                         SEQUENCE LISTING

<110>  SUTROVAX, INC.
 
<120>  IMPROVEMENTS IN IMMUNOGENIC CONJUGATES

<130>  STRO-005/01WO 331540-2034

<150>  US 62/693,981
<151>  2018-07-04

<160>  5     

<170>  PatentIn version 3.5

<210>  1
<211>  535
<212>  PRT
<213>  Corynebacterium diphtheriae

<400>  1

Gly Ala Asp Asp Val Val Asp Ser Ser Lys Ser Phe Val Met Glu Asn 
1               5                   10                  15      


Phe Ser Ser Tyr His Gly Thr Lys Pro Gly Tyr Val Asp Ser Ile Gln 
            20                  25                  30          


Lys Gly Ile Gln Lys Pro Lys Ser Gly Thr Gln Gly Asn Tyr Asp Asp 
        35                  40                  45              


Asp Trp Lys Glu Phe Tyr Ser Thr Asp Asn Lys Tyr Asp Ala Ala Gly 
    50                  55                  60                  


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


Val Lys Val Thr Tyr Pro Gly Leu Thr Lys Val Leu Ala Leu Lys Val 
                85                  90                  95      


Asp Asn Ala Glu Thr Ile Lys Lys Glu Leu Gly Leu Ser Leu Thr Glu 
            100                 105                 110         


Pro Leu Met Glu Gln Val Gly Thr Glu Glu Phe Ile Lys Arg Phe Gly 
        115                 120                 125             


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


Ser Ser Val Glu Tyr Ile Asn Asn Trp Glu Gln Ala Lys Ala Leu Ser 
145                 150                 155                 160 


Val Glu Leu Glu Ile Asn Phe Glu Thr Arg Gly Lys Arg Gly Gln Asp 
                165                 170                 175     


Ala Met Tyr Glu Tyr Met Ala Gln Ala Cys Ala Gly Asn Arg Val Arg 
            180                 185                 190         


Arg Ser Val Gly Ser Ser Leu Ser Cys Ile Asn Leu Asp Trp Asp Val 
        195                 200                 205             


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


Pro Ile Lys Asn Lys Met Ser Glu Ser Pro Asn Lys Thr Val Ser Glu 
225                 230                 235                 240 


Glu Lys Ala Lys Gln Tyr Leu Glu Glu Phe His Gln Thr Ala Leu Glu 
                245                 250                 255     


His Pro Glu Leu Ser Glu Leu Lys Thr Val Thr Gly Thr Asn Pro Val 
            260                 265                 270         


Phe Ala Gly Ala Asn Tyr Ala Ala Trp Ala Val Asn Val Ala Gln Val 
        275                 280                 285             


Ile Asp Ser Glu Thr Ala Asp Asn Leu Glu Lys Thr Thr Ala Ala Leu 
    290                 295                 300                 


Ser Ile Leu Pro Gly Ile Gly Ser Val Met Gly Ile Ala Asp Gly Ala 
305                 310                 315                 320 


Val His His Asn Thr Glu Glu Ile Val Ala Gln Ser Ile Ala Leu Ser 
                325                 330                 335     


Ser Leu Met Val Ala Gln Ala Ile Pro Leu Val Gly Glu Leu Val Asp 
            340                 345                 350         


Ile Gly Phe Ala Ala Tyr Asn Phe Val Glu Ser Ile Ile Asn Leu Phe 
        355                 360                 365             


Gln Val Val His Asn Ser Tyr Asn Arg Pro Ala Tyr Ser Pro Gly His 
    370                 375                 380                 


Lys Thr Gln Pro Phe Leu His Asp Gly Tyr Ala Val Ser Trp Asn Thr 
385                 390                 395                 400 


Val Glu Asp Ser Ile Ile Arg Thr Gly Phe Gln Gly Glu Ser Gly His 
                405                 410                 415     


Asp Ile Lys Ile Thr Ala Glu Asn Thr Pro Leu Pro Ile Ala Gly Val 
            420                 425                 430         


Leu Leu Pro Thr Ile Pro Gly Lys Leu Asp Val Asn Lys Ser Lys Thr 
        435                 440                 445             


His Ile Ser Val Asn Gly Arg Lys Ile Arg Met Arg Cys Arg Ala Ile 
    450                 455                 460                 


Asp Gly Asp Val Thr Phe Cys Arg Pro Lys Ser Pro Val Tyr Val Gly 
465                 470                 475                 480 


Asn Gly Val His Ala Asn Leu His Val Ala Phe His Arg Ser Ser Ser 
                485                 490                 495     


Glu Lys Ile His Ser Asn Glu Ile Ser Ser Asp Ser Ile Gly Val Leu 
            500                 505                 510         


Gly Tyr Gln Lys Thr Val Asp His Thr Lys Val Asn Ser Lys Leu Ser 
        515                 520                 525             


Leu Phe Phe Glu Ile Lys Ser 
    530                 535 


<210>  2
<211>  535
<212>  PRT
<213>  Artificial Sequence

<220>  
<223>  CRM197 with Arg-Asn substitution

<400>  2

Gly Ala Asp Asp Val Val Asp Ser Ser Lys Ser Phe Val Met Glu Asn 
1               5                   10                  15      


Phe Ser Ser Tyr His Gly Thr Lys Pro Gly Tyr Val Asp Ser Ile Gln 
            20                  25                  30          


Lys Gly Ile Gln Lys Pro Lys Ser Gly Thr Gln Gly Asn Tyr Asp Asp 
        35                  40                  45              


Asp Trp Lys Glu Phe Tyr Ser Thr Asp Asn Lys Tyr Asp Ala Ala Gly 
    50                  55                  60                  


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


Val Lys Val Thr Tyr Pro Gly Leu Thr Lys Val Leu Ala Leu Lys Val 
                85                  90                  95      


Asp Asn Ala Glu Thr Ile Lys Lys Glu Leu Gly Leu Ser Leu Thr Glu 
            100                 105                 110         


Pro Leu Met Glu Gln Val Gly Thr Glu Glu Phe Ile Lys Arg Phe Gly 
        115                 120                 125             


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


Ser Ser Val Glu Tyr Ile Asn Asn Trp Glu Gln Ala Lys Ala Leu Ser 
145                 150                 155                 160 


Val Glu Leu Glu Ile Asn Phe Glu Thr Arg Gly Lys Arg Gly Gln Asp 
                165                 170                 175     


Ala Met Tyr Glu Tyr Met Ala Gln Ala Cys Ala Gly Asn Arg Val Arg 
            180                 185                 190         


Asn Ser Val Gly Ser Ser Leu Ser Cys Ile Asn Leu Asp Trp Asp Val 
        195                 200                 205             


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


Pro Ile Lys Asn Lys Met Ser Glu Ser Pro Asn Lys Thr Val Ser Glu 
225                 230                 235                 240 


Glu Lys Ala Lys Gln Tyr Leu Glu Glu Phe His Gln Thr Ala Leu Glu 
                245                 250                 255     


His Pro Glu Leu Ser Glu Leu Lys Thr Val Thr Gly Thr Asn Pro Val 
            260                 265                 270         


Phe Ala Gly Ala Asn Tyr Ala Ala Trp Ala Val Asn Val Ala Gln Val 
        275                 280                 285             


Ile Asp Ser Glu Thr Ala Asp Asn Leu Glu Lys Thr Thr Ala Ala Leu 
    290                 295                 300                 


Ser Ile Leu Pro Gly Ile Gly Ser Val Met Gly Ile Ala Asp Gly Ala 
305                 310                 315                 320 


Val His His Asn Thr Glu Glu Ile Val Ala Gln Ser Ile Ala Leu Ser 
                325                 330                 335     


Ser Leu Met Val Ala Gln Ala Ile Pro Leu Val Gly Glu Leu Val Asp 
            340                 345                 350         


Ile Gly Phe Ala Ala Tyr Asn Phe Val Glu Ser Ile Ile Asn Leu Phe 
        355                 360                 365             


Gln Val Val His Asn Ser Tyr Asn Arg Pro Ala Tyr Ser Pro Gly His 
    370                 375                 380                 


Lys Thr Gln Pro Phe Leu His Asp Gly Tyr Ala Val Ser Trp Asn Thr 
385                 390                 395                 400 


Val Glu Asp Ser Ile Ile Arg Thr Gly Phe Gln Gly Glu Ser Gly His 
                405                 410                 415     


Asp Ile Lys Ile Thr Ala Glu Asn Thr Pro Leu Pro Ile Ala Gly Val 
            420                 425                 430         


Leu Leu Pro Thr Ile Pro Gly Lys Leu Asp Val Asn Lys Ser Lys Thr 
        435                 440                 445             


His Ile Ser Val Asn Gly Arg Lys Ile Arg Met Arg Cys Arg Ala Ile 
    450                 455                 460                 


Asp Gly Asp Val Thr Phe Cys Arg Pro Lys Ser Pro Val Tyr Val Gly 
465                 470                 475                 480 


Asn Gly Val His Ala Asn Leu His Val Ala Phe His Arg Ser Ser Ser 
                485                 490                 495     


Glu Lys Ile His Ser Asn Glu Ile Ser Ser Asp Ser Ile Gly Val Leu 
            500                 505                 510         


Gly Tyr Gln Lys Thr Val Asp His Thr Lys Val Asn Ser Lys Leu Ser 
        515                 520                 525             


Leu Phe Phe Glu Ile Lys Ser 
    530                 535 


<210>  3
<211>  536
<212>  PRT
<213>  Artificial Sequence

<220>  
<223>  CRM197 with 6 preferred nnAA sites and N-terminus Met


<220>
<221>  misc_feature
<222>  (34)..(34)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (213)..(213)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (245)..(245)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (265)..(265)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (386)..(386)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (527)..(527)
<223>  Xaa can be any non-naturally occurring amino acid

<400>  3

Met Gly Ala Asp Asp Val Val Asp Ser Ser Lys Ser Phe Val Met Glu 
1               5                   10                  15      


Asn Phe Ser Ser Tyr His Gly Thr Lys Pro Gly Tyr Val Asp Ser Ile 
            20                  25                  30          


Gln Xaa Gly Ile Gln Lys Pro Lys Ser Gly Thr Gln Gly Asn Tyr Asp 
        35                  40                  45              


Asp Asp Trp Lys Glu Phe Tyr Ser Thr Asp Asn Lys Tyr Asp Ala Ala 
    50                  55                  60                  


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


Val Val Lys Val Thr Tyr Pro Gly Leu Thr Lys Val Leu Ala Leu Lys 
                85                  90                  95      


Val Asp Asn Ala Glu Thr Ile Lys Lys Glu Leu Gly Leu Ser Leu Thr 
            100                 105                 110         


Glu Pro Leu Met Glu Gln Val Gly Thr Glu Glu Phe Ile Lys Arg Phe 
        115                 120                 125             


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


Ser Ser Ser Val Glu Tyr Ile Asn Asn Trp Glu Gln Ala Lys Ala Leu 
145                 150                 155                 160 


Ser Val Glu Leu Glu Ile Asn Phe Glu Thr Arg Gly Lys Arg Gly Gln 
                165                 170                 175     


Asp Ala Met Tyr Glu Tyr Met Ala Gln Ala Cys Ala Gly Asn Arg Val 
            180                 185                 190         


Arg Arg Ser Val Gly Ser Ser Leu Ser Cys Ile Asn Leu Asp Trp Asp 
        195                 200                 205             


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


Gly Pro Ile Lys Asn Lys Met Ser Glu Ser Pro Asn Lys Thr Val Ser 
225                 230                 235                 240 


Glu Glu Lys Ala Xaa Gln Tyr Leu Glu Glu Phe His Gln Thr Ala Leu 
                245                 250                 255     


Glu His Pro Glu Leu Ser Glu Leu Xaa Thr Val Thr Gly Thr Asn Pro 
            260                 265                 270         


Val Phe Ala Gly Ala Asn Tyr Ala Ala Trp Ala Val Asn Val Ala Gln 
        275                 280                 285             


Val Ile Asp Ser Glu Thr Ala Asp Asn Leu Glu Lys Thr Thr Ala Ala 
    290                 295                 300                 


Leu Ser Ile Leu Pro Gly Ile Gly Ser Val Met Gly Ile Ala Asp Gly 
305                 310                 315                 320 


Ala Val His His Asn Thr Glu Glu Ile Val Ala Gln Ser Ile Ala Leu 
                325                 330                 335     


Ser Ser Leu Met Val Ala Gln Ala Ile Pro Leu Val Gly Glu Leu Val 
            340                 345                 350         


Asp Ile Gly Phe Ala Ala Tyr Asn Phe Val Glu Ser Ile Ile Asn Leu 
        355                 360                 365             


Phe Gln Val Val His Asn Ser Tyr Asn Arg Pro Ala Tyr Ser Pro Gly 
    370                 375                 380                 


His Xaa Thr Gln Pro Phe Leu His Asp Gly Tyr Ala Val Ser Trp Asn 
385                 390                 395                 400 


Thr Val Glu Asp Ser Ile Ile Arg Thr Gly Phe Gln Gly Glu Ser Gly 
                405                 410                 415     


His Asp Ile Lys Ile Thr Ala Glu Asn Thr Pro Leu Pro Ile Ala Gly 
            420                 425                 430         


Val Leu Leu Pro Thr Ile Pro Gly Lys Leu Asp Val Asn Lys Ser Lys 
        435                 440                 445             


Thr His Ile Ser Val Asn Gly Arg Lys Ile Arg Met Arg Cys Arg Ala 
    450                 455                 460                 


Ile Asp Gly Asp Val Thr Phe Cys Arg Pro Lys Ser Pro Val Tyr Val 
465                 470                 475                 480 


Gly Asn Gly Val His Ala Asn Leu His Val Ala Phe His Arg Ser Ser 
                485                 490                 495     


Ser Glu Lys Ile His Ser Asn Glu Ile Ser Ser Asp Ser Ile Gly Val 
            500                 505                 510         


Leu Gly Tyr Gln Lys Thr Val Asp His Thr Lys Val Asn Ser Xaa Leu 
        515                 520                 525             


Ser Leu Phe Phe Glu Ile Lys Ser 
    530                 535     


<210>  4
<211>  536
<212>  PRT
<213>  Artificial Sequence

<220>  
<223>  CRM197 with Arg-Asn substitution, 6 preferred nnAA sites, and N-terminus Met


<220>
<221>  misc_feature
<222>  (34)..(34)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (213)..(213)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (245)..(245)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (265)..(265)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (386)..(386)
<223>  Xaa can be any non-naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (527)..(527)
<223>  Xaa can be any non-naturally occurring amino acid

<400>  4

Met Gly Ala Asp Asp Val Val Asp Ser Ser Lys Ser Phe Val Met Glu 
1               5                   10                  15      


Asn Phe Ser Ser Tyr His Gly Thr Lys Pro Gly Tyr Val Asp Ser Ile 
            20                  25                  30          


Gln Xaa Gly Ile Gln Lys Pro Lys Ser Gly Thr Gln Gly Asn Tyr Asp 
        35                  40                  45              


Asp Asp Trp Lys Glu Phe Tyr Ser Thr Asp Asn Lys Tyr Asp Ala Ala 
    50                  55                  60                  


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


Val Val Lys Val Thr Tyr Pro Gly Leu Thr Lys Val Leu Ala Leu Lys 
                85                  90                  95      


Val Asp Asn Ala Glu Thr Ile Lys Lys Glu Leu Gly Leu Ser Leu Thr 
            100                 105                 110         


Glu Pro Leu Met Glu Gln Val Gly Thr Glu Glu Phe Ile Lys Arg Phe 
        115                 120                 125             


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


Ser Ser Ser Val Glu Tyr Ile Asn Asn Trp Glu Gln Ala Lys Ala Leu 
145                 150                 155                 160 


Ser Val Glu Leu Glu Ile Asn Phe Glu Thr Arg Gly Lys Arg Gly Gln 
                165                 170                 175     


Asp Ala Met Tyr Glu Tyr Met Ala Gln Ala Cys Ala Gly Asn Arg Val 
            180                 185                 190         


Arg Asn Ser Val Gly Ser Ser Leu Ser Cys Ile Asn Leu Asp Trp Asp 
        195                 200                 205             


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


Gly Pro Ile Lys Asn Lys Met Ser Glu Ser Pro Asn Lys Thr Val Ser 
225                 230                 235                 240 


Glu Glu Lys Ala Xaa Gln Tyr Leu Glu Glu Phe His Gln Thr Ala Leu 
                245                 250                 255     


Glu His Pro Glu Leu Ser Glu Leu Xaa Thr Val Thr Gly Thr Asn Pro 
            260                 265                 270         


Val Phe Ala Gly Ala Asn Tyr Ala Ala Trp Ala Val Asn Val Ala Gln 
        275                 280                 285             


Val Ile Asp Ser Glu Thr Ala Asp Asn Leu Glu Lys Thr Thr Ala Ala 
    290                 295                 300                 


Leu Ser Ile Leu Pro Gly Ile Gly Ser Val Met Gly Ile Ala Asp Gly 
305                 310                 315                 320 


Ala Val His His Asn Thr Glu Glu Ile Val Ala Gln Ser Ile Ala Leu 
                325                 330                 335     


Ser Ser Leu Met Val Ala Gln Ala Ile Pro Leu Val Gly Glu Leu Val 
            340                 345                 350         


Asp Ile Gly Phe Ala Ala Tyr Asn Phe Val Glu Ser Ile Ile Asn Leu 
        355                 360                 365             


Phe Gln Val Val His Asn Ser Tyr Asn Arg Pro Ala Tyr Ser Pro Gly 
    370                 375                 380                 


His Xaa Thr Gln Pro Phe Leu His Asp Gly Tyr Ala Val Ser Trp Asn 
385                 390                 395                 400 


Thr Val Glu Asp Ser Ile Ile Arg Thr Gly Phe Gln Gly Glu Ser Gly 
                405                 410                 415     


His Asp Ile Lys Ile Thr Ala Glu Asn Thr Pro Leu Pro Ile Ala Gly 
            420                 425                 430         


Val Leu Leu Pro Thr Ile Pro Gly Lys Leu Asp Val Asn Lys Ser Lys 
        435                 440                 445             


Thr His Ile Ser Val Asn Gly Arg Lys Ile Arg Met Arg Cys Arg Ala 
    450                 455                 460                 


Ile Asp Gly Asp Val Thr Phe Cys Arg Pro Lys Ser Pro Val Tyr Val 
465                 470                 475                 480 


Gly Asn Gly Val His Ala Asn Leu His Val Ala Phe His Arg Ser Ser 
                485                 490                 495     


Ser Glu Lys Ile His Ser Asn Glu Ile Ser Ser Asp Ser Ile Gly Val 
            500                 505                 510         


Leu Gly Tyr Gln Lys Thr Val Asp His Thr Lys Val Asn Ser Xaa Leu 
        515                 520                 525             


Ser Leu Phe Phe Glu Ile Lys Ser 
    530                 535     


<210>  5
<211>  346
<212>  PRT
<213>  Haemophilus influenzae

<400>  5

Cys Ser Ser His Ser Ser Asn Met Ala Asn Thr Gln Met Lys Ser Asp 
1               5                   10                  15      


Lys Ile Ile Ile Ala His Arg Gly Ala Ser Gly Tyr Leu Pro Glu His 
            20                  25                  30          


Thr Leu Glu Ser Lys Ala Leu Ala Phe Ala Gln Gln Ala Asp Tyr Leu 
        35                  40                  45              


Glu Gln Asp Leu Ala Met Thr Lys Asp Gly Arg Leu Val Val Ile His 
    50                  55                  60                  


Asp His Phe Leu Asp Gly Leu Thr Asp Val Ala Lys Lys Phe Pro His 
65                  70                  75                  80  


Arg His Arg Lys Asp Gly Arg Tyr Tyr Val Ile Asp Phe Thr Leu Lys 
                85                  90                  95      


Glu Ile Gln Ser Leu Glu Met Thr Glu Asn Phe Glu Thr Lys Asp Gly 
            100                 105                 110         


Lys Gln Ala Gln Val Tyr Pro Asn Arg Phe Pro Leu Trp Lys Ser His 
        115                 120                 125             


Phe Arg Ile His Thr Phe Glu Asp Glu Ile Glu Phe Ile Gln Gly Leu 
    130                 135                 140                 


Glu Lys Ser Thr Gly Lys Lys Val Gly Ile Tyr Pro Glu Ile Lys Ala 
145                 150                 155                 160 


Pro Trp Phe His His Gln Asn Gly Lys Asp Ile Ala Ala Glu Thr Leu 
                165                 170                 175     


Lys Val Leu Lys Lys Tyr Gly Tyr Asp Lys Lys Thr Asp Met Val Tyr 
            180                 185                 190         


Leu Gln Thr Phe Asp Phe Asn Glu Leu Lys Arg Ile Lys Thr Glu Leu 
        195                 200                 205             


Leu Pro Gln Met Gly Met Asp Leu Lys Leu Val Gln Leu Ile Ala Tyr 
    210                 215                 220                 


Thr Asp Trp Lys Glu Thr Gln Glu Lys Asp Pro Lys Gly Tyr Trp Val 
225                 230                 235                 240 


Asn Tyr Asn Tyr Asp Trp Met Phe Lys Pro Gly Ala Met Ala Glu Val 
                245                 250                 255     


Val Lys Tyr Ala Asp Gly Val Gly Pro Gly Trp Tyr Met Leu Val Asn 
            260                 265                 270         


Lys Glu Glu Ser Lys Pro Asp Asn Ile Val Tyr Thr Pro Leu Val Lys 
        275                 280                 285             


Glu Leu Ala Gln Tyr Asn Val Glu Val His Pro Tyr Thr Val Arg Lys 
    290                 295                 300                 


Asp Ala Leu Pro Glu Phe Phe Thr Asp Val Asn Gln Met Tyr Asp Ala 
305                 310                 315                 320 


Leu Leu Asn Lys Ser Gly Ala Thr Gly Val Phe Thr Asp Phe Pro Asp 
                325                 330                 335     


Thr Gly Val Glu Phe Leu Lys Gly Ile Lys 
            340                 345     


