USE OF REPLACED HEXITOLS INCLUDING DIANIDROGALACTITOL AND ANALOGS TO TREAT NEOPLASTIC DISEASE AND CA

专利摘要:
USE OF REPLACED HEXITOLS INCLUDING DIANIDROGALACTITOL AND ANALOGS TO TREAT NEOPLASTIC DISEASE AND CELLS - CANCER STEM INCLUDING MULTIFORM GLIOBLASTOMA AND MEDULOBLASTOMA. It is the use of dianhydrogalactitol that provides an innovative therapeutic modality for the treatment of glioblastoma multiforme and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent in DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide; the drug acts independently of the MGMT repair mechanism.
公开号:BR112014017833A2
申请号:R112014017833-0
申请日:2013-01-22
公开日:2021-03-23
发明作者:Dennis Brown；Jeffrey Bacha；Sandra Dunn
申请人:Dennis Brown；
IPC主号:

专利说明:

OF REPLACED HEXITOLS INCLUDING DIANIDROGALACTITOL AND ANALOGS TO TREAT NEOPLASTIC DISEASE AND CANCER STEM CELLS INCLUDING MULTIFORM GLIOBLASTOMA AND MEDULOBLASTOMA ” CROSS REFERENCES THE INVENTION THE INVENTION THE INVENTION DESCRIPTION OF THE DRAWINGS
DETAILS OF THE INVENTION vivo al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al. al.
al.
al.
al.
al. al.
al. al.
al. al. al.
al.
al.
al.
al.
al.
al.
tetranda c-erbB1 al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al. al.
al. al. al. al.
Science and Practice of Pharmacy
Science and Practice of Pharmacy and Controlled Release Drug Delivery Systems al.
al. al.
vitro AND METHODS:
live vitro THE INVENTION

权利要求:
Claims (46)
[1]
1. Method for producing a drug to improve efficacy and / or reduce the side effects of administering a substituted hexitol derivative for the treatment of GBM or medulloblastoma CHARACTERIZED by the fact that it comprises the steps of: (a) identifying by at least one factor or parameter associated with the efficacy and / or occurrence of side effects from the administration of the substituted hexitol derivative for the treatment of GBM or medulloblastoma; and (b) modify the factor or parameter to improve efficacy and / or reduce the side effects of administering the substituted hexitol derivative for the treatment of GBM or medulloblastoma to produce a drug to treat GBM or medulloblastoma, in which the derivative of Substituted hexitol is selected from the group consisting of dianhydrogalactitol, dianhydrogalactitol derivatives, diacetyldianhydrogalactitol, diacetyldianhydrogalactitol derivatives, dibromodulcitol and dibromodulcitol derivatives.
[2]
2. Method according to claim 1, CHARACTERIZED by the fact that the substituted hexitol derivative is dianhydrogalactitol.
[3]
3. Method, according to claim 1, CHARACTERIZED by the fact that the factor or parameter is selected from the group consisting of: (a) dose modification; (b) route of administration; (c) administration schedule; (d) indications for use; (e) selection of disease stage; (f) other indications; (g) patient selection; (h) patient / disease phenotype; (i) patient / disease genotype;
(j) pre / post-treatment preparation (k) toxicity management; (l) pharmacokinetic / pharmacodynamic monitoring; (m) drug combinations; (n) chemosensitization; (o) chemo-potentiation; (p) post-treatment patient management; (q) alternative therapeutic / medicinal support; (r) bulk drug enhancements; (s) diluent systems; (t) solvent systems; (u) excipients; (v) dosage forms; (w) packaging and dosing kits; (x) drug delivery systems; (y) conjugated forms of drug; (z) compound analogs; (aa) prodrugs; (ab) multi-drug systems; (ac) biotherapeutic intensification; (ad) modulation of biotherapeutic resistance; (ae) intensification of radiotherapy; (af) innovative mechanisms of action; and (ag) selective target cell population therapy.
[4]
4. Method, according to claim 1, CHARACTERIZED by the fact that the improvement is carried out through patient selection and in which the patient selection is at least a patient selection performed through a criterion selected from the group consisting of:
(i) selecting patients with a disease condition characterized by a high level of a metabolic enzyme selected from the group consisting of histone deacetylase and ornithine decarboxylase; (ii) selecting patients with a low or high susceptibility to a condition selected from the group consisting of thrombocytopenia and neutropenia; (iii) selecting patients intolerant of GI toxicities; (iv) select patients characterized by over- or under-expression of a gene selected from the group consisting of c-Jun, a GPCR, a signal transduction protein, VEGF, a prostate-specific gene and a protein kinase. (v) select patients characterized by carrying extra copies of the EGFR gene for GBM; (vi) select patients characterized by mutations in at least one gene selected from the group consisting of TP53, PDGFRA, IDH1 and NF1 for GBM; (vii) select patients characterized by methylation or lack of methylation of the MGMT gene promoter; (viii) selecting patients characterized by one or more deletions of the distal part of chromosome 17, distal to the p53 gene for medulloblastoma; and (ix) selecting patients characterized by a particular cytogenic subgroup selected from the group consisting of: (i) a 6q gain or amplification of MYC or MYCN; (ii) 17q gain or an i (17q) without 6q gain or MYC or MYCN amplification; and (iii) balanced 6q and 17q or 6q deletion for medulloblastoma; (x) select patients characterized for the existence of an IDH1 mutation; (xi) select patients characterized for the presence of wild-type gene IDH1;
(xii) select patients characterized for the presence of 1p / 19q codelection; (xiii) select patients characterized for the absence of a 1p / 19q codelection; (xiv) select patients characterized by an unmethylated promoter region of MGMT (O6-methylguanine methyltransferase); (xv) select patients characterized by a methylated promoter region of MGMT; (xvi) select patients characterized by high MGMT expression; (xvii) select patients characterized by low MGMT expression; and (xviii) select patients characterized by an EGFR mutation.
[5]
5. Method, according to claim 1, CHARACTERIZED by the fact that the improvement is carried out through analysis of disease or patient genotype and analysis of disease or patient genotype is a method of analysis of disease or patient genotype performed by a method selected from the group consisting of: (i) use of a diagnostic tool, a diagnostic technique, a diagnostic kit or a diagnostic assay to confirm a patient's particular genotype; (ii) use of a gene chip; (iii) use of gene expression analysis; (iv) use of simple nucleotide polymorphism (SNP) analysis; (v) measuring the level of a metabolite or a metabolic enzyme; (vi) determination of PDGFRA gene mutation; (vii) determination of IDH1 gene mutation;
(viii) determination of NF1 gene mutation; (ix) determining the copy number of the EGFR gene; (x) determination of the methylation status of the MGMT gene promoter; (xi) determination of classification of cytogenic subgroup (for medulloblastoma); (xii) determination of the existence of an IDH1 mutation; (xiii) determination of the existence of wild HDI1; (xiv) determination of the existence of a 1p / 19q codelection; (xv) determination of the absence of a 1p / 19q codelection; (xvi) determination of the existence of an unmethylated promoter region of the MGMT gene; (xvii) determination of the existence of a methylated promoter region of the MGMT gene; (xviii) determination of the existence of high MGMT expression; and (xix) determination of the existence of low MGMT expression.
[6]
6. Composition to improve efficacy and / or reduce side effects of drug therapy administered below the ideal level that employs a substituted hexitol derivative for the treatment of GBM or medulloblastoma CHARACTERIZED by the fact that it comprises an alternative selected from the group consisting of: (a) a therapeutically effective amount of a modified substituted hexitol derivative or a derivative, analog, prodrug of a substituted hexitol derivative or a modified substituted hexitol derivative, wherein the modified substituted hexitol derivative or the derivative, analogue or prodrug of the substituted hexitol derivative or modified substituted hexitol derivative has increased therapeutic efficacy or reduced side effects for the treatment of GBM or medulloblastoma compared to an unmodified substituted hexitol derivative;
(b) a composition comprising: (i) a therapeutically effective amount of a substituted hexitol derivative, a modified substituted hexitol derivative or a derivative, analog, prodrug of a substituted hexitol derivative or a modified substituted hexitol derivative ; and (ii) at least one additional therapeutic agent, therapeutic agent subjected to chemosensitization, therapeutic agent subjected to chemopotentiation, diluent, excipient, solvent system or drug delivery system, where the composition has increased therapeutic efficacy or reduced side effects for the treatment of GBM or medulloblastoma compared to an unmodified substituted hexitol derivative; (c) a therapeutically effective amount of a substituted hexitol derivative, a modified substituted hexitol derivative or a derivative, analog, prodrug of a substituted hexitol derivative or a modified substituted hexitol derivative that is incorporated into a dosage form , wherein the substituted hexitol derivative, the modified substituted hexitol derivative, or the pro-drug derivative of a substituted hexitol derivative or a modified substituted hexitol derivative incorporated into the dosage form has increased therapeutic efficacy or reduced side effects for the treatment of GBM or medulloblastoma compared to an unmodified substituted hexitol derivative; (d) a therapeutically effective amount of a substituted hexitol derivative, a modified substituted hexitol derivative or a derivative, analog, prodrug of a substituted hexitol derivative or a modified substituted hexitol derivative that is incorporated into a dosage kit and packaging, in which the substituted hexitol derivative, the modified substituted hexitol derivative or the derivative, analog, prodrug of a substituted hexitol derivative or a modified substituted hexitol derivative incorporated into the dosing and packaging kit has increased therapeutic efficacy or reduced side effects for the treatment of GBM or medulloblastoma compared to an unmodified substituted hexitol derivative; and (e) a therapeutically effective amount of a substituted hexitol derivative, a modified substituted hexitol derivative or a derivative, analog, prodrug of a substituted hexitol derivative or a modified substituted hexitol derivative that is subjected to an enhancement of bulk drug, in which a substituted hexitol derivative, a modified substituted hexitol derivative or a derivative, analog, prodrug of a substituted hexitol derivative or a modified substituted hexitol derivative subjected to bulk drug enhancement has increased therapeutic efficacy or reduced side effects for the treatment of GBM or medulloblastoma compared to an unmodified substituted hexitol derivative.
[7]
7. Composition according to claim 6, CHARACTERIZED by the fact that the unmodified substituted hexitol derivative is selected from the group consisting of dianhydrogalactitol, dianhydrogalactitol derivatives, diacetyldianhydrogalactitol, diacetyldianhydrogalactitol derivatives, dibromodulcitol and dibromodulcitol derivatives.
[8]
8. Composition according to claim 7, CHARACTERIZED by the fact that the unmodified substituted hexitol derivative is dianhydrogalactitol.
[9]
9. Composition according to claim 6, the composition being CHARACTERIZED in that it comprises a drug combination comprising: (a) a substituted hexitol derivative; and (b) an additional therapeutic agent selected from the group consisting of: (i) topoisomerase inhibitors; (ii) fraudulent nucleosides;
(iii) fraudulent nucleotides; (iv) thymidylate synthase inhibitors; (v) signal transduction inhibitors; (vi) platinum or cisplatin analogs; (vii) alkylating agents; (viii) anti-tubulin agents; (ix) antimetabolites; (x) berberine; (xi) apigenin; (xii) amonafide; (xiii) vinca alkaloids; (xiv) 5-fluorouracil; (xv) curcumin; (xvi) NF- (xvii) rosmarinic acid inhibitors; (xviii) mitoguazone; (xix) tetrandrine; (xx) tyrosine kinase inhibitors; (xxi) epidermal growth factor inhibitors; and (xxii) poly-ADP ribose polymerase (PARP) inhibitors.
[10]
10. Composition, according to claim 6, the composition being CHARACTERIZED by the fact that it comprises: (a) a substituted hexitol derivative; and (b) a therapeutic agent subjected to chemosensitization selected from the group consisting of: (i) topoisomerase inhibitors; (ii) fraudulent nucleosides; (iii) fraudulent nucleotides; (iv) thymidylate synthase inhibitors; (v) signal transduction inhibitors;
(vi) platinum or cisplatin analogs; (vii) alkylating agents; (viii) anti-tubulin agents; (ix) antimetabolites; (x) berberine; (xi) apigenin; (xii) amonafide; (xiii) vinca alkaloids; (xiv) 5-fluorouracil; (xv) curcumin; (xvi) NF- (xvii) rosmarinic acid inhibitors; (xviii) mitoguazone; and (xix) tetrandrine; (xx) tyrosine kinase inhibitors; (xxi) epidermal growth factor inhibitors; and (xxii) poly-ADP ribose polymerase (PARP) inhibitors; wherein the substituted hexitol derivative acts as a chemosensitizer.
[11]
11. Composition, according to claim 6, the composition being CHARACTERIZED by the fact that it comprises: (a) a substituted hexitol derivative; and (b) a therapeutic agent submitted to chemopotentiation selected from the group consisting of: (i) topoisomerase inhibitors; (ii) fraudulent nucleosides; (iii) fraudulent nucleotides; (iv) thymidylate synthase inhibitors; (v) signal transduction inhibitors; (vi) platinum or cisplatin analogs;
(vii) alkylating agents; (viii) anti-tubulin agents; (ix) antimetabolites; (x) berberine; (xi) apigenin; (xii) amonafide; (xiii) vinca alkaloids; (xiv) 5-fluorouracil; (xv) curcumin; (xvi) NF- (xvii) rosmarinic acid inhibitors; (xviii) mitoguazone; (xix) tetrandrine; (xx) biotherapeutics; (xxi) a tyrosine kinase inhibitor; (xxii) an EGFR inhibitor; and (xxiii) a PARP inhibitor; wherein the substituted hexitol derivative acts as a chemopotentiator.
[12]
12. Composition, according to claim 6, CHARACTERIZED by the fact that the substituted hexitol derivative is subjected to a bulk drug enhancement, in which the bulk drug enhancement is selected from the group consisting of: ( i) salt formation; (ii) preparation as a homogeneous crystal structure; (iii) preparation as a pure isomer; (iv) increased purity; (v) preparation with a lower residual solvent content; and (vi) preparation with a lower residual heavy metal content.
[13]
13. Composition, according to claim 6, the composition being CHARACTERIZED by the fact that it comprises a substituted hexitol derivative and a diluent, in which the diluent is selected from the group consisting of: (i) an emulsion ; (ii) dimethyl sulfoxide (DMSO); (iii) N-methylformamide (NMF) (iv) DMF; (v) ethanol; (vi) benzyl alcohol; (vii) water containing dextrose for injection; (viii) Cremofor; (ix) cyclodextrin; and (x) PEG.
[14]
14. Composition, according to claim 6, the composition being CHARACTERIZED by the fact that it comprises a substituted hexitol derivative and a solvent system, in which the solvent system is selected from the group consisting of: ( i) an emulsion; (ii) dimethyl sulfoxide (DMSO); (iii) N-methylformamide (NMF) (iv) DMF; (v) ethanol; (vi) benzyl alcohol; (vii) water containing dextrose for injection; (viii) Cremofor; (ix) cyclodextrin; and (x) PEG.
[15]
15. Composition, according to claim 6, the composition being CHARACTERIZED by the fact that it comprises a substituted hexitol derivative and an excipient, in which the excipient is selected from the group consisting of: (i) mannitol; (ii) albumin; (iii) EDTA; (iv) sodium bisulfite; (v) benzyl alcohol; (vi) a carbonate buffer; and (vii) a phosphate buffer.
[16]
16. Composition, according to claim 6, CHARACTERIZED by the fact that the substituted hexitol derivative is incorporated into a dosage form selected from the group consisting of: (i) tablets; (ii) capsules; (iii) topical gels; (iv) topical creams; (v) plasters; (vi) suppositories; and (vii) freeze-dried dosing loads.
[17]
17. Composition, according to claim 6, the composition being CHARACTERIZED by the fact that it comprises a substituted hexitol derivative and a drug distribution system selected from the group consisting of: (i) nanocrystals; (ii) bioerodible polymers; (iii) liposomes; (iv) slow-release injectable gels; and (v) microspheres.
[18]
18. Composition according to claim 6, CHARACTERIZED by the fact that the substituted hexitol derivative is present in the composition in a conjugated form of drug selected from the group consisting of: (i) a polymer system; (ii) polylactides; (iii) polyglycolides; (iv) amino acids; (v) peptides; and (vi) multivalent ligands.
[19]
19. Composition, according to claim 6, CHARACTERIZED by the fact that the therapeutic agent is a modified substituted hexitol derivative and the modification is selected from the group consisting of: (i) alteration of side chains to increase or decrease lipophilic capacity; (ii) adding additional chemical functionality to alter a property selected from the group consisting of reactivity, electronic affinity and binding capacity; and (iii) change in the shape of the salt.
[20]
20. Composition according to claim 6, the composition being CHARACTERIZED in that it comprises a substituted hexitol derivative and at least one additional therapeutic agent to form a multiple drug system, wherein the at least one therapeutic agent additional is selected from the group consisting of: (i) a multi-drug resistance inhibitor; (ii) a specific drug resistance inhibitor; (iii) a specific inhibitor of a selective enzyme; (iv) a signal transduction inhibitor; (v) a repair enzyme inhibitor; and
(vi) a topoisomerase inhibitor with no overlapping side effects.
[21]
21. Method for preparing a drug to treat a malignancy selected from the group consisting of glioblastoma multiforme and medulloblastoma, CHARACTERIZED by the fact that the drug comprises a therapeutically effective amount of a substituted hexitol derivative for administration to a patient who suffers from malignancy.
[22]
22. Method according to claim 21, CHARACTERIZED by the fact that the substituted hexitol derivative is selected from the group consisting of galactitols, substituted galactitols, dulcitols and substituted dulcitols.
[23]
23. Method, according to claim 22, CHARACTERIZED by the fact that the substituted hexitol derivative is selected from the group consisting of dianhydrogalactitol, dianhydrogalactitol derivatives, diacetildyanhydrogalactitol, diacetildyanhydrogalactitol derivatives, dibromodulcitol and dibromodulcitol derivatives.
[24]
24. Method according to claim 23, CHARACTERIZED by the fact that the substituted hexitol derivative is dianhydrogalactitol.
[25]
25. Method, according to claim 21, CHARACTERIZED by the fact that the malignancy is glioblastoma multiforme.
[26]
26. Method, according to claim 21, CHARACTERIZED by the fact that the malignancy is medulloblastoma.
[27]
27. Method according to claim 24, CHARACTERIZED by the fact that the therapeutically effective amount of dianhydrogalactitol is an amount of dianhydrogalactitol which results in a dosage of about 1 mg / m2 to about 40 mg / m2.
[28]
28. Method according to claim 27, CHARACTERIZED by the fact that the therapeutically effective amount of dianhydrogalactitol is an amount of dianhydrogalactitol that results in a dosage of about 5 mg / m2 to about 25 mg / m2.
[29]
29. Method, according to claim 21, CHARACTERIZED by the fact that the substituted hexitol derivative is administered by a route selected from the group consisting of intravenous and oral route.
[30]
30. Method according to claim 29, CHARACTERIZED by the fact that the substituted hexitol derivative is dianhydrogalactitol.
[31]
31. Method according to claim 29, CHARACTERIZED by the fact that the substituted hexitol derivative is administered intravenously.
[32]
32. Method, according to claim 21, CHARACTERIZED by the fact that the drug must be administered together with a therapeutically effective dose of ionizing radiation.
[33]
33. Method, according to claim 21, CHARACTERIZED by the fact that the drug must be administered together with a therapeutically effective amount of temozolomide.
[34]
34. Method according to claim 21, CHARACTERIZED by the fact that the drug must be administered together with a therapeutically effective amount of bevacizumab.
[35]
35. Method according to claim 21, CHARACTERIZED by the fact that the drug must be administered together with a therapeutically effective amount of a corticosteroid.
[36]
36. Method, according to claim 21, CHARACTERIZED by the fact that the drug must be administered together with at least one chemotherapeutic agent selected from the group consisting of lomustine, cisplatin, carboplatin, vincristine and cyclophosphamide.
[37]
37. Method, according to claim 21, CHARACTERIZED by the fact that dianhydrogalactitol substantially suppresses the growth of cancer stem cells (CSCs).
[38]
38. Method, according to claim 37, CHARACTERIZED by the fact that the suppression of cancer stem cell growth is at least 50%.
[39]
39. Method, according to claim 38, CHARACTERIZED by the fact that the suppression of the growth of cancer stem cells is at least 99%.
[40]
40. Method according to claim 24, CHARACTERIZED by the fact that dianhydrogalactitol is effective in suppressing the growth of cancer cells that have drug resistance triggered by O6-methylguanine-DNA methyltransferase (MGMT).
[41]
41. Method according to claim 24, CHARACTERIZED by the fact that dianhydrogalactitol is effective in suppressing the growth of temozolomide-resistant cancer cells.
[42]
42. Method according to claim 21, CHARACTERIZED by the fact that the drug must be administered together with a therapeutically effective amount of a tyrosine kinase inhibitor.
[43]
43. Method according to claim 21, CHARACTERIZED by the fact that the drug must be administered together with a therapeutically effective amount of an EGFR inhibitor.
[44]
44. Method according to claim 43, CHARACTERIZED by the fact that the EGFR inhibitor affects wild-type binding sites.
[45]
45. Method according to claim 43, CHARACTERIZED by the fact that the EGFR inhibitor affects mutated binding sites.
[46]
46. Method, according to claim 43, CHARACTERIZED by the fact that the EGFR inhibitor affects the EGFR III variant.

类似技术:

---

公开号 | 公开日 | 专利标题

---

BR112014017833A2|2021-03-23|USE OF REPLACED HEXITOLS INCLUDING DIANIDROGALACTITOL AND ANALOGS TO TREAT NEOPLASTIC DISEASE AND CANCER STEM CELLS INCLUDING MULTIFORM GLIOBLASTOMA AND MEDULOBLASTOMA

---

JP2013537552A5|2014-09-04|Compositions for improving the therapeutic efficacy of suboptimally administered compounds containing substituted hexitols such as dianhydrogalactitol and diacetyldianhydrogalactitol and methods for preparing medicaments containing substituted hexitols

---

AU2019240599A1|2019-10-17|Therapeutic benefit of suboptimally administered chemical compounds

---

US11026914B2|2021-06-08|Use of dianhydrogalactitol and analogs and derivatives thereof to treat recurrent malignant glioma or progressive secondary brain tumor

---

JP2016520622A5|2017-07-13|

---

US20180042938A1|2018-02-15|Novel compositions of combinations of non-covalent dna binding agents and anti-cancer and/or anti-inflammatory agents and their use in disease treatment

---

ES2414861T3|2013-07-23|Use of FTS for the treatment of malignant disorders

---

He et al.2017|Novel PARP1/2 inhibitor mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution

---

Pathak et al.2018|A designer bow-tie combination therapeutic platform: An approach to resistant cancer treatment by simultaneous delivery of cytotoxic and anti-inflammatory agents and radiation

---

Pang et al.2017|Design, synthesis, and biological evaluation of deuterated apalutamide with improved pharmacokinetic profiles

---

US20200360523A1|2020-11-19|Anti-cancer nuclear hormone receptor-targeting compounds

---

Kiaris et al.1999|Apoptosis versus necrosis: which should be the aim of cancer therapy?

---

US20080032966A1|2008-02-07|Small Molecule Inhibitors of Mrp1 and Other Multidrug Transporters

---

WO2013169600A1|2013-11-14|Veterinary use of dianhydrogalactitol, diacetyldianhydrogalactitol, and dibromodulcitol to treat malignancies

---

Arora et al.2021|Vinca Alkaloid Toxicity

---

RU2516027C2|2014-05-20|Combination of anticancer agents

---

Aregbe et al.2012|Population pharmacokinetic analysis of 17-dimethylaminoethylamino-17-demethoxygeldanamycin | in adult patients with solid tumors

---

BRPI0810697A2|2019-08-27|controlled release oral formulations of ion channel modulation compounds and methods related to arrhythmia prevention

---

Maurya et al.2022|Challenges and Recent Advances of Novel Chemical Inhibitors in Medulloblastoma Therapy

---

US20200306258A1|2020-10-01|Targeting the tlk1/nek1 axis in prostate cancer

---

NL2020004B1|2018-07-02|Treatment of diffuse intrinsic pontine glioma

---

US20210070803A1|2021-03-11|Modified peptides and associated methods of use

---

KR20190058568A|2019-05-29|Methods for treating ovarian cancer

---

Nalawade et al.2021|Olaparib an anticancer drug: A review

---

WO2021053523A1|2021-03-25|Compositions and methods to improve the therapeutic benefit of bis-dioxopiperazines

同族专利:

---

公开号 | 公开日

---

EP2804602A2|2014-11-26|

---

US20170266150A1|2017-09-21|

---

US10201521B2|2019-02-12|

---

JP2018109051A|2018-07-12|

---

EP2804602A4|2016-08-10|

---

US11234955B2|2022-02-01|

---

AU2013209394A1|2014-08-28|

---

MX367614B|2019-08-28|

---

US20190142783A1|2019-05-16|

---

SG11201404216TA|2014-08-28|

---

IL233722D0|2014-09-30|

---

AU2017251718B2|2019-05-23|

---

JP2015511936A|2015-04-23|

---

US20140377336A1|2014-12-25|

---

CN110711188A|2020-01-21|

---

US9687466B2|2017-06-27|

---

AU2019210610A1|2019-08-22|

---

IL233722A|2021-09-30|

---

WO2013110058A3|2015-01-22|

---

WO2013110058A2|2013-07-25|

---

CA2862706A1|2013-07-25|

---

AU2017251718A1|2017-11-09|

---

JP2021004244A|2021-01-14|

---

US20140221442A1|2014-08-07|

---

CN104427984A|2015-03-18|

---

MX2014008751A|2016-01-08|

---

KR20210048608A|2021-05-03|

---

IL285905D0|2021-09-30|

---

AU2019210610B2|2021-06-24|

---

KR20150018765A|2015-02-24|

---

CA2862706C|2021-08-03|

---

HK1208365A1|2016-03-04|

---

MX2019002917A|2019-07-18|

---

CL2014001917A1|2015-08-28|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US4801575A|1986-07-30|1989-01-31|The Regents Of The University Of California|Chimeric peptides for neuropeptide delivery through the blood-brain barrier|

---

US5294430A|1988-09-12|1994-03-15|University Of Rochester|Use of dithiocarbamates to treat myelosuppression|

---

US5035878A|1988-09-12|1991-07-30|University Of Rochester|Use of dithiocarbamates to counteract myelosuppression|

---

US5542935A|1989-12-22|1996-08-06|Imarx Pharmaceutical Corp.|Therapeutic delivery systems related applications|

---

US6287792B1|1991-06-17|2001-09-11|The Regents Of The University Of California|Drug delivery of antisense oligonucleotides and peptides to tissues in vivo and to cells using avidin-biotin technology|

---

US5789000A|1994-11-14|1998-08-04|Bionumerik Pharmaceuticals, Inc.|Sterile aqueous parenteral formulations of cis-diammine dichloro platinum|

---

US6011069A|1995-12-26|2000-01-04|Nisshin Flour Milling Co., Ltd.|Multidrug resistance inhibitors|

---

US5789700A|1996-01-19|1998-08-04|Young; J. Ronald|Grounding device with mounting brackets|

---

AU4543899A|1998-06-08|1999-12-30|Advanced Medicine, Inc.|Multibinding inhibitors of microsomal triglyceride transferase protein|

---

DK1104297T3|1998-07-09|2006-05-29|Cephalon Inc|Compositions for the treatment of chronic lymphocytic leukemia|

---

WO2001007084A1|1999-07-23|2001-02-01|Regents Of The University Of California|Anti-growth factor receptor avidin fusion proteins as universal vectors for drug delivery|

---

US6635677B2|1999-08-13|2003-10-21|Case Western Reserve University|Methoxyamine combinations in the treatment of cancer|

---

US6322828B1|1999-09-13|2001-11-27|Deseret Laboratories, Inc.|Process for manufacturing a pharmaceutical chewing gum|

---

US6372250B1|2000-04-25|2002-04-16|The Regents Of The University Of California|Non-invasive gene targeting to the brain|

---

US6921722B2|2000-05-30|2005-07-26|Ebara Corporation|Coating, modification and etching of substrate surface with particle beam irradiation of the same|

---

US20020037328A1|2000-06-01|2002-03-28|Brown Dennis M.|Hexitol compositions and uses thereof|

---

CN1116875C|2000-10-19|2003-08-06|南京振中生物工程有限公司|Taxusol-lipid composition and its preparing process|

---

ITMI20002358A1|2000-10-31|2002-05-01|Flavio Moroni|TIENO DERIVATIVES, 2, 3-C | ISOCHINOLIN-3-ONE AS INHIBITORS OF POLY POLYMERASE|

---

US7619005B2|2000-11-01|2009-11-17|Cognition Pharmaceuticals Llc|Methods for treating cognitive impairment in humans with Multiple Sclerosis|

---

DK1397155T3|2001-06-21|2015-12-07|Genentech Inc|Prolonged release formulation|

---

WO2003070823A2|2002-02-20|2003-08-28|The General Hospital Corporation|Conjugates comprising a biodegradable polymer and uses therefor|

---

US7101576B2|2002-04-12|2006-09-05|Elan Pharma International Limited|Nanoparticulate megestrol formulations|

---

US7388079B2|2002-11-27|2008-06-17|The Regents Of The University Of California|Delivery of pharmaceutical agents via the human insulin receptor|

---

NZ567952A|2003-03-24|2009-12-24|Sequoia Pharmaceuticals Inc|Long acting biologically active conjugates|

---

EP1462119A1|2003-03-24|2004-09-29|Schering AG|Modulators of the megalin-mediated uptake of radiotherapeutics and/or radiodiagnostics into kidney cells and their use in therapy and diagnostics|

---

ZA200507752B|2003-03-28|2007-01-31|Threshold Pharmaceuticals Inc|Compositions and methods for treating cancer|

---

WO2005023246A1|2003-09-04|2005-03-17|Aventis Pharmaceuticals Inc.|Substituted indoles as inhibitors of poly polymerase |

---

US20050181385A1|2003-09-22|2005-08-18|Linsley Peter S.|Synthetic lethal screen using RNA interference|

---

US7314886B2|2003-10-02|2008-01-01|Cephalon, Inc.|Tetrahydropyrano-indole derivatives|

---

HU0303313A2|2003-10-09|2005-07-28|Richter Gedeon Vegyészeti Gyár Rt.|Transdermal pharmaceutical compositions|

---

BR0318659A|2003-12-18|2006-11-28|Zoser B Salama|proline derivatives used as active pharmaceutical ingredients in the treatment of tumors|

---

CA2551524A1|2003-12-24|2005-07-21|Scios, Inc.|Treatment of malignant gliomas with tgf-beta inhibitors|

---

KR101184036B1|2004-06-30|2012-09-18|얀센 파마슈티카 엔.브이.|Substituted 2-alkyl qunazolinone derivatives as parp inhibitors|

---

EP2319847A3|2005-01-19|2012-06-20|Eisai Inc.|Diazabenzo[de]anthracen-3-one compounds and methods for inhibiting PARP|

---

US7705010B2|2005-02-22|2010-04-27|Cedars-Sinai Medical Center|Use of minoxidil sulfate as an anti-tumor drug|

---

WO2006110683A1|2005-04-11|2006-10-19|Abbott Laboratories|2-substituted-1h-benzimidazole-4-carboxamides are parp inhibitors|

---

EP1915340B1|2005-06-15|2013-08-07|Cardiome Pharma Corp.|Synthetic processes for the preparation of aminocyclohexyl ether compounds|

---

AT520979T|2005-08-24|2011-09-15|Squibb Bristol Myers Co|BIOMARKERS AND METHOD FOR DETERMINING SENSITIVITY AGAINST MODULATORS OF EGF RECEPTORS|

---

US8124095B2|2005-10-07|2012-02-28|Armagen Technologies, Inc.|Fusion proteins for delivery of erythropoietin to the CNS|

---

US8324175B2|2006-02-16|2012-12-04|Young Hee Ko|Compositions and methods for the treatment of cancer|

---

JP5284955B2|2006-06-20|2013-09-11|アボット・ラボラトリーズ|Pyrazoloquinazolinones as PARP inhibitors|

---

PT2061765E|2006-09-01|2015-02-06|Senhwa Biosciences Inc|Serine-threonine protein kinase and parp modulators|

---

US8277807B2|2006-10-12|2012-10-02|Astex Therapeutics Limited|Pharmaceutical combinations|

---

UY30639A1|2006-10-17|2008-05-31|Kudos Pharm Ltd|SUBSTITUTED DERIVATIVES OF 2H-FTALAZIN-1-ONA, ITS CRYSTAL FORMS, PREPARATION PROCESS AND APPLICATIONS|

---

US8349822B2|2007-02-27|2013-01-08|Cedars-Sinai Medical Center|Treatment of cancer with bio and chemotherapy|

---

US20100121049A1|2007-02-28|2010-05-13|Inotek Pharmaceuticals Corporation|Indenoisoquinolinone analogs and methods of use thereof|

---

CA2679943A1|2007-03-02|2008-09-12|Board Of Regents, The University Of Texas System|Multigene assay to predict outcome in an individual with glioblastoma|

---

DK2134691T3|2007-03-08|2012-05-07|Janssen Pharmaceutica Nv|QUINOLINONDERIVATIVES AS PARP AND TANK INHIBITORS|

---

TWI448284B|2007-04-24|2014-08-11|Theravance Inc|Dual-acting antihypertensive agents|

---

GB0710536D0|2007-06-01|2007-07-11|Veritron Ltd|Plant extract and its therapeutic use|

---

JP5282037B2|2007-08-10|2013-09-04|田辺三菱製薬株式会社|Novel isoquinoline compound salt and crystal thereof|

---

WO2009063244A1|2007-11-15|2009-05-22|Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A.|Pyridazinone derivatives as parp inhibitors|

---

EP2224804A4|2007-12-07|2011-06-01|Bipar Sciences Inc|Treatment of cancer with combinations of topoisomerase inhibitors and parp inhibitors|

---

JP2011511078A|2008-02-06|2011-04-07|レアドトヘラペウトイクス，インコーポレーテッド|Benzoxazole carboxamide inhibitors of poly polymerase |

---

US20090318561A1|2008-06-23|2009-12-24|Mutual Pharmaceutical Company, Inc.|Colchicine products, method of manufacture, and methods of use|

---

US8338477B2|2008-07-11|2012-12-25|Neumedics|Tetracycline derivatives with reduced antibiotic activity and neuroprotective benefits|

---

ES2532732T3|2008-07-29|2015-03-31|Nerviano Medical Sciences S.R.L.|Use of a CDK inhibitor for the treatment of glioma|

---

MX2011001328A|2008-08-06|2011-04-04|Biomarin Pharm Inc|Dihydropyridophthalazinone inhibitors of polypolymera se .|

---

ES2536465T3|2008-10-01|2015-05-25|Immatics Biotechnologies Gmbh|Composition of tumor-associated and cancer-related peptides for the treatment of glioblastoma and other cancers|

---

KR101779137B1|2009-01-23|2017-09-18|다케다 야쿠힌 고교 가부시키가이샤|Polypolymerase inhibitors|

---

US8323270B2|2009-10-19|2012-12-04|Pharmaco-Kinesis Corporation|Enhanced method for delivering bevacizumab into a brain tumor using an implanted magnetic breather pump|

---

WO2012024367A2|2010-08-18|2012-02-23|Del Mar Pharmaceuticals|Compositions and methods to improve the therapeutic benefit of suboptimally administered chemical compounds including substituted hexitols such as dianhydrogalactitol and diacetyldianhydrogalactitol|

---

WO2014081405A2|2011-08-17|2014-05-30|Dennis Brown|Compositions and methods to improve the therapeutic benefit of suboptimally administered chemical compounds including substituted hexitols such as dibromodulcitol|

---

CA2862706C|2012-01-20|2021-08-03|Dennis Brown|Use of substituted hexitols including dianhydrogalactitol and analogs to treat neoplastic disease and cancer stem cells including glioblastoma multforme and medulloblastoma|

---

US9901563B2|2013-03-11|2018-02-27|Delmar Pharmaceuticals, Inc.|Compositions to improve the therapeutic benefit of suboptimally administered chemical compounds including substituted hexitols such as dianhydrogalactitol and diacetyldianhydrogalactitol|

---

CN203476250U|2013-04-08|2014-03-12|山特维克知识产权股份有限公司|Drilling-rod hanger|WO2014081405A2|2011-08-17|2014-05-30|Dennis Brown|Compositions and methods to improve the therapeutic benefit of suboptimally administered chemical compounds including substituted hexitols such as dibromodulcitol|

---

CA2862706C|2012-01-20|2021-08-03|Dennis Brown|Use of substituted hexitols including dianhydrogalactitol and analogs to treat neoplastic disease and cancer stem cells including glioblastoma multforme and medulloblastoma|

---

WO2014179528A2|2013-05-01|2014-11-06|Brown Dennis M|Compositions and methods to improve the therapeutic benefit of suboptimally administered chemical compounds including substituted naphthalimides such as amonafide for the treatment of immunological, metabolic, infectious, and benign or neoplastic hyperproliferative disease conditions|

---

TW201536278A|2013-05-31|2015-10-01|Del Mar Pharmaceuticals|Use of dianhydrogalactitol and analogs and derivatives thereof to treat recurrent malignant glioma or progressive secondary brain tumor|

---

CA2946538A1|2014-04-04|2015-10-08|Del Mar Pharmaceuticals|Use of dianhydrogalactitol and analogs or derivatives thereof to treat non-small-cell carcinoma of the lung and ovarian cancer|

---

AU2015346598B2|2014-11-10|2020-09-03|Del Mar Pharmaceuticals|Dianhydrogalactitol together with radiation to treat non-small-cell carcinoma of the lung and glioblastoma multiforme|

---

US9375478B1|2015-01-30|2016-06-28|Par Pharmaceutical, Inc.|Vasopressin formulations for use in treatment of hypotension|

---

US9744209B2|2015-01-30|2017-08-29|Par Pharmaceutical, Inc.|Vasopressin formulations for use in treatment of hypotension|

---

US9937223B2|2015-01-30|2018-04-10|Par Pharmaceutical, Inc.|Vasopressin formulations for use in treatment of hypotension|

---

US9925233B2|2015-01-30|2018-03-27|Par Pharmaceutical, Inc.|Vasopressin formulations for use in treatment of hypotension|

---

US9750785B2|2015-01-30|2017-09-05|Par Pharmaceutical, Inc.|Vasopressin formulations for use in treatment of hypotension|

---

US9687526B2|2015-01-30|2017-06-27|Par Pharmaceutical, Inc.|Vasopressin formulations for use in treatment of hypotension|

---

US10654783B2|2015-06-16|2020-05-19|Targent, Llc|Crystalline polymorphs of 1,6-dibromo-1,6-dideoxy-dulcitol|

---

TW201722421A|2015-09-10|2017-07-01|德瑪製藥公司|Use of dianhydrogalactitol or derivatives and analogs thereof for treatment of non-small-cell lung carcinoma, glioblastoma, and ovarian carcinoma by induction of DNA damage and stalling of cell cycle|

---

WO2017075052A1|2015-10-28|2017-05-04|Delmar Pharmaceuticals, Inc.|Use of dianhydrogalactitol or derivatives or analogs thereof for treatment of pediatric central nervous system malignancies|

---

CN105663072B|2016-02-23|2018-09-28|广西梧州制药（集团）股份有限公司|A kind of dianhydrogalactitol thin membrane coated tablet and preparation method thereof|

---

CN105663075B|2016-02-23|2018-09-14|广西梧州制药（集团）股份有限公司|A kind of mitolactol enteric coatel tablets and preparation method thereof|

---

CN105663076A|2016-02-23|2016-06-15|广西梧州制药（集团）股份有限公司|Dianhydrodulcitol thin membrane coated tablet with rapid effect taking and good damp-proof functions and preparation method thereof|

---

CN105663060B|2016-02-23|2018-08-14|广西梧州制药（集团）股份有限公司|A kind of dianhydrogalactitol lipidosome freeze-dried injection and preparation method thereof|

---

US20190133980A1|2016-06-02|2019-05-09|Yale University|Compositions and methods for targeting and treating homologous recombination-deficient tumors|

---

US20200062839A1|2017-05-01|2020-02-27|Del Mar PharmaceuticalsLtd.|Use of dianhydrogalactitol or analogs and derivatives in combination with vegf inhibitors to treat cancer|

---

WO2019106424A1|2017-12-01|2019-06-06|Del Mar PharmaceuticalsLimited|Dianhydrogalactitol for the treatment of diffuse intrinsic pontine gliomas|

---

KR102130501B1|2019-06-12|2020-07-07|브렉소젠 주식회사|Composition For Promoting Production of Stem Cell-derived Exosomes and Increasing Stemness comprising Tetrandrine|

---

CN110283047A|2019-07-11|2019-09-27|夏永刚|The synthetic method of monosaccharide moieties methylation Alday alcohol acetic ester|

法律状态:
2018-01-16| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|

---

2018-03-27| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

---

2019-04-24| B07E| Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]|Free format text: NOTIFICACAO DE ANUENCIA RELACIONADA COM O ART 229 DA LPI |

---

2019-08-20| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

优先权:

---

申请号 | 申请日 | 专利标题

---

US201261589029P| true| 2012-01-20|2012-01-20|

---

US61/589,029|2012-01-20|

---

PCT/US2013/022505|WO2013110058A2|2012-01-20|2013-01-22|Use of substituted hexitols including dianhydrogalactitol and analogs to treat neoplastic disease and cancer stem cells including glioblastoma multforme and medulloblastoma|

---