MODIFIED THERAPEUTIC AGENTS AND COMPOSITIONS THEREOF

1 .- 11 . (canceled)

12 . A modified therapeutic agent comprising:

(i) a therapeutic agent (TA) comprising a relaxin A-chain amino acid sequence that is at least 90% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 54, 55, 59 and 60; and

(ii) a half-life extending moiety;

wherein the TA is covalently attached to the half-life extending moiety via a cysteine residue of the TA.

13 . (canceled)

14 . The modified therapeutic agent of claim 12 , wherein the relaxin A-chain amino acid sequence is selected from the group consisting of SEQ ID NO: 54, 55, 59 and 60.

15 . The modified therapeutic agent of claim 12 , wherein the cysteine residue is in the relaxin A-chain amino acid sequence.

16 . (canceled)

17 . (canceled)

18 . (canceled)

19 . The modified therapeutic agent of claim 12 , wherein the therapeutic agent further comprises a relaxin B-chain.

20 . (canceled)

21 . (canceled)

22 . The modified therapeutic agent of claim 12 , wherein the therapeutic agent further comprises a relaxin B-chain amino acid sequence that is at least 90% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 16, 40, 48-52, 56, 58, and 61.

23 . The modified therapeutic agent of claim 12 , wherein the therapeutic agent further comprises a relaxin B-chain amino acid sequence SEQ ID NO: 48.

24 . The modified therapeutic agent of claim 12 , wherein the half-life of the modified therapeutic agent is longer than the half-life of the therapeutic agent alone.

25 .- 52 . (canceled)

53 . The modified therapeutic agent of claim 12 , wherein the modified therapeutic agent has the following formula:

TA-A 1 -P 1 -L   Formula (A)

wherein:

TA is the therapeutic agent;

 is the half-life extending moiety.

54 . The modified therapeutic agent of claim 53 , wherein:

A 1 is a chemical group linking TA and P 1 or L;

P 1 is a bond or -PEG-A 2 -; and

L is a lipid derivative selected from the group consisting of sterol derivatives, bile acid derivatives, vitamin E derivatives, fatty di-acid derivatives, fatty acid derivatives, fatty amide derivatives, fatty amine amine derivatives, and fatty alcohol derivatives; wherein the lipid derivative is linked to P 1 via an amide or an ether linkage.

55 . (canceled)

56 . The modified therapeutic agent of claim 54 , wherein

A 1 is selected from

PEG is selected from

A 2 is selected from a bond,

L is an acid moiety selected from tetradecanoic acid, octadecanedioic acid, myristic acid, stearic acid, docosahexaenoic acid, lithocholic acid, cholic acid, and palmitic acid; wherein the acid moiety is linked to P 1 via an amide linkage;

X is a bond, —N(R 5 )—, —S—, or —O—;

each R 1 , R 2 , R 3 , and R 4 is independently H, halo, —CN, —SR 5 , alkyl, cycloalkyl, haloalkyl, —NR 5 R 5 , or —OR 5 ;

each R 5 is independently H, alkyl, haloalkyl, arylalkyl, or heteroalkyl;

R 6 is OH or —NR 5 R 5 ;

each R 7 is independently H, alkyl, haloalkyl, arylalkyl, or heteroalkyl;

m and n are independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

s is 1, 2, 3, 4, or 5;

k is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

p is 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

q is 2, 3, 4, 5, 6, 7, 8, 9, or 10.

57 . The modified therapeutic agent of claim 56 , wherein:

A 1 is

58 . The modified therapeutic agent of claim 56 , wherein:

PEG is

59 . The modified therapeutic agent of claim 56 , wherein:

A 2 is

60 . The modified therapeutic agent of claim 56 , wherein

each R 1 , R 2 , R 3 , and R 4 is H;

each R 5 is independently H;

each R 6 is OH or NH 2 ;

each R 7 is H;

m is 1, 2, 3, 4, 5, 6, 7, 8, or 9;

n is 1, 2, 3, 4, or 5;

r is 1, 2, or 3;

s is 2 or 4;

p is 2; and

X is —O—.

61 .- 69 . (canceled)

70 . The modified therapeutic agent of claim 53 , wherein the modified therapeutic agent is selected from the following:

71 . The modified therapeutic agent of claim 53 , wherein the modified therapeutic agent is:

72 . (canceled)

73 . A pharmaceutical composition comprising the modified therapeutic agent of claim 12 .

74 . A method for treating a disease or condition in a subject in need thereof, the method comprising administering to the subject a composition comprising a therapeutically effective amount of the modified therapeutic agent of claim 12 .

75 . The method of claim 74 , wherein the disease or condition is a cardiovascular disorder, acute heart failure, fibrosis, or pain.

76 .- 79 . (canceled)

80 . The method of claim 74 , wherein the modified therapeutic agent is administered with one or more additional therapeutic agents selected from group consisting of an anti-inflammatory drug and a drug to treat pain, or any combination thereof.

81 . (canceled)

82 . (canceled)