Bovine fusion antibodies
Disclosed herein are immunoglobulin constructs comprising at least one immunoglobulin domain or fragment thereof; and a therapeutic polypeptide or derivative or variant thereof attached to or inserted into said immunoglobulin domain. Also provided are immunoglobulin constructs comprising a mammalian immunoglobulin heavy chain comprising at least a portion of a knob domain in the complementarity-determining region 3 (CDR3H) or fragment thereof; and a therapeutic polypeptide attached to or inserted into the CDR3H. Also provided are immunoglobulin constructs comprising a mammalian immunoglobulin heavy chain comprising at least a portion of a stalk domain in the complementarity-determining region 3 (CDR3H) or fragment thereof; and a therapeutic polypeptide attached to or inserted into said stalk domain of the CDR3H. Also described herein are methods and compositions comprising the immunoglobulin constructs described herein for treatment and prevention of a disease or condition in a subject.
1. A fusion protein comprising:
a. a non-antibody region comprising a polypeptide selected from a group consisting of relaxin, betatrophin, elafin, and BCCX2;
b. an antibody variable domain;
c. a stalk domain of an ultralong complementarity determining region 3 (CDR3) comprising at least one of SEQ ID NOs: 18-21, 25, 26, and 34-37; and
d. one or more serine residues from a knob domain of an ultralonq CDR3; wherein the non-antibody region is inserted into or replaces at least a portion of a complementarity-determining region (CDR) of the antibody variable domain;
wherein the non-antibody sequence is connected to the antibody variable domain by the stalk domain and knob domain; and
wherein the polypeptide within the antibody variable domain is functional to treat or ameliorate a disease, disorder or condition when the fusion protein is administered to a subject in need thereof.
2. The fusion protein of claim 1 , wherein the polypeptide is relaxin.
3. The fusion protein of claim 2 , wherein the relaxin is human relaxin 2.
4. The fusion protein of claim 1 , wherein the polypeptide is betatrophin.
5. The fusion protein of claim 1 , wherein the polypeptide is elafin.
6. The fusion protein of claim 1 , wherein the polypeptide is BCCX2.
7. The fusion protein of claim 1 , wherein the antibody is selected from a human antibody, a humanized antibody, a human engineered antibody, a chimeric antibody, a bovine antibody, and fragments thereof.
8. A pharmaceutical composition comprising a therapeutically effective amount of the fusion protein of claim 1 , and a pharmaceutically acceptable carrier.
9. The fusion protein of claim 1 , wherein the non-antibody region contains a polypeptide encoded by a polynucleotide sequence selected from SEQ ID NOS: 123, 124, 131, and 132, or an amino acid sequence selected from SEQ ID NOs: 142, 143, 150, and 151.
10. The fusion protein of claim 1 , wherein the non-antibody region is inserted into or replaces at least a portion of a CDR3 of the antibody variable domain.
11. A method of treating a disease or condition in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the fusion protein of claim 1 .
12. The method of claim 11 , wherein the disease or condition is selected from a group consisting of autoimmune disease, heteroimmune disease or condition, inflammatory disease, pathogenic infection, thromboembolic disorder, respiratory disease or condition, metabolic disease, central nervous system (CNS) disorder, bone disease, cancer, blood disorder, obesity, diabetes, osteoporosis, anemia, and pain.