Compositions for treating cancer and methods for making the same

Patent metadata

Field	Value
Publication number	US-9789193-B2
Application number	US-201314406938-A
Country	US
Kind code	B2
Filing date	Jun 14, 2013
Priority date	Jun 15, 2012
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

Described herein are compositions and methods relating to chemotherapeutic agent conjugates and the treatment of cancer.

First claim

What is claimed is:

1. A composition comprising a conjugate, the conjugate comprising a chemotherapeutic agent conjugated to cholesterol, wherein conjugate is of Formula (III):

2. The composition of claim 1 , wherein the composition further comprises a lipid in addition to the conjugate.

3. The composition of claim 2 , wherein the lipid is a lipid conjugated with polyethylene glycol (PEG).

4. The composition of claim 3 , 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-glycem-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000); and any combinations thereof.

5. The composition of any of claim 1 or 2 - 4 , wherein the composition further comprises a phospholipid.

6. The composition of claim 5 , wherein the 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; sphingomyelin; phosphatidyl glycerols; phosphatidylcholine; phosphatidylglycerol; lecithin; β,γ-dipalmitoyl-α-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); distearoylphosphatidylcholine (DSPC); dioleoylphosphatidylcholine (DOPC); dipalmitoylphosphatidylcholine (DPPC); dioleoylphosphatidylglycerol (DOPG); dipalmitoylphosphatidylglycerol (DPPG); -phosphatidylethanolamine (POPE); dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal); L-a-phosphatidylcholine; and any combinations thereof.

7. The composition of any of claim 1 or 2 - 6 , further comprising a targeting agent.

8. The composition of claim 7 , wherein the targeting agent 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 iRGD (amino acid sequence CRGDKGPDC (SEQ ID NO: 1.

9. The composition of any of claim 1 or 2 - 8 , wherein the composition further comprises an anticancer agent in addition to the conjugate.

10. The composition of claim 9 , wherein the anticancer agent is selected from the group consisting of:
a platinum compound, paclitaxel; carboplatin; bortezomib; vorinostat; rituximab; temozolomide; rapamycin; an alkylating agent; cyclosphosphamide; an alkyl sulfonate; busulfan; improsulfan; piposulfan; an aziridine; an ethylenimine; a methylamelamine; an acetogenin; a camptothecin; a cryptophycin; a nitrogen mustard; a nitrosurea; an antibiotic; a enediyne antibiotic; a bisphosphonate; doxorubicin; a mitomycin; an anti-metabolite; a folic acid analogue; a purine analog; a pyrimidine analog; an androgen; an anti-adrenal; an epothilone; a maytansinoid; a trichothecene; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; vinblastine; etoposide; ifosfamide; mitoxantrone; vincristine; vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan; a topoisomerase inhibitor; a retinoid; capecitabine; combretastatin; leucovorin; lapatinib; erlotinib; and a compound having the structure of formula (IV):

11. The composition of any of claim 1 or 2 - 10 , wherein the composition comprises the conjugate, a PEG conjugated lipid, and a phospholipid.

12. The composition of claim 11 , wherein the PEG conjugated lipid is DSPE-PEG2000 and the phospholipid is phosphatidylcholine.

Assignees

• Brigham & Womens Hospital Inc

Inventors

• Sengupta Shiladitya
• Kulkarni Ashish
• Rao Poornima
• Roy Bhaskar

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K47/55 Primary

  the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug · CPC title

• A61K47/554

  the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid · CPC title