US2016319040A1PendingUtilityA1

Antigen binding polypeptides

63
Assignee: ARGEN-X B VPriority: Jul 2, 2008Filed: Apr 8, 2016Published: Nov 3, 2016
Est. expiryJul 2, 2028(~1.9 yrs left)· nominal 20-yr term from priority
Inventors:Torsten DreierChristophe BlanchetotJohannes Joseph Wilhelmus De Haard
C07K 2317/22C07K 2317/24C07K 2317/55C07K 2317/56C12Q 1/6883C12Q 2600/158C12P 21/00C07K 2317/76C07K 16/245C07K 16/462C07K 16/2866A61P 43/00
63
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Claims

Abstract

The invention relates to a platform technology for production of antigen binding polypeptides having specificity for a desired target antigen which is based on the conventional antibody repertoire of species in the family Camelidae, and to antigen binding polypeptides obtained using this technology platform. In particular, the invention provides an antigen binding polypeptide comprising a VH domain and a VL domain, wherein at least one hypervariable loop or complementarity determining region (CDR) in the VH domain or the VL domain is obtained from a VH or VL domain of a species in the family Camelidae.

Claims

exact text as granted — not AI-modified
1 . An antigen binding polypeptide comprising a VH domain and a VL domain, wherein at least one hypervariable loop or complementarity determining region (CDR) in the VH domain or the VL domain is obtained from a VH or VL domain of a species in the family Camelidae. 
     
     
         2 - 7 . (canceled) 
     
     
         8 . The antigen binding polypeptide of  claim 1  which contains at least one amino acid substitution in at least one hypervariable loop or complementarity determining region of either the VH domain or the VL domain in comparison to a Camelidae VH or VL domain obtained by active immunisation of a species in the family Camelidae, or in comparison to a VH or VL domain encoded by a VH or VL gene of a species in the family Camelidae. 
     
     
         9 . The antigen binding polypeptide of  claim 1  which contains at least one amino acid substitution in at least one framework region of either the VH domain or the VL domain, in comparison to a Camelidae VH or VL domain obtained by active immunisation of a species in the family Camelidae or in comparison to a VH or VL domain encoded by a VH or VL gene of a species in the family Camelidae. 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . The antigen binding polypeptide of  claim 1  comprising a VH domain, wherein the VH domain exhibits a sequence identity of 80% or greater with one or more human VH domains across the framework regions FR1, FR2, FR3 and FR4. 
     
     
         13 . The antigen binding polypeptide of  claim 12  wherein the VH domain exhibits a sequence identity of 90% or greater with one or more human VH domains across the framework regions FR1, FR2, FR3 and FR4. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . The antigen binding polypeptide of  claim 1  comprising a VL domain, wherein the VL domain exhibits a sequence identity of 80% or greater with one or more human VL domains across the framework regions FR1, FR2, FR3 and FR4. 
     
     
         17 . The antigen binding polypeptide of  claim 16  wherein the VL domain exhibits a sequence identity of 90% or greater with one or more human VL domains across the framework regions FR1, FR2, FR3 and FR4. 
     
     
         18 - 31 . (canceled) 
     
     
         32 . The antigen binding polypeptide of  claim 1  which is immunoreactive with a non-camelid target antigen. 
     
     
         33 . The antigen binding polypeptide of  claim 32  wherein the non-camelid target antigen is a human antigen. 
     
     
         34 . (canceled) 
     
     
         35 . The antigen binding polypeptide of  claim 32 , wherein the non-camelid target antigen is a target of therapeutic or diagnostic importance. 
     
     
         36 . The antigen binding polypeptide of  claim 1  which comprises at least one constant domain having an amino acid sequence which is encoded by a human immunoglobulin gene, or an amino acid sequence at least 90% identical thereto. 
     
     
         37 . The antigen binding polypeptide of  claim 1  which is an Fab, Fab′, F(ab′) 2 , bi-specific Fab′, Fv fragments, diabody, linear antibody, a single chain variable fragment (scFv), antibody or multispecific antibody formed from antibody fragments. 
     
     
         38 . A chimeric antigen binding polypeptide comprising a VH domain and a VL domain, wherein at least one hypervariable loop or complementarity determining region (CDR) in the VH domain or the VL domain is obtained from a VH or VL domain of a species in the family Camelidae. 
     
     
         39 . The chimeric antigen binding polypeptide of  claim 38 , wherein said chimeric antigen binding polypeptide is recombinantly expressed. 
     
     
         40 . The chimeric antigen binding polypeptide of  claim 38 , wherein said chimeric antigen binding polypeptide is a monoclonal antibody. 
     
     
         41 . An antigen binding polypeptide comprising a VH domain and a VL domain, wherein at least one hypervariable loop or complementarity determining region (CDR) in the VH domain or the VL domain is obtained from a VH or VL domain of a species in the family Camelidae and wherein said antigen binding polypeptide is immunoreactive with a target antigen of therapeutic or diagnostic importance. 
     
     
         42 . A chimeric antigen binding polypeptide comprising or consisting of a VH domain of a conventional antibody of Llama ( Llama glama ) or alpaca ( Llama pacos ) and a VL domain of a conventional antibody of Llama ( Llama glama ) or alpaca ( Llama pacos ) and one or more constant domains of a human antibody. 
     
     
         43 . The chimeric antigen binding polypeptide of  claim 42 , wherein said chimeric antigen binding polypeptide is an antigen binding polypeptide immunoreactive with a target antigen of therapeutic or diagnostic importance, which antigen binding polypeptide comprises or consists of a VH domain of a conventional antibody of Llama ( Llama glama ) or alpaca ( Llama pacos ), a VL domain of a conventional antibody of Llama ( Llama glama ) or alpaca ( Llama pacos ) and one or more constant domains of a human antibody. 
     
     
         44 . The chimeric antigen binding polypeptide of  claim 42 , wherein said chimeric antigen binding polypeptide is a chimeric antibody comprising or consisting of a VH domain of a conventional antibody of Llama ( Llama glama ) or alpaca ( Llama pacos ), a VL domain of a conventional antibody of Llama ( Llama glama ) or alpaca ( Llama pacos ) and the constant domains of a human antibody of an isotype selected from the group consisting of: IgG, IgM, IgD, IgE and IgA. 
     
     
         45 . The chimeric antigen binding polypeptide of  claim 42 , wherein said chimeric antigen binding polypeptide is an antigen binding polypeptide immunoreactive with a target antigen of therapeutic or diagnostic importance, which antigen binding polypeptide comprises or consists of a VH domain of a conventional antibody of Llama ( Llama glama ) or alpaca ( Llama pacos ), a VL domain of a conventional antibody of Llama ( Llama glama ) or alpaca ( Llama pacos ) and the constant domains of a human antibody of an isotype selected from the group consisting of: IgG, IgM, IgD, IgE, IgA. 
     
     
         46 - 93 . (canceled)

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