Human antibodies to Fel d1 and methods of use thereof
The present invention provides antibodies that bind to the cat allergen, Fel d1, compositions comprising the antibodies, nucleic acids encoding the antibodies and methods of use of the antibodies. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to Fel d1. The antibodies of the invention are useful for binding to the Fel d1 allergen in vivo, thus preventing binding of the Fel d1 allergen to pre-formed IgE on the surface of mast cells or basophils. In doing so, the antibodies act to prevent the release of histamine and other inflammatory mediators from mast cells and/or basophils, thus ameliorating the untoward response to the cat allergen in sensitized individuals. The antibodies of the invention may also be useful for diagnostic purposes to determine if a patient is allergic to the Fel d1 cat allergen.
1. An isolated human monoclonal antibody or antigen-binding fragment thereof that binds specifically to Fel d1, wherein the antibody or antigen-binding fragment thereof comprises the three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within the heavy chain variable region (HCVR) sequence of SEQ ID NO: 18; and the three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within the light chain variable region (LCVR) sequence of SEQ ID NO: 26.
2. The isolated human monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the human antibody or antigen-binding fragment thereof binds specifically to Fel d1 with a K D equal to or less than 10 −6 M, as measured by surface plasmon resonance.
3. An isolated human monoclonal antibody or antigen-binding fragment thereof that binds specifically to Fel d1, wherein the antibody comprises: (a) the HCVR of SEQ ID NO: 18; and (b) the LCVR of SEQ ID NO: 26.
4. The isolated human monoclonal antibody or antigen-binding fragment thereof of claim 3 , wherein the HCVR and LCVR comprise the three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) and the three light chain CDRs (LCDR1, LCDR2 and LCDR3) consisting of:
(a) the HCDR1 domain of SEQ ID NO: 20;
(b) the HCDR2 domain of SEQ ID NO: 22;
(c) the HCDR3 domain of SEQ ID NO: 24;
(d) the LCDR1 domain of SEQ ID NO: 28;
(e) the LCDR2 domain of SEQ ID NO: 30; and
(f) the LCDR3 domain of SEQ ID NO: 32.
5. The isolated human monoclonal antibody or an antigen binding fragment thereof of claim 1 , wherein the antibody or fragment thereof interacts with at least one amino acid sequence selected from the group consisting of amino acid residues ranging from position 85 to position 103 of SEQ ID NO: 396; amino acid residues ranging from position 85 to position 104 of SEQ ID NO: 396; and amino acid residues ranging from position 113 to position 127 of SEQ ID NO: 396.
6. The isolated human monoclonal antibody or an antigen binding fragment thereof of claim 1 , wherein the antibody or fragment thereof interacts with at least one amino acid sequence selected from the group consisting of SEQ ID NO: 402, 403, and 404.
7. A pharmaceutical composition comprising a therapeutically effective amount of the isolated human monoclonal antibody or an antigen-binding fragment thereof of claim 1 that binds specifically to Fel d1, together with one or more pharmaceutically acceptable excipients.
8. A pharmaceutical composition comprising a therapeutically effective amount of a first isolated human monoclonal antibody, or an antigen-binding fragment thereof that binds specifically to Fel d1, of claim 1 ; and a second isolated human monoclonal antibody, or an antigen-binding fragment thereof that binds specifically to Fel d1, together with one or more pharmaceutically acceptable excipients.
9. The pharmaceutical composition of claim 8 , wherein:
a) the isolated first human monoclonal antibody or antigen-binding fragment thereof that binds specifically to Fel d1, comprises the HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 18/26; and
b) the isolated second human monoclonal antibody or antigen-binding fragment thereof that binds specifically to Fel d1, comprises the HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 306/314.
10. A pharmaceutical composition comprising the human antibody or an antigen-binding fragment thereof having the HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 18/26, further comprising three or more isolated human monoclonal antibodies that bind specifically to Fel d1, or antigen-binding fragments thereof, comprising the HCVR/LCVR amino acid sequence pairs selected from the group consisting of SEQ ID NOs: 66/74, 130/138, 306/314 and 162/170.
11. The pharmaceutical composition of claim 9 , wherein the isolated second human monoclonal antibody, or an antigen binding fragment thereof, interacts with amino acid residues ranging from position 15 to position 24 of SEQ ID NO: 396.
12. The pharmaceutical composition of claim 9 , wherein the isolated second human monoclonal antibody, or an antigen binding fragment thereof, interacts with an amino acid sequence of SEQ ID NO: 412.