                              Sequence Listing

<110> GENENTECH, INC.
      GENNARO, LYNN A.
      KAO, YUNG-HSIANG
      ZHANG, YONGHUA

<120> PERTUZUMAB VARIANTS AND EVALUATION THEREOF

<130> P5584R1-WO

<141> 2014-04-15

<150> US 61/812,603
<151> 2013-04-16

<160> 24

<210> 1
<211> 195
<212> PRT
<213> Homo sapiens

<400> 1
 Thr Gln Val Cys Thr Gly Thr Asp Met Lys Leu Arg Leu Pro Ala
   1               5                  10                  15

 Ser Pro Glu Thr His Leu Asp Met Leu Arg His Leu Tyr Gln Gly
                  20                  25                  30

 Cys Gln Val Val Gln Gly Asn Leu Glu Leu Thr Tyr Leu Pro Thr
                  35                  40                  45

 Asn Ala Ser Leu Ser Phe Leu Gln Asp Ile Gln Glu Val Gln Gly
                  50                  55                  60

 Tyr Val Leu Ile Ala His Asn Gln Val Arg Gln Val Pro Leu Gln
                  65                  70                  75

 Arg Leu Arg Ile Val Arg Gly Thr Gln Leu Phe Glu Asp Asn Tyr
                  80                  85                  90

 Ala Leu Ala Val Leu Asp Asn Gly Asp Pro Leu Asn Asn Thr Thr
                  95                 100                 105

 Pro Val Thr Gly Ala Ser Pro Gly Gly Leu Arg Glu Leu Gln Leu
                 110                 115                 120

 Arg Ser Leu Thr Glu Ile Leu Lys Gly Gly Val Leu Ile Gln Arg
                 125                 130                 135

 Asn Pro Gln Leu Cys Tyr Gln Asp Thr Ile Leu Trp Lys Asp Ile
                 140                 145                 150

 Phe His Lys Asn Asn Gln Leu Ala Leu Thr Leu Ile Asp Thr Asn
                 155                 160                 165

 Arg Ser Arg Ala Cys His Pro Cys Ser Pro Met Cys Lys Gly Ser
                 170                 175                 180

 Arg Cys Trp Gly Glu Ser Ser Glu Asp Cys Gln Ser Leu Thr Arg
                 185                 190                 195

<210> 2
<211> 124
<212> PRT
<213> Homo sapiens

<400> 2
 Thr Val Cys Ala Gly Gly Cys Ala Arg Cys Lys Gly Pro Leu Pro
   1               5                  10                  15

 Thr Asp Cys Cys His Glu Gln Cys Ala Ala Gly Cys Thr Gly Pro
                  20                  25                  30

 Lys His Ser Asp Cys Leu Ala Cys Leu His Phe Asn His Ser Gly
                  35                  40                  45

 Ile Cys Glu Leu His Cys Pro Ala Leu Val Thr Tyr Asn Thr Asp
                  50                  55                  60

 Thr Phe Glu Ser Met Pro Asn Pro Glu Gly Arg Tyr Thr Phe Gly
                  65                  70                  75

 Ala Ser Cys Val Thr Ala Cys Pro Tyr Asn Tyr Leu Ser Thr Asp
                  80                  85                  90

 Val Gly Ser Cys Thr Leu Val Cys Pro Leu His Asn Gln Glu Val
                  95                 100                 105

 Thr Ala Glu Asp Gly Thr Gln Arg Cys Glu Lys Cys Ser Lys Pro
                 110                 115                 120

 Cys Ala Arg Val
                

<210> 3
<211> 169
<212> PRT
<213> Homo sapiens

<400> 3
 Cys Tyr Gly Leu Gly Met Glu His Leu Arg Glu Val Arg Ala Val
   1               5                  10                  15

 Thr Ser Ala Asn Ile Gln Glu Phe Ala Gly Cys Lys Lys Ile Phe
                  20                  25                  30

 Gly Ser Leu Ala Phe Leu Pro Glu Ser Phe Asp Gly Asp Pro Ala
                  35                  40                  45

 Ser Asn Thr Ala Pro Leu Gln Pro Glu Gln Leu Gln Val Phe Glu
                  50                  55                  60

 Thr Leu Glu Glu Ile Thr Gly Tyr Leu Tyr Ile Ser Ala Trp Pro
                  65                  70                  75

 Asp Ser Leu Pro Asp Leu Ser Val Phe Gln Asn Leu Gln Val Ile
                  80                  85                  90

 Arg Gly Arg Ile Leu His Asn Gly Ala Tyr Ser Leu Thr Leu Gln
                  95                 100                 105

 Gly Leu Gly Ile Ser Trp Leu Gly Leu Arg Ser Leu Arg Glu Leu
                 110                 115                 120

 Gly Ser Gly Leu Ala Leu Ile His His Asn Thr His Leu Cys Phe
                 125                 130                 135

 Val His Thr Val Pro Trp Asp Gln Leu Phe Arg Asn Pro His Gln
                 140                 145                 150

 Ala Leu Leu His Thr Ala Asn Arg Pro Glu Asp Glu Cys Val Gly
                 155                 160                 165

 Glu Gly Leu Ala
                

<210> 4
<211> 142
<212> PRT
<213> Homo sapiens

<400> 4
 Cys His Gln Leu Cys Ala Arg Gly His Cys Trp Gly Pro Gly Pro
   1               5                  10                  15

 Thr Gln Cys Val Asn Cys Ser Gln Phe Leu Arg Gly Gln Glu Cys
                  20                  25                  30

 Val Glu Glu Cys Arg Val Leu Gln Gly Leu Pro Arg Glu Tyr Val
                  35                  40                  45

 Asn Ala Arg His Cys Leu Pro Cys His Pro Glu Cys Gln Pro Gln
                  50                  55                  60

 Asn Gly Ser Val Thr Cys Phe Gly Pro Glu Ala Asp Gln Cys Val
                  65                  70                  75

 Ala Cys Ala His Tyr Lys Asp Pro Pro Phe Cys Val Ala Arg Cys
                  80                  85                  90

 Pro Ser Gly Val Lys Pro Asp Leu Ser Tyr Met Pro Ile Trp Lys
                  95                 100                 105

 Phe Pro Asp Glu Glu Gly Ala Cys Gln Pro Cys Pro Ile Asn Cys
                 110                 115                 120

 Thr His Ser Cys Val Asp Leu Asp Asp Lys Gly Cys Pro Ala Glu
                 125                 130                 135

 Gln Arg Ala Ser Pro Leu Thr
                 140        

<210> 5
<211> 107
<212> PRT
<213> Mus musculus

<400> 5
 Asp Thr Val Met Thr Gln Ser His Lys Ile Met Ser Thr Ser Val
   1               5                  10                  15

 Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser
                  20                  25                  30

 Ile Gly Val Ala Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Lys
                  35                  40                  45

 Leu Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Thr Gly Val Pro Asp
                  50                  55                  60

 Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile
                  65                  70                  75

 Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln
                  80                  85                  90

 Tyr Tyr Ile Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu
                  95                 100                 105

 Ile Lys
        

<210> 6
<211> 119
<212> PRT
<213> Mus musculus

<400> 6
 Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly
   1               5                  10                  15

 Thr Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr
                  20                  25                  30

 Asp Tyr Thr Met Asp Trp Val Lys Gln Ser His Gly Lys Ser Leu
                  35                  40                  45

 Glu Trp Ile Gly Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr
                  50                  55                  60

 Asn Gln Arg Phe Lys Gly Lys Ala Ser Leu Thr Val Asp Arg Ser
                  65                  70                  75

 Ser Arg Ile Val Tyr Met Glu Leu Arg Ser Leu Thr Phe Glu Asp
                  80                  85                  90

 Thr Ala Val Tyr Tyr Cys Ala Arg Asn Leu Gly Pro Ser Phe Tyr
                  95                 100                 105

 Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
                 110                 115                

<210> 7
<211> 107
<212> PRT
<213> Artificial Sequence

<220>
<223> Sequence is synthesized.

<400> 7
 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
   1               5                  10                  15

 Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Ser
                  20                  25                  30

 Ile Gly Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys
                  35                  40                  45

 Leu Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Thr Gly Val Pro Ser
                  50                  55                  60

 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
                  65                  70                  75

 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
                  80                  85                  90

 Tyr Tyr Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu
                  95                 100                 105

 Ile Lys
        

<210> 8
<211> 119
<212> PRT
<213> Artificial Sequence

<220>
<223> Sequence is synthesized.

<400> 8
 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
   1               5                  10                  15

 Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr
                  20                  25                  30

 Asp Tyr Thr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
                  35                  40                  45

 Glu Trp Val Ala Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr
                  50                  55                  60

 Asn Gln Arg Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Arg Ser
                  65                  70                  75

 Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
                  80                  85                  90

 Thr Ala Val Tyr Tyr Cys Ala Arg Asn Leu Gly Pro Ser Phe Tyr
                  95                 100                 105

 Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
                 110                 115                

<210> 9
<211> 107
<212> PRT
<213> Artificial Sequence

<220>
<223> Sequence is synthesized.

<400> 9
 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
   1               5                  10                  15

 Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser
                  20                  25                  30

 Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys
                  35                  40                  45

 Leu Leu Ile Tyr Ala Ala Ser Ser Leu Glu Ser Gly Val Pro Ser
                  50                  55                  60

 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
                  65                  70                  75

 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
                  80                  85                  90

 Tyr Asn Ser Leu Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu
                  95                 100                 105

 Ile Lys
        

<210> 10
<211> 119
<212> PRT
<213> Artificial Sequence

<220>
<223> Sequence is synthesized.

<400> 10
 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
   1               5                  10                  15

 Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
                  20                  25                  30

 Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
                  35                  40                  45

 Glu Trp Val Ala Val Ile Ser Gly Asp Gly Gly Ser Thr Tyr Tyr
                  50                  55                  60

 Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
                  65                  70                  75

 Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
                  80                  85                  90

 Thr Ala Val Tyr Tyr Cys Ala Arg Gly Arg Val Gly Tyr Ser Leu
                  95                 100                 105

 Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
                 110                 115                

<210> 11
<211> 214
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 11
 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
   1               5                  10                  15

 Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Ser
                  20                  25                  30

 Ile Gly Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys
                  35                  40                  45

 Leu Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Thr Gly Val Pro Ser
                  50                  55                  60

 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
                  65                  70                  75

 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
                  80                  85                  90

 Tyr Tyr Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu
                  95                 100                 105

 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
                 110                 115                 120

 Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu
                 125                 130                 135

 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val
                 140                 145                 150

 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu
                 155                 160                 165

 Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr
                 170                 175                 180

 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu
                 185                 190                 195

 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn
                 200                 205                 210

 Arg Gly Glu Cys
                

<210> 12
<211> 448
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 12
 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
   1               5                  10                  15

 Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr
                  20                  25                  30

 Asp Tyr Thr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
                  35                  40                  45

 Glu Trp Val Ala Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr
                  50                  55                  60

 Asn Gln Arg Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Arg Ser
                  65                  70                  75

 Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
                  80                  85                  90

 Thr Ala Val Tyr Tyr Cys Ala Arg Asn Leu Gly Pro Ser Phe Tyr
                  95                 100                 105

 Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala
                 110                 115                 120

 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
                 125                 130                 135

 Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
                 140                 145                 150

 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu
                 155                 160                 165

 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
                 170                 175                 180

 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu
                 185                 190                 195

 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn
                 200                 205                 210

 Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
                 215                 220                 225

 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
                 230                 235                 240

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

 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
                 275                 280                 285

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

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

 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
                 320                 325                 330

 Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
                 335                 340                 345

 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
                 350                 355                 360

 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
                 365                 370                 375

 Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
                 380                 385                 390

 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
                 395                 400                 405

 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
                 410                 415                 420

 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
                 425                 430                 435

 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
                 440                 445            

<210> 13
<211> 214
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 13
 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
   1               5                  10                  15

 Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn
                  20                  25                  30

 Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys
                  35                  40                  45

 Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser
                  50                  55                  60

 Arg Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile
                  65                  70                  75

 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
                  80                  85                  90

 His Tyr Thr Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu
                  95                 100                 105

 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
                 110                 115                 120

 Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu
                 125                 130                 135

 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val
                 140                 145                 150

 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu
                 155                 160                 165

 Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr
                 170                 175                 180

 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu
                 185                 190                 195

 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn
                 200                 205                 210

 Arg Gly Glu Cys
                

<210> 14
<211> 449
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 14
 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
   1               5                  10                  15

 Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys
                  20                  25                  30

 Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
                  35                  40                  45

 Glu Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr
                  50                  55                  60

 Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser
                  65                  70                  75

 Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
                  80                  85                  90

 Thr Ala Val Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr
                  95                 100                 105

 Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
                 110                 115                 120

 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser
                 125                 130                 135

 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys
                 140                 145                 150

 Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
                 155                 160                 165

 Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser
                 170                 175                 180

 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser
                 185                 190                 195

 Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
                 200                 205                 210

 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
                 215                 220                 225

 Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
                 230                 235                 240

 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
                 260                 265                 270

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

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

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

 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
                 320                 325                 330

 Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
                 335                 340                 345

 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu
                 350                 355                 360

 Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
                 365                 370                 375

 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
                 380                 385                 390

 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
                 395                 400                 405

 Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
                 410                 415                 420

 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
                 425                 430                 435

 His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
                 440                 445                

<210> 15
<211> 217
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 15
 Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser
   1               5                  10                  15

 Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln
                  20                  25                  30

 Asp Val Ser Ile Gly Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys
                  35                  40                  45

 Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Thr Gly
                  50                  55                  60

 Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
                  65                  70                  75

 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr
                  80                  85                  90

 Cys Gln Gln Tyr Tyr Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr
                  95                 100                 105

 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile
                 110                 115                 120

 Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val
                 125                 130                 135

 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln
                 140                 145                 150

 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser
                 155                 160                 165

 Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
                 170                 175                 180

 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
                 185                 190                 195

 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
                 200                 205                 210

 Ser Phe Asn Arg Gly Glu Cys
                 215        

<210> 16
<211> 449
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 16
 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
   1               5                  10                  15

 Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr
                  20                  25                  30

 Asp Tyr Thr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
                  35                  40                  45

 Glu Trp Val Ala Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr
                  50                  55                  60

 Asn Gln Arg Phe Lys Gly Arg Phe Thr Leu Ser Val Asp Arg Ser
                  65                  70                  75

 Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
                  80                  85                  90

 Thr Ala Val Tyr Tyr Cys Ala Arg Asn Leu Gly Pro Ser Phe Tyr
                  95                 100                 105

 Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala
                 110                 115                 120

 Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
                 125                 130                 135

 Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
                 140                 145                 150

 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu
                 155                 160                 165

 Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
                 170                 175                 180

 Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu
                 185                 190                 195

 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn
                 200                 205                 210

 Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
                 215                 220                 225

 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
                 230                 235                 240

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

 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
                 275                 280                 285

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

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

 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
                 320                 325                 330

 Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
                 335                 340                 345

 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
                 350                 355                 360

 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
                 365                 370                 375

 Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
                 380                 385                 390

 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
                 395                 400                 405

 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
                 410                 415                 420

 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
                 425                 430                 435

 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
                 440                 445                

<210> 17
<211> 10
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<220>
<221> Xaa
<222> 10
<223> Xaa is preferrably D or S

<400> 17
 Gly Phe Thr Phe Thr Asp Tyr Thr Met Xaa
                   5                  10

<210> 18
<211> 17
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 18
 Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr Asn Gln Arg Phe
   1               5                  10                  15

 Lys Gly
        

<210> 19
<211> 10
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 19
 Asn Leu Gly Pro Ser Phe Tyr Phe Asp Tyr
                   5                  10

<210> 20
<211> 11
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 20
 Lys Ala Ser Gln Asp Val Ser Ile Gly Val Ala
                   5                  10    

<210> 21
<211> 7
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<220>
<221> Xaa
<222> 5
<223> Xaa is preferably R or L

<220>
<221> Xaa
<222> 6
<223> Xaa is preferably Y or E

<220>
<221> Xaa
<222> 7
<223> Xaa is preferably T or S

<400> 21
 Ser Ala Ser Tyr Xaa Xaa Xaa
                   5        

<210> 22
<211> 9
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 22
 Gln Gln Tyr Tyr Ile Tyr Pro Tyr Thr
                   5                

<210> 23
<211> 10
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 23
 Gly Phe Thr Phe Thr Asp Tyr Thr Met Asp
                   5                  10

<210> 24
<211> 7
<212> PRT
<213> Artificial sequence

<220>
<223> Sequence is synthesized.

<400> 24
 Ser Ala Ser Tyr Arg Tyr Thr
                   5        

