US 2025/0051445 A1Published application

Bma031 antigen binding polypeptides

AssigneeImmatics Biotechnologies GmbH

InventorsSebastian BUNK, Felix UNVERDORBEN, Martin HOFMANN

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Abstract

Antigen binding polypeptide specifically binding to a α/β T cell receptor (TCR)/cluster of differentiation 3 (CD3) complex. Nucleic acid containing a sequence encoding for the antigen binding polypeptide or a vector containing the nucleic acid. Recombinant host cells containing the antigen binding polypeptide, and pharmaceutical compositions containing the antigen binding polypeptide, the nucleic acid, the vector and/or the host cell. Use of the antigen binding polypeptide, the nucleic acid, the vector, the host cell, or the pharmaceutical composition in medicine, in particular for use in the diagnosis, prevention, and/or treatment of a proliferative disease. Methods for improving or maintaining the binding and/or improving the stability of the antigen binding polypeptides. Methods for detecting, determining or enriching T cells expressing the α/β TCR/CD3 complex.

Claims20

Dependent claims

An antigen binding polypeptide comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein

(1) the VH comprises
(a) a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
52,
(b) a HCDR2 comprising the amino acid sequence of YINPYNDVTKYX1X2KFX3G (SEQ ID NO:
53), wherein
X1 is A or N;
X2 is E or Q;
and/or
X3 is Q or K
(c) a HCDR3, and
(d) heavy chain framework regions (HFR) 1-4;
(2) the VL comprises
(a) a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
54,
(b) a LCDR2 comprising the amino acid sequence of SEQ ID NO:
55,
(c) a LCDR3, and
(d) light chain framework regions (LFR) 1-4;
wherein
(i) at least one amino acid of HCDR1 comprising the amino acid sequence of SEQ ID NO:
52 and/or at least one amino acid of HCDR2 comprising the amino acid sequence of SEQ ID NO:
53 that is not positively charged is substituted with a positively charged amino acid;
and/or
(ii) at least one amino acid of LCDR1 comprising the amino acid of SEQ ID NO:
54 and/or at least one amino acid of LCDR2 comprising the amino acid sequence of SEQ ID NO:
55 that is not positively charged is substituted with a positively charged amino acid;
and/or
(iii) position 30 in HFR1 according to Kabat numbering is substituted with a positively charged amino acid, and/or
(iv) position 90 in HFR3 according to Kabat numbering is substituted with a tyrosine (Y) residue,
and wherein the antigen binding polypeptide specifically binds to an α/β T cell receptor (TCR)/CD3 complex.

27 more elements

A method for improving or maintaining the binding and/or improving the stability of the antigen binding polypeptide comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein

(1) the VH comprises
(a) a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
52 (SYVMH),
(b) a HCDR2 comprising the amino acid sequence of YINPYNDVTKYX1X2KFX3G (SEQ ID NO:
53), wherein
X1 is A or N;
X2 is E or Q;
and/or
X3 is Q or K
(c) a HCDR3, and
(d) heavy chain framework regions (HFR) 1-4;
(2) the VL comprises
(a) a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
54 (SATSSVSYMH),
(b) a LCDR2 comprising the amino acid sequence of SEQ ID NO:
55 (DTSKLAS),
(c) a LCDR3, and
(d) light chain frameworks (LCR) 1-4;
wherein
(i) at least one amino acid of HCDR1 comprising the amino acid sequence of SEQ ID NO:
52 and/or at least one amino acid of HCDR2 comprising the amino acid sequence of SEQ ID NO:
53 that is not positively charged is substituted with a positively charged amino acid;
and/or
(ii) at least one amino acid of LCDR1 comprising the amino acid of SEQ ID NO:
54 and/or at least one amino acid of LCDR2 comprising the amino acid sequence of SEQ ID NO:
55 that is not positively charged is substituted with a positively charged amino acid;
and/or
(iii) position 30 in HFR1 according to Kabat numbering is substituted with a positively charged amino acid, and/or
(iv) position 90 in HFR3 according to Kabat numbering is substituted with a tyrosine (Y) residue,
wherein
(1) the binding of the antigen binding polypeptide to an α/β T cell receptor (TCR)/CD3 complex is increased compared to the parental antigen binding polypeptide;
(2) the binding of the antigen binding polypeptide to an α/β T cell receptor (TCR)/CD3 complex is maintained or increased and the stability of the antigen binding polypeptide is increased compared to the parental antigen binding polypeptide;
or
(3) the stability of the antigen binding polypeptide is increased compared to the parental antigen binding polypeptide.

31 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/929,969Filed 29 Oct 2024
Priority: EP 21172352.35 May 2021
Published: 13 Feb 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07K 16/2809
Against the immunoglobulin superfamily: against the 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 40/428
Cancer antigens: undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
C07K 14/7051
Immunoglobulin superfamily: t-cell receptor -CD3 complex

Family

Application63/184,698Us provisional application · filed 5 May 2021
Application17/736,699Division · filed 4 May 2022
Application18/929,969Division
US 12,162,940 B2Related patent
US 2022/0356252 A1Published application
US 2025/0051445 A1This patent

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