US 12,448,427 B2
Binding proteins specific for HA-1H and uses thereof
Mirjam H.M. Heemskerk, Leiden (NL); and J.H. Frederik Falkenburg, Leiden (NL)
Assigned to ACADEMISCH ZIEKENHUIS LEIDEN (H.O.D.N. LUMC), Leiden (NL)
Appl. No. 17/283,786
Filed by ACADEMISCH ZIEKENHUIS LEIDEN (H.O.D.N. LUMC), Leiden (NL)
PCT Filed Oct. 9, 2019, PCT No. PCT/NL2019/050671
§ 371(c)(1), (2) Date Apr. 8, 2021,
PCT Pub. No. WO2020/076156, PCT Pub. Date Apr. 16, 2020.
Claims priority of application No. 2021789 (NL), filed on Oct. 10, 2018.
Prior Publication US 2021/0380656 A1, Dec. 9, 2021
Int. Cl. C07K 14/725 (2006.01); A61K 35/17 (2025.01); A61K 40/11 (2025.01); A61K 40/32 (2025.01); A61K 40/42 (2025.01); A61K 40/46 (2025.01); A61P 35/00 (2006.01); C12N 5/0783 (2010.01)
CPC C07K 14/7051 (2013.01) [A61K 40/11 (2025.01); A61K 40/32 (2025.01); A61K 40/42 (2025.01); A61K 40/46 (2025.01); A61P 35/00 (2018.01); C12N 5/0636 (2013.01); A61K 2239/48 (2023.05); C12N 2510/00 (2013.01)] 20 Claims
 
1. An isolated nucleic acid composition that encodes an HA-1H antigen-specific binding protein having a TCR α chain variable (Vα) domain and a TCR β chain variable (Vβ) domain, the composition comprising:
(i)
(a) a nucleic acid sequence that encodes a TCR Vα domain comprising a CDR3 amino acid sequence, a CDR1 amino acid sequence, and a CDR2 amino acid sequence, wherein the CDR3 amino acid sequence comprises the sequence of SEQ ID NO: 1, wherein the CDR1 amino acid sequence comprises the sequence of SEQ ID NO: 80, and wherein the CDR2 amino acid sequence comprises the sequence of SEQ ID NO: 83; and
(b) a nucleic acid sequence that encodes a TCR Vβ domain having an amino acid sequence encoded by a TRBV7-9 gene, wherein the Vβ domain comprises a CDR3 amino acid sequence, a CDR1 amino acid sequence, and a CDR2 amino acid sequence, wherein the CDR3 amino acid sequence comprises the sequence of SEQ ID NO: 4, wherein the CDR1 amino acid sequence comprises the sequence of SEQ ID NO: 7 and wherein the CDR2 amino acid sequence comprises the sequence of SEQ ID NO: 86; or
(ii)
(a) a nucleic acid sequence that encodes a TCR Vα domain comprising a CDR3 amino acid sequence, a CDR1 amino acid sequence, and a CDR2 amino acid sequence, wherein the CDR3 amino acid sequence comprises the sequence of SEQ ID NO: 2, wherein the CDR1 amino acid sequence comprises the sequence of SEQ ID NO: 8, and wherein the CDR2 amino acid sequence comprises the sequence of SEQ ID NO: 28; and
(b) a nucleic acid sequence that encodes a TCR Vβ domain having an amino acid sequence encoded by a TRBV7-9 gene, wherein the Vβ domain comprises a CDR3 amino acid sequence, a CDR1 amino acid sequence, and a CDR2 amino acid sequence, wherein the CDR3 amino acid sequence comprises the sequence of SEQ ID NO: 5, wherein the CDR1 amino acid sequence comprises the sequence of SEQ ID NO: 7 and wherein the CDR2 amino acid sequence comprises the sequence of SEQ ID NO: 86; or
(iii)
(a) a nucleic acid sequence that encodes a TCR Vα domain comprising a CDR3 amino acid sequence, a CDR1 amino acid sequence, and a CDR2 amino acid sequence, wherein the CDR3 amino acid sequence comprises the sequence of SEQ ID NO: 3, wherein the CDR1 amino acid sequence comprises the sequence of SEQ ID NO: 8, and wherein the CDR2 amino acid sequence comprises the sequence of SEQ ID NO: 28; and
(b) a nucleic acid sequence that encodes a TCR Vβ domain having an amino acid sequence encoded by a TRBV7-9 gene, wherein the Vβ domain comprises a CDR3 amino acid sequence, a CDR1 amino acid sequence, and a CDR2 amino acid sequence, wherein the CDR3 amino acid sequence comprises the sequence of SEQ ID NO: 6, wherein the CDR1 amino acid sequence comprises the sequence of SEQ ID NO: 7, and wherein the CDR2 amino acid sequence comprises the sequence of SEQ ID NO: 86; or
(iv)
(a) a nucleic acid sequence that encodes a TCR Vα domain comprising a CDR3 amino acid sequence, a CDR1 amino acid sequence, and a CDR2 amino acid sequence, wherein the CDR3 amino acid sequence comprises the sequence of SEQ ID NO: 2, wherein the CDR1 amino acid sequence comprises the sequence of SEQ ID NO: 8, and wherein the CDR2 amino acid sequence comprises the sequence of SEQ ID NO: 28; and
(b) a nucleic acid sequence that encodes a TCR Vβ domain having an amino acid sequence encoded by a TRBV7-9 gene, wherein the Vβ domain comprises a CDR3 amino acid sequence, a CDR1 amino acid sequence, and a CDR2 amino acid sequence, wherein the CDR3 amino acid sequence comprises the sequence of SEQ ID NO: 4, wherein the CDR1 amino acid sequence comprises the sequence of SEQ ID NO: 7, and wherein the CDR2 amino acid sequence comprises the sequence of SEQ ID NO: 86.