Fc binding fragments comprising a CD137 antigen-binding site

1. A specific binding member that binds CD137 and comprises a CD137 antigen-binding site located in a CH3 domain of the specific binding member, the CD137 antigen-binding site comprising a first sequence located in the AB structural loop of the CH3 domain, wherein said first sequence comprises the sequence PPY (SEQ ID NO: 10), and wherein:

(i) when the specific binding member comprises the sequences set forth in SEQ ID NO: 138 and SEQ ID NO: 111 [FS22-172-003] in the AB and EF structural loops of the CH3 domain, respectively, the specific binding member does not comprise a CDR-based antigen-binding site that binds PD-L1 or MSLN, and

(ii) when the specific binding member comprises the sequences set forth in SEQ ID NO: 19 and SEQ ID NO: 20 [FS22-053-008] in the AB and EF structural loops of the CH3 domain, respectively, the specific binding member does not comprise a CDR-based antigen-binding site that binds PD-L1.

2. The specific binding member according to claim 1 , wherein the specific binding member comprises an insertion in the AB structural loop.

3. The specific binding member according to claim 2 , wherein said insertion is 5 amino acids in length.

4. The specific binding member according to claim 1 , wherein the first sequence is the first sequence of specific binding member:

(i) FS22-172-003 set forth in SEQ ID NO: 138;

(ii) FS22-172-002 set forth in SEQ ID NO: 129;

(iii) FS22-172-004 set forth in SEQ ID NO: 147;

(iv) FS22-172-001 set forth in SEQ ID NO: 120;

(v) FS22-172-005 set forth in SEQ ID NO: 156;

(vi) FS22-172-006 set forth in SEQ ID NO: 110; or

(vii) FS22-172 set forth in SEQ ID NO: 110.

5. The specific binding member according to claim 4 , wherein the specific binding member further comprises a second sequence located in the EF structural loop of the CH3 domain, and wherein the second sequence is the second sequence of specific binding member FS22-172-003, FS22-172-002, FS22-172-004, FS22-172-001, FS22-172-005, FS22-172-006, or FS22-172 set forth in SEQ ID NO: 111.

6. The specific binding member according to claim 1 , wherein the specific binding member comprises the CH3 domain sequence of specific binding member:

(i) FS22-172-003 set forth in SEQ ID NO: 139;

(ii) FS22-172-002 set forth in SEQ ID NO: 130;

(iii) FS22-172-004 set forth in SEQ ID NO: 148;

(iv) FS22-172-001 set forth in SEQ ID NO: 121;

(v) FS22-172-005 set forth in SEQ ID NO: 157;

(vi) FS22-172-006 set forth in SEQ ID NO: 165; or

(vii) FS22-172 set forth in SEQ ID NO: 112.

7. The specific binding member according to claim 1 , wherein the specific binding member comprises the sequence of specific binding member FS22-172-003, FS22-172-002, FS22-172-004, FS22-172-001, FS22-172-005, FS22-172-006, or FS22-172 set forth in SEQ ID NO: 141, 132, 150, 123, 159, 167, and 114, respectively.

8. The specific binding member according to claim 1 , wherein the first sequence is the first sequence of specific binding member FS22-053-008, FS22-053-009, FS22-053-011, FS22-053-017, FS22-053-014, FS22-053-010, FS22-053-012, FS22-053-013, FS22-053-015, FS22-053-016, and/or FS22-053 set forth in SEQ ID NO: 19.

9. The specific binding member according to claim 8 , wherein the specific binding member further comprises a second sequence located in the EF structural loop of the CH3 domain, and wherein the second sequence is the second sequence of specific binding member:

(i) FS22-053-008 set forth in SEQ ID NO: 20;

(ii) FS22-053-009 set forth in SEQ ID NO: 29;

(iii) FS22-053-011 set forth in SEQ ID NO: 47;

(iv) FS22-053-017 set forth in SEQ ID NO: 101;

(v) FS22-053-014 set forth in SEQ ID NO: 74;

(vi) FS22-053-010 set forth in SEQ ID NO: 38;

(vii) FS22-053-012 set forth in SEQ ID NO: 56;

(viii) FS22-053-013 set forth in SEQ ID NO: 65;

(ix) FS22-053-015 set forth in SEQ ID NO: 83;

(x) FS22-053-016 set forth in SEQ ID NO: 92; or

(xi) FS22-053 set forth in SEQ ID NO: 174.

10. The specific binding member according to claim 1 , wherein the specific binding member comprises the CH3 domain sequence of specific binding member:

(i) FS22-053-008 set forth in SEQ ID NO: 21;

(ii) FS22-053-009 set forth in SEQ ID NO: 30;

(iii) FS22-053-011 set forth in SEQ ID NO: 48;

(iv) FS22-053-017 set forth in SEQ ID NO: 102;

(v) FS22-053-014 set forth in SEQ ID NO: 75;

(vi) FS22-053-010 set forth in SEQ ID NO: 39;

(vii) FS22-053-012 set forth in SEQ ID NO: 57;

(viii) FS22-053-013 set forth in SEQ ID NO: 66;

(ix) FS22-053-015 set forth in SEQ ID NO: 84;

(x) FS22-053-016 set forth in SEQ ID NO: 93; or

(xi) FS22-053 set forth in SEQ ID NO: 175.

11. The specific binding member according to claim 1 , wherein the specific binding member comprises the sequence of: specific binding member FS22-053-008, FS22-053-009, FS22-053-011, FS22-053-017, FS22-053-014, FS22-053-010, FS22-053-012, FS22-053-013, FS22-053-015, FS22-053-016, or FS22-053 set forth in SEQ ID NO: 23, 32, 50, 104, 77, 41, 59, 68, 86, 95, and 15, respectively.

12. The specific binding member according to claim 1 , wherein the specific binding member comprises the first sequence, first and second sequence, CH3 domain sequence, or sequence of specific binding member FS22-172-003 or FS22-053-008, preferably FS22-172-003.

13. The specific binding member according to claim 1 , wherein the specific binding member further comprises a CDR-based antigen-binding site.

14. The specific binding member according to claim 13 , wherein the specific binding member is an antibody molecule.

15. The antibody molecule according to claim 14 , wherein the CDR-based antigen-binding site binds a second antigen selected from the group consisting of: an immune cell antigen, a tumour antigen, and a pathogenic antigen.

16. The specific binding member according to claim 1 , wherein the specific binding member has been modified to reduce or abrogate binding of the specific binding member to one or more Fcγ receptors.

17. A nucleic acid molecule encoding the specific binding member according to claim 1 .

18. A method of producing a specific binding member according to claim 1 , comprising culturing a recombinant host cell comprising a nucleic acid encoding the specific binding member of claim 1 under conditions for production of the specific binding member.

19. The specific binding member according to claim 1 , wherein the specific binding member is conjugated to a bioactive molecule.

20. A pharmaceutical composition comprising the antibody molecule according to claim 14 and a pharmaceutically acceptable excipient.

21. A method of treating a disease or disorder in an individual comprising administering to the individual a therapeutically effective amount of the antibody molecule according to claim 14 .

22. A method according to claim 21 , wherein the treatment is the treatment of cancer or an infectious disease in an individual.