Antigens Associated with Inflammatory Bowel Disease Including Ulcerative Colitis

Abstract

Specific binding members that bind the ED-A isoform of fibronectin for use in methods of diagnosis, detection, imaging and/or treatment of inflammatory bowel disease such as ulcerative colitis and/or for use in delivery to the neovasculature of intestinal tissue of a molecule conjugated to the specific binding member. Specific binding members that bind tenascin-C, especially the A1, A2, A3, A4 and/or D domain tenascin-C large isoform, for use in methods of diagnosis, detection, imaging and/or treatment of ulcerative colitis and/or for use in delivery to the neovasculature of inflammatory bowel disease tissue of a molecule conjugated to the specific binding member.

1 - 86 . (canceled) 
     
     
         87 . A method of detecting or diagnosing inflammatory bowel disease in a human or animal, wherein the method comprises the steps of
 (a) administering a specific binding member which binds the ED-A domain of fibronectin; and   (b) determining the presence or absence of the specific binding member in sites of bowel inflammation in the human or animal body; wherein localization of the specific binding member to sites of inflammation indicates the presence of inflammatory bowel disease in said human or animal.   
     
     
         88 . The method of  claim 87 , wherein the specific binding member is conjugated to a detectable label or a radioisotope. 
     
     
         89 . The method of  claim 88  comprising imaging said site of inflammation. 
     
     
         90 . The method of  claim 87 , wherein the specific binding member comprises a VH domain comprising a framework and a set of complementarity determining regions HCDR1, HCDR2 and HCDR3, wherein HCDR1 has amino acid sequence SEQ ID NO: 42, HCDR2 has amino acid sequence SEQ ID NO: 56, HCDR3 has amino acid sequence SEQ ID NO 60; or wherein the VH domain comprises a set of complementarity determining regions having ten or fewer amino acid substitutions within the complementarity determining regions HCDR1, HCDR2 and HCDR3. 
     
     
         91 . The method of  claim 90 , wherein the VH domain framework is a human germline framework, and wherein the VH domain optionally has amino acid sequence SEQ ID NO: 14 or 16. 
     
     
         92 . The method  claim 87 , wherein the specific binding member further comprises a VL domain comprising a set of complementarity determining regions LCDR1, LCDR2 and LCDR3 and a framework. 
     
     
         93 . The method of  claim 92 , wherein LCDR1 has amino acid sequence SEQ ID NO: 102, LCDR2 has amino acid sequence SEQ ID NO: 114, and LCDR3 has amino acid sequence SEQ ID NO: 118; or wherein the VL domain comprises a set of complementarity determining regions having ten or fewer amino acid substitutions within the complementarity determining regions LCDR1, LCDR2 and LCDR3. 
     
     
         94 . The method of  claim 92 , wherein the VL domain framework is a human germline framework, wherein the VL domain optionally has amino acid sequence SEQ ID NO: 76 or 78. 
     
     
         95 . The method of  claim 92 , wherein the specific binding member comprises a single chain Fv. 
     
     
         96 . The method of  claim 95 , wherein the binding member is a small immunoprotein (SIP). 
     
     
         97 . The method of  claim 92 , wherein the specific binding member is a diabody. 
     
     
         98 . The method of  claim 87 , wherein said inflammatory bowel disease is ulcerative colitis and said binding member is anti-ED-A F8 antibody. 
     
     
         99 . A method of treating inflammatory bowel disease in a patient, the method comprising administering to a patient a therapeutically effective amount of a medicament comprising a specific binding member which binds the ED-A isoform of fibronectin. 
     
     
         100 . The method of  claim 99 , wherein the specific binding member is conjugated to a detectable label or a radioisotope. 
     
     
         101 . The method of  claim 99 , wherein the specific binding member is conjugated to a bioactive molecule, such as a cytokine, hormone, a therapeutic radioisotope or a cytotoxic drug, and wherein the bioactive molecule is optionally conjugated to the specific binding member by a cleavable linker. 
     
     
         102 . The method of  claim 99 , wherein said cytokine is selected from the group consisting of a cytokine selected from the group consisting of IL-10, TGF-beta, IL-2, IL-12, IL-15, IL-21, IL-24, IL-33, tumour necrosis factor (TNF), interferon-alpha, interferon-beta and interferon-gamma. 
     
     
         103 . The method of  claim 99 , wherein the specific binding member comprises a VH domain comprising a framework and a set of complementarity determining regions HCDR1, HCDR2 and HCDR3, wherein HCDR1 has amino acid sequence SEQ ID NO: 42, HCDR2 has amino acid sequence SEQ ID NO: 56, HCDR3 has amino acid sequence SEQ ID NO 60; or wherein the VH domain comprises a set of complementarity determining regions having ten or fewer amino acid substitutions within the complementarity determining regions HCDR1, HCDR2 and HCDR3. 
     
     
         104 . The method of  claim 103 , wherein the VH domain framework is a human germline framework, and wherein the VH domain optionally has amino acid sequence SEQ ID NO: 14 or 16. 
     
     
         105 . The method  claim 99 , wherein the specific binding member further comprises a VL domain comprising a set of complementarity determining regions LCDR1, LCDR2 and LCDR3 and a framework. 
     
     
         106 . The method of  claim 105 , wherein LCDR1 has amino acid sequence SEQ ID NO: 102, LCDR2 has amino acid sequence SEQ ID NO: 114, and LCDR3 has amino acid sequence SEQ ID NO: 118; or wherein the VL domain comprises a set of complementarity determining regions having ten or fewer amino acid substitutions within the complementarity determining regions LCDR1, LCDR2 and LCDR3. 
     
     
         107 . The method of  claim 106 , wherein the VL domain framework is a human germline framework, wherein the VL domain optionally has amino acid sequence SEQ ID NO: 76 or 78. 
     
     
         108 . The method of  claim 99 , wherein the specific binding member comprises a single chain Fv. 
     
     
         109 . The method of  claim 108 , wherein the binding member is a small immunoprotein (SIP). 
     
     
         110 . The method of  claim 99 , wherein the specific binding member is a diabody. 
     
     
         111 . The method of  claim 102 , wherein said inflammatory bowel disease is ulcerative colitis and said binding member is anti-ED-A F8 antibody and said cytokine is IL-10. 
     
     
         112 . The method of  claim 109 , wherein the binding member is a small immunoprotein (SIP).