Anti-allergen antibodies

Abstract

The present invention generally relates to antibodies or binding fragments thereof capable of binding an allergen, in particular a food allergen as well as pharmaceutical compositions comprising such antibodies or binding fragments thereof for the treatment of allergy, in particular food allergy. In addition the invention relates to methods for evaluating the capacity of a candidate antibody or binding fragment thereof to inhibit allergen binding/and/or allergen- induced activity in a human and methods of detecting or quantifying whether an allergen is present in a sample.

1 . Antibody or binding fragment thereof capable of binding to a food allergen. 
     
     
         2 . Antibody or binding fragment thereof according to  claim 1 , wherein the antibody is human-derived. 
     
     
         3 . Antibody or binding fragment thereof according to  claim 1  or  2 , wherein the food allergen is a peanut allergen. 
     
     
         4 . Antibody or binding fragment thereof according to  claim 3 , wherein the peanut allergen is selected from the group consisting of Ara h 1, Ara h 2, Ara h 3, Ara h 4, Ara h 5, Ara h 6/7, Ara h 8, Ara h 9 and Ara h 10/11. 
     
     
         5 . Antibody or binding fragment thereof according to any one of embodiments 1 to 4, wherein the antibody is capable of binding at least one of the Ara h2 epitopes selected from the group consisting of the amino acid sequences set forth in SEQ ID NOs: 84, 88, 89, 90 and 91. 
     
     
         6 . Antibody or binding fragment thereof according to any one of the preceding claims, wherein the antibody is a monoclonal antibody and/or a recombinant antibody. 
     
     
         7 . Antibody or binding fragment thereof according to any one of the preceding claims, wherein the antibody is an IgG or IgA antibody. 
     
     
         8 . Antibody or binding fragment thereof according to any one of the preceding claims, wherein variable regions, portions thereof or the CDRs are derived from an IgE antibody and grafted in a scaffold of an IgG or IgA antibody. 
     
     
         9 . Antibody or binding fragment thereof according to any one of  claims 2  to  8 , wherein the human is selected from the group of a human suffering from peanut allergy, a peanut-sensitized human without clinical relevant allergy, a human suffering from peanut allergy that underwent immunotherapy, a human that has outgrown peanut allergy and a human of unknown clinical history for peanut allergy. 
     
     
         10 . Antibody or binding fragment thereof according to any one of the preceding claims, wherein the antibody is capable of reducing, inhibiting or neutralizing allergen-mediated biological activity. 
     
     
         11 . Antibody or binding fragment thereof according to any one of the preceding claims, wherein the antibody is capable of reducing or inhibiting the binding of an IgE antibody to the food allergen. 
     
     
         12 . Antibody or binding fragment thereof according to any of the preceding claims, wherein the antibody is selected from the group consisting of the following antibodies:
 a) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 1 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 2 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 3 or sequences at least 65% identical thereto; wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 4 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 5 or sequences at least 65% identical thereto, and a CDR3 set forth in SEQ ID No: 6 or sequences at least 65% identical thereto;   b) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 15 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 16 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 17 or sequences at least 65% identical thereto; wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 18 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 19 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 20 or sequences at least 65% identical thereto;   c) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 29 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 30 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 31 or sequences at least 65% identical thereto; wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 32 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 33 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 34 or sequences at least 65% identical thereto;   d) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 43 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 44 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 45 or sequences at least 65% identical thereto; and/or wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 46 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 47 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 48 or sequences at least 65% identical thereto;   e) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 57 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 58 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 59 or sequences at least 65% identical thereto; and/or wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 60 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 61 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 62 or sequences at least 65% identical thereto; and   f) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 71 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 72 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 73 or sequences at least 65% identical thereto; and/or wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 74 or sequences at least 65% identical thereto, a CDR2 set forth in SEQ ID No: 75 or sequences at least 65% identical thereto, a CDR3 set forth in SEQ ID No: 76 or sequences at least 65% identical thereto.   
     
     
         13 . Antibody or binding fragment thereof according to  claim 12 , wherein the antibody is selected from the group consisting of the following antibodies:
 a) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 1, a CDR2 set forth in SEQ ID No: 2, and a CDR3 set forth in SEQ ID No: 3, wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 4, a CDR2 set forth in SEQ ID No: 5, and a CDR3 set forth in SEQ ID No: 6;   b) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 15, a CDR2 set forth in SEQ ID No: 16, and a CDR3 set forth in SEQ ID No: 17 or sequences at least 65% identical thereto; wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 18, a CDR2 set forth in SEQ ID No: 19, and a CDR3 set forth in SEQ ID No: 20;   c) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 29, a CDR2 set forth in SEQ ID No: 30, and a CDR3 set forth in SEQ ID No: 31; wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 32, a CDR2 set forth in SEQ ID No: 33, a CDR3 set forth in SEQ ID No: 34;   d) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 43, a CDR2 set forth in SEQ ID No: 44, and a CDR3 set forth in SEQ ID No: 45; and/or wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 46, a CDR2 set forth in SEQ ID No: 47, and a CDR3 set forth in SEQ ID No: 48;   e) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 57, a CDR2 set forth in SEQ ID No: 58, and a CDR3 set forth in SEQ ID No: 59; and/or wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 60, a CDR2 set forth in SEQ ID No: 61, and a CDR3 set forth in SEQ ID No: 62; and   f) antibody or binding fragment thereof comprising a light chain variable region and/or a heavy chain variable region, wherein the light chain variable region comprises a CDR1 set forth in SEQ ID No: 71, a CDR2 set forth in SEQ ID No: 72, and a CDR3 set forth in SEQ ID No: 73 or sequences at least 65% identical thereto; and/or wherein the heavy chain variable region comprises a CDR1 set forth in SEQ ID No: 74, a CDR2 set forth in SEQ ID No: 75, and a CDR3 set forth in SEQ ID No: 76.   
     
     
         14 . Antibody composition comprising at least two antibodies, wherein at least one of the antibodies is selected from the antibodies as defined in  claim 12 . 
     
     
         15 . Pharmaceutical composition comprising at least one of the compounds selected from the group consisting of antibody or binding fragment of any one of  claims 1  to  13 , or the antibody composition according to  claim 14 . 
     
     
         16 . Pharmaceutical composition according to  claim 15 , further comprising a pharmaceutically acceptable carrier. 
     
     
         17 . Kit comprising (i) the pharmaceutical composition according to  claim 15 , (ii) at least one additional agent useful for treating peanut allergy selected from the group β-adrenergic agonist, antihistamine, corticosteroid, anti-IgE antibody, anti-IgE antibody binding fragment, peptide vaccine and further antibodies capable of binding to a peanut allergen. 
     
     
         18 . Kit according to  claim 17 , wherein the at least one additional agent is epinephrine. 
     
     
         19 . Antibody or binding fragment thereof according to any one of  claims 1  to  13 , antibody composition according to  claims 14  or pharmaceutical composition according to  claims 15  and  16 , kit according to  claims 17  and  18  for use in the treatment of peanut allergy. 
     
     
         20 . Method of evaluating the capability of a candidate antibody or binding fragment thereof to inhibit allergen binding and/or allergen-induced activity in a human, comprising the following steps:
 (i) incubating the candidate antibody or binding fragment thereof together with basophils derived from the human and a food allergen;   (ii) measuring the level of activated basophils;   wherein decreased levels of activated basophils compared to a control indicate that the antibody is capable of inhibiting allergen binding and/or allergen induced activity in a human.   
     
     
         21 . The method of  claim 20 , further comprising the step of
 (iii) determining whether the administration of the candidate antibody is a suitable treatment for a patient suffering from food allergy based on the result of step (ii).   
     
     
         22 . Method according to  claims 20  and  21 , wherein the candidate antibody is an antibody as defined in  claims 1  to  14 . 
     
     
         23 . Method according to  claims 20  to  22 , wherein in step (i) the composition comprising IgEs from the human comprises basophils. 
     
     
         24 . Method according to  claims 20  to  23 , wherein the basophils are derived from an allergic patient. 
     
     
         25 . Method according to  claims 20  to  24 , wherein the basophils are donor-derived IgE-stripped basophils. 
     
     
         26 . Method according to  claims 20  to  25 , wherein the basophils are donor-derived IgE-stripped basophils incubated with plasma from an allergy patient. 
     
     
         27 . Method according to  claims 20  to  26 , wherein the secretion of a mediator from basophils is measured. 
     
     
         28 . Method according to  claim 27 , wherein the mediator is leukotriene. 
     
     
         29 . Method according to  claim 28 , wherein the mediator is sulfidoleukotrine. 
     
     
         30 . Method according to any one of  claims 20  to  29 , wherein the composition comprising IgEs derived from the human is plasma, sera, blood, saliva, peripheral blood mononuclear cell (PBMC), leukocytes, basophils or IgEs stripped from basophils. 
     
     
         31 . Method according to  claims 30 , wherein the composition comprising IgEs derived from the human are leukocytes. 
     
     
         32 . Method according to any one of  claims 20  to  31 , wherein the human is suffering from food allergy. 
     
     
         33 . Method according to any one of  claims 20  to  32 , wherein the human is suffering from peanut allergy. 
     
     
         34 . Method according to any one of  claims 20  to  33 , wherein the food allergen is a peanut allergen. 
     
     
         35 . Method according to  claim 34 , wherein the peanut allergen is selected from the group consisting of Ara h 1, Ara h 2, Ara h 3, Ara h 4, Ara h 5, Ara h 6/7, Ara h 8, Ara h 9 and Ara h 10/11. 
     
     
         36 . Method according to  claim 35 , wherein the peanut allergen is selected from the group consisting of Ara h 1, Ara h 2, Ara h 3 and Ara h 6, or a combination thereof 
     
     
         37 . Method according to any one of  claims 20  to  36 , wherein the peanut allergen is recombinantly expressed, synthetically generated or is of peanut origin. 
     
     
         38 . Method of  claims 20  to  37 , wherein decreased levels of activated basophils compared to the control indicated that the antibody is suitable for the treatment of a patient suffering from food allergy. 
     
     
         39 . Method according to any one of  claims 20  and  21 , wherein the control comprises basophils derived from the human and a food allergen but does not contain the candidate antibody. 
     
     
         40 . A method of evaluating the capability of a candidate antibody or binding fragment thereof to inhibit allergen binding, comprising the following steps:
 (i) incubating the candidate antibody or binding fragment thereof together with a composition comprising IgEs derived from the human and a food allergen;   (ii) measuring the level of IgE bound to antigen;   wherein decreased levels of IgE bound to antigen compared to a control indicate that the antibody is capable of inhibiting allergen binding.   
     
     
         41 . Method according to  claim 40 , wherein decreased levels of IgE bound to antigen compared to the control indicated that the antibody is suitable for the treatment of a patient suffering from food allergy. 
     
     
         42 . Method according to any one of  claims 40  and  41 , wherein the control comprises IgEs derived from the human and a food allergen but does not contain the candidate antibody. 
     
     
         43 . Method according to any one of  claims 40  to  42 , wherein the candidate antibody is an antibody as defined in  claims 1  to  13 . 
     
     
         44 . A method of detecting or quantifying whether an allergen is present in a sample comprising the following steps:
 i) incubation of the sample with an antibody according to any one of  claims 1  to  13  or with an antibody composition according to  claim 14 ,   ii) detecting the antibody which is bound to allergen in the sample.