Claims for Patent: 10,426,753

Summary for Patent: 10,426,753

Title:	Supramolecular combinatorial therapeutics
Abstract:	The present disclosure relates generally to supramolecular combinatorial therapeutics, compositions comprising same, and uses thereof. In particular, the present disclosure provides hydrophobic taxane-lipid covalent conjugates which create supramolecular assembly, for example, within lipid bilayer, providing an extra stabilization resulting in increased intratumoral concentration and hence increased efficacy. The present disclosure also provides supramolecular combinatorial therapeutics, wherein a taxane-lipid conjugate is combined with one or more of a platinum compound, a kinase inhibitor, and an immunoregulator, each of which is optionally conjugated with a lipid.
Inventor(s):	Roy; Monideepa (Delhi, IN), Hossain; Samad (Delhi, IN), Sengupta; Aniruddha (Delhi, IN), Mylavarapu; Sanghamitra (Delhi, IN), Sengupta; Shiladitya (Waltham, MA), Mukherjee; Anubhab (Delhi, IN)
Assignee:	INVICTUS ONCOLOGY PVT. LTD. (Delhi, IN)
Application Number:	15/301,570
Patent Claims:	1. A supramolecular combinatorial therapeutic (SCT) comprising a taxane-lipid conjugate, wherein the taxane-lipid conjugate is a cabazitaxel-lipid conjugate; and wherein the cabazitaxel-lipid conjugate is selected from the group consisting of conjugates 1-15 and 21-32 ##STR00048## ##STR00049## ##STR00050## ##STR00051## ##STR00052## ##STR00053## ##STR00054## ##STR00055## ##STR00056## ##STR00057## 2. The supramolecular combinatorial therapeutic of claim 1, wherein the supramolecular combinatorial therapeutic is a liposome, emulsion, micelle, or particle; the supramolecular combinatorial therapeutic comprises from about 1% to about 99% (w/w) of the taxane conjugate. 3. The supramolecular combinatorial therapeutic of claim 1, wherein the supramolecular combinatorial therapeutic further comprises a lipid conjugated PI3K inhibitor, a lipid conjugated platinum compound, a lipid conjugated antibody, a neutral lipid, a cationic lipid, an anionic lipid, an amphiphilic lipid, a sterol, a programmable fusion lipid and combinations thereof or a pharmaceutically acceptable carrier; wherein the antibody is a therapeutic agent or a targeting ligand or is an immunomodulatory comprising an anti-PD-1 antibody, an anti-PD-L1 antibody and combinations thereof; wherein the lipid is cholesterol, 1,3-Propanediol Dicaprylate/Dicaprate, 10-undecenoic acid, 1-dotriacontanol, 1-heptaconsanol, 1-nonacosanol, 2-ethyl hexanol, Androstanes, Arachidic acid, Arachidonic acid, arachidyl alcohol, Benenic acid, behenyl alcohol, Capmul MCM C10, Capric acid, capric alcohol, capryl alcohol, Caprylic acid, Caprylic/Capric Acid Ester of Saturated Fatty Alcohol C12-C18, Caprylic/Capric Triglyceride, Cermide phosphorylcholine (Sphingomyelin, SPH), Ceramide phosphorylethanolamine (Sphingomyelin, Cer-PE), Ceramide phosphorylglycerol, Ceroplastic acid, Cerotic acid, ceryl alcohol, Cetearyl alcohol, Ceteth-10, cetyl alcohol, Cholanes, Cholestanes, cholesterol, cis-11-eicosenoic acid, cis-11-octadecenoic acid, cis-13-docosenoic acid, cluytyl alcohol, Dihomo-.gamma.-linolenic, Docohexaenoic acid, egg lecithin, Eicosapentaenoic acid, Eicosenoic acid, Elaidic acid, elaidolinolenyl alcohol, elaidolinoleyl alcohol, elaidyl alcohol, Erucic acid, erucyl alcohol, Estranes, Ethylene glycol distearate (EGDS), Geddic acid, geddyl alcohol, glycerol distearate (type I) EP (Precirol ATO 5), Glycerol Tricaprylate/Caprate, Glycerol Tricaprylate/Caprate (CAPTEX.RTM. 355 EP/NF), glyceryl monocaprylate (Capmul MCM C8 EP), Glyceryl Triacetate, Glyceryl Tricaprylate, Glyceryl Tricaprylate/Caprate/Laurate, Glyceryl Tricaprylate/Tricaprate, glyceryl tripalmitate (Tripalmitin), Henatriacontylic acid, Heneicosyl alcohol, Heneicosyl acid, Heptacosylic acid, Heptadecanoic acid, Heptadecyl alcohol, Hexatriacontylic acid, isostearic acid, isostearyl alcohol, Lacceroic acid, Lauric acid, Lauryl alcohol, Lignoceric acid, Lignoceryl alcohol, Linoelaidic acid, Linoleic acid, Linolenyl alcohol, linoleyl alcohol, Margaric acid, Mead, Melissic acid, melissyl alcohol, Montanic acid, montanyl alcohol, myricyl alcohol, Myrisitic acid, Myristoleic acid, Myristyl alcohol, neodecanoic acid, neohaptanoic acid, neononanoic acid, Nevronic, Nonacosylic acid, Nonadecyl alcohol, Nonadecylic acid, Oleic acid, oleyl alcohol, Palmitic acid, Palmitoleic acid, palmitoleyl alcohol, Pelargonic acid, Pelargonic alcohol, Pentacosylic acid, Pentadecyl alcohol, Pentadecylic acid, Phosphatidic acid (phosphatidate, PA), Phosphatidylcholine (lecithin, PC), Phosphatidylethanolamine (cephalin, PE) Phosphatidylinositol (PI), Phosphatidylinositol bisphosphate (PEP2) Phosphatidylinositol phosphate (PIP), Phosphatidylinositol triphosphate (PIP3), Phosphatidylserine (PS), Polyglycerol-6-disearate, Pregananes, Propylene Glycol Dicaprate, Propylene Glycol Dicaprylocaprate, Propylene Glycol Dicaprylocaprate, Psyllic acid, recinoleaic acid, recinoleyl alcohol, Sapienic acid, soy lecithin, Stearic acid, Stearidonic, stearyl alcohol, Tricosylic acid, Tridecyl alcohol, Tridecyclic acid, Triolein, Undecyl alcohol, undecylenic acid, Undecylic acid, Vaccenic acid, .alpha.-Linolenic acid, .gamma.-Linolenic acid, alpha-tocopherol, or a fatty acid; wherein the PI3K inhibitor conjugate is ##STR00058## wherein the supramolecular combinatorial therapeutic comprises from about 1% to about 99% (w/w) of the PI3K inhibitor conjugate or the platinum conjugate or the conjugated antibody; and wherein the supramolecular combinatorial therapeutic comprises the taxane conjugate and the PI3K inhibitor conjugate or taxane conjugate and the platinum conjugate, or the taxane conjugate and the antibody conjugate in about 10:1 to about 1:10 molar ratio. 4. The supramolecular combinatorial therapeutic of claim 1, wherein the supramolecular combinatorial therapeutic further comprises at least one additional lipid, a polyethylene glycol (PEG), targeting ligand or a chemotherapeutic agent; wherein the at least one additional lipid is a phospholipid; wherein each phospholipid is selected from the group consisting of phosphatidyl cholines, phosphatidyl cholines with acyl groups having 6 to 22 carbon atoms, phosphatidyl ethanolamines, phosphatidyl inositols, phosphatidic acids, phosphatidyl serines, phosphatidyl glycerols, phosphatidylglycerol, lecithin, .beta.,.gamma.-dipalmitoyl-.alpha.-lecithin, sphingomyelin, phosphatidylserine, phosphatidic acid, N-(2,3-di(9-(Z)-octadecenyloxy))-prop-1-yl-N,N,N-trimethylammonium chloride, phosphatidylethanolamine, lysolecithin, lysophosphatidylethanolamine, phosphatidylinositol, cephalin, cardiolipin, cerebrosides, dicetylphosphate, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, dioleoylphosphatidylglycerol, palmitoyl-oleoyl-phosphatidylcholine, di-stearoyl-phosphatidylcholine, stearoyl-palmitoyl-phosphatidylcholine, di-palmitoyl-phosphatidylethanolamine, di-stearoyl-phosphatidylethanolamine, di-myrstoyl-phosphatidylserine, di-oleyl-phosphatidylcholine, dimyristoyl phosphatidyl choline (DMPC), dioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), egg phosphatidylcholine (EPC), di stearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), -phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), 1-stearoyl-2-oleoyl phosphatidylcholine (SOPC), 1,2-di stearoyl-sn-glycerol-3-phosphoethanolamine (DSPE), and any combinations thereof; wherein the first and second lipid, or the conjugate and total lipid are in about 10:1 to about 1:10 molar ratio; wherein the supramolecular combinatorial therapeutic comprises about 1% to about 99% (w/w) of total lipid; wherein the PEG is conjugated with a component of the supramolecular combinatorial therapeutic, or the PEG is conjugated to a lipid; wherein the PEG conjugated lipid is selected from the group consisting of PEG conjugated diacylglycerols and dialkylglycerols, PEG-conjugated phosphatidylethanolamine and phosphatidic acid, PEG conjugated ceramides, PEG conjugated dialkylamines, PEG conjugated 1,2-diacyloxypropan-3-amines, 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) and any combinations thereof; wherein the targeting ligand is selected from the group consisting of peptides, polypeptides, proteins, enzymes, peptidomimetics, glycoproteins, antibodies (monoclonal or polyclonal) and portions and fragments thereof, lectins, nucleosides, nucleotides, nucleoside and nucleotide analogues, nucleic acids, monosaccharides, disaccharides, trisaccharides, oligosaccharides, polysaccharides, lipopolysaccharides, vitamins, steroids, hormones, cofactors, receptors, receptor ligands, and analogs and derivatives thereof; wherein the targeting ligand binds a protein, receptor, or marker expressed on the surface of a cancer cell; the targeting ligand or the chemotherapeutic agent is conjugated with a component of the composition; wherein the component is a lipid or PEG or cholesterol; wherein the supramolecular combinatorial therapeutic comprises about 1% to about 99% (w/w) of the chemotherapeutic agent; wherein the chemotherapeutic agent is selected from the group consisting of PI3K inhibitors, platinum compounds, inhibitors of topoisomerase I and II, alkylating agents, microtubule inhibitors, angiogenesis inhibitors, germicitibine, Aldesleukin, Alemtuzumab, alitretinoin, allopurinol, altretamine, amifostine, anastrozole, arsenic trioxide, Asparaginase, BCG Live, bexarotene capsules, bexarotene gel, bleomycin, busulfan intravenous, busulfanoral, calusterone, capecitabine, platinate, carmustine, carmustine with Polifeprosan Implant, celecoxib, chlorambucil, cladribine, cyclophosphamide, cytarabine, cytarabine liposomal, dacarbazine, dactinomycin, actinomycin D, Darbepoetin alfa, daunorubicin liposomal, daunorubicin, daunomycin, Denileukin diftitox, dexrazoxane, docetaxel, doxorubicin, doxorubicin liposomal, Dromostanolone propionate, Elliott's B Solution, epirubicin, Epoetin alfa estramustine, etoposide phosphate, etoposide (VP-16), exemestane, Filgrastim, floxuridine (intraarterial), fludarabine, fluorouracil (5-FU), fulvestrant, gemtuzumab ozogamicin, goserelin acetate, hydroxyurea, Ibritumomab Tiuxetan, idarubicin, ifosfamide, imatinib mesylate, Interferon alfa-2a, Interferon alfa-2b, irinotecan, letrozole, leucovorin, levamisole, lomustine (CCNU), mechlorethamine (nitrogenmustard), megestrol acetate, melphalan (L-PAM), mercaptopurine (6-MP), mesna, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone phenpropionate, Nofetumomab, LOddC, Oprelvekin, pamidronate, pegademase, Pegaspargase, Pegfilgrastim, pentostatin, pipobroman, plicamycin, mithramycin, porfimer sodium, procarbazine, quinacrine, Rasburicase, Rituximab, Sargramostim, streptozocin, talbuvidine (LDT), talc, tamoxifen, temozolomide, teniposide (VM-26), testolactone, thioguanine (6-TG), thiotepa, topotecan, toremifene, Tositumomab, Trastuzumab, tretinoin (ATRA), Uracil Mustard, valrubicin, valtorcitabine (monoval LDC), vinblastine, vinorelbine, zoledronate and any combinations thereof; and wherein the PI3K inhibitor is selected from the group consisting of PI103, P1828, LY294002, wortmannin, demethoxyviridin, IC486068, IC87114, GDC-0941, perifosine, CAL101, PX-866, IPI-145, BAY 80-6946, BEZ235, P6503, TGR1202, SF1126, INK1117, BKM120, IL147, XL765, Palomid 529, GSK1059615, ZSTK474, PWT33597, TG100-115, CAL263, GNE-447, CUDC-907, and AEZS-136, and any combinations thereof. 5. The supramolecular combinatorial therapeutic of claim 1, wherein the supramolecular combinatorial therapeutic comprises at least one taxane lipid conjugate in combination with a conjugate selected from the group consisting of the PI3K inhibitor-lipid conjugate, the platinum-lipid conjugate and the antibody-lipid conjugate; a PEG conjugated lipid; and a phospholipid; wherein the taxane-lipid conjugate, the phospholipid, and the PEG conjugated lipid is in a molar ratio from about 10-0.1:10-0.1:10-0.01; wherein the phospholipid is phosphatidylcholine and the PEG conjugated lipid is DSPE-PEG.sub.2000; and wherein the phosphatidylcholine is selected from the group consisting of SOPC, POPC, Egg PC, HSPC, and any combinations thereof. 6. The supramolecular combinatorial therapeutic of claim 1, wherein the supramolecular combinatorial therapeutic is in the form of a composition or a nanoparticle; wherein said composition comprises supramolecular combinatorial therapeutic and a pharmaceutically acceptable carrier; wherein said nanoparticle comprises supramolecular combinatorial therapeutic and a co-lipid, and wherein the nanoparticle is about 5 nm to about 500 nm in diameter. 7. A method of treating cancer, comprising administering a supramolecular combinatorial therapeutic of claim 1, optionally along with co-administering one or more additional anti-cancer therapy, chemotherapeutic agent or immunomodulatory to a subject in need of treatment for cancer, thereby treating the cancer. 8. The method of claim 7, wherein the cancer is selected from the group consisting of breast cancer; ovarian cancer; glioma; gastrointestinal cancer; prostate cancer; carcinoma, lung carcinoma, hepatocellular carcinoma, testicular cancer; cervical cancer; endometrial cancer; bladder cancer; head and neck cancer; lung cancer; gastro-esophageal cancer, and gynecological cancer; wherein the additional therapy is selected from the group consisting of surgery, chemotherapy, radiation therapy, thermotherapy, immunotherapy, hormone therapy, laser therapy, anti-angiogenic therapy, and any combinations thereof; and wherein the immunomodulator selected from the group consisting of natural killer cells, lymphokine-activated killer cells, cytotoxic T cells and dendritic cells, anti-PD-L1 antibodies, anti-PD-1 antibodies, anti-CD52 antibodies, anti-VEGF-A antibodies, anti-CD30 antibodies, anti-EGFR antibodies, anti-CD33 antibodies, anti-CD20 antibodies, anti-CTLA4 antibodies, anti-HER-2 antibodies, interferons and interleukins. 9. A composition comprising a conjugate of claim 1 and a pharmaceutically acceptable carrier. 10. The composition of claim 1, wherein the composition comprises from about 1% to about 99% (w/w) of the conjugate, a first lipid, and a second lipid, optionally along with a pharmaceutically acceptable carrier; wherein the first lipid and second lipid are phospholipids, wherein the phospholipids are selected from the group consisting of phosphatidyl cholines, phosphatidyl cholines with acyl groups having 6 to 22 carbon atoms, phosphatidyl ethanolamines, phosphatidyl inositols, phosphatidic acids, phosphatidyl serines, sphingomyelin, phosphatidyl glycerols, lecithin, .beta.,.gamma.-dipalmitoyl-.alpha.-lecithin, phosphatidylserine, phosphatidic acid, N-(2,3-di(9-(Z)-octadecenyloxy))-prop-1-yl-N,N,N-trimethylammonium chloride, lysolecithin, lysophosphatidylethanolamine, cephalin, cardiolipin, cerebrosides, dicetylphosphate, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, dioleoylphosphatidylglycerol, palmitoyl-oleoyl-phosphatidylcholine, di-stearoyl-phosphatidylcholine, stearoyl-palmitoyl-phsophatidylcholine, di-palmitoyl-pohsophatidylethanolamine, di-stearoyl-phosphatidylethanolamine, di-myrstoyl-phosphatidylserine, di-oleyl-phosphatidylcholine, dimyristoyl phosphatidyl choline (DPMC), dioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), egg phosphatidylcholine (EPC), disearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), diplamitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), 1-stearoyl-2-oleoyl phosphatidylcholine (SOPC), 1,2-disearoyl-sn-glycerol-3-phosphatidylethanolamine (DSPE), and any combination thereof; wherein the first and second lipid are in about 10:1 to about 1:10 ratio; wherein the composition comprises about 1% to about 99% of total lipid; and wherein the composition comprises the conjugate and total lipid in about 10:1 to about 1:10 ratio. 11. The composition of claim 10, wherein the composition further comprises polyethylene glycol (PEG), a targeting ligand, a chemotherapeutic agent, an immunodulator, a neutral lipid, a cationic lipid, an anionic lipid, an amphiphilic lipid, a sterol, a programmable fusion lipid, or any combinations thereof; wherein the PEG is conjugated with a component of the composition, wherein the component is a lipid; wherein the PEG conjugated lipid is selected from the group consisting of PEG conjugated diacylglycerols and dialkylglycerols, PEG-conjugated phosphatidylethanolamine and phosphatidic acid, PEG conjugated ceramides, PEG conjugated dialkylamines, PEG conjugated 1,2-diacyloxypropan-3-amines, 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) and any combinations thereof; wherein the targeting ligand is selected from the group consisting of peptides, polypeptides, proteins, enzymes, peptidomimetics, glycoproteins, antibodies (monoclonal or polyclonal) and portions and fragments thereof, lectins, nucleosides, nucleotides, nucleoside and nucleotide analogues, nucleic acids, monosaccharides, disaccharides, trisaccharides, oligosaccharides, polysaccharides, lipopolysaccharides, vitamins, steroids, hormones, cofactors, receptors, receptor ligands, or markers expressed on the surface of a cancer cell and analogs and derivatives thereof; wherein the targeting ligand, chemotherapeutic agent or the immunomodulator is conjugated with a component of the composition; wherein the component is a lipid or PEG or cholesterol; wherein the chemotherapeutic agent is present in about 1% to 99% (w/w); the chemotherapeutic agent is selected from the group consisting of PI3K inhibitors, platinum compounds, inhibitors of topoisomerase I and II, alkylating agents, microtubule inhibitors, angiogenesis inhibitors, gemcitibine, Aldesleukin, Alemtuzumab, alitretinoin, allopurinol, altretamine, amifostine, anastrozole, arsenic trioxide, Asparaginase, BCG Live, bexarotene capsules, bexarotene gel, bleomycin, bisulfan intravenous, busulfanoral, calusterone, capecitabine, platinate, carmustine, carmustine with Polifeprosan Implant, celecoxib, chlorambucil, cladribine, cyclophosphamide, cytarabine, cytarabine liposomal, dacarbazine, dactinomycin, actinomycin D, Darbepoetin alfa, daunorubicin, doxorubicin liposomal, Dromostanolone propionate, Elliott's B Solution, epirubicin, Epoetin alfa estramustine, etoposide phosphate, etoposide (VP-16), exemestane, Filgrastim, floxuridine (intraarterial), fludarabine, fluorouracil (5-FU), fulvestrant, gemtuzumab ozogamicin, goserelin acetate, hydroxyurea, Ibritumomab Tiuxetan, idarubicin, ifosfamide, imatinib mesylate, Interferon alfa-2a, Interferon alfa-2b, irinotecan, letrozole, leucovorin, levamisole, lomustine (CCNU), mechlorethamine (nitrogenmustard), megestrol acetate, melphalan (L-PAM), mercaptopurine (6-MP), mesna, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone phenpropionate, Nofetumomab, LOddC, Oprelvekin, pamidronate, pegademase, Pegasparagase, Pegfilgrastim, pentostatin, pipobroman, plicamycin, mithramycin, porfimer sodium, procarbazine, quinacrine, Rasburicase, Rituximab, Sargramostim, streptozocin, talbuvidine (LDT), talc, tamoxifen, temozolomide, teniposide (VM-26), testolactone, thioguanine (6-TG), thiotepa, topotecan, toremifene, Tostumomab, Trastuzumab, tretinoin (ATRA), Uracil Mustard, valrubicin, valtorcitabine (monoval LDC), vinblastine, vinorelbine, zoledronate, and any combinations thereof; wherein the PI3K inhibitor is selected from the group consisting of PI103, PI828, LY294002, wortmannin, demethoxyviridin, IC486068, IC87114, GDC-0941, perfoxine, CAL101, PX-866, IPI-145, BAY 80-6946, BEZ235, P6503, TGR1202, SF1126, INK1117, BKM120, IL147, XL765, Palomid 529, GSK1059615, ZSTK474, PWT33597, TG100-115, CAL263, GNW-447, CUDC-907, and AEZS-136, and any combinations thereof; wherein the lipid conjugated chemotherapeutic agent ##STR00059## wherein the composition further comprises an immunomodulator comprising and anti-PD-1 antibody, an anti-PD-LI antibody or combination thereof; wherein the composition comprises the conjugate, a phospholipid, and a PEG conjugated lipid; wherein the conjugate, the phospholipid, and the PEG conjugated lipid are present in a ratio from about 10-0.1:10-0.1:10-0.1; wherein the phospholipid is phosphatidycholine and the PEG conjugated lipid is DSPE-PEG2000; wherein the composition is a liposome, emulsion, micelle or a nanoparticle; and wherein the nanoparticle is about 5 nm to about 500 nm in diameter. 12. A method of treating cancer, comprising administering a composition of claim 10, and optionally co-administering one or more of an additional anti-cancer therapy, and an immunomodulator to a subject in need of treatment for cancer, thereby treating the cancer. 13. The method of claim 12, wherein the cancer is selected from the group consisting of breast cancer; ovarian cancer; glioma; gastrointestinal cancer; prostate cancer; carcinoma, lung carcinoma, hepatocellular carcinoma, testicular cancer; cervical cancer; endometrial cancer; bladder cancer; head and neck cancer; lung cancer; gastro-esophageal cancer, and gynecological cancer; wherein the additional therapy is selected from the group consisting of surgery, chemotherapy, radiation therapy, thermotherapy, immunotherapy, hormone therapy, laser therapy, anti-angiogenic therapy, and any combinations thereof; wherein the additional therapy comprises administering a chemotherapeutic agent to the patient; wherein the additional therapy comprises administering a chemotherapeutic agent to the patient; wherein the immunomodulator activates an immune response against cancer cells; and wherein the immunomodulator is selected from the group consisting of natural killer cells, lymphokine-activated killer cells, cytotoxic T cells and dendritic cells, anti-PD-L1 antibodies, anti-PD-1 antibodies, anti-CD52 antibodies, anti-VEGF-A antibodies, anti-CD30 antibodies, anti-EGFR antibodies, anti-CD33 antibodies, anti-CD20 antibodies, anti-CTLA4 antibodies, anti-HER-2 antibodies, interferons and interleukins. 14. A supramolecular combinatorial therapeutic (SCT) comprising a taxane-lipid conjugate, wherein the taxane-lipid conjugate is a paclitaxel-lipid conjugate or a docetaxel-lipid conjugate; and wherein the paclitaxel-lipid conjugate is selected from the group consisting of conjugate 16 and conjugate 17 ##STR00060## ##STR00061## wherein the docetaxel-lipid conjugate is selected from the group consisting of conjugates 18-20 and conjugate 33 ##STR00062## ##STR00063##

Details for Patent 10,426,753

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2034-04-03
Merck Teknika Llc	TICE BCG	bcg live	For Injection	102821	06/21/1989		2034-04-03
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2034-04-03
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2034-04-03
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2034-04-03