Human monoclonal antibodies against orexin receptor type 1
The present disclosure relates to human monoclonal antibodies against orexin receptor type 1 (OX1R, hyprocretin 1) and uses thereof for the treatment of cancer. The antibodies are characterized by their CDRs: NYYMN, YISGSSRNIYYADFVKG, SNYDGMDV (Heavy chain) and AGTSSDVGGSNYVS, PGKAP, SSYTYYSTRV (Light Chain)) or the CDRS having at least 50% or 70% identity with the above listed sequences.
1. An isolated human monoclonal antibody against orexin receptor type 1 (OXIR) comprising a heavy chain comprising i) the H-CDR1 of C2, ii) the H-CDR2 of C2 and iii) the H-CDR3 of C2 and a light chain comprising i) the L-CDR1 of C2, ii) the L-CDR2 of C2 and iii) the L-CDR3 of C2 wherein
the H-CDR1 of C2 is defined by the sequence ranging from the amino acid residue at position 31 to the amino acid residue at position 35 in SEQ ID NO:1,
the H-CDR2 of C2 is defined by the sequence ranging from the amino acid residue at position 50 to the amino acid residue at position 66 in SEQ ID NO:1,
the H-CDR3 of C2 is defined by the sequence ranging from the amino acid residue at position 99 to the amino acid residue at position 109 in SEQ ID NO:1,
the L-CDR1 of C2 is defined by the sequence ranging from the amino acid residue at position 23 to the amino acid residue at position 36 in SEQ ID NO:2,
the L-CDR2 of C2 is defined by the sequence ranging from the amino acid residue at position 52 to the amino acid residue at position 58 in SEQ ID NO:2, and,
the L-CDR3 of C2 is defined by the sequence ranging from the amino acid residue at position 91 to the amino acid residue at position 100 in SEQ ID NO:2.
2. The isolated human monoclonal antibody of claim 1 wherein the variable region of the heavy chain has at least 70% identity with SEQ ID NO:1, wherein any variation from SEQ ID NO:1 does not occur within H-CDR1, H-CDR-2, or H-CDR3.
3. The isolated human monoclonal antibody of claim 1 wherein the variable region of the light chain has at least 70% identity with SEQ ID NO:2, wherein any variation from SEQ ID NO:2 does not occur within L-CDR1, L-CDR-2, or L-CDR3.
4. The isolated human monoclonal antibody of claim 1 wherein the variable region of the heavy chain has at least 70% identity with SEQ ID NO:1 and wherein the variable region of the light chain has at least 70% identity with SEQ ID NO:2, wherein any variation from SEQ ID NO:1 does not occur within H-CDR1, H-CDR-2, or H-CDR3 and wherein any variation from SEQ ID NO:2 does not occur within L-CDR1, L-CDR-2, or L-CDR3.
5. The isolated human monoclonal antibody of claim 1 wherein the variable region of the heavy chain is identical to SEQ ID NO:1.
6. The isolated human monoclonal antibody of claim 1 wherein the variable region of the light chain is identical to SEQ ID NO:2.
7. The isolated human monoclonal antibody of claim 1 wherein the variable region of the heavy chain is identical to SEQ ID NO:1 and wherein the variable region of the light chain is identical to SEQ ID NO:2.
8. An isolated fragment of the isolated human monoclonal antibody of claim 1 which is selected from the group consisting of Fv, Fab, F(ab')2, Fab', dsFv, scFv, sc(Fv)2 and diabodies.
9. An isolated nucleic acid molecule which encodes the heavy chain and the light chain of the human monoclonal antibody of claim 1 .
10. An isolated vector comprising the nucleic acid molecule of claim 9 .
11. An isolated host cell comprising the nucleic acid molecule of claim 9 .
12. A method of treating cancer in a subject in need thereof wherein cells of the cancer express OX1R comprising administering to the subject a therapeutically effective amount of the human monoclonal antibody of claim 1 .
13. A pharmaceutical composition comprising the isolated human monoclonal antibody of claim 1 and a pharmaceutically acceptable carrier.
14. An isolated host cell comprising the vector of claim 10 .