
`35
`40
`45
`
`Gln Asp I le Asn Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly
`55
`~
`~
`
`Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Thr Leu His Ser
`65
`70
`75
`
`Gly Va l Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr
`80
`85
`90
`
`Thr Leu Thr I l e Ser ser Leu Gln Pro Gl u Asp Phe Ala Thr Tyr
`9 5
`1 00
`1 OS
`
`Tyr Cys Gln Gln Gly Asn Thr Leu Pro Pro Thr Phe Gly Gln Gly
`110
`115
`1 20
`
`Thr Lys Val Glu Ile Lys Arg Th r Val Ala Ala Pro Ser Va l Phe
`125
`1 30
`135
`
`Ile Phe Pro Pro Ser Asp Gl u Gln Leu Lys Ser Gly Thr Al a Ser
`140
`145
`150
`
`Va l Val Cys Leu Leu Asn Asn Phe Ty r Pro Arg Glu Al a Lys Va l
`155
`160
`165
`
`Gin Trp Lys Val Asp Asn Ala Leu Gl n Ser Gly Asn Ser Gl n Gl u
`175
`180
`170
`
`Ser Val Thr Glu Gln Asp Ser Ly s Asp Ser Thr Ty r Ser Leu Ser
`185
`190
`195
`
`Board Ass gne
`
`BIOEPIS EX. 1095
`Page 252
`
`

`

`85
`
`US 6,407,213 Bl
`
`-continued
`
`86
`
`Ser Th r Le u Thr Leu Ser Lys Al a Asp Tyr Glu Lys Hi s Lys Va l
`200
`205
`2 10
`
`Tyr Ala Cy s Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Th r
`220
`225
`2 15
`
`Lys ser Phe Asn Arg Gly Gl u c ys
`230
`233
`
`(2) INFORMAT ION FOR S EQ ID N0 :26:
`
`(i) SEQUENCE CHARACTERISTICS :
`(A) LENGTH: 122 amino aci ds
`(B) TYPE : Amino Acid
`( D) TOPOLOGY : Linea r
`
`(xi) SEQUENCE DESCRIPTI ON: SEQ ID N0 :26:
`
`Glu Val Gin Leu Val Glu Ser Gl y Gly Gl y Le u Va l Gl n Pro Gly
`5
`1 0
`1 5
`
`Gl y Ser Leu Ar9 Leu Ser Cys Ala Al a Ser Gl y Tyr Ser P he Thr
`20
`25
`30
`
`Gl y Ty r Thr Met Asn Tr p Val Ar9 Gin Al a Pro Gly Lys Gl y Le u
`35
`40
`45
`
`Glu Trp Va l Al a Leu I le ASn Pro Tyr Lys Gl y Va l Thr Th r Tyr
`55
`~
`~
`
`Ala Asp Ser Val Lys Gly Ar9 Ph e Thr I le Ser Val Asp Lys Ser
`65
`70
`75
`
`Lys Asn Thr Al a Tyr Leu Gl n Met Asn Ser Le u Arg Ala Gl u Asp
`8 5
`H
`~
`
`Thr Ala Val Tyr Tyr Cys Ala Ar9 Ser Gly Tyr Tyr Gl y Asp Ser
`1 00
`1 OS
`95
`
`Asp Trp Tyr Phe Asp Va l Trp Gl y Gin Gl y Thr Leu Val Th r Va l
`120
`110
`115
`
`ser ser
`122
`
`50
`
`We claim:
`1. A humanized antibody variable domain compnsmg
`non-human Complementarity Determining Region (CDR) 45
`amino acid residues which bind an antigen incorporated into
`a human antibody variable domain, and further comprising
`a Framework Region (FR) amino acid substitution at a site
`selected from the group consisting of: 4L, 38L, 43L, 44L,
`58L, 62L, 65L, 66L, 67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H,
`36H, 39H, 43H, 45H, 69H, 70H, 74H, and 92H, utilizing the
`numbering system set forth in Kabat.
`2. The humanized variable domain of claim 1 wherein the
`substituted residue is the residue found at the corresponding
`location of the non-human antibody from which the non(cid:173)
`human CDR amino acid residues are obtained.
`3. The humanized variable domain of claim 1 wherein no
`human Framework Region (FR) residue other than those set
`forth in the group has been substituted.
`4. The humanized variable domain of claim 1 wherein the
`human antibody variable domain is a consensus human 60
`variable domain.
`5. The humanized variable domain of claim 1 wherein the
`residue at site 4L has been substituted.
`6. The humanized variable domain of claim 1 wherein the
`residue at site 38L has been substituted.
`7. The humanized variable domain of claim 1 wherein the
`residue at site 43L has been substituted.
`
`8. The humanized variable domain of claim 1 wherein the
`residue at site 44L has been substituted.
`9. 'lbe humanized variable domain of claim 1 wherein the
`residue at site 58L has been substituted.
`10. The humanir..ed variable domain of claim 1 wherein
`the residue at site 62L bas been substituted.
`11. The humanized variable domain of claim 1 wherein
`the residue at site 65L has been substituted.
`12. The humanized variable domain of claim 1 wherein
`the residue at site 66L has been substituted.
`13. The humanized variable domain of claim 1 wherein
`the residue at site 67L has been substituted.
`14. The humanized variable domain of claim 1 wherein
`55 the residue at site 68L bas been substituted.
`15. The humanized variable domain of claim 1 wherein
`the residue at site 69L has been substituted.
`16. The humanized variable domain of claim 1 wherein
`the residue at site 73L has been substituted.
`17. The humanized ''ariable domain of claim 1 wherein
`the residue at site 85L has been substituted.
`18. The humanized variable domain of claim 1 wherein
`the residue at site 98L has been substituted.
`19. The humanized variable domain of claim 1 wherein
`65 the residue at site 2H has been substituted.
`20. The humanized variable domain of claim 1 wherein
`the residue at site 4H has been substituted.
`
`Board Ass gne
`
`BIOEPIS EX. 1095
`Page 253
`
`

`

`US 6,407,213 Bl
`
`J5
`
`87
`21. The humanized variable domain of claim 1 wherein
`the residue at site 36H has been substituted.
`22. The humanized variable domain of claim 1 wherein
`the residue at site 39H bas been substituted.
`23. The humanized variable domain of claim 1 wherein
`the residue at site 43H has been substituted.
`24. The humanized variable domain of claim 1 wherein
`the residue at site 45H has been substituted.
`25. The humanized variable domain of claim 1 wherein
`the residue at site 69H has been substituted.
`26. The humanized variable domain of claim 1 wherein
`the residue at site 70H has been substituted.
`27. The humanized variable domain of claim 1 wherein
`the residue at site 74H has been substituted.
`28. The humanized variable domain of claim 1 wherein
`the residue at site 92H has been substituted.
`29. An antibody comprising the humanized variable
`domain of claim 1.
`30. An antibody which binds p185HERZ and comprises a
`humanized antibody variable domain, wherein the human(cid:173)
`ized an tibody variable domain comprises non-human
`Complementarity Determining Region (CDR) amino acid
`residues which bind p185HEm incorporated into a human
`antibody variable domain, and further comprises a Frame(cid:173)
`work Region (FR) amino acid substitution at a site selected
`from the group consisting of: 4L, 38L, 43L, 44L, 46L, 58L, 25
`62L, 65L, 66L, 67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H, 36H,
`39H, 43H, 45H, 69H, 70H, 74H, 75H, 76H, 78H and 92H,
`utilizing the numbering system set forth in Kabat.
`31. The antibody of claim 30 wherein the substituted
`residue is the residue found at the corresponding location of
`the non-human antibody from which the non-human CDR
`amino acid residues are obtained.
`32. The antibody of claim 30 wherein no human Frame(cid:173)
`work Region (FR) residue other than those set forth in the
`group has been substituted.
`33. The antibody of claim 30 wherein the human antibody
`variable domain is a consensus human variable domain.
`34. The antibody of claim 30 wherein the residue at site
`4L has been substituted.
`35. The antibody of claim 30 wherein the residue at site
`38L has been substituted.
`36. The antibody of claim 30 wherein the residue at site
`43L bas been substituted.
`37. The antibody of claim 30 wherein the residue at site
`44L has been substituted.
`38. The antibody of claim 30 wherein the residue at site
`46L has been substituted.
`39. The antibody of claim 30 wherein the residue at site
`58L bas been substituted.
`40. The antibody of claim 30 wherein the residue at site
`62L bas been substituted.
`41. The antibody of claim 30 wherein the residue at site
`65L has been substituted.
`42. The antibody of claim 30 wherein the residue at site
`66L bas been substituted.
`43. The antibody of claim 30 wherein the residue at site
`67L has been substituted.
`44. The antibody of claim 30 wherein the residue at site
`68L has been substituted.
`45. The antibody of claim 30 wherein the residue at site
`69L bas been substituted.
`46. The antibody of claim 30 wherein the residue at site
`73L has been substituted.
`47. The antibody of claim 30 wherein the residue at site
`85L has been substituted.
`48. The antibody of claim 30 wherein the residue at site
`98L has been substituted.
`
`88
`49. The antibody of claim 30 wherein the residue at site
`2H has been substituted.
`50. The antibody of claim 30 wherein the residue at site
`4H has been substituted.
`51. The antibody of claim 30 wherein the residue at site
`36H bas been substituted.
`52. The antibody of claim 30 wherein the residue at site
`39H has been substituted.
`53. The antibody of claim 30 wherein the residue at site
`tO 43H bas been substituted.
`54. The antibody of claim 30 wherein the residue at site
`45H has been substituted.
`55. The antibody of claim 30 wherein the residue at site
`69H has been substituted.
`56. The antibody of claim 30 wherein the residue at site
`70H bas been substituted.
`57. The antibody of claim 30 wherein the residue at site
`74H has been substituted.
`58. The antibody of claim 30 wherein the residue at site
`20 75H has been substituted.
`59. The antibody of claim 30 wherein the residue at site
`76H bas been substituted.
`60. The antibody of claim 30 wherein the residue at site
`78H has been substituted.
`61. The antibody of claim 30 wherein the residue at site
`92H has been substituted.
`62. A humanized antibody variable domain comprising
`non-human Complementarity Determining Region (CDR)
`amino acid residues which bind an antigen incorporated into
`30 a consensus human variable domain, and further comprising
`an amino acid substitution at a site selected from the group
`consisting of: 4L, 38L, 43L, 44L, 46L, 58L, 62L, 65L, 66L,
`67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H, 36H, 39H, 43H,
`45H, 69H, 70H, 74H, 75H, 76H, 78H and 92H, utilizing the
`35 numbering system set forth in Kabat.
`63. A humanized antibody which lacks immunogenicity
`compared to a non-human parent antibody upon repeated
`administration to a human patient in order to treat a chronic
`disease in that patient, wherein the humanized antibody
`40 comprises non-human Complementarity Determining
`Region (CDR) amino acid residues which bind an antigen
`incorporated into a human antibody variable domain, and
`further comprises an amino acid substitution at a site
`selected from the group consisting of: 4L, 38L, 43L, 44L,
`45 46L, 58L, 62L, 65L, 66L, 67L, 68L, 69L, 73L, 85L, 98L,
`2H, 4H, 36H, 39H, 43H, 45H, 69H, 70H, 74H, 75H, 76H,
`78H and 92H, utilizing the numbering system set forth in
`Kabat.
`64. A humanized variant of a non-human parent antibody
`so which binds an antigen and comprises a human variable
`domain comprising the most frequently occurring amino
`acid residues at each location in all human immunoglobulins
`of a human heavy chain immunoglobulin subgroup wherein
`amino acid residues forming Complementarity Determining
`55 Regions (CDRs) thereof comprise non-human antibody
`amino acid residues, and further comprises a Framework
`Region (FR) substitution where the substituted FR residue:
`(a) noncovalently binds antigen directly; (b) interacts with a
`CDR; (c) introduces a glycosylation site which affects the
`60 antigen binding or affinity of the antibody; or (d) participates
`in the Vc V H interface by affecting the proximity or orien(cid:173)
`tation of the V L and V H regions with respect to one another.
`65. The humanized variant of claim 63 which binds the
`antigen up to 3-fold more in the binding affinity than the
`65 parent antibody binds antigen.
`66. A humanized antibody heavy chain variable domain
`comprising non-human Complementarity Determining
`
`Board Ass gne
`
`BIOEPIS EX. 1095
`Page 254
`
`

`

`US 6,407,213 Bl
`
`10
`
`89
`Region (CDR) amino acid residues which bind antigen
`incorporated into a human antibody variable domain, and
`further comprising a Framework Region (FR) amino acid
`substitution at a site selected from the group consisting of:
`24H, 73H, 76H, 78H, and 93H, utilizing the numbering
`system set forth in Kabat.
`67. The humanized variable domain of claim 66 wherein
`the substituted residue is the residue found at the corre(cid:173)
`sponding location of the non-human antibody from which
`the non-human CDR amino acid residues are obtained.
`68. The humanized variable domain of claim 66 wherein
`no human Framework Region (FR) residue other than those
`set forth in the group bas been substituted.
`69. The humanized variable domain of claim 66 wherein
`the human antibody variable domain is a consensus human
`variable domain.
`70. The humanized variable domain of claim 66 wherein
`the residue at site 24H has been substituted.
`71. The humanized variable domain of claim 66 wherein
`the residue at site 73H has been substituted.
`72. The humanized variable domain of claim 66 wherein
`the residue at site 76H has been substituted.
`73. The humanized variable domain of claim 66 wherein
`the residue at site 78H has been substituted.
`74. The humanized variable domain of claim 66 wherein 25
`the residue at site 93H has been substituted.
`75. The humanized variable domain of claim 66 which
`further comprises an amino acid substitution at site 71H.
`76. The humanized variable domain of claim 66 which
`further comprises amino acid substitutions at sites 71H and 30
`73H.
`77. The humanized variable domain of claim 66 which
`further comprises amino acid substitutions at sites 71H, 73H
`and 78H.
`
`20
`
`90
`78. An antibody compnsmg the humanized variable
`domain of claim 66.
`79. A humanized variant of a non-human parent antibody
`which binds an antigen, wherein the humanized variant
`comprises Complementarity Determining Region (CDR)
`amino acid residues of the non-human parent antibody
`incorporated into a human antibody variable domain, and
`further comprises Framework Region (FR) substitutions at
`heavy chain positions 71H, 73H, 78H and 93H, utilizing the
`numbering system set forth in KabaL
`80. A humanized antibody variable domain comprising
`non-human Complementarity Determining Region (CDR)
`amino acid residues which bind an antigen incorporated into
`a human antibody variable domain, and further comprising
`a Framework Region (FR) amino acid substitution where the
`JS substituted FR residue:
`(a) noncovalently binds antigen directly;
`(b) interacts with a CDR; or
`(c) participates in the Yc V H interface by affecting the
`proximity or orientation of the V L and V n regions with
`respect to one another, and wherein the substituted FR
`residue is at a site selected from the group consisting of:
`4L, 38L, 43L, 44L, 58L, 62L, 65L, 66L, 67L, 68L, 69L,
`73L, 85L, 98L, 2H, 4H, 24H, 36H, 39H, 43H, 4SH,
`69H, 70H, 73H, 74H, 76H, 78H, 92H and 93H, utiliz(cid:173)
`ing the numbering system set forth in Kabat.
`81. The humanized variable domain of claim 80 wherein
`the substituted residue is the residue found at the corre(cid:173)
`sponding location of the non-human antibody from which
`the non-human CDR amino acid residues are obtained.
`82. The humanized variable domain of claim 80 wherein
`no human Framework Region (FR) residue other than those
`set forth in the group has been substituted.
`
`* * * * *
`
`Board Ass gne
`
`BIOEPIS EX. 1095
`Page 255
`
`

`

`UNITRD STATES PATENT AND TI~AI>EMAIU< OFFlCR
`CERTIFICATE OF CORRECTION
`
`I'A'I l~N 'I' NO.
`DATI:iD
`INVLlN'I'Ol{(S)
`
`: 6,407,21 :l tH
`:June 18, 2002
`: O~rter el al.
`
`l'age 1 t)f l
`
`It is certifi ed that error appears in the above-identified patent <~nd 1hat said Letters Patent is
`hereby corrected as shown below:
`
`Column 88.
`1 ,ine 63, t)lease delete "(13" and i11serl therefor-- 71} --.
`
`Signed and Sealed this
`
`'ll1ird Day of December, 2002
`
`I1\MES E. ROO AN
`fJireclor af 1.~~ Ut~if~<1 ,)tnl~s l'N~Jlf UJ>d Tnult:•nurA 01Jice
`
`Board Assigned Pag
`
`BIOEPIS EX. 1095
`Page 256
`
`

`

`DATE. FIL;ED: 05/28/2010
`DOCUMENT NO: 27
`
`PTOISB/05 (~)
`Approved for use lluougll 0713112006. OMB 055HI032
`U.S. Patent and Tr.>demari< Ollic:e. U.S. DEPARTME:.NT OF COMMERCE
`Under lhe Pa~ Reduction /ld of 1995. no pers<li\S ate reqWed to .espond !o a oolledion of inlonnallal unless ~ diSPlays a vaid OMS control number.
`
`UTILITY
`PATENT APPLICATION
`TRANSMITTAL
`'-.(Only for new nonprovlSional applialtions under 37 C.F.R. 1.53/b))
`
`Att...,ey Docket No.
`
`CARP0001·t12
`
`FirSt Inventor
`
`John R. Adair ot aL
`
`Tille
`
`HUMANISED ANTIBODIES
`
`Express Maill..abel No.
`
`EV146 601 565US
`
`(")
`~..- ~
`(0
`'o
`(/'~~
`:::>.;.,.
`d>C\,1
`'<:'-
`.,.... ..-
`
`!T-_
`~~.
`
`=
`
`-
`
`I
`
`APPUCATION ELEMENTS
`See MPEP chapter 600 r;oncemlng UIJ1/ty patent application contents.
`1. 1:81 Fee Transmittal Fonn (e.g~ PTO/SB/17)
`(Submit an otiginal and a duph'cate fOr fee pi'OC(Js.s/ng)
`2. 0
`Applicant claims small entity status.
`See 37 CFR 1.27.
`l2
`3. 1:81 Spec ification
`!Total Pages
`Both lhe claims and abstract must start on a new page
`(FeY inffltmiiiJon M the pml- """ngemMI, SM MPt:P 608.0I{b}}
`4. [81 Drawing(s) (35 U. S:C. 113)
`(Total Sheets 1ft
`
`I
`
`I
`
`[Tola/ Sheets ~ I
`5. Oath or Declaration
`a. 0 Newly executed (original or copy)
`b . t8J Copy from a prior application (37 CFR 1.63 (d))
`(for a continuation/divisional with Box 18 completed)
`1. 0 DELETION OF IM~t;;MIQ~S}
`Signed slat€1me n l attached deleting inventol(s)
`named in tna pnor appli<2tion, see 37 CFR
`1.63(d)(2) and 1.33(b).
`6.181 Application Data Sheet. See 37 CFR 1.76
`CD-ROM or CD-R in duplicate, large table or
`Computer Program {Appendix}
`0 Landscape Table on CD
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`7.0
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`' J•
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`ADDRESS TO:
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`P.O. Box 1450
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`ACCOMPANYING APPLICATIONS PARTS
`9.0 Assl9nment Papers (CO\/et sheet & document(s))
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`10.0
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`37 C.F.R. 3.73(b) Statement ~ Copy of Power of
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`11.0
`12.0
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`English Translation Document (if applicable)
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`Information Dlselosuro Statement (PTOISB/08 or PT~144S)
`0 Copies of foreign patent documents,
`publications & other Information
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`Preliminary Amendment and Request for Interference
`u nder 37 C.F.R. § 42.202
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`14. 1:81 Retum Receipt Postcard (MPEP 503)
`(Should be specifically itemized)
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`15. ~ Certified Copy of Priority Docume nt Was Recel\/ed In
`Parent Application Serial No. 07n43,329, Filed September 17,
`1991 (if foreign priority is claimed)
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`16. 0
`
`Nonpubllcation Request under 35 U.S.C. 122(b)(2)(B}(i).
`Applicant must attach form PTO/SB/35 or equi\lalent.
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`8. Nucleotide and/or Amino Acid Sequence Submission
`(If applicable, Items a. -c. 81'9 1'9qUired)
`a. Computer Readable Form (CRF)
`i. 0 Computer Readable Form (CRF)
`II. 181 Trans rer Request (37 CFR 1.821(e))
`b. Specification Sequence Listing on:
`I. 0 CD-ROM or CD-R (2 copies); or
`ii. 181 Paper Copy
`c. 181 Statements verifying Identity of above copie s
`18. If a CONTINUING APPLICATION. cfleck appropriate box, and SUpply the requisite Information lletow and in the first sent1311ce of the
`spec!fteafion following the litte, or in an Application Dala Sheet under 37 CFR 1. 76:
`J:ii1 Continuation
`of pnur AppliCation No. Serial No 08184fJ!59.. Flies! May 11 1997,
`(J ConUnuatil»ln·part (CIP)
`(J Oivlsianal
`which is a Cont lny;Won of Aog!lc.aiJon Strlal No 08J303 589 FUad Stptember 7 1994 now U.S 4 patent No 5 85! 1C)S. !!sued Januarv 12 1998 wh1ch Is a FDa
`Wc:~12Q~r ~nUDI!IUSl.O S!f. ~galhilti2D ~!dil ~ g7n43 ~~ fil~ SeQUtml!!r 17 J99j 8b!!JSigQst£2 ~DI~D I§ a 35 !.! :i ~ 371 N!Jioni!J ~east! Aeelfeitloa of
`lo tewtloN!I Apptleatlon No. PCT/GQ!0/020171 lnJernatiol!al Filing Date of DocomPtt 21· 1999, Which claim& priority So Great Brilain Application No. 8928874.0.
`Eil~ Dtte:l!I!!!i.E i!a :129.~. ill i!!RQl~l!!!gn§ iDcorDO!i1!$11l1: !Jfgnce her!! a In tbtir i!!!iretiK.
`·
`Examiner Mlnll Tam 8 . Davis
`Prior app/icaliotllnlormarion:
`Art U/111: 1642
`19. CORRESPONDENCE ADDRESS
`
`1 7 . ~
`Other: CORl£ of Change of Co11'eseond enca Address -
`Ageneatlon dated Deceml!er 2;!, 2002, f[Om ~121ication Serial No.
`08/8461658, Filed Mal£ 1, 19!1Z,
`
`~ The address associated wilh Custom&r Number
`
`1 34132
`
`I OR 0
`
`Correspondeoc:e address below
`
`Nam&
`
`Addtess
`
`City
`
`Counlly
`
`Signature
`
`I State I
`I Telephone
`I
`/1
`/()()...-{ g .I AA (9l -~""A_moate No .. amber 21, 2005
`'
`Registration No.
`Narru>
`Coreon Valko Trujillo {}
`135,718
`(Printlrvoe)
`(AIIomtJYIAgenl/
`"TW5 ODII6C1iOC\ Of lnformaDOn i$ t eQUtte<ll bY 37 a'R 1.53(bJ. The inf~ b; n:::quiA!d tO Ol»taln Of tetain a~~ by d'le pubk wtli;h B to file .and by thO USPTO CO ptCC:OS$) 11A apoJcatiOn.
`Conlld..,OOiily Is governed by 3$ U.S.C. 122 and 37 Cffll.11 .,-.~ 1.14. No C<>IIOdion b coOimaled 101o1<e 1~ ml• .-ro <llfrol;lote. lncllldlng golhurinv. po-NoQ. Olldcu...,;rtlnq 1McCIIIII>.....,
`· - - """'to,.. USPTO. 11me wtl vary~ upon lhe - a l """"' tv.y"""""""' on C.. . -o/- )'OU """'"" to C'""PieiD.,.. form .,.....,.. GU91Je51lcn:s fo< """"*"' Ol>io
`I»La'den. $houl<l bG r;:mt \o N 0\lef lnlo:matlcn Otf'il:tll', U.S. Pat.enl Vld "J'ra<<&mart ~ U.S, Oep.wnent ol COmn-oen:», P .O. Bcw 1450. AJ~Ill. VA 2'2313- tc.!O. DO NOT SEND FEES OR
`COMF'LETeo FORt.IS TOT.HIS AOORESS. SENO TO:- SlOp Pa .. nl AppllCII!On, Com-IIOf><lt lot Pa....,., P.O. DO>< 14$0, Aloxandl1o, VA 22)13-14$0.
`llyov--nceiii""""'IOiil>g 1110 fctm. COl J-B>)I>PfO-I>Jg,)OIJ<f-op<lon 2.
`
`Zip Code
`
`Email adrJtess
`
`Carter Exhibit 2002
`
`Board Assigned Pag
`
`BIOEPIS EX. 1095
`Page 257
`
`

`

`PTO/SBI17 ( 12-04v2)
`Approved for use tnrough 07131/2006. OMB 0651-0032
`U .S. Patent and Trademark Office: U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons ara required to respond to a collection of informatio n unless tt displays a vaUd OMB control number.
`
`~ r.
`Effecllve on 1 VOB/2004.
`~ ' Fee$ putsUanl 10 lhe ConsollcJated Appropriations Act. 2005 (H.R. 48 1 8).
`~
`c
`
`FEE TRANSMITTAL
`for FY 2005
`D Applicant daims small entity status. See 37 CFR 1.27
`
`\,.TOTALAMOUNTOFPAYMENT
`
`($) 1,000.00
`
`Complete If Known
`
`Application Number
`
`N01 Yet ~igned
`
`Fiting Date
`
`November 21, 2005
`
`First Named Inventor
`
`John R. Adair et al.
`
`Examiner Name
`
`N01 Yet Anigned
`
`Art Unit
`
`N01 Yet Assigned
`
`Attorney Docket No.
`
`CARP0001· t12
`
`METHOD OF PAYMENT (check all that apply)
`0 Check 0 Credit Card 0 M oney Order 0 None 0 Other (please identify) : - -- - - - - --
`- - - - --
`181 Deposit Acco unt Deposit Account Number: 50·1275
`Deposit Account Name: Cozen O'Connor. P.C.
`For the above-identified deposit account. the Director is hereby authorized to: (check all that apply)
`I2J Charge fee(s) indicated below
`0 Charge fee(s) indicated below, except for the filing fee
`I2J Charge any additional fee(s) or underpayments of fee(s)
`[8] Credit any overpayments
`Under 37 CFR 1.16 and 1.17
`WARNING: Information on this form may become public. Credit card lnfonnation shou ld not be Included on this form. Provide credit card
`lnfonnation and authorization on PT0.2038.
`FEE CALCULATION
`1. BASIC FILING, SEARCH, AND EXAMINATION FEES
`FILING FEES
`SEARCH FEES
`Small Entity
`Small Entity
`Fee($)
`Fee($)
`150
`250
`50
`100
`100
`150
`150
`250
`100
`0
`
`EXAMINATION FEES
`Small Entity
`Fee ($)
`100
`65
`80
`300
`0
`
`Fee($)
`200
`130
`160
`600
`0
`
`Fees Paid ($)
`$1 000 00
`
`Fee($)
`500
`100
`300
`500
`0
`
`Application Type Ett.ill
`Utility
`300
`200
`Design
`200
`Plant
`Reissue
`300
`Provisional
`200
`EXCESS CLAIM FEES
`2.
`Fee Description
`Each claim over 20 (including Reissues)
`Each independent claim over 3 (including Reissues)
`Multiple dependent claims
`Total Claims
`Extra Claims
`- 20 or HP= 00
`02
`X
`HP = highest number of total claims paid lor, If greater than 20.
`lndep. Claims
`Extra Claims
`Fee($)
`=
`x __
`01
`• 03 or HP= 00
`HP = highest number of independent claims paid for, if greater than 3.
`3. APPLICATION SIZE FEE
`If the speci fication and drawings exceed 100 sheets of paper (excluding electronically filed sequence or computer
`listings under 37 CFR I .52( e)), the application size fee due is $250 ($ 125 for small entity) for each additional 50
`sheets or fraction thereof. See 35 U .S.C . 41(a)(I)(G) and 37 CFR 1.16(s).
`Nymber of each additional 50 or fraction thereof
`Total Sheets Extra Sheets
`__ - __ =
`/50 =
`__ (round up to a whole number) x
`4 . OTHER FEE(S)
`Non· English Specification, $130 fee (no small entity discount)
`Other (e.g., late filing surcharge) :
`
`Fee Paid($)
`
`=
`
`Fee Paid($)
`
`Small Entity
`f!!LW
`ftt.W
`25
`50
`100
`200
`ISO
`360
`Multiple Dependent Claims
`Fee ($)
`Fee Paid ($)
`
`fu..W Fee Paid ($)
`=
`
`Fees Paid IS)
`
`SUBMinEDBY
`
`fl
`
`Signa tum
`
`A
`
`n
`
`35,718
`
`Telephone
`
`Doreen Yall<o TruJillo
`
`(}
`
`Date
`November ~. 2005
`This c:ollectlon ollnfonnahon is required by 37 CFR 1. 136. The inlormation is required to Obtain 0< retain a benefit by lhe publiC whiCh is to r~e (and bv the USPTO to piOCCI$$) an application.
`Confldentlalhy Is go.emad by 35 U.S.C. 122 and 37 CFR 1.14. This colectlon is estimated tO take 30 minuteS 10 complete. induding galhaling. povparing. and submitting Ole oomj)looted
`application fonn to lhe USPTO. Time will vary depending upon the individual case. Artt C<>mfTleRS on lhe amount ollime you require to oomplete this fonn and/or suggestions for reducing !his
`bunlen, shOUld be sent to tile cnief tnfonnation Offocer. U.S. Patent and Traclemall< Office, U.S. Department Of Commerce. P.O. BO>C 1450. Alel<andria. VA 22313·1450. DO NOT SEND FEES
`OR COMPLETED FORMS TO THIS ADDRESS. SEN D TO: COmmlaeloner fo< Patents, P.O. Box 1450, Aleundrla, VA 22313-1450.
`II )'OU n<10d B$Si$/1Jf1CIJ in completing !his /otm, CIJU 1-IWO·PT0-9199 (f-8Q0-786-9f99) 8fld sel«l Oplion 2.
`
`1
`
`Board Assigned Pag
`
`BIOEPIS EX. 1095
`Page 258
`
`

`

`PTO/SBI17 ( 12-04v2)
`Approved for use tnrough 07131/2006. OMB 0651-0032
`U .S. Patent and Trademark Office: U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons ara required to respond to a collection of informatio n unless tt displays a vaUd OMB control number.
`
`~ r.
`Effecllve on 1 VOB/2004.
`~ ' Fee$ putsUanl 10 lhe ConsollcJated Appropriations Act. 2005 (H.R. 48 1 8).
`~
`c
`
`FEE TRANSMITTAL
`for FY 2005
`D Applicant daims small entity status. See 37 CFR 1.27
`
`\,.TOTALAMOUNTOFPAYMENT
`
`($) 1,000.00
`
`Complete If Known
`
`Application Number
`
`N01 Yet ~igned
`
`Fiting Date
`
`November 21, 2005
`
`First Named Inventor
`
`John R. Adair et al.
`
`Examiner Name
`
`N01 Yet Anigned
`
`Art Unit
`
`N01 Yet Assigned
`
`Attorney Docket No.
`
`CARP0001· t12
`
`METHOD OF PAYMENT (check all that apply)
`0 Check 0 Credit Card 0 M oney Order 0 None 0 Other (please identify) : - -- - - - - --
`- - - - --
`181 Deposit Acco unt Deposit Account Number: 50·1275
`Deposit Account Name: Cozen O'Connor. P.C.
`For the above-identified deposit account. the Director is hereby authorized to: (check all that apply)
`I2J Charge fee(s) indicated below
`0 Charge fee(s) indicated below, except for the filing fee
`I2J Charge any additional fee(s) or underpayments of fee(s)
`[8] Credit any overpayments
`Under 37 CFR 1.16 and 1.17
`WARNING: Information on this form may become public. Credit card lnfonnation shou ld not be Included on this form. Provide credit card
`lnfonnation and authorization on PT0.2038.
`FEE CALCULATION
`1. BASIC FILING, SEARCH, AND EXAMINATION FEES
`FILING FEES
`SEARCH FEES
`Small Entity
`Small Entity
`Fee($)
`Fee($)
`150
`250
`50
`100
`100
`150
`150
`250
`100
`0
`
`EXAMINATION FEES
`Small Entity
`Fee ($)
`100
`65
`80
`300
`0
`
`Fee($)
`200
`130
`160
`600
`0
`
`Fees Paid ($)
`$1 000 00
`
`Fee($)
`500
`100
`300
`500
`0
`
`Application Type Ett.ill
`Utility
`300
`200
`Design
`200
`Plant
`Reissue
`300
`Provisional
`200
`EXCESS CLAIM FEES
`2.
`Fee Description
`Each claim over 20 (including Reissues)
`Each independent claim over 3 (including Reissues)
`Multiple dependent claims
`Total Claims
`Extra Claims
`- 20 or HP= 00
`02
`X
`HP = highest number of total claims paid lor, If greater than 20.
`lndep. Claims
`Extra Claims
`Fee($)
`=
`x __
`01
`• 03 or HP= 00
`HP = highest number of independent claims paid for, if greater than 3.
`3. APPLICATION SIZE FEE
`If the speci fication and drawings exceed 100 sheets of paper (excluding electronically filed sequence or computer
`listings under 37 CFR I .52( e)), the application size fee due is $250 ($ 125 for small entity) for each additional 50
`sheets or fraction thereof. See 35 U .S.C . 41(a)(I)(G) and 37 CFR 1.16(s).
`Nymber of each additional 50 or fraction thereof
`Total Sheets Extra Sheets
`__ - __ =
`/50 =
`__ (round up to a whole number) x
`4 . OTHER FEE(S)
`Non· English Specification, $130 fee (no small entity discount)
`Other (e.g., late filing surcharge) :
`
`Fee Paid($)
`
`=
`
`Fee Paid($)
`
`Small Entity
`f!!LW
`ftt.W
`25
`50
`100
`200
`ISO
`360
`Multiple Dependent Claims
`Fee ($)
`Fee Paid ($)
`
`fu..W Fee Paid ($)
`=
`
`Fees Paid IS)
`
`SUBMinEDBY
`
`fl
`
`Signa tum
`
`A
`
`n
`
`35,718
`
`Telephone
`
`Doreen Yall<o TruJillo
`
`(}
`
`Date
`November ~. 2005
`This c:ollectlon ollnfonnahon is required by 37 CFR 1. 136. The inlormation is required to Obtain 0< retain a benefit by lhe publiC whiCh is to r~e (and bv the USPTO to piOCCI$$) an application.
`Confldentlalhy Is go.emad by 35 U.S.C. 122 and 37 CFR 1.14. This colectlon is estimated tO take 30 minuteS 10 complete. induding galhaling. povparing. and submitting Ole oomj)looted
`application fonn to lhe USPTO. Time will vary depending upon the individual case. Artt C<>mfTleRS on lhe amount ollime you require to oomplete this fonn and/or suggestions for reducing !his
`bunlen, shOUld be sent to tile cnief tnfonnation Offocer. U.S. Patent and Traclemall< Office, U.S. Department Of Commerce. P.O. BO>C 1450. Alel<andria. VA 22313·1450. DO NOT SEND FEES
`OR COMPLETED FORMS TO THIS ADDRESS. SEN D TO: COmmlaeloner fo< Patents, P.O. Box 1450, Aleundrla, VA 22313-1450.
`II )'OU n<10d B$Si$/1Jf1CIJ in completing !his /otm, CIJU 1-IWO·PT0-9199 (f-8Q0-786-9f99) 8fld sel«l Oplion 2.
`