US2015065690A1PendingUtilityA1

Modified antibody regions and uses thereof

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Assignee: BIOATLA LLCPriority: Apr 27, 2012Filed: Apr 26, 2013Published: Mar 5, 2015
Est. expiryApr 27, 2032(~5.8 yrs left)· nominal 20-yr term from priority
Inventors:Gerhard FreyJay M. ShortHwai Wen Chang
A61P 37/02A61P 35/00A61P 29/00A61P 31/00C07K 2317/94A61K 2039/505C07K 2317/52C07K 16/00A61P 25/00A61P 17/02
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Claims

Abstract

The present invention relates to modified Fc regions of antibodies, and uses thereof, such as in antibodies that contain an Fc region of the present invention.

Claims

exact text as granted — not AI-modified
1 . An antibody comprising a modified Fc region, wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at positions 252, 257, 258, 259, 260, 426, 427, 428, 430, 431, 433, 434, or 435, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: M252I, P257C, P257I, P257T, E258D, E258F, E258G, E258I, E258L, E258Q, E258V, E258W, V259E, V259G, V259I, V259R, T260A, T260C, T260F, T260L, T260N, T260S, T260W, S426C, S426N, V427S, V427T, M428Y, E430I, E430L, E430Q, A431F, A431H, A431P, H433A, H433E, N434G, N434I, N434M, N434R, N434V, N434W, and H435E. 
     
     
         2 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at positions 257, 258, 434, or 435, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: P257C, E258V, N434G, N434I, N434M, and H435K. 
     
     
         3 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 252, wherein the numbering of the position in the Fc region is that of the EU index as in Kabat, and wherein the substitution is M252I. 
     
     
         4 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 257, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: P257C, P257I, and P257T. 
     
     
         5 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 258, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: E258D, E258F, E258G, E258I, E258L, E258Q, E258V, and E258W. 
     
     
         6 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 259, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: V259E, V259G, V259I, and V259R. 
     
     
         7 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 260, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: T260A, T260C, T260F, T260L, T260N, and T260S. 
     
     
         8 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 426, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: S426C, and S426N. 
     
     
         9 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 427, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: V427S, and V427T. 
     
     
         10 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 428, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat and wherein the substitution is M428Y. 
     
     
         11 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 430, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: E430I, E430L, and E430Q. 
     
     
         12 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 431, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: A431F, A431H, and A431P. 
     
     
         13 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 433, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: H433A, and H433E. 
     
     
         14 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 434, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat in the Fc region selected from the following group: N434G, N434I, N434M, N434R, N434V, and N434W. 
     
     
         15 . The antibody of  claim 1 , wherein the modified Fc region comprises an amino acid substitution relative to a parent IgG Fc region at position 435, wherein the numbering of the positions in the Fc region is that of the EU index as in Kabat, and wherein the substitution is H435K. 
     
     
         16 . The antibody of  claim 1 , wherein the antibody comprising the modified Fc region has an enhanced antibody dependent cellular cytotoxicity (ADCC) relative to a corresponding antibody comprising the parent Fc region. 
     
     
         17 . The antibody of  claim 1 , wherein the parent Fc region comprises a human IgG Fc region. 
     
     
         18 - 19 . (canceled) 
     
     
         20 . A method to produce an antibody with enhanced antibody dependent cellular cytotoxicity comprising:
 a) providing a host cell which expresses the antibody of  claim 1 ; and   b) selecting a host cell that expresses an antibody comprising the modified Fc region which has an enhanced antibody dependent cellular cytotoxicity relative to a corresponding antibody comprising the parent Fc region.   
     
     
         21 . (canceled) 
     
     
         22 . A method to produce an antibody with enhanced antibody dependent cellular cytotoxicity comprising:
 a) introducing one or more substitutions to a parent IgG Fc region of an antibody to yield an antibody comprising the modified Fc region of  claim 1 ; and   b) identifying an antibody comprising the modified Fc region which has enhanced antibody dependent cellular cytotoxicity.   
     
     
         23 . The antibody of  claim 1 , wherein the modified Fc region comprises a plurality of amino acid substitutions relative to a parent IgG Fc region at positions selected from 252, 257, 258, 259, 260, 426, 427, 428, 430, 431, 433, 434, and 435. 
     
     
         24 . (canceled) 
     
     
         25 . The antibody of  claim 14 , wherein the modified Fc region has a decreased FcRn binding. 
     
     
         26 . The antibody of  claim 14 , wherein the antibody has an increased half life. 
     
     
         27 . The antibody of  claim 14 , wherein the antibody has a decreased half life. 
     
     
         28 - 29 . (canceled)

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