Neuropilin/VEGF-C/VEGFR-3 materials and methods
OwnerKari Alitalo, Marika Karkkainen +1inventors
InventorsKari Alitalo, Marika Karkkainen, Kaisa Karila
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Abstract
The present invention relates to identifying modulators of VEGF-C or VEGF-D ligand binding to the nervous system transmembrane protein neuropilin-2 and materials and methods for detecting said modulators.
Claims39
A method of screening for modulators of binding between a neuropilin growth factor receptor and a VEGF-C polypeptide comprising steps of:
- a) contacting a neuropilin composition that comprises a neuropilin polypeptide with a VEGF-C composition that comprises a VEGF-C polypeptide, in the presence and in the absence of a putative modulator compound;
- b) detecting binding between the neuropilin polypeptide and the VEGF-C polypeptide in the presence and absence of the putative modulator compound;
- and
- c) identifying a modulator compound based on a decrease or increase in binding between the neuropilin polypeptide and the VEGF-C polypeptide in the presence of the putative modulator compound, as compared to binding in the absence of the putative modulator compound.
A method for screening for selectivity of a modulator of VEGF-C biological activity, comprising steps of:
- a) contacting a VEGF-C composition with a neuropilin composition in the presence and in the absence of a compound and detecting binding between the VEGF-C and the neuropilin in the presence and absence of the compound, wherein differential binding in the presence and absence of the compound identifies the compound as a modulator of binding between the VEGF-C and the neuropilin;
- b) contacting a VEGF-C composition with a composition comprising a VEGF-C binding partner in the presence and in the absence of the compound and detecting binding between the VEGF-C and the binding partner in the presence and absence of the compound, wherein differential binding in the presence and absence of the compound identifies the compound as a modulator of binding between the VEGF-C and the binding partner;
- and wherein the binding partner is selected from the group consisting of:
- (i) a polypeptide comprising a VEGFR-3 extracellular domain;
- and
- (ii) a polypeptide comprising a VEGFR-2 extracellular domain;
- and
- (c) identifying the selectivity of the modulator compound in view of the binding detected in steps (a) and (b).
A method for screening for selectivity of a modulator of neuropilin biological activity, comprising steps of:
- a) contacting a neuropilin composition with a VEGF-C composition in the presence and in the absence of a compound and detecting binding between the neuropilin and the VEGF-C in the presence and absence of the compound, wherein differential binding in the presence and absence of the compound identifies the compound as a modulator of binding between the neuropilin and the VEGF-C;
- b) contacting a neuropilin composition with a composition comprising a neuropilin binding partner in the presence and in the absence of the compound and detecting binding between the neuropilin and the binding partner in the presence and absence of the compound, wherein differential binding in the presence and absence of the compound identifies the compound as a modulator of binding between the neuropilin and the binding partner;
- and wherein the binding partner is a polypeptide comprising an amino acid sequence selected from the group consisting of:
- an amino acid sequence of a semaphorin 3 polypeptide;
- a VEGF-A amino acid sequence, a VEGF-B amino acid sequence, a VEGF-D amino acid sequence, a PlGF-2 amino acid sequence, a VEGFR-1 amino acid sequence, a VEGFR-2 amino acid sequence, a VEGFR-3 amino acid sequence;
- and an amino acid sequence of a plexin polypeptide;
- and
- c) identifying the selectivity of the modulator compound in view of the binding detected in steps (a) and (b).
A method of screening for modulators of binding between a neuropilin growth factor receptor and a VEGFR-3 polypeptide comprising steps of:
- a) contacting a neuropilin composition with a VEGFR-3 composition in the presence and in the absence of a putative modulator compound;
- b) detecting binding between the neuropilin and the VEGFR-3 in the presence and absence of the putative modulator compound;
- and
- c) identifying a modulator compound based on a decrease or increase in binding between the neuropilin composition and the VEGFR-3 composition in the presence of the putative modulator compound, as compared to binding in the absence of the putative modulator compound.
A method for screening for selectivity of a modulator of VEGFR-3 biological activity, comprising steps of:
- a) contacting a VEGFR-3 composition with a neuropilin composition in the presence and in the absence of a compound and detecting binding between the VEGFR-3 and the neuropilin in the presence and absence of the compound, wherein differential binding in the presence and absence of the compound identifies the compound as a modulator of binding between the VEGFR-3 and the neuropilin;
- b) contacting a VEGFR-3 composition with a composition comprising a VEGFR-3 binding partner in the presence and in the absence of the compound and detecting binding between the VEGFR-3 and the binding partner in the presence and absence of the compound, wherein differential binding in the presence and absence of the compound identifies the compound as a modulator of binding between the VEGFR-3 and the binding partner;
- and wherein the binding partner is selected from the group consisting of:
- (i) a polypeptide comprising a VEGF-C polypeptide;
- and
- (ii) a polypeptide comprising a VEGF-D polypeptide;
- and
- c) identifying the selectivity of the modulator compound in view of the binding detected in steps (a) and (b).
A method of modulating growth, migration, or proliferation of cells in a mammalian organism, comprising a step of:
- (a) identifying a mammalian organism having cells that express a neuropilin receptor;
- and
- (b) administering to said mammalian organism a composition, said composition comprising a neuropilin polypeptide or fragment thereof that binds to the VEGF-C polypeptide;
- wherein the composition is administered in an amount effective to modulate growth, migration, or proliferation of cells that express neuropilin in the mammalian organism.
A method of modulating growth, migration, or proliferation of cells in a mammalian organism, comprising steps of:
- (a) identifying a mammalian organism having cells that express a neuropilin receptor;
- and
- (b) administering to said mammalian organism a composition, said composition comprising a bispecific antibody specific for the neuropilin receptor and for a VEGF-C polypeptide,
- wherein the composition is administered in an amount effective to modulate growth, migration, or proliferation of cells that express the neuropilin receptor in the mammalian organism.
A bispecific antibody which specifically binds to a neuropilin receptor and a VEGF-C polypeptide.
A method of modulating growth, migration, or proliferation of cells in a mammalian organism, comprising steps of:
- (a) identifying a mammalian organism having cells that express a neuropilin receptor and a VEGFR-3 polypeptide;
- and
- (b) administering to said mammalian organism a composition, said composition comprising a bispecific antibody specific for the neuropilin receptor and a VEGFR-3 polypeptide,
- wherein the composition is administered in an amount effective to modulate growth, migration, or proliferation of cells that express the neuropilin receptor and the VEGFR-3 polypeptide in the mammalian organism.
A bispecific antibody which specifically binds to a neuropilin receptor and a VEGFR-3 polypeptide.
A method of modulating neuronal growth, or neuronal scarring in a mammalian organism, comprising a step of:
- (a) identifying a mammalian organism having neuronal cells that express a neuropilin receptor;
- and
- (b) administering to said mammalian organism a composition, said composition comprising a VEGF-C polypeptide or fragment thereof that binds to the neuropilin receptor,
- wherein said polypeptide or fragment is administered in an amount effective to modulate the growth, survival or migration of the neuronal cells.
A polypeptide comprising a fragment of a VEGF-C that binds to a neuropilin receptor, for use in the manufacture of a medicament for the treatment of diseases characterized by aberrant growth, migration, or proliferation of cells that express a neuropilin receptor.
Dependencies are inferred from the claim text.