                              Sequence Listing

<110> GENENTECH, INC. et al.

<120> METHOD AND FORMULATION FOR REDUCING AGGREGATION OF A 
      MACROMOLECULE UNDER PHYSIOLOGICAL CONDITIONS

<130> P2391R1 WO

<141> 2009-11-16

<150> US 61/115,441
<151> 2008-11-17

<160> 15

<210> 1
<211> 107
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 1
 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 Ser Ser Val Ser
                  20                  25                  30

 Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Pro
                  35                  40                  45

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

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

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

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

 Lys Arg
        

<210> 2
<211> 122
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 2
 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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Asn Ser
                  95                 100                 105

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

 Ser Ser
        

<210> 3
<211> 107
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 3
 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 Ser Ser Val Ser
                  20                  25                  30

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

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

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

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

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

 Lys Arg
        

<210> 4
<211> 122
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 4
 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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Ala Ser
                  95                 100                 105

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

 Ser Ser
        

<210> 5
<211> 122
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 5
 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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Tyr Arg
                  95                 100                 105

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

 Ser Ser
        

<210> 6
<211> 213
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 6
 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 Ser Ser Val Ser
                  20                  25                  30

 Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Pro
                  35                  40                  45

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

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

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

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

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

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

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

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

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

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

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

 Gly Glu Cys
            

<210> 7
<211> 452
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 7
 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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Asn Ser
                  95                 100                 105

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

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

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

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

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

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

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

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

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

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

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

 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
                 290                 295                 300

 Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
                 305                 310                 315

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

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

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

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

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

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

 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
                 410                 415                 420

 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
                 425                 430                 435

 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
                 440                 445                 450

 Gly Lys
        

<210> 8
<211> 452
<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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Asn Ser
                  95                 100                 105

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

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

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

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

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

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

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

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

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

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

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

 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
                 290                 295                 300

 Tyr Asn Ala Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
                 305                 310                 315

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

 Lys Ala Leu Pro Ala Pro Ile Ala Ala Thr Ile Ser Lys Ala Lys
                 335                 340                 345

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

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

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

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

 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
                 410                 415                 420

 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
                 425                 430                 435

 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
                 440                 445                 450

 Gly Lys
        

<210> 9
<211> 213
<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 Ser Ser Val Ser
                  20                  25                  30

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

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

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

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

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

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

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

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

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

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

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

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

 Gly Glu Cys
            

<210> 10
<211> 452
<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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Ala Ser
                  95                 100                 105

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

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

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

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

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

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

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

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

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

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

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

 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
                 290                 295                 300

 Tyr Asn Ala Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
                 305                 310                 315

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

 Lys Ala Leu Pro Ala Pro Ile Ala Ala Thr Ile Ser Lys Ala Lys
                 335                 340                 345

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

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

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

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

 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
                 410                 415                 420

 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
                 425                 430                 435

 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
                 440                 445                 450

 Gly Lys
        

<210> 11
<211> 452
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 11
 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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Ala Ser
                  95                 100                 105

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

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

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

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

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

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

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

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

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

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

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

 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
                 290                 295                 300

 Tyr Asn Ala Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
                 305                 310                 315

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

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

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

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

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

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

 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
                 410                 415                 420

 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
                 425                 430                 435

 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
                 440                 445                 450

 Gly Lys
        

<210> 12
<211> 452
<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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Ala Ser
                  95                 100                 105

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

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

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

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

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

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

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

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

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

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

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

 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
                 290                 295                 300

 Tyr Asn Ala Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
                 305                 310                 315

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

 Ala Ala Leu Pro Ala Pro Ile Ala Ala Thr Ile Ser Lys Ala Lys
                 335                 340                 345

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

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

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

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

 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
                 410                 415                 420

 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
                 425                 430                 435

 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
                 440                 445                 450

 Gly Lys
        

<210> 13
<211> 452
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 13
 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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Ala Ser
                  95                 100                 105

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

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

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

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

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

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

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

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

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

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

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

 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
                 290                 295                 300

 Tyr Asn Ala Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
                 305                 310                 315

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

 Ala Ala Leu Pro Ala Pro Ile Ala Ala Thr Ile Ser Lys Ala Lys
                 335                 340                 345

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

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

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

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

 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
                 410                 415                 420

 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
                 425                 430                 435

 Ala Leu His Trp His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
                 440                 445                 450

 Gly Lys
        

<210> 14
<211> 452
<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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Tyr Arg
                  95                 100                 105

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

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

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

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

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

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

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

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

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

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

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

 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
                 290                 295                 300

 Tyr Asn Ala Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
                 305                 310                 315

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

 Ala Ala Leu Pro Ala Pro Ile Ala Ala Thr Ile Ser Lys Ala Lys
                 335                 340                 345

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

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

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

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

 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
                 410                 415                 420

 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
                 425                 430                 435

 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
                 440                 445                 450

 Gly Lys
        

<210> 15
<211> 452
<212> PRT
<213> Artificial sequence

<220>
<223> sequence is synthesized

<400> 15
 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 Tyr Thr Phe Thr
                  20                  25                  30

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

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

 Asn Gln Lys Phe Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Val Val Tyr Tyr Ser Asn Ser
                  95                 100                 105

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

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

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

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

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

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

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

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

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

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

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

 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
                 290                 295                 300

 Tyr Asn Ala Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
                 305                 310                 315

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

 Ala Ala Leu Pro Ala Pro Ile Ala Ala Thr Ile Ser Lys Ala Lys
                 335                 340                 345

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

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

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

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

 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
                 410                 415                 420

 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
                 425                 430                 435

 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
                 440                 445                 450

 Gly Lys
        

