DOCKING PEPTIDES AND RELATED ANTIBODY-BASED DRUG CONJUGATES
Provided herein are novel docking peptides and antibody-based drug conjugates that include such docking peptides. In embodiments, the subject docking peptide allows for the controlled attachment of one or more drug moieties and a tumor targeting moiety that allows for the targeting of the drug moiety to the tumor microenvironment. In some embodiments, the antibody-based drug conjugates provided herein advantageously allows for enhanced targeted delivery of a drug payload having a controlled drug-to-antibody ratio (DAR) to a target site.
1 .- 48 . (canceled)
49 . A composition comprising:
a) a targeting moiety; and
b) a drug conjugate moiety comprising:
i) a docking peptide comprising the amino acid sequence of SEQ ID NO:5; and
ii) one or more drug moieties,
wherein each of the one or more drug moieties is attached to a lysine residue of the docking peptide, and
wherein the targeting moiety is attached to the drug conjugate moiety by a linker.
50 . The composition of claim 49 , wherein the targeting moiety is a tumor targeting moiety.
51 . The composition of claim 49 , wherein the tumor targeting moiety binds to one or more of the following tumor antigens: CD33, CD30, HER2, HER3, CD22, CD79b, NaPi 2b, glycoprotein NMB, CD19, CD138, PSMA, CEA, guanlyl cyclase C, CD198, EGFR, CD52, CD74, FOLR1, CD37, mesothelin, CECAMS, LAMP1, GPNMB, CD56, TROP2, Mucin 1, STEAP1, Mesotehlin, Nectin 4, ENP3, guanylyl cyclase C (GCC), SLC44A4, NaPi2b, CD70 (TNFSF7), Cap, 5T4, SLTRK6, SC-16, LIV-1 (ZIP6), and P-Cadherin.
52 . The composition of claim 50 , wherein the tumor targeting moiety comprises one or more anti-tumor antigen scFvs.
53 . The composition of claim 52 , wherein the anti-tumor antigen scFvs comprises two anti-tumor antigen scFvs that each bind to the same tumor antigen.
54 . The composition of claim 52 , wherein the anti-tumor antigen scFvs comprises two anti-tumor antigen scFvs that each bind to a different tumor antigen.
55 . The composition of 49 , wherein the composition further comprises an anti-human serum albumin scFv, wherein the anti-human serum albumin scFv is attached to the targeting moiety and the drug conjugate moieties by linkers.
56 . The composition of claim 49 , wherein each of the one or more drug moieties comprises a nuclear localization signal.
57 . The composition of 49 , wherein each of the one or more drug moieties comprises a nuclear localization signal.
58 . The composition of claim 49 , wherein the one or more drug moieties are each attached to a lysine residue of the docking peptide by a linker.
59 . The composition of claim 58 , wherein the linker is a cleavable linker.
60 . The composition of claim 59 , wherein the cleavable linker is a cathepsin B cleavable linker.
61 . The composition of claim 58 , wherein the linker is selected from a hydrazone linker, a peptide linker, a disulfide linker and a thioether linker.
62 . The composition of claim 49 , wherein the drug moiety is selected from the group consisting of a microtubule inhibitor, a DNA cleavage enzyme, an Akt inhibitor, a DNA intercalator, a DNA transcription factor inhibitor, a DNA cross linker, and a Dihydrofolate Reductase (DHFR) inhibitor.
63 . The composition of claim 55 , wherein anti-human serum albumin scFv has the amino acid sequence of SEQ ID NO: 54.
64 . A method of treating cancer in a patient in need thereof comprising administering to the patient the composition of claim 49 .
65 . A docking peptide comprising the amino acid sequence of SEQ ID NO:5.
66 . The docking peptide of claim 65 , wherein the docking peptide further comprises a lysosome targeting peptide.
67 . The docking peptide of claim 65 , wherein the docking peptide further comprises one or more drug moieties, wherein each of the drug moieties is attached to one of the lysine residues of the docking peptide.
68 . The docking peptide of claim 67 , wherein the one or more drug moieties each further comprises a nuclear localization signal.
69 . A nucleic acid encoding the docking peptide of claim 65 .
70 . An expression vector comprising the nucleic acid of claim 69 .
71 . A host cell comprising the expression vector of claim 70
72 . A method of making a docking peptide comprising culture the host cell of claim 71 under conditions for expressing the docking peptide and recovering the docking peptide.