Anti-4-1BB antibodies and their uses
The present disclosure provides novel anti-4-1BB antibodies, compositions including the new antibodies, nucleic acids encoding the antibodies, and methods of making and using the same.
1. An anti-4-1BB antibody or binding fragment thereof comprising (i) a V H chain comprising three CDRs; and (ii) a V L chain comprising three CDRs, wherein:
V H CDR #1 is GYTFTSYYIY (SEQ ID NO:16);
V H CDR #2 is NIWPGNGGTFYGEKFMG (SEQ ID NO:26);
V H CDR #3 is RPDYSGDDYFDY (SEQ ID NO:36);
V L CDR #1 is KLNSGNIGSYYVH (SEQ ID NO:56);
V L CDR #2 is RDDKRPD (SEQ ID NO:66); and
V L CDR #3 is HSYDSTITPV (SEQ ID NO:76),
or
V H CDR #1 is DYTFNDYWVS (SEQ ID NO:17);
V H CDR #2 is EIYPNSGATNFNGKFRG (SEQ ID NO:27);
V H CDR #3 is EYTRDWFAY (SEQ ID NO:37);
V L CDR #1 is RSSQSLLDSDGNTYLY (SEQ ID NO:57);
V L CDR #2 is LVSNLGS (SEQ ID NO:67); and
V L CDR #3 is MQPTHAPYT (SEQ ID NO:77).
2. The anti-4-1BB antibody or binding fragment of claim 1 which is human or humanized.
3. The anti-4-1BB antibody or binding fragment of claim 2 , which comprises a V H chain corresponding in sequence to SEQ ID NO:109 and a V L chain corresponding in sequence to SEQ ID NO:161.
4. The anti-4-1BB antibody or binding fragment claim 2 , which comprises a V H chain corresponding in sequence to SEQ ID NO:109 and a V L chain corresponding in sequence to SEQ ID NO:159.
5. The anti-4-1BB antibody or binding fragment claim 2 , which comprises a V H chain corresponding in sequence to SEQ ID NO:111 and a V L chain corresponding in sequence to SEQ ID NO:165.
6. The anti-4-1BB antibody or binding fragment of claim 3 , which is an IgG, optionally an IgG 1 or IgG 4 .
7. The anti-4-1BB antibody of claim 6 , which comprises a variant IgG 1 CH2 region comprising the amino acid substitution V273E or V273Y.
8. The anti-4-1BB antibody of claim 6 , which comprises a variant IgG 4 hinge region comprising the amino acid substitution S228P.
9. A pharmaceutical composition comprising an anti-4-1BB antibody or binding fragment of claim 1 , and a pharmaceutically acceptable carrier.
10. A nucleic acid comprising a nucleotide sequence encoding an anti-4-1BB antibody or binding fragment of claim 1 .
11. A eukaryotic host cell transformed with a vector comprising the nucleic acid of claim 10 .
12. A method of producing an anti-4-1BB antibody or binding fragment thereof, comprising: (a) culturing the host cell of claim 11 and (b) recovering the antibody or binding fragment.
13. The anti-4-1BB antibody or binding fragment of claim 4 , which is an IgG, optionally an IgG1 or IgG4.
14. The anti-4-1BB antibody of claim 13 , which comprises a variant IgG1 CH2 region comprising the amino acid substitution V273E or V273Y.
15. The anti-4-1BB antibody of claim 13 , which comprises a variant IgG4 hinge region comprising the amino acid substitution S228P.
16. The anti-4-1BB antibody or binding fragment of claim 5 , which is an IgG, optionally an IgG1 or IgG4.
17. The anti-4-1BB antibody of claim 16 , which comprises a variant IgG1 CH2 region comprising the amino acid substitution V273E or V273Y.
18. The anti-4-1BB antibody of claim 16 , which comprises a variant IgG4 hinge region comprising the amino acid substitution S228P.