Humanized anti-IL-1β antibodies
The present invention encompasses isolated antibodies, or antigen-binding portions thereof, that specifically bind mature human IL-1 Beta. These antibodies, or antigen-binding portions thereof, generally exhibit high binding affinities (low k oo ff values), reduced deamidation compared to the native antibody, and can be used to treat various diseases such as rheumatoid arthritis, osteoarthritis, or neuroinflammation.
1. An antibody, or an antigen-binding portion thereof, that specifically binds human IL-1β, comprising a light chain variable region and a heavy chain variable region selected from the group consisting of:
(a) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:60 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:55;
(b) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:61 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:56;
(c) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:62 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:57;
(d) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:63 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:58; and,
(e) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:64 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:59.
2. An antibody, or an antigen-binding portion thereof, that specifically binds human IL-1β, comprising a light chain and a heavy chain wherein the amino acid sequences of the light and heavy chains are selected from the group consisting of:
(a) a light chain of SEQ ID NO:46 and a heavy chain of SEQ ID NO: 45;
(b) a light chain of SEQ ID NO:48 and a heavy chain of SEQ ID NO:47;
(c) a light chain of SEQ ID NO:48 and a heavy chain of SEQ ID NO:68;
(d) a light chain of SEQ ID NO:50 and a heavy chain of SEQ ID NO:49;
(e) a light chain of SEQ ID NO:52 and a heavy chain of SEQ ID NO:51 and,
(f) a light chain of SEQ ID NO:54 and a heavy chain of SEQ ID NO:53.
3. An antibody, or an antigen-binding portion thereof, that specifically binds human IL-1β, comprising a light chain and a heavy chain, wherein the amino acid sequence of the light chain is given by SEQ ID NO:48 and the amino acid sequence of the heavy chain is given by SEQ ID NO:68.
4. A pharmaceutical composition comprising the antibody or antigen binding portion thereof of claim 1 .
5. A method of treating rheumatoid arthritis or osteoarthritis, comprising administering to a patient in need thereof an effective amount of the antibody or antigen binding portion thereof, of claim 1 .
6. A pharmaceutical composition comprising the antibody or antigen binding portion thereof of claim 2 .
7. A method of treating rheumatoid arthritis or osteoarthritis, comprising administering to a patient in need thereof an effective amount of the antibody or antigen binding portion thereof, of claim 2 .