                         SEQUENCE LISTING

<110>  NantBio
 
<120>  TARGETED IL-12 TREATMENTS AND METHODS TO STIMULATE haNK AND 
       NK92mi CELLS

<130>  102719.0016PRO

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  994
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric Sequence for leader peptide/mouse scIL-12/hu51-4 heavy 
       chain

<400>  1

Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu 
1               5                   10                  15      


Ala Ser Pro Leu Met Trp Glu Leu Glu Lys Asp Val Tyr Val Val Glu 
            20                  25                  30          


Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val Asn Leu Thr Cys 
        35                  40                  45              


Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln Arg His 
    50                  55                  60                  


Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr Val Lys Glu Phe 
65                  70                  75                  80  


Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Thr Leu Ser 
                85                  90                  95      


His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly Ile Trp Ser Thr 
            100                 105                 110         


Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys Glu Ala 
        115                 120                 125             


Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu Val Gln Arg Asn 
    130                 135                 140                 


Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro Asp Ser 
145                 150                 155                 160 


Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala Glu Lys Val Thr 
                165                 170                 175     


Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln Glu Asp 
            180                 185                 190         


Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu Ala Leu 
        195                 200                 205             


Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser Phe Phe 
    210                 215                 220                 


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Met Lys 
225                 230                 235                 240 


Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Ser 
                245                 250                 255     


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe Phe Val Arg Ile 
            260                 265                 270         


Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu Gly Cys Asn Gln 
        275                 280                 285             


Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu Val Gln Cys Lys 
    290                 295                 300                 


Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn Ser Ser 
305                 310                 315                 320 


Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg Ser Gly Gly Gly 
                325                 330                 335     


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Val Ile Pro 
            340                 345                 350         


Val Ser Gly Pro Ala Arg Cys Leu Ser Gln Ser Arg Asn Leu Leu Lys 
        355                 360                 365             


Thr Thr Asp Asp Met Val Lys Thr Ala Arg Glu Lys Leu Lys His Tyr 
    370                 375                 380                 


Ser Cys Thr Ala Glu Asp Ile Asp His Lys Asp Ile Thr Arg Asp Gln 
385                 390                 395                 400 


Thr Ser Thr Leu Lys Thr Cys Leu Pro Leu Glu Leu His Lys Asn Glu 
                405                 410                 415     


Ser Cys Leu Ala Thr Arg Glu Thr Ser Ser Thr Thr Arg Gly Ser Cys 
            420                 425                 430         


Leu Pro Pro Gln Lys Thr Ser Leu Met Met Thr Leu Cys Leu Gly Ser 
        435                 440                 445             


Ile Tyr Glu Asp Leu Lys Met Tyr Gln Thr Glu Phe Gln Ala Ile Asn 
    450                 455                 460                 


Ala Ala Leu Gln Asn His Asn His Gln Gln Ile Ile Leu Asp Lys Gly 
465                 470                 475                 480 


Met Leu Val Ala Ile Asp Glu Leu Met Gln Ser Leu Asn His Asn Gly 
                485                 490                 495     


Glu Thr Leu Arg Gln Lys Pro Pro Val Gly Glu Ala Asp Pro Tyr Arg 
            500                 505                 510         


Val Lys Met Lys Leu Cys Ile Leu Leu His Ala Phe Ser Thr Arg Val 
        515                 520                 525             


Val Thr Ile Asn Arg Val Met Gly Tyr Leu Ser Ser Ala Leu Glu Gln 
    530                 535                 540                 


Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser 
545                 550                 555                 560 


Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr Trp 
                565                 570                 575     


Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly 
            580                 585                 590         


Ala Ile Tyr Pro Gly Asn Ser Asp Thr Ser Tyr Asn Gln Lys Phe Lys 
        595                 600                 605             


Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr Met 
    610                 615                 620                 


Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
625                 630                 635                 640 


Arg Gly Glu Glu Ile Gly Ser Arg Arg Trp Phe Ala Tyr Trp Gly Gln 
                645                 650                 655     


Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
            660                 665                 670         


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
        675                 680                 685             


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
    690                 695                 700                 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
705                 710                 715                 720 


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
                725                 730                 735     


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
            740                 745                 750         


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
        755                 760                 765             


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
    770                 775                 780                 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
785                 790                 795                 800 


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                805                 810                 815     


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
            820                 825                 830         


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
        835                 840                 845             


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
    850                 855                 860                 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
865                 870                 875                 880 


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                885                 890                 895     


Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
            900                 905                 910         


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
        915                 920                 925             


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
    930                 935                 940                 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
945                 950                 955                 960 


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                965                 970                 975     


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
            980                 985                 990         


Gly Lys 
        


<210>  2
<211>  991
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric Sequence for leader peptide/human scIL-12/hu51-4 heavy 
       chain

<400>  2

Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu 
1               5                   10                  15      


Ala Ser Pro Leu Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu 
            20                  25                  30          


Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys 
        35                  40                  45              


Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser 
    50                  55                  60                  


Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe 
65                  70                  75                  80  


Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser 
                85                  90                  95      


His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr 
            100                 105                 110         


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


Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr 
    130                 135                 140                 


Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser 
145                 150                 155                 160 


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


Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln 
            180                 185                 190         


Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val 
        195                 200                 205             


Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser 
    210                 215                 220                 


Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln 
225                 230                 235                 240 


Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr 
                245                 250                 255     


Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys 
            260                 265                 270         


Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe 
        275                 280                 285             


Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile 
    290                 295                 300                 


Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp 
305                 310                 315                 320 


Ala Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
                325                 330                 335     


Gly Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly 
            340                 345                 350         


Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser 
        355                 360                 365             


Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr 
    370                 375                 380                 


Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr 
385                 390                 395                 400 


Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu 
                405                 410                 415     


Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser 
            420                 425                 430         


Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu 
        435                 440                 445             


Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu 
    450                 455                 460                 


Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala 
465                 470                 475                 480 


Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val 
                485                 490                 495     


Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile 
            500                 505                 510         


Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile 
        515                 520                 525             


Asp Arg Val Met Ser Tyr Leu Asn Ala Ser Leu Glu Gln Val Gln Leu 
    530                 535                 540                 


Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val 
545                 550                 555                 560 


Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr Trp Met His Trp 
                565                 570                 575     


Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Ile Tyr 
            580                 585                 590         


Pro Gly Asn Ser Asp Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys Ala 
        595                 600                 605             


Thr Ile Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser 
    610                 615                 620                 


Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Glu 
625                 630                 635                 640 


Glu Ile Gly Ser Arg Arg Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu 
                645                 650                 655     


Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
            660                 665                 670         


Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
        675                 680                 685             


Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
    690                 695                 700                 


Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
705                 710                 715                 720 


Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                725                 730                 735     


Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
            740                 745                 750         


Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His 
        755                 760                 765             


Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
    770                 775                 780                 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
785                 790                 795                 800 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                805                 810                 815     


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
            820                 825                 830         


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
        835                 840                 845             


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
    850                 855                 860                 


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
865                 870                 875                 880 


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                885                 890                 895     


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
            900                 905                 910         


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
        915                 920                 925             


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
    930                 935                 940                 


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
945                 950                 955                 960 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                965                 970                 975     


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
            980                 985                 990     


<210>  3
<211>  236
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric Sequence for leader peptide/hu51-4 light chain

<400>  3

Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser 
1               5                   10                  15      


Val Ala Met Ser Arg Gly Glu Ile Val Leu Thr Gln Ser Pro Ala Thr 
            20                  25                  30          


Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Arg 
        35                  40                  45              


Gln Ser Ile Ser Asn Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln 
    50                  55                  60                  


Ala Pro Arg Leu Leu Ile Tyr Tyr Ala Ser Gln Ser Ile Ser Gly Ile 
65                  70                  75                  80  


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


Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
            100                 105                 110         


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


Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
    130                 135                 140                 


Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
145                 150                 155                 160 


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


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


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


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


Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 235     


