<110>	NBE Therapeutics
<120>	Maytansine-drug conjugates of HER-2 specific binding proteins generated by site specific sortase-enzyme conjugation
<130>	ND40435
<160>	8
<170>	Excel Makro
	
	
<210>	1
<212>	PRT
<213>	artificial
<220>	Trastuzumab-HC-LPETG-Strep
<211>	0
<400>	1
Met Lys Lys Asn Ile Ala Phe Leu Leu Ala Ser Met Phe Val Phe Ser 
Ile Ala Thr Asn Ala Tyr Ala Gly Val Gln Leu Val Gly Ser Gly Gly 
Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 
Gly Phe Asn Ile Lys Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro 
Gly Lys Gly Leu Gly Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr 
Thr Arg Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp 
Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Gly 
Asp Thr Ala Val Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr 
Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala 
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser 
Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 
Pro Gly Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 
Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 
Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys 
Val Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
Ala Pro Gly Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Gly Val Thr Cys Val 
Val Val Asp Val Ser His Gly Asp Pro Gly Val Lys Phe Asn Trp Tyr 
Val Asp Gly Val Gly Val His Asn Ala Lys Thr Lys Pro Arg Gly Gly 
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
Gln Asp Trp Leu Asn Gly Lys Gly Tyr Lys Cys Lys Val Ser Asn Lys 
Ala Leu Pro Ala Pro Ile Gly Lys Thr Ile Ser Lys Ala Lys Gly Gln 
Pro Arg Gly Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Gly Leu 
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
Ser Asp Ile Ala Val Gly Trp Gly Ser Asn Gly Gln Pro Gly Asn Asn 
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
Phe Ser Cys Ser Val Met His Gly Ala Leu His Asn His Tyr Thr Gln 
Lys Ser Leu Ser Leu Ser Pro Gly Lys Leu Pro Gly Thr Gly Gly Trp 
Ser His Pro Gln Phe Gly Lys 
         	
	
<210>	2
<212>	PRT
<213>	artificial
<220>	Trastuzumab-LC-GGGGS-LPETG-Strep
<211>	257
<400>	2
Met Lys Lys Asn Ile Ala Phe Leu Leu Ala Ser Met Phe Val Phe Ser 
Ile Ala Thr Asn Ala Tyr Ala Asp Ile Gln Met Thr Gln Ser Pro Ser 
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala 
Ser Gln Asp Val Asn Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly 
Lys Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly 
Val Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu 
Thr Ile Ser Ser Leu Gln Pro Gly Asp Phe Ala Thr Tyr Tyr Cys Gln 
Gln His Tyr Thr Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Gly 
Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 
Asp Gly Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 
Asn Phe Tyr Pro Arg Gly Ala Lys Val Gln Trp Lys Val Asp Asn Ala 
Leu Gln Ser Gly Asn Ser Gln Gly Ser Val Thr Gly Gln Asp Ser Lys 
Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 
Tyr Gly Lys His Lys Val Tyr Ala Cys Gly Val Thr His Gln Gly Leu 
Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Gly Cys Gly Gly Gly 
Gly Ser Leu Pro Gly Thr Gly Gly Trp Ser His Pro Gln Phe Gly Lys 
         	
	
<210>	3
<212>	PRT
<213>	artificial
<220>	FRP-5-HC-LPETG-Strep

<211>	483
<400>	3
Met Asn Phe Gly Leu Arg Leu Ile Phe Leu Val Leu Thr Leu Lys Gly 
Val Gln Cys Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Lys Lys 
Pro Gly Gly Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Pro Phe 
Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Ala Pro Gly Gln Gly Leu 
Lys Trp Met Gly Trp Ile Asn Thr Ser Thr Gly Gly Ser Thr Phe Ala 
Asp Asp Phe Lys Gly Arg Phe Asp Phe Ser Leu Gly Thr Ser Ala Asn 
Thr Ala Tyr Leu Gln Ile Asn Asn Leu Lys Ser Gly Asp Met Ala Thr 
Tyr Phe Cys Ala Arg Trp Gly Val Tyr His Gly Tyr Val Pro Tyr Trp 
Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Gly Pro Val Thr 
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Gly Pro Lys Ser 
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Gly Leu Leu 
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
Met Ile Ser Arg Thr Pro Gly Val Thr Cys Val Val Val Asp Val Ser 
His Gly Asp Pro Gly Val Lys Phe Asn Trp Tyr Val Asp Gly Val Gly 
Val His Asn Ala Lys Thr Lys Pro Arg Gly Gly Gln Tyr Asn Ser Thr 
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
Gly Lys Gly Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
Ile Gly Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Gly Pro Gln 
Val Tyr Thr Leu Pro Pro Ser Arg Asp Gly Leu Thr Lys Asn Gln Val 
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
Gly Trp Gly Ser Asn Gly Gln Pro Gly Asn Asn Tyr Lys Thr Thr Pro 
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
Met His Gly Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
Ser Pro Gly Lys Leu Pro Gly Thr Gly Gly Trp Ser His Pro Gln Phe 
Gly Lys 
         	
	
<210>	4
<212>	PRT
<213>	artificial
<220>	FRP-5-LC-GGGGS-LPETG-Strep
<211>	253
<400>	4
Met Asn Phe Gly Leu Arg Leu Ile Phe Leu Val Leu Thr Leu Lys Gly 
Val Gln Cys Asp Ile Gln Leu Thr Gln Ser His Lys Phe Leu Ser Thr 
Ser Val Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val 
Tyr Asn Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys 
Leu Leu Ile Tyr Ser Ala Ser Ser Arg Tyr Thr Gly Val Pro Ser Arg 
Phe Thr Gly Ser Gly Ser Gly Pro Asp Phe Thr Phe Thr Ile Ser Ser 
Val Gln Ala Gly Asp Leu Ala Val Tyr Phe Cys Gln Gln His Phe Arg 
Thr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Gly Ile Lys Arg Thr 
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Gly Gln Leu 
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 
Arg Gly Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 
Asn Ser Gln Gly Ser Val Thr Gly Gln Asp Ser Lys Asp Ser Thr Tyr 
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Gly Lys His 
Lys Val Tyr Ala Cys Gly Val Thr His Gln Gly Leu Ser Ser Pro Val 
Thr Lys Ser Phe Asn Arg Gly Gly Cys Gly Gly Gly Gly Ser Leu Pro 
Gly Thr Gly Gly Trp Ser His Pro Gln Phe Gly Lys 
         	
	
<210>	5
<212>	PRT
<213>	artificial
<220>	Trastuzumab-HC-LPETGGGGG-maytansine-toxin
<211>	459
<400>	5
Gly Val Gln Leu Val Gly Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr 
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Gly Trp Val 
Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val 
Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr 
Leu Gln Met Asn Ser Leu Arg Ala Gly Asp Thr Ala Val Tyr Tyr Cys 
Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Gly Pro Val Thr Val Ser 
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Gly Pro Lys Ser Cys Asp 
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Gly Leu Leu Gly Gly 
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
Ser Arg Thr Pro Gly Val Thr Cys Val Val Val Asp Val Ser His Gly 
Asp Pro Gly Val Lys Phe Asn Trp Tyr Val Asp Gly Val Gly Val His 
Asn Ala Lys Thr Lys Pro Arg Gly Gly Gln Tyr Asn Ser Thr Tyr Arg 
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
Gly Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Gly 
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Gly Pro Gln Val Tyr 
Thr Leu Pro Pro Ser Arg Asp Gly Leu Thr Lys Asn Gln Val Ser Leu 
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Gly Trp 
Gly Ser Asn Gly Gln Pro Gly Asn Asn Tyr Lys Thr Thr Pro Pro Val 
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
Gly Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
Gly Lys Leu Pro Gly Thr Gly Gly Gly Gly Gly          	
	
<210>	6
<212>	PRT
<213>	artificial
<220>	Trastuzumab-LC-GGGGS-LPETGGGGG-maytansine-toxin
<211>	228
<400>	6
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala 
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
Gly Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 
Thr Phe Gly Gln Gly Thr Lys Val Gly Ile Lys Arg Thr Val Ala Ala 
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Gly Gln Leu Lys Ser Gly 
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Gly Ala 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
Gly Ser Val Thr Gly Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Gly Lys His Lys Val Tyr 
Ala Cys Gly Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
Phe Asn Arg Gly Gly Cys Gly Gly Gly Gly Ser Leu Pro Gly Thr Gly 
Gly Gly Gly Gly          	
	
<210>	7
<212>	PRT
<213>	artificial
<220>	FRP5-HC-LPETGGGGG-toxin
<211>	458
<400>	7
Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Lys Lys Pro Gly Gly 
Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Pro Phe Thr Asn Tyr 
Gly Met Asn Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Lys Trp Met 
Gly Trp Ile Asn Thr Ser Thr Gly Gly Ser Thr Phe Ala Asp Asp Phe 
Lys Gly Arg Phe Asp Phe Ser Leu Gly Thr Ser Ala Asn Thr Ala Tyr 
Leu Gln Ile Asn Asn Leu Lys Ser Gly Asp Met Ala Thr Tyr Phe Cys 
Ala Arg Trp Gly Val Tyr His Gly Tyr Val Pro Tyr Trp Gly Gln Gly 
Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Gly Pro Val Thr Val Ser Trp 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
Ser Asn Thr Lys Val Asp Lys Lys Val Gly Pro Lys Ser Cys Asp Lys 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Gly Leu Leu Gly Gly Pro 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
Arg Thr Pro Gly Val Thr Cys Val Val Val Asp Val Ser His Gly Asp 
Pro Gly Val Lys Phe Asn Trp Tyr Val Asp Gly Val Gly Val His Asn 
Ala Lys Thr Lys Pro Arg Gly Gly Gln Tyr Asn Ser Thr Tyr Arg Val 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Gly 
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Gly Lys 
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Gly Pro Gln Val Tyr Thr 
Leu Pro Pro Ser Arg Asp Gly Leu Thr Lys Asn Gln Val Ser Leu Thr 
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Gly Trp Gly 
Ser Asn Gly Gln Pro Gly Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Gly 
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
Lys Leu Pro Gly Thr Gly Gly Gly Gly Gly          	
	
<210>	8
<212>	PRT
<213>	artificial
<220>	FRP5-LC-GGGGS-LPETGGGGG-maytansine-toxin
<211>	228
<400>	8
Asp Ile Gln Leu Thr Gln Ser His Lys Phe Leu Ser Thr Ser Val Gly 
Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Tyr Asn Ala 
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile 
Tyr Ser Ala Ser Ser Arg Tyr Thr Gly Val Pro Ser Arg Phe Thr Gly 
Ser Gly Ser Gly Pro Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala 
Gly Asp Leu Ala Val Tyr Phe Cys Gln Gln His Phe Arg Thr Pro Phe 
Thr Phe Gly Ser Gly Thr Lys Leu Gly Ile Lys Arg Thr Val Ala Ala 
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Gly Gln Leu Lys Ser Gly 
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Gly Ala 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
Gly Ser Val Thr Gly Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Gly Lys His Lys Val Tyr 
Ala Cys Gly Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
Phe Asn Arg Gly Gly Cys Gly Gly Gly Gly Ser Leu Pro Gly Thr Gly 
Gly Gly Gly Gly          	
	





