JPWO2020016662A5 - - Google Patents

Claims (20)

An isolated antibody that binds to Trop2, said antibody.
Heavy Chain Variable Region ( _VH ): Containing one or more of the following:
(A) Heavy chain complementarity determining regions 1 (HCCDR1) shown as GYX ₁ FTX ₂ YX ₃ where X ₁ is R or T, X ₂ is D, S or N, and X ₃ is V or W. );
(B) X ₁ is Y or F, X ₂ is G or S, X ₃ is S, H or G, X ₄ is D or S, and X ₅ is S, Y, T or Heavy chain complementarity determination region 2 (HCCDR2) represented as IX ₁ PX ₂ X ₃ X ₄ X ₅ X ₆ where G and X ₆ is F or T; and (c) X ₁ is A or T. Yes, X ₂ is F, G or S, X ₃ is F or S, X ₄ is E, Y or nonexistent, X ₅ is G or nonexistent, X ₆ is L, F Or heavy chain complementarity determination region 3 (HCCDR3) shown as X ₁ RX ₂ X ₃ X ₄ X ₅ X ₆ X ₇ Y, which is absent and X ₇ is A or D; and / or 1 below. Light chain variable region ( _VL ), including one or more:
(D) QX ₁ IX ₂ X ₃ X where X ₁ is G, N or D, X ₂ is N or G, X ₃ is N, T or W and X ₄ is Y or S. Light chain complementarity determining regions 1 (LCCDR1), shown as ₄ .
(E) Light chain complementarity determination region 2 (LCCDR2) represented as X ₁ X ₂ X ₃ where X ₁ is R or Y, X ₂ is A or S, and X ₃ is N or S; And (f) X ₁ is L or Q, X ₂ is Q or H, X ₃ is Y or S, X ₄ is D, Y or E, and X ₅ is E, S or T. Light chain complementarity determination region 3 (LCCDR3), where X ₆ is F or W and X ₇ is L or F, as shown as X ₁ X ₂ X ₃ X ₄ X ₅ X ₆ PX ₇ T;
The isolated antibody comprising. Claimed that the antibody binds to the same human TROP2 epitope as the reference antibody selected from the group consisting of Trop2-Ab7, Trop2-Ab8, Trop2-Ab22, Trop2-Ab40, Trop2-Ab46, Trop2-Ab50 and Trop2-Ab51. Item 1. The isolated antibody according to Item 1. The isolated antibody of claim 2, wherein the antibody comprises _VH , wherein the HCCDR1, HCCDR2 and HCCDR3 are at least 85% identical to the reference antibodies HCCDR1, HCCDR2 and HCCDR3 overall. The isolated antibody of claim 3, wherein the V _H comprises the same HCCDR1, HCCDR2 and HCCDR3 as the reference antibody. The isolated antibody of claim 2, wherein the antibody comprises _VL , wherein the LCCDR1, LCCDR2 and LCCDR3 are at least 85% identical to the reference antibodies LCCDR1, LCCDR2 and LCCDR3. The isolated antibody of claim 5, wherein the _VL comprises the same LCCDR1, LCCDR2 and LCCDR3 as the reference antibody. The isolated antibody according to claim 2, wherein the antibody has the same heavy chain CDR and light chain CDR as the reference antibody. The isolated antibody according to claim 1, wherein the antibody is an IgG molecule. The isolated antibody of claim 5, wherein the antibody comprises the same V _H and / or _VL as the reference antibody. A nucleic acid or nucleic acid set that totally encodes the anti-Trop2 antibody of claim 1. A vector or vector set comprising the nucleic acid of claim 10. A host cell comprising the vector or vector set according to claim 11. (I) The antibody according to claim 1; and (ii) at least one therapeutic agent;
Including
The antibody is a antibody-pharmaceutical complex (ADC) that is covalently complexed to the at least one therapeutic agent. The antibody-pharmaceutical complex according to claim 13, wherein the antibody is complexed with the therapeutic agent via a linker. The linker comprises a molecular spacer of formula I.

In the formula, R1 is optionally substituted C1-6 alkyl group, optionally substituted phenyl group, optionally substituted C2-6 alkylene group, optionally substituted C2-6 alkenylene group, optionally substituted. The antibody-pharmaceutical complex of claim 14, wherein the C2-6 alkynylene group or optionally substituted triazole is and X is O, S or N. The antibody-pharmaceutical complex of claim 13, wherein the at least one therapeutic agent is a cytotoxic agent. (I) An extracellular domain comprising an antigen-binding fragment that binds to Trop2 and comprising the HC CDRs (s) and / or LC CDRs (s) according to claim 1.
(Ii) transmembrane domain; and (iii) one or more intracellular co-stimulation domains;
Chimeric antigen receptor, including. (I) The antibody of claim 1, optionally conjugated to a therapeutic agent; and (ii) a pharmaceutically acceptable carrier;
A pharmaceutical composition comprising. The pharmaceutical composition of claim 18, for use in a method of reducing the number of TROP2 ⁺ cells in a subject in need thereof, wherein the method is an effective amount of the said in a subject in need thereof. The pharmaceutical composition comprising administering the pharmaceutical composition. A method for detecting Trop2 ⁺ cells in a sample from a subject suspected of having Trop2 ⁺ cells, wherein the method is:
i, contacting the sample with the antibody of claim 1, which is complexed with a labeling reagent; and ii, Trop2 ⁺ cells in the sample based on the binding of the antibody to the cells in the sample. To detect the presence of;
The method described above.