               Sequence listing

<110> JSC "BIOCAD"

<120> Isolated bispecific antibody that specifically binds to CD47 and PD-L1

<160> 35

<170> BiSSAP 1.3.6

<210> 1
<211> 5
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR1 (Kabat) of the variable domain of the heavy chain of the first antigen-binding fragment, which specifically binds to CD47

<400> 1
Arg Tyr Trp Met Tyr 
1               5   

<210> 2
<211> 24
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR2 (Kabat) of the variable domain of the heavy chain of the first antigen-binding fragment, which specifically binds to CD47

<400> 2
Ser Ile Glu Asp Ser Ser Ile Asn Thr Gly Gly Gly Thr Glu Thr Thr 
1               5                   10                  15      
Tyr Tyr Thr Asp Ser Val Lys Gly 
            20                  

<210> 3
<211> 18
<212> PRT
<213> Artificial sequence

<220> 
<223> amino acid sequence CDR3 (Kabat) of the variable domain of the heavy chain of the first antigen-binding fragment, which specifically binds to CD47

<400> 3
Gly Asp Tyr Tyr Cys Thr Thr Tyr Glu Cys Gln His Tyr Tyr Gly Met 
1               5                   10                  15      
Asp Tyr 
        

<210> 4
<211> 14
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR1 (Kabat) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 4
Gly Leu Ser Ser Gly Thr Val Thr Ala Ile Asn Tyr Pro Gly 
1               5                   10                  

<210> 5
<211> 7
<212> PRT
<213> Artificial sequence

<220> 
<223> amino acid sequence CDR2 (Kabat) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 5
Asn Thr Asn Thr Arg His Ser 
1               5           

<210> 6
<211> 10
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR3 (Kabat) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 6
Ala Leu Tyr Met Gly Asn Gly Gly His Met 
1               5                   10  

<210> 7
<211> 5
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR1 (Kabat) of the variable heavy chain domain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 7
Asp Tyr Ala Met Ser 
1               5   

<210> 8
<211> 17
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR2 (Kabat) of the variable heavy chain domain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 8
Asp Ile Ser Trp Ser Gly Ser Asn Thr Asn Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      
Gly 
    

<210> 9
<211> 13
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR3 (Kabat) of the variable heavy chain domain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 9
Ala Pro Leu Leu Leu Ala Met Thr Phe Gly Val Gly Ser 
1               5                   10              

<210> 10
<211> 7
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of CDR1 (Chothia) of the variable domain of the heavy chain of the first antigen-binding fragment, which specifically binds to CD47

<400> 10
Gly Phe Thr Phe Ser Arg Tyr 
1               5           

<210> 11
<211> 13
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of CDR2 (Chothia) of the variable domain of the heavy chain of the first antigen-binding fragment, which specifically binds to CD47

<400> 11
Glu Asp Ser Ser Ile Asn Thr Gly Gly Gly Thr Glu Thr 
1               5                   10              

<210> 12
<211> 18
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of CDR3 (Chothia) of the variable domain of the heavy chain of the first antigen-binding fragment, which specifically binds to CD47

<400> 12
Gly Asp Tyr Tyr Cys Thr Thr Tyr Glu Cys Gln His Tyr Tyr Gly Met 
1               5                   10                  15      
Asp Tyr 
        

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


<220> 
<223> amino acid sequence CDR1 (Chothia) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 13
Gly Leu Ser Ser Gly Thr Val Thr Ala Ile Asn Tyr Pro Gly 
1               5                   10                  

<210> 14
<211> 7
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR2 (Chothia) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 14
Asn Thr Asn Thr Arg His Ser 
1               5           

<210> 15
<211> 10
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR3 (Chothia) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 15
Ala Leu Tyr Met Gly Asn Gly Gly His Met 
1               5                   10  

<210> 16
<211> 7
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of CDR1 (Chothia) of the variable heavy chain domain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 16
Gly Phe Thr Phe Asp Asp Tyr 
1               5           

<210> 17
<211> 6
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of CDR2 (Chothia) of the variable heavy chain domain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 17
Ser Trp Ser Gly Ser Asn 
1               5       

<210> 18
<211> 13
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of CDR3 (Chothia) of the variable heavy chain domain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 18
Ala Pro Leu Leu Leu Ala Met Thr Phe Gly Val Gly Ser 
1               5                   10              

<210> 19
<211> 9
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR1 (IMG) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 19
Ser Gly Thr Val Thr Ala Ile Asn Tyr 
1               5                   

<210> 20
<211> 4
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR2 (IMG) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 20
Asn Thr Asn
1               

<210> 21
<211> 10
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence CDR3 (IMG) of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 21
Ala Leu Tyr Met Gly Asn Gly Gly His Met 
1               5                   10  

<210> 22
<211> 134
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence of the variable domain of the heavy chain of the first antigen-binding fragment that specifically binds to CD47

<400> 22
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Arg Tyr 
            20                  25                  30          
Trp Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Ser Ile Glu Asp Ser Ser Ile Asn Thr Gly Gly Gly Thr Glu Thr 
    50                  55                  60                  
Thr Tyr Tyr Thr Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 
65                  70                  75                  80  
Asn Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 
                85                  90                  95      
Asp Thr Ala Val Tyr Tyr Cys Ala Lys Gly Asp Tyr Tyr Cys Thr Thr 
            100                 105                 110         
Tyr Glu Cys Gln His Tyr Tyr Gly Met Asp Tyr Trp Gly Gln Gly Thr 
        115                 120                 125             
Thr Val Thr Val Ser Ser 
    130                 

<210> 23
<211> 110
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence of the variable domain of the common light chain for the first and second antigen-binding fragment

<400> 23
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Ser Val Ser Pro Gly Gly 
1               5                   10                  15      
Thr Val Thr Leu Thr Cys Gly Leu Ser Ser Gly Thr Val Thr Ala Ile 
            20                  25                  30          
Asn Tyr Pro Gly Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Thr 
        35                  40                  45              
Leu Ile Tyr Asn Thr Asn Thr Arg His Ser Gly Val Pro Asp Arg Phe 
    50                  55                  60                  
Ser Gly Ser Ile Ser Gly Asn Lys Ala Ala Leu Thr Ile Thr Gly Ala 
65                  70                  75                  80  
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Tyr Met Gly Asn 
                85                  90                  95      
Gly Gly His Met Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 110 

<210> 24
<211> 122
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence of the variable domain of the heavy chain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 24
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Asp Ile Ser Trp Ser Gly Ser Asn Thr Asn Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr His Cys 
                85                  90                  95      
Ala Arg Ala Pro Leu Leu Leu Ala Met Thr Phe Gly Val Gly Ser Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210> 25
<211> 464
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of the heavy chain of the first antigen-binding fragment that specifically binds to CD47

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



<210> 26
<211> 216
<212> PRT
<213> Artificial sequence


<220> 
<223> amino acid sequence of a common light chain for the first and second antigen-binding fragment

<400> 26
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Ser Val Ser Pro Gly Gly 
1               5                   10                  15      
Thr Val Thr Leu Thr Cys Gly Leu Ser Ser Gly Thr Val Thr Ala Ile 
            20                  25                  30          
Asn Tyr Pro Gly Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Thr 
        35                  40                  45              
Leu Ile Tyr Asn Thr Asn Thr Arg His Ser Gly Val Pro Asp Arg Phe 
    50                  55                  60                  
Ser Gly Ser Ile Ser Gly Asn Lys Ala Ala Leu Thr Ile Thr Gly Ala 
65                  70                  75                  80  
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Tyr Met Gly Asn 
                85                  90                  95      
Gly Gly His Met Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 
            100                 105                 110         
Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu 
        115                 120                 125             
Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 
    130                 135                 140                 
Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys 
145                 150                 155                 160 
Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr 
                165                 170                 175     
Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 
            180                 185                 190         
Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 
        195                 200                 205             
Thr Val Ala Pro Thr Glu Cys Ser 
    210                 215     

<210> 27
<211> 453
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of the heavy chain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 27
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Asp Ile Ser Trp Ser Gly Ser Asn Thr Asn Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr His Cys 
                85                  90                  95      
Ala Arg Ala Pro Leu Leu Leu Ala Met Thr Phe Gly Val Gly Ser Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
        115                 120                 125             
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 
    130                 135                 140                 
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
                165                 170                 175     
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
        195                 200                 205             
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser 
    210                 215                 220                 
Cys Asp Gly Pro Gly Gly Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala 
225                 230                 235                 240 
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
                245                 250                 255     
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
            260                 265                 270         
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
        275                 280                 285             
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
    290                 295                 300                 
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
305                 310                 315                 320 
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
                325                 330                 335     
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
            340                 345                 350         
Gln Val Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 
        355                 360                 365             
Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
    370                 375                 380                 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
385                 390                 395                 400 
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 
                405                 410                 415     
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
            420                 425                 430         
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
        435                 440                 445             
Leu Ser Pro Gly Lys 
    450             

<210> 28
<211> 402
<212> DNA
<213> Artificial sequence


<220> 
<223> A nucleic acid that encodes the amino acid sequence of the variable domain of the heavy chain of the first antigen-binding fragment that specifically binds to CD47

<400> 28
caagtacagt tggtagagtc tggaggtgga ttagtgcagc ccggagggag cctgcgattg      60

tcatgtgccg caagcggttt caccttctcc cgctattgga tgtattgggt tagacaggct     120

cctgggaagg gtcttgagtg ggtttcctcc atcgaggact cttcaattaa cacaggagga     180

gggacggaaa caacttacta cactgatagc gtgaaaggac ggtttaccat ctctcgcgac     240

aacgcgaaga acaccttata cctccagatg aattccctca gggcagaaga caccgcagtc     300

tattattgcg ctaaagggga ctactactgc accacatatg agtgtcagca ctattatggc     360

atggattatt ggggccaagg tactacagtg actgtttcga gt                        402


<210> 29
<211> 330
<212> DNA
<213> Artificial sequence


<400> 29
cagactgtgg tgacccagga gccatccctg tcagtgtctc caggagggac ggtcaccctc      60

acctgcggcc tcagttctgg gactgtcact gccattaact accctggttg gtaccagcag     120

acgccaggcc aggctccccg aacccttatc tacaacacaa acacccgaca ctccggcgtc     180

cccgatcgct tctccggatc catctctggt aacaaagccg ccctcaccat cacaggagcc     240

caggccgagg acgaggccga ctattactgt gctctgtaca tgggtaatgg tggccacatg     300

ttcggcggag ggaccaagct gaccgtccta                                      330


<210> 30
<211> 366
<212> DNA
<213> Artificial sequence


<220> 
<223> A nucleic acid that encodes the amino acid sequence of the variable domain of the heavy chain of the second antigen-binding fragment, which specifically binds to PD-L1

<400> 30
gaagtgcagc tggtggagtc tgggggaggc gtggtgaggc ctggtgggtc tctgagactc      60

tcctgtgcag cctctggatt cacttttgat gattatgcca tgagctgggt ccgccaggct     120

ccagggaagg ggctggagtg ggtctcagat attagctgga gtggtagtaa cacaaactat     180

gcagactccg tgaagggccg attcaccatc tccagagaca acgccaagaa cagcctgtat     240

ctgcaaatga acagtctgag agctgaggac acggccctgt atcactgtgc aagagccccc     300

ttgctcctgg ctatgacttt tggggttggt tcctggggcc aggggaccct ggtcaccgtc     360

tcctca                                                                366


<210> 31
<211> 1392
<212> DNA
<213> Artificial sequence


<220> 
<223> A nucleic acid that encodes the amino acid sequence of the heavy chain of the first antigen-binding fragment that specifically binds to CD47


<400> 31
caagtacagt tggtagagtc tggaggtgga ttagtgcagc ccggagggag cctgcgattg      60

tcatgtgccg caagcggttt caccttctcc cgctattgga tgtattgggt tagacaggct     120

cctgggaagg gtcttgagtg ggtttcctcc atcgaggact cttcaattaa cacaggagga     180

gggacggaaa caacttacta cactgatagc gtgaaaggac ggtttaccat ctctcgcgac     240

aacgcgaaga acaccttata cctccagatg aattccctca gggcagaaga caccgcagtc     300

tattattgcg ctaaagggga ctactactgc accacatatg agtgtcagca ctattatggc     360

atggattatt ggggccaagg tactacagtg actgtttcga gtgctagcac caagggccca     420

tcggtcttcc ccctggcacc ctcctccaag agcacctctg ggggcacagc ggccctgggc     480

tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg     540

accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc     600

agcgtggtga ccgtgccctc cagcagcttg ggcacccaga cctacatctg caacgtgaat     660

cacaagccca gcaacaccaa ggtggacaag agagttgagc ccaaatcttg tgacaaaact     720

cacacatgcc caccgtgccc agcacctgaa gccgcagggg gaccgtcagt cttcctcttc     780

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg     840

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag     900

gtgcataatg ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgtgtggtc     960

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc    1020

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc    1080

cgagaaccac aggtgtacac cctgccccca tgccgggatg agctgaccaa gaaccaggtc    1140

agcctgtggt gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc    1200

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc    1260

ttcttcctct atagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc    1320

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg    1380

tccccgggta aa                                                        1392


<210> 32
<211> 648
<212> DNA
<213> Artificial sequence


<220> 
<223> A nucleic acid that encodes the amino acid sequence of a common light chain for the first and second antigen-binding fragment


<400> 32
cagactgtgg tgacccagga gccatccctg tcagtgtctc caggagggac ggtcaccctc      60

acctgcggcc tcagttctgg gactgtcact gccattaact accctggttg gtaccagcag     120

acgccaggcc aggctccccg aacccttatc tacaacacaa acacccgaca ctccggcgtc     180

cccgatcgct tctccggatc catctctggt aacaaagccg ccctcaccat cacaggagcc     240

caggccgagg acgaggccga ctattactgt gctctgtaca tgggtaatgg tggccacatg     300

ttcggcggag ggaccaagct gaccgtccta ggtcagccca aggctgcccc ctccgtcact     360

ctgttccctc cctcctctga ggagcttcaa gccaacaagg ccacactggt gtgtctcatc     420

agtgacttct accctggagc cgtgacagtg gcttggaaag cagatagcag ccccgtcaag     480

gccggagtgg agaccaccac accctccaaa caaagcaaca acaagtacgc tgccagcagc     540

tatctgagcc tgacccctga gcagtggaag tcccacagaa gctacagctg ccaggtcacg     600

catgaaggga gcaccgtgga gaagacagtg gcccctacag aatgttca                  648


<210> 33
<211> 1359
<212> DNA
<213> Artificial sequence


<220> 
<223> Nucleic acid, which encodes the amino acid sequence of the heavy chain of the second antigen-binding fragment, which specifically binds to PD-L1


<400> 33
gaagtgcagc tggtggagtc tgggggaggc gtggtgaggc ctggtgggtc tctgagactc      60

tcctgtgcag cctctggatt cacttttgat gattatgcca tgagctgggt ccgccaggct     120

ccagggaagg ggctggagtg ggtctcagat attagctgga gtggtagtaa cacaaactat     180

gcagactccg tgaagggccg attcaccatc tccagagaca acgccaagaa cagcctgtat     240

ctgcaaatga acagtctgag agctgaggac acggccctgt atcactgtgc aagagccccc     300

ttgctcctgg ctatgacttt tggggttggt tcctggggcc aggggaccct ggtcaccgtc     360

tcctcagcta gcaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc     420

tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acccgtgacc     480

gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccagc tgtccttcag     540

tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc     600

cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagaaagtt     660

gagcccaaat cttgtgacgg tcctggaggc acatgcccac cgtgcccagc acctgaagcc     720

gcagggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc     780

cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag     840

ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag     900

cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg     960

aatggcaagg agtacaagtg caaggtctcc aacaaagccc tcccagcccc catcgagaaa    1020

accatctcca aagccaaagg gcagccccga gaaccacagg tgtgcaccct gcccccatcc    1080

cgggaggaga tgaccaagaa ccaggtcagc ctgtcctgcg ccgtcaaagg cttctatccc    1140

agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg    1200

cctcccgtgc tggactccga cggctccttc ttcctcgtca gcaagctcac cgtggacaag    1260

agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac    1320

cactacacgc agaagagcct ctccctgtct cccgggaaa                           1359


<210> 34
<211> 104
<212> PRT
<213> Artificial sequence


<220> 
<223> Amino acid sequence of the variable domain of the light chain of the first antigen-binding fragment that specifically binds to CD47, antibody BCD106-02-001

<400> 34
Glu Leu Thr Gln Pro Ser Ala Val Ser Val Ser Leu Gly Gln Thr Val 
1               5                   10                  15      
Arg Ile Thr Cys Gln Gly Asp Arg Ile Glu Asn Tyr Tyr Thr Ser Trp 
            20                  25                  30          
Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Gly Asn 
        35                  40                  45              
Ala Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser Ser Ser 
    50                  55                  60                  
Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu 
65                  70                  75                  80  
Ala Asp Tyr Tyr Cys Gln Ser Gly Ser Ser Thr Glu Asn Ile Phe Gly 
                85                  90                  95      
Gly Gly Thr Lys Leu Thr Val Leu 
            100                 

<210> 35
<211> 210
<212> PRT
<213> Artificial sequence


<220> 
<223> the amino acid sequence of the light chain of the first antigen-binding fragment, which specifically binds to CD47, antibodies BCD106-02-001

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

