Antibodies specific to fcrn

Abstract

The disclosure relates to antibodies specific to FcRn, formulations comprising the same, use of each in therapy, processes for expressing and optionally formulating said antibody, DNA encoding the antibodies and hosts comprising said DNA.

We claim: 
     
         1 . A method of treating an autoimmune disease, the method comprising administering to a patient a therapeutically effective amount of an anti-FcRn antibody or FcRn-binding fragment thereof, wherein the anti-FcRn antibody or FcRn-binding fragment thereof comprises (i) a heavy chain or heavy chain fragment having a variable region, and (ii) a complementary light chain or light chain fragment having a variable region,
 wherein said heavy chain variable region comprises three CDRs, wherein CDR H1 has the sequence given in SEQ ID NO: 1, CDR H2 has the sequence given in SEQ ID NO: 2, and CDR H3 has the sequence given in SEQ ID NO: 3, and   wherein said light chain variable region comprises three CDRs, wherein CDR L1 has the sequence given in SEQ ID NO: 4, CDR L2 has the sequence given in SEQ ID NO: 5 or SEQ ID NO: 7 and CDR L3 has the sequence given in SEQ ID NO: 6.   
     
     
         2 . The method of  claim 1 , wherein the heavy chain comprises the sequence given in SEQ ID NO:12 and the light chain comprises the sequence given in SEQ ID NO: 8. 
     
     
         3 . The method of  claim 1 , wherein the anti-FcRn antibody or FcRn-binding fragment thereof is humanized. 
     
     
         4 . The method of  claim 1 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 25 and the light chain comprises the sequence given in SEQ ID NO: 16. 
     
     
         5 . The method of  claim 1 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 59 and the light chain comprises the sequence given in SEQ ID NO: 51. 
     
     
         6 . The method of  claim 1 , wherein the heavy chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 25 and the light chain comprises a sequence having at least 80% identity to the sequence given in SEQ ID NO: 16. 
     
     
         7 . The method of  claim 1 , wherein the anti-FcRn binding fragment thereof is a scFv, Fv, Fab or Fab′ fragment. 
     
     
         8 . The method of  claim 7 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 33 and the light chain comprises the sequence given in SEQ ID NO: 20. 
     
     
         9 . The method of  claim 7 , wherein the FcRn-binding fragment is a Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO: 29 and a light chain comprising the sequence given in SEQ ID NO: 20. 
     
     
         10 . The method of  claim 7  wherein the FcRn-binding fragment is a Fab′ fragment having a heavy chain comprising the sequence given in SEQ ID NO: 63 and a light chain comprising the sequence given in SEQ ID NO: 55. 
     
     
         11 . The method of  claim 7  wherein the FcRn-binding fragment is a Fab-dsFv fragment having a heavy chain comprising the sequence given in SEQ ID NO: 42 and a light chain comprising the sequence given in SEQ ID NO: 40. 
     
     
         12 . The method of  claim 1 , wherein the antibody or binding fragment is conjugated to a polymer comprising a starch, albumin or polyethylene glycol. 
     
     
         13 . The method of  claim 12 , wherein the polymer is PEG, comprising a molecular weight in the range 5 to 50 kDa. 
     
     
         14 . The method of  claim 1  wherein the anti-FcRn antibody is a full length antibody. 
     
     
         15 . The method of  claim 14  wherein the full length anti-FcRn antibody is selected from the group consisting of an IgG1, IgG4, and IgG4P. 
     
     
         16 . The method according to  claim 15 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 37, SEQ ID NO:39 or SEQ ID NO:73 and the light chain comprises the sequence given in SEQ ID NO: 20. 
     
     
         17 . A method comprising administering to a patient a therapeutically effective amount of an anti-FcRn antibody or FcRn-binding fragment thereof, wherein the anti-FcRn antibody or FcRn-binding fragment thereof comprises (i) a heavy chain or heavy chain fragment having a variable region, and (ii) a complementary light chain or light chain fragment having a variable region,
 wherein   said heavy chain variable region comprises three CDRs, wherein CDR H1 has the sequence given in SEQ ID NO: 1, CDR H2 has the sequence given in SEQ ID NO: 2, and CDR H3 has the sequence given in SEQ ID NO: 3, and   said light chain variable region comprises three CDRs, wherein CDR L1 has the sequence given in SEQ ID NO: 4, CDR L2 has the sequence given in SEQ ID NO: 5 or SEQ ID NO: 7 and CDR L3 has the sequence given in SEQ ID NO: 6; and   the patient has a disease selected from the group consisting of myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, Guillain-Barré syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, antiphospholipid syndrome (APS), autoimmune urticarial, chronic inflammatory demyelinating polyneuropathy (CIDP), Goodpasture's syndrome, Graves' disease, hemolytic anemia, neutropenia, paraneoplastic cerebellar degeneration, paraproteinemic polyneuropathies, primary biliary cirrhosis, stiff person syndrome, vitiligo and warm idiopathic haemolytic anaemia, or combinations thereof.   
     
     
         18 . The method of  claim 17 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 25 and the light chain comprises the sequence given in SEQ ID NO: 16. 
     
     
         19 . The method of  claim 17 , wherein the FcRn-binding fragment is a Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO: 29 and a light chain comprising the sequence given in SEQ ID NO: 20. 
     
     
         20 . A method of treating an autoimmune disease, the method comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising an anti-FcRn antibody or FcRn-binding fragment thereof in combination with one or more of a pharmaceutically acceptable excipient, diluent, or carrier,
 wherein   the anti-FcRn antibody or FcRn-binding fragment thereof comprises (i) a heavy chain or heavy chain fragment having a variable region, and (ii) a complementary light chain or light chain fragment having a variable region,   said heavy chain variable region comprises three CDRs, wherein CDR H1 has the sequence given in SEQ ID NO: 1, CDR H2 has the sequence given in SEQ ID NO: 2, and CDR H3 has the sequence given in SEQ ID NO: 3, and   said light chain variable region comprises three CDRs, wherein CDR L1 has the sequence given in SEQ ID NO: 4, CDR L2 has the sequence given in SEQ ID NO: 5 or SEQ ID NO: 7 and CDR L3 has the sequence given in SEQ ID NO: 6.   
     
     
         21 . The method of  claim 20 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 25 and the light chain comprises the sequence given in SEQ ID NO: 16. 
     
     
         22 . The method of  claim 20 , wherein the FcRn-binding fragment is a Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO: 29 and a light chain comprising the sequence given in SEQ ID NO: 20. 
     
     
         23 . The method of  claim 20  wherein the pharmaceutical composition comprises other active ingredients. 
     
     
         24 . The method of  claim 21  wherein the pharmaceutical composition comprises other active ingredients. 
     
     
         25 . The method of  claim 22  wherein the pharmaceutical composition comprises other active ingredients. 
     
     
         26 . The method of  claim 20  wherein the autoimmune disease is selected from the group consisting of myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, Guillain-Barré syndrome, lupus, idiopathic thrombocytopenic purpura or thrombotic thrombocytopenic purpura, antiphospholipid syndrome (APS), autoimmune urticarial, chronic inflammatory demyelinating polyneuropathy (CIDP), Goodpasture's syndrome, Graves' disease, hemolytic anemia, neutropenia, paraneoplastic cerebellar degeneration, paraproteinemic polyneuropathies, primary biliary cirrhosis, stiff person syndrome, vitiligo and warm idiopathic haemolytic anaemia, or combinations thereof. 
     
     
         27 . The method of  claim 21  wherein the autoimmune disease is selected from the group consisting of myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, Guillain-Barré syndrome, lupus, idiopathic thrombocytopenic purpura or thrombotic thrombocytopenic purpura, antiphospholipid syndrome (APS), autoimmune urticarial, chronic inflammatory demyelinating polyneuropathy (CIDP), Goodpasture's syndrome, Graves' disease, hemolytic anemia, neutropenia, paraneoplastic cerebellar degeneration, paraproteinemic polyneuropathies, primary biliary cirrhosis, stiff person syndrome, vitiligo and warm idiopathic haemolytic anaemia, or combinations thereof. 
     
     
         28 . The method of  claim 22  wherein the autoimmune disease is selected from the group consisting of myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, Guillain-Barré syndrome, lupus, idiopathic thrombocytopenic purpura or thrombotic thrombocytopenic purpura, antiphospholipid syndrome (APS), autoimmune urticarial, chronic inflammatory demyelinating polyneuropathy (CIDP), Goodpasture's syndrome, Graves' disease, hemolytic anemia, neutropenia, paraneoplastic cerebellar degeneration, paraproteinemic polyneuropathies, primary biliary cirrhosis, stiff person syndrome, vitiligo and warm idiopathic haemolytic anaemia, or combinations thereof.