Nucleic acids encoding antibodies against IL-1 beta
The present invention relates to anti-IL-1 beta antibodies and in particular to monovalent high potency IL-1 beta-binding antibody fragments being highly stable. Such antibodies can be used in the treatment of inflammatory and other diseases as well as in diagnostics. Also provided are related nucleic acids, vectors, cells, and compositions.
1. An isolated nucleic acid molecule encoding a humanized antibody against IL-1 beta, wherein the antibody comprises a light chain variable region (VL) sequence having at least 90% identity to SEQ ID NO: 8; and a heavy chain variable region (VH) sequence having at least 90% identity to SEQ ID NO: 12, and wherein said VH comprises heavy chain complementary determining region (CDR) CDR-H1 as set forth in SEQ ID NO: 4, CDR-H2 as set forth SEQ ID NO: 21, and CDR-H3 as set forth in SEQ ID NO: 6 and said VL comprises CDR-L1 as set forth in SEQ ID NO: 1, CDR-L2 as set forth in SEQ ID NO: 2, and CDR-L3 as set forth in SEQ ID NO: 3.
2. The isolated nucleic acid molecule of claim 1 , wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 12.
3. The isolated nucleic acid molecule of claim 1 , wherein the VL comprises the amino acid sequence as set forth in SEQ ID NO: 7, 8 or 24.
4. The isolated nucleic acid molecule of claim 1 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab, a Fab′, a F(ab)′2, and an scFv.
5. The isolated nucleic acid molecule of claim 1 , wherein the antibody is an scFv fragment.
6. The isolated nucleic acid molecule of claim 1 , wherein the antibody is a single chain antibody and comprises the amino acid sequence as set forth in SEQ ID NO: 19.
7. The isolated nucleic acid molecule of claim 1 , wherein
said VL further comprises one or more amino acids according to AHo numbering selected from the group consisting of an alanine residue (A) at position 24, a phenylalanine residue (F) at position 25, an isoleucine residue (I) at position 44, a serine residue (S) at position 56, lysine residue (K) at position 82, an arginine residue (R) at position 86, a phenylalanine residue (F) at position 105, and combinations thereof, and
said VH further comprises one or more amino acids according to AHo numbering selected from the group consisting of: an aspartic acid residue (D) at position 1, a glutamine residue (Q) at position 3, a threonine residue (T) at position 20, a glutamic acid residue (E) at position 99, a phenylalanine residue (F) at position 105, a glutamic residue (E) at position 146, an isoleucine residue (I) at position 147, a lysine residue (K) at position 148, an arginine residue (R) at position 149, and combinations thereof.
8. The isolated nucleic acid molecule of claim 7 , wherein said VH chain further comprises at least one of the following residues:
(i) Serine (S) at heavy chain amino acid position 12 (according to AHo numbering);
(i) Serine (S) or Threonine (T) at heavy chain amino acid position 103 (according to AHo numbering);
(iii) Serine (S) or Threonine (T) at heavy chain amino acid position 144 (according to AHo numbering), or
(iv) combinations thereof.
9. The isolated nucleic acid molecule of claim 7 , wherein said VL chain sequence comprises the sequence as set forth in SEQ ID NO: 8 and VH chain sequence comprises the sequence as set forth in SEQ ID NO: 12.
10. The isolated nucleic acid molecule of claim 9 , wherein the antibody further comprises a linker sequence set forth in SEQ ID NO: 14.
11. The isolated nucleic acid molecule of claim 7 , wherein the antibody is a full-length immunoglobulin.
12. The isolated nucleic acid molecule of claim 7 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab, a Fab′, a F(ab)′2, and an scFv.
13. The isolated nucleic acid molecule of claim 7 , wherein the antibody is an scFv fragment.
14. A vector comprising a nucleic acid molecule encoding a humanized antibody against IL-1 beta, wherein the antibody comprises a light chain variable region (VL) sequence having at least 90% identity to SEQ ID NO: 8 and light chain complementary determining regions CDR-L1, CDR-L2 and CDR-L3 sequences as set forth in SEQ ID NO: 1, 2; and 3, respectively; and a heavy chain variable region (VH) sequence having at least 90% identity to SEQ ID NO: 12 and heavy chain complementary determining regions CDR-H1, CDR-H2, and CDR-H3, as set forth in SEQ ID NO: 4, 21, and 6, respectively.
15. The vector of claim 14 , wherein the VH comprises the amino acid sequence as set forth in SEQ ID NO: 12.
16. The vector of claim 14 , wherein the VL comprises the amino acid sequence as set forth in SEQ ID NO: 7, 8, or 24.