US 2023/0406929 A1 · POLYPEPTIDE CONSTRUCTS BINDING TO CD3

Abstract

The invention relates to a polypeptide or polypeptide construct comprising: a binding domain binding to an extracellular epitope of the human CD3s chain comprising or consisting of a VH region and a VL region, wherein i) the VH region comprises: a CDR-H1 sequence of X1YAX2N, where X1 is K, V, S, G, R, T, or I; and X2 is M or I; a CDR-H2 sequence of RIRSKYNNYATYYADX1VKX2, where X1 is S or Q; and X2 is D, G, K, S, or E; and a CDR-H3 sequence of HX1NFGNSYX2SX3X4AY, where X1 is G, R, or A; X2 is I, L, V, or T; X3 is Y, W or F; and X4 is W, F or Y; and ii) wherein the VL region comprises: a CDR-L1 sequence of X1 SSTGAVTX2X3X4YX5N, where X1 is G, R, or A; X2 is S or T; X3 is G or S; X4 is N or Y and X5 is P or A; a CDR-L2 sequence of X1TX2X3X4X5X6; where X1 is G or A; X2 is K, D, or N; X3 is F, M or K; X4 is L or R; X5 is A, P, or V; and X6 is P or S; and a CDR-L3 sequence of X1LWYSNX2VW, where X1 is V, A, or T; and X2 is R or L; and iii) wherein one or more of CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one amino acid substitution or a combination thereof selected from X24V and X24F in CDR-H1; D15, and X116A in CDR-H2; H1, X12E, F4, and N6 in CDR-H3; and X11L and W3 in CDR-L3. The invention also relates to a polynucleotide encoding the polypeptide or polypeptide construct of the invention, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or with said vector. Moreover, the invention also provides for a process for the production of said polypeptide or polypeptide construct and a pharmaceutical composition comprising said polypeptide or polypeptide construct of the invention. Furthermore, the invention relates to medical uses of said polypeptide or polypeptide construct and kits comprising said polypeptide or polypeptide construct.

Claims28

Dependent claims

A polypeptide or polypeptide construct comprising:

a binding domain binding to an extracellular epitope of the human CD3ε chain comprising or consisting of a VH region and a VL region, wherein
i) the VH region comprises:
a CDR-H1 sequence of X1YAX2N, where X, is K, V, S, G, R, T, or I;
and X2 is M or I;
a CDR-H2 sequence of RIRSKYNNYATYYADX1VKX2, where X, is S or Q;
and X2 is D, G, K, S, or E;
and
a CDR-H3 sequence of HX1NFGNSYX2SX3X4AY, where X, is G, R, or A;
X2 is I, L, V, or T;
X3 is Y, W or F;
and X4 is W, F or Y;
and
ii) wherein the VL region comprises:
a CDR-L1 sequence of X1SSTGAVTX2X3X4YX5N, where X, is G, R, or A;
X2 is S or T;
X3 is G or S;
X4 is N or Y;
and X5 is P or A;
a CDR-L2 sequence of X1TX2X3X4X5X6;
where X, is G or A;
X2 is K, D, or N;
X3 is F, M or K;
X4 is L or R;
X5 is A, P, or V;
and X6 is P or S;
and
a CDR-L3 sequence of X1LWYSNX2WV, where X, is V, A, or T;
and X2 is R or L;
and
iii) wherein one or more of CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one amino acid substitution or a combination thereof selected from X24V and X24F in CDR-H1;
D15, and X116A in CDR-H2;
H1, X12E, F4, and N6 in CDR-H3;
and
X11L and W3 in CDR-L3.

31 more elements

A polypeptide or polypeptide construct comprising:

a binding domain binding to an extracellular epitope of the human CD3ε chain comprising or consisting of a VH region and a VL region, wherein
i) the VH region comprises the sequence of EVX1LX2ESGGGLX3QPX4GSLKLSCAASGFTFNX5YAX6NWVRQAPGKGLEWVAR IRSKYNNYATYYADX7VKX8RFTISRDDSXX10X11X12YLQMNNLKTEDTAX13YYCV RHX14NFGNSYX15SX16X17AYWGQGTLVTVSX18, where X1 is Q or K;
X2 is V or L;
X3 is V or E;
X4 is G or K;
X5 is K, V, S, G, R, T, or I;
X6 is M or I;
X7 is S or Q;
X8 is D, G, K, S, or E;
X9 is K or Q;
X10 is N or S;
X11 is T or I;
X12 is A or L;
X13 is V or M;
X14 is G, R or A;
X15 is I, L, V, or T;
X16 is Y, W or F;
X17 is W, F or Y;
and X18 is S or A;
and
ii) the VL region comprises the sequence of QX1VVTQEX2X3LTX4SPGX5TVTLTCX6SSTGAVTX7X8X9YX10NWVQX11KPX12X13X14X15X16GLIGX17TX18X19X20X21X22GX23PARFSGSLX24GX25KAALTX26X27GX28QX29E DEAX30YX31CX32LWYSNX33WVFGGGTKLTVL, where X1 is T or A;
X2 is P or S;
X3 is S or A;
X4 is V or T;
X5 is G or E;
X6 is G, R, or A;
X7 is S or T;
X8 is G or S;
X9 is N or Y;
X10 is P or A;
X11 is Q or E;
X12 is G or D;
X13 is Q or H;
X14 is A or L;
X15 is P or F;
X16 is R or T;
X17 is G or A;
X18 is K or D;
X19 is F or M;
X20 is L or R;
X21 is A, P or V;
X22 is P or S;
X23 is T or V;
X24 is L or I;
X25 is G or D;
X26 is L or I;
X27 is S or T;
X28 is V or A;
X29 is P or T;
X30 is E or I;
X31 is Y or F;
X32 is V, A, or T;
X33 is R or L;
and
iii) wherein the VH and/or VL region sequence comprises one amino acid substitution or a combination thereof selected from
a. N30, X634V, X634F, Q39, L45, D64, X765A, X1281V, X1281T, X12811, V99, H101, X14102E, F104, and N106 in the VH region sequence in i);
and
b. L20, V38, X1140R, X1140K, X2469, X3291L, X3393, and G102 in the VL region sequence in ii).

55 more elements

Dependencies are inferred from the claim text.

Polypeptide constructs binding to cd3

Life of this patent

Polypeptide constructs binding to cd3

Life of this patent

Abstract

Claims28