Patents by Inventor Alberto Gabizon
Alberto Gabizon has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20220087975Abstract: A liposome composition comprising a lipophilic prodrug of mitomycin C having an improved pharmacokinetic profile is described. A method for preparing the composition with a solvent system comprised of ethanol and tertiary butanol mixed at an adequate ratio is also described. In an embodiment, the liposome composition is a population of lipid nanoparticles and a pharmaceutically acceptable vehicle, wherein the population of lipid nanoparticles is comprised of a first fraction of spherical liposomes and a second fraction of rod-shaped lipid nanoparticles, where the second fraction is less than about 15% of the population of lipid nanoparticles.Type: ApplicationFiled: January 11, 2020Publication date: March 24, 2022Inventors: Alberto Gabizon, Patricia Ohana, Hilary Shmeeda
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Patent number: 10617672Abstract: A composition comprising liposomes comprising a lipid layer defining an internal aqueous compartment, an anthracycline drug entrapped in the internal aqueous phase and mitomycin C prodrug incorporated into the lipid layer is described.Type: GrantFiled: October 14, 2016Date of Patent: April 14, 2020Assignees: Lipomedix Pharmaceuticals Ltd., Shaare Zedek Scientific Ltd.Inventors: Alberto Gabizon, Patricia Ohana, Hilary Shmeeda
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Publication number: 20180296529Abstract: A composition comprising liposomes comprising a lipid layer defining an internal aqueous compartment, an anthracycline drug entrapped in the internal aqueous phase and mitomycin C prodrug incorporated into the lipid layer is described.Type: ApplicationFiled: October 14, 2016Publication date: October 18, 2018Inventors: Alberto GABIZON, Patricia OHANA, Hilary SHMEEDA
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Patent number: 10085940Abstract: The present disclosure provides liposomes comprising a membrane and an intraliposomal aqueous water phase, the membrane comprising at least one liposome forming lipid and the intraliposomal aqueous water phase comprises a salt of a bisphosphonate together with an amphipathic weak base agent (PLAD). An example of a liposome is one comprising co encapsulated in the intraliposomal aqueous water phase N-containing bisphosphonate, such as alendronate, and an anthracycline such as doxorubicin which was shown to increase survival as compared to Doxil or to administrations of liposomal alendronate (PLA) and Doxil (separate liposomes). Such liposomes may carry a targeting moiety exposed at the liposome's outer surface, for example, conjugate of folic acid as a targeting moiety to folate receptor (FT-PLAD). Also provided by the present disclosure is a method of preparing the liposomes and methods of use of the liposomes, at times, in combination with additional active ingredients, such as ?? T-cells.Type: GrantFiled: July 12, 2012Date of Patent: October 2, 2018Assignees: YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD., KINGS COLLEGE LONDON, SHAARE ZEDEK SCIENTIFIC LTD.Inventors: Alberto A. Gabizon, Yechezkel Barenholz, Hilary Shmeeda, John Maher, Ana Catarina Parente Pereira
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Patent number: 10080807Abstract: The present invention is based on a finding of an unexpected synergistic and safe combination of antineoplastic agents which when administered in combination provides greater efficacy than the single agents alone. Accordingly, a method of treating neoplasia in a subject in need of treatment is provided, by administering to the subject an amount of a prodrug of mitomycin C that yields a therapeutically effective amount of mitomycin C, in combination with an amount of a chemotherapeutic agent. In one embodiment, the prodrug of mitomycin C is a liposomal-prodrug of mitomycin C. Together, the prodrug of mitomycin C and chemotherapeutic agent provide a synergistic antineoplastic effect.Type: GrantFiled: June 9, 2015Date of Patent: September 25, 2018Assignees: Lipomedix Pharmaceuticals Ltd., Shaare Zedek Scientific Ltd.Inventors: Alberto Gabizon, Patricia Ohana, Hilary Shmeeda
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Patent number: 9937261Abstract: A method of treating neoplasia in a subject in need of treatment is provided by administering to the subject an amount of a prodrug of mitomycin C that yields a therapeutically effective amount of mitomycin C, in combination with radiation therapy. In one embodiment, the prodrug of mitomycin C is a liposomal-prodrug of mitomycin C. Together, the prodrug of mitomycin C and radiation therapy provide a synergistic antineoplastic effect.Type: GrantFiled: June 9, 2015Date of Patent: April 10, 2018Assignees: Lipomedix Pharmaceuticals Ltd., The University of North Carolina at Chapel HillInventors: Alberto Gabizon, Patricia Ohana, Andrew Wang
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Publication number: 20180071253Abstract: The present disclosure related to a method of treating bladder cancer in a subject in need of treatment, by administering to the subject an amount of a prodrug of mitomycin C that yields a therapeutically effective amount of mitomycin C. In one embodiment, the prodrug of mitomycin C is a liposomal-prodrug of mitomycin C. In another embodiment, the liposomal-prodrug of mitomycin C is a folate-targeted liposomal-prodrug of mitomycin C.Type: ApplicationFiled: March 17, 2016Publication date: March 15, 2018Inventors: Alberto Gabizon, Patricia Ohana
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Publication number: 20170119895Abstract: A method of treating neoplasia in a subject in need of treatment is provided by administering to the subject an amount of a prodrug of mitomycin C that yields a therapeutically effective amount of mitomycin C, in combination with radiation therapy. In one embodiment, the prodrug of mitomycin C is a liposomal-prodrug of mitomycin C. Together, the prodrug of mitomycin C and radiation therapy provide a synergistic antineoplastic effect.Type: ApplicationFiled: June 9, 2015Publication date: May 4, 2017Inventors: Alberto Gabizon, Patricia Ohana, Andrew Wang
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Publication number: 20170112807Abstract: The present invention is based on a finding of an unexpected synergistic and safe combination of antineoplastic agents which when administered in combination provides greater efficacy than the single agents alone. Accordingly, a method of treating neoplasia in a subject in need of treatment is provided, by administering to the subject an amount of a prodrug of mitomycin C that yields a therapeutically effective amount of mitomycin C, in combination with an amount of a chemotherapeutic agent. In one embodiment, the prodrug of mitomycin C is a liposomal-prodrug of mitomycin C. Together, the prodrug of mitomycin C and chemotherapeutic agent provide a synergistic antineoplastic effect.Type: ApplicationFiled: June 9, 2015Publication date: April 27, 2017Inventors: Alberto Gabizon, Patricia Ohana, Hilary Shmeeda
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Publication number: 20150093434Abstract: Provided are pharmaceutical compositions including a glucocorticoid or glucocorticoid derivative stably encapsulated in a liposome. The glucocorticoid or glucocorticoid derivative is selected from an amphipathic weak base glucocorticoid or glucocorticoid derivative having a pKa equal or below 11 and a logD at pH 7 in the range between ?2.5 and 1.5; or an amphipathic weak acid GC or GC derivative having a pKa above 3.5 and a logD at pH 7 in the range between ?2.5 and 1.5. The therapeutic effect of the pharmaceutical composition of the invention was exhibited in vivo with appropriate models of multiple sclerosis and cancer.Type: ApplicationFiled: December 4, 2014Publication date: April 2, 2015Applicant: YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERSUSALEMInventors: Yechezkel BARENHOLZ, Alberto A. GABIZON, Yuval AVNIR
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Patent number: 8932627Abstract: The present invention provides pharmaceutical compositions comprising a glucocorticoid or glucocorticoid derivative stably encapsulated in a liposome. The glucocorticoid or glucocorticoid derivative is selected from an amphipathic weak base glucocorticoid or glucocorticoid derivative having a pKa equal or below 11 and a logD at pH 7 in the range between ?2.5 and 1.5; or an amphipathic weak acid GC or GC derivative having a pKa above 3.5 and a logD at pH 7 in the range between ?2.5 and 1.5. The therapeutic effect of the pharmaceutical composition of the invention was exhibited in vivo with appropriate models of multiple sclerosis and cancer.Type: GrantFiled: September 11, 2005Date of Patent: January 13, 2015Assignee: Yissum Research Development Company of the Hebrew University of JerusalemInventors: Yechezkel Barenholz, Alberto A. Gabizon, Yuval Avnir
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Publication number: 20140328899Abstract: The present disclosure provides liposomes comprising a membrane and an intraliposomal aqueous water phase, the membrane comprising at least one liposome forming lipid and the intraliposomal aqueous water phase comprises a salt of a bisphosphonate together with an amphipathic weak base agent (PLAD). An example of a liposome is one comprising co encapsulated in the intraliposomal aqueous water phase N-containing bisphosphonate, such as alendronate, and an anthracycline such as doxorubicin which was shown to increase survival as compared to Doxil or to administrations of liposomal alendronate (PLA) and Doxil (separate liposomes). Such liposomes may carry a targeting moiety exposed at the liposome's outer surface, for example, conjugate of folic acid as a targeting moiety to folate receptor (FT-PLAD). Also provided by the present disclosure is a method of preparing the liposomes and methods of use of the liposomes, at times, in combination with additional active ingredients, such as ?? T-cells.Type: ApplicationFiled: July 7, 2012Publication date: November 6, 2014Applicants: SHAARE ZEDEK MEDICAL CENTER, YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD.Inventors: Alberto A. Gabizon, Yechezkel Barenholz, Hilary Shmeeda
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Publication number: 20120288558Abstract: An embodiment of the present invention comprises a method of treating malignancies in a subject in need of treatment comprising administering to the subject a high loading dose of a pegylated liposomal doxorubicin (PLD) in an initial cycle, followed by a reduced dose in a second cycle, wherein the second cycle reduced dose is in the range of 20% to 50%, preferably 50%, of the initial loading dose, and thereafter one or more maintenance doses in further cycles. The interval between dose cycles is in the range of about three-to-four weeks, preferably about four weeks. The initial loading dose is in the range of between the maximum tolerated dose (MTD) and the recommended dose, preferably the MTD (for instance, in the range of about 70 mg/m2 to 50 mg/m2, preferably 60 mg/m2). The one or more maintenance doses are in the range of about 40 mg/m2 to 50 mg/m2, preferably 45 mg/m2).Type: ApplicationFiled: July 18, 2012Publication date: November 15, 2012Inventor: Alberto A. Gabizon
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Publication number: 20120100206Abstract: The present is based on the finding that folate targeted liposomal alendronate (FT-AL-L) was significantly more potent against two tested cancer cell lines than the free alendronate (AL) or the non-targeted liposomal alendronate (AL-L), as observed by the increased cytotoxicity of the folate targeted liposomal alendronate. Thus, the present disclosure provides targeted liposomes comprising a membrane and an intraliposomal core, the membrane comprising at least one liposome forming lipid and a targeting moiety, such as folate, exposed at the membrane's outer surface; and the intraliposomal core comprising encapsulated therein least one N-containing bisphosphonate. Also provided by the present disclosure are methods of use of the targeted liposomes such as for the treatment of a disease or disorder.Type: ApplicationFiled: June 10, 2010Publication date: April 26, 2012Applicant: Yissum Research Development Company of the Hebrew University of Jerusalem, Ltd.Inventors: Hilary Shmeeda, Alberto A. Gabizon
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Publication number: 20100297216Abstract: An embodiment of the present invention comprises a method of treating malignancies in a subject in need of treatment comprising administering to the subject a high loading dose of a pegylated liposomal doxorubicin (PLD) in an initial cycle, followed by a reduced dose in a second cycle, wherein the second cycle reduced dose is in the range of 20% to 50%, preferably 50%, of the initial loading dose, and thereafter one or more maintenance doses in further cycles. The interval between dose cycles is in the range of about three-to-four weeks, preferably about four weeks. The initial loading dose is in the range of between the maximum tolerated dose (MTD) and the recommended dose, preferably the MTD (for instance, in the range of about 70 mg/m2 to 50 mg/m2, preferably 60 mg/m2). The one or more maintenance doses are in the range of about 40 mg/m2 to 50 mg/m2, preferably 45 mg/m2).Type: ApplicationFiled: January 21, 2007Publication date: November 25, 2010Inventor: Alberto A. Gabizon
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Publication number: 20100247629Abstract: A liposome composition having a protonatable therapeutic agent entrapped in the form of a salt with a glucuronate anion is disclosed. Methods for preparing the composition using an ammonium ion transmembrane gradient having glucuronate as the counterion are also disclosed. In one embodiment where the protonatable agent is doxorubicin, the method of the invention has comparable loading efficiency, faster release rate, without compromising the therapeutic efficacy compared to loading with an ammonium ion gradient having sulfate as the counterion.Type: ApplicationFiled: June 9, 2010Publication date: September 30, 2010Inventors: Alberto A. Gabizon, Yechezkel Barenholz
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Publication number: 20080058294Abstract: The present invention provides pharmaceutical compositions comprising a glucocorticoid or glucocorticoid derivative stably encapsulated in a liposome. The glucocorticoid or glucocorticoid derivative is selected from an amphipathic weak base glucocorticoid or glucocorticoid derivative having a pKa equal or below 11 and a logD at pH 7 in the range between ?2.5 and 1.5; or an amphipathic weak acid GC or GC derivative having a pKa above 3.5 and a logD at pH 7 in the range between ?2.5 and 1.5. The therapeutic effect of the pharmaceutical composition of the invention was exhibited in vivo with appropriate models of multiple sclerosis and cancer.Type: ApplicationFiled: September 11, 2005Publication date: March 6, 2008Applicant: Yissum Research Development Company of the Hebrew University of JerusalemInventors: Yechezkel Barenholz, Alberto Gabizon, Yuval Avnir
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Patent number: 7303760Abstract: Methods for administering mitomycin C to a multi-drug resistant cell and for reducing the toxicity of the compound are described. In the methods, mitoymic C is provided in the form of a prodrug conjugate, where the drug is linked to a hydrophobic moiety, such as a lipid, through a cleavable dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of mitomycin C in its original form. The linkage is stable under nonreducing conditions. The prodrug conjugate can be incorporated into liposomes for administration in vivo and release of mitomycin C in response to endogenous in vivo reducing conditions or in response to administration of an exogenous reducing agent.Type: GrantFiled: November 14, 2003Date of Patent: December 4, 2007Assignees: Alza Corporation, Yissum Research Development Company of the Hebrew University of JerusalemInventors: Samuel Zalipsky, Alberto Gabizon
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Patent number: 7276248Abstract: Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.Type: GrantFiled: August 12, 2005Date of Patent: October 2, 2007Assignee: ALZA CorporationInventors: Samuel Zalipsky, Alberto A. Gabizon
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Publication number: 20060062842Abstract: A composition for administration of a therapeutic compound to a multi-drug resistant cell in a person suffering from a drug-resistant cancer is described. The composition is composed of a carrier molecule and a folate targeting ligand, which is covalently attached to the carrier, and the therapeutic compound. In one preferred embodiment, the carrier is a liposome having a surface coating of hydrophilic polymer chains where a folate ligand is attached to the free distal end of at least a portion of the hydrophilic polymer chains, and the therapeutic agent is entrapped in the liposomes. The composition is effective to achieve accumulation of the therapeutic compound in the cell in an amount sufficient to be cytotoxic. Also described are methods for administering a therapeutic compound to a person suffering from a multi-drug resistant condition.Type: ApplicationFiled: September 6, 2005Publication date: March 23, 2006Inventors: Alberto Gabizon, Samuel Zalipsky, Dorit Goren-Rubel, Aviva Horowitz