Agent for Eliminating Pluripotent Stem Cells

Patent metadata

Field	Value
Publication number	US-2022202948-A1
Application number	US-202017430312-A
Country	US
Kind code	A1
Filing date	Feb 12, 2020
Priority date	Feb 13, 2019
Publication date	Jun 30, 2022
Grant date	—

Abstract

An agent for eliminating a pluripotent stem cell, the agent comprising an antibody-drug conjugate that releases a compound represented by formula (1-1):

wherein
b represents an integer of 1 to 5; and Z represents a group represented by formula (Z-1) or formula (Z-2),

or a salt thereof.

First claim

1 - 35 . (canceled)

36 : A method for eliminating a pluripotent stem cell, comprising:
a step of adding the antibody-drug conjugate that releases a compound represented by formula (1-1) or formula (1-3):

wherein
b represents an integer of 1 to 5; and
Z is a group represented by formula (Z-1) or formula (Z-2):

where
W represents a group represented by formula (W-1) or formula (W-2):

where
Q represents a group represented by formula (Q-1) or formula (Q-2):

f represents 1 or 2;
R 1 represents —(CH 2 ) u —COOH; and
u represents 1 or 2;

wherein
R 2 represents a glutamic acid residue (Glu), an aspartic acid residue (Asp) or a lysine residue (Lys);
an N-terminal nitrogen atom of R 2 forms an amide bond together with carbonyl (a); and
W is a group represented by formula (W-1) or formula (W-2):

where
Q represents a group represented by formula (Q-1) or formula (Q-2):

or a salt thereof to a culture solution containing a pluripotent stem cell.

37 : The method for eliminating a pluripotent stem cell according to claim 36 , wherein
W is a group represented by formula (W-1).

38 : The method for eliminating a pluripotent stem cell according to claim 36 , wherein
an antibody-drug conjugate releases the compound selected from the following compounds:

or a salt thereof.

39 : The method for eliminating a pluripotent stem cell according to claim 36 , wherein
an antibody-drug conjugate releases the compound selected from the following compounds:

or a salt thereof.

40 : The method for eliminating a pluripotent stem cell according to claim 36 , wherein the pluripotent stem cell is an ES cell or an PS cell.

41 : The method for eliminating a pluripotent stem cell according to claim 36 , wherein the pluripotent stem cell is an iPS cell.

42 : A method for eliminating a pluripotent stem cell, comprising:
a step of adding the antibody-drug conjugate that releases a compound represented by formula (1-1) or formula (1-3):

wherein
b represents an integer of 1 to 5; and
Z is a group represented by formula (Z-1) or formula (Z-2):

where
W represents a group represented by formula (W-1) or formula (W-2):

where
Q represents a group represented by formula (Q-1) or formula (Q-2):

f represents 1 or 2;
R 1 represents —(CH 2 ) u —COOH; and
u represents 1 or 2;

wherein
R 2 represents a glutamic acid residue (Glu), an aspartic acid residue (Asp) or a lysine residue (Lys);
an N-terminal nitrogen atom of R 2 forms an amide bond together with carbonyl (a); and
W is a group represented by formula (W-1) or formula (W-2):

where
Q represents a group represented by formula (Q-1) or formula (Q-2):

or a salt thereof to a culture solution containing a cell cluster produced by culturing a pluripotent stem cell.

43 : The method for eliminating a pluripotent stem cell according to claim 42 , wherein the pluripotent stem cell is an ES cell or an PS cell.

44 : The method for eliminating a pluripotent stem cell according to claim 42 , wherein the pluripotent stem cell is an iPS cell.

45 : A method for producing a cell population including a differentiated cell derived from a pluripotent stem cell with substantially no pluripotent stem cell, comprising:
a step of contacting an antibody-drug conjugate that releases a compound represented by formula (1-1) or formula (1-3):

wherein
b represents an integer of 1 to 5; and
Z is a group represented by formula (Z-1) or formula (Z-2):

where
W represents a group represented by formula (W-1) or formula (W-2):

where
Q represents a group represented by formula (Q-1) or formula (Q-2):

f represents 1 or 2;
R 1 represents —(CH 2 ) u —COOH; and
u represents 1 or 2;

wherein
R 2 represents a glutamic acid residue (Glu), an aspartic acid residue (Asp) or a lysine residue (Lys);
an N-terminal nitrogen atom of R 2 forms an amide bond together with carbonyl (a); and
W is a group represented by formula (W-1) or formula (W-2):

where
Q represents a group represented by formula (Q-1) or formula (Q-2):

or a salt thereof and
a cell population including a differentiated cell derived from a pluripotent stem cell.

46 : The method for eliminating a pluripotent stem cell according to claim 45 , wherein
W is a group represented by formula (W-1).

47 : The method for producing a cell population according to claim 45 , wherein
an antibody-drug conjugate releases the compound selected from the following compounds:

or a salt thereof.

48 : The method for producing a cell population according to claim 45 , wherein
an antibody-drug conjugate releases the compound selected from the following compounds:

Assignees

• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Suwa Atsushi
• FUJIKI Ayaka
• TSUJIUCHI Makiko

Classifications

• C07K5/06156

  and Trp-amino acid; Derivatives thereof · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K5/06078

  and aromatic or cycloaliphatic · CPC title

• A61K47/6849 Primary

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• A61K47/6889

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title