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US 2022/0031750 A1Published application
Dimerizing agent regulated immunoreceptor complexes
Assigneebluebird bio, Inc.
InventorsJORDAN JARJOUR, ALEXANDER ASTRAKHAN, WAI-HANG LEUNG
Life of this patent
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Abstract
The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.
Claims309
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- a first multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a first costimulatory domain;
- and/or a primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an extracellular binding domain;
- a second multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a second costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the first and second multimerization domains.
9 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FK506 binding protein (FKBP) multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP-rapamycin binding (FRB) multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and an OX40 costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FKBP multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a TNFR2 costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and an OX40 costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a TNFR2 costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and a TNFR2 costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and an OX40 costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and a TNFR2 costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and an OX40 costimulatory domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- a first multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a first costimulatory domain;
- and/or a primary signaling domain;
- and
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an extracellular binding domain;
- a second multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a second costimulatory domain.
10 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- a first multimerization domain polypeptide or variant thereof a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an extracellular binding domain;
- a second multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and an OX40 costimulatory domain.
8 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- a first multimerization domain polypeptide or variant thereof a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an extracellular binding domain;
- a second multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a TNFR2 costimulatory domain.
8 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FKBP multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and an OX40 costimulatory domain.
9 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FKBP multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a TNFR2 costimulatory domain.
9 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and an OX40 costimulatory domain.
7 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a TNFR2 costimulatory domain.
9 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and a TNFR2 costimulatory domain.
9 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and an OX40 costimulatory domain.
9 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and a TNFR2 costimulatory domain.
9 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and an OX40 costimulatory domain.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- a first multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a first costimulatory domain;
- and/or a primary signaling domain;
- and
- (b) a second polypeptide comprising:
- an extracellular binding domain;
- a second multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a second costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
10 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- a first multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a second polypeptide comprising:
- an extracellular binding domain;
- a second multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and an OX40 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- a first multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a second polypeptide comprising:
- an extracellular binding domain;
- a second multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a TNFR2 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FKBP multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and an OX40 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FKBP multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a TNFR2 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and an OX40 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof;
- a first transmembrane domain;
- a costimulatory domain;
- and/or a primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP multimerization domain polypeptide or variant thereof;
- a second transmembrane domain;
- and a TNFR2 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and a TNFR2 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and an OX40 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and a TNFR2 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FRB T2098L multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- an antibody or antigen binding fragment thereof;
- an FKBP12 multimerization domain polypeptide or variant thereof;
- a CD4 transmembrane domain;
- and an OX40 costimulatory domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
9 more elements
Dependencies are inferred from the claim text.