Therapeutic uses of modified relaxin polypeptides
First Claim
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1. A method of treating a patient having a fibrotic disorder, comprising administering to said patient an effective amount of a biologically active modified relaxin polypeptide, wherein (a) said modified relaxin polypeptide comprises an A chain and a B chain linked by at least one disulfide bond, wherein said A chain comprises SEQ ID NO:
- 4 substituted with a non-naturally encoded amino acid at position 1 and said B chain comprises SEQ ID NO;
5 or SEQ ID NO;
6, and (b) the non-naturally encoded amino acid is linked to a linker, polymer, or biologically active molecule, wherein said non-naturally encoded amino acid comprises a first functional group and the linker, polymer, or biologically active molecule comprises a second functional group, wherein the first functional group and second functional group are not identical and each comprise a carbonyl group, an aminooxy group, a hydrazide group, a hydrazine group, a semicarbazide group, an azide group, or an alkyne group, and the non-naturally encoded amino acid is linked to the linker, polymer, or biologically active molecule by the resultant covalent linkage created by the reaction of the first and second functional groups.
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Abstract
Modified relaxin polypeptides and their uses, including therapeutic uses thereof for the treatment of a fibrotic disorder or heart failure are provided. Exemplary embodiments provide for the use of relaxin polypeptides which include one or more amino acid substitutions with natural or non-naturally encoded amino acids, and/or linkage to a water-soluble polymer, such as polyethylene glycol.
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12 Claims
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1. A method of treating a patient having a fibrotic disorder, comprising administering to said patient an effective amount of a biologically active modified relaxin polypeptide, wherein (a) said modified relaxin polypeptide comprises an A chain and a B chain linked by at least one disulfide bond, wherein said A chain comprises SEQ ID NO:
- 4 substituted with a non-naturally encoded amino acid at position 1 and said B chain comprises SEQ ID NO;
5 or SEQ ID NO;
6, and (b) the non-naturally encoded amino acid is linked to a linker, polymer, or biologically active molecule, wherein said non-naturally encoded amino acid comprises a first functional group and the linker, polymer, or biologically active molecule comprises a second functional group, wherein the first functional group and second functional group are not identical and each comprise a carbonyl group, an aminooxy group, a hydrazide group, a hydrazine group, a semicarbazide group, an azide group, or an alkyne group, and the non-naturally encoded amino acid is linked to the linker, polymer, or biologically active molecule by the resultant covalent linkage created by the reaction of the first and second functional groups. - View Dependent Claims (2, 3, 4, 5, 6, 7)
- 4 substituted with a non-naturally encoded amino acid at position 1 and said B chain comprises SEQ ID NO;
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8. A method of treating heart failure in a patient in need thereof, comprising administering to said patient an effective amount of a biologically active modified relaxin polypeptide, said modified relaxin polypeptide comprising an A chain and a B chain linked by at least one disulfide bond, wherein said A chain comprises SEQ ID NO:
- 4 substituted with a non-naturally encoded amino acid at position 1 and said B chain comprises SEQ ID NO;
5 or SEQ ID NO;
6, wherein the non-naturally encoded amino acid at position 1 of the A chain is linked to a water soluble polymer, and said non-naturally encoded amino acid comprises para-acetyl-L-phenylalanine. - View Dependent Claims (9, 10, 11, 12)
- 4 substituted with a non-naturally encoded amino acid at position 1 and said B chain comprises SEQ ID NO;
Specification