METHODS OF TREATING BRONCHOPULMONARY DYSPLASIA

1 . A method of treating bronchopulmonary dysplasia (BPD) in a subject, the method comprising administering to the subject a therapeutically effective amount of a multi-chain chimeric polypeptide, wherein the multi-chain chimeric polypeptide comprises:

(a) a first chimeric polypeptide comprising:

(i) a first target-binding domain;

(ii) a soluble tissue factor domain comprising a sequence that is at least 80% identical to SEQ ID NO: 1; and

(iii) a first domain of a pair of affinity domains comprising a sequence that is at least 80% identical to SEQ ID NO: 45;

(b) a second chimeric polypeptide comprising:

(i) a second domain of a pair of affinity domains comprising a sequence that is at least 80% identical to SEQ ID NO: 43; and

(ii) a second target-binding domain,

wherein:

the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains; and

the first target-binding domain and the second target-binding domain each comprise a soluble TGF-β receptor II (TGF-βRII) and each comprise a first sequence that is at least 80% identical to SEQ ID NO: 2 and a second sequence that is at least 80% identical to SEQ ID NO: 2.

2 . The method of claim 1 , wherein the first target-binding domain and the soluble tissue factor domain directly abut each other in the first chimeric polypeptide.

3 . The method of claim 1 , wherein the first chimeric polypeptide further comprises a linker sequence between the first target-binding domain and the soluble tissue factor domain in the first chimeric polypeptide.

4 . The method of claim 1 , wherein the soluble tissue factor domain and the first domain of the pair of affinity domains directly abut each other in the first chimeric polypeptide.

5 . The method of claim 1 , wherein the first chimeric polypeptide further comprises a linker sequence between the soluble tissue factor domain and the first domain of the pair of affinity domains in the first chimeric polypeptide.

6 . The method of claim 1 , wherein the second domain of the pair of affinity domains and the second target-binding domain directly abut each other in the second chimeric polypeptide.

7 . The method of claim 1 , wherein the second chimeric polypeptide further comprises a linker sequence between the second domain of the pair of affinity domains and the second target-binding domain in the second chimeric polypeptide.

8 - 12 . (canceled)

13 . The method of claim 1 , wherein the first chimeric polypeptide further comprises one or more additional target-binding domain(s).

14 . The method of claim 1 , wherein the second chimeric polypeptide further comprises one or more additional target-binding domains.

15 . The method of claim 1 , wherein the soluble tissue factor domain is a soluble human tissue factor domain.

16 - 18 . (canceled)

19 . The method of claim 1 , wherein the first chimeric polypeptide and/or the second chimeric polypeptide further comprises a signal sequence at its N-terminal end.

20 - 23 . (canceled)

24 . The method of claim 1 , wherein:

the first target-binding domain comprises a sequence that is at least 80% identical to SEQ ID NO: 6; and

the second target-binding domain comprises a sequence that is at least 80% identical to SEQ ID NO: 6.

25 . The method of claim 24 , wherein:

the first target-binding domain comprises a sequence that is at least 90% identical to SEQ ID NO: 6;

the soluble tissue factor domain comprises a sequence that is at least 90% identical to SEQ ID NO: 1;

the first domain of the pair of affinity domains comprises a sequence that is at least 90% identical to SEQ ID NO: 45;

the second target-binding domain comprises a sequence that is at least 90% identical to SEQ ID NO: 6; and

the second domain of the pair of affinity domains comprises a sequence that is at least 90% identical to SEQ ID NO: 43.

26 . The method of claim 25 , wherein:

the first target-binding domain comprises a sequence of SEQ ID NO: 6,

the soluble tissue factor domain comprises a sequence of SEQ ID NO: 1;

the first domain of the pair of affinity domains comprises a sequence of SEQ ID NO: 45;

the second target-binding domain comprises a sequence of SEQ ID NO: 6; and

the second domain of the pair of affinity domains comprises a sequence of SEQ ID NO: 43.

27 . The method of claim 1 , wherein:

the first chimeric polypeptide comprises a sequence that is at least 80% identical to SEQ ID NO: 8; and

the second chimeric polypeptide comprises a sequence that is at least 80% identical to SEQ ID NO: 16.

28 . The method of claim 27 , wherein:

the first chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 8; and

the second chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 16.

29 . The method of claim 28 , wherein:

the first chimeric polypeptide comprises a sequence of SEQ ID NO: 8 and

the second chimeric polypeptide comprises a sequence of SEQ ID NO: 16.

30 . (canceled)

31 . The method of claim 28 , wherein:

the first chimeric polypeptide comprises a sequence of SEQ ID NO: 12; and

the second chimeric polypeptide comprises a sequence of SEQ ID NO: 16.

32 - 43 . (canceled)

44 . The method of claim 1 , wherein the subject has been identified or diagnosed as having bronchopulmonary dysplasia (BPD).

45 . A method of treating bronchopulmonary dysplasia (BPD) in a subject, the method comprising administering to the subject a therapeutically effective amount of a multi-chain chimeric polypeptide, wherein the multi-chain chimeric polypeptide comprises:

(a) a first chimeric polypeptide comprising:

(i) a first target-binding domain comprising:

a first sequence that is at least 80% identical to SEQ ID NO: 20, wherein one or both of (A) the amino acid at position 32 in SEQ ID NO: 20 is asparagine and (B) the amino acid at position 119 in SEQ ID NO: 20 is alanine; and

a second sequence that is at least 80% identical to SEQ ID NO: 20, wherein one or both of (A) the amino acid at position 32 in SEQ ID NO: 20 is asparagine and (B) the amino acid at position 119 in SEQ ID NO: 20 is alanine;

(ii) a soluble tissue factor domain comprises a sequence that is at least 80% identical to SEQ ID NO: 1; and

(iii) a first domain of a pair of affinity domains comprising a sequence that is at least 80% identical to SEQ ID NO: 45; and

(b) a second chimeric polypeptide comprising:

(i) a second domain of a pair of affinity domains comprising a sequence that is at least 80% identical to SEQ ID NO: 43; and

(ii) a second target-binding domain comprising:

a first sequence that is at least 80% identical to SEQ ID NO: 20, wherein one or both of (A) the amino acid at position 32 in SEQ ID NO: 20 is asparagine and (B) the amino acid at position 119 in SEQ ID NO: 20 is alanine; and

a second sequence that is at least 80% identical to SEQ ID NO: 20, wherein one or both of (A) the amino acid at position 32 in SEQ ID NO: 20 is asparagine and (B) the amino acid at position 119 in SEQ ID NO: 20 is alanine,

wherein:

the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains; and

the first target-binding domain and the second target-binding domain each comprise a soluble TGF-β receptor II (TGF-αRII).

46 - 94 . (canceled)