Hybrid immunoglobulins

Abstract

Novel polypeptides are provided, together with methods for making and using them, and nucleic acids encoding them. These polypeptides are useful as cell surface adhesion molecules and ligands, and are useful in therapeutic or diagnostic compositions and methods.

We claim:  
     
         1 . A polypeptide fusion comprising a ligand binding partner protein and a stable plasma protein, wherein the ligand binding partner protein is not a platelet growth factor receptor or an insulin receptor.  
     
     
         2 . The polypeptide of  claim 1 , wherein the stable plasma protein is an immunoglobulin chain and the ligand binding partner protein and immunoglobulin are fused through C- or N-terminal amino or carboxyl groups.  
     
     
         3 . The polypeptide of  claim 2 , wherein a portion of the constant domain of the immunoglobulin is linked at its N-terminus to the C-terminus of said ligand binding partner.  
     
     
         4 . The polypeptide of  claim 2 , wherein the Fc portion of the constant domain of the immunoglobulin is linked at its N-terminus to the C-terminus of said ligand binding partner.  
     
     
         5 . The polypeptide of  claim 2 , wherein the immunoglobulin sequence is obtained from IgG1, IgG2, IgG3, IgG4, IgA, IgE, IgD or IgM.  
     
     
         6 . The polypeptide of  claim 2 , wherein the ligand binding partner comprises a LHR.  
     
     
         7 . The polypeptide of  claim 2 , wherein the ligand binding partner comprises a cell surface adhesion molecule.  
     
     
         8 . The polypeptide of  claim 2 , joined to a detectable marker.  
     
     
         9 . The polypeptide of  claim 2 , wherein said immunoglobulin sequence is human.  
     
     
         10 . The polypeptide of  claim 2 , wherein said ligand binding partner is human.  
     
     
         11 . The polypeptide of  claim 2 , wherein the constant domain is the constant domain of an IgG heavy chain.  
     
     
         12 . The polypeptide of  claim 2 , wherein the ligand binding partner is an LHR which binds to the high endothelial venules of lymphoid tissue.  
     
     
         13 . The polypeptide of  claim 2 , unassociated with glycosylation.  
     
     
         14 . The polypeptide of  claim 2  in a physiologically acceptable carrier.  
     
     
         15 . The polypeptide of  claim 14 , wherein the carrier is a sterile, isotonic solution.  
     
     
         16 . The polypeptide of  claim 14 , wherein the carrier is a sustained-release formulation.  
     
     
         17 . The polypeptide of  claim 14 , wherein the carrier is a liposome.  
     
     
         18 . The polypeptide of  claim 2 , wherein said ligand binding partner protein in the fusion is incapable of cell membrane anchorage.  
     
     
         19 . The polypeptide of  claim 2 , wherein said immunoglobulin is from a different species than said binding partner.  
     
     
         20 . The polypeptide of  claim 2 , wherein the ligand binding partner is a single chain.  
     
     
         21 . The polypeptide of  claim 2 , wherein the ligand binding partner contains more than one polypeptide chain, one chain of which is fused to an immunoglobulin constant region.  
     
     
         22 . The polypeptide of  claim 21 , wherein the fused chain of the ligand binding partner is devoid of its transmembrane and cytoplasmic domains.  
     
     
         23 . The polypeptide of  claim 2 , wherein said ligand binding partner is a cell membrane protein.  
     
     
         24 . The polypeptide of  claim 2 , wherein said ligand binding partner is a constant region-like domain of an immunoglobulin superfamily member.  
     
     
         25 . The polypeptide fusion of  claim 2 , wherein the ligand binding partner is a first ligand binding partner, said fusion further comprising an additional fusion of a second ligand binding partner and an immunoglobulin.  
     
     
         26 . The polypeptide fusion of  claim 25  wherein the second ligand binding partner is different from the first ligand binding partner.  
     
     
         27 . The polypeptide fusion of  claim 26  wherein the first ligand binding partner is LHR and the second ligand binding partner is CD4.  
     
     
         28 . The polypeptide fusion of  claim 25  wherein the first ligand binding partner fusion and second ligand binding partner fusion are crosslinked by disulfide bonds.  
     
     
         29 . The polypeptide fusion of  claim 25  wherein the first ligand binding partner fusion and second ligand binding partner fusion are noncovalently aggregated.  
     
     
         30 . The polypeptide of  claim 27 , wherein said ligand binding partner is a LHR having a LHR carbohydrate binding domain, a LHR epidermal growth factor domain, and a LHR complement binding domain, and wherein said LHR carbohydrate binding domain has been deleted or replaced by a heterologous carbohydrate binding domain.  
     
     
         31 . The polypeptide of  claim 27 , wherein said ligand binding partner is a LHR having a LHR carbohydrate binding domain, a LHR epidermal growth factor domain, and a LHR complement binding domain, and wherein said LHR epidermal growth factor binding domain has been deleted or replaced by a heterologous epidermal growth factor binding domain.  
     
     
         32 . The polypeptide of  claim 27 , wherein said ligand binding partner is a LHR having a LHR carbohydrate binding domain, a LHR epidermal growth factor domain, and a LHR complement binding domain, and wherein said LHR complement binding domain has been deleted or replaced by a heterologous complement binding domain.  
     
     
         33 . The polypeptide of  claim 27 , wherein said ligand binding partner is a LHR having a LHR carbohydrate binding domain, a LHR epidermal growth factor domain, a LHR complement binding domain, a LHR cytoplasmic domain and a LHR transmembrane domain, and wherein said LHR cytoplasmic and transmembrane domains have been inactivated.  
     
     
         34 . The polypeptide of  claim 1  wherein the stable plasma protein is selected from the group consisting of serum albumin, transferrin, lipoprotein and apolipoprotein.  
     
     
         35 . The polypeptide of  claim 34  wherein the plasma protein is albumin.  
     
     
         36 . The polypeptide of  claim 1  wherein the ligand binding partner is a CD antigen.  
     
     
         37 . The polypeptide of  claim 1  wherein the ligand binding partner is a LHR.  
     
     
         38 . A polypeptide fusion comprising a first ligand binding partner and a stable plasma protein, said fusion further comprising an additional fusion of a second ligand binding partner and a second stable plasma protein, wherein said first and second ligand binding partners are different.  
     
     
         39 . A polypeptide fusion comprising a ligand binding partner and a stable plasma protein, wherein said stable plasma protein is not an immunoglobulin.  
     
     
         40 . A polypeptide fusion comprising a ligand binding partner and a stable plasma protein, said fusion comprising a single chain fusion.  
     
     
         41 . A polypeptide fusion comprising a first ligand binding partner and a stable plasma protein, said fusion further comprising an additional fusion of a second ligand binding partner and a second stable plasma protein, wherein each of said stable plasma proteins are immunoglobulin constant domains.  
     
     
         42 . Nucleic acid encoding the polypeptide of  claim 1 .  
     
     
         43 . A replicable expression vector comprising the nucleic acid of  claim 42 .  
     
     
         44 . A composition comprising a cell transformed with the recombinant expression vector of  claim 43 .  
     
     
         45 . The composition of  claim 44  wherein the cell is a mammalian cell.  
     
     
         46 . The composition of  claim 44  wherein the cell is a chinese hamster ovary cell line.  
     
     
         47 . A method of culturing the cell of  claim 44  which comprises culturing the transformed cell and recovering a polypeptide from the cell culture.  
     
     
         48 . The method of  claim 47  wherein the polypeptide is recovered from the host cell.  
     
     
         49 . The method of  claim 47  wherein the polypeptide is secreted into the culture medium and recovered from the culture medium.