                         SEQUENCE LISTING

<110>  Lpath, Inc.
       Sabbadini, Roger
       Huxford, Tom
       Wojciak, Jon
 
<120>  ANTIBODY DESIGN USING ANTI-LIPID ANTIBODY CRYSTAL STRUCTURES

<130>  LPT-4000-PC

<140>  PCT/US09/66862
<141>  2009-12-04

<150>  61/120318
<151>  2008-12-05

<150>  61/155895
<151>  2009-02-26

<150>  61/231258
<151>  2009-08-04

<160>  36    

<170>  PatentIn version 3.5

<210>  1
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  1
atggratgga gckggrtctt tmtctt                                            26


<210>  2
<211>  21
<212>  DNA
<213>  Artificial sequence

<220>
<223>  primer

<400>  2
cagtggatag acagatgggg g                                                 21


<210>  3
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  3
cagtggatag accgatgggg c                                                 21


<210>  4
<211>  21
<212>  DNA
<213>  Artificial sequence

<220>
<223>  primer

<400>  4
cagtggatag actgatgggg g                                                 21


<210>  5
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  5
caagggatag acagatgggg c                                                 21


<210>  6
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  6
gtctctgatt ctagggca                                                     18


<210>  7
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  7
actggatggt gggaagatgg                                                   20


<210>  8
<211>  82
<212>  PRT
<213>  Mus musculus

<400>  8

Ala His Ser Asp Ala Val Lys Gly Ala Ser Val Lys Ser Cys Lys Val 
1               5                   10                  15      


Ser Gly Asp His Thr His Trp Met Lys Arg Gly Trp Gly Cys Ser Arg 
            20                  25                  30          


His Asp Thr Lys Tyr Asn Met Arg Gly Lys Ala Thr Thr Ala Asp Lys 
        35                  40                  45              


Ser Ser Thr Thr Ala Tyr Val Asn Ser Thr Asp Ser Ala Val Tyr Cys 
    50                  55                  60                  


Ala Arg Gly Gly Tyr Gly Ser Thr Trp Asp Trp Gly Gly Thr Thr Thr 
65                  70                  75                  80  


Val Ser 
        


<210>  9
<211>  66
<212>  PRT
<213>  Mus musculus

<400>  9

Thr Thr Val Thr Ser Ala Ser Ser Met Ala Gly Lys Val Thr Arg Cys 
1               5                   10                  15      


Thr Thr Thr Asp Asp Asp Asp Met Asn Trp Lys Gly Asn Ser Gly Asn 
            20                  25                  30          


Arg Gly Val Ser Arg Ser Ser Ser Gly Tyr Gly Thr Asp Thr Asn Met 
        35                  40                  45              


Ser Asp Val Ala Asp Tyr Tyr Cys Ser Asp Asn Thr Gly Ser Gly Thr 
    50                  55                  60                  


Lys Lys 
65      


<210>  10
<211>  11
<212>  PRT
<213>  Mus musculus

<400>  10

Ile Thr Thr Thr Asp Ile Asp Asp Asp Met Asn 
1               5                   10      


<210>  11
<211>  7
<212>  PRT
<213>  Mus musculus

<400>  11

Glu Gly Asn Ile Leu Arg Pro 
1               5           


<210>  12
<211>  9
<212>  PRT
<213>  Mus musculus

<400>  12

Leu Gln Ser Asp Asn Leu Pro Phe Thr 
1               5                   


<210>  13
<211>  5
<212>  PRT
<213>  Mus musculus

<400>  13

Asp His Thr Ile His 
1               5   


<210>  14
<211>  17
<212>  PRT
<213>  Mus musculus

<400>  14

Cys Ile Ser Pro Arg His Asp Ile Thr Lys Tyr Asn Glu Met Phe Arg 
1               5                   10                  15      


Gly 
    


<210>  15
<211>  12
<212>  PRT
<213>  Mus musculus

<400>  15

Gly Gly Phe Tyr Gly Ser Thr Ile Trp Phe Asp Phe 
1               5                   10          


<210>  16
<211>  147
<212>  PRT
<213>  Mus musculus

<400>  16

Met Gly Ser Thr Ala Ile Leu Ala Leu Leu Leu Ala Val Leu Gln Gly 
1               5                   10                  15      


Val Cys Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
            20                  25                  30          


Pro Gly Glu Ser Leu Lys Ile Ser Cys Gln Ser Phe Gly Tyr Ile Phe 
        35                  40                  45              


Ile Asp His Thr Ile His Trp Val Arg Gln Met Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Met Gly Cys Ile Ser Pro Arg His Asp Ile Thr Lys Tyr Asn 
65                  70                  75                  80  


Glu Met Phe Arg Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ser Ser 
                85                  90                  95      


Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met 
            100                 105                 110         


Tyr Phe Cys Ala Arg Gly Gly Phe Tyr Gly Ser Thr Ile Trp Phe Asp 
        115                 120                 125             


Phe Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys 
    130                 135                 140                 


Gly Pro Ser 
145         


<210>  17
<211>  134
<212>  PRT
<213>  Mus musculus

<400>  17

Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp 
1               5                   10                  15      


Leu Pro Gly Ala Arg Cys Glu Thr Thr Leu Thr Gln Ser Pro Ser Phe 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ile Thr Thr 
        35                  40                  45              


Thr Asp Ile Asp Asp Asp Met Asn Trp Tyr Gln Gln Glu Pro Gly Lys 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr Glu Gly Asn Ile Leu Arg Pro Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
                85                  90                  95      


Ile Ser Lys Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln 
            100                 105                 110         


Ser Asp Asn Leu Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
        115                 120                 125             


Lys Arg Glu Trp Ile Pro 
    130                 


<210>  18
<211>  17
<212>  PRT
<213>  Mus musculus

<400>  18

Ala Ile Ser Pro Arg His Asp Ile Thr Lys Tyr Asn Glu Met Phe Arg 
1               5                   10                  15      


Gly 
    


<210>  19
<211>  140
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  19

Met Glu Trp Ser Trp Val Phe Leu Phe Phe Leu Ser Val Thr Thr Gly 
1               5                   10                  15      


Val His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
            20                  25                  30          


Pro Gly Glu Ser Leu Lys Ile Ser Cys Gln Ser Phe Gly Tyr Ile Phe 
        35                  40                  45              


Ile Asp His Thr Ile His Trp Met Arg Gln Met Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Met Gly Ala Ile Ser Pro Arg His Asp Ile Thr Lys Tyr Asn 
65                  70                  75                  80  


Glu Met Phe Arg Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ser Ser 
                85                  90                  95      


Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met 
            100                 105                 110         


Tyr Phe Cys Ala Arg Gly Gly Phe Tyr Gly Ser Thr Ile Trp Phe Asp 
        115                 120                 125             


Phe Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 
    130                 135                 140 


<210>  20
<211>  127
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  20

Met Ser Val Pro Thr Gln Val Leu Gly Leu Leu Leu Leu Trp Leu Thr 
1               5                   10                  15      


Asp Ala Arg Cys Glu Thr Thr Val Thr Gln Ser Pro Ser Phe Leu Ser 
            20                  25                  30          


Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ile Thr Thr Thr Asp 
        35                  40                  45              


Ile Asp Asp Asp Met Asn Trp Phe Gln Gln Glu Pro Gly Lys Ala Pro 
    50                  55                  60                  


Lys Leu Leu Ile Ser Glu Gly Asn Ile Leu Arg Pro Gly Val Pro Ser 
65                  70                  75                  80  


Arg Phe Ser Ser Ser Gly Tyr Gly Thr Asp Phe Thr Leu Thr Ile Ser 
                85                  90                  95      


Lys Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Ser Asp 
            100                 105                 110         


Asn Leu Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
        115                 120                 125         


<210>  21
<211>  435
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  21
aagcttgccg ccaccatgga atggagctgg gtgttcctgt tctttctgtc cgtgaccaca       60

ggcgtgcatt ctgaggtgca gctggtgcag tctggagcag aggtgaaaaa gcccggggag      120

tctctgaaga tctcctgtca gagttttgga tacatcttta tcgaccatac tattcactgg      180

atgcgccaga tgcccgggca aggcctggag tggatggggg ctatttctcc cagacatgat      240

attactaaat acaatgagat gttcaggggc caggtcacca tctcagccga caagtccagc      300

agcaccgcct acttgcagtg gagcagcctg aaggcctcgg acaccgccat gtatttctgt      360

gcgagagggg ggttctacgg tagtactatc tggtttgact tttggggcca agggacaatg      420

gtcaccgtct cttca                                                       435


<210>  22
<211>  396
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  22
aagcttgccg ccaccatgtc tgtgcctacc caggtgctgg gactgctgct gctgtggctg       60

acagacgccc gctgtgaaac gacagtgacg cagtctccat ccttcctgtc tgcatctgta      120

ggagacagag tcaccatcac ttgcataacc accactgata ttgatgatga tatgaactgg      180

ttccagcagg aaccagggaa agcccctaag ctcctgatct ccgaaggcaa tattcttcgt      240

cctggggtcc catcaagatt cagcagcagt ggatatggca cagatttcac tctcaccatc      300

agcaaattgc agcctgaaga ttttgcaact tattactgtt tgcagagtga taacttacca      360

ttcactttcg gccaagggac caagctggag atcaaa                                396


<210>  23
<211>  1428
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  23
aagcttgccg ccaccatgga atggagctgg gtgttcctgt tctttctgtc cgtgaccaca       60

ggcgtgcatt ctgaggtgca gctggtgcag tctggagcag aggtgaaaaa gcccggggag      120

tctctgaaga tctcctgtca gagttttgga tacatcttta tcgaccatac tattcactgg      180

atgcgccaga tgcccgggca aggcctggag tggatggggg ctatttctcc cagacatgat      240

attactaaat acaatgagat gttcaggggc caggtcacca tctcagccga caagtccagc      300

agcaccgcct acttgcagtg gagcagcctg aaggcctcgg acaccgccat gtatttctgt      360

gcgagagggg ggttctacgg tagtactatc tggtttgact tttggggcca agggacaatg      420

gtcaccgtct cttcagcctc caccaagggc ccatcggtct tccccctggc accctcctcc      480

aagagcacct ctgggggcac agcggccctg ggctgcctgg tcaaggacta cttccccgaa      540

ccggtgacgg tgtcgtggaa ctcaggcgcc ctgaccagcg gcgtgcacac cttcccggct      600

gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcagc      660

ttgggcaccc agacctacat ctgcaacgtg aatcacaagc ccagcaacac caaggtggac      720

aagagagttg agcccaaatc ttgtgacaaa actcacacat gcccaccgtg cccagcacct      780

gaactcctgg ggggaccgtc agtcttcctc ttccccccaa aacccaagga caccctcatg      840

atctcccgga cccctgaggt cacatgcgtg gtggtggacg tgagccacga agaccctgag      900

gtcaagttca actggtacgt ggacggcgtg gaggtgcata atgccaagac aaagccgcgg      960

gaggagcagt acaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac     1020

tggctgaatg gcaaggagta caagtgcaag gtctccaaca aagccctccc agcccccatc     1080

gagaaaacca tctccaaagc caaagggcag ccccgagaac cacaggtgta caccctgccc     1140

ccatcccggg aggagatgac caagaaccag gtcagcctga cctgcctggt caaaggcttc     1200

tatcccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag     1260

accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctatagcaa gctcaccgtg     1320

gacaagagca ggtggcagca ggggaacgtc ttctcatgct ccgtgatgca tgaggctctg     1380

cacaaccact acacgcagaa gagcctctcc ctgtctccgg gtaaatag                  1428


<210>  24
<211>  455
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  24

Met Glu Trp Ser Trp Val Phe Leu Phe Phe Leu Ser Val Thr Thr Gly 
1               5                   10                  15      


Val His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
            20                  25                  30          


Pro Gly Glu Ser Leu Lys Ile Ser Cys Gln Ser Phe Gly Tyr Ile Phe 
        35                  40                  45              


Ile Asp His Thr Ile His Trp Met Arg Gln Met Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Met Gly Ala Ile Ser Pro Arg His Asp Ile Thr Lys Tyr Asn 
65                  70                  75                  80  


Glu Met Phe Arg Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ser Ser 
                85                  90                  95      


Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met 
            100                 105                 110         


Tyr Phe Cys Ala Arg Gly Gly Phe Tyr Gly Ser Thr Ile Trp Phe Asp 
        115                 120                 125             


Phe Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys 
    130                 135                 140                 


Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 
145                 150                 155                 160 


Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 
                165                 170                 175     


Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
            180                 185                 190         


Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
        195                 200                 205             


Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 
    210                 215                 220                 


Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Ala Pro 
225                 230                 235                 240 


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                245                 250                 255     


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
            260                 265                 270         


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
        275                 280                 285             


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
    290                 295                 300                 


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
305                 310                 315                 320 


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                325                 330                 335     


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
            340                 345                 350         


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
        355                 360                 365             


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
    370                 375                 380                 


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
385                 390                 395                 400 


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                405                 410                 415     


Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
            420                 425                 430         


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
        435                 440                 445             


Leu Ser Leu Ser Pro Gly Lys 
    450                 455 


<210>  25
<211>  720
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  25
aagcttgccg ccaccatgtc tgtgcctacc caggtgctgg gactgctgct gctgtggctg       60

acagacgccc gctgtgaaac gacagtgacg cagtctccat ccttcctgtc tgcatctgta      120

ggagacagag tcaccatcac ttgcataacc accactgata ttgatgatga tatgaactgg      180

ttccagcagg aaccagggaa agcccctaag ctcctgatct ccgaaggcaa tattcttcgt      240

cctggggtcc catcaagatt cagcagcagt ggatatggca cagatttcac tctcaccatc      300

agcaaattgc agcctgaaga ttttgcaact tattactgtt tgcagagtga taacttacca      360

ttcactttcg gccaagggac caagctggag atcaaacgta cggtggctgc accatctgtc      420

ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg      480

ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa      540

tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc      600

agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa      660

gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgttag      720


<210>  26
<211>  234
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  26

Met Ser Val Pro Thr Gln Val Leu Gly Leu Leu Leu Leu Trp Leu Thr 
1               5                   10                  15      


Asp Ala Arg Cys Glu Thr Thr Val Thr Gln Ser Pro Ser Phe Leu Ser 
            20                  25                  30          


Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ile Thr Thr Thr Asp 
        35                  40                  45              


Ile Asp Asp Asp Met Asn Trp Phe Gln Gln Glu Pro Gly Lys Ala Pro 
    50                  55                  60                  


Lys Leu Leu Ile Ser Glu Gly Asn Ile Leu Arg Pro Gly Val Pro Ser 
65                  70                  75                  80  


Arg Phe Ser Ser Ser Gly Tyr Gly Thr Asp Phe Thr Leu Thr Ile Ser 
                85                  90                  95      


Lys Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Ser Asp 
            100                 105                 110         


Asn Leu Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
        115                 120                 125             


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
    130                 135                 140                 


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
145                 150                 155                 160 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
                165                 170                 175     


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
            180                 185                 190         


Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
        195                 200                 205             


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
    210                 215                 220                 


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 


<210>  27
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  27

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      


Ser Leu Lys Ile Ser Cys Gln Ser Phe Gly Tyr Ile Phe Ile Asp His 
            20                  25                  30          


Thr Ile His Trp Met Arg Gln Met Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Ala Ile Ser Pro Arg His Asp Ile Thr Lys Tyr Asn Glu Met Phe 
    50                  55                  60                  


Arg Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Phe Cys 
                85                  90                  95      


Ala Arg Gly Gly Phe Tyr Gly Ser Thr Ile Trp Phe Asp Phe Trp Gly 
            100                 105                 110         


Gln Gly Thr Met Val Thr Val Ser Ser 
        115                 120     


<210>  28
<211>  363
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  28
gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaagatc       60

tcctgtcaga gttttggata catctttatc gaccatacta ttcactggat gcgccagatg      120

cccgggcaag gcctggagtg gatgggggct atttctccca gacatgatat tactaaatac      180

aatgagatgt tcaggggcca ggtcaccatc tcagccgaca agtccagcag caccgcctac      240

ttgcagtgga gcagcctgaa ggcctcggac accgccatgt atttctgtgc gagagggggg      300

ttctacggta gtactatctg gtttgacttt tggggccaag ggacaatggt caccgtctct      360

tca                                                                    363


<210>  29
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  29

Glu Thr Thr Val Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Ile Thr Thr Thr Asp Ile Asp Asp Asp 
            20                  25                  30          


Met Asn Trp Phe Gln Gln Glu Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Ser Glu Gly Asn Ile Leu Arg Pro Gly Val Pro Ser Arg Phe Ser Ser 
    50                  55                  60                  


Ser Gly Tyr Gly Thr Asp Phe Thr Leu Thr Ile Ser Lys Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Ser Asp Asn Leu Pro Phe 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  30
<211>  321
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  30
gaaacgacag tgacgcagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc       60

atcacttgca taaccaccac tgatattgat gatgatatga actggttcca gcaggaacca      120

gggaaagccc ctaagctcct gatctccgaa ggcaatattc ttcgtcctgg ggtcccatca      180

agattcagca gcagtggata tggcacagat ttcactctca ccatcagcaa attgcagcct      240

gaagattttg caacttatta ctgtttgcag agtgataact taccattcac tttcggccaa      300

gggaccaagc tggagatcaa a                                                321


<210>  31
<211>  451
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  31

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      


Ser Leu Lys Ile Ser Cys Gln Ser Phe Gly Tyr Ile Phe Ile Asp His 
            20                  25                  30          


Thr Ile His Trp Met Arg Gln Met Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Ala Ile Ser Pro Arg His Asp Ile Thr Lys Tyr Asn Glu Met Phe 
    50                  55                  60                  


Arg Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Phe Cys 
                85                  90                  95      


Ala Arg Gly Gly Phe Tyr Gly Ser Thr Ile Trp Phe Asp Phe Trp Gly 
            100                 105                 110         


Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             


Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
    130                 135                 140                 


Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
145                 150                 155                 160 


Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                165                 170                 175     


Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         


Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
        195                 200                 205             


Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 
    210                 215                 220                 


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
225                 230                 235                 240 


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                245                 250                 255     


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
            260                 265                 270         


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
        275                 280                 285             


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
    290                 295                 300                 


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
305                 310                 315                 320 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                325                 330                 335     


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
            340                 345                 350         


Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
        355                 360                 365             


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
    370                 375                 380                 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
385                 390                 395                 400 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                405                 410                 415     


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
            420                 425                 430         


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
        435                 440                 445             


Pro Gly Lys 
    450     


<210>  32
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  32

Glu Thr Thr Val Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Ile Thr Thr Thr Asp Ile Asp Asp Asp 
            20                  25                  30          


Met Asn Trp Phe Gln Gln Glu Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Ser Glu Gly Asn Ile Leu Arg Pro Gly Val Pro Ser Arg Phe Ser Ser 
    50                  55                  60                  


Ser Gly Tyr Gly Thr Asp Phe Thr Leu Thr Ile Ser Lys Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Ser Asp Asn Leu Pro Phe 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  33
<211>  1356
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  33
gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaagatc       60

tcctgtcaga gttttggata catctttatc gaccatacta ttcactggat gcgccagatg      120

cccgggcaag gcctggagtg gatgggggct atttctccca gacatgatat tactaaatac      180

aatgagatgt tcaggggcca ggtcaccatc tcagccgaca agtccagcag caccgcctac      240

ttgcagtgga gcagcctgaa ggcctcggac accgccatgt atttctgtgc gagagggggg      300

ttctacggta gtactatctg gtttgacttt tggggccaag ggacaatggt caccgtctct      360

tcagcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct      420

gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg      480

tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc      540

tcaggactct actccctcag cagcgtggtg accgtgccct ccagcagctt gggcacccag      600

acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gagagttgag      660

cccaaatctt gtgacaaaac tcacacatgc ccaccgtgcc cagcacctga actcctgggg      720

ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc      780

cctgaggtca catgcgtggt ggtggacgtg agccacgaag accctgaggt caagttcaac      840

tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagtac      900

aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaatggc      960

aaggagtaca agtgcaaggt ctccaacaaa gccctcccag cccccatcga gaaaaccatc     1020

tccaaagcca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggag     1080

gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta tcccagcgac     1140

atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc     1200

gtgctggact ccgacggctc cttcttcctc tatagcaagc tcaccgtgga caagagcagg     1260

tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac     1320

acgcagaaga gcctctccct gtctccgggt aaatag                               1356


<210>  34
<211>  645
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  34
gaaacgacag tgacgcagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc       60

atcacttgca taaccaccac tgatattgat gatgatatga actggttcca gcaggaacca      120

gggaaagccc ctaagctcct gatctccgaa ggcaatattc ttcgtcctgg ggtcccatca      180

agattcagca gcagtggata tggcacagat ttcactctca ccatcagcaa attgcagcct      240

gaagattttg caacttatta ctgtttgcag agtgataact taccattcac tttcggccaa      300

gggaccaagc tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca      360

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat      420

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag      480

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg      540

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc      600

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag                      645


<210>  35
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  35

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      


Ser Leu Lys Ile Ser Cys Gln Ser Phe Gly Tyr Ile Phe Ile Asp His 
            20                  25                  30          


Thr Ile His Trp Met Arg Gln Met Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Ala Ile Ser Pro Arg His Asp Ile Thr Lys Tyr Asn Glu Met Phe 
    50                  55                  60                  


Arg Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Phe Cys 
                85                  90                  95      


Ala Arg Gly Gly Phe Tyr Gly Ser Thr Ile Trp Phe Asp Phe Trp Gly 
            100                 105                 110         


Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             


Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
    130                 135                 140                 


Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
145                 150                 155                 160 


Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                165                 170                 175     


Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         


Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
        195                 200                 205             


Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 
    210                 215                 220                 


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
225                 230                 235                 240 


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                245                 250                 255     


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
            260                 265                 270         


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
        275                 280                 285             


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
    290                 295                 300                 


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
305                 310                 315                 320 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                325                 330                 335     


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
            340                 345                 350         


Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
        355                 360                 365             


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
    370                 375                 380                 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
385                 390                 395                 400 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                405                 410                 415     


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
            420                 425                 430         


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
        435                 440                 445             


Pro Gly 
    450 


<210>  36
<211>  1959
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody sequence

<400>  36
gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaagatc       60

tcctgtcaga gttttggata catctttatc gaccatacta ttcactggat gcgccagatg      120

cccgggcaag gcctggagtg gatgggggct atttctccca gacatgatat tactaaatac      180

aatgagatgt tcaggggcca ggtcaccatc tcagccgaca agtccagcag caccgcctac      240

ttgcagtgga gcagcctgaa ggcctcggac accgccatgt atttctgtgc gagagggggg      300

ttctacggta gtactatctg gtttgacttt tggggccaag ggacaatggt caccgtctct      360

tcagcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct      420

gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg      480

tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc      540

tcaggactct actccctcag cagcgtggtg accgtgccct ccagcagctt gggcacccag      600

acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gagagttggt      660

gagaggccag cacagggagg gagggtgtct gctggaagcc aggctcagcg ctcctgcctg      720

gacgcatccc ggctatgcag tcccagtcca gggcagcaag gcaggccccg tctgcctctt      780

cacccggagg cctctgcccg ccccactcat gctcagggag agggtcttct ggctttttcc      840

ccaggctctg ggcaggcaca ggctaggtgc ccctaaccca ggccctgcac acaaaggggc      900

aggtgctggg ctcagacctg ccaagagcca tatccgggag gaccctgccc ctgacctaag      960

cccaccccaa aggccaaact ctccactccc tcagctcgga caccttctct cctcccagat     1020

tccagtaact cccaatcttc tctctgcaga gcccaaatct tgtgacaaaa ctcacacatg     1080

cccaccgtgc ccaggtaagc cagcccaggc ctcgccctcc agctcaaggc gggacaggtg     1140

ccctagagta gcctgcatcc agggacaggc cccagccggg tgctgacacg tccacctcca     1200

tctcttcctc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc cccccaaaac     1260

ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga     1320

gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg     1380

ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgtgtggtc agcgtcctca     1440

ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag     1500

ccctcccagc ccccatcgag aaaaccatct ccaaagccaa aggtgggacc cgtggggtgc     1560

gagggccaca tggacagagg ccggctcggc ccaccctctg ccctgagagt gaccgctgta     1620

ccaacctctg tccctacagg gcagccccga gaaccacagg tgtacaccct gcccccatcc     1680

cgggaggaga tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc     1740

agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg     1800

cctcccgtgc tggactccga cggctccttc ttcctctata gcaagctcac cgtggacaag     1860

agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac     1920

cactacacgc agaagagcct ctccctgtct ccgggttag                            1959


