IP Library › Granted Patent US 12,221,482
Granted Patent B2
US 12,221,482 · App. 16/909,553 · Granted Feb 11, 2025

Protein-based T-cell receptor knockdown

Inventors: Martin Pule (London, GB); Paul Maciocia (Ricksmanworth, GB); Ben Grimshaw (Cambridge, GB)
Assignee: UCL BUSINESS LTD
C07K16/2809A61K39/0008A61K39/001A61K39/0011A61P35/00A61P35/02A61P37/06C12N5/0636C12N15/86A61K35/00A61K38/00A61K2039/5156A61K2039/5158C07K2317/56C07K2317/622C07K2317/76C07K2317/80C07K2319/04C07K2319/05C07K2319/74C12N2510/00C12N2740/10043
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Quick Facts
Patent No.
US 12,221,482
App. No.
16/909,553
Granted
Feb 11, 2025
Kind
B2
Abstract

The invention relates to protein-based T-cell receptor knockdown, and its use in T-cell therapies.

Claims (12)

1. A nucleic acid sequence encoding a molecule which disrupts the expression of native T cell-receptor (TCR) on the surface of a T cell, which molecule comprises a binding portion comprising a binding domain which binds to one or more components of the TCR/CD3 complex and which is a UCHT1 antibody or a Jovi.1 antibody or is derived from a UCHT1 antibody or a Jovi.1 antibody, and a retention portion comprising a retention domain that intracellularly retains the one or more components within the endoplasmic reticulum (ER) or Golgi apparatus and which is a KDEL sequence, wherein the retention domain is in frame at the C-terminal to the binding domain, and wherein the binding domain comprises:

(a) three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained within the heavy chain variable region (HCVR) sequence of SEQ ID NO: 7, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within the light chain variable region (LCVR) sequence of SEQ ID NO: 8; or

(b) three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) contained within the HCVR sequence of SEQ ID NO: 15, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within the LCVR sequence of SEQ ID NO: 16.

2. A nucleic acid construct comprising (a) a first nucleic acid sequence according to claim 1 , and a second nucleic acid sequence which encodes a chimeric antigen receptor (CAR) and a third nucleic acid sequence which encodes a suicide gene, or (b) a first nucleic acid sequence according to claim 1 and a second nucleic acid sequence which encodes a suicide gene.

3. A nucleic acid construct according to claim 2 , wherein (a) the suicide gene is RQR8, inducible caspace-9 (iCasp9) or thymidine kinase.

4. A vector comprising the nucleic acid sequence according to claim 1 .

5. A vector according to claim 4 , wherein the vector is a viral vector or a non-viral vector.

6. A vector according to claim 5 , wherein the viral vector is a retrovirus, a gamma-retrovirus, a lentivirus, an adenovirus, an adeno-associated virus, a vaccinia virus or a herpes simplex virus.

7. The nucleic acid sequence of claim 1 , wherein the binding domain is a single chain variable fragment (scFv), a scFv-Fc, a single-domain antibody, or a monoclonal antibody.

8. The nucleic acid sequence of claim 7 , wherein the single-domain antibody is a camelid antibody, an artificial V H H fragment or an immunoglobulin new antigen receptor (IgNAR).

9. A nucleic acid construct according to claim 2 , wherein one or more of the nucleic acid sequences of claim 2 (a) are linked by a nucleic acid sequence encoding a foot-and-mouth disease 2A-like peptide.

10. A nucleic acid construct according to claim 2 , wherein one or more of the nucleic acid sequences of claim 2 (b) are linked by a nucleic acid sequence encoding a foot-and-mouth disease 2A-like peptide.

Assignments (2)
CHANGE OF NAME Recorded Oct 9, 2020
From: UCL BUSINESS PLC
To: UCL BUSINESS LTD
Reel/Frame 054038/0500 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2020
From: PULE, MARTIN; MACIOCIA, PAUL; GRIMSHAW, BEN
To: UCL BUSINESS PLC
Reel/Frame 053016/0387 →
Priority Claims (1)
CA CA 2937157 · Jul 25, 2016 · national
Continuity (2)
Continuation 15657981 · Jul 24, 2017
Related Publication 20200317782A1 · Oct 8, 2020
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