Nucleic acids encoding neutralizing anti-CCL20 antibodies
The present invention relates to novel humanized, chimeric and murine antibodies that have binding specificity for the human CC chemokine ligand 20 (CCL20). The present invention further relates to heavy chains and light chains of said antibodies. The invention also relates to isolated nucleic acids, recombinant vectors and host cells that comprise a sequence which encodes a heavy chain and/or a light chain of said antibodies, and to a method of preparing said antibodies. The anti-CCL20 antibodies of the invention can be used in therapeutic applications to treat, for example, inflammatory and autoimmune disorders and cancer.
1. An isolated nucleic acid molecule encoding
a) the heavy chain of a monoclonal anti-human CCL20 antibody or an antigen-binding portion thereof, wherein the complementarity determining region (CDR) 1, CDR2, and CDR3 of said heavy chain comprise the amino acid sequences shown in
i) SEQ ID NOS: 60, 64, and 67, respectively, or
ii) SEQ ID NOS: 77, 79, and 67, respectively; and
b) the light chain of the monoclonal anti-human CCL20 antibody or antigen-binding portion, wherein the CDR1, CDR2, and CDR3 of said light chain comprise the amino acid sequences shown in
i) SEQ ID NOS: 70, 73, and 75, respectively, or
ii) SEQ ID NOS: 71, 73, and 75, respectively.
2. The isolated nucleic acid molecule of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 1, 9, or 108; or said amino acid sequence without a signal sequence, if present; or said amino acid sequence without a C-terminal lysine, if present.
3. The isolated nucleic acid molecule of claim 2 , wherein the light chain comprises the amino acid sequence of SEQ ID NO: 7, 8, 15, 16, 110, or 112.
4. The isolated nucleic acid molecule of claim 1 , wherein the light chain comprises the amino acid sequence of SEQ ID NO: 7, 8, 15, 16, 110, or 112.
5. An isolated nucleic acid molecule encoding the amino acid sequence of SEQ ID NO: 1, 9, or 108, or said amino acid sequence without the C-terminal lysine, if present.
6. An isolated nucleic acid molecule encoding the amino acid sequence of SEQ ID NO: 7, 8, 15, 16, 110, or 112.
7. An isolated nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 17, 25, or 109, or said nucleotide sequence without the sequence encoding the heavy chain C-terminal lysine, if present.
8. An isolated nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 23, 24, 31, 32, 111, or 113.
9. An isolated vector comprising the isolated nucleic acid molecule of any one of claims 1 - 8 .
10. An isolated host cell comprising the isolated vector of claim 9 .
11. An isolated host cell comprising
a) a first nucleotide sequence encoding the heavy chain of a monoclonal anti-human CCL20 antibody or an antigen-binding portion thereof, wherein the complementarity determining region (CDR) 1, CDR2, and CDR3 of said heavy chain comprise the amino acid sequences shown in
i) SEQ ID NOS: 60, 64, and 67, respectively, or
ii) SEQ ID NOS: 77, 79, and 67; and
b) a second nucleotide sequence encoding the light chain of the monoclonal anti-human CCL20 antibody or antigen-binding portion, wherein the CDR1, CDR2, and CDR3 of said light chain comprise the amino acid sequences shown in
i) SEQ ID NOS: 70, 73, and 75, respectively, or
ii) SEQ ID NOS: 71, 73, and 75, respectively.
12. The host cell of claim 11 , wherein the first and second nucleotide sequences are located on separate nucleic acid molecules.
13. A method of making an anti-human CCL20 antibody or an antigen-binding portion thereof, comprising maintaining the isolated host cell of claim 11 under conditions appropriate for expression of the antibody or portion, and recovering the antibody or portion produced.