US 12,643,931 B2Granted

CALR and JAK2 T-cell receptors

AssigneeJanssen Biotech, Inc.

InventorsRebecca Hanson, Vinod Krishna, Manuel Alejandro Sepulveda, Patrick Wilkinson

Life of this patent

Estimating the term…

Abstract

Described herein are T-cell receptors (TCRs) that bind to CALR or JAK2 antigens. Also described are T-cell receptors (TCRs), polynucleotides, vectors that encode the TCRs, and cells comprising the TCRs, and methods of treatment.

Claims20

Dependent claims

A T-cell receptor (TCR) comprising an alpha chain and a beta chain, wherein:

(a) Lathe alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
10, a CDR2 comprising the amino acid sequence of SEQ ID NO:
126, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
14, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
218, a CDR2 comprising the amino acid sequence of SEQ ID NO:
264, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
266;
(b) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
31, a CDR2 comprising the amino acid sequence of SEQ ID NO:
33, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
35, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
269, a CDR2 comprising the amino acid sequence of SEQ ID NO:
271, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
273;
(c) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
38, a CDR2 comprising the amino acid sequence of SEQ ID NO:
40, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
42, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
276, a CDR2 comprising the amino acid sequence of SEQ ID NO:
278, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
280;
(d) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
45, a CDR2 comprising the amino acid sequence of SEQ ID NO:
47, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
49, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
283, a CDR2 comprising the amino acid sequence of SEQ ID NO:
285, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
287;
(e) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
59, a CDR2 comprising the amino acid sequence of SEQ ID NO:
61, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
63, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
297, a CDR2 comprising the amino acid sequence of SEQ ID NO:
299, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
301;
(f) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
66, a CDR2 comprising the amino acid sequence of SEQ ID NO:
68, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
70, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
304, a CDR2 comprising the amino acid sequence of SEQ ID NO:
306, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
308;
(g) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
73, a CDR2 comprising the amino acid sequence of SEQ ID NO:
75, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
77, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
311, a CDR2 comprising the amino acid sequence of SEQ ID NO:
313, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
315;
(h) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
80, a CDR2 comprising the amino acid sequence of SEQ ID NO:
82, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
84, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
318, a CDR2 comprising the amino acid sequence of SEQ ID NO:
320, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
322;
(i) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
101, a CDR2 comprising the amino acid sequence of SEQ ID NO:
103, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
105, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
339, a CDR2 comprising the amino acid sequence of SEQ ID NO:
341, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
343;
(j) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
108, a CDR2 comprising the amino acid sequence of SEQ ID NO:
110, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
112, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
346, a CDR2 comprising the amino acid sequence of SEQ ID NO:
348, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
350;
(k) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
115, a CDR2 comprising the amino acid sequence of SEQ ID NO:
117, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
119, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
353, a CDR2 comprising the amino acid sequence of SEQ ID NO:
355, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
357;
(l) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
122, a CDR2 comprising the amino acid sequence of SEQ ID NO:
124, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
126, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
360, a CDR2 comprising the amino acid sequence of SEQ ID NO:
362, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
364;
(m) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
129, a CDR2 comprising the amino acid sequence of SEQ ID NO:
131, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
133, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
367, a CDR2 comprising the amino acid sequence of SEQ ID NO:
369, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
371;
(n) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
136, a CDR2 comprising the amino acid sequence of SEQ ID NO:
138, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
140, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
374, a CDR2 comprising the amino acid sequence of SEQ ID NO:
376, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
378;
(o) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
143, a CDR2 comprising the amino acid sequence of SEQ ID NO:
145, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
147, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
381, a CDR2 comprising the amino acid sequence of SEQ ID NO:
383, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
385;
(p) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
157, a CDR2 comprising the amino acid sequence of SEQ ID NO:
159, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
161, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
395, a CDR2 comprising the amino acid sequence of SEQ ID NO:
397, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
399;
(q) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
164, a CDR2 comprising the amino acid sequence of SEQ ID NO:
166, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
168, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
402, a CDR2 comprising the amino acid sequence of SEQ ID NO:
404, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
406;
(r) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
178, a CDR2 comprising the amino acid sequence of SEQ ID NO:
180, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
182, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
416, a CDR2 comprising the amino acid sequence of SEQ ID NO:
418, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
420;
(s) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
119, a CDR comprising the amino acid sequence of SEQ ID NO:
1, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
203, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
437, a CDR2 comprising the amino acid sequence of SEQ ID NO:
439, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
441;
(t) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
220, a CDR2 comprising the amino acid sequence of SEQ ID NO:
222, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
224, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
458, a CDR2 comprising the amino acid sequence of SEQ ID NO:
460, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
462;
(u) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
227, a CDR2 comprising the amino acid sequence of SEQ ID NO:
229, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
231, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
451, a CDR2 comprising the amino acid sequence of SEQ ID NO:
467, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
469;
(v) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
22, a CDR2 comprising the amino acid sequence of SEQ ID NO:
22, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
238, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
475, a CDR2 comprising the amino acid sequence of SEQ ID NO:
474, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
476.

151 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/712,661Filed 4 Apr 2022 · us provisional application
Priority: 5 Apr 2021
Published: US 2023/0079750 A116 Mar 2023
Granted: 2 Jun 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07K 14/4748
Not used: tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
C07K 14/7051
Immunoglobulin superfamily: t-cell receptor -CD3 complex
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/32
Characterised by the recombinant expression of specific molecules in the cells of the immune system: t-cell receptors [TCR]

Family

Application63/170,711Us provisional application · filed 5 Apr 2021
US 2023/0079750 A1Pre-grant publication · published 16 Mar 2023
US 12,643,931 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A T-cell receptor (TCR) comprising an alpha chain and a beta chain, wherein:

(a) Lathe alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
10, a CDR2 comprising the amino acid sequence of SEQ ID NO:
126, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
14, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
218, a CDR2 comprising the amino acid sequence of SEQ ID NO:
264, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
266;
(b) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
31, a CDR2 comprising the amino acid sequence of SEQ ID NO:
33, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
35, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
269, a CDR2 comprising the amino acid sequence of SEQ ID NO:
271, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
273;
(c) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
38, a CDR2 comprising the amino acid sequence of SEQ ID NO:
40, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
42, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
276, a CDR2 comprising the amino acid sequence of SEQ ID NO:
278, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
280;
(d) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
45, a CDR2 comprising the amino acid sequence of SEQ ID NO:
47, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
49, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
283, a CDR2 comprising the amino acid sequence of SEQ ID NO:
285, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
287;
(e) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
59, a CDR2 comprising the amino acid sequence of SEQ ID NO:
61, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
63, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
297, a CDR2 comprising the amino acid sequence of SEQ ID NO:
299, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
301;
(f) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
66, a CDR2 comprising the amino acid sequence of SEQ ID NO:
68, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
70, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
304, a CDR2 comprising the amino acid sequence of SEQ ID NO:
306, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
308;
(g) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
73, a CDR2 comprising the amino acid sequence of SEQ ID NO:
75, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
77, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
311, a CDR2 comprising the amino acid sequence of SEQ ID NO:
313, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
315;
(h) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
80, a CDR2 comprising the amino acid sequence of SEQ ID NO:
82, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
84, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
318, a CDR2 comprising the amino acid sequence of SEQ ID NO:
320, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
322;
(i) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
101, a CDR2 comprising the amino acid sequence of SEQ ID NO:
103, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
105, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
339, a CDR2 comprising the amino acid sequence of SEQ ID NO:
341, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
343;
(j) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
108, a CDR2 comprising the amino acid sequence of SEQ ID NO:
110, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
112, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
346, a CDR2 comprising the amino acid sequence of SEQ ID NO:
348, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
350;
(k) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
115, a CDR2 comprising the amino acid sequence of SEQ ID NO:
117, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
119, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
353, a CDR2 comprising the amino acid sequence of SEQ ID NO:
355, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
357;
(l) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
122, a CDR2 comprising the amino acid sequence of SEQ ID NO:
124, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
126, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
360, a CDR2 comprising the amino acid sequence of SEQ ID NO:
362, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
364;
(m) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
129, a CDR2 comprising the amino acid sequence of SEQ ID NO:
131, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
133, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
367, a CDR2 comprising the amino acid sequence of SEQ ID NO:
369, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
371;
(n) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
136, a CDR2 comprising the amino acid sequence of SEQ ID NO:
138, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
140, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
374, a CDR2 comprising the amino acid sequence of SEQ ID NO:
376, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
378;
(o) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
143, a CDR2 comprising the amino acid sequence of SEQ ID NO:
145, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
147, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
381, a CDR2 comprising the amino acid sequence of SEQ ID NO:
383, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
385;
(p) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
157, a CDR2 comprising the amino acid sequence of SEQ ID NO:
159, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
161, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
395, a CDR2 comprising the amino acid sequence of SEQ ID NO:
397, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
399;
(q) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
164, a CDR2 comprising the amino acid sequence of SEQ ID NO:
166, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
168, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
402, a CDR2 comprising the amino acid sequence of SEQ ID NO:
404, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
406;
(r) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
178, a CDR2 comprising the amino acid sequence of SEQ ID NO:
180, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
182, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
416, a CDR2 comprising the amino acid sequence of SEQ ID NO:
418, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
420;
(s) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
119, a CDR comprising the amino acid sequence of SEQ ID NO:
1, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
203, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
437, a CDR2 comprising the amino acid sequence of SEQ ID NO:
439, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
441;
(t) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
220, a CDR2 comprising the amino acid sequence of SEQ ID NO:
222, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
224, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
458, a CDR2 comprising the amino acid sequence of SEQ ID NO:
460, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
462;
(u) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
227, a CDR2 comprising the amino acid sequence of SEQ ID NO:
229, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
231, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
451, a CDR2 comprising the amino acid sequence of SEQ ID NO:
467, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
469;
(v) the alpha chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
22, a CDR2 comprising the amino acid sequence of SEQ ID NO:
22, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
238, and the beta chain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:
475, a CDR2 comprising the amino acid sequence of SEQ ID NO:
474, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
476.

151 more elements

Facts

Application

17/712,661Filed 4 Apr 2022 · us provisional application

Priority

5 Apr 2021

Published

US 2023/0079750 A116 Mar 2023

Granted

2 Jun 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07K 14/4748
Not used: tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
C07K 14/7051
Immunoglobulin superfamily: t-cell receptor -CD3 complex
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/32
Characterised by the recombinant expression of specific molecules in the cells of the immune system: t-cell receptors [TCR]