T cell recruiting polypeptides capable of binding CD123 and TCR α/β
AssigneeAblynx N.V.
InventorsDiane Van Hoorick, Annelies Roobrouck, Catelijne Stortelers, João Vieira, Edward McGowan
Life of this patent
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Abstract
Polypeptides are provided that bind CD123 on a target cell and the constant domain of TCR on a T cell. The polypeptides can be used in methods for treatment of CD123 associated cancers or inflammatory conditions.
Claims19
A nucleic acid encoding a polypeptide comprising a first immunoglobulin single variable domain (ISV) and a second ISV, wherein the first ISV specifically binds TCR and essentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), in which:
- i) CDR1 is chosen from the group consisting of:
- a) SEQ ID NO:
- 181;
- and
- b) amino acid sequences that have 3, 2 or 1 amino acid(s) difference with the amino acid sequence of SEQ ID NO:
- 181, wherein
- at position 2 the D has been changed into A, S, E, or G;
- at position 4 the H has been changed into Y;
- at position 5 the K has been changed into L;
- at position 6 the I has been changed into L;
- at position 8 the F has been changed into I or V;
- and/or
- at position 10 the G has been changed into S;
- and
- ii) CDR2 is chosen from the group consisting of:
- c) SEQ ID NO:
- 192;
- and
- d) amino acid sequences that have 3, 2 or 1 amino acid(s) difference with the amino acid sequence of SEQ ID NO:
- 192, wherein
- at position 1 the D has been changed into T or R;
- at position 3 the S has been changed into T or A;
- at position 5 the G has been changed into S or A;
- at position 7 the Q has been changed into D, E, T, A or V;
- at position 8 the T has been changed into A or V;
- and/or
- at position 9 the D has been changed into A, Q, N, V or S;
- and
- iii) CDR3 is chosen from the group consisting of:
- e) SEQ ID NO:
- 218;
- and
- f) amino acid sequences that have 3, 2 or 1 amino acid(s) difference with the amino acid sequence of SEQ ID NO:
- 218, wherein
- at position 1 the F has been changed into Y, L or G;
- at position 4 the I has been changed into L;
- at position 5 the Y has been changed into W;
- and/or
- at position 8 the D has been changed into N or S;
- and wherein the second ISV specifically binds CD123 and essentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), in which:
- i) CDR1 is chosen from the group consisting of:
- a) SEQ ID NO:
- 11;
- and
- b) amino acid sequences that have 3, 2 or 1 amino acid(s) difference with the amino acid sequence of SEQ ID NO:
- 11, wherein
- at position 3 the T has been changed into S or P;
- at position 6 the I has been changed into S;
- at position 7 the N has been changed into D;
- and/or
- at position 8 the D has been changed into V or A;
- and
- ii) CDR2 is SEQ ID NO:
- 17;
- and
- iii) CDR3 is chosen from the group consisting of:
- c) SEQ ID NO:
- 21;
- and
- d) amino acid sequences that have 1 amino acid(s) difference with the amino acid sequence of SEQ ID NO:
- 21, wherein at position 3 the P has been changed into A.
A nucleic acid encoding a polypeptide comprising a first immunoglobulin single variable domain (ISV) and a second ISV, wherein the first ISV specifically binds TCR and essentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), in which:
- i) CDR1 is chosen from the group consisting of:
- a) SEQ ID NO:
- 181;
- and
- b) amino acid sequences that have 1 amino acid difference with the amino acid sequence of SEQ ID NO:
- 181;
- and
- ii) CDR2 is chosen from the group consisting of:
- c) SEQ ID NO:
- 192;
- and
- d) amino acid sequences that have 1 amino acid difference with the amino acid sequence of SEQ ID NO:
- 192;
- and
- iii) CDR3 is chosen from the group consisting of:
- e) SEQ ID NO:
- 218;
- and
- f) amino acid sequences that have 1 amino acid difference with the amino acid sequence of SEQ ID NO:
- 218;
- and wherein the second ISV specifically binds CD123 and essentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), in which:
- i) CDR1 is chosen from the group consisting of:
- a) SEQ ID NO:
- 11;
- and
- b) amino acid sequences that have 1 amino acid difference with the amino acid sequence of SEQ ID NO:
- 11;
- and
- ii) CDR2 is chosen from the group consisting of:
- c) SEQ ID NO:
- 17;
- and
- d) amino acid sequences that have 1 amino acid difference with the amino acid sequence of SEQ ID NO:
- 17;
- and
- iii) CDR3 is chosen from the group consisting of:
- e) SEQ ID NO:
- 21;
- and
- f) amino acid sequences that have 1 amino acid difference with the amino acid sequence of SEQ ID NO:
- 21.
Dependencies are inferred from the claim text.