Vegf pathway blockade
AssigneeBristol-Myers Squibb Company
InventorsJohn Mendlein, Eric Furfine
Life of this patent
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Abstract
The present invention relates to innovative proteins that block the VEGF-VEGFR pathway mediated biology and pathology, as well as pharmaceutical formulations of these proteins. The invention also relates to dosage therapies for the administration of these proteins. The invention further relates to the use of VEGF-A as a biomarker for determining an effective dosage and predicting the efficacy of these proteins.
Claims18
A pharmaceutical formulation comprising from 1 to 15 mg/ml of a polypeptide, 5 to 100 mM sodium acetate, 0 to 200 mM sodium chloride, and 50 to 150 mM mannitol, wherein the pH of the formulation is from 4.5 to 6.0, and wherein the polypeptide comprises a tenth fibronectin type III (10Fn3) domain, wherein the 10Fn3 domain (i) comprises a loop, AB;
- a loop, BC;
- a loop, CD;
- a loop, DE;
- a loop EF;
- and a loop FG;
- (ii) has at least one loop selected from loop BC, DE, and FG with an altered amino acid sequence relative to the sequence of the corresponding loop of the human 10Fn3 domain;
- and (iii) binds human VEGFR2 with a disassociation constant of 1 μM or less.
A method for treating a subject having a condition associated with inappropriate angiogenesis, the method comprising administering intravenously to a subject in need thereof between 0.5 to 3 mg/kg of a polypeptide, wherein the polypeptide comprises a tenth fibronectin type III (10Fn3) domain, and wherein the 10Fn3 domain (i) comprises a loop, AB;
- a loop, BC;
- a loop, CD;
- a loop, DE;
- a loop EF;
- and a loop FG;
- (ii) has at least one loop selected from loop BC, DE, and FG with an altered amino acid sequence relative to the sequence of the corresponding loop of the human 10Fn3 domain, and (iii) binds human VEGFR2 with a disassociation constant of 1 μM or less.
A method for treating a subject having a condition associated with inappropriate angiogenesis comprising administering subcutaneously to a subject in need thereof between 0.05 to 0.8 mg/kg of a polypeptide, wherein the polypeptide comprises a tenth fibronectin type III (10Fn3) domain, wherein the 10Fn3 domain (i) comprises a loop, AB;
- a loop, BC;
- a loop, CD;
- a loop, DE;
- a loop EF;
- and a loop FG;
- (ii) has at least one loop selected from loop BC, DE, and FG with an altered amino acid sequence relative to the sequence of the corresponding loop of the human 10Fn3 domain, and (iii) binds human VEGFR2 with a disassociation constant of 1 μM or less.
Dependencies are inferred from the claim text.