Anti-inflammatory molecules with tissue-targeting functions

Abstract

The present disclosure provides various molecular constructs having a targeting element and an effector element. Methods for treating osteoporosis using such molecular constructs are also disclosed.

What is claimed is: 
     
         1 . A method for treating osteoporosis, comprising the step of administering to a subject in need thereof an effective amount of a molecular construct that comprises,
 a pair of CH2-CH3 segments of an IgG.Fc;   a first pair of effector elements, wherein the effector element is a receptor activator of nuclear factor kappa-B ligand (RANKL); and   a first pair of targeting elements, wherein the targeting element is an antibody fragment specific for osteonectin, wherein,   when the first pair of effector elements is linked to the N-termini of the pair of CH2-CH3 segments, then the first pair of targeting elements is linked to the C-termini of the pair of CH2-CH3 segments, and vice versa, or   when the first pair of effectors elements and the first pair of targeting elements are both in the form of single-chain variable fragments (scFvs), then the first pair of targeting elements is linked to the N-termini of the first pair of effector elements in a tandem or diabody configuration, thereby forming a pair of bispecific scFvs that are linked to the N-termini of the pair of CH2-CH3 segments.   
     
     
         2 . The method of  claim 1 , wherein the pair of CH2-CH3 segments is derived from human γ4 or γ1 immunoglobulin. 
     
     
         3 . The method of  claim 1 , wherein when the first pair of effector elements is in the form of an antigen-binding fragment (Fab), and the first pair of targeting elements is in the form of scFvs, and vice versa; then the Fab and scFvs are respectively linked to the N-termini and C-termini of the CH2-CH3 segments, so that molecular construct adopts an extended IgG configuration. 
     
     
         4 . The method of  claim 1 , wherein,
 the effector element is an scFv specific for RANKL; and   the targeting element is an scFv specific for osteonectin.   
     
     
         5 . The method of  claim 1 , wherein,
 the two effector elements are in the form of a Fab specific for RANKL; and   the targeting element is an scFv specific for osteonectin.   
     
     
         6 . A molecular construct, comprises,
 a pair of CH2-CH3 segments of an IgG.Fc;   a first pair of effector elements, wherein the effector element is a receptor activator of nuclear factor kappa-B ligand (RANKL); and   a first pair of targeting elements, wherein the targeting element is an antibody fragment specific for osteonectin, wherein,   when the first pair of effector elements is linked to the N-termini of the pair of CH2-CH3 segments, then the first pair of targeting elements is linked to the C-termini of the pair of CH2-CH3 segments, and vice versa, or   when the first pair of effectors elements and the first pair of targeting elements are both in the form of single-chain variable fragments (scFvs), then the first pair of targeting elements is linked to the N-termini of the first pair of effector elements in a tandem or diabody configuration, thereby forming a pair of bispecific scFvs that are linked to the N-termini of the pair of CH2-CH3 segments.   
     
     
         7 . The molecular construct of  claim 6 , wherein the pair of CH2-CH3 segments is derived from human γ4 or γ1 immunoglobulin. 
     
     
         8 . The molecular construct of  claim 6 , wherein when the first pair of effector elements is in the form of an antigen-binding fragment (Fab), and the first pair of targeting elements is in the form of scFvs, and vice versa; then the Fab and scFvs are respectively linked to the N-termini and C-termini of the CH2-CH3 segments, so that molecular construct adopts an extended IgG configuration. 
     
     
         9 . The molecular construct of  claim 6 , wherein,
 the effector element is an scFv specific for RANKL; and   the targeting element is an scFv specific for osteonectin.   
     
     
         10 . The molecular construct of  claim 6 , wherein,
 the two effector elements are in the form of a Fab specific for RANKL; and   the targeting element is an scFv specific for osteonectin.