Pharmaceutical formulation comprising heterodimeric relaxin fusion proteins and uses thereof
AssigneeAstraZeneca AB
InventorPeng KE
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Abstract
The present disclosure relates to pharmaceutical formulations comprising heterodimeric Relaxin fusion polypeptides, in particular heterodimeric Relaxin 2 fusion polypeptides and uses thereof. Thus, the disclosure provides pharmaceutical formulations comprising Relaxin fusion polypeptides and kits comprising the same and uses of the same including methods of treatment. The pharmaceutical formulations of the disclosure may be useful, in particular, in the treatment of cardiovascular diseases, for example for the treatment of heart failure.
Claims71
A pharmaceutical formulation comprising a heterodimeric fusion and a lipase-resistant surfactant, wherein the heterodimeric fusion comprises:
- (i) a first heterodimerisation domain connected to at least one Relaxin A chain polypeptide or a variant thereof;
- and
- (ii) a second heterodimerisation domain connected to at least one Relaxin B chain polypeptide or a variant thereof,
- wherein the first heterodimerisation domain heterodimerises with the second heterodimerisation domain, and wherein the heterodimeric fusion has Relaxin activity.
The pharmaceutical formulation according to any one of the preceding claims, wherein the Relaxin A chain is a Relaxin-2 A chain and the Relaxin B chain is a Relaxin-2 B chain.
The pharmaceutical formulation according to any one of the preceding claims, wherein the Relaxin A chain is connected to the first heterodimerisation domain via a connector and the Relaxin B chain is connected to the second heterodimerisation domain via a connector, optionally wherein one or both connectors are polypeptides.
The pharmaceutical formulation according to any one of the preceding claims, wherein the first and second heterodimerisation domains are derived from an immunoglobulin Fc region (“first Fc region” and “second Fc region”, respectively), optionally wherein the first and second Fc regions comprise the constant domains CH2 and CH3.
The pharmaceutical formulation according to any one of the preceding claims, wherein the heterodimeric fusion comprises a fusion polypeptide with the amino acid sequence of SEQ ID NO:
- 11 and a fusion polypeptide with the amino acid sequence of SEQ ID NO:
- 20.
The pharmaceutical formulation of any of the preceding claims, wherein the formulation comprises less than about 10,000, about 6000, about 5,000, about 1,000, about 750, about 600, about 500, about 250, about 150, about 100, or about 50 particles/mL greater than 2 μm, 5 μm, 10 μm, 15 μm, 20 μm or 25 μm diameter.
The pharmaceutical formulation according to any one of the preceding claims, wherein the concentration of the lipase-resistant surfactant is from 0.001% (w/v) to 1% (w/v).
The pharmaceutical formulation according to any one of the preceding claims, wherein the concentration of the lipase-resistant surfactant is from 0.02% (w/v) to 0.06% (w/v), optionally 0.04% (w/v).
The pharmaceutical formulation according to any one of the preceding claims, wherein the lipase-resistant surfactant cannot be enzymatically hydrolysed by lipase, optionally wherein the lipase is selected from lipoprotein lipase, Lipase 9, Phospholipase 2 and Phospholipase 2A.
The pharmaceutical formulation according to any one of the preceding claims, wherein the lipase-resistant surfactant does not comprise an ester bond capable of being enzymatically hydrolysed by lipase, optionally wherein the lipase is selected from lipoprotein lipase, Lipase 9, Phospholipase 2 and Phospholipase 2A.
The pharmaceutical formulation according to any one of the preceding claims, wherein the lipase-resistant surfactant is a water-soluble non-ionic triblock copolymer formed by polyethylene oxide (PEO) and polypropylene oxide (PPO) blocks, optionally wherein the water-soluble nonionic triblock copolymer is poloxamer 188 (P188).
The pharmaceutical formulation according to any one of the preceding claims, wherein the formulation further comprises a buffer at a pH from about 3 to about 10, optionally about 5.5 to about 7.5.
The pharmaceutical formulation according to any one of the preceding claims, wherein the formulation additionally comprises an excipient, optionally wherein the excipient is an ionic excipient.
The pharmaceutical formulation according to any one of the preceding claims, wherein the formulation further comprises a sugar, optionally wherein the sugar is sucrose.
The pharmaceutical formulation according to any one of the preceding claims, wherein the concentration of heterodimeric fusion is from 0.1 to 100 mg/mL, optionally 0.2 to 50 mg/mL.
The pharmaceutical formulation according to any one of the preceding claims, wherein the formulation comprises 50 mg/ml of heterodimeric fusion.
The pharmaceutical formulation according to any one of the preceding claims for use in therapy.
Dependencies are inferred from the claim text.