Function of a haptoglobin-haemoglobin receptor and the uses thereof

Abstract

The present invention relates to haptoglobin-haemoglobin (Hp-Hb) complex or a part thereof or a mimic thereof being operably linked to a substance and capable of binding a CD163 receptor. Furthermore, the invention relates to a CD163 variant, membrane bound or soluble, capable of binding at least one haptoglobin-haemoglobin (Hp-Hb) complex, and the use of the Hp-Hb complex and the CD163 receptor for therapy.

1 . A Hp-Hb complex (haptoglobin-haemoglobin complex) or a part thereof or a mimic thereof being operably linked to a substance, wherein the Hp-Hb complex or the part thereof or the mimic thereof is capable of binding a CD163 receptor and/or a CD163 receptor variant.  
     
     
         2 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 1 , in a purified form.  
     
     
         3 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 1 , in an isolated form.  
     
     
         4 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 1 , wherein the complex is dimeric.  
     
     
         5 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 1 , wherein the complex is multimeric.  
     
     
         6 . The Hp-Hb part or mimic according to  claim 1 , capable of binding to a region in one or more of the SRCR domains I-IX of the CD163 receptor.  
     
     
         7 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 1 , wherein the substance comprises a medicament.  
     
     
         8 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 7 , wherein the medicament is selected from antibiotics and anticancer drugs.  
     
     
         9 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 7 , wherein the medicament is selected from anti-HIV drugs.  
     
     
         10 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 1 , wherein the substance comprises a gene.  
     
     
         11 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 10 , wherein the gene comprises a nucleic acid, such as PNA, LNA, DNA or RNA.  
     
     
         12 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 10 , wherein the gene comprises cDNA.  
     
     
         13 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 10 , wherein the gene is encoding CD163.  
     
     
         14 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 1 , wherein the substance comprises an antibody or an antigen.  
     
     
         15 . The Hp-Hb complex, or a part thereof, or a mimic thereof according to any of the claims  1 - 14 , wherein the substance comprises a tracer or a marker.  
     
     
         16 . The Hp-Hb as mimic, according to any of the claims, wherein the mimic is an antibody.  
     
     
         17 . A method of treatment of an individual comprising administration of the Hp-Hb complex, or a part thereof, or a mimic thereof according to  claim 1 , the method comprising the steps of: 
 iv) providing a Hp-Hb complex, or a part thereof, or a mimic thereof as defined in  claim 1  capable of binding to the CD163 variant,    v) operably linking a substance as defined in the claims  1 - 16  to the Hp-Hb complex, or a part thereof, or a mimic thereof,    vi) administering the substance operably linked to the Hp-Hb complex, or a part thereof, or a mimic thereof to an individual in need thereof.    
     
     
         18 . A composition comprising a Hp-Hb complex, or a part thereof, or a mimic thereof as defined in  claim 1 .  
     
     
         19 . A CD163 variant capable of binding at least one haptoglobin-haemoglobin (Hp-Hb) complex.  
     
     
         20 . The CD163 variant according to  claim 19 , wherein the at least one Hp-Hb complex is dimeric.  
     
     
         21 . The CD163 variant according to  claim 19 , wherein the at least one Hp-Hb complex is multimeric.  
     
     
         22 . The CD163 variant according to  claim 19 , comprising the SRCR domains I-IX of the CD 163 receptor, or a variant thereof.  
     
     
         23 . The CD163 variant according to  claim 22 , comprising at least the Hp-Hb binding region.  
     
     
         24 . The CD163 variant according to  claim 19 , wherein the binding affinity has a Kd of 100 nM or less.  
     
     
         25 . The CD163 variant according to  claim 19 , wherein the binding affinity has a Kd of 10 nM or less.  
     
     
         26 . A CD163 variant according to  claim 19 , which is soluble  
     
     
         27 . A medicament comprising the CD163 variant as defined in  claim 18 .  
     
     
         28 . A method of treatment of an individual comprising administration of a CD163 variant according to any of  claims 19  to  26 .  
     
     
         29 . The method according to  claim 17 , wherein the method comprises drug-delivery treatment of an individual in need of such treatment.  
     
     
         30 . The method according to  claim 17 , wherein the method comprises gene delivery treatment of an individual in need of such treatment.  
     
     
         31 . The method according to  claim 17  or  28 , wherein the method comprises treatment of haemolysis in an individual in need of such treatment.  
     
     
         32 . A diagnostic composition comprising a CD 163 variant as defined in  claim 19 .  
     
     
         33 . The composition according to  claim 32 , said CD163 being expressed by a cell said method comprising administrating a Hp-Hb complex operably linked to a marker for marking the CD163 representing cell.  
     
     
         34 . The composition according to  claim 33 , for identifying macrophages in a biological sample from an individual.  
     
     
         35 . A composition comprising at least one purified CD163 receptor and/or at least one purified CD163 variant as defined in  claim 19 .  
     
     
         36 . A method for diagnosing a pathological condition comprising administrating a composition as defined in  claim 35 .  
     
     
         37 . A medicament comprising at least one Hp-Hb complex, or a part thereof or a mimic thereof as defined in  claim 1.