Anti-flt-1 antibodies in treating bronchopulmonary dysplasia
AssigneeShire Human Genetic Therapies, Inc.
InventorsDennis Keefe, Jennifer Bosco, Steven Abman
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Abstract
The present invention provides, among other things, methods and compositions for treating chronic lung disorders, in particular, bronchopulmonary dysplasia (BPD). In some embodiments, a method according to the present invention includes administering to an individual who is suffering from or susceptible to BPD an effective amount of an anti-Flt-1 antibody, or antigen binding fragment thereof such that at least one symptom or feature of BPD is reduced in intensity, severity, or frequency, or has delayed onset.
Claims38
A method of treating bronchopulmonary dysplasia (BPD) comprising
- administering to an individual in need of treatment an effective amount of an anti-Flt-1 antibody or antigen binding fragment thereof.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof has binding affinity to human Flt-1 greater than 10−12M in a surface plasmon resonance binding assay.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is characterized with an IC50 below 100 pM in a competition assay with human Flt-1.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is characterized with an IC50 below 10 pM in a competition assay with human Flt-1.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is characterized with an IC50 below 1 pM in a competition assay with hum an Flt-1.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof does not bind to VEGFR2 and/or VEGFR3.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof does not bind to a mouse or monkey Flt-1.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is selected from the group consisting of IgG, F(ab′)2, F(ab)2, Fab′, Fab, ScFvs, diabodies, triabodies and tetrabodies.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is administered parenterally.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is administered bimonthly, monthly, triweekly, biweekly, weekly, daily, or at variable intervals.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is delivered to one or more target tissues selected from lungs and heart.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is delivered to the lungs.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is delivered to the heart.
The method of any one of the preceding claims, wherein the administration of the anti-Flt-1 antibody or antigen binding fragment thereof results in growth of healthy lung tissue, decreased lung inflammation, increased alveologenesis, increased angiogenesis, improved structure of pulmonary vascular bed, reduced lung scarring, improved lung growth, reduced respiratory insufficiency, improved exercise tolerance, reduced adverse neurological outcome, and/or improved pulmonary function relative to a control.
The method of any one of the preceding claims, further comprising co-administering at least one additional agent or therapy selected from a surfactant, oxygen therapy, ventilator therapy, a steroid, vitamin A, inhaled nitric oxide, high calorie nutritional formulation, a diuretic, and/or a bronchodilator.
The method of any one of the preceding claims, wherein the anti-Flt-1 antibody or antigen binding fragment thereof is administered to a subject in need thereof at a dose of about between 0.5 mg/kg body weight to about 100 mg/kg body weight.
The method of any one of the preceding claims, where the administration of the anti-Flt-1 antibody or antigen binding fragment thereof results in increased cardiac output in comparison to a baseline measurement.
The method of any one of the preceding claims, wherein the administration of the anti-Flt-1 antibody or antigen binding fragment thereof decreases blood pressure.
The method of any one of the preceding claims, wherein the administration of the anti-Flt-1 antibody or antigen binding fragment thereof dose-dependently increases cardiac output, cardiac stoke volume, and/or LV-diastolic area.
Dependencies are inferred from the claim text.