The University of Texas System

Wilk Patent Development Corporation

Board of Regents

Nanoco, LLC

Ellen S Vitetta

Jonathan W Uhr

Victor F Ghetie

Roxana G Baluna

Joan Elizabeth Smallshaw

Peter J Wilk

Robert C Stirbl

Jimmy Xu

Malcolm L Snead

Maria-Ana Ghetie

Richard H Scheuermann

Louis J Picker

The present invention provides for methods of identifying peptoid mimetics that will mimic B cell epitopes when delivered as vaccine compositions. One aspects of the invention is the use of monoclonal antibody that is broadly protective to select the mimetics, thereby identifying an epitope from a pathogen or other disease-causing agent that will be common among most or all variants of that pathogen or agent.

Generating peptoid vaccines

This invention discloses monoclonal antibodies (MAbs) which have little or no signaling activity as monomers become potent anti-tumor agents when they are converted into homoconjugates. The homoconjugates exert anti-growth activity by signaling G/Garrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and does not require an Fc portion. These conjugates are potent, anti-tumor agents.

Compositions and methods for homoconjugates of antibodies which induce growth arrest of apoptosis of tumor cells

The present invention provides methods to produce toxoid vaccines, such as ricin A chain vaccines, with reduced ability to promote vascular leak syndrome (VLS) and catalytic toxicity associated with various proteinaceous toxins, such as ribosome inactivating proteins. The invention also provides toxoids which have been mutated to lack amino acid sequences which induce VLS and toxic catalytic activity.

Ricin A chain mutants lacking enzymatic activity as vaccines to protect against aerosolized ricin

The present invention provides methods to produce immunotoxins (ITs) and cytokines with a reduced ability to promote vascular leak syndrome (VLS). The invention also provides ITs and cytokines which have been mutated to lack amino acid sequences which induce VLS. Also disclosed are methods for producing peptides that inhibit the induction of VLS by ITs and cytokines. Also disclosed are peptides comprising the (x)D(y) sequence to promote the extravasation of other molecules. Toxins mutated in the (x)D(y) motif or active site residues are disclosed for used in vaccines.

Compositions and methods for modifying toxic effects of proteinaceous compounds

A composition of microscopic devices utilizable in a medical diagnostic or therapeutic procedure. Each microscopic device includes a nanostructure provided with a ligand for effectively coupling the nanostructure to a predetermined chemical or molecular site. A medical method in part comprises inserting the medical devices into a patient, attaching the nanostructures via the respective ligands to instances of a predetermined type of target structure inside the patient, and thereafter activating the nanostructures to perform a preselected medical diagnostic or therapeutic function.

Medical composition employing nanostructures

The present invention provides methods to produce immunotoxins (ITs) and cytokines with a reduced ability to promote vascular leak syndrome (VLS). The invention also provides ITs and cytokines which have been mutated to lack amino acid sequences which induce VLS.

Method and related composition employing nanostructures

This invention discloses monoclonal antibodies (MAbs) which have little or no signaling activity as monomers become potent anti-tumor agents when they are converted into homoconjugates. The homoconjugates exert anti-growth activity by signaling G /G arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and does not require an Fc portion. These conjugates are potent, anti-tumor agents.

Compositions and methods for homoconjugates of antibodies which induce growth arrest or apoptosis of tumor cells

Disclosed are methods and compositions for the treatment of HIV infections through the specific elimination of cells which express HIV env determinants such as gp120. The compositions of the invention include toxin conjugates composed of a CD4 derived gp120 binding ligand conjugated to a toxin A chain moiety such as ricin A chain or deglycosylated ricin A chain. Where a therapeutic composition is desired, the conjugates are formed by means of a cross linker which includes a disulfide bond. Disulfide linkages are not crucial where non-therapeutic uses, such as antibody generation, is intended. In preferred aspects of the invention, conjugates incorporating shorter CD4 peptides, such as those incorporating amino acids 41-57 or 41-84 of CD4, are disclosed. Therapeutic amounts of conjugates composed of soluble CD4 or a CD4 peptide cross-linked to deglycosylated A chain by means of as SMPT linker is administered to an HIV infected patient so as to specifically eliminate HIV infected cells without exerting significant toxicity against uninfected or class II cells.

Therapeutic compositions comprising a CD4 peptide and methods of

The anti-tumor activity of a mixture of anti-CD22 and anti-CD19 immunotoxins is shown to be significantly enhanced in SCID/Daudi mice with disseminated human Daudi lymphoma. Unexpectedly identical enhancement was observed employing a combination of the anti-CD22 immunotoxin with unconjugated anti-CD19 antibodies. Thus combinations of an anti-CD22 immunotoxin and an anti-CD19 immunotoxin or antibody act synergistically and provide advantageous compositions and methods for immunotherapeutic treatment of various diseases including cancer and autoimmune disorders. Also disclosed is data indicating that certain anti-CD19 antibodies alone inhibit proliferation of CD19-positive cells by inducing cell cycle arrest.

Epitope-specific monoclonal antibodies and immunotoxins and uses thereof

Disclosed are methods for the identification and characterization of tumor cell types present within malignant populations, and novel methods of cancer treatment. Tumor cells in cell cycle arrest have been identified, purified and characterized according to their size, altered morphology, surface phenotype and expression of oncogenes. Tumor cell cycle arrest can be induced in mice lacking an immune system solely upon administration of anti-idiotype antibodies. Methods of manipulating specific signals from the cell surface to alter the malignant phenotype of transformed cells are disclosed, as are methods for either eliminating or specifically maintaining tumor cells in cell cycle arrest.

Method for identifying tumor cells in cell cycle arrest

Immunotoxin preparations are described in which the preparations are enriched for a single species of immunotoxin. Also described are methods for the preparation of the substantially purified immunotoxins (ITs). Also disclosed are methods for determining the most effective species of immunotoxin conjugates for treated diseases and pharmaceutical preparations for such treatments.

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Dallas, TX, United States of America

Ellen S Vitetta