Methods of reducing neuroinflammation
AssigneeImmunityBio, Inc.
InventorsHing C. Wong, Varghese George, Niraj Shrestha, Pallavi Chaturvedi
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Abstract
Provided herein are multi-chain chimeric polypeptides and use thereof in reducing neuroinflammation in a subject.
Claims26
A method of reducing the level of neuroinflammation in a tissue of a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a multi-chain chimeric polypeptide comprising:
- (a) a first chimeric polypeptide comprising:
- (i) a first target-binding domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 2;
- (ii) a soluble tissue factor domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 1;
- and
- (iii) a first domain of a pair of affinity domains comprising a sequence that is at least 90% identical to SEQ ID NO:
- 18;
- (b) a second chimeric polypeptide comprising:
- (i) a second domain of a pair of affinity domains comprising a sequence that is at least 90% identical to SEQ ID NO:
- 16;
- and
- (ii) a second target-binding domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 2,
- wherein:
- the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains;
- and
- the first target-binding domain and the second target-binding domain each bind specifically to a ligand of TGF-β receptor II (TGF-βRII).
A method of treating a neuroinflammatory disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of a multi-chain chimeric polypeptide comprising:
- (a) a first chimeric polypeptide comprising:
- (i) a first target-binding domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 2;
- (ii) a soluble tissue factor domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 1;
- and
- (iii) a first domain of a pair of affinity domains comprising a sequence that is at least 90% identical to SEQ ID NO:
- 18;
- (b) a second chimeric polypeptide comprising:
- (i) a second domain of a pair of affinity domains comprising a sequence that is at least 90% identical to SEQ ID NO:
- 16;
- and
- (ii) a second target-binding domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 2,
- wherein:
- the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains;
- and
- the first target-binding domain and the second target-binding domain each bind specifically to a ligand of TGF-β receptor II (TGF-βRII).
A method of maintaining and/or improving learning and memory in a subject, the method comprising administering to the subject a therapeutically effective amount of a multi-chain chimeric polypeptide comprising:
- (a) a first chimeric polypeptide comprising:
- (i) a first target-binding domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 2;
- (ii) a soluble tissue factor domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 1;
- and
- (iii) a first domain of a pair of affinity domains comprising a sequence that is at least 90% identical to SEQ ID NO:
- 18;
- (b) a second chimeric polypeptide comprising:
- (i) a second domain of a pair of affinity domains comprising a sequence that is at least 90% identical to SEQ ID NO:
- 16;
- and
- (ii) a second target-binding domain comprising a sequence that is at least 90% identical to SEQ ID NO:
- 2,
- wherein:
- the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains;
- and
- the first target-binding domain and the second target-binding domain each bind specifically to a ligand of TGF-β receptor II (TGF-βRII).
Dependencies are inferred from the claim text.