Anti-ilt4 antibodies and antigen-binding fragments
AssigneesMerck Sharp & Dohme Corp., Agenus Inc.
InventorsMilan BLANUSA, Barbara JOYCE-SHAIKH, Andrea Claudia SCHUSTER, Kornelia SCHULTZE, Luis A. ZUNIGA
Life of this patent
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Abstract
The present invention provides antibodies and antigen-binding fragments thereof that bind to ILT4 (immunoglobulin-like transcript 4) and combinations thereof, e.g., with an anti-PD1 antibody. Also provided are methods of use thereof, for example, for treating or preventing cancer in a subject; and methods of making such antibodies and fragments.
Claims42
An antibody or antigen-binding fragment thereof that binds one or more amino acid residues in a human immunoglobulin-like transcript 4 (ILT4) epitope selected from the group consisting of LYREKKSASW (SEQ ID NO:59), TRIRPEL (SEQ ID NO:60), NGQF (SEQ ID NO:61), and HTGRYGCQ (SEQ ID NO:62) and protects the epitope from deuterium exchange in the presence of a deuterium source.
An antibody or antigen-binding fragment thereof that competes with a reference antibody for binding to a human ILT4 epitope selected from the group consisting of LYREKKSASW (SEQ ID NO:59), TRIRPEL (SEQ ID NO:60), NGQF (SEQ ID NO:61), and HTGRYGCQ (SEQ ID NO:62), wherein the reference antibody comprises a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO:2 and a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO:7.
An antibody or antigen-binding fragment thereof that binds human ILT4, comprising:
- (1) a heavy chain variable domain comprising:
- CDR-H1:
- (SEQ ID NO:
- 16)
- GYYWS,
- CDR-H2:
- (SEQ ID NO:
- 17)
- EINHXGSTNYNPSLKS wherein X is S or A,
- and
- CDR-H3:
- (SEQ ID NO:
- 18)
- LPTRWVTTRYFDL;
- and,
- a light chain variable domain comprising:
- CDR-L1:
- (SEQ ID NO:
- 19)
- TGSSSNIGAGYDVH.
- CDR-L2:
- (SEQ ID NO:
- 20)
- GX1X2NRPS, wherein X1 is N, Q, E or D and
- X2 is S or A,
- and
- CDR-L3:
- (SEQ ID NO:
- 21)
- QSFDNSLSAYV;
- (2) a heavy chain variable domain comprising:
- CDR-H1:
- (SEQ ID NO:
- 22)
- SYAIS,
- CDR-H2:
- (SEQ ID NO:
- 23)
- GIIPIFGTANYAQKFQG,
- and
- CDR-H3:
- (SEQ ID NO:
- 24)
- YFX1X2SGWYKGGAFDI, wherein X1 is D or S and
- X2 is S or A;
- and,
- a light chain variable domain comprising:
- CDR-L1:
- (SEQ ID NO:
- 25)
- TLRSGINVDTYRIH,
- CDR-L2:
- (SEQ ID NO:
- 26)
- YKSDSDKHQGS,
- and
- CDR-L3:
- (SEQ ID NO:
- 27)
- AIWYSSTWV;
- (3) a heavy chain variable domain comprising:
- CDR-H1:
- (SEQ ID NO:
- 28)
- SYAMH,
- CDR-H2:
- (SEQ ID NO:
- 29)
- VISYDGSNKYYADSVKG,
- and
- CDR-H3:
- (SEQ ID NO:
- 30)
- VGEWIQLWSPFDY;
- and,
- a light chain variable domain comprising:
- CDR-L1:
- (SEQ ID NO:
- 31)
- RASQGISSWLA,
- CDR-L2:
- (SEQ ID NO:
- 32)
- AASSLQS,
- and
- CDR-L3:
- (SEQ ID NO:
- 33)
- QQYNSYPPT;
- or
- (4) a heavy chain variable domain comprising:
- CDR-H1:
- (SEQ ID NO:
- 34)
- ELSMH,
- CDR-H2:
- (SEQ ID NO:
- 35)
- GFDPEDGETIYAQKFQG,
- and
- CDR-H3:
- (SEQ ID NO:
- 36)
- AGPLYTIFGVVIIPDNWFDP;
- and,
- a light chain variable domain comprising:
- CDR-L1:
- (SEQ ID NO:
- 37)
- TGSSSNIGAGYDVH,
- CDR-L2:
- (SEQ ID NO:
- 38)
- GNSNRPS,
- and
- CDR-L3:
- (SEQ ID NO:
- 39)
- QSYDSSLSGSGVV.
An antibody that consists of two heavy chains and two light chains, wherein each light chain comprises the amino acid sequence set forth in SEQ ID NO:58 and each heavy chain comprises the amino acid sequence set forth in SEQ ID NO:57.
An antibody that consists of two heavy chains and two light chains, wherein each light chain comprises the amino acid sequence set forth in SEQ ID NO:7 and each heavy chain comprises the amino acid sequence set forth in SEQ ID NO:2.
An antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in SEQ ID NO:7 and each heavy chain consists of the amino acid sequence set forth in SEQ ID NO:2.
A pharmaceutical composition comprising:
- (i) an antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in SEQ ID NO:7 and each heavy chain consists of the amino acid sequence set forth in SEQ ID NO:2, and (ii) pembrolizumab.
Dependencies are inferred from the claim text.