Multispecific antibodies targeting cd3 and cd22
OwnerJoseph M. TUSCANO, Joshua Farrell MECKLER +1inventors
InventorsJoseph M. TUSCANO, Joshua Farrell MECKLER, Gustavo BARISONE
Life of this patent
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Abstract
Provided are CD22xCD3 and multispecific binding polypeptides that can include a cytokine domain. Pharmaceutical compositions and methods of treatment using the binding polypeptides to treat cancer are also provided.
Claims119
A CD22xCD3 binding polypeptide comprising a CD22 binding domain and a CD3 binding domain,
- a. wherein the CD22 binding domain comprises a first variable heavy chain comprising heavy chain complementarity determining region (HCDR) 1, HCDR2 and HCDR3 of SEQ ID NO:
- 1 and a first variable light chain comprising light chain complementarity determining region (LCDR) 1, LCDR2 and LCDR3 of SEQ ID NO:
- 8, and
- b. wherein the CD3 binding domain comprises a second variable heavy chain comprising heavy chain complementarity determining region (HCDR) 1, HCDR2 and HCDR3 of SEQ ID NO:
- 16 and a second variable light chain comprising light chain complementarity determining region (LCDR) 1, LCDR2 and LCDR3 of SEQ ID NO:
- 23.
The CD22xCD3 binding polypeptide wherein the complementarity determining regions are according to the Kabat numbering scheme or according to the Chothia numbering scheme.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the first variable heavy chain comprises a sequence having at least 80% sequence identity to the sequence of SEQ ID NO:
- 1.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the first variable light chain comprises a sequence having at least 80% sequence identity to the sequence of SEQ ID NO:
- 8.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD22 binding domain comprises a sequence having at least 80% sequence identity to SEQ ID NO:
- 15.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the HCDR3 of the second variable heavy chain comprises the sequence of SEQ ID NOs:
- 17 or 20, wherein the HCDR2 of the second variable heavy chain comprises the sequence of SEQ ID NOs:
- 18 or 21, and wherein the HCDR1 of the second variable heavy chain comprises the sequence of SEQ ID NOs:
- 19 or 22.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the LCDR3 of the second variable light chain comprises the sequence of SEQ ID NOs:
- 24 or 27, wherein the LCDR2 of the second variable light chain comprises the sequence of SEQ ID NOs:
- 25 or 28, and wherein the LCDR1 of the second variable light chain comprises the sequence of SEQ ID NOs:
- 26 or 29.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the second variable heavy chain comprises a sequence having at least 80% sequence identity to the sequence of SEQ ID NO:
- 16.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the second variable light chain comprises a sequence having at least 80% sequence identity to the sequence of SEQ ID NO:
- 23.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD3 binding domain comprises a sequence having at least 80% sequence identity to SEQ ID NO:
- 30.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD22 binding domain further comprises a first linker positioned between the first variable heavy chain and the first variable light chain.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD3 binding domain further comprises a second linker positioned between the second variable heavy chain and the second variable light chain.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD22 binding domain is linked to the CD3 binding domain by a third linker selected from the group consisting of SEQ ID NO:
- 38, SEQ ID NO:
- 39, SEQ ID NO:
- 40, SEQ ID NO:
- 41, SEQ ID NO:
- 42, SEQ ID NO:
- 43, SEQ ID NO:
- 45, SEQ ID NO:
- 46, SEQ ID NO:
- 47, SEQ ID NO:
- 48, SEQ ID NO:
- 49, SEQ ID NO:
- 50, SEQ ID NO:
- 51, SEQ ID NO:
- 84, SEQ ID NO:
- 85, SEQ ID NO:
- 86, SEQ ID NO:
- 87, SEQ ID NO:
- 88, SEQ ID NO:
- 89, SEQ ID NO:
- 92, SEQ ID NO:
- 93, SEQ ID NO:
- 94, and SEQ ID NO:
- 99.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD3 binding domain is a scFv.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD22 binding domain is a scFv.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the first variable heavy chain and the first variable light chain are oriented in order from N- to C-terminus.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the second variable heavy chain and the second variable light chain are oriented in order from N- to C-terminus.
The CD22xCD3 binding polypeptide of any one of the preceding claims wherein the CD22 binding domain and the CD3 binding domain are oriented in order from N- to C-terminus.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD22 binding domain comprises the sequence of SEQ ID NO:
- 15.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD3 binding domain comprises the sequence of SEQ ID NO:
- 30.
A CD22xCD3 binding polypeptide comprising a CD22 binding domain and a CD3 binding domain, wherein
- a. the CD22 binding domain comprises a first variable heavy chain comprising a sequence having at least 80% sequence identity to SEQ ID NO:
- 1 and a first variable light chain comprising a sequence having at least 80% sequence identity to SEQ ID NO:
- 8, and
- b. wherein the CD3 binding domain comprises a second variable heavy chain comprising a sequence having at least 80% sequence identity to SEQ ID NO:
- 16 and a second variable light chain comprising a sequence having at least 80% sequence identity to SEQ ID NO:
- 23.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the first variable heavy chain and the first variable light chain are oriented in order from N- to C-terminus.
The CD22xCD3 binding polypeptide of any one of the preceding claims, wherein the CD22 binding domain is capable of blocking binding of the natural ligand to CD22.
A CD22xCD3 binding polypeptide comprising a CD22 binding domain and a CD3 binding domain, wherein the CD22 binding domain is capable of blocking binding of the natural ligand to CD22.
The CD22xCD3 binding polypeptide of any one of the preceding claims, further comprising a cytokine domain comprising a cytokine, a mutant, variant or functional fragment thereof.
A CD22xCD3 binding polypeptide comprising the sequence of SEQ ID NO:
- 52.
A CD22xCD3 binding polypeptide comprising the sequence of SEQ ID NO:
- 96.
A multispecific binding polypeptide comprising a first binding domain that specifically binds to CD3, a second binding domain that specifically binds to CD22, and a cytokine domain comprising a cytokine or a mutant, variant, or functional fragment thereof.
Dependencies are inferred from the claim text.