Other

Hadasit Medical Research Services and Development Ltd.

Insight Biopharmaceuticals Ltd.

Hadasit Medical Research Services and Development Company

Technion Research & Development Foundation Limited

Agricultural Research Organization Ministry of Agriculture

Compugen Ltd. Corporation

Carmel—haifa University Economic Corp Ltd.

Rappaport Family Institute for Research in the Medical Sciences

Insight Strategy Marketing Ltd.

Shenzhen Hepalink Pharmaceutical Co., Ltd.

Agricultural Research Org. Ministry of Agriculture (gov.)

Hadasitmedical Research Serv. & Devel. Ltd.

Agricultural Organization Ministry of Agriculture State of Israel

Insight Biopharmacenticals Ltd.

Israel Vlodavsky

Iris Pecker

Mark Pines

Arnon Nagler

Tuvia Peretz

Yael Friedmann

Elena Feinstein

Yael Friedman

Tuvia Perets

Shimon Slavin

Gera Neufeld

Maty Ayal-Hershkovitz

Daphna Miron

Zoya Poltorak

Eli Keshet

Neta Ilan

Yinon Shlomi

Eyal Zcharia

Zurit Levine

Gad S Cojocaru

Ronen Shemesh

Michal Ayalon-Soffer

Sergey Nemzer

Iris Hecht

Ulf Lindahl

Hanna Ben-Artzi

Jin-ping Li

Yoav Peleg

Eviatar Nevo

Aaron Avivi

Israel Michal

Orit Goldshmidt

Ehud Geller

Eli Hazum

Hua-Quan Miao

Hua-Quan Mian

Tomer Zekharya

Nicola J Nasser

Uri Barash

Marina Weissmann

Gil Arvatz

Flonia Levy-Adam

The present invention relates to heparanase-neutralizing monoclonal antibodies (m Abs), pharmaceutical composition comprising same, and use thereof for treating a disease or disorder associated with heparanase activity, including but not limited to cancer, inflammation, diabetes and related complications. The present invention further provides combined therapies comprising the heparanase-neutralizing m Ab and an anti-cancer treatment such as chemotherapy or radiation, for treating a proliferative disease in a subject.

Heparanase-neutralizing monoclonal antibodies

The present invention, in at least some aspects, is of splice variants of heparanase, as well as diagnostic kits and methods of use, and therapeutic agents and methods of use based thereon, and antibodies specifically binding thereof.

Heparanase splice variant

The invention relates to cells and transgenic non-human mammals having at least one disrupted heparanase allele. The invention further relates to methods of screening therapeutic drug candidates utilizing the heparanase deficient non-human mammals and cells.

Heparanase deficient non-human mammals

The invention relates to novel heparanases, heparanase splice variants, and to polynucleotides encoding them. Particularly, the invention relates toheparanases, and toand human heparanase splice variants. Heparanase splice variants can be used, for example, to modulate the activity of heparanase in diseases disorders or conditions caused by or associated with the enzymatic activity of heparanase. For instance, a splice variant capable of down regulating the activity of heparanase can be used to treat primary tumors and/or to prevent or treat metastasis.

Heparanases and splice variants thereof, polynucleotides encoding them and uses thereof

According to the present invention there is provided an antibody that specifically binds an epitope of a heparanase protein, the heparanase protein including an amino acid sequence as set forth in SEQ ID NO:2, provided that phenylalanine replaces tyrosine at position 246. The present invention also provides an antibody elicited by an epitope of a heparanase protein, the heparanase protein including an amino acid sequence as set forth in SEQ ID NO:2, provided that phenylalanine replaces tyrosine at position 246.

Heparanase specific molecular probes and their use in research and medical applications

Heparanase specific molecular probes which can be used for detection of the presence, absence or level of heparanase expression and methods of utilizing same are provided.

An amino acid sequence derived from the N' terminus region of the 50 Kd subunit of heparanase, preferably, the sequence including amino acid residues Lys-Asnof human heparanase and any functional fragments thereof. Compositions for the inhibition of heparanase glycosidase catalytic activity, having as an active ingredient an isolated and purified peptide as the amino acid sequence. An antibody directed to the sequence and compositions and uses thereof as heparanase inhibitor. The use of the amino acid sequence in a screening method for specific heparanase inhibitors. Compositions including the heparanase inhibitors and methods for the treatment of heparanase related disorders.

Substances directed against a specific sequence essential for heparanase catalytic activity and uses thereof as heparanase inhibitors

A polynucleotide (hpa) encoding a polypeptide having heparanase activity, vectors including same, genetically modified cells expressing heparanase, a recombinant protein having heparanase activity and antisense oligonucleotides and constructs for modulating heparanase expression.

Polypeptide having heparanase activity

A variety of heparanase specific molecular probes which can be used for research and medical applications including diagnosis and therapy. Specific applications include the use of a heparanase specific molecular probe for detection of the presence, absence or level of heparanase expression; the use of a heparanase specific molecular probe for therapy of a condition associated with expression of heparanase; the use of a heparanase specific molecular probe for quantification of heparanase in a body fluid; the use of a heparanase specific molecular probe for targeted drug delivery; and the use of a heparanase specific molecular probe as a therapeutic agent.

The invention provides a composition for attenuating neovascularization and treating malignancies, including a pharmaceutically effective amount of a compound having a formula:wherein:

Quinazolinone containing pharmaceutical compositions for prevention of neovascularization and for treating malignancies

A variety of heparanase specific antibodies which can be used for research and medical applications including diagnosis and therapy. Specific applications include the use of a heparanase specific antibodies for detection of the presence, absence or level of heparanase expression; the use of a heparanase specific antibodies for therapy of a condition associated with expression of heparanase; the use of a heparanase specific antibodies for quantification of heparanase in a body fluid; the use of a heparanase specific antibodies for targeted drug delivery; and the use of a heparanase specific antibodies as a therapeutic agent.

Heparanase specific antibodies and their use in research and medical applications

Polynucleotide encoding a polypeptide having heparanase activity and expression of same in genetically modified cells

A method of treating a condition associated with heparanase expression by administering a heparanase activity neutralizing monoclonal anti-heparanase antibody, the monoclonal anti-heparanase antibody being for neutralizing heparanase catalytic activity.

Heparanase activity neutralizing anti-heparanase monoclonal antibody

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Mevaseret Zion, Israel

Israel Vlodavsky