Optimized CD3 Antigen Binding Domains
AssigneeMedImmune, LLC
InventorsYariv MAZOR, Zachary BRITTON, Xiuling LI, Sterling PAYNE, Even WALSENG, Chunning YANG
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Abstract
The present disclosure relates to antibodies or fragments thereof comprising an antigen binding domain capable of binding to a CD3 protein or a fragment thereof. The present disclosure also relates to such antibodies that bind to CD3 having optimized affinity to induce T cell activation, but without being associated with excessive cytokine release and reduced tolerability. The disclosure also relates to methods of producing these antibodies and their therapeutic uses.
Claims37
An antibody comprising an antigen binding domain that is capable of binding to a CD3 protein or a fragment thereof, wherein the CD3 antigen binding domain comprises a heavy chain variable (VH) region according to any one of the following:
- a VH region comprising the following CDRs:
- HCDR1 having the amino acid sequence of SEQ ID NO:
- 90;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 91;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 92,
- a VH region comprising the following CDRs:
- HCDR 1 having the amino acid sequence of SEQ ID NO:
- 82;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 83;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 84,
- a VH region comprising the following CDRs:
- HCDR 1 having the amino acid sequence of SEQ ID NO:
- 78;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 79;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 80,
- a VH region comprising the following CDRs:
- HCDR1 having the amino acid sequence of SEQ ID NO:
- 66;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 67;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 68,
- a VH region comprising the following CDRs:
- HCDR1 having the amino acid sequence of SEQ ID NO:
- 70;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 71;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 72,
- a VH region comprising the following CDRs:
- HCDR 1 having the amino acid sequence of SEQ ID NO:
- 74;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 75;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 76,
- a VH region comprising the following CDRs:
- HCDR 1 having the amino acid sequence of SEQ ID NO:
- 86;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 87;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 88,
- a VH region comprising the following CDRs:
- HCDR 1 having the amino acid sequence of SEQ ID NO:
- 94;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 95;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 96, and
- a VH region comprising the following CDRs:
- HCDR1 having the amino acid sequence of SEQ ID NO:
- 98;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 99;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 100,
- and wherein the CD3 antigen binding domain comprises a light chain variable (VL) region according to any one of the following:
- a VL region comprising the following CDRs:
- HCDR1 having the amino acid sequence of SEQ ID NO:
- 46;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 47;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 48,
- a VL region comprising the following CDRs:
- HCDR1 having the amino acid sequence of SEQ ID NO:
- 58;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 59;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 60, and
- a VL region comprising the following CDRs:
- HCDR 1 having the amino acid sequence of SEQ ID NO:
- 62;
- HCDR2 having the amino acid sequence of SEQ ID NO:
- 63;
- and
- HCDR3 having the amino acid sequence of SEQ ID NO:
- 64.
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21-24. (canceled)
34-35. (canceled)
Dependencies are inferred from the claim text.