Combination therapy of antibodies against human csf-1r and tlr9 agonist
US-2016220669-A1 · Aug 4, 2016 · US
US9499625B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9499625-B2 |
| Application number | US-201514640183-A |
| Country | US |
| Kind code | B2 |
| Filing date | Mar 6, 2015 |
| Priority date | Dec 10, 2009 |
| Publication date | Nov 22, 2016 |
| Grant date | Nov 22, 2016 |
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The present invention relates to antibodies against human CSF-1R (anti-CSF-1R antibody), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.
Opening claim text (preview).
The invention claimed is: 1. An isolated nucleic acid encoding an antibody binding to human CSF-1R, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain, and wherein: a) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:7 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:8; b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:15 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:16; c) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:75 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:76; d) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:83 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO84; or a humanized version thereof. 2. An isolated nucleic acid encoding an antibody binding to human CSF-1R, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain, and wherein: a) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:23 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:24, b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:31 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:32, c) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:39 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:40, d) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:47 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:48, or e) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:55 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:56. 3. An isolated nucleic acid encoding an antibody binding to human CSF-1R, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain, and wherein: a) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 1, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 2, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:3, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 region comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:6; b) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 9, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 10, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 11, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:12, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 13, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 14; c) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 17, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 18, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:19, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 20, a CDR2 region comprising the amino acid sequence of SEQ ID NO:21, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:22; d) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 25, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 26, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 27, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:28, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 29, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 30; e) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 33, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 34, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 35, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:36, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 37, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 38; f) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:41, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 42, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:43, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 44, a CDR2 region comprising the amino acid sequence of SEQ ID NO:45, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:46; g) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 49, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 50, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 51, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:52, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 53, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 54; h) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:69, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 70, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:71, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 72, a CDR2 region comprising the amino acid sequence of SEQ ID NO:73, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:74; or i) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 77, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 78, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 79, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:80, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 81, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 82. 4. The isolated nucleic acid of claim 3 , wherein the antibody is of human IgGlsubclass or is of human IgG4 subclass. 5. The isolated nucleic acid of claim 3 , wherein the antibody is a chimeric, single chain, multispecific, or humanized antibody. 6. The isolated nucleic acid of claim 3 , wherein the antibody is an antigen binding fragment. 7. An expression vector comprising the nucleic acid of claim 3 for the expression of the antibody in a prokaryotic or eukaryotic host cell. 8. A prokaryotic or eukaryotic host cell comprising the vector of claim 7 . 9. A method for the production of a recombinant antibody, the method comprising expressing the nucleic acid of claim 3 in a prokaryotic or eukaryotic host cell and recovering the antibody from said cell or cell culture supernatant. 10. The isolated nucleic acid of claim 1 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:7 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:8. 11. The isolated nucleic acid of claim 1 , wherein the heavy chain variable domain co
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