Diagnostic tests and methods for assessing safety, efficacy or outcome of allergen-specific immunotherapy (sit)

Abstract

The present invention provides in vitro and in vivo diagnostic tests and methods for determining the safety, efficacy, or outcome of allergen-specific immunotherapy (SIT) in a patient. The present invention also provides for the measurement of allergen specific IgG and IgE in a patient tissue sample, or extract thereof, or in a biological fluid or blood sample, and determining whether the allergen-specific immunoglobulins contained in the patient sample(s), upon injection into an allergen-sensitized animal, will protect the animal following challenge with the allergen. The invention also provides methods for determining whether a patient suffering from an allergy is responsive to therapy with one or more therapeutic antibodies specific for the allergen.

1 - 65 . (canceled) 
     
     
         66 . A method of determining if a patient suffering from an allergy to an allergen is responsive to therapy with one or more antibodies or antigen binding fragments thereof specific for the allergen, the method comprising:
 (a) collecting a sample of tissue or an extract thereof, or a biological fluid, or a blood sample from the patient;   (b) extracting an allergen-specific IgE from one or more of the patient samples of (a);   (c) mixing the IgE from the patient sample with the allergen and with one or more antibodies or antigen binding fragments thereof specific for the allergen; and   (d) determining if the addition of the antibodies or antigen binding fragments thereof specific for the allergen blocks the binding of the allergen specific IgE from step b) to the allergen,   wherein the ability of the one or more antibodies or antigen binding fragments thereof specific for the allergen to block the binding of allergen specific IgE from step b) to the allergen is indicative that the patient suffering from an allergy is responsive to therapy with the one or more antibodies specific for the allergy.   
     
     
         67 . (canceled) 
     
     
         68 . The method of  claim 66 , wherein the allergen is Fel d1. 
     
     
         69 . The method of  claim 66 , wherein the one or more antibodies specific for the allergen are human monoclonal antibodies that bind specifically to Fel d1, and wherein the one or more antibodies comprise the heavy chain complementary determining regions (HCDRs) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2 or 18 and the light chain complementarity determining regions (LCDRs) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 10 or 26. 
     
     
         70 . The method of  claim 66 , wherein the one or more human monoclonal antibodies or antigen binding fragments that bind specifically to Fel d1 comprise three HCDRs (HCDR1, HCDR2 and HCDR3) and three LCDRs (LCDR1, LCDR2 and LDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 2 or 20; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 6 or 22; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 8 or 24; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 12 or 28; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or 30; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16 or 32. 
     
     
         71 . The method of  claim 66 , wherein the one or more human monoclonal antibodies that bind specifically to Fel d1 comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 2 or 18 and a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 26. 
     
     
         72 . The method of  claim 66 , wherein the one or more human monoclonal antibodies that bind specifically to Fel d1 comprise the HCVR/LCVR amino acid sequence pairs of SEQ ID NOs: 2/10 or SEQ ID NOs:18/26.