Heterodimeric antibodies that bind fibroblast activation protein
The present invention relates to novel antigen binding domains and heterodimeric antibodies that bind Fibroblast Activation Protein (FAP).
1. A composition comprising a fibroblast activation protein (FAP) binding domain, the FAP binding domain comprising:
a) a variable heavy domain comprising a vhCDR1, vhCDR2, and vhCDR3; and
b) a variable light domain comprising a vlCDR1, vlCDR2, and vlCDR3;
wherein vhCDR1-3 and vlCDR1-3 are selected from the following:
i) a vhCDR1 having the amino acid sequence of SEQ ID NO: 158, a vhCDR2 having the amino acid sequence of SEQ ID NO: 159, a vhCDR3 having the amino acid sequence of SEQ ID NO: 160, a vlCDR1 having the amino acid sequence of SEQ ID NO: 162, a vlCDR2 having the amino acid sequence of SEQ ID NO: 163, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 164;
ii) a vhCDR1 having the amino acid sequence of SEQ ID NO: 166, a vhCDR2 having the amino acid sequence of SEQ ID NO: 167, a vhCDR3 having the amino acid sequence of SEQ ID NO: 168, a vlCDR1 having the amino acid sequence of SEQ ID NO: 170, a vlCDR2 having the amino acid sequence of SEQ ID NO: 171, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 172;
iii) a vhCDR1 having the amino acid sequence of SEQ ID NO: 182, a vhCDR2 having the amino acid sequence of SEQ ID NO: 183, a vhCDR3 having the amino acid sequence of SEQ ID NO: 184, a vlCDR1 having the amino acid sequence of SEQ ID NO: 186, a vlCDR2 having the amino acid sequence of SEQ ID NO: 187, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 188; and
iv) a vhCDR1 having the amino acid sequence of SEQ ID NO: 190, a vhCDR2 having the amino acid sequence of SEQ ID NO: 191, a vhCDR3 having the amino acid sequence of SEQ ID NO: 192, a vlCDR1 having the amino acid sequence of SEQ ID NO: 194, a vlCDR2 having the amino acid sequence of SEQ ID NO: 195, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 196.
2. The composition of claim 1 , wherein the variable heavy domain has the amino acid sequence of SEQ ID NO: 157 and the variable light domain has the amino acid sequence of SEQ ID NO: 161.
3. The composition of claim 1 , wherein the variable heavy domain has the amino acid sequence of SEQ ID NO: 165 and the variable light domain has the amino acid sequence of SEQ ID NO: 169.
4. The composition of claim 1 , wherein the variable heavy domain has the amino acid sequence of SEQ ID NO: 181 and the variable light domain has the amino acid sequence of SEQ ID NO: 185.
5. The composition of claim 1 wherein the variable heavy domain has the amino acid sequence of SEQ ID NO: 189 and the variable light domain has the amino acid sequence of SEQ ID NO: 193.
6. A nucleic acid composition encoding the FAP binding domain of claim 1 , comprising:
a) a first nucleic acid encoding the variable heavy domain; and
b) a second nucleic acid encoding the variable light domain.
7. An expression vector composition encoding the FAP binding domain of claim 1 , comprising:
a) a first expression vector comprising a nucleic acid encoding the variable heavy domain; and
b) a second expression vector comprising second nucleic acid encoding the variable light domain.
8. A host cell comprising the expression vector composition of claim 7 .
9. A method of making a FAP binding domain comprising culturing the host cell of claim 8 under conditions wherein the FAP binding domain is expressed and recovering the FAP binding domain.
10. A composition comprising a fibroblast activation protein (FAP) binding domain, wherein the FAP binding domain comprises a variable heavy domain and a variable light domain selected from the following:
i) a variable heavy domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 157, and a variable light domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 161;
ii) a variable heavy domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 165, and a variable light domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 169;
iii) a variable heavy domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 181, and a variable light domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 185; and
iv) a variable heavy domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 189, and a variable light domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 193.