Immunoglobulins devoid of light chains

Abstract

There is provided an isolated immunoglobulin comprising two heavy polypeptide chains sufficient for the formation of a complete antigen binding site or several antigen binding sites, wherein the immunoglobulin is further devoid of light polypeptide chains.

1 . A method for synthesising a single-domain-effector group (dAb-effector group) suitable for in vivo use comprising the steps of: (a) selecting an antibody single variable domain having an epitope binding specificity; and (b) attaching the single domain of step (a) to an effector group.  
     
     
         2 . A method according to  claim 1  wherein the antibody single variable domain is a heavy chain variable domain.  
     
     
         3 . A method according to  claim 1  wherein the effector group comprises any one or more of those groups selected from the group consisting of: an antibody CH1 heavy chain domain, an antibody CH2 heavy chain domain, an antibody CH3 heavy chain domain, an Fc region of an antibody and a hinge region of an antibody molecule.  
     
     
         4 . A method according to  claim 1 , wherein the effector group constitutes an Fc region of an antibody.  
     
     
         5 . A method according to  claim 1 , wherein the effector group consists of a CH2 and CH3 domain.  
     
     
         6 . A method according to  claim 3 , wherein the effector group consists of a CH2 domain, a CH3 domain and the hinge region of an antibody molecule.  
     
     
         7 . A method according to  claim 1 , wherein the antibody single variable domain is a non-Camelid variable domain.  
     
     
         8 . A method according to  claim 1 , wherein the antibody single variable domain comprises one or more human framework regions.  
     
     
         9 . A method according to  claim 1 , wherein the antibody single variable domain comprises four framework regions as defined by Kabat, which are derived from a human.  
     
     
         10 . A method according to  claim 9 , wherein one or more of the human framework regions as defined by Kabat are identical on the amino acid level to those encoded by human germline antibody genes.  
     
     
         11 . A method according to  claim 1 , wherein the antibody single variable domain is isolated, in part, by human immunisation.  
     
     
         12 . A method according to  claim 1 , wherein the antibody single variable domain is not isolated by animal immunisation.  
     
     
         13 . A method according to  claim 1 , wherein the effector group is of Camelid or human origin.  
     
     
         14 . A method according to  claim 1 , wherein the single variable domain comprises one or more human framework regions and the immunoglobulin effector group is of human origin.  
     
     
         15 . A method according to  claim 14 , wherein the single variable domain comprises four human framework regions and the immunoglobulin effector group is of human origin.  
     
     
         16 . A method according to  claim 1 , wherein attaching of the single variable domain to the effector group in step (b) is effected by expressing the single-domain-effector group as a fusion polypeptide.  
     
     
         17 . A dAb-effector group comprising: (a) an antibody single variable domain having an epitope binding specificity; and (b) an effector group attached to said antibody single variable domain.  
     
     
         18 . A medicament comprising the dAb-effector group of  claim 17 .  
     
     
         19 . A dAb-effector group according to  claim 17 , wherein the antibody single variable domain is a heavy chain variable domain.  
     
     
         20 . A dAb-effector group according to  claim 17 , wherein the effector group comprises any one or more of those groups selected from the group consisting of: an antibody CH1 heavy chain domain, an antibody CH2 heavy chain domain, an antibody CH3 heavy chain domain, an Fe region of an antibody and a hinge region of an antibody molecule.  
     
     
         21 . A dAb-effector group according to  claim 20  wherein the effector group consists of a CH2 and CH3 domain.  
     
     
         22 . A dAb-effector group according to  claim 20  wherein the effector group consists of a CH2 domain, a CH3 domain and the hinge region of an antibody molecule.  
     
     
         23 . A dAb-effector group according to  claim 20  wherein the effector group constitutes an Fc region of an antibody.  
     
     
         24 . A dAb-effector group according to  claim 17 , wherein the antibody single variable domain comprises human framework regions.  
     
     
         25 . A dAb-effector group according to  claim 17 , wherein the effector group is of Camelid or human origin.  
     
     
         26 . A dAb-effector group according to  claim 17 , wherein the single variable domain comprises one or more human framework regions and the immunoglobulin effector group is of human origin.  
     
     
         27 . Two or more dAb-effector groups according to  claim 17  provided as a higher order structure selected from the group consisting of the following: dimers, trimers and multimers.  
     
     
         28 . Two dAb-effector groups according to  claim 27  provided as a heterodimer or a homodimer.  
     
     
         29 . Two dAb-effector groups according to  claim 28  provided as a homodimer.  
     
     
         30 . A nucleic acid molecule encoding a dAb-effector group according to  claim 17 .  
     
     
         31 . A nucleic acid molecule according to  claim 30  further encoding a signal sequence for export of the dAb and effector group from the cytoplasm of a host cell upon expression.  
     
     
         32 . A vector comprising nucleic acid according to  claim 30 .  
     
     
         33 . A host cell transfected with a vector according to  claim 32 .  
     
     
         34 . A composition comprising a dAb-effector group(s) according to  claim 17  and a pharmaceutically acceptable carrier, diluent or excipient.  
     
     
         35 . A method of treating and/or preventing disease in a patient, wherein the method comprises administering to the patient a dAb-effector group(s) according to  claim 17  or a composition according to claims  34 .  
     
     
         36 . A medicament for the treatment and/or prevention of disease, comprising the dAb-effector group of  claim 17  or the composition of  claim 34.