Antibodies binding to phosphorylcholine (pc) and/or pc conjugates

Abstract

The present invention relates to an antibody or antibody fragment capable of binding to phosphorylcholine and/or a phosphorylcholine conjugate, wherein the antibody or antibody fragment comprises a variable heavy chain (VH) domain and/or a variable light chain (VL) domain, and wherein— (a) the VH domain comprises an amino acid sequence that includes one, two or three complementarity determining regions (CDRs) selected from the group consisting of: a CDR1 sequence comprising an amino acid sequence having at least 20%, 40%, 60%, 80% or 100% sequence identity to the sequence of SEQ ID NO: 7; a CDR2 sequence comprising an amino acid sequence having at least 5%, 11%, 17%, 23%, 29%, 35%, 41%, 47%, 52%, 58%, 64%, 70%, 76%, 82%, 88%, 94%, or 100% sequence identity to the sequence of SEQ ID NO: 8; and a CDR3 sequence comprising an amino acid sequence having at least 11%, 22%, 33%, 44%, 55%, 66%, 77%, 88% or 100% sequence identity to the sequence of SEQ ID NO: 9 or 10; and/or (b) the VL domain comprises an amino acid sequence that includes one, two or three complementarity determining regions (CDRs) selected from the group consisting of: a CDR4 sequence comprising an amino acid sequence having at least 7.5%, 15%, 23%, 30%, 38%, 46%, 53%, 61%, 69%, 76%, 84%, 92% or 100% sequence identity to the sequence of SEQ ID NO: 11; a CDR5 sequence comprising an amino acid sequence having at least 14%, 28%, 42%, 57%, 71%, 85% or 100% sequence identity to the sequence of SEQ ID NO: 12; a CDR6 sequence comprising an amino acid sequence having at least 9%, 18%, 27%, 36%, 45%, 54%, 63%, 72%, 81%, 90% or 100% sequence identity to the sequence of SEQ ID NO: 13.

1 . An antibody or antibody fragment capable of binding to phosphorylcholine and/or a phosphorylcholine conjugate,
 wherein the antibody or antibody fragment comprises a variable heavy chain (VH) domain and/or a variable light chain (VL) domain, and wherein—
 (a) the VH domain comprises an amino acid sequence that includes one, two or three complementarity determining regions (CDRs) selected from the group consisting of:
 a CDR1 sequence comprising an amino acid sequence having at least 20%, 40%, 60%, 80% or 100% sequence identity to the sequence of SEQ ID NO: 7; 
 a CDR2 sequence comprising an amino acid sequence having at least 5%, 11%, 17%, 23%, 29%, 35%, 41%, 47%, 52%, 58%, 64%, 70%, 76%, 82%, 88%, 94%, or 100% sequence identity to the sequence of SEQ ID NO: 8; and 
 a CDR3 sequence comprising an amino acid sequence having at least 11%, 22%, 33%, 44%, 55%, 66%, 77%, 88% or 100% sequence identity to the sequence of SEQ ID NO: 9 or 10; and/or 
 
 (b) the VL domain comprises an amino acid sequence that includes one, two or three complementarity determining regions (CDRs) selected from the group consisting of:
 a CDR4 sequence comprising an amino acid sequence having at least 7.5%, 15%, 23%, 30%, 38%, 46%, 53%, 61%, 69%, 76%, 84%, 92% or 100% sequence identity to the sequence of SEQ ID NO: 11; 
 a CDR5 sequence comprising an amino acid sequence having at least 14%, 28%, 42%, 57%, 71%, 85% or 100% sequence identity to the sequence of SEQ ID NO: 12; 
 a CDR6 sequence comprising an amino acid sequence having at least 9%, 18%, 27%, 36%, 45%, 54%, 63%, 72%, 81%, 90% or 100% sequence identity to the sequence of SEQ ID NO: 13. 
 
   
     
     
         2 . The antibody or antibody fragment of  claim 1  wherein the VH domain comprises an amino acid sequence that includes a CDR1 sequence, a CDR2 and a CDR3 sequence as defined by  claim 1 , and/or the VL domain comprises an amino acid sequence that includes a CDR4 sequence, a CDR5 and a CDR6 sequence as defined by  claim 1 . 
     
     
         3 . The antibody or antibody fragment of  claim 1  wherein:
 the VH domain comprises an amino acid sequence that includes the CDR1, CDR2 and CDR3 sequences present in an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 3 or 5 or an amino acid sequence having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence of any of SEQ ID NOs: 1, 3 or 5; and/or 
 the VL domain comprises an amino acid sequence that includes the CDR4, CDR5 and CDR6 sequences present in an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4 or 6 or an amino acid sequence having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence of any of SEQ ID NOs: 2, 4 or 6. 
 
     
     
         4 . The antibody or antibody fragment of  claim 1  wherein:
 the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, or 5 or an amino acid sequence having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence of any of SEQ ID NOs: 1, 3, or 5; and 
 the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4, or 6 or an amino acid sequence having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence of any of SEQ ID NOs: 2, 4, or 6. 
 
     
     
         5 . The antibody or antibody fragment according to  claim 1 , wherein:
 the VH domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO:1; and   the VL domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO: 2.   
     
     
         6 . The antibody or antibody fragment according to  claim 1 , wherein:
 the VH domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO:3; and   the VL domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO: 4.   
     
     
         7 . The antibody or antibody fragment according to  claim 1 , wherein:
 the VH domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO:5; and   the VL domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO: 6.   
     
     
         8 . The antibody or antibody fragment according to  claim 1 , wherein the VH domain, the VL domain, or preferably both of the VH and VL domains, comprise an amino acid sequence having 100% sequence identity to the, or one or more (such as all) of each, stated SEQ ID NO. 
     
     
         9 . The antibody or antibody fragment according to  claim 1 , wherein the VH domain, the VL domain, or both of the VH and VL domains, comprise an amino acid sequence having less than 100%, but at least 80%, 85%, 90%, 95%, sequence identity to the, or one or more (such as all) of each, stated SEQ ID NO. 
     
     
         10 . The antibody or antibody fragment according to  claim 1 ,
 wherein the VH domain, the VL domain, or both of the VH and VL domains, comprise an amino acid sequence having less than 100%, but at least 80%, 85%, 90%, 95%, sequence identity to the, or one or more (such as all) of each, stated SEQ ID NO, and wherein   the ability of the antibody or antibody fragment to bind to phosphorylcholine and/or a phosphorylcholine conjugate is equivalent to (that is, at least 80%, 85%, 90% or 95%, of), or greater than, the ability of a corresponding antibody or antibody fragment, wherein the VH domain and the VL domain of the corresponding antibody or antibody fragment each comprise an antigen-binding sequence comprising an amino acid sequence having 100% sequence identity to the, or each, stated SEQ ID NO.   
     
     
         11 . The antibody or antibody fragment according to  claim 1 , wherein the VH domain and the VL domain are present in a linear polypeptide sequence. 
     
     
         12 . The antibody or antibody fragment according to  claim 1 , wherein the VH domain and the VL domain are each present in a separate polypeptide sequence, and preferably wherein the separate polypeptide sequence are directly or indirectly bound together (such as by one or more disulphide bonds between the separate polypeptide sequence). 
     
     
         13 . The antibody according to  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         14 . The antibody fragment according to  claim 1  wherein the antibody fragment is a single chain antibody, Fv, scFv, Fab, F(ab′) 2 , Fab′, Fd, dAb, CDR, or scFv-Fc fragment, a nanobody, and diabody, or any such fragment that has been stabilized such as by PEGylation. 
     
     
         15 . The antibody or antibody fragment according to  claim 1  which is a human or humanized antibody or antibody fragment, such as a human or humanized monoclonal antibody. 
     
     
         16 . The antibody or antibody fragment according to  claim 1  which is capable of binding to a phosphorylcholine conjugate. 
     
     
         17 . The antibody or antibody fragment according to  claim 16 , wherein the phosphorylcholine conjugate is a phosphorylcholine moiety linked to a carrier, optionally via a spacer, and preferably the antibody or antibody fragment binds specifically to the phosphorylcholine moiety in the phosphorylcholine conjugate. 
     
     
         18 . A pharmaceutical composition comprising or consisting essentially of an antibody or an antibody fragment according to the preceding claims and a pharmaceutically acceptable carrier or excipient, optionally wherein the only antibodies or antibody fragments present in the composition are those defined by any of the preceding claims. 
     
     
         19 - 24 . (canceled) 
     
     
         25 . A method for the immunization or prophylaxis against, or the treatment of, metabolic diseases in a mammal, such as a human, the method comprising the step of administering to the mammal an antibody or antibody fragment according to  claim 1 . 
     
     
         26 . The method according to  claim 25 , wherein the metabolic disease is a condition selected from the group consisting of metabolic syndrome, insulin resistance, glucose intolerance, hyperglycemia, type I diabetes, type II diabetes, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and polycystic ovary syndrome (PCOS). 
     
     
         27 - 37 . (canceled)