Dual specificity antibodies and methods of making and using

Abstract

Antibodies having dual specificity for two different but structurally related antigens are provided. The antibodies can be, for example, entirely human antibodies, recombinant antibodies, or monoclonal antibodies. Preferred antibodies have dual specificity for IL-1α and IL-1β and neutralize IL-1α and IL-1β activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting two different but structurally related antigens (e.g., IL-1α and IL-1β) and for inhibiting the activity of the antigens, e.g., in a human subject suffering from a disorder in which IL-1α and/or IL-1β activity is detrimental.

1 . A dual-specificity antibody, or antigen-binding portion thereof, comprising an antigen binding site that specifically binds to a first and a second antigen. 
     
     
         2 .- 88 . (canceled) 
     
     
         89 . The dual-specificity antibody or fragment of  claim 1 , wherein the first and second antigens are structurally related antigens. 
     
     
         90 . The dual-specificity antibody or fragment of  claim 1 , wherein the first and second antigens are each independently selected from the group consisting of caspases, cytokines, TNF family members, IL-6 family members, interferons, TGFβ family members EGF family members, FGF family members, PDGF family members, VEGF family members, angiopoietins, bone morphogenic proteins, secreted proteinases (metallo-proteinases), and cytokine receptor families, TNF receptor family members, TGFβ receptor family members, EGF receptor family members, FGF receptor family members, PDGF receptor family members, VEGF receptor family members and Angiopoietin receptor family members. 
     
     
         91 . The dual-specificity antibody or fragment of  claim 1 , wherein the first and second antigens are each independently selected from the group consisting of IP-10, PF4, a GRO, 9E3, EMAP-II, a CSF, an FGF, and a PDGF. 
     
     
         92 . The dual-specificity antibody or fragment of  claim 1 , wherein the first or second antigens are cytokines. 
     
     
         93 . The dual-specificity antibody or fragment of  claim 1 , wherein the first and second antigens are cytokines. 
     
     
         94 . The dual-specificity antibody or fragment of  claim 1 , wherein the first or second antigens are interleukins. 
     
     
         95 . The dual-specificity antibody or fragment of  claim 1 , wherein the first and second antigens are interleukins. 
     
     
         96 . The dual-specificity antibody or fragment of  claim 1 , wherein the first antigen or second antigen is IL-1a, Il-1b or IL-18. 
     
     
         97 . The dual-specificity antibody or fragment of  claim 1 , wherein the first antigen is IL-1a and the second antigen is Il-1b. 
     
     
         98 . The dual-specificity antibody or fragment of  claim 1 , wherein the first antigen is IL-1a and the second antigen is Il-18. 
     
     
         99 . The dual-specificity antibody or fragment of  claim 1 , wherein the first antigen is IL-1b and the second antigen is Il-18. 
     
     
         100 . The dual-specificity antibody or fragment of  claim 1 , which binds to the first and second antigen with a k off  rate constant of 0.1 s −1  or less, as determined by surface plasmon resonance, or which inhibits the activity of interleukin-1α with an IC 50  of 1×10 −5  M or less.