Biopharmaceutical compositions comprising nucleic acids encoding IL-5 binding proteins
The present disclosure relates to compositions, for treating interleukin 5 (IL-5) mediated diseases, and related methods.
1. A composition comprising a nucleic acid encoding an IL-5 binding protein or a fragment thereof comprising a heavy chain and a light chain, wherein a) the heavy chain comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and b) the light chain comprises a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10; and wherein the IL-5 binding protein comprises a human IgG1 heavy chain Fc domain comprising:
a) a tyrosine residue at position 252 (265 according to Kabat numbering), a threonine residue at position 254 (267 according to Kabat numbering) and a glutamic acid residue at position 256 (269 according to Kabat numbering);
b) a leucine residue at position 108 according to Kabat numbering in the heavy chain variable region; or
c) a combination thereof.
2. The composition of claim 1 , wherein the IL-5 binding protein comprises a human IgG1 heavy chain Fc domain having a tyrosine residue at position 252 (265 according to Kabat numbering), a threonine residue at position 254 (267 according to Kabat numbering) and a glutamic acid residue at position 256 (269 according to Kabat numbering).
3. The composition of claim 2 , wherein the IL-5 binding protein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1.
4. The composition of claim 3 , wherein the nucleic acid comprises the sequence of SEQ ID NO:17.
5. The composition of claim 1 , wherein the IL-5 binding protein comprises a leucine residue at position 108 according to Kabat numbering in the heavy chain variable region.
6. The composition of claim 5 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 3.
7. The composition of claim 6 , wherein the nucleic acid comprises the sequence of SEQ ID NO: 15.
8. The composition of claim 1 , wherein the IL-5 binding protein comprises a light chain variable region comprising at least 85% sequence identity with SEQ ID NO: 4.
9. The composition of claim 8 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 4.
10. The composition of claim 9 , wherein the nucleic acid comprises the sequence of SEQ ID NO: 16.
11. The composition of claim 1 , wherein the IL-5 binding protein comprises a light chain comprising at least 85% sequence identity with SEQ ID NO: 2.
12. The composition of claim 11 , wherein the light chain comprises the amino acid sequence of SEQ ID NO: 2.
13. The composition of claim 12 , wherein the nucleic acid comprises the sequence of SEQ ID NO: 18.
14. The composition of claim 1 , wherein the nucleic acid comprises the sequences of SEQ ID NO: 17 and SEQ ID NO: 18.
15. The composition of claim 1 , wherein the nucleic acid comprises the sequences of SEQ ID NO: 15 and SEQ ID NO: 16.
16. The composition of claim 1 , wherein the nucleic acid comprises the sequences of SEQ ID NO: 13 and SEQ ID NO: 14.