Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Other

Bioblast Pharma Ltd.

Haya Lorberboum-Galski

Shai Yarkoni

Irina Marianovsky

Ahmi Ben-Yehudah

Amotz Nechushtan

Ala Fishman

Rami Ishaq Aqeilan

Ruth Belostotsky

Ida Steinberger

Eveline Beraud

Hagar Greif

Alla Fishman

Yehudith Azar

Disclosed are fusion protein constructs comprising a functional mitochondrial protein, that can enter mitochondria within intact cells. Further disclosed are methods of treating mitochondrial disorders by the disclosed fusion proteins and compositions therefor.

Mitochondrial proteins constructs and uses thereof

The invention provides fusion protein constructs comprising a functional mitochondrial protein and methods of treating mitochondrial disorders by the fusion proteins and compositions thereof.

The present invention generally relates to a new approach for the therapy of allergic responses, based on targeted elimination of cells expressing the Fc&#x3b5;RI receptor by a chimeric cytotoxin Fc-PE. A sequence encoding amino acids 301-437 of the Fc region of the mouse IgE molecule was genetically fused to PE'&#x2014;a truncated form of PE lacking the cell binding domain. The chimeric protein, produced in, specifically and efficiently kills mouse mast cell lines expressing the Fc&#x3b5;RI receptor, as well as primary mast cells derived from bone marrow. The present invention provides a chimeric protein for targeted elimination of Fc&#x3b5;RI expressing cells especially useful for the therapy of allergic responses. The said chimeric protein is comprised of a cell targeting moiety for Fc&#x3b5;RI expressing cells and a cell killing moiety. The preferred killing moiety is the bacterial toxin Pseudomonas exotoxin (PE). This Pseudomonas exotoxin is a product of. The present invention also relates to a method for the preparation of said protein. This chimeric protein is prepared by genetically fusing the Fc region of the mouse IgE molecule to PE, a truncated form of PE lacking the cell binding domain. The present invention also provides pharmaceutical compositions, for the treatment of allergic diseases and for the treatment of hyperplasias and malignancies, comprising as an active ingredient the above mentioned chimeric protein and a conventional adjuvant product.

Fcepsilon-pe chimeric protein for targeted treatment of allergy responses a method for its production and pharmaceutical compositions containing the same

The present invention generally relates to a new approach for the therapy of allergic responses, based on targeted elimination of cells expressing the Fc&#x3b5;RI receptor by a chimeric cytotoxin FC-PE. A sequence encoding amino acids 301-437 of the Fc region of the mouse IgE molecule was genetically fused to PE&#x2014;a truncated form of PE lacking the cell binding domain. The chimeric protein, produced in, specifically and efficiently kills mouse mast cell lines expressing the Fc&#x3b5;RI receptor, as well as primary mast cells derived from bone marrow. The present invention provides a chimeric protein for targeted elimination of Fc&#x3b5;RI expressing cells especially useful for the therapy of allergic responses. The said chimeric protein is comprised of a cell targeting moiety for Fc&#x3b5;RI expressing cells and a cell killing moiety. The preferred killing moiety is the bacterial toxinexotoxin (PE). Thisexotoxin is a product of. The present invention also relates to a method for the preparation of said protein. This chimeric protein is prepared by genetically fusing the Fc region of the mouse IgE molecule to PE, a truncated form of PE lacking the cell binding domain. The present invention also provides pharmaceutical compositions, for the treatment of allergic diseases and for the treatment of hyperplasias and malignancies, comprising as an active ingredient the above mentioned chimeric protein and a conventional adjuvant product.

Fc&#x3b5;-PE chimeric protein for targeted treatment of allergy responses a method for its production and pharmaceutical compositions containing the same

The present invention relates particularly to neoplastic cells targeted chimeric toxins comprising of cell targeting moieties and cell killing moieties for recognizing and for destroying the neoplastic cells, wherein the cell targeting moieties consist of gonadotropin releasing hormone homologues and the cell killing moieties consist ofExotoxin A. The present invention further relates to pharmaceutical compositions containing as an active ingredient these neoplastic cells targeted chimeric toxins and to a method for the production of these chimeric toxins. The said invention also relates to a method for cancer therapy, treating malignant carcinoma cells and benign hyperplasia including uterine lyomyoma cells, extra uterian endometrial island cells, benign hyperplasia of prostate and breast and pituitary tumor adenoma cells, by the use of the above-mentioned chimeric toxins.

Chimeric toxins for targeted therapy

The present invention relates to chimeric proteins with cell-targeting specificity and apoptosis-inducing activities. In particular, the invention is illustrated by a recombinant chimeric protein between human interleukin-2 (IL2) and Bax. The chimeric protein specifically targets IL2 receptor (IL2R)-expressing cells and induces cell-specific apoptosis.

Chimeric proteins with cell-targeting specificity and apoptosis-inducing activities

A chimeric protein comprising a exotoxin (PE) moiety linked to a myelin basic protein (MBP) moiety is disclosed. The MBP moiety is selected from the group comprising: (a) MBP; (b) amino acids 69-88 of guinea-pig myelin basic protein or an antigenic portion thereof; (c) amino acids 84-102 of human myelin basic protein or an antigenic portion thereof; (d) amino acids 143-168 of human myelin basic protein or an antigenic portion thereof; and (e) an amino acid sequence in which one or more amino acids have been deleted, added, substituted or mutated in the amino acid sequences of (a), (b), (c) or (d), the modified sequence of (e) retaining at least 75% homology with the amino acid sequences of (a), (b), (c) or (d), respectively. Each of the MBP moieties of (b), (c) and (d) are linked to the PE moiety by a pentapeptide linker repeated 1-3 times. The chimeric protein is useful in treating autoimmune diseases, and especially multiple sclerosis.

Pseudomonas exotoxin-myelin basic protein chimeric proteins

The present invention relates to methods for cancer diagnosis using a chimeric toxin. In particular, the invention relates to the use of a chimeric toxin composed of gonadotropin releasing hormone (GnRH) and Pseudomonas exotoxin A (PE) to detect a tumor-associated epitope expressed by human adenocarcinomas. Mutated GnRH-PE molecules that bind but do not kill tumor cells are exemplified.

Growing community of inventors

Jerusalem, Israel

Haya Lorberboum-Galski