Eggehard J Holler

US Patent:

8309614, Nov 13, 2012

Filed:

Apr 10, 2009

Appl. No.:

12/935110

Inventors:

Hui Ding - Los Angeles CA, US
Julia Y. Ljubimova - Studio City CA, US
Eggehard Holler - Los Angeles CA, US
Keith L. Black - Los Angeles CA, US

Assignee:

Cedars-Sinai Medical Center - Los Angeles CA

International Classification:

A61K 47/14
C07H 21/02

US Classification:

514772, 536 245, 977704, 977906

Abstract:

The invention relates to the use of Polycefin-LLL nanoconjugate as a means of cytoplasmic delivery of drugs. In one embodiment, the present invention provides a drug delivery molecule, comprising a polymerized carboxylic acid molecular scaffold covalently linked to L-leucylleucylleucine. In another embodiment, the Polycefin-LLL includes drug antisense morpholino oligos, targeting antibodies, and a pH-sensitive endosome escape unit. In addition, the drug could be siRNA, microRNA, and aptamer.

US Patent:

8562964, Oct 22, 2013

Filed:

Apr 29, 2011

Appl. No.:

13/097364

Inventors:

Julia Y. Ljubimova - Studio City CA, US
Keith Black - Los Angeles CA, US
Eggehard Holler - Los Angeles CA, US

Assignee:

Cedars-Sinai Medical Center - Los Angeles CA
Arrogene Nanotechnology, Inc. - Los Angeles CA

International Classification:

A61K 47/48
A61P 35/00
C08F 8/30

US Classification:

424 7817, 525 541, 525 542

Abstract:

A structured drug system that is useful for delivering a drug payload to a specific tissue or cell type is disclosed. The system is based on purified polymalic acid. This polymer isolated from natural sources is biocompatible, biodegradable and of very low toxicity. The polymer is extremely water soluble and contains a large number of free carboxyl groups which can used to attach a number of different active molecules. In the examples disclosed N-hydroxysuccinimide esters of the carboxyl groups are used to attach such molecules. The active molecules include monoclonal antibodies to promote specific cellular uptake and specific pro-drugs such as antisense nucleic acids designed to modify the cellular metabolism of a target cell. The pro-drugs are advantageously linked by a somewhat labile bond so that they will be released under specific conditions. In addition, the system contains amide-linked valine to encourage membrane disruption under lysosomal conditions.

US Patent:

20120258049, Oct 11, 2012

Filed:

Apr 6, 2012

Appl. No.:

13/441599

Inventors:

Keith L. Black - Los Angeles CA, US
Julia Ljubimova - Studio City CA, US
Alexander Ljubimov - Studio City CA, US
Eggehard Holler - Los Angeles CA, US

Assignee:

CEDARS-SINAI MEDICAL CENTER - Los Angeles CA

International Classification:

A61B 5/055
C08G 63/91

US Classification:

424 934, 525 541

Abstract:

Nanoconjugates that include a polymalic-based molecular scaffold with one or more imaging moiety and one or more targeting modules attached to the scaffold are provided. Methods of targeting a diseased cell or a diseased tissue in a subject by administering the nanoconjugate are described. Methods of synthesizing the nanoconjugate are also provided.

US Patent:

20120328555, Dec 27, 2012

Filed:

Dec 10, 2010

Appl. No.:

13/513145

Inventors:

Rameshwar Patil - Los Angeles CA, US
Eggehard Holler - Los Angeles CA, US
Keith L. Black - Los Angeles CA, US
Julia Y. Ljubimova - Studio City CA, US

Assignee:

CEDARS-SINAI MEDICAL CENTER - Los Angeles CA

International Classification:

A61K 47/48
C08G 63/91
A61P 31/00

US Classification:

424 7817, 525 541, 525419

Abstract:

The present invention relates to methods of drug delivery for the treatment of a condition or disease, such as cancer. In one embodiment, the invention provides a method of preparing a multifunctional nanoconjugate of temozolomide (TMZ) by conjugating TMZ in its hydrazide form to a polymalic acid platform. In another embodiment, the polymalic acid platform is conjugated to a monoclonal antibody to transferrin receptor, a trileucine (LLL) moiety, and/or a polyethylene glycol (PEG) moiety. The present invention relates to methods of drug delivery for the treatment of a condition or disease, such as cancer. In one embodiment, the invention provides a method of preparing a multifunctional nanoconjugate of temozolomide (TMZ) by conjugating TMZ in its hydrazide form to a polymalic acid platform. In another embodiment, the polymalic acid platform is conjugated to a monoclonal antibody to transferrin receptor, a trileucine (LLL) moiety, and/or a polyethylene glycol (PEG) moiety.

US Patent:

20130084261, Apr 4, 2013

Filed:

Oct 8, 2012

Appl. No.:

13/646947

Inventors:

Julia Y. Ljubimova - Studio City CA, US
Eggehard Holler - Los Angeles CA, US
Keith L. Black - Los Angeles CA, US

Assignee:

CEDARS-SINAI MEDICAL CENTER - Los Angeles CA

International Classification:

A61K 47/48
A61K 31/711

US Classification:

424 7817

Abstract:

The invention relates to the use of Polycefin-LLL nanoconjugate as a means of cytoplasmic delivery of drugs. In one embodiment, the present invention provides a drug delivery molecule, comprising a polymerized carboxylic acid molecular scaffold covalently linked to L-leucylleucylleucine. In another embodiment, the Polycefin-LLL includes drug antisense morpholino oligos, targeting antibodies, and a pH-sensitive endosome escape unit. In addition, the drug could be siRNA, microRNA, and aptamer.

US Patent:

20140039125, Feb 6, 2014

Filed:

Sep 19, 2013

Appl. No.:

14/031561

Inventors:

Eggehard Holler - Los Angeles CA, US

Assignee:

Arrogene Nanotechnology, Inc. - Los Angeles CA
Cedars-Sinai Medical Center - Los Angeles CA

International Classification:

A61K 47/48

US Classification:

525 541

Abstract:

A drug delivery system for delivering a drug payload to a specific tissue or cell type is disclosed. The system includes a polymalic acid molecular scaffold which can be used for attaching a plurality of molecular modules. Molecular modules include targeting antibodies for promoting cellular uptake by a target cell, and pro-drugs for altering cellular metabolism, for example, a pro-drug that alters expression of protein kinase CK2.

US Patent:

20200155593, May 21, 2020

Filed:

Jan 27, 2020

Appl. No.:

16/773769

Inventors:

- LOS ANGELES CA, US
Hui Ding - Los Angeles CA, US
Eggehard Holler - Los Angeles CA, US
Keith L. Black - Los Angeles CA, US
Julia Y. Ljubimova - Studio City CA, US

International Classification:

A61K 31/713
C07K 16/32
C07K 16/28

Abstract:

Nanobiopolymeric conjugates based on biodegradable, non-toxic and non-immunogenic poly (β-L-malic acid) PMLA covalently linked to molecular modules that include morpholino antisense oligonucleotides (AONa), an siRNA or an antibody specific for an oncogenic protein in a cancer cell, and an antibody specific for a transferrin receptor protein, are provided. Methods for treating a cancer in subject with nanobiopolymeric conjugates are described.

US Patent:

20190321494, Oct 24, 2019

Filed:

Jun 7, 2019

Appl. No.:

16/434545

Inventors:

- Los Angeles CA, US
Julia Ljubimova - Studio City CA, US
Alexander Ljubimov - Studio City CA, US
Eggehard Holler - Los Angeles CA, US

Assignee:

Cedars-Sinai Medical Center - Moscow

International Classification:

A61K 49/16
A61K 49/08
A61K 49/10
C07K 16/22
C07K 16/32

Abstract:

Nanoconjugates that include a polymalic-based molecular scaffold with one or more imaging moiety and one or more targeting modules attached to the scaffold are provided. Methods of targeting a diseased cell or a diseased tissue in a subject by administering the nanoconjugate are described. Methods of synthesizing the nanoconjugate are also provided.