Alan Paul Epstein

US Patent:

6403096, Jun 11, 2002

Filed:

Nov 18, 1999

Appl. No.:

09/443061

Inventors:

Alan L. Epstein - La Canada CA
Leslie A. Khawli - Arcadia CA

Assignee:

University of Southern California - Los Angeles CA

International Classification:

A61K 3820

US Classification:

42419511, 530324, 530351, 530402, 514 2, 514 8, 514 12, 4241921, 424 852

Abstract:

A novel permeability enhancing peptide (PEP) is a fragment of interleukin-2. When joined to a delivery vehicle that can target a tumor site, the PEP can increase the subsequent uptake of antineoplastic or tumor imaging agents. The PEP can be chemically joined to a monoclonal antibody to form an immunoconjugate. Alternatively, an expression vector is genetically engineered to express a fusion protein. The fusion protein has an antigen-binding portion joined to the PEP. The PEP is most effective when it takes the form of a dimer, linked by a disulfide bridge. The PEP is substantially free of cytokine activity and produces minimal toxic side effects on normal tissues.

US Patent:

6524823, Feb 25, 2003

Filed:

Jul 27, 2001

Appl. No.:

09/916883

Inventors:

Alan L. Epstein - La Canada CA
Michael Glovsky - Los Angeles CA

Assignee:

The University of Southern California - Los Angeles CA

International Classification:

C12P 2104

US Classification:

435 696, 435 7021, 4241781, 4241551, 4241761, 4241801, 4241831, 530350, 530380, 530382, 5303871, 5303881, 5303911

Abstract:

Liposomal conjugates having a clinically useful delivery vehicle linked to a biologically active species which acts to increase vascular permeability and expand blood volume at or in proximity to the tumor site are disclosed. The vehicle-linked species may be, for example, a vasoactive agent, a substance that recruits or amplifies a vasoactive species, a drug, or a pharmaceutical compound. Suitable biological species comprises peptides, lipids, carbohydrates, or their derivatives. Chemical or recombinant DNA methods suitable for linking the species to the vehicles are indicated. A therapy is disclosed which comprises administering the vasoactive conjugate and delivering a diagnostic agent or a therapeutic agent at an optimal time thereafter, when tumor vasculature is maximally affected.

US Patent:

6696276, Feb 24, 2004

Filed:

Jan 13, 2003

Appl. No.:

10/342426

Inventors:

Alan L. Epstein - La Canada CA
Michael Glovsky - Los Angeles CA

Assignee:

University of Southern California - Los Angeles CA

International Classification:

C12P 2104

US Classification:

435 696, 4241781, 530382

Abstract:

Liposomal conjugates having a clinically useful delivery vehicle linked to a biologically active species which acts to increase vascular permeability and expand blood volume at or in proximity to the tumor site are disclosed. The vehicle-linked species may be, for example, a vasoactive agent, a substance that recruits or amplifies a vasoactive species, a drug, or a pharmaceutical compound. Suitable biological species comprises peptides, lipids, carbohydrates, or their derivatives. Chemical or recombinant DNA methods suitable for linking the species to the vehicles are indicated. A therapy is disclosed which comprises administering the vasoactive conjugate and delivering a diagnostic agent or a therapeutic agent at an optimal time thereafter, when tumor vasculature is maximally affected.

US Patent:

6737064, May 18, 2004

Filed:

May 9, 2002

Appl. No.:

10/142120

Inventors:

Alan L. Epstein - La Canada CA
Leslie A. Khawli - Arcadia CA

Assignee:

The University of Southern California - Los Angeles CA

International Classification:

A61K 3820

US Classification:

42419511, 514 2, 514 8, 514 12, 4241931, 424 91

Abstract:

A novel permeability enhancing peptide (PEP) is a fragment of interleukin-2. When joined to a delivery vehicle that can target a tumor site, the PEP can increase the subsequent uptake of antineoplastic or tumor imaging agents. The PEP can be chemically joined to a monoclonal antibody to form an immunoconjugate. Alternatively, an expression vector is genetically engineered to express a fusion protein. The fusion protein has an antigen-binding portion joined to the PEP. The PEP is most effective when it takes the form of a dimer, linked by a disulfide bridge. The PEP is substantially free of cytokine activity and produces minimal toxic side effects on normal tissues.

US Patent:

7371371, May 13, 2008

Filed:

Aug 12, 2002

Appl. No.:

10/218197

Inventors:

Alan L. Epstein - La Canada CA, US
Peisheng Hu - Covina CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

A61K 38/20
C07K 14/55

US Classification:

424 852, 530351

Abstract:

Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildtype form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

US Patent:

7514073, Apr 7, 2009

Filed:

Mar 29, 2005

Appl. No.:

11/093073

Inventors:

Alan L. Epstein - La Canada CA, US
Peisheng Hu - Covina CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

A61K 38/20

US Classification:

424 852, 514885

Abstract:

Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildytpe form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

US Patent:

7696175, Apr 13, 2010

Filed:

Oct 28, 2005

Appl. No.:

11/262286

Inventors:

Alan Epstein - La Canada CA, US
Peishing Hu - Covina CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

A61K 38/17
A61K 38/16
A61K 39/395

US Classification:

514 21, 514 12, 4241341

Abstract:

Provided are methods of reducing the size of a tumor or inhibiting the growth of cancer cells in an individual or inhibiting the development of metastatic cancer by administering an effective amount of a soluble form of a co-stimulatory molecule from an antigen presenting cell and by reducing the activity of immunoregulatory T cells in the individual. Methods of reduction in the activity of immunoregulatory T cells involve removing them ex vivo or depleting or inactivating them in vivo. Also provided are cancer therapeutic compositions comprising a soluble form of a co-stimulatory molecule from an antigen presenting cell and an antibody specific for an intracellular antigen.

US Patent:

7803361, Sep 28, 2010

Filed:

Apr 7, 2009

Appl. No.:

12/419960

Inventors:

Alan L. Epstein - La Canada CA, US
Peisheng Hu - Covina CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

A61K 38/20

US Classification:

424 852, 514885

Abstract:

Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildytpe form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.