Anti-GITR antibodies
View Patent ↗Antibodies to human GITR are provided, as well as uses thereof, e.g., in treatment of proliferative and immune disorders.
1. An isolated nucleic acid encoding:
a light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 105.
2. The isolated nucleic acid of claim 1 encoding:
a light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 105, wherein residue 31 is Q and residue 57 is Q.
3. The nucleic acid of claim 1 encoding:
(i) a light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 105, wherein residue 31 is Q and residue 57 is Q;
and
(ii) a heavy chain immunoglobulin variable region that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 104.
4. The nucleic acid of claim 3 encoding;
(i) a humanized light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 105, wherein residue 31 is Q and residue 57 is Q;
and
(ii) a humanized heavy chain immunoglobulin variable region that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 104.
5. The nucleic acid of claim 4 encoding:
(i) a humanized light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 105 wherein residue 31 is Q and residue 57 is Q, and a human light chain constant region;
and
(ii) a humanized heavy chain immunoglobulin variable region that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 104, and a human heavy chain constant region.
6. The nucleic acid of claim 5 wherein the human light chain constant region is kappa and the human heavy chain constant region is gamma-1.
7. The nucleic acid of claim 6 encoding:
(i) a humanized light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 105 wherein residue 31 is Q and residue 57 is Q, and a human kappa light chain constant region; which is operably linked to a promoter;
and
(ii) a humanized heavy chain immunoglobulin variable region that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 104, and a human gamma-1 heavy chain constant region; which is operably linked to a promoter.
8. The nucleic acid of claim 7 wherein (i) further comprises a secretory leader and (ii) further comprises a secretory leader.
9. The nucleic acid of claim 8 which is DNA.
10. An expression vector comprising the nucleic acid of claim 9 .
11. A host cell comprising the nucleic acid of claim 9 .
12. The host cell of claim 11 which is a mammalian cell.
13. The host cell of claim 11 which is a Chinese hamster ovary cell.
14. The host cell of claim 11 which is a yeast cell.
15. The host cell of claim 11 which is a Pichia pastoris cell.
16. The host cell of claim 11 which is an insect cell.
17. The host cell of claim 11 which is a human embryonic kidney 293 cell, a mouse myeloma NSO cell, a baby hamster kidney cell, or a Spodoptera frugiperda ovarian cell.
18. An isolated nucleic acid encoding:
a heavy chain immunoglobulin variable region that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 104.