Amino acid sequences which enhance peptide conjugate solubility
View Patent ↗The present invention provides peptide conjugates having improved solubility as well as increased secretion during cell based production, as well as methods of utilizing such peptides. The peptide conjugates include a short peptide domain defined by the amino acid sequence AGIH (SEQ ID NO: 8) and may include a biologically active molecule useful in intracellular and intranuclear transport of the biologically active molecule to treat various disorders and diseases.
1. A peptide-antibody conjugate comprising,
a peptide of about 4 to 50 amino acid residues comprising the amino acid sequence AGIH (SEQ ID NO: 8); and
mAb 3E10, or functional fragment thereof, having a binding specificity as produced by a hybridoma having ATCC accession number PTA 2439, wherein the peptide is conjugated to the N-terminus of the antibody or functional fragment thereof.
2. The conjugate of claim 1 , wherein the functional fragment is selected from the group consisting of Fab, F(ab′) 2 , Fv, and single chain Fv (scFv) fragments.
3. The conjugate of claim 1 , wherein the functional fragment is an scFv fragment of mAb 3E10.
4. The conjugate of claim 1 , wherein the functional fragment comprises the variable region of the heavy chain (VH) and variable region of the kappa light chain (Vκ) of mAb 3E10.
5. The conjugate of claim 4 , wherein the antigen-binding portion of mAb 3E10 further comprises the signal peptide of the Vκ.
6. The conjugate of claim 1 , wherein the peptide is joined to the antibody by a linker molecule.
7. The conjugate of claim 1 , wherein the conjugate is a genetic fusion.
8. The conjugate of claim 1 , wherein the conjugate further includes an additional biologically active molecule, wherein the biologically active molecule is a nucleic acid sequence or a protein.
9. The conjugate of claim 8 , wherein the additional biologically active molecule is selected from the group consisting of an antibody, an antibody fragment, an enzyme, a transcription factor, an siRNA molecule, a DNA molecule, an RNA molecule, an siRNA-protein conjugate, an siRNA-peptide conjugate, and siRNA-antibody conjugate.
10. The conjugate of claim 9 , wherein the additional biologically active molecule comprises an antibody fragment selected from the group consisting of a Fab fragment, a F(ab)2 fragment, an FV fragment, a single chain FV (scFV) fragment, a dsFV fragment, and a dimeric scFV.
11. The conjugate of claim 9 , wherein the additional biologically active molecule comprises an antibody selected from the group consisting of a chimeric antibody, a humanized antibody, a CDR-grafted antibody, a bifunctional antibody, a single chain antibody, and an antibody polypeptide dimer.
12. The conjugate of claim 8 , wherein the additional biologically active molecule is HSP70.
13. The conjugate of claim 8 , wherein the peptide-antibody conjugate is joined to the additional biologically active molecule by a linker molecule.
14. The conjugate of claim 8 , wherein the biologically active molecule is a protein and the conjugate is a genetic fusion.