US2016060345A1PendingUtilityA1

Novel EGFR-Binding Molecules and Immunoconjugates Thereof

48
Assignee: IMMUNOGEN INCPriority: Oct 29, 2010Filed: Aug 7, 2015Published: Mar 3, 2016
Est. expiryOct 29, 2030(~4.2 yrs left)· nominal 20-yr term from priority
Inventors:Julianto SetiadyPeter U. ParkLingyun RuiThomas ChittendenGillian Payne
A61P 5/38A61P 43/00A61P 35/00C07K 2317/34C07K 2317/33A61P 1/16A61P 15/14A61K 47/6849A61K 2039/505C07K 16/2863A61P 13/08C07K 2317/24C07K 2317/73C07K 2317/732A61K 45/06A61P 17/00C07K 2317/92C07K 2317/76A61K 39/39558C07K 2317/565A61K 47/68033C07K 16/28A61K 39/395
48
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Cited by
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Claims

Abstract

Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to EGFR are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.

Claims

exact text as granted — not AI-modified
1 - 76 . (canceled) 
     
     
         77 . An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:42, or SEQ ID NO:80. 
     
     
         78 . The polynucleotide of  claim 77 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:41. 
     
     
         79 . The polynucleotide of  claim 78 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:51. 
     
     
         80 . The polynucleotide of  claim 77 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:42. 
     
     
         81 . The polynucleotide of  claim 80 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:54. 
     
     
         82 . The polynucleotide of  claim 77 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:80. 
     
     
         83 . The polynucleotide of  claim 82 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:84. 
     
     
         84 . The polynucleotide of  claim 77 , wherein the polynucleotide further comprises the nucleotide sequence of SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:47, or SEQ ID NO:48. 
     
     
         85 . A vector comprising the polynucleotide of  claim 77 . 
     
     
         86 . A vector comprising the polynucleotide of  claim 84 . 
     
     
         87 . A host cell comprising the polynucleotide of  claim 77 . 
     
     
         88 . A host cell comprising the polynucleotide of  claim 84 . 
     
     
         89 . An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:47, or SEQ ID NO:48. 
     
     
         90 . The polynucleotide of  claim 89 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:46. 
     
     
         91 . The polynucleotide of  claim 90 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:52. 
     
     
         92 . The polynucleotide of  claim 89 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:47. 
     
     
         93 . The polynucleotide of  claim 92 , wherein the polynucleotide comprises the nucleotide sequence of SEQ NO:53. 
     
     
         94 . The polynucleotide of  claim 89 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:48. 
     
     
         95 . The polynucleotide of  claim 94 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:55. 
     
     
         96 . A vector comprising the polynucleotide of  claim 89 . 
     
     
         97 . A host cell comprising the polynucleotide of  claim 89 . 
     
     
         98 . An isolated polynucleotide encoding a polypeptide comprising a heavy chain (HC) variable domain, wherein the HC variable domain comprises: (a) a HC CDR1 comprising the amino acid sequence of ESYWMQ (SEQ ID NO:1); (b) a HC CDR2 comprising the amino acid sequence of Xaa 1 Xaa 2 YPGDGDXaa 3 Xaa4 (SEQ ID NO:4); and (c) a HC CDR3 comprising the amino acid sequence of YDAPGYXaa 1 MDY (SEQ ID NO:5), and
 wherein Xaa 1  of HC CDR2 is T or A; Xaa 2  of HC CDR2 is I or L; Xaa 3  of HC CDR2 is T or A; Xaa 4  of HC CDR2 is T, R, or 5; and Xaa 1  of CDR3 is A or T.   
     
     
         99 . The isolated polynucleotide of  claim 98 , wherein the HC CDR2 comprises the amino acid sequence of TIYPGDGDTT (SEQ ID NO:2), and wherein the HC CDR3 comprises the amino acid sequence of YDAPGYAMDY (SEQ ID NO:3). 
     
     
         100 . The isolated polynucleotide of  claim 99 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, or SEQ ID NO:73. 
     
     
         101 . The isolated polynucleotide of  claim 100 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, or SEQ ID NO:76. 
     
     
         102 . The isolated polynucleotide of  claim 98 , wherein the HC CDR2 comprises the amino acid sequence of TIYPGDGDTTYTQKFKG (SEQ ID NO:63). 
     
     
         103 . The isolated polynucleotide of  claim 102 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:19 or SEQ ID NO:22. 
     
     
         104 . The isolated polynucleotide of  claim 103 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:32. 
     
     
         105 . The isolated polynucleotide of  claim 98 , wherein the HC CDR2 comprises the amino acid sequence of TIYPGDGDTTYTQKFQG (SEQ ID NO:64). 
     
     
         106 . The isolated polynucleotide of  claim 105 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:21 or SEQ ID NO:73. 
     
     
         107 . The isolated polynucleotide of  claim 106 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 31 or SEQ 11) NO:76. 
     
     
         108 . The isolated polynucleotide of  claim 98 , wherein the polynucleotide further encodes a polypeptide comprising a light chain (LC) variable domain, wherein the LC variable domain comprises the amino acid sequence of SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. 
     
     
         109 . A vector comprising the polynucleotide of  claim 98 . 
     
     
         110 . A vector comprising the polynucleotide of  claim 108 . 
     
     
         111 . A host cell comprising the polynucleotide of  claim 98 . 
     
     
         112 . A host cell comprising the polynucleotide of  claim 108 . 
     
     
         113 . An isolated polynucleotide encoding a polypeptide comprising a LC variable domain, wherein the LC variable domain comprises: (a) a LC CDR1 comprising the amino acid sequence of Xaa 1 ASQDINNYXaa 2 A (SEQ ID NO:14); (b) a LC CDR2 comprising the amino acid sequence of YTSTLHP (SEQ ID NO:11); and (c) a LC CDR3 comprising the amino acid sequence of LQYDNLLYT (SEQ ID NO:12), and
 wherein Xaa 1  of LC CDR1 is K or R.   
     
     
         114 . The isolated polynucleotide of  claim 113 , wherein the HC CDR1 comprises the amino acid sequence of KASQDINNYLA (SEQ ID NO:10). 
     
     
         115 . The isolated polynucleotide of  claim 114 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO:24 or SEQ ID NO:27. 
     
     
         116 . The isolated polynucleotide of  claim 115 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:34. 
     
     
         117 . The isolated polynucleotide of  claim 113 , wherein the HC CDR1 comprises the amino acid sequence of RASQDINNYLA (SEQ ID NO:13). 
     
     
         118 . The isolated polynucleotide of  claim 117 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO:26 or SEQ ID NO:28. 
     
     
         119 . The isolated polynucleotide of  claim 118 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:33 or SEQ ID NO:35. 
     
     
         120 . The isolated polynucleotide of  claim 113 , wherein the polynucleotide further encodes a polypeptide comprising a HG variable domain, wherein the 1-IC variable domain comprises the amino acid sequence of SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:73. 
     
     
         121 . A vector comprising the polynucleotide of  claim 113 . 
     
     
         122 . A vector comprising the polynucleotide of  claim 120 . 
     
     
         123 . A host cell comprising the polynucleotide of  claim 113 . 
     
     
         124 . A host cell comprising the polynucleotide of  claim 120 .

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