AVEO Oncology recently filed provisional patent applications with the United States Patent and Trademark Office (USPTO) covering composition of matter claims for AV-353, its Notch 3 inhibitory antibody. These are the second set of patent applications associated to AV-353 and the AVEOS’ Notch 3 antibody program.
The Notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms. Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembrane receptor protein.
The Notch 3 signaling pathway is vital in cell-to-cell communication including mechanisms of gene regulation that control multiple processes of cell differentiation during the entire life cycle. The Notch 3 receptor pathway has been recently implicated in pulmonary arterial hypertension (PAH) pathology.
PAH is an increase of blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, leg swelling and other symptoms. Pulmonary hypertension is a life-threatening condition that gets worse over time, and treatments can only help patients cope with the disease symptoms.
Now, in a recent study funded by AVEO, AV-353 generated preclinical data supporting its ability to reverse the PAH phenotype, which would represent a potential disease-modifying approach to treatment. An article reporting these results will soon be submitted to a peer-reviewed journal.
“Like AV-380 in cachexia, which AVEO licensed to Novartis in 2015, AV-353 is an AVEO legacy discovery program that, with the appropriate development support from a partner, has the potential to transform the treatment paradigm for a debilitating disorder and underserved patient population,” said Michael Bailey, president and chief executive officer of AVEO, in a recent press release. “We believe that AV-353’s selectivity and high affinity to Notch 3, as demonstrated in preclinical studies, makes it unique relative to pan-notch inhibitory or ligand inhibitory approaches in PAH treatment, allowing us to potentially build a broad patent estate around this program. Consistent with our current focus on developing oncology therapeutics, AVEO is currently seeking an appropriate partner to develop and commercialize AV-353 worldwide in PAH.”
Although PAH is a rare disease, with an estimated prevalence of 15-50 cases per million, the prevalence of PAH in certain at-risk groups is substantially higher. For example, in HIV-infected patients the prevalence is 0.5%, in patients with systemic sclerosis it has been reported to be 7-12%, and in patients with sickle cell disease the prevalence is around 2-3.75%.