﻿               SEQUENCE LISTING

<110> Immunwork Inc.

<120> MOLECULAR CONSTRUCTS FOR INHIBITING THE FORMATION OF BLOOD CLOT AND/OR TREATING THROMBOSIS

<130> P2955-PCT

<150> US 62/308,349
<151> 2016-03-15
<150> PCT/CN2016/071184
<151> 2016-01-18
<150> US 62/213,012
<151> 2015-09-01

<160> 35

<170> BiSSAP 1.3

<210> 1
<211> 4
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-1

<400> 1
Gly Gly Gly Ser 
1               

<210> 2
<211> 4
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-2

<400> 2
Gly Ser Gly Ser 
1               

<210> 3
<211> 4
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-3

<400> 3
Gly Gly Ser Gly 
1               

<210> 4
<211> 5
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-4

<400> 4
Gly Ser Gly Gly Ser 
1               5   

<210> 5
<211> 5
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-5

<400> 5
Ser Gly Gly Ser Gly 
1               5   

<210> 6
<211> 5
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-6

<400> 6
Gly Gly Gly Gly Ser 
1               5   

<210> 7
<211> 6
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-7

<400> 7
Gly Gly Ser Gly Gly Ser 
1               5       

<210> 8
<211> 7
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-8

<400> 8
Gly Gly Ser Gly Gly Ser Gly 
1               5           

<210> 9
<211> 8
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-9

<400> 9
Ser Gly Ser Gly Gly Ser Gly Ser 
1               5               

<210> 10
<211> 9
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-10

<400> 10
Gly Ser Gly Gly Ser Gly Ser Gly Ser 
1               5                   

<210> 11
<211> 10
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-11

<400> 11
Ser Gly Gly Ser Gly Gly Ser Gly Ser Gly 
1               5                   10  

<210> 12
<211> 11
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-12

<400> 12
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser 
1               5                   10      

<210> 13
<211> 12
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-13

<400> 13
Ser Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser 
1               5                   10          

<210> 14
<211> 13
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-14

<400> 14
Gly Gly Gly Gly Ser Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10              

<210> 15
<211> 14
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-15

<400> 15
Gly Gly Gly Ser Gly Ser Gly Ser Gly Ser Gly Gly Gly Ser 
1               5                   10                  

<210> 16
<211> 15
<212> PRT
<213> Artificial Sequence

<220> 
<223> filler sequence-16

<400> 16
Ser Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Ser Gly Ser Gly 
1               5                   10                  15  

<210> 17
<211> 16
<212> PRT
<213> Artificial Sequence

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptide core

<400> 17
Cys Gly Gly Ser Gly Gly Ser Gly Gly Ser Lys Gly Ser Gly Ser Lys 
1               5                   10                  15      



<210> 18
<211> 19
<212> PRT
<213> Artificial Sequence

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptitde core-1

<400> 18
Cys Gly Gly Ser Gly Gly Ser Gly Gly Ser Lys Gly Ser Gly Ser Lys 
1               5                   10                  15      
Gly Ser Lys 
            

<210> 19
<211> 31
<212> PRT
<213> Artificial Sequence

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptide core

<400> 19
Cys Gly Ser Lys Gly Ser Lys Gly Ser Lys Gly Ser Lys Gly Ser Lys 
1               5                   10                  15      
Gly Ser Lys Gly Ser Lys Gly Ser Lys Gly Ser Lys Gly Ser Lys 
            20                  25                  30      

<210> 20
<211> 16
<212> PRT
<213> Artificial Sequence

<220> 
<221> MOD_RES
<222> 1
<223> Xaa is homopropargylglycine

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptide core

<400> 20
Xaa Gly Gly Ser Gly Gly Ser Gly Gly Ser Lys Gly Ser Gly Ser Lys 
1               5                   10                  15      



<210> 21
<211> 19
<212> PRT
<213> Artificial Sequence

<220> 
<221> MOD_RES
<222> 1
<223> Xaa is homopropargylglycine

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptide core

<400> 21
Xaa Gly Gly Ser Gly Gly Ser Gly Gly Ser Lys Gly Ser Gly Ser Lys 
1               5                   10                  15      
Gly Ser Lys 
            

<210> 22
<211> 19
<212> PRT
<213> Artificial Sequence

<220> 
<221> MOD_RES
<222> 1
<223> Xaa is L-azidohomoalanine

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptide core

<400> 22
Xaa Gly Gly Ser Gly Gly Ser Gly Gly Ser Lys Gly Ser Gly Ser Lys 
1               5                   10                  15      
Gly Ser Lys 
            

<210> 23
<211> 21
<212> PRT
<213> Artificial Sequence

<220> 
<221> MOD_RES
<222> 1
<223> Xaa is homopropargylglycine

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptide core

<400> 23
Xaa Gly Gly Ser Gly Gly Ser Gly Gly Ser Lys Gly Ser Gly Ser Lys 
1               5                   10                  15      
Gly Ser Gly Ser Cys 
            20      

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

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptide core

<220> 
<221> MOD_RES
<222> 2,4,6
<223> Xaa is PEGylated amino acid with two EG units

<400> 24
Cys Xaa Lys Xaa Lys Xaa Lys 
1               5           

<210> 25
<211> 11
<212> PRT
<213> Artificial Sequence

<220> 
<221> MOD_RES
<222> 1
<223> ACETYLATION

<220> 
<223> polypeptide core

<220> 
<221> MOD_RES
<222> 2,4,6,8,10
<223> Xaa is PEGylated amino acid with six EG units

<400> 25
Cys Xaa Lys Xaa Lys Xaa Lys Xaa Lys Xaa Lys 
1               5                   10      

<210> 26
<211> 16
<212> PRT
<213> Artificial Sequence

<220> 
<223> polypeptide core-2

<400> 26
Cys Gly Ser Lys Gly Ser Lys Gly Ser Lys Gly Ser Lys Gly Ser Lys 
1               5                   10                  15      



<210> 27
<211> 250
<212> PRT
<213> Artificial Sequence

<220> 
<223> anti-fibrin scFv 102-10

<400> 27
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly 
1               5                   10                  15      
Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Lys Tyr 
            20                  25                  30          
Ile Ala Trp Phe Gln His Lys Pro Gly Lys Gly Pro Arg Leu Leu Ile 
        35                  40                  45              
His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser Asn Leu Glu Pro 
65                  70                  75                  80  
Glu Asp Leu Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp Asn Leu Thr Trp 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Gly Ser Thr Ser 
            100                 105                 110         
Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Gln Ile 
        115                 120                 125             
Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu Thr Val 
    130                 135                 140                 
Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Met 
145                 150                 155                 160 
Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met Gly Trp 
                165                 170                 175     
Ile Asn Thr Tyr Thr Gly Glu Ala Thr Tyr Ala Asp Asp Phe Lys Gly 
            180                 185                 190         
Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Asn Thr Ala Tyr Val Gln 
        195                 200                 205             
Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg 
    210                 215                 220                 
Leu Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Gly 
225                 230                 235                 240 
Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys 
                245                 250 

<210> 28
<211> 366
<212> PRT
<213> Artificial Sequence

<220> 
<223> reteplase-Cys

<400> 28
Ser Tyr Gln Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr 
1               5                   10                  15      
Arg Gly Thr His Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro Trp 
            20                  25                  30          
Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser 
        35                  40                  45              
Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp 
    50                  55                  60                  
Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr 
65                  70                  75                  80  
Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln 
                85                  90                  95      
Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile 
            100                 105                 110         
Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser 
        115                 120                 125             
Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp 
    130                 135                 140                 
Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His 
145                 150                 155                 160 
Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu 
                165                 170                 175     
Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp 
            180                 185                 190         
Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp 
        195                 200                 205             
Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu 
    210                 215                 220                 
Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser 
225                 230                 235                 240 
Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu 
                245                 250                 255     
Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln 
            260                 265                 270         
His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp 
        275                 280                 285             
Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly 
    290                 295                 300                 
Asp Ser Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu 
305                 310                 315                 320 
Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro 
                325                 330                 335     
Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn 
            340                 345                 350         
Met Arg Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys 
        355                 360                 365     

<210> 29
<211> 244
<212> PRT
<213> Artificial Sequence

<220> 
<223> Phage-displayed anti-fibrin scFv D10

<400> 29
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Gly Phe Tyr 
            20                  25                  30          
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Ser Tyr Pro Ser Gly Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Tyr Asp Tyr Pro Ile 
                85                  90                  95      
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly Ser Thr Ser 
            100                 105                 110         
Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val 
        115                 120                 125             
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
    130                 135                 140                 
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ile Asn Asp Phe Ser Ile 
145                 150                 155                 160 
His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Gly 
                165                 170                 175     
Ile Trp Pro Tyr Gly Gly Tyr Thr Phe Tyr Ala Asp Ser Val Lys Gly 
            180                 185                 190         
Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Arg 
        195                 200                 205             
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 
Phe Gly Tyr Tyr Ser Phe Gly Asp Tyr Trp Gly Gln Gly Thr Leu Val 
225                 230                 235                 240 
Thr Val Ser Ser 
                

<210> 30
<211> 599
<212> PRT
<213> Artificial Sequence

<220> 
<223> 2-chain IgG4.Fc fusion protein containing reteplase

<400> 30
Ser Tyr Gln Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr 
1               5                   10                  15      
Arg Gly Thr His Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro Trp 
            20                  25                  30          
Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser 
        35                  40                  45              
Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp 
    50                  55                  60                  
Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr 
65                  70                  75                  80  
Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln 
                85                  90                  95      
Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile 
            100                 105                 110         
Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser 
        115                 120                 125             
Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp 
    130                 135                 140                 
Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His 
145                 150                 155                 160 
Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu 
                165                 170                 175     
Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp 
            180                 185                 190         
Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp 
        195                 200                 205             
Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu 
    210                 215                 220                 
Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser 
225                 230                 235                 240 
Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu 
                245                 250                 255     
Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln 
            260                 265                 270         
His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp 
        275                 280                 285             
Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly 
    290                 295                 300                 
Asp Ser Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu 
305                 310                 315                 320 
Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro 
                325                 330                 335     
Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn 
            340                 345                 350         
Met Arg Pro Ala Ser Gly Gly Ser Pro Pro Cys Pro Ser Cys Pro Ala 
        355                 360                 365             
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
    370                 375                 380                 
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
385                 390                 395                 400 
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
                405                 410                 415     
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
            420                 425                 430         
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
        435                 440                 445             
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 
    450                 455                 460                 
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
465                 470                 475                 480 
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr 
                485                 490                 495     
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
            500                 505                 510         
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
        515                 520                 525             
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
    530                 535                 540                 
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 
545                 550                 555                 560 
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                565                 570                 575     
Ser Leu Ser Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly 
            580                 585                 590         
Gly Ser Gly Gly Gly Gly Ser 
        595                 

<210> 31
<211> 838
<212> PRT
<213> Artificial Sequence

<220> 
<223> (reteplase)-hIgG4.Fc-(scFv α fibrin 102-10)

<400> 31
Ser Tyr Gln Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr 
1               5                   10                  15      
Arg Gly Thr His Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro Trp 
            20                  25                  30          
Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser 
        35                  40                  45              
Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp 
    50                  55                  60                  
Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr 
65                  70                  75                  80  
Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln 
                85                  90                  95      
Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile 
            100                 105                 110         
Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser 
        115                 120                 125             
Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp 
    130                 135                 140                 
Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His 
145                 150                 155                 160 
Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu 
                165                 170                 175     
Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp 
            180                 185                 190         
Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp 
        195                 200                 205             
Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu 
    210                 215                 220                 
Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser 
225                 230                 235                 240 
Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu 
                245                 250                 255     
Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln 
            260                 265                 270         
His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp 
        275                 280                 285             
Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly 
    290                 295                 300                 
Asp Ser Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu 
305                 310                 315                 320 
Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro 
                325                 330                 335     
Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn 
            340                 345                 350         
Met Arg Pro Ala Ser Gly Gly Ser Pro Pro Cys Pro Ser Cys Pro Ala 
        355                 360                 365             
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
    370                 375                 380                 
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
385                 390                 395                 400 
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
                405                 410                 415     
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
            420                 425                 430         
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
        435                 440                 445             
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 
    450                 455                 460                 
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
465                 470                 475                 480 
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr 
                485                 490                 495     
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
            500                 505                 510         
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
        515                 520                 525             
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
    530                 535                 540                 
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 
545                 550                 555                 560 
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                565                 570                 575     
Ser Leu Ser Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly 
            580                 585                 590         
Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser 
        595                 600                 605             
Ser Leu Ser Ala Ser Leu Gly Gly Lys Val Thr Ile Thr Cys Lys Ala 
    610                 615                 620                 
Ser Gln Asp Ile Asn Lys Tyr Ile Ala Trp Phe Gln His Lys Pro Gly 
625                 630                 635                 640 
Lys Gly Pro Arg Leu Leu Ile His Tyr Thr Ser Thr Leu Gln Pro Gly 
                645                 650                 655     
Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Arg Asp Tyr Ser Phe 
            660                 665                 670         
Ser Ile Ser Asn Leu Glu Pro Glu Asp Leu Ala Thr Tyr Tyr Cys Leu 
        675                 680                 685             
Gln Tyr Asp Asn Leu Thr Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu 
    690                 695                 700                 
Ile Lys Arg Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu 
705                 710                 715                 720 
Gly Ser Thr Lys Gly Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu 
                725                 730                 735     
Lys Lys Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr 
            740                 745                 750         
Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys 
        755                 760                 765             
Gly Leu Lys Trp Met Gly Trp Ile Asn Thr Tyr Thr Gly Glu Ala Thr 
    770                 775                 780                 
Tyr Ala Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser 
785                 790                 795                 800 
Ala Asn Thr Ala Tyr Val Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr 
                805                 810                 815     
Ala Thr Tyr Phe Cys Ala Arg Leu Met Asp Tyr Trp Gly Gln Gly Thr 
            820                 825                 830         
Ser Val Thr Val Ser Ser 
        835             

<210> 32
<211> 611
<212> PRT
<213> Artificial Sequence

<220> 
<223> (reteplase)-(scFv α fibrin 102-10)

<400> 32
Ser Tyr Gln Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr 
1               5                   10                  15      
Arg Gly Thr His Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro Trp 
            20                  25                  30          
Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser 
        35                  40                  45              
Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp 
    50                  55                  60                  
Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr 
65                  70                  75                  80  
Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln 
                85                  90                  95      
Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile 
            100                 105                 110         
Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser 
        115                 120                 125             
Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp 
    130                 135                 140                 
Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His 
145                 150                 155                 160 
Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu 
                165                 170                 175     
Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp 
            180                 185                 190         
Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp 
        195                 200                 205             
Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu 
    210                 215                 220                 
Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser 
225                 230                 235                 240 
Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu 
                245                 250                 255     
Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln 
            260                 265                 270         
His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp 
        275                 280                 285             
Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly 
    290                 295                 300                 
Asp Ser Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu 
305                 310                 315                 320 
Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro 
                325                 330                 335     
Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn 
            340                 345                 350         
Met Arg Pro Ala Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
        355                 360                 365             
Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser 
    370                 375                 380                 
Ala Ser Leu Gly Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp 
385                 390                 395                 400 
Ile Asn Lys Tyr Ile Ala Trp Phe Gln His Lys Pro Gly Lys Gly Pro 
                405                 410                 415     
Arg Leu Leu Ile His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser 
            420                 425                 430         
Arg Phe Ser Gly Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser 
        435                 440                 445             
Asn Leu Glu Pro Glu Asp Leu Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp 
    450                 455                 460                 
Asn Leu Thr Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
465                 470                 475                 480 
Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr 
                485                 490                 495     
Lys Gly Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro 
            500                 505                 510         
Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr 
        515                 520                 525             
Asn Tyr Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys 
    530                 535                 540                 
Trp Met Gly Trp Ile Asn Thr Tyr Thr Gly Glu Ala Thr Tyr Ala Asp 
545                 550                 555                 560 
Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Asn Thr 
                565                 570                 575     
Ala Tyr Val Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr 
            580                 585                 590         
Phe Cys Ala Arg Leu Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
        595                 600                 605             
Val Ser Ser 
    610     

<210> 33
<211> 771
<212> PRT
<213> Artificial Sequence

<220> 
<223> 2-chain IgG4.Fc fusion protein containing TNK-tPA

<400> 33
Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met Ile Tyr Gln 
1               5                   10                  15      
Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn Arg Val Glu 
            20                  25                  30          
Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser Val Pro Val 
        35                  40                  45              
Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr Cys Gln Gln 
    50                  55                  60                  
Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu Gly Phe Ala 
65                  70                  75                  80  
Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr Glu Asp Gln 
                85                  90                  95      
Gly Ile Ser Tyr Arg Gly Asn Trp Ser Thr Ala Glu Ser Gly Ala Glu 
            100                 105                 110         
Cys Thr Gln Trp Asn Ser Ser Ala Leu Ala Gln Lys Pro Tyr Ser Gly 
        115                 120                 125             
Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His Asn Tyr Cys 
    130                 135                 140                 
Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val Phe Lys Ala 
145                 150                 155                 160 
Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys Ser Glu Gly 
                165                 170                 175     
Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg Gly Thr His 
            180                 185                 190         
Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro Trp Asn Ser Met Ile 
        195                 200                 205             
Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala Gln Ala Leu 
    210                 215                 220                 
Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly Asp Ala Lys 
225                 230                 235                 240 
Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp Glu Tyr Cys 
                245                 250                 255     
Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr Ser Gln Pro 
            260                 265                 270         
Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala Ser His Pro 
        275                 280                 285             
Trp Gln Ala Ala Ala Ala Ala Lys His Arg Arg Ser Pro Gly Glu Arg 
    290                 295                 300                 
Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile Leu Ser Ala 
305                 310                 315                 320 
Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu Thr Val Ile 
                325                 330                 335     
Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu Gln Lys Phe 
            340                 345                 350         
Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp Asp Thr Tyr 
        355                 360                 365             
Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser Ser Arg Cys 
    370                 375                 380                 
Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu Pro Pro Ala Asp 
385                 390                 395                 400 
Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly Tyr Gly Lys 
                405                 410                 415     
His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys Glu Ala His 
            420                 425                 430         
Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His Leu Leu Asn 
        435                 440                 445             
Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr Arg Ser Gly 
    450                 455                 460                 
Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp Ser Gly Gly 
465                 470                 475                 480 
Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val Gly Ile Ile 
                485                 490                 495     
Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly Val Tyr Thr 
            500                 505                 510         
Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met Arg Pro Ala 
        515                 520                 525             
Ser Gly Gly Ser Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe Leu 
    530                 535                 540                 
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
545                 550                 555                 560 
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                565                 570                 575     
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
            580                 585                 590         
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
        595                 600                 605             
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    610                 615                 620                 
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
625                 630                 635                 640 
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                645                 650                 655     
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
            660                 665                 670         
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        675                 680                 685             
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    690                 695                 700                 
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
705                 710                 715                 720 
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
                725                 730                 735     
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            740                 745                 750         
Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
        755                 760                 765             
Gly Gly Ser 
    770     

<210> 34
<211> 1015
<212> PRT
<213> Artificial Sequence

<220> 
<223> (TNK-tPA)-hIgG4.Fc-(scFv α fibrin D10)

<400> 34
Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met Ile Tyr Gln 
1               5                   10                  15      
Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn Arg Val Glu 
            20                  25                  30          
Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser Val Pro Val 
        35                  40                  45              
Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr Cys Gln Gln 
    50                  55                  60                  
Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu Gly Phe Ala 
65                  70                  75                  80  
Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr Glu Asp Gln 
                85                  90                  95      
Gly Ile Ser Tyr Arg Gly Asn Trp Ser Thr Ala Glu Ser Gly Ala Glu 
            100                 105                 110         
Cys Thr Gln Trp Asn Ser Ser Ala Leu Ala Gln Lys Pro Tyr Ser Gly 
        115                 120                 125             
Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His Asn Tyr Cys 
    130                 135                 140                 
Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val Phe Lys Ala 
145                 150                 155                 160 
Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys Ser Glu Gly 
                165                 170                 175     
Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg Gly Thr His 
            180                 185                 190         
Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro Trp Asn Ser Met Ile 
        195                 200                 205             
Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala Gln Ala Leu 
    210                 215                 220                 
Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly Asp Ala Lys 
225                 230                 235                 240 
Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp Glu Tyr Cys 
                245                 250                 255     
Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr Ser Gln Pro 
            260                 265                 270         
Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala Ser His Pro 
        275                 280                 285             
Trp Gln Ala Ala Ala Ala Ala Lys His Arg Arg Ser Pro Gly Glu Arg 
    290                 295                 300                 
Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile Leu Ser Ala 
305                 310                 315                 320 
Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu Thr Val Ile 
                325                 330                 335     
Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu Gln Lys Phe 
            340                 345                 350         
Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp Asp Thr Tyr 
        355                 360                 365             
Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser Ser Arg Cys 
    370                 375                 380                 
Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu Pro Pro Ala Asp 
385                 390                 395                 400 
Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly Tyr Gly Lys 
                405                 410                 415     
His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys Glu Ala His 
            420                 425                 430         
Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His Leu Leu Asn 
        435                 440                 445             
Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr Arg Ser Gly 
    450                 455                 460                 
Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp Ser Gly Gly 
465                 470                 475                 480 
Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val Gly Ile Ile 
                485                 490                 495     
Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly Val Tyr Thr 
            500                 505                 510         
Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met Arg Pro Ala 
        515                 520                 525             
Ser Gly Gly Ser Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe Leu 
    530                 535                 540                 
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
545                 550                 555                 560 
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                565                 570                 575     
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
            580                 585                 590         
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
        595                 600                 605             
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    610                 615                 620                 
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
625                 630                 635                 640 
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                645                 650                 655     
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
            660                 665                 670         
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        675                 680                 685             
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    690                 695                 700                 
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
705                 710                 715                 720 
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
                725                 730                 735     
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            740                 745                 750         
Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
        755                 760                 765             
Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 
    770                 775                 780                 
Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val 
785                 790                 795                 800 
Gly Phe Tyr Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 
                805                 810                 815     
Leu Leu Ile Ser Tyr Pro Ser Gly Leu Tyr Ser Gly Val Pro Ser Arg 
            820                 825                 830         
Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser 
        835                 840                 845             
Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Tyr Asp 
    850                 855                 860                 
Tyr Pro Ile Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly 
865                 870                 875                 880 
Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys 
                885                 890                 895     
Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
            900                 905                 910         
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ile Asn Asp 
        915                 920                 925             
Phe Ser Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
    930                 935                 940                 
Val Ala Gly Ile Trp Pro Tyr Gly Gly Tyr Thr Phe Tyr Ala Asp Ser 
945                 950                 955                 960 
Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala 
                965                 970                 975     
Tyr Leu Arg Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr 
            980                 985                 990         
Cys Ala Arg Phe Gly Tyr Tyr Ser Phe Gly Asp Tyr Trp Gly Gln Gly 
        995                 1000                1005            
Thr Leu Val Thr Val Ser Ser 
    1010                1015

<210> 35
<211> 788
<212> PRT
<213> Artificial Sequence

<220> 
<223> (TNK-tPA)-(scFv α fibrin)

<400> 35
Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met Ile Tyr Gln 
1               5                   10                  15      
Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn Arg Val Glu 
            20                  25                  30          
Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser Val Pro Val 
        35                  40                  45              
Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr Cys Gln Gln 
    50                  55                  60                  
Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu Gly Phe Ala 
65                  70                  75                  80  
Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr Glu Asp Gln 
                85                  90                  95      
Gly Ile Ser Tyr Arg Gly Asn Trp Ser Thr Ala Glu Ser Gly Ala Glu 
            100                 105                 110         
Cys Thr Gln Trp Asn Ser Ser Ala Leu Ala Gln Lys Pro Tyr Ser Gly 
        115                 120                 125             
Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His Asn Tyr Cys 
    130                 135                 140                 
Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val Phe Lys Ala 
145                 150                 155                 160 
Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys Ser Glu Gly 
                165                 170                 175     
Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg Gly Thr His 
            180                 185                 190         
Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro Trp Asn Ser Met Ile 
        195                 200                 205             
Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala Gln Ala Leu 
    210                 215                 220                 
Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly Asp Ala Lys 
225                 230                 235                 240 
Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp Glu Tyr Cys 
                245                 250                 255     
Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr Ser Gln Pro 
            260                 265                 270         
Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala Ser His Pro 
        275                 280                 285             
Trp Gln Ala Ala Ala Ala Ala Lys His Arg Arg Ser Pro Gly Glu Arg 
    290                 295                 300                 
Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile Leu Ser Ala 
305                 310                 315                 320 
Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu Thr Val Ile 
                325                 330                 335     
Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu Gln Lys Phe 
            340                 345                 350         
Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp Asp Thr Tyr 
        355                 360                 365             
Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser Ser Arg Cys 
    370                 375                 380                 
Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu Pro Pro Ala Asp 
385                 390                 395                 400 
Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly Tyr Gly Lys 
                405                 410                 415     
His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys Glu Ala His 
            420                 425                 430         
Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His Leu Leu Asn 
        435                 440                 445             
Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr Arg Ser Gly 
    450                 455                 460                 
Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp Ser Gly Gly 
465                 470                 475                 480 
Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val Gly Ile Ile 
                485                 490                 495     
Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly Val Tyr Thr 
            500                 505                 510         
Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met Arg Pro Ala 
        515                 520                 525             
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    530                 535                 540                 
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
545                 550                 555                 560 
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Gly Phe Tyr 
                565                 570                 575     
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
            580                 585                 590         
Ser Tyr Pro Ser Gly Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
        595                 600                 605             
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
    610                 615                 620                 
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Tyr Asp Tyr Pro Ile 
625                 630                 635                 640 
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly Ser Thr Ser 
                645                 650                 655     
Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val 
            660                 665                 670         
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
        675                 680                 685             
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ile Asn Asp Phe Ser Ile 
    690                 695                 700                 
His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Gly 
705                 710                 715                 720 
Ile Trp Pro Tyr Gly Gly Tyr Thr Phe Tyr Ala Asp Ser Val Lys Gly 
                725                 730                 735     
Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Arg 
            740                 745                 750         
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
        755                 760                 765             
Phe Gly Tyr Tyr Ser Phe Gly Asp Tyr Trp Gly Gln Gly Thr Leu Val 
    770                 775                 780                 
Thr Val Ser Ser 
785             

