	US 11,732,045 B2
	Multi-specific binding proteins for cancer treatment
Susanne Hipp, Fuessen (DE); Paul Adam, Vienna (AT); Michael Dziegelewski, Newburgh, NY (US); Rajkumar Ganesan, Blue Bell, PA (US); Philip Nicholas Gorman, Prospect, CT (US); Pankaj Gupta, Scarsdale, NY (US); Priyanka Gupta, Danbury, CT (US); Marcio Lasaro, Sandy Hook, CT (US); Justin M. Scheer, Ridgefield, CT (US); and Vladimir H. Voynov, Danbury, CT (US)
Assigned to Boehringer Ingelheim International GmbH, Ingelheim am Rhein (DE)
Filed by Boehringer Ingelheim International GmbH, Ingelheim am Rhein (DE)
Filed on Oct. 1, 2020, as Appl. No. 17/60,111.
Claims priority of application No. 19201200 (EP), filed on Oct. 2, 2019.
Prior Publication US 2021/0107983 A1, Apr. 15, 2021
Int. Cl. C07K 16/28 (2006.01); A61P 35/00 (2006.01)

CPC C07K 16/2827 (2013.01) [A61P 35/00 (2018.01); C07K 16/2809 (2013.01); C07K 2317/31 (2013.01); C07K 2317/565 (2013.01)]

20 Claims

1. A protein comprising a first antigen binding unit specifically binding to B7H6 and a second antigen binding unit specifically binding to CD3, wherein said first antigen binding unit specifically binding to B7H6 is selected from the group consisting of i) to xxiv):

i) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:1 (CDR1), SEQ ID NO:2 (CDR2) and SEQ ID NO:3 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:4 (CDR1), SEQ ID NO:5 (CDR2) and SEQ ID NO:6 (CDR3);

ii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:7 (CDR1), SEQ ID NO:8 (CDR2) and SEQ ID NO:9 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:10 (CDR1), SEQ ID NO:11 (CDR2) and SEQ ID NO:12 (CDR3);

iii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:13 (CDR1), SEQ ID NO:14 (CDR2) and SEQ ID NO:15 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:16 (CDR1), SEQ ID NO:17 (CDR2) and SEQ ID NO:18 (CDR3);

iv) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:19 (CDR1), SEQ ID NO:20 (CDR2) and SEQ ID NO:21 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:22 (CDR1), SEQ ID NO:23 (CDR2) and SEQ ID NO:24 (CDR3);

v) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:25 (CDR1), SEQ ID NO:26 (CDR2) and SEQ ID NO:27 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:28 (CDR1), SEQ ID NO:29 (CDR2) and SEQ ID NO:30 (CDR3);

vi) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:31 (CDR1), SEQ ID NO:32 (CDR2) and SEQ ID NO:33 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:34 (CDR1), SEQ ID NO:35 (CDR2) and SEQ ID NO:36 (CDR3);

vii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:37 (CDR1), SEQ ID NO:38 (CDR2) and SEQ ID NO:39 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:40 (CDR1), SEQ ID NO:41 (CDR2) and SEQ ID NO:42 (CDR3);

viii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:43 (CDR1), SEQ ID NO:44 (CDR2) and SEQ ID NO:45 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:46 (CDR1), SEQ ID NO:47 (CDR2) and SEQ ID NO:48 (CDR3);

ix) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:49 (CDR1), SEQ ID NO:50 (CDR2) and SEQ ID NO:51 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:52 (CDR1), SEQ ID NO:53 (CDR2) and SEQ ID NO:54 (CDR3);

x) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:55 (CDR1), SEQ ID NO:56 (CDR2) and SEQ ID NO:57 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:58 (CDR1), SEQ ID NO:59 (CDR2) and SEQ ID NO:60 (CDR3);

xi) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:61 (CDR1), SEQ ID NO:62 (CDR2) and SEQ ID NO:63 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:64 (CDR1), SEQ ID NO:65 (CDR2) and SEQ ID NO:66 (CDR3);

xii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:67 (CDR1), SEQ ID NO:68 (CDR2) and SEQ ID NO:69 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:70 (CDR1), SEQ ID NO:71 (CDR2) and SEQ ID NO:72 (CDR3);

xiii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:73 (CDR1), SEQ ID NO:74 (CDR2) and SEQ ID NO:75 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:76 (CDR1), SEQ ID NO:77 (CDR2) and SEQ ID NO:78 (CDR3);

xiv) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:79 (CDR1), SEQ ID NO:80 (CDR2) and SEQ ID NO:81 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:82 (CDR1), SEQ ID NO:83 (CDR2) and SEQ ID NO:84 (CDR3);

xv) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:85 (CDR1), SEQ ID NO:86 (CDR2) and SEQ ID NO:87 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:88 (CDR1), SEQ ID NO:89 (CDR2) and SEQ ID NO:90 (CDR3);

xvi) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:91 (CDR1), SEQ ID NO:92 (CDR2) and SEQ ID NO:93 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:94 (CDR1), SEQ ID NO:95 (CDR2) and SEQ ID NO:96 (CDR3);

xvii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:97 (CDR1), SEQ ID NO:98 (CDR2) and SEQ ID NO:99 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:100 (CDR1), SEQ ID NO:101 (CDR2) and SEQ ID NO:102 (CDR3);

xviii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:103 (CDR1), SEQ ID NO:104 (CDR2) and SEQ ID NO:105 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:106 (CDR1), SEQ ID NO:107 (CDR2) and SEQ ID NO:108 (CDR3);

xix) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:109 (CDR1), SEQ ID NO:110 (CDR2) and SEQ ID NO:111 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:112 (CDR1), SEQ ID NO:113 (CDR2) and SEQ ID NO:114 (CDR3);

xx) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:115 (CDR1), SEQ ID NO:116 (CDR2) and SEQ ID NO:117 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:118 (CDR1), SEQ ID NO:119 (CDR2) and SEQ ID NO:120 (CDR3);

xxi) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:121 (CDR1), SEQ ID NO:122 (CDR2) and SEQ ID NO:123 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:124 (CDR1), SEQ ID NO:125 (CDR2) and SEQ ID NO:126 (CDR3);

xxii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:127 (CDR1), SEQ ID NO:128 (CDR2) and SEQ ID NO:129 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:130 (CDR1), SEQ ID NO:131 (CDR2) and SEQ ID NO:132 (CDR3);

xxiii) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:133 (CDR1), SEQ ID NO:134 (CDR2) and SEQ ID NO:135 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:136 (CDR1), SEQ ID NO:137 (CDR2) and SEQ ID NO:138 (CDR3); and

xxiv) an antigen binding unit comprising light chain CDRs comprising the amino acid sequences of SEQ ID NO:139 (CDR1), SEQ ID NO:140 (CDR2) and SEQ ID NO:141 (CDR3) and heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:142 (CDR1), SEQ ID NO:143 (CDR2) and SEQ ID NO:144 (CDR3).