IP Library Patent Application 15568440
Patent Application
App. No. 15/568,440

T CELL RECEPTOR

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Patent No.
US None
App. No.
15/568,440
Abstract

The present invention provides an engineered T cell receptor (TCR) comprising at least one of the following amino acid residues: L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; V19 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; S86 of the α chain; F39 of the α chain; D55 of the α chain; R43 of the β chain; A66 of the α chain; V19 of the β chain; L21 of the β chain; L103 of the β chain; T3 of the α chain; S7 of the α chain; P9 of the α chain; M11 of the α chain; A16 of the α chain; T18 of the α chain; L21 of the α chain; S22 of the α chain; D26 of the α chain; F40 of the α chain; S47 of the α chain; R48 of the α chain; Q49 of the α chain; I51 of the α chain; L52 of the α chain; V53 of the α chain; T67 of the α chain; E68 of the α chain; N74 of the α chain; F76 of the α chain; N79 of the α chain; Q81 of the α chain; A83 of the α chain; K90 of the α chain; S92 of the α chain; D93 of the α chain; and M101 of the α chain; wherein the at least one amino acid residue is not present in the corresponding germline TCR amino acid sequence.

Claims (73)

1 . An engineered T cell receptor (TCR) comprising at least one of the following amino acid residues:

L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; S86 of the α chain; F39 of the α chain; D55 of the α chain; R43 of the β chain; A66 of the α chain; L21 of the β chain; L103 of the chain; T3 of the α chain; P9 of the α chain; A16 of the α chain; T18 of the α chain; L21 of the α chain; S22 of the α chain; D26 of the α chain; F40 of the α chain; S47 of the α chain; R48 of the α chain; Q49 of the α chain; I51 of the α chain; L52 of the α chain; V53 of the α chain; T67 of the α chain; E68 of the α chain; N74 of the α chain; F76 of the α chain; N79 of the α chain; Q81 of the α chain; A83 of the α chain; K90 of the α chain; S92 of the α chain; D93 of the α chain; and M101 of the α chain;

wherein the at least one amino acid residue is not present in the corresponding germline TCR amino acid sequence.

2 . An engineered TCR according to claim 1 wherein the at least one amino acid residue is selected from:

L96 of the α chain;

R9 of the β chain;

Y10 of the β chain;

T24 of the α chain;

T20 of the α chain;

M50 of the α chain;

T5 of the α chain;

Q8 of the α chain;

S86 of the α chain;

F39 of the α chain;

D55 of the α chain; or

R43 of the β chain.

3 . An engineered cell surface expressed T cell receptor (TCR) comprising at least one of the following amino acid residues:

L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; V19 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; S86 of the α chain; F39 of the α chain; D55 of the α chain; R43 of the β chain; A66 of the α chain; V19 of the chain; L21 of the β chain; L103 of the β chain; T3 of the α chain; S7 of the α chain; P9 of the α chain; M11 of the α chain; A16 of the α chain; T18 of the α chain; L21 of the α chain; S22 of the α chain; D26 of the α chain; F40 of the α chain; S47 of the α chain; R48 of the α chain; Q49 of the α chain; I51 of the α chain; L52 of the α chain; V53 of the α chain; T67 of the α chain; E68 of the α chain; N74 of the α chain; F76 of the α chain; N79 of the α chain; Q81 of the α chain; A83 of the α chain; K90 of the α chain; S92 of the α chain; D93 of the α chain; and M101 of the α chain;

wherein the cell is human, and the at least one amino acid residue is not present in the corresponding germline TCR amino acid sequence.

4 . An engineered TCR according to claim 3 wherein the at least one amino acid residue is selected from:

L96 of the α chain;

R9 of the β chain;

Y10 of the β chain;

T24 of the α chain;

V19 of the α chain;

T20 of the α chain;

M50 of the α chain;

T5 of the α chain;

Q8 of the α chain;

S86 of the α chain;

F39 of the α chain;

D55 of the α chain; or

R43 of the chain.

5 . An engineered TCR which comprises L96 of the α chain, R9 of the β chain, Y10 of the β chain, T24 of the α chain, or a plurality of amino acid residues set forth in claim 1 .

6 - 9 . (canceled)

10 . An engineered TCR according to claim 5 , further comprising V19 of the α chain; V19 of the β chain; S7 of the α chain; or M11 of the α chain.

11 . An engineered TCR according to claim 5 which comprises L96 of the α chain; R9 of the β chain and Y10 of the β chain.

12 . An engineered TCR according to claim 3 which comprises

(i) V19 of the α chain; R9 of the β chain and Y10 of the β chain;

(ii) of L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; V19 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; S86 of the α chain; F39 of the α chain; D55 of the α chain; and R43 of the β chain;

(iii) L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; V19 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; and S86 of the α chain; or

(iv) L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; V19 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; S86 of the α chain; F39 of the α chain; D55 of the α chain; R43 of the β chain; A66 of the α chain; V19 of the β chain; L21 of the β chain; L103 of the β chain; T3 of the α chain; S7 of the α chain; P9 of the α chain; M11 of the α chain; A16 of the α chain; T18 of the α chain; L21 of the α chain; S22 of the α chain; D26 of the α chain; F40 of the α chain; S47 of the α chain; R48 of the α chain; Q49 of the α chain; I51 of the α chain; L52 of the α chain; V53 of the α chain; T67 of the α chain; E68 of the α chain; N74 of the α chain; F76 of the α chain; N79 of the α chain; Q81 of the α chain; A83 of the α chain; K90 of the α chain; S92 of the α chain; D93 of the α chain; and M101 of the α chain.

13 - 15 . (canceled)

16 . A nucleic acid sequence encoding a TCR α chain and/or a β chain as defined in claim 1 .

17 . (canceled)

18 . A vector comprising a nucleic acid sequence according to claim 16 .

19 . (canceled)

20 . A cell comprising a vector according claim 18 .

21 - 22 . (canceled)

23 . A pharmaceutical composition comprising a vector according to claim 18 .

24 - 25 . (canceled)

26 . A method for treating a disease which comprises the step of administering a cell according to claim 20 to a subject.

27 . A method for producing a cell according to claim 20 which comprises the step of transducing a cell in vitro or ex vivo with a vector.

28 . A method for increasing the cell surface expression of a TCR which comprises the steps of:

(i) providing a TCR α chain and/or β chain sequence;

(ii) determining an amino acid residue of the TCR α chain and/or β chain at one or more positions selected from:

96 of the α chain; 9 of the β chain; 10 of the β chain; 24 of the α chain; 19 of the α chain; 20 of the α chain; 50 of the α chain; 5 of the α chain; 8 of the α chain; 86 of the α chain; 39 of the α chain; 55 of the α chain; 43 of the β chain; 66 of the α chain; 19 of the β chain; 21 of the β chain; 103 of the β chain; 3 of the α chain; 7 of the α chain; 9 of the α chain; 11 of the α chain; 16 of the α chain; 18 of the α chain; 21 of the α chain; 22 of the α chain; 26 of the α chain; 40 of the α chain; 47 of the α chain; 48 of the α chain; 49 of the α chain; 51 of the α chain; 52 of the α chain; 53 of the α chain; 67 of the α chain; 68 of the α chain; 74 of the α chain; 76 of the α chain; 79 of the α chain; 81 of the α chain; 83 of the α chain; 90 of the α chain; 92 of the α chain; 93 of the α chain; and 101 of the α chain; and

(iii) altering the amino acid residue at one or more of the positions listed in step (ii) to an amino acid residue selected from:

L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; V19 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; S86 of the α chain; F39 of the α chain; D55 of the α chain; R43 of the β chain; A66 of the α chain; V19 of the β chain; L21 of the β chain; L103 of the β chain; T3 of the α chain; S7 of the α chain; P9 of the α chain; M11 of the α chain; A16 of the α chain; T18 of the α chain; L21 of the α chain; S22 of the α chain; D26 of the α chain; F40 of the α chain; S47 of the α chain; R48 of the α chain; Q49 of the α chain; I51 of the α chain; L52 of the α chain; V53 of the α chain; T67 of the α chain; E68 of the α chain; N74 of the α chain; F76 of the α chain; N79 of the α chain; Q81 of the α chain; A83 of the α chain; K90 of the α chain; S92 of the α chain; D93 of the α chain; and M101 of the α chain.

29 - 31 . (canceled)

32 . A method for selecting a high expression TCR which comprises the steps of:

(i) providing a group of TCR amino acid sequences; and

(ii) selecting a TCR amino acid sequence comprising at least one amino acid residue selected from:

L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; V19 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; S86 of the α chain; F39 of the α chain; D55 of the α chain; R43 of the β chain; A66 of the α chain; V19 of the β chain; L21 of the β chain; L103 of the β chain; T3 of the α chain; S7 of the α chain; P9 of the α chain; M11 of the α chain; A16 of the α chain; T18 of the α chain; L21 of the α chain; S22 of the α chain; D26 of the α chain; F40 of the α chain; S47 of the α chain; R48 of the α chain; Q49 of the α chain; I51 of the α chain; L52 of the α chain; V53 of the α chain; T67 of the α chain; E68 of the α chain; N74 of the α chain; F76 of the α chain; N79 of the α chain; Q81 of the α chain; A83 of the α chain; K90 of the α chain; S92 of the α chain; D93 of the α chain; and M101 of the α chain.

33 - 34 . (canceled)

35 . A method for determining the strength of a TCR which comprises the steps of:

(i) providing a TCR α chain and/or β chain sequence; and

(ii) determining if the TCR sequence comprises at least one amino acid residue selected from:

L96 of the α chain; R9 of the β chain; Y10 of the β chain; T24 of the α chain; V19 of the α chain; T20 of the α chain; M50 of the α chain; T5 of the α chain; Q8 of the α chain; S86 of the α chain; F39 of the α chain; D55 of the α chain; R43 of the β chain; A66 of the α chain; V19 of the β chain; L21 of the β chain; L103 of the β chain; T3 of the α chain; S7 of the α chain; P9 of the α chain; M11 of the α chain; A16 of the α chain; T18 of the α chain; L21 of the α chain; S22 of the α chain; D26 of the α chain; F40 of the α chain; S47 of the α chain; R48 of the α chain; Q49 of the α chain; I51 of the α chain; L52 of the α chain; V53 of the α chain; T67 of the α chain; E68 of the α chain; N74 of the α chain; F76 of the α chain; N79 of the α chain; Q81 of the α chain; A83 of the α chain; K90 of the α chain; S92 of the α chain; D93 of the α chain; and M101 of the α chain;

wherein a sequence which comprises at least one of the recited amino acid residues is determined to be a high expression TCR and a sequence which does not comprise at least one of the recited amino acid sequences is determined to be a low expression TCR.

36 - 37 . (canceled)

38 . A cell, isolated from a human subject and transduced with a nucleic acid sequence according to claim 16 .

39 . (canceled)

Assignments (2)
CHANGE OF NAME Recorded Dec 6, 2021
From: UCL BUSINESS PLC
To: UCL BUSINESS LTD
Reel/Frame 058314/0420 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 16, 2019
From: STAUSS, HANS; THOMAS, SHARYN; WILLCOX, BEN; MOHAMMED, FIYAZ
To: UCL BUSINESS PLC
Reel/Frame 051316/0146 →