The present invention concerns compositions of matter, for example, but not limited to, modified antibodies, in which one or more biologically active peptides are incorporated into a loop region of a non-terminal domain of an immunoglobulin Fc domain.
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What is claimed is: 1. A composition of matter of the formula (X1)a—F1—(X2)b and multimers thereof, wherein: F1 is an IgG1 Fc domain comprising SEQ ID NO: 603 modified so that it comprises at least one X3 inserted into or replacing all or part of a sequence selected from SEQ ID N
What is claimed is: 1. A composition of matter of the formula (X1)a—F1—(X2)b and multimers thereof, wherein: F1 is an IgG1 Fc domain comprising SEQ ID NO: 603 modified so that it comprises at least one X3 inserted into or replacing all or part of a sequence selected from SEQ ID NOS: 621, 622, 624, 625, 627, 628, 630, 632, 634, and 636 within a loop region of the IgG1 Fc domain, said loop region being in a non-terminal domain of the Fc domain; X1 and X2 are each independently selected from -(L1)c-P1, -(L1)c-P1-(L2)d-P2, -(L1)c-P1-(L2)d-P2-(L3)e-P3, and -(L1)c-P1-(L1)d-P2-(L3)e-P3-(L4)f-P4; X3 is independently selected from -(L5)c-P5, -(L5)c-P5-(L6)d-P6, -(L5)c-P5-(L6)d-P6-(L7)e-P7, and -(L5)c-P5-(L6)d-P6-(L7)e-P7-(L8)f-P8; P1, P2, P3, and P4 are each independently sequences of pharmacologically active polypeptides or pharmacologically active peptides; P5, P6, P7, and P8 are each independently sequences of pharmacologically active peptides; L1, L2, L3, L4, L5, L6, L7, and L8 are each independently linkers; and a, b, c, d, e, and f are each independently 0 or 1. 2. The composition of matter of claim 1, wherein X3 is inserted at H53/E54, Y81/N82, N110/K111, L143/T144, Q171/P172, E173/N174, S185/D186, G187/S188, or G205/N206. 3. The composition of matter of claim 1, wherein X3 comprises a myostatin binding peptide sequence, an erythropoietin-mimetic (EPO-mimetic) peptide sequence, an angiotensin-2 (ang-2) binding peptide sequence, a thrombopoietin-mimetic (TPO-mimetic) peptide sequence, an angiotensin-2 (ang-2) binding peptide sequence, a nerve growth factor (NGF) binding peptide sequence, or a B cell activating factor (BAFF) binding peptide sequence. 4. The composition of matter of claim 3, wherein the myostatin binding peptide sequence is selected from SEQ ID NOS: 218 to 509. 5. The composition of matter of claim 3, wherein the EPO-mimetic peptide sequence is selected from SEQ ID NOS: 1 to 27. 6. The composition of matter of claim 3, wherein the TPO-mimetic peptide sequence is selected from SEQ ID NOS: 28 to 99. 7. The composition of matter of claim 3, wherein the ang-2 binding peptide sequence is selected from SEQ ID NOS: 100 to 189. 8. The composition of matter of claim 3, wherein the NGF binding peptide sequence is selected from SEQ ID NOS: 190 to 218. 9. The composition of matter of claim 3, wherein the BAFF binding peptide sequence is selected from SEQ ID NOS: 510 to 594. 10. A modified antibody, comprising an Fc domain, F1, wherein: F1 is an IgG1 Fc domain comprising SEQ ID NO: 603 modified so that it comprises at least one X3 inserted into or replacing all or part of a sequence selected from SEQ ID NOS: 621, 622, 624, 625, 627, 628, 630, 632, 634, and 636 within a loop region of the IgG1 Fc domain, said loop region being in a non-terminal domain of the Fc domain, wherein: X3 is independently selected from -(L5)c-P5, -(L5)c-P5-(L6)d-P6, -(L5)c-P5-(L6)d-P6-(L7)e-P7, and -(L5)c-P5-(L6)d-P6-(L7)e-P7-(L8)f-P8; P5, P6, P7, and P8 are each independently sequences of pharmacologically active peptides; L5, L6, L7, and L8 are each independently linkers; and c, d, e, and f are each independently 0 or 1. 11. The modified antibody of claim 10, wherein X3 is inserted at H53/E54, Y81/N82, N110/K111, L143/T144, Q171/P172, E173/N174, S185/D186, G187/S188, or G205/N206. 12. The modified antibody of claim 10, wherein X3 comprises a myostatin binding peptide sequence, an erythropoietin-mimetic (EPO-mimetic) peptide sequence, a thrombopoietin-mimetic (TPO-mimetic) peptide sequence, an angiotensin-2 (ang-2) binding peptide sequence, a nerve growth factor (NGF) binding peptide sequence, or a B cell activating factor (BAFF) binding peptide sequence. 13. The modified antibody of claim 12, wherein the myostatin binding peptide sequence is selected from SEQ ID NOS: 218 to 509. 14. The modified antibody of claim 12, wherein the EPO-mimetic peptide sequence is selected from SEQ ID NOS: 1 to 27. 15. The modified antibody of claim 12, wherein the TPO-mimetic peptide sequence is selected from SEQ ID NOS: 28 to 99. 16. The modified antibody of claim 12, wherein the ang-2 binding peptide sequence is selected from SEQ ID NOS: 100 to 189. 17. The modified antibody of claim 12, wherein the NGF binding peptide sequence is selected from SEQ ID NOS: 190 to 218. 18. The modified antibody of claim 12, wherein the BAFF binding peptide sequence is selected from SEQ ID NOS: 510 to 594.
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