IP Library › Granted Patent US 11,084,862
Granted Patent B2
US 11,084,862 · App. 16/416,907 · Granted Aug 10, 2021

T cell receptors

Inventors: Peter Molloy (Abingdon, GB); Nicholas Pumphrey (Abingdon, GB)
Assignee: ADAPTIMMUNE LIMITED
C07K14/7051A61K39/0011A61K39/001181C12N5/0637A61K38/00C12N2740/15043C12N2799/027
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Quick Facts
Patent No.
US 11,084,862
App. No.
16/416,907
Granted
Aug 10, 2021
Kind
B2
Abstract

The present invention relates to T cell receptors (TCRs) which bind the HLA-A2 restricted FMNKFIYEI (158-166) peptide epitope derived from α Fetoprotein (AFP). Certain preferred TCRs of the invention demonstrate excellent binding characteristics and specificity profiles for this AFP epitope. T cell receptors of the invention may comprise at least one TCR alpha chain variable domain and/or at least one TCR beta chain variable domain, the alpha chain variable domain which may comprise an amino acid sequence that has at least 90% identity to the sequence of amino acid residues 1-112 of SEQ ID No: 2, and/or the beta chain variable domain which may comprise an amino acid sequence that has at least 90% identity to the sequence of amino acid residues 1-112 of SEQ ID No: 3.

Claims (182)

1. “A method for treating a patient expressing a FMNKFIYEI (SEQ ID NO: 1)-HLA-A2 complex comprising: (a) administering to the patient an immune cell comprising a non-naturally occurring and/or purified and/or engineered T cell receptor (TCR) having the property of binding to said FMNKFIYEI (SEQ ID NO: 1) HLA-A2 complex or (b) administering to the patient a non-naturally occurring and/or purified and/or engineered T cell receptor (TCR) having the property of binding to said FMNKFIYEI (SEQ ID NO: 1) HLA-A2 complex wherein said TCR further comprises a therapeutic agent, wherein the TCR of (a) or (b) comprises at least one TCR alpha chain variable domain and at least one TCR beta chain variable domain, wherein the alpha chain variable domain comprises at least one of the following sets of CDR sequences:”

CDR1

DRGSQA

residues 27 to 32 of SEQ ID NO: 6

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 6

CDR3

AVNSDS

residues 90 to 101 of SEQ ID NO: 6

GYALNF

or

CDR1

DRGSQS

residues 27 to 32 of SEQ ID NO: 7

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 7

CDR3

AVNSDS

residues 90 to 101 of SEQ ID NO: 7

SYALNF

or

CDR1

DRGSQS

residues 27 to 32 of SEQ ID NO: 8

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 8

CDR3

AVNSDS

residues 90 to 101 of SEQ ID NO: 8

GVALNF

or

CDR1

DRGSQA

residues 27 to 32 of SEQ ID NO: 9

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 9

CDR3

AVNSDS

residues 90 to 101 of SEQ ID NO: 9

GVALNF

or

CDR1

DRGSQS

residues 27 to 32 of SEQ ID NO: 10

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 10

CDR3

AVNSQS

residues 90 to 101 of SEQ ID NO: 10

GYALNF

or

CDR1

DRGSQS

residues 27 to 32 of SEQ ID NO: 11

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 11

CDR3

AVNSQS

residues 90 to 101 of SEQ ID NO: 11

GYSLNF

or

CDR1

DRGSQS

residues 27 to 32 of SEQ ID NO: 12

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 12

CDR3

AVNSQS

residues 90 to 101 of SEQ ID NO: 12

SYALNF

or

CDR1

DRGSQA

residues 27 to 32 of SEQ ID NO: 13

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 13

CDR3

AVNSQS

residues 90 to 101 of SEQ ID NO: 13

GYALNF

or

CDR1

DRGSQS

residues 27 to 32 of SEQ ID NO: 14

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 14

CDR3

AVNSQS

residues 90 to 101 of SEQ ID NO: 14

GVALNF

or

CDR1

DRGSQS

residues 27 to 32 of SEQ ID NO: 15

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 15

CDR3

AVNSQN

residues 90 to 101 of SEQ ID NO: 15

GYALNF

or

CDR1

DRGSFS

residues 27 to 32 of SEQ ID NO: 16

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 16

CDR3

AVNSDS

residues 90 to 101 of SEQ ID NO: 16

GYALNF

or

CDR1

DRGSYS

residues 27 to 32 of SEQ ID NO: 17

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 17

CDR3

AVNSDS

residues 90 to 101 of SEQ ID NO: 17

GYALNF

or

CDR1

DRGSYS

residues 27 to 32 of SEQ ID NO: 18

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 18

CDR3

AVNSDS

residues 90 to 101 of SEQ ID NO: 18

SYALNF

or

CDR1

DRGSYS

residues 27 to 32 of SEQ ID NO: 19

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 19

CDR3

AVNSDS

residues 90 to 101 of SEQ ID NO: 19

GVALNF

or

CDR1

DRGSYS

residues 27 to 32 of SEQ ID NO: 20

CDR2

IYSNGD

residues 50 to 55 of SEQ ID NO: 20

CDR3

AVNSQS

residues 90 to 101 of SEQ ID NO: 20

GYALNF

and the wherein the beta chain variable domain comprises the following set of CDR sequences:

CDR1

SGDLS

residues 27 to 31 of SEQ ID NO: 5

CDR2

YYNGEE

residues 49 to 54 of SEQ ID NO: 5

CDR3

ASSLGG

residues 92 to 102 of SEQ ID NO: 5

ESEQF

wherein the TCR further comprises a therapeutic agent or is expressed in an immune cell.

2. The method of claim 1 wherein the treating is treating cancer.

3. The method of claim 2 wherein the treating cancer is treating hepatocellular carcinoma.

4. The method of claim 1 wherein the treating comprises treating hepatocellular carcinoma.

5. The method of claim 1 wherein the treating comprises adoptive therapy.

6. The method of claim 1 , wherein the treating comprises treating alpha Fetoprotein (AFP) positive tumor cells.

Assignments (3)
RELEASE OF SECURITY INTEREST Recorded Jul 31, 2025
From: HERCULES CAPITAL, INC., AS AGENT
To: TCR2 THERAPEUTICS INC.; ADAPTIMMUNE LIMITED
Reel/Frame 072313/0252 →
SECURITY INTEREST Recorded May 14, 2024
From: TCR2 THERAPEUTICS INC.; ADAPTIMMUNE LIMITED
To: HERCULES CAPITAL, INC., AS AGENT
Reel/Frame 067410/0105 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 22, 2019
From: MOLLOY, PETER; PUMPHREY, NICHOLAS
To: ADAPTIMMUNE LIMITED
Reel/Frame 049249/0882 →
Priority Claims (1)
GB 1313377.2 · Jul 26, 2013 · national
Continuity (3)
Division 15006224 · Jan 26, 2016
Continuation In Part PCTGB2014052199 · Jul 18, 2014
Related Publication 20190330301A1 · Oct 31, 2019