University of Bristol

Philogene, Inc.

David O Bates

Steven J Harper

Dawid Grzegorz Nowak

Miriam Y Mengelus

Menachem Ze'evi

Victoria Louise Bills

Yan Qiu

The invention provides a method of selectively pro-oranti-angiogenic treatment of a mammalian subject, comprising site-specific control of alternative splicing during processing of VEGF pre-mRNA transcribed from the C terminal exon 8 of the VEGF gene using controlling agents for the splicing, wherein one or more controlling agent which favors proximal splice site (PSS) splicing in said processing is used in the pro-angiogenic treatment and one or more controlling agent which favors distal splice site (DSS) splicing in said processing is used in the anti-angiogenic treatment.

Pro- and anti-angiogenic treatments

An isolated VEGF polypeptide having anti-angiogenic activity, said polypeptide including the amino acid sequence of SEQ. ID NO. 1, or variants thereof.

Growth factor isoform

The present invention provides antibodies, as well as molecules having at least the antigen-binding portion of an antibody, against agonist pro-angiogenic, pro-permeability, vasodilatory isoforms of VEGF. Disclosed antibodies and antibody fragments are characterized by being capable of binding to and neutralizing pro-angiogenic forms of VEGF while not effecting isoforms of VEGF which are anti angiogenic. Methods of production and use in therapy and diagnosis, of such antibodies and antibody fragments are also provided.

Antibodies specific to pro-angiogenic isoforms of vascular endothelial growth factor (VEGF)

A method of detecting a risk of a pregnant female mammal developing pre-eclampsia or a complication linked thereto, or of a fetus of the pregnant female mammal developing a fetal or neonatal deficiency linked to maternal pre-eclampsia, comprises detecting the level of a VEGFb in a sample from the pregnant female mammal at less than about 24 weeks of gestation and comparing the detected level with a reference level. A reduced level in the sample from the pregnant female mammal is indicative of a risk of the pregnant female mammal developing pre-eclampsia or a complication linked thereto or of the fetus developing the fetal or neonatal deficiency linked to maternal pre-eclampsia.

Detection of risk of pre-eclampsia

An isolated VEGF polypeptide having anti-angiogenic activity, said polypeptide including the amino acid sequence of SEQ.ID NO.1, or variants thereof.

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Bishopston Bristol, United Kingdom

David O Bates