Polypeptide
AssigneeUCL Business PLC
InventorsPaul Maciocia, Martin Pulé
Life of this patent
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Abstract
The present invention provides a polypeptide comprising: (i) a first domain which is capable of downregulating cell surface expression of an MHC class I molecule; and (ii) a second domain which is capable of binding to a target molecule.
Claims45
A polypeptide comprising:
- (i) a first domain which is capable of downregulating cell surface expression of an MHC class I molecule;
- and
- (ii) a second domain which is capable of binding a target molecule.
The polypeptide according to any one of the preceding claims, wherein the second domain is selected from an scFv, a full-length antibody, a single chain antibody fragment, a F(ab) fragment, a F(ab′)2 fragment, a F(ab′) fragment, a single domain antibody (sdAb), a VHH/nanobody and a nanobody.
The polypeptide according to any one of the preceding claims, wherein the second domain is an scFv.
The polypeptide according to any one of the preceding claims, wherein the second domain comprises:
- (i) a sequence comprising the complementarity determining regions (CDRs) as shown in any one of SEQ ID NO:
- 19, SEQ ID NO:
- 21, SEQ ID NO:
- 23 or SEQ ID NO:
- 25;
- or
- (ii) a sequence as set forth in SEQ ID NO:
- 19, SEQ ID NO:
- 21, SEQ ID NO:
- 23, SEQ ID NO:
- 25 or SEQ ID NO:
- 42, or a sequence having at least 80% identity thereto or a functional fragment thereof.
The polypeptide according to any one of the preceding claims, wherein the second domain comprises:
- (i) a sequence comprising the CDRs as shown in SEQ ID NO:
- 19;
- or (ii) a sequence as set forth in SEQ ID NO:
- 19, or a sequence having at least 80% identity thereto or a functional fragment thereof.
The polypeptide according to any one of the preceding claims, wherein the polypeptide further comprises a signal peptide.
The polypeptide according to any one of the preceding claims, wherein the first domain is a viral protein which is capable of downregulating cell surface expression of an MHC class I molecule or a functional fragment thereof.
The polypeptide according to any one of the preceding claims, wherein the first domain is a viral protein, or a functional fragment thereof, which:
- (i) induces MHC class I translocation from the ER to the cytosol and subsequent MHC class I degradation by the proteasome;
- (ii) prevents transport of the MHC class I molecule from the ER to the plasma membrane;
- and/or
- (iii) induces internalisation of the MHC class I molecule via endocytosis and subsequent degradation or sequestration of the MHC class I molecule.
The polypeptide according to any one of the preceding claims, wherein the first domain, when expressed in a cell, decreases cell surface expression of an MHC class I molecule by at least 10%.
The polypeptide according to any one of the preceding claims, wherein the first domain comprises human cytomegalovirus (HCMV) unique short 11 (US11), HCMV US2, adenovirus E3/19K (E19), HCMV US3, HCMV US10, human herpesvirus 7 (HHV-7) U21, human immunodeficiency virus type 1(HIV-1) negative factor (Nef), Kaposi's sarcoma-associated herpesvirus (KSHV) K3, KSHV K5, or a functional fragment thereof.
The polypeptide according to any one of the preceding claims, wherein the first domain comprises HCMV US11 or HCMV US2, or a functional fragment thereof.
The polypeptide according to any one of the preceding claims, wherein the first domain is HCMV US11 or a functional fragment thereof.
The polypeptide according to any one of the preceding claims, wherein the first domain comprises a sequence as set forth in SEQ ID NO:
- 1, SEQ ID NO:
- 3, SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 9, SEQ ID NO:
- 11, SEQ ID NO:
- 13, SEQ ID NO:
- 15, SEQ ID NO:
- 17, SEQ ID NO:
- 43 or a sequence having at least 80% identity thereto or a functional fragment thereof.
The polypeptide according to any one of the preceding claims, wherein the first domain comprises a sequence as set forth in SEQ ID NO:
- 1, SEQ ID NO:
- 3, SEQ ID NO:
- 43 or a sequence having at least 80% identity thereto or a functional fragment thereof.
The polypeptide according to any one of the preceding claims, wherein (i) the first domain is directly fused to the second domain;
- or (ii) the first domain is connected to the second domain by a linker sequence.
A polynucleotide encoding the polypeptide according to any one of the preceding claims.
Dependencies are inferred from the claim text.