Cellular uptake peptide-therapeutic payload compositions and methods of use
AssigneeNighthawk Biosciences, Inc.
InventorsKarla FRIETZE, Neil GOLDSTEIN, Jeffrey WOLF, John PRENDERGAST
Life of this patent
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Abstract
The present disclosure relates to, among others, a composition comprising an internalization peptide, also called a cellular uptake peptide, connected to a drug product, also called a therapeutic payload, by a linker.
Claims99
A composition according to the formula:
- J-Y-Z, wherein:
- J comprises a cellular uptake peptide and optionally, a cell surface receptor targeting peptide and/or an organelle uptake peptide and/or a protein detection peptide
- when there is a cell surface receptor targeting peptide and/or an organelle uptake peptide and/or protein detection peptide, there is optionally a cleavage site between each of these peptides and also between these peptides and the cellular uptake peptide;
- the cellular uptake peptide is capable of binding to a marker which is internalized by a cell, optionally expressed on a cancer cell, optionally selected from OVCAR, MIA, A549, A431, G292, HCT116, CHLA02, CHLA04, CHLA05, CHLA06, or
- has an amino acid sequence selected from:
- (SEQ ID NO:
- 48)
- DFYGCLLDLSLGVPSLGWRRRCITA (″429″);
- (SEQ ID NO:
- 43)
- YQWVSWWHRGLLRPVLRGSLKPWYIFVRIHISWGQVHVG,
- (SEQ ID NO:
- 44)
- TGWWFFWSYVCSVRLLAVTCSFWCTEQGEESLPRAGTHTH,
- (SEQ ID NO:
- 45)
- YTLGLGKSQRWNLFRNFFCYMPRVTVFCKSCRCVSFQTSG,
- (SEQ ID NO:
- 46)
- HYLLIRCARGFCEVRLVDAMCSITIVIDCVLFTSQRERAE;
- (SEQ ID NO:
- 47)
- QGSLISCWVTFVQESWDAYSLCSDLFKCQGGQVFSICEPE,
- (SEQ ID NO:
- 49)
- FSFGNSSLRKLPGWVRRRRCARGVWR (″OV-8″);
- (SEQ ID NO:
- 48)
- DFYGCLLDLSLGVPSLGWRRRCITA (″1 429-M″);
- (SEQ ID NO:
- 49)
- FSFGNSSLRKLPGWRRRRCARGVWR (″#3 OvB8-M″);
- (SEQ ID NO:
- 48)
- DFYGCLLDLSLGVPSLGWRRRCITA (″429-F″);
- and
- (SEQ ID NO:
- 49)
- FSFGNSSLRKLPGVVRRRRCARGVWR (″#4 OVB8-F″);
- or a variant thereof, or
- has an amino acid sequence selected from Table 1 or FIG. 1, or a variant thereof;
- Z comprises a therapeutic payload;
- and
- Y is a linker covalently attaching J and Z.
The composition of any one of the above claims, wherein the cellular uptake peptide is capable of binding to Ovcar-3 cells and/or has an amino acid sequence selected from:
- (SEQ ID NO:
- 50)
- PRGWRRCLGWSVGPASGSGP,
- (SEQ ID NO:
- 49)
- FSFGNSSLRKLPGWRRRRCARGVWR,
- (SEQ ID NO:
- 51)
- CLGVCISGDPEQADMWGCRP,
- (SEQ ID NO:
- 52)
- ILSRSQYLVFGYAWARGSR,
- (SEQ ID NO:
- 53)
- GSGLCSVCQCGGMYSRVVLGQRRWM,
- (SEQ ID NO:
- 54)
- GVSPIVHGDAGLLQPRNTRL,
- (SEQ ID NO:
- 55)
- CRQRGDGGAMRRGSVCLRGW,
- (SEQ ID NO:
- 56)
- GDGTGVQRAAVGFDLTGHSP,
- (SEQ ID NO:
- 57)
- AVSACGRCRHCRVPGVPCWLYCVCT,
- (SEQ ID NO:
- 58)
- PSTMSIAGGGFCGHPRRGTI,
- (SEQ ID NO:
- 59)
- DQCAGHDSVQRHALHGLAVM,
- (SEQ ID NO:
- 60)
- GASPCVFRVDSTSGGPLVFPDLQST,
- (SEQ ID NO:
- 61)
- RREDSLTRVRQALREALGAG,
- and
- (SEQ ID NO:
- 62)
- LDVGVAQHRGGTVIRVAMRA,
- or a variant thereof.
The composition of any one of the above claims, wherein the cellular uptake peptide has an amino acid sequence which is FSFGNSSLRKLPGWRRRRCARGVWR (SEQ ID NO:
- 49), or a variant thereof.
The composition of any one of the above claims, wherein the variant comprises about 1, or about 2, or about 3, or about 4, or about 5 mutations, the mutations selected from substitutions or deletions.
The composition of any one of the above claims, wherein the linker is a flexible linker.
The composition of any one of the above claims, wherein the linker comprises a cleavage site.
A composition comprising an amino acid sequence of:
- DFYGCLLDLSLGVPSLGWRRRCITADYKDDDDKWLPSSIPKKKRKVDGQKLRDAFTWNMNEKLMTPEMFSEILCDDL D (SEQ ID NO:
- 110), or an amino acid sequence having at least about 90%, or at least about 95%, or at least about 97%, or at least about 98%, or at least about 99% identity thereof.
A composition comprising an amino acid sequence of:
- DFYGCLLDLSLGVPSLGWRRRCITAWLPSSIPKKKRKVDGQKLRDAFTWNMNEKLMTPEMFSEILCDDLD (SEQ ID NO:
- 111), or an amino acid sequence having at least about 90%, or at least about 95%, or at least about 97%, or at least about 98%, or at least about 99% identity thereof.
A composition comprising an amino acid sequence of:
- QVQLVESGGGVVQPGRSLRLSCAASGGGGSGGGGSWFRQAPGKEREFVAGGGGSGGGGSYADSVKGRFTISRD NSKNTLYLQMNSLRAEDTAVYYCARDFYGCLLDLSLGVPSLGWRRRCITAWGQGLVTVSSGPGGQWLPSSIPKKKR KVDGQKLRDAFTWNMNEKLMTPEMFSEILCDDLD (SEQ ID NO:
- 112), or an amino acid sequence having at least about 90%, or at least about 95%, or at least about 97%, or at least about 98%, or at least about 99% identity thereof.
A polynucleotide comprising a nucleic acid sequence encoding the amino acid sequence, or variant thereof of any of the above claims.
A composition comprising a glycoprotein non-metastatic melanoma protein b (GPNMB) recognition domain linked to a therapeutic payload.
Dependencies are inferred from the claim text.