US2020140525A1PendingUtilityA1

Non-Immunogenic Single Domain Antibodies

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Assignee: INHIBRX INCPriority: Jan 21, 2015Filed: Nov 15, 2019Published: May 7, 2020
Est. expiryJan 21, 2035(~8.5 yrs left)· nominal 20-yr term from priority
Inventors:Brendan P. EckelmanJohn C. TimmerQuinn Deveraux
C07K 16/00C07K 2317/569C07K 16/4283A61P 29/00C07K 2317/567C07K 2317/56A61P 37/06C07K 2317/24
66
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Claims

Abstract

The invention provides modifications within human or humanized single domain antibody fragments (sdAbs) that prevent recognition by pre-existing antibodies, to isolated polypeptides that include these modifications, and to methods and uses thereof.

Claims

exact text as granted — not AI-modified
1 .- 20 . (canceled) 
     
     
         21 . A single domain antibody (sdAb) comprising a mutation at position Ala88 according to Kabat, wherein the mutation at position Ala88 is Ala88Glu (A88E), Ala88Asp (A88D), Ala88Arg (A88R), or Ala88Lys (A88K). 
     
     
         22 . The single domain antibody of  claim 21 , wherein the carboxy terminus comprises an amino acid sequence selected from TVE, TVK, LVTVS (SEQ ID NO: 7), LVTVSS (SEQ ID NO: 113), TVSE (SEQ ID NO: 24), TVEG (SEQ ID NO: 25), TVSEG (SEQ ID NO: 26), TVSK (SEQ ID NO: 27), TVKG (SEQ ID NO: 28), TVSKG (SEQ ID NO: 29), TVSKPG (SEQ ID NO: 44), TVSKPGG (SEQ ID NO: 45), TVKP (SEQ ID NO: 46), TVKPG (SEQ ID NO: 47), TVKPGG (SEQ ID NO: 48), TVRP (SEQ ID NO: 49), TVRPG (SEQ ID NO: 50), TVRPGG (SEQ ID NO: 51), TVEP (SEQ ID NO: 52), TVEPG (SEQ ID NO: 53), TVEPGG (SEQ ID NO: 54), TVDP (SEQ ID NO: 55), TVDPG (SEQ ID NO: 56), and TVDPGG (SEQ ID NO: 57). 
     
     
         23 . The single domain antibody of  claim 21 , wherein the carboxy terminus comprises an amino acid sequence selected from SEQ ID NOs: 2-10 and 30-43. 
     
     
         24 . The single domain antibody of  claim 21 , wherein the mutation at position Ala88 is Ala88Lys (A88K) and the carboxy terminus comprises an amino acid sequence selected from TVE, TVSE (SEQ ID NO: 24), TVEG (SEQ ID NO: 25), TVSEG (SEQ ID NO: 26), TVEP (SEQ ID NO: 52), TVEPG (SEQ ID NO: 53), TVEPGG (SEQ ID NO: 54), TVDP (SEQ ID NO: 55), TVDPG (SEQ ID NO: 56), and TVDPGG (SEQ ID NO: 57). 
     
     
         25 . The single domain antibody of  claim 21 , wherein the mutation at position Ala88 is Ala88Lys (A88K) and the carboxy terminus comprises an amino acid sequence selected from TVK, TVSK (SEQ ID NO: 27), TVKG (SEQ ID NO: 28), TVSKG (SEQ ID NO: 29), TVSKPG (SEQ ID NO: 44), TVSKPGG (SEQ ID NO: 45), TVKP (SEQ ID NO: 46), TVKPG (SEQ ID NO: 47), TVKPGG (SEQ ID NO: 48), TVRP (SEQ ID NO: 49), TVRPG (SEQ ID NO: 50), and TVRPGG (SEQ ID NO: 51). 
     
     
         26 . The single domain antibody of  claim 21 , wherein the mutation at position Ala88 is Ala88Glu (A88E) and the carboxy terminus comprises an amino acid sequence selected from TVE, TVSE (SEQ ID NO: 24), TVEG (SEQ ID NO: 25), TVSEG (SEQ ID NO: 26), TVEP (SEQ ID NO: 52), TVEPG (SEQ ID NO: 53), TVEPGG (SEQ ID NO: 54), TVDP (SEQ ID NO: 55), TVDPG (SEQ ID NO: 56), and TVDPGG (SEQ ID NO: 57). 
     
     
         27 . The single domain antibody of  claim 21 , wherein the mutation at position Ala88 is Ala88Glu (A88E) and the carboxy terminus comprises an amino acid sequence selected from TVK, TVSK (SEQ ID NO: 27), TVKG (SEQ ID NO: 28), TVSKG (SEQ ID NO: 29), TVSKPG (SEQ ID NO: 44), TVSKPGG (SEQ ID NO: 45), TVKP (SEQ ID NO: 46), TVKPG (SEQ ID NO: 47), TVKPGG (SEQ ID NO: 48), TVRP (SEQ ID NO: 49), TVRPG (SEQ ID NO: 50), and TVRPGG (SEQ ID NO: 51). 
     
     
         28 . The single domain antibody of  claim 21 , wherein the mutation at position Ala88 is Ala88Arg (A88R) and the carboxy terminus comprises an amino acid sequence selected from TVE, TVSE (SEQ ID NO: 24), TVEG (SEQ ID NO: 25), TVSEG (SEQ ID NO: 26), TVEP (SEQ ID NO: 52), TVEPG (SEQ ID NO: 53), TVEPGG (SEQ ID NO: 54), TVDP (SEQ ID NO: 55), TVDPG (SEQ ID NO: 56), and TVDPGG (SEQ ID NO: 57). 
     
     
         29 . The single domain antibody of  claim 21 , wherein the mutation at position Ala88 is Ala88Arg (A88R) and the carboxy terminus comprises an amino acid sequence selected from TVK, TVSK (SEQ ID NO: 27), TVKG (SEQ ID NO: 28), TVSKG (SEQ ID NO: 29), TVSKPG (SEQ ID NO: 44), TVSKPGG (SEQ ID NO: 45), TVKP (SEQ ID NO: 46), TVKPG (SEQ ID NO: 47), TVKPGG (SEQ ID NO: 48), TVRP (SEQ ID NO: 49), TVRPG (SEQ ID NO: 50), and TVRPGG (SEQ ID NO: 51). 
     
     
         30 . The single domain antibody of  claim 21 , wherein the mutation at position Ala88 is Ala88Asp (A88D) and the carboxy terminus comprises an amino acid sequence selected from TVE, TVSE (SEQ ID NO: 24), TVEG (SEQ ID NO: 25), TVSEG (SEQ ID NO: 26), TVEP (SEQ ID NO: 52), TVEPG (SEQ ID NO: 53), TVEPGG (SEQ ID NO: 54), TVDP (SEQ ID NO: 55), TVDPG (SEQ ID NO: 56), and TVDPGG (SEQ ID NO: 57). 
     
     
         31 . The single domain antibody of  claim 21 , wherein the mutation at position Ala88 is Ala88Asp (A88D) and the carboxy terminus comprises an amino acid sequence selected from TVK, TVSK (SEQ ID NO: 27), TVKG (SEQ ID NO: 28), TVSKG (SEQ ID NO: 29), TVSKPG (SEQ ID NO: 44), TVSKPGG (SEQ ID NO: 45), TVKP (SEQ ID NO: 46), TVKPG (SEQ ID NO: 47), TVKPGG (SEQ ID NO: 48), TVRP (SEQ ID NO: 49), TVRPG (SEQ ID NO: 50), and TVRPGG (SEQ ID NO: 51).

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