Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Reexamination Certificate
1996-09-30
2001-04-17
Huff, Sheela (Department: 1642)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
C435S007200, C424S145100
Reexamination Certificate
active
06218516
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to immunointeractive molecules to an animal growth factor receptor and, more particularly, to animal neuroepithelial kinase/fetal liver kinase-1 receptor (NYK/flk-1). The immunointeractive molecules provide the basis for new therapeutic and diagnostic agents which can be used, for example, in the treatment, prophylaxis and diagnosis of an angiogenic-dependent phenotype.
Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers.
BACKGROUND OF THE INVENTION
Angiogenesis is the formation of new blood vessels from those which preexist within the body (1). It is of fundamental importance for the development of the embryo and a number of roles in post-natal life (e.g. wound healing, tissue regeneration, cyclical growth of the corpus luteum and endometrium). Angiogenesis is also important in a number of pathological conditions including the growth of solid tumors (1). Recent studies have suggested that the acquistion of an angiogenic-dependent phenotype is a key factor in the development of metastasis.
The introduction of techniques based on the polymerase chain reaction (PCR) for amplifying protein tyrosien kinase sequences has enabled the rapid isolation of novel members of the growth factor receptor family. Two of the putative receptors isolated NYK/flk-1 (2) (neuroepithelial kinase/fetal liver kinase) and tie2/Tek (3) have been shown to be expressed on endothelial cells and their precursors. NYK and its human equivalent KDR (4) have been shown to bind and be activated by the endothelial cell mitogen VEGF/VPF (vascular endothelial growth factor/vascular premeability factor) (5). VEGF has a mitagenic effect on endothelial cells but is also a potent mediator of vascular permeability. VEGF has in recent studies been shown to play a role in the hypoxia induced angiogenesis seen in a glioma model suggesting the VEGF may play a role in meadiating angiogenesis in other tumour systems (6). Other studies have shown that anti-VEGF monoclonal antibodies have an anti-tumour effect in vivo (7).
In work leading up to the present inventions the inventors developed a series of antibodies to the NYK (VEGF2R) receptor extracellular domain. These antibodies are useful in the development of a new range of therapeutic molecules such as agonists and antagonists of the NYK-VEGF interaction as well as a range of diagnostic agents capable of, for example, detecting normal or mutated NYK receptors, receptor expression on a cell surface and/or receptor-ligand interaction.
SUMMARY OF THE INVENTION
One aspect of the present invention provides an immunointeractive molecules capable of binding or otherwise associated with an animal NYK/flk-1 receptor extracellular domain. Preferably, the animal is a mammal such as a human or murine animals. Preferably, the immunointeractive molecule is a polyclonal or monoclonal antibody.
Another aspect of the present invention is directed to a diagnostic agent comprising an immunointeractive molecule capable of binding or otherwise associating with an animal NYK/flk-1 receptor extracellular domain. Preferably, the immunointeractive molecule is an antibody labelled with a reporter molecule.
Yet another aspect of the present invention relates to a pharmaceutical composition comprising an immunointeractive molecule as contemplated above together with one or more pharmaceutically acceptable carriers and/or diluents.
Still another aspect of the present invention provides a method for treating an angiogenic-dependent phenotype or disease condition resulting therefrom in a mammal, said method comprising administering to said mammal an effective amount of an immunointeractive molecule capable of binding or otherwise associating with an animal NYK/flk-1 receptor extracellular domain. The method is particulary useful in the treatment of metastasis.
A further aspect of the present invention is the use of the subject interactive molecules to treat metastases by targeting isotypes such as
125
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131
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REFERENCES:
patent: 5747651 (1998-05-01), Lemischka
Millauer et al. Cell 72:835-46 (1993).
Matthews et al. Proc. Natl. Acad. Sci. 88:9026-30 (1991).
Oelrichs et al. Oncogene 8:11-18 (1993).
Harlow & Lane (1988) Cold Spr. Harbor Lab. Press. Chapters 5, 6, & 9.
Oelrichs Robert B
Stacker Steven A
Wilks Andrew F
Eyler Yvonne
Fulbright & Jaworski LLP
Huff Sheela
Ludwig Institute for Cancer Research
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