	US 12,188,932 B2
	Method for high throughput peptide-MHC affinity screening for TCR ligands
Andreas Moritz, Tuebingen (DE); Dominik Maurer, Moessingen (DE); Sebastian Bunk, Tuebingen (DE); and Claudia Wagner, Tuebingen (DE)
Assigned to Immatics Biotechnologies GmbH, Tübingen (DE)
Filed by Immatics Biotechnologies GmbH, Tuebingen (DE)
Filed on Sep. 13, 2019, as Appl. No. 16/569,691.
Claims priority of provisional application 62/873,102, filed on Jul. 11, 2019.
Claims priority of provisional application 62/731,337, filed on Sep. 14, 2018.
Claims priority of application No. 102018122546.6 (DE), filed on Sep. 14, 2018.
Prior Publication US 2020/0088726 A1, Mar. 19, 2020
Int. Cl. A61K 38/17 (2006.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); C07K 14/74 (2006.01); G01N 33/569 (2006.01); G01N 33/50 (2006.01)

CPC G01N 33/56977 (2013.01) [A61K 38/1774 (2013.01); A61K 39/00 (2013.01); A61K 39/39541 (2013.01); C07K 14/70539 (2013.01); A61K 2039/505 (2013.01); A61K 2039/57 (2013.01); G01N 2333/7051 (2013.01); G01N 2333/70539 (2013.01)]

11 Claims

1. A polypeptide comprising a stabilized human HLA-A*0201 molecule capable of binding to a peptide ligand,

wherein said HLA-A molecule comprises an artificially introduced covalent bridge between a first amino acid within the β1 unit at the amino acid position 22 in the alpha 1 domain and a second amino acid within the α1 unit at the amino acid position 71 in the alpha 1 domain of the HLA-A molecule based on IGMT numbering excluding the first 24 amino acids,

wherein the first and the second amino acids are each modified to a cysteine forming a first disulfide bridge,

wherein the first amino acid at position 22 is modified from phenylalanine (F) to cysteine (C) and the second amino acid at position 71 is modified from serine (S) to cysteine (C), and

wherein the first disulfide bridge stabilizes the HLA-A molecule in the absence of the peptide ligand.