US 12,221,482 B2
Protein-based T-cell receptor knockdown
Martin Pule, London (GB); Paul Maciocia, Ricksmanworth (GB); and Ben Grimshaw, Cambridge (GB)
Assigned to UCL BUSINESS LTD, (GB)
Filed by UCL Business Ltd, London (GB)
Filed on Jun. 23, 2020, as Appl. No. 16/909,553.
Application 16/909,553 is a continuation of application No. 15/657,981, filed on Jul. 24, 2017, granted, now 10,730,942.
Claims priority of application No. CA 2937157 (CA), filed on Jul. 25, 2016.
Prior Publication US 2020/0317782 A1, Oct. 8, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 35/17 (2015.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); A61P 37/06 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01); C12N 15/86 (2006.01); A61K 35/00 (2006.01); A61K 38/00 (2006.01)
CPC C07K 16/2809 (2013.01) [A61K 39/0008 (2013.01); A61K 39/001 (2013.01); A61K 39/0011 (2013.01); A61P 35/00 (2018.01); A61P 35/02 (2018.01); A61P 37/06 (2018.01); C12N 5/0636 (2013.01); C12N 15/86 (2013.01); A61K 35/00 (2013.01); A61K 38/00 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); C07K 2317/56 (2013.01); C07K 2317/622 (2013.01); C07K 2317/76 (2013.01); C07K 2317/80 (2013.01); C07K 2319/04 (2013.01); C07K 2319/05 (2013.01); C07K 2319/74 (2013.01); C12N 2510/00 (2013.01); C12N 2740/10043 (2013.01)] 10 Claims
 
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.