                         SEQUENCE LISTING

<110>  KAHR Medical Ltd.
       SHANI, Noam
       GOZLAN, Yosi
       DRANITZKI ELHALEL, Michal
       BREMER, Edwin
       KAMINSKY, Ido
 
<120>  A SIRP1 alpha-41BBL FUSION PROTEIN AND METHODS OF USE THEREOF

<130>  72308

<150>  US 62/442,469
<151>  2017-01-05

<160>  15    

<170>  PatentIn version 3.5

<210>  1
<211>  549
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of the chimera protein (SIRP alpha-G-41BBL)

<400>  1

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


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


Val Gly Pro Ile Gln Trp Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu 
        35                  40                  45              


Ile Tyr Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser 
    50                  55                  60                  


Asp Leu Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Gly Asn 
65                  70                  75                  80  


Ile Thr Pro Ala Asp Ala Gly Thr Tyr Tyr Cys Val Lys Phe Arg Lys 
                85                  90                  95      


Gly Ser Pro Asp Asp Val Glu Phe Lys Ser Gly Ala Gly Thr Glu Leu 
            100                 105                 110         


Ser Val Arg Ala Lys Pro Ser Ala Pro Val Val Ser Gly Pro Ala Ala 
        115                 120                 125             


Arg Ala Thr Pro Gln His Thr Val Ser Phe Thr Cys Glu Ser His Gly 
    130                 135                 140                 


Phe Ser Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu 
145                 150                 155                 160 


Leu Ser Asp Phe Gln Thr Asn Val Asp Pro Val Gly Glu Ser Val Ser 
                165                 170                 175     


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


His Ser Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp 
        195                 200                 205             


Pro Leu Arg Gly Thr Ala Asn Leu Ser Glu Thr Ile Arg Val Pro Pro 
    210                 215                 220                 


Thr Leu Glu Val Thr Gln Gln Pro Val Arg Ala Glu Asn Gln Val Asn 
225                 230                 235                 240 


Val Thr Cys Gln Val Arg Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr 
                245                 250                 255     


Trp Leu Glu Asn Gly Asn Val Ser Arg Thr Glu Thr Ala Ser Thr Val 
            260                 265                 270         


Thr Glu Asn Lys Asp Gly Thr Tyr Asn Trp Met Ser Trp Leu Leu Val 
        275                 280                 285             


Asn Val Ser Ala His Arg Asp Asp Val Lys Leu Thr Cys Gln Val Glu 
    290                 295                 300                 


His Asp Gly Gln Pro Ala Val Ser Lys Ser His Asp Leu Lys Val Ser 
305                 310                 315                 320 


Ala His Pro Lys Glu Gln Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly 
                325                 330                 335     


Ser Asn Glu Arg Asn Ile Tyr Gly Ala Cys Pro Trp Ala Val Ser Gly 
            340                 345                 350         


Ala Arg Ala Ser Pro Gly Ser Ala Ala Ser Pro Arg Leu Arg Glu Gly 
        355                 360                 365             


Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln 
    370                 375                 380                 


Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly 
385                 390                 395                 400 


Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr 
                405                 410                 415     


Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys 
            420                 425                 430         


Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val 
        435                 440                 445             


Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro 
    450                 455                 460                 


Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu 
465                 470                 475                 480 


Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly 
                485                 490                 495     


Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His 
            500                 505                 510         


Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr 
        515                 520                 525             


Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Pro 
    530                 535                 540                 


Ser Pro Arg Ser Glu 
545                 


<210>  2
<211>  343
<212>  PRT
<213>  homo sapiens

<400>  2

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


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


Val Gly Pro Ile Gln Trp Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu 
        35                  40                  45              


Ile Tyr Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser 
    50                  55                  60                  


Asp Leu Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Gly Asn 
65                  70                  75                  80  


Ile Thr Pro Ala Asp Ala Gly Thr Tyr Tyr Cys Val Lys Phe Arg Lys 
                85                  90                  95      


Gly Ser Pro Asp Asp Val Glu Phe Lys Ser Gly Ala Gly Thr Glu Leu 
            100                 105                 110         


Ser Val Arg Ala Lys Pro Ser Ala Pro Val Val Ser Gly Pro Ala Ala 
        115                 120                 125             


Arg Ala Thr Pro Gln His Thr Val Ser Phe Thr Cys Glu Ser His Gly 
    130                 135                 140                 


Phe Ser Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu 
145                 150                 155                 160 


Leu Ser Asp Phe Gln Thr Asn Val Asp Pro Val Gly Glu Ser Val Ser 
                165                 170                 175     


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


His Ser Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp 
        195                 200                 205             


Pro Leu Arg Gly Thr Ala Asn Leu Ser Glu Thr Ile Arg Val Pro Pro 
    210                 215                 220                 


Thr Leu Glu Val Thr Gln Gln Pro Val Arg Ala Glu Asn Gln Val Asn 
225                 230                 235                 240 


Val Thr Cys Gln Val Arg Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr 
                245                 250                 255     


Trp Leu Glu Asn Gly Asn Val Ser Arg Thr Glu Thr Ala Ser Thr Val 
            260                 265                 270         


Thr Glu Asn Lys Asp Gly Thr Tyr Asn Trp Met Ser Trp Leu Leu Val 
        275                 280                 285             


Asn Val Ser Ala His Arg Asp Asp Val Lys Leu Thr Cys Gln Val Glu 
    290                 295                 300                 


His Asp Gly Gln Pro Ala Val Ser Lys Ser His Asp Leu Lys Val Ser 
305                 310                 315                 320 


Ala His Pro Lys Glu Gln Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly 
                325                 330                 335     


Ser Asn Glu Arg Asn Ile Tyr 
            340             


<210>  3
<211>  205
<212>  PRT
<213>  homo sapiens

<400>  3

Ala Cys Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser Ala 
1               5                   10                  15      


Ala Ser Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro 
            20                  25                  30          


Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala 
        35                  40                  45              


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


Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp 
65                  70                  75                  80  


Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe 
                85                  90                  95      


Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val 
            100                 105                 110         


Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala 
        115                 120                 125             


Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg 
    130                 135                 140                 


Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly 
145                 150                 155                 160 


Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala 
                165                 170                 175     


Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr 
            180                 185                 190         


Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 
        195                 200                 205 


<210>  4
<211>  548
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of the chimera protein (SIRPalpha- 41BBL, no
       linker)

<400>  4

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


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


Val Gly Pro Ile Gln Trp Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu 
        35                  40                  45              


Ile Tyr Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser 
    50                  55                  60                  


Asp Leu Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Gly Asn 
65                  70                  75                  80  


Ile Thr Pro Ala Asp Ala Gly Thr Tyr Tyr Cys Val Lys Phe Arg Lys 
                85                  90                  95      


Gly Ser Pro Asp Asp Val Glu Phe Lys Ser Gly Ala Gly Thr Glu Leu 
            100                 105                 110         


Ser Val Arg Ala Lys Pro Ser Ala Pro Val Val Ser Gly Pro Ala Ala 
        115                 120                 125             


Arg Ala Thr Pro Gln His Thr Val Ser Phe Thr Cys Glu Ser His Gly 
    130                 135                 140                 


Phe Ser Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu 
145                 150                 155                 160 


Leu Ser Asp Phe Gln Thr Asn Val Asp Pro Val Gly Glu Ser Val Ser 
                165                 170                 175     


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


His Ser Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp 
        195                 200                 205             


Pro Leu Arg Gly Thr Ala Asn Leu Ser Glu Thr Ile Arg Val Pro Pro 
    210                 215                 220                 


Thr Leu Glu Val Thr Gln Gln Pro Val Arg Ala Glu Asn Gln Val Asn 
225                 230                 235                 240 


Val Thr Cys Gln Val Arg Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr 
                245                 250                 255     


Trp Leu Glu Asn Gly Asn Val Ser Arg Thr Glu Thr Ala Ser Thr Val 
            260                 265                 270         


Thr Glu Asn Lys Asp Gly Thr Tyr Asn Trp Met Ser Trp Leu Leu Val 
        275                 280                 285             


Asn Val Ser Ala His Arg Asp Asp Val Lys Leu Thr Cys Gln Val Glu 
    290                 295                 300                 


His Asp Gly Gln Pro Ala Val Ser Lys Ser His Asp Leu Lys Val Ser 
305                 310                 315                 320 


Ala His Pro Lys Glu Gln Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly 
                325                 330                 335     


Ser Asn Glu Arg Asn Ile Tyr Ala Cys Pro Trp Ala Val Ser Gly Ala 
            340                 345                 350         


Arg Ala Ser Pro Gly Ser Ala Ala Ser Pro Arg Leu Arg Glu Gly Pro 
        355                 360                 365             


Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly 
    370                 375                 380                 


Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile Asp Gly Pro 
385                 390                 395                 400 


Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser Leu Thr Gly 
                405                 410                 415     


Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val Ala Lys Ala 
            420                 425                 430         


Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg Val Val Ala 
        435                 440                 445             


Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu Gln Pro Leu 
    450                 455                 460                 


Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val Asp Leu Pro 
465                 470                 475                 480 


Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg 
                485                 490                 495     


Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His Leu His Thr 
            500                 505                 510         


Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly Ala Thr Val 
        515                 520                 525             


Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser 
    530                 535                 540                 


Pro Arg Ser Glu 
545             


<210>  5
<211>  554
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of His-tagged SIRP alpha -41BBL

<400>  5

His His His His His His Glu Glu Glu Leu Gln Val Ile Gln Pro Asp 
1               5                   10                  15      


Lys Ser Val Leu Val Ala Ala Gly Glu Thr Ala Thr Leu Arg Cys Thr 
            20                  25                  30          


Ala Thr Ser Leu Ile Pro Val Gly Pro Ile Gln Trp Phe Arg Gly Ala 
        35                  40                  45              


Gly Pro Gly Arg Glu Leu Ile Tyr Asn Gln Lys Glu Gly His Phe Pro 
    50                  55                  60                  


Arg Val Thr Thr Val Ser Asp Leu Thr Lys Arg Asn Asn Met Asp Phe 
65                  70                  75                  80  


Ser Ile Arg Ile Gly Asn Ile Thr Pro Ala Asp Ala Gly Thr Tyr Tyr 
                85                  90                  95      


Cys Val Lys Phe Arg Lys Gly Ser Pro Asp Asp Val Glu Phe Lys Ser 
            100                 105                 110         


Gly Ala Gly Thr Glu Leu Ser Val Arg Ala Lys Pro Ser Ala Pro Val 
        115                 120                 125             


Val Ser Gly Pro Ala Ala Arg Ala Thr Pro Gln His Thr Val Ser Phe 
    130                 135                 140                 


Thr Cys Glu Ser His Gly Phe Ser Pro Arg Asp Ile Thr Leu Lys Trp 
145                 150                 155                 160 


Phe Lys Asn Gly Asn Glu Leu Ser Asp Phe Gln Thr Asn Val Asp Pro 
                165                 170                 175     


Val Gly Glu Ser Val Ser Tyr Ser Ile His Ser Thr Ala Lys Val Val 
            180                 185                 190         


Leu Thr Arg Glu Asp Val His Ser Gln Val Ile Cys Glu Val Ala His 
        195                 200                 205             


Val Thr Leu Gln Gly Asp Pro Leu Arg Gly Thr Ala Asn Leu Ser Glu 
    210                 215                 220                 


Thr Ile Arg Val Pro Pro Thr Leu Glu Val Thr Gln Gln Pro Val Arg 
225                 230                 235                 240 


Ala Glu Asn Gln Val Asn Val Thr Cys Gln Val Arg Lys Phe Tyr Pro 
                245                 250                 255     


Gln Arg Leu Gln Leu Thr Trp Leu Glu Asn Gly Asn Val Ser Arg Thr 
            260                 265                 270         


Glu Thr Ala Ser Thr Val Thr Glu Asn Lys Asp Gly Thr Tyr Asn Trp 
        275                 280                 285             


Met Ser Trp Leu Leu Val Asn Val Ser Ala His Arg Asp Asp Val Lys 
    290                 295                 300                 


Leu Thr Cys Gln Val Glu His Asp Gly Gln Pro Ala Val Ser Lys Ser 
305                 310                 315                 320 


His Asp Leu Lys Val Ser Ala His Pro Lys Glu Gln Gly Ser Asn Thr 
                325                 330                 335     


Ala Ala Glu Asn Thr Gly Ser Asn Glu Arg Asn Ile Tyr Gly Ala Cys 
            340                 345                 350         


Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser Ala Ser Pro 
        355                 360                 365             


Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu 
    370                 375                 380                 


Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val 
385                 390                 395                 400 


Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala 
                405                 410                 415     


Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu 
            420                 425                 430         


Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu 
        435                 440                 445             


Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala 
    450                 455                 460                 


Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala 
465                 470                 475                 480 


Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala 
                485                 490                 495     


Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu 
            500                 505                 510         


Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu 
        515                 520                 525             


Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile 
    530                 535                 540                 


Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 
545                 550                 


<210>  6
<211>  312
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of PD1-CD70

<400>  6

His His His His His His Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg 
1               5                   10                  15      


Pro Trp Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu 
            20                  25                  30          


Gly Asp Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser 
        35                  40                  45              


Phe Val Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys 
    50                  55                  60                  


Leu Ala Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg 
65                  70                  75                  80  


Phe Arg Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val 
                85                  90                  95      


Val Arg Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile 
            100                 105                 110         


Ser Leu Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu 
        115                 120                 125             


Arg Val Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro 
    130                 135                 140                 


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


Ala Gln Ala Gln Gln Gln Leu Pro Leu Glu Ser Leu Gly Trp Asp Val 
                165                 170                 175     


Ala Glu Leu Gln Leu Asn His Thr Gly Pro Gln Gln Asp Pro Arg Leu 
            180                 185                 190         


Tyr Trp Gln Gly Gly Pro Ala Leu Gly Arg Ser Phe Leu His Gly Pro 
        195                 200                 205             


Glu Leu Asp Lys Gly Gln Leu Arg Ile His Arg Asp Gly Ile Tyr Met 
    210                 215                 220                 


Val His Ile Gln Val Thr Leu Ala Ile Cys Ser Ser Thr Thr Ala Ser 
225                 230                 235                 240 


Arg His His Pro Thr Thr Leu Ala Val Gly Ile Cys Ser Pro Ala Ser 
                245                 250                 255     


Arg Ser Ile Ser Leu Leu Arg Leu Ser Phe His Gln Gly Cys Thr Ile 
            260                 265                 270         


Ala Ser Gln Arg Leu Thr Pro Leu Ala Arg Gly Asp Thr Leu Cys Thr 
        275                 280                 285             


Asn Leu Thr Gly Thr Leu Leu Pro Ser Arg Asn Thr Asp Glu Thr Phe 
    290                 295                 300                 


Phe Gly Val Gln Trp Val Arg Pro 
305                 310         


<210>  7
<211>  1665
<212>  DNA
<213>  Artificial sequence

<220>
<223>   Nucleic-acid sequence of SIRP alpha-41BBL (with his tag)

<400>  7
caccatcatc accaccatga agaggaactg caagtgatcc agcctgacaa gagcgtgctg       60

gtggctgctg gcgaaacagc cacactgaga tgtaccgcca cctctctgat ccctgtgggc      120

cctatccagt ggtttagagg cgctggacct ggcagagagc tgatctacaa ccagaaagag      180

ggacacttcc ccagagtgac caccgtgtcc gacctgacca agcggaacaa catggacttc      240

agcatccgga tcggcaacat cacccctgcc gatgccggca cctactactg cgtgaagttc      300

agaaagggca gccccgacga cgtcgagttt aaaagcggag ccggcacaga gctgagcgtg      360

cgggctaaac cttctgctcc tgtggtgtct ggacctgccg ctagagctac acctcagcac      420

accgtgtctt ttacctgcga gagccacggc ttcagcccca gagatatcac cctgaagtgg      480

ttcaagaacg gcaacgagct gtccgacttc cagaccaacg tggaccctgt gggagagagc      540

gtgtcctaca gcatccacag cacagccaag gtggtgctga cccgggaaga tgtgcactcc      600

caagtgattt gcgaggtggc ccacgttacc ctgcaaggcg atcctctgag aggcaccgcc      660

aatctgagcg agacaatccg ggtgccacct acactggaag tgacccagca gcctgtgcgg      720

gccgagaatc aagtgaacgt gacctgccaa gtgcggaagt tctaccctca gagactgcag      780

ctgacctggc tggaaaacgg caatgtgtcc agaaccgaga cagccagcac cgtgaccgag      840

aacaaggatg gcacctacaa ttggatgagc tggctgctcg tgaatgtgtc tgcccaccgg      900

gacgatgtga agctgacatg ccaggtggaa cacgatggcc agcctgccgt gtctaagagc      960

cacgacctga aggtgtccgc tcatcccaaa gagcagggct ctaatactgc cgccgagaac     1020

accggcagca acgagagaaa tatctacggc gcttgtcctt gggccgtttc tggcgctaga     1080

gcctctcctg gatctgccgc ttctcccaga ctgagagagg gacctgagct gagccctgat     1140

gatcctgctg gactgctgga tctgagacag ggcatgtttg cccagctggt ggcccagaat     1200

gtgctgctga ttgatggccc tctgtcctgg tacagcgatc ctggacttgc tggcgttagc     1260

ctgactggcg gcctgagcta caaagaggac accaaagaac tggtggtggc caaggccggc     1320

gtgtactacg tgttctttca gctggaactg cggagagtgg tggccggcga aggatctgga     1380

tctgtgtctc tggctctgca tctgcagcct ctgagatctg ctgctggtgc tgctgctctg     1440

gccctgacag ttgatctgcc tcctgcctct agcgaggcca gaaactccgc ctttggcttc     1500

caaggcagac tgctgcacct gagcgctgga cagagactgg gagtccatct gcacacagaa     1560

gccagagcta gacacgcctg gcagctgaca caaggcgcta cagtgctggg cctgttcaga     1620

gtgacccctg agattccagc cggcctgcca tctcctagat ctgag                     1665


<210>  8
<211>  1647
<212>  DNA
<213>  Artificial sequence

<220>
<223>   Nucleic-acid sequence of SIRP alpha-41BBL

<400>  8
gaagaggaac tgcaagtgat ccagcctgac aagagcgtgc tggtggctgc tggcgaaaca       60

gccacactga gatgtaccgc cacctctctg atccctgtgg gccctatcca gtggtttaga      120

ggcgctggac ctggcagaga gctgatctac aaccagaaag agggacactt ccccagagtg      180

accaccgtgt ccgacctgac caagcggaac aacatggact tcagcatccg gatcggcaac      240

atcacccctg ccgatgccgg cacctactac tgcgtgaagt tcagaaaggg cagccccgac      300

gacgtcgagt ttaaaagcgg agccggcaca gagctgagcg tgcgggctaa accttctgct      360

cctgtggtgt ctggacctgc cgctagagct acacctcagc acaccgtgtc ttttacctgc      420

gagagccacg gcttcagccc cagagatatc accctgaagt ggttcaagaa cggcaacgag      480

ctgtccgact tccagaccaa cgtggaccct gtgggagaga gcgtgtccta cagcatccac      540

agcacagcca aggtggtgct gacccgggaa gatgtgcact cccaagtgat ttgcgaggtg      600

gcccacgtta ccctgcaagg cgatcctctg agaggcaccg ccaatctgag cgagacaatc      660

cgggtgccac ctacactgga agtgacccag cagcctgtgc gggccgagaa tcaagtgaac      720

gtgacctgcc aagtgcggaa gttctaccct cagagactgc agctgacctg gctggaaaac      780

ggcaatgtgt ccagaaccga gacagccagc accgtgaccg agaacaagga tggcacctac      840

aattggatga gctggctgct cgtgaatgtg tctgcccacc gggacgatgt gaagctgaca      900

tgccaggtgg aacacgatgg ccagcctgcc gtgtctaaga gccacgacct gaaggtgtcc      960

gctcatccca aagagcaggg ctctaatact gccgccgaga acaccggcag caacgagaga     1020

aatatctacg gcgcttgtcc ttgggccgtt tctggcgcta gagcctctcc tggatctgcc     1080

gcttctccca gactgagaga gggacctgag ctgagccctg atgatcctgc tggactgctg     1140

gatctgagac agggcatgtt tgcccagctg gtggcccaga atgtgctgct gattgatggc     1200

cctctgtcct ggtacagcga tcctggactt gctggcgtta gcctgactgg cggcctgagc     1260

tacaaagagg acaccaaaga actggtggtg gccaaggccg gcgtgtacta cgtgttcttt     1320

cagctggaac tgcggagagt ggtggccggc gaaggatctg gatctgtgtc tctggctctg     1380

catctgcagc ctctgagatc tgctgctggt gctgctgctc tggccctgac agttgatctg     1440

cctcctgcct ctagcgaggc cagaaactcc gcctttggct tccaaggcag actgctgcac     1500

ctgagcgctg gacagagact gggagtccat ctgcacacag aagccagagc tagacacgcc     1560

tggcagctga cacaaggcgc tacagtgctg ggcctgttca gagtgacccc tgagattcca     1620

gccggcctgc catctcctag atctgag                                         1647


<210>  9
<211>  504
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of full length SIRP alpha

<400>  9

Met Glu Pro Ala Gly Pro Ala Pro Gly Arg Leu Gly Pro Leu Leu Cys 
1               5                   10                  15      


Leu Leu Leu Ala Ala Ser Cys Ala Trp Ser Gly Val Ala Gly Glu Glu 
            20                  25                  30          


Glu Leu Gln Val Ile Gln Pro Asp Lys Ser Val Leu Val Ala Ala Gly 
        35                  40                  45              


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


Pro Ile Gln Trp Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu Ile Tyr 
65                  70                  75                  80  


Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu 
                85                  90                  95      


Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Gly Asn Ile Thr 
            100                 105                 110         


Pro Ala Asp Ala Gly Thr Tyr Tyr Cys Val Lys Phe Arg Lys Gly Ser 
        115                 120                 125             


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


Arg Ala Lys Pro Ser Ala Pro Val Val Ser Gly Pro Ala Ala Arg Ala 
145                 150                 155                 160 


Thr Pro Gln His Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser 
                165                 170                 175     


Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu Leu Ser 
            180                 185                 190         


Asp Phe Gln Thr Asn Val Asp Pro Val Gly Glu Ser Val Ser Tyr Ser 
        195                 200                 205             


Ile His Ser Thr Ala Lys Val Val Leu Thr Arg Glu Asp Val His Ser 
    210                 215                 220                 


Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp Pro Leu 
225                 230                 235                 240 


Arg Gly Thr Ala Asn Leu Ser Glu Thr Ile Arg Val Pro Pro Thr Leu 
                245                 250                 255     


Glu Val Thr Gln Gln Pro Val Arg Ala Glu Asn Gln Val Asn Val Thr 
            260                 265                 270         


Cys Gln Val Arg Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr Trp Leu 
        275                 280                 285             


Glu Asn Gly Asn Val Ser Arg Thr Glu Thr Ala Ser Thr Val Thr Glu 
    290                 295                 300                 


Asn Lys Asp Gly Thr Tyr Asn Trp Met Ser Trp Leu Leu Val Asn Val 
305                 310                 315                 320 


Ser Ala His Arg Asp Asp Val Lys Leu Thr Cys Gln Val Glu His Asp 
                325                 330                 335     


Gly Gln Pro Ala Val Ser Lys Ser His Asp Leu Lys Val Ser Ala His 
            340                 345                 350         


Pro Lys Glu Gln Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly Ser Asn 
        355                 360                 365             


Glu Arg Asn Ile Tyr Ile Val Val Gly Val Val Cys Thr Leu Leu Val 
    370                 375                 380                 


Ala Leu Leu Met Ala Ala Leu Tyr Leu Val Arg Ile Arg Gln Lys Lys 
385                 390                 395                 400 


Ala Gln Gly Ser Thr Ser Ser Thr Arg Leu His Glu Pro Glu Lys Asn 
                405                 410                 415     


Ala Arg Glu Ile Thr Gln Asp Thr Asn Asp Ile Thr Tyr Ala Asp Leu 
            420                 425                 430         


Asn Leu Pro Lys Gly Lys Lys Pro Ala Pro Gln Ala Ala Glu Pro Asn 
        435                 440                 445             


Asn His Thr Glu Tyr Ala Ser Ile Gln Thr Ser Pro Gln Pro Ala Ser 
    450                 455                 460                 


Glu Asp Thr Leu Thr Tyr Ala Asp Leu Asp Met Val His Leu Asn Arg 
465                 470                 475                 480 


Thr Pro Lys Gln Pro Ala Pro Lys Pro Glu Pro Ser Phe Ser Glu Tyr 
                485                 490                 495     


Ala Ser Val Gln Val Pro Arg Lys 
            500                 


<210>  10
<211>  1512
<212>  DNA
<213>  Artificial sequence

<220>
<223>   Nucleic-acid sequence of full length SIRP alpha

<400>  10
atggagcccg ccggcccggc ccccggccgc ctcgggccgc tgctctgcct gctgctcgcc       60

gcgtcctgcg cctggtcagg agtggcgggt gaggaggagc tgcaggtgat tcagcctgac      120

aagtccgtat cagttgcagc tggagagtcg gccattctgc actgcactgt gacctccctg      180

atccctgtgg ggcccatcca gtggttcaga ggagctggac cagcccggga attaatctac      240

aatcaaaaag aaggccactt cccccgggta acaactgttt cagagtccac aaagagagaa      300

aacatggact tttccatcag catcagtaac atcaccccag cagatgccgg cacctactac      360

tgtgtgaagt tccggaaagg gagccctgac acggagttta agtctggagc aggcactgag      420

ctgtctgtgc gtgccaaacc ctctgccccc gtggtatcgg gccctgcggc gagggccaca      480

cctcagcaca cagtgagctt cacctgcgag tcccacggct tctcacccag agacatcacc      540

ctgaaatggt tcaaaaatgg gaatgagctc tcagacttcc agaccaacgt ggaccccgta      600

ggagagagcg tgtcctacag catccacagc acagccaagg tggtgctgac ccgcgaggac      660

gttcactctc aagtcatctg cgaggtggcc cacgtcacct tgcaggggga ccctcttcgt      720

gggactgcca acttgtctga gaccatccga gttccaccca ccttggaggt tactcaacag      780

cccgtgaggg cagagaacca ggtgaatgtc acctgccagg tgaggaagtt ctacccccag      840

agactacagc tgacctggtt ggagaatgga aacgtgtccc ggacagaaac ggcctcaacc      900

gttacagaga acaaggatgg tacctacaac tggatgagct ggctcctggt gaatgtatct      960

gcccacaggg atgatgtgaa gctcacctgc caggtggagc atgacgggca gccagcggtc     1020

agcaaaagcc atgacctgaa ggtctcagcc cacccgaagg agcagggctc aaataccgcc     1080

gctgagaaca ctggatctaa tgaacggaac atctatattg tggtgggtgt ggtgtgcacc     1140

ttgctggtgg ccctactgat ggcggccctc tacctcgtcc gaatcagaca gaagaaagcc     1200

cagggctcca cttcttctac aaggttgcat gagcccgaga agaatgccag agaaataaca     1260

caggacacaa atgatatcac atatgcagac ctgaacctgc ccaaggggaa gaagcctgct     1320

ccccaggctg cggagcccaa caaccacacg gagtatgcca gcattcagac cagcccgcag     1380

cccgcgtcgg aggacaccct cacctatgct gacctggaca tggtccacct caaccggacc     1440

cccaagcagc cggcccccaa gcctgagccg tccttctcag agtacgccag cgtccaggtc     1500

ccgaggaagt ga                                                         1512


<210>  11
<211>  1029
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleic-acid sequence encoding the extracellular domain of the 
       human SIRP alpha protein

<400>  11
gaggaggagc tgcaggtgat tcagcctgac aagtccgtat cagttgcagc tggagagtcg       60

gccattctgc actgcactgt gacctccctg atccctgtgg ggcccatcca gtggttcaga      120

ggagctggac cagcccggga attaatctac aatcaaaaag aaggccactt cccccgggta      180

acaactgttt cagagtccac aaagagagaa aacatggact tttccatcag catcagtaac      240

atcaccccag cagatgccgg cacctactac tgtgtgaagt tccggaaagg gagccctgac      300

acggagttta agtctggagc aggcactgag ctgtctgtgc gtgccaaacc ctctgccccc      360

gtggtatcgg gccctgcggc gagggccaca cctcagcaca cagtgagctt cacctgcgag      420

tcccacggct tctcacccag agacatcacc ctgaaatggt tcaaaaatgg gaatgagctc      480

tcagacttcc agaccaacgt ggaccccgta ggagagagcg tgtcctacag catccacagc      540

acagccaagg tggtgctgac ccgcgaggac gttcactctc aagtcatctg cgaggtggcc      600

cacgtcacct tgcaggggga ccctcttcgt gggactgcca acttgtctga gaccatccga      660

gttccaccca ccttggaggt tactcaacag cccgtgaggg cagagaacca ggtgaatgtc      720

acctgccagg tgaggaagtt ctacccccag agactacagc tgacctggtt ggagaatgga      780

aacgtgtccc ggacagaaac ggcctcaacc gttacagaga acaaggatgg tacctacaac      840

tggatgagct ggctcctggt gaatgtatct gcccacaggg atgatgtgaa gctcacctgc      900

caggtggagc atgacgggca gccagcggtc agcaaaagcc atgacctgaa ggtctcagcc      960

cacccgaagg agcagggctc aaataccgcc gctgagaaca ctggatctaa tgaacggaac     1020

atctatatt                                                             1029


<210>  12
<211>  254
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of full length 41BBL

<400>  12

Met Glu Tyr Ala Ser Asp Ala Ser Leu Asp Pro Glu Ala Pro Trp Pro 
1               5                   10                  15      


Pro Ala Pro Arg Ala Arg Ala Cys Arg Val Leu Pro Trp Ala Leu Val 
            20                  25                  30          


Ala Gly Leu Leu Leu Leu Leu Leu Leu Ala Ala Ala Cys Ala Val Phe 
        35                  40                  45              


Leu Ala Cys Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser 
    50                  55                  60                  


Ala Ala Ser Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp 
65                  70                  75                  80  


Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val 
                85                  90                  95      


Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp 
            100                 105                 110         


Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu 
        115                 120                 125             


Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe 
    130                 135                 140                 


Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser 
145                 150                 155                 160 


Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala 
                165                 170                 175     


Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala 
            180                 185                 190         


Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala 
        195                 200                 205             


Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His 
    210                 215                 220                 


Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val 
225                 230                 235                 240 


Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 
                245                 250                 


<210>  13
<211>  765
<212>  DNA
<213>  Artificial sequence

<220>
<223>   Nucleic-acid sequence of full length 41BBL

<400>  13
atggaatacg cctctgacgc ttcactggac cccgaagccc cgtggcctcc cgcgccccgc       60

gctcgcgcct gccgcgtact gccttgggcc ctggtcgcgg ggctgctgct gctgctgctg      120

ctcgctgccg cctgcgccgt cttcctcgcc tgcccctggg ccgtgtccgg ggctcgcgcc      180

tcgcccggct ccgcggccag cccgagactc cgcgagggtc ccgagctttc gcccgacgat      240

cccgccggcc tcttggacct gcggcagggc atgtttgcgc agctggtggc ccaaaatgtt      300

ctgctgatcg atgggcccct gagctggtac agtgacccag gcctggcagg cgtgtccctg      360

acggggggcc tgagctacaa agaggacacg aaggagctgg tggtggccaa ggctggagtc      420

tactatgtct tctttcaact agagctgcgg cgcgtggtgg ccggcgaggg ctcaggctcc      480

gtttcacttg cgctgcacct gcagccactg cgctctgctg ctggggccgc cgccctggct      540

ttgaccgtgg acctgccacc cgcctcctcc gaggctcgga actcggcctt cggtttccag      600

ggccgcttgc tgcacctgag tgccggccag cgcctgggcg tccatcttca cactgaggcc      660

agggcacgcc atgcctggca gcttacccag ggcgccacag tcttgggact cttccgggtg      720

acccccgaaa tcccagccgg actcccttca ccgaggtcgg aataa                      765


<210>  14
<211>  615
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleic-acid sequence encoding the extracellular domain of the 
       human 41BBL

<400>  14
gcctgcccct gggccgtgtc cggggctcgc gcctcgcccg gctccgcggc cagcccgaga       60

ctccgcgagg gtcccgagct ttcgcccgac gatcccgccg gcctcttgga cctgcggcag      120

ggcatgtttg cgcagctggt ggcccaaaat gttctgctga tcgatgggcc cctgagctgg      180

tacagtgacc caggcctggc aggcgtgtcc ctgacggggg gcctgagcta caaagaggac      240

acgaaggagc tggtggtggc caaggctgga gtctactatg tcttctttca actagagctg      300

cggcgcgtgg tggccggcga gggctcaggc tccgtttcac ttgcgctgca cctgcagcca      360

ctgcgctctg ctgctggggc cgccgccctg gctttgaccg tggacctgcc acccgcctcc      420

tccgaggctc ggaactcggc cttcggtttc cagggccgct tgctgcacct gagtgccggc      480

cagcgcctgg gcgtccatct tcacactgag gccagggcac gccatgcctg gcagcttacc      540

cagggcgcca cagtcttggg actcttccgg gtgacccccg aaatcccagc cggactccct      600

tcaccgaggt cggaa                                                       615


<210>  15
<211>  1749
<212>  DNA
<213>  Artificial sequence

<220>
<223>  cloning sequence of His-tagged SIRP alpha -41BBL in the vector

<400>  15
gaattcccgc cgccaccatg ggctggtcct gcatcattct gtttctggtg gccacagcca       60

ccggcgtgca ctctcaccat catcaccacc atgaagagga actgcaagtg atccagcctg      120

acaagagcgt gctggtggct gctggcgaaa cagccacact gagatgtacc gccacctctc      180

tgatccctgt gggccctatc cagtggttta gaggcgctgg acctggcaga gagctgatct      240

acaaccagaa agagggacac ttccccagag tgaccaccgt gtccgacctg accaagcgga      300

acaacatgga cttcagcatc cggatcggca acatcacccc tgccgatgcc ggcacctact      360

actgcgtgaa gttcagaaag ggcagccccg acgacgtcga gtttaaaagc ggagccggca      420

cagagctgag cgtgcgggct aaaccttctg ctcctgtggt gtctggacct gccgctagag      480

ctacacctca gcacaccgtg tcttttacct gcgagagcca cggcttcagc cccagagata      540

tcaccctgaa gtggttcaag aacggcaacg agctgtccga cttccagacc aacgtggacc      600

ctgtgggaga gagcgtgtcc tacagcatcc acagcacagc caaggtggtg ctgacccggg      660

aagatgtgca ctcccaagtg atttgcgagg tggcccacgt taccctgcaa ggcgatcctc      720

tgagaggcac cgccaatctg agcgagacaa tccgggtgcc acctacactg gaagtgaccc      780

agcagcctgt gcgggccgag aatcaagtga acgtgacctg ccaagtgcgg aagttctacc      840

ctcagagact gcagctgacc tggctggaaa acggcaatgt gtccagaacc gagacagcca      900

gcaccgtgac cgagaacaag gatggcacct acaattggat gagctggctg ctcgtgaatg      960

tgtctgccca ccgggacgat gtgaagctga catgccaggt ggaacacgat ggccagcctg     1020

ccgtgtctaa gagccacgac ctgaaggtgt ccgctcatcc caaagagcag ggctctaata     1080

ctgccgccga gaacaccggc agcaacgaga gaaatatcta cggcgcttgt ccttgggccg     1140

tttctggcgc tagagcctct cctggatctg ccgcttctcc cagactgaga gagggacctg     1200

agctgagccc tgatgatcct gctggactgc tggatctgag acagggcatg tttgcccagc     1260

tggtggccca gaatgtgctg ctgattgatg gccctctgtc ctggtacagc gatcctggac     1320

ttgctggcgt tagcctgact ggcggcctga gctacaaaga ggacaccaaa gaactggtgg     1380

tggccaaggc cggcgtgtac tacgtgttct ttcagctgga actgcggaga gtggtggccg     1440

gcgaaggatc tggatctgtg tctctggctc tgcatctgca gcctctgaga tctgctgctg     1500

gtgctgctgc tctggccctg acagttgatc tgcctcctgc ctctagcgag gccagaaact     1560

ccgcctttgg cttccaaggc agactgctgc acctgagcgc tggacagaga ctgggagtcc     1620

atctgcacac agaagccaga gctagacacg cctggcagct gacacaaggc gctacagtgc     1680

tgggcctgtt cagagtgacc cctgagattc cagccggcct gccatctcct agatctgagt     1740

gataagctt                                                             1749


