Claims for Patent: 9,095,601

Summary for Patent: 9,095,601

Title:	Cell permeable nanoconjugates of shell-crosslinked knedel (SCK) and peptide nucleic acids (\"PNAs\") with uniquely expressed or over-expressed mRNA targeting sequences for early diagnosis and therapy of cancer
Abstract:	A functional biologically active particle conjugate useful for diagnosis and treating cancer as a bioportal comprises a nanoscale particle having associated therewith an intracellular targeting ligand comprising a PNA, or another nuclease resistant oligonucleotide analog such as MOE-mRNA (2\'-methoxyethyl mRNA) or LNA (locked nucleic acid), having a sequence that binds selectively to an uniquely expressed or overexpressed mRNA specific to the cancer or disease state in a living mammal. In one aspect the uniquely overexpressed target specific to the cancer or disease state is the unr mRNA which can be targeted by the antisense sequence PNA50.
Inventor(s):	Becker; Matthew L. (St. Louis, MO), Fang; Huafeng (St. Louis, MO), Li; Xiaoxu (St. Louis, MO), Pan; Dipanjan (St. Louis, MO), Rossin; Raffaella (St. Louis, MO), Sun; Xiankai (St. Louis, MO), Taylor; John Stephen (St. Louis, MO), Turner; Jeffrey L. (St. Louis, MO), Welch; Michael John (St. Louis, MO), Wooley; Karen L. (St. Louis, MO)
Assignee:	WASHINGTON UNIVERSITY IN ST. LOUIS (St. Louis, MO)
Application Number:	13/705,682
Patent Claims:	1. An anticancer composition for treating a cancer comprising an intracellular targeting ligand comprising a peptide nucleic acid, wherein the peptide nucleic acid is SEQ ID NO: 3, or a nuclease resistant oligonucleotide analog of SEQ ID NO: 3, wherein the nuclease resistant oligonucleotide analog of SEQ ID NO: 3 is selected from the group consisting of a methoxyethyl-mRNA of SEQ ID NO: 3 or a locked nucleic acid of SEQ ID NO: 3, and wherein the peptide nucleic acid SEQ ID NO: 3 or the nuclease resistant oligonucleotide analog of SEQ ID NO: 3 binds selectively to an uniquely expressed or overexpressed mRNA, wherein the uniquely expressed or overexpressed mRNA is an unr mRNA; a permeation peptide, wherein the permeation peptide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and a therapeutic compound. 2. The anticancer composition of claim 1, further comprising a shell crosslinked knedel shell crosslinked nanoparticle. 3. The anticancer composition of claim 1, further comprising a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, a pharmaceutically acceptable diluent, or a pharmaceutically acceptable saline composition. 4. The anticancer composition of claim 1, wherein the therapeutic compound is selected from the group consisting of a radionuclide, a cytotoxic compound and a prodrug. 5. The anticancer composition of claim 4, wherein the cytotoxic compound is selected from the group consisting of aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, amifostine, anastrozole, arsenic trioxide, BCG Live, bexarotene, bleomycin, calusterone, capecitabine, carboplatin, carmustine, celecoxib, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, darbepoetin alfa, denileukin diftitox, dexrazoxane, docetaxel, doxorubicin, dromostanolone, Elliot's B solution, epirubicin, epoetin alfa, estramustine, etoposide phosphate, exemestane, filgrastim, floxuridine, fludarabine, fulvestrant, gemcitabine, gemtuzumab, goserelin acetate, hydroxyurea, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, interferon alfa-2a, interferon alfa-2b, irinotecan, letrozole, leucovorin, levamisole, mechlorethamine, megestrol acetate, melphalan, L-PAM, mercaptopurine 6-MP, mesna, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, androlone phenpropionate, nofetumomab, oprelvekin, oxaliplatin, paclitaxel, pamidronate, pegademase, pegaspargase, pegfilgrastim, entostatin, pipobroman, plicamycin, mithramycin, porfimer sodium, procarbazine, quinacrine, rasburicase, rituximab, sargramostim, streptozocin, talc, tamoxifen, trastuzumab, tretinoin, uracil mustard, valrubicin, vinblastine, tamoxifen, temozolomide, teniposide, testolactone, 6-thioguanine, thiotepa, topotecan, toremifene, tositumomab, vincristine, vinorelbine and zoledronate. 6. The anticancer composition of claim 4, wherein the prodrug is selected from the group consisting of 5-(aziridine-1-yl)-2,4-nitrobenzamide, peptidyl-p-phenylenediamine-mustard, benzoic acid mustard glutamates, 6-methoxypurine arabinonucleoside, 5-fluorocytosine, glucose, hypoxanithine, methotrexate-alane, N-(94-(-D-galactopyranosyl), benzyloxycarbonyl)-daunorubicine, amygdalin, azobenzene mustards, gamma-glutamyl-p-phenylenediamine mustard, phenolmustard-glucuronide, epirubicin-glucuronide, vinca-cephalosporin, nitrogen-mustard-cephalosporin, phenolmustard phosphate, doxorubicine phosphate, mitomycin phosphate, etoposide phosphate, palytoxin-4-hydroxyphenyl-acetamide, cyclophosphamide isofamide and 4-nitrobenzyloxycarbonyl. 7. An anticancer composition comprising an intracellular targeting ligand comprising a peptide nucleic acid, wherein the peptide nucleic acid is SEQ ID NO: 3; a permeation peptide, wherein the permeation peptide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and a therapeutic compound. 8. The anticancer composition of claim 7, further comprising a shell crosslinked knedel shell crosslinked nanoparticle. 9. The anticancer composition of claim 7, further comprising a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, a pharmaceutically acceptable diluent, or a pharmaceutically acceptable saline composition. 10. The anticancer composition of claim 7, wherein the therapeutic compound is selected from the group consisting of a radionuclide, a cytotoxic compound and a prodrug. 11. A method of treating a cancer comprising administering an effective amount of an anticancer composition comprising an intracellular targeting ligand comprising a peptide nucleic acid, wherein the peptide nucleic acid is SEQ ID NO: 3, or a nuclease resistant oligonucleotide analog of SEQ ID NO: 3, wherein the nuclease resistant oligonucleotide analog is selected from the group consisting of a methoxyethyl-mRNA of SEQ ID NO: 3 or a locked nucleic acid of SEQ ID NO: 3, and wherein the peptide nucleic acid SEQ ID NO: 3 or the nuclease resistant oligonucleotide analog of SEQ ID NO: 3 binds selectively to an uniquely expressed or overexpressed mRNA, wherein the uniquely expressed or overexpressed mRNA is an unr mRNA; a permeation peptide, wherein the permeation peptide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and a therapeutic compound. 12. The method of claim 11, wherein the anticancer composition further comprises a shell crosslinked knedel shell crosslinked nanoparticle. 13. The method of claim 11, wherein the anticancer composition further comprises a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, a pharmaceutically acceptable diluent, or a pharmaceutically acceptable saline composition. 14. The method of claim 11, wherein the therapeutic compound is selected from the group consisting of a radionuclide, a cytotoxic compound and a prodrug. 15. The method of claim 11, wherein the cancer is selected from the group consisting of lung cancer, breast cancer, melanoma, colon cancer, renal cancer, testicular cancer, ovarian cancer, prostate cancer, hepatic cancer, germ cancer, epithelial cancer, head and neck cancer, pancreatic cancer, glioblastoma, astrocytoma, oligodendroglioma, ependymomas, neurofibrosarcoma, meningioma, liver cancer, spleen cancer, lymph node cancer, small intestine cancer, colon cancer, stomach cancer, thyroid cancer, endometrium cancer, skin cancer, esophagus cancer, and bone marrow cancer. 16. The method of claim 14, wherein the cytotoxic compound is selected from the group consisting of aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, amifostine, anastrozole, arsenic trioxide, BCG Live, bexarotene, bleomycin, calusterone, capecitabine, carboplatin, carmustine, celecoxib, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, darbepoetin alfa, denileukin diftitox, dexrazoxane, docetaxel, doxorubicin, dromostanolone, Elliot's B solution, epirubicin, epoetin alfa, estramustine, etoposide phosphate, exemestane, filgrastim, floxuridine, fludarabine, fulvestrant, gemcitabine, gemtuzumab, goserelin acetate, hydroxyurea, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, interferon alfa-2a, interferon alfa-2b, irinotecan, letrozole, leucovorin, levamisole, mechlorethamine, megestrol acetate, melphalan, L-PAM, mercaptopurine 6-MP, mesna, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, androlone phenpropionate, nofetumomab, oprelvekin, oxaliplatin, paclitaxel, pamidronate, pegademase, pegaspargase, pegfilgrastim, entostatin, pipobroman, plicamycin, mithramycin, porfimer sodium, procarbazine, quinacrine, rasburicase, rituximab, sargramostim, streptozocin, talc, tamoxifen, trastuzumab, tretinoin, uracil mustard, valrubicin, vinblastine, tamoxifen, temozolomide, teniposide, testolactone, 6-thioguanine, thiotepa, topotecan, toremifene, tositumomab, vincristine, vinorelbine and zoledronate. 17. The method of claim 14, wherein the prodrug is selected from the group consisting of 5-(aziridine-1-yl)-2,4-nitrobenzamide, peptidyl-p-phenylenediamine-mustard, benzoic acid mustard glutamates, 6-methoxypurine arabinonucleoside, 5-fluorocytosine, glucose, hypoxanithine, methotrexate-alane, N-(94-(-D-galactopyranosyl), benzyloxycarbonyl)-daunorubicine, amygdalin, azobenzene mustards, gamma-glutamyl-p-phenylenediamine mustard, phenolmustard-glucuronide, epirubicin-glucuronide, vinca-cephalosporin, nitrogen-mustard-cephalosporin, phenolmustard phosphate, doxorubicine phosphate, mitomycin phosphate, etoposide phosphate, palytoxin-4-hydroxyphenyl-acetamide, cyclophosphamide isofamide and 4-nitrobenzyloxycarbonyl.

Details for Patent 9,095,601

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Teknika Llc	TICE BCG	bcg live	For Injection	102821	06/21/1989		2024-10-15
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2024-10-15
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2024-10-15
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2024-10-15
Hoffmann-la Roche Inc.	ROFERON-A	interferon alfa-2a	For Injection	103145	06/04/1986		2024-10-15
Amgen, Inc.	EPOGEN/PROCRIT	epoetin alfa	Injection	103234	06/01/1989		2024-10-15