CONSTANT REGION ANTIBODY FUSION PROTEINS AND COMPOSITIONS THEREOF
Disclosed herein are antibody fusion constructs and uses thereof. The antibody fusion construct may comprise an antibody fusion protein. The antibody fusion protein may comprise a non-antibody peptide inserted into an antibody portion of the antibody fusion protein. Alternatively, the antibody fusion construct may comprise a bispecific antibody. The bispecific antibody may comprise a second antibody or antibody fragment inserted into a first antibody or antibody fragment. Insertion of the non-antibody peptide (or second antibody or antibody fragment) into the antibody portion (or first antibody or antibody fragment) may comprise replacement of one or more amino acids in a constant domain of the antibody portion (or first antibody or antibody fragment). The antibody fusion constructs disclosed herein may be used to treat a disease, such as a cancer, an autoimmune disorder or an infection.
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34 . A bispecific antibody comprising:
a) a first antibody or antibody fragment comprising a modified constant domain or portion thereof; and
b) a second antibody or antibody fragment,
wherein the second antibody or antibody fragment is located within the modified constant domain or portion thereof.
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37 . The bispecific antibody of claim 34 , wherein the modified constant domain comprises a CH1 or portion thereof.
38 . The bispecific antibody of claim 34 , wherein the modified constant domain comprises a CH2 or portion thereof.
39 . The bispecific antibody of claim 34 , wherein the modified constant domain comprises a CH3 or portion thereof.
40 . The bispecific antibody of claim 34 , wherein the modified constant domain comprises a hinge region or portion thereof.
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43 . The bispecific antibody of claim 34 , wherein the second antibody or antibody fragment is a single chain variable fragment.
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52 . The bispecific antibody of claim 34 , wherein the first antibody or antibody fragment comprises 50 or more consecutive amino acids from any one of SEQ ID NO: 33-44.
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59 . A method of treating a disease or condition in a subject in need thereof, the method comprising administering to the subject the bispecific antibody of claim 34 .
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65 . An antibody fusion protein comprising an antibody or antibody fragment comprising a constant domain modified by insertion of a non-antibody polypeptide region comprising 15 or more amino acids within the constant domain, wherein the constant domain is modified from (i) a first constant domain of an antibody heavy chain (CH1) or a portion thereof, or (ii) a constant domain of an antibody light chain (CL) or a portion thereof.
66 . The antibody fusion protein of claim 65 , wherein the constant domain is modified by replacing 0 to about 20 amino acids of the constant domain with the non-antibody polypeptide
67 . The antibody fusion protein of claim 65 , wherein the constant domain is modified from the first constant domain of an antibody heavy chain (CH1) or portion thereof.
68 . The antibody fusion protein of claim 65 , wherein the constant domain is modified from the constant domain of an antibody light chain (CL1) or portion thereof.
69 . The antibody fusion protein of claim 65 , wherein the antibody fusion protein comprises 50 or more consecutive amino acids from any one of SEQ ID NOs: 33-44.
70 . The antibody fusion protein of claim 65 , wherein the non-antibody polypeptide region comprises erythropoietin, chemokine receptor-4 binding peptide, a tumor-homing peptide, an integrin αvβ3 binding peptide, or a T-cell epitope peptide.
71 . An antibody fusion protein comprising an antibody or antibody fragment comprising a constant domain modified with a non-antibody polypeptide region comprising 15 or more amino acids, wherein the non-antibody polypeptide region is located within the modified constant domain, and the non-antibody region comprises a linker peptide having a coiled-coil secondary structure.
72 . The antibody fusion protein of claim 71 , wherein the modified constant domain is modified from a heavy chain constant domain or a portion thereof.
73 . The antibody fusion protein of claim 71 , wherein the modified constant domain is modified from a light chain constant domain or a portion thereof.
74 . The antibody fusion protein of claim 71 , wherein the modified constant domain comprises an antibody hinge region or a portion thereof.
75 . The antibody fusion protein of claim 71 , comprising 50 or more consecutive amino acids from any one of SEQ ID NOs: 33-44.
76 . The antibody fusion protein of claim 71 , wherein the linker peptide is not an amino acid sequence from the antibody or antibody fragment.