US2018221505A1PendingUtilityA1

Novel Antibody And Use In Diagnosis And Therapy Of Arthropathies

Assignee: QUEEN MARY & WESTFIELD COLLEGEPriority: May 3, 2007Filed: Dec 18, 2017Published: Aug 9, 2018
Est. expiryMay 3, 2027(~0.8 yrs left)· nominal 20-yr term from priority
A61K 47/6811A61K 47/6817C07K 2317/569C07K 2317/76A61K 47/6849C07K 16/18A61K 47/6813C07K 2317/565C07K 2317/55C07K 2317/622A61P 19/02A61K 51/1096A61K 47/6803A61K 47/6851A61K 47/6843
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Claims

Abstract

The present invention provides a composition comprising an antibody or fragment thereof against oxidised Collagen II (CII) in which the antibody or fragment thereof is conjugated to a pharmaceutically active moiety. The invention also provides a composition comprising an antibody or fragment thereof against oxidised Collagen II (Gil) and a detectable label. The invention further provides the use of such compositions in medicine, in particular for the treatment of an arthropathy, and in methods of diagnosis.

Claims

exact text as granted — not AI-modified
1 - 26 . (canceled) 
     
     
         27 . A composition comprising an antibody or fragment thereof against oxidised Collagen II (CII) in which the antibody or fragment thereof is conjugated to a pharmaceutically active moiety, wherein the antibody or fragment thereof comprises CDR sequences in the Variable Heavy (VH) chains and Variable Light (VL) chains as shown below, wherein the CDRH1 and CDRL1 sequences are the same as those of scFv 1-11E; 
       
         
           
                 
                 
                 
                 
               
                     
                 
                   CDRH2 
                   CDRH3 
                   CDRL2 
                   CDRL3 
                 
                     
                 
                   SIDSAGDSTYYADSVKG 
                   SYSYFDY 
                   TASYLQS 
                   QQASDYPTT 
                 
                   (SEQ ID NO: 35) 
                   (SEQ ID NO: 58) 
                   (SEQ ID NO: 85) 
                   (SEQ ID NO: 122) 
                 
                     
                 
                   SISNSGTNTDYADSVKG 
                   NYASFDY 
                   YASYLQS 
                   QQGSASPST 
                 
                   (SEQ ID NO: 7) 
                   (SEQ ID NO: 45) 
                   (SEQ ID NO: 65) 
                   (SEQ ID NO: 92) 
                 
                     
                 
                   SIASSGTTTYYADSVKG 
                   SYADFDY 
                   AASNLQS 
                   QQADTYPTT 
                 
                   (SEQ ID NO: 31) 
                   (SEQ ID NO: 54) 
                   (SEQ ID NO: 82) 
                   (SEQ ID NO: 118) 
                 
                     
                 
                   SIDTGGSYTDYADSVKG 
                   SYTTFDY 
                   SASYLQS 
                   QQGSNSPTT 
                 
                   (SEQ ID NO: 37) 
                   (SEQ ID NO: 59) 
                   (SEQ ID NO: 75) 
                   (SEQ ID NO: 124). 
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         28 . The composition as claimed in  claim 27 , in which the antibody is a polyclonal antibody or a monoclonal antibody. 
     
     
         29 . The composition as claimed in  claim 27 , in which the antibody fragment is a Fc, Fab, scFv, single domain (dAb) antibody, diabody, minibody, or scFv-Fc fragment. 
     
     
         30 . The composition as claimed in  claim 27 , in which the antibody is an scFv selected from the group consisting of 1-12A, 4-6A, 4-8A, 4-9F, 4-4H, 3-3A, 3-6F, 3-9D, 3-11E, 6-11D, 4-5H, 6-5F, and 6-7F. 
     
     
         31 . The composition as claimed in  claim 27 , in which the composition comprises a proteolytic cleavage site between the antibody or fragment thereof and the pharmaceutically active moiety. 
     
     
         32 . The composition as claimed in  claim 31 , in which the proteolytic cleavage site is a matrix metalloproteinase (MMP) cleavage site, a serine protease cleavage site, or a site cleavable by a parasitic protease derived from a pathogenic organism. 
     
     
         33 . The composition as claimed in  claim 32 , in which the proteolytic cleavage site is a MMP cleavage site. 
     
     
         34 . The composition as claimed in  claim 33 , in which the MMP cleavage site is one or more of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, and MMP10 as shown in  FIG. 5 . 
     
     
         35 . The composition as claimed in  claim 27 , in which the pharmaceutically active moiety is an antibody or a fragment thereof, a growth factor, a differentiation factor, a cytokine molecule, an interferon, a bone morphogenetic protein (BMP), a chemokine, a MCP (Monocyte Chemotactic Protein), a cytokine inhibitor, a cytokine receptor, a free-radical scavenging enzyme, or a toxin, or an active fragment or portion thereof. 
     
     
         36 . The composition as claimed in  claim 35 , in which the pharmaceutically active moiety is an interferon. 
     
     
         37 . The composition as claimed in  claim 36 , in which the pharmaceutically active moiety is interferon beta (IFN-β). 
     
     
         38 . The composition as claimed in  claim 35 , in which the pharmaceutically active moiety is a TNF receptor (TNFR) antibody fusion protein. 
     
     
         39 . The composition as claimed in  claim 38 , in which the pharmaceutically active moiety is TNFR2-Fc. 
     
     
         40 . The composition as claimed in  claim 27 , in which the pharmaceutically active moiety is a glycosaminoglycan molecule, chondroitin, a non-steroidal anti-inflammatory drug (NSAID), a steroid, sodium hyaluronate or hyaluronic acid, colchicine, or hydroxychloroquine. 
     
     
         41 . A composition comprising an antibody or fragment thereof against oxidised Collagen II (CII) and a detectable label, wherein the antibody or fragment thereof comprises CDR sequences in the Variable Heavy (VH) chains and Variable Light (VL) chains as shown below, wherein the CDRH1 and CDRL1 sequences are the same as those of scFv 1-11E; 
       
         
           
                 
                 
                 
                 
               
                     
                 
                   CDRH2 
                   CDRH3 
                   CDRL2 
                   CDRL3 
                 
                     
                 
                   SIDSAGDSTYYADSVKG 
                   SYSYFDY 
                   TASYLQS 
                   QQASDYPTT 
                 
                   (SEQ ID NO: 35) 
                   (SEQ ID NO: 58) 
                   (SEQ ID NO: 85) 
                   (SEQ ID NO: 122) 
                 
                     
                 
                   SISNSGTNTDYADSVKG 
                   NYASFDY 
                   YASYLQS 
                   QQGSASPST 
                 
                   (SEQ ID NO: 7) 
                   (SEQ ID NO: 45) 
                   (SEQ ID NO: 65) 
                   (SEQ ID NO: 92) 
                 
                     
                 
                   SIASSGTTTYYADSVKG 
                   SYADFDY 
                   AASNLQS 
                   QQADTYPTT 
                 
                   (SEQ ID NO: 31) 
                   (SEQ ID NO: 54) 
                   (SEQ ID NO: 82) 
                   (SEQ ID NO: 118) 
                 
                     
                 
                   SIDTGGSYTDYADSVKG 
                   SYTTFDY 
                   SASYLQS 
                   QQGSNSPTT 
                 
                   (SEQ ID NO: 37) 
                   (SEQ ID NO: 59) 
                   (SEQ ID NO: 75) 
                   (SEQ ID NO: 124). 
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         42 . The composition as claimed in  claim 41 , in which the detectable label is a radionuclide or a dye. 
     
     
         43 . The composition as claimed in  claim 42 , in which the detectable label is a dye. 
     
     
         44 . A method of treatment of an arthropathy, comprising administering to a subject a composition as claimed in  claim 27 . 
     
     
         45 . A method for the diagnosis of an arthropathy comprising administering a composition of  claim 27  and subsequently detecting the composition.

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