Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease
First Claim
Patent Images
1. A drug-linker-antibody conjugate of Formula Ia:
-
LAa-Ww—
Yy-D)p
Iaor a pharmaceutically acceptable salt thereof,wherein,L- is an antibody that immunospecifically binds to a cancer cell antigen which is on the surface of a cancer cell;
-Aa-Ww—
Yy—
is an enzymatically cleavable linker unit that links the Drug unit and the antibody, wherein;
-A- is a Stretcher unit;
a is 1;
each —
W—
is independently an Amino Acid unit;
—
Y—
is a self-immolative Spacer unit;
w is an integer ranging from 2 to 12,y is 1 or 2;
p ranges from 1 to about 20; and
-D is a Drug unit of the formula
1 Assignment
0 Petitions
Accused Products
Abstract
Drug-Linker-Ligand Conjugates are disclosed in which a Drug is linked to a Ligand via a peptide-based Linker unit. In one embodiment, the Ligand is an Antibody. Drug-Linker compounds and Drug compounds are also disclosed. Methods for treating cancer, an autoimmune disease or an infectious disease using the compounds and compositions of the invention are also disclosed.
-
Citations
81 Claims
-
1. A drug-linker-antibody conjugate of Formula Ia:
-
LAa-Ww—
Yy-D)p
Iaor a pharmaceutically acceptable salt thereof, wherein, L- is an antibody that immunospecifically binds to a cancer cell antigen which is on the surface of a cancer cell; -Aa-Ww—
Yy—
is an enzymatically cleavable linker unit that links the Drug unit and the antibody, wherein;-A- is a Stretcher unit; a is 1; each —
W—
is independently an Amino Acid unit;—
Y—
is a self-immolative Spacer unit;w is an integer ranging from 2 to 12, y is 1 or 2; p ranges from 1 to about 20; and -D is a Drug unit of the formula - View Dependent Claims (3, 5, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 65, 66, 67, 68, 75, 76, 77)
-
-
2. A drug-linker-antibody conjugate of the formula Ia:
-
LAa-Ww—
Yy-D)p
Iaor a pharmaceutically acceptable salt thereof, wherein, L- is an antibody that immunospecifically binds to a cancer cell antigen which is on the surface of a cancer cell; -Aa-Ww—
Yy—
is an enzymatically cleavable linker unit that links the Drug unit and the antibody, wherein;-A- is a Stretcher unit; a is 1; each —
W—
is independently an Amino Acid unit;—
Y—
is a self-immolative Spacer unit;w is an integer ranging from 2 to 12; y is 1 or 2; p ranges from 1 to about 20; and -D is a Drug unit having the structure - View Dependent Claims (4, 6, 14, 20, 59, 60, 61, 62, 63, 64)
-
-
32. A composition comprising drug-linker-antibody conjugates having Formula Ia:
-
LAa-Ww—
Yy-D)p
Iaor a pharmaceutically acceptable salt thereof; wherein, L- is an antibody that immunospecifically binds to a cancer cell antigen which is on the surface of a cancer cell; -Aa-Ww—
Yy—
is an enzymatically cleavable linker unit that links the Drug unit and the antibody, wherein;-A- is a Stretcher unit; a is 1; each —
W—
is independently an Amino Acid unit;—
Y—
is a self-immolative Spacer unit;w is an integer ranging from 2 to 12; y is 1 or 2; p ranges from 1 to 10 and is the average number of -Aa-Ww—
Yy-D units per antibody in the composition; and-D is a Drug unit of the formula - View Dependent Claims (34, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 69, 70, 71, 72, 73, 74, 78, 79)
-
-
33. A composition comprising drug-linker-antibody conjugates having Formula Ia:
-
LAa-Ww—
Yy-D)p
Iaor a pharmaceutically acceptable salt thereof, wherein, L- is an antibody that immunospecifically binds to a cancer cell antigen which is on the surface of a cancer cell; -Aa-Ww—
Yy—
is an enzymatically cleavable linker unit that links the Drug unit and the antibody , wherein;-A- is a Stretcher unit; a is 1; each —
W—
is independently an Amino Acid unit;—
Y—
is a self-immolative Spacer unit;w is an integer ranging from 2 to 12; y is 1 or 2; p ranges from 1 to 10 and is the average number of -Aa-Ww—
Yy-D units per antibody in the composition; and-D is a Drug unit having the structure - View Dependent Claims (35)
-
-
47. A method for the treatment of Hodgkin'"'"'s Disease or Anaplastic Large Cell Lymphoma in a human, the method comprising administering to the human an effective amount of a drug-linker-antibody conjugate wherein the drug-linker-antibody conjugate is taken up inside the cancer cell and, once inside the cancer cell, the linker unit is cleaved, resulting in release of drug;
- the drug-linker-antibody conjugate having formula Ia;
LAa-Ww—
Yy-D)p
Iaor a pharmaceutically acceptable salt thereof wherein, L- is an antibody that immunospecifically binds to human CD30 antigen; -Aa-Ww—
Yy—
is an enzymatically cleavable linker unit that links the Drug unit and the antibody, wherein;-A- is a Stretcher unit; a is 1; each —
W—
is independently an Amino Acid unit;—
Y—
is a self-immolative Spacer unit;w is an integer ranging from 2 to 12; y is 1 or 2; p ranges from 1 to about 20; and -D is a Drug unit having the structure - View Dependent Claims (48, 49, 50, 51, 52)
- the drug-linker-antibody conjugate having formula Ia;
-
53. A method for the treatment of Hodgkin'"'"'s Disease or Anaplastic Large Cell Lymphoma in a human, the method comprising administering to the human an effective amount of a composition comprising drug-linker-antibody conjugates and a pharmaceutically acceptable carrier wherein the drug-linker-antibody conjugates are taken up inside the cancer cell and, once inside the cancer cell, the linker units of the drug-linker-antibody conjugates are cleaved, resulting in release of drug;
- the drug-linker-antibody conjugates having Formula Ia;
LAa-Ww—
Yy-D)p
Iaor a pharmaceutically acceptable salt thereof; wherein, L- is an antibody that immunospecifically binds to human CD30 antigen; -Aa-Ww—
Yy—
is an enzymatically cleavable linker unit that links the Drug unit and the antibody, wherein;-A- is a Stretcher unit; a is 1; each —
W—
is independently an Amino Acid unit;—
Y—
is a self-immolative Spacer unit;w is an integer ranging from 2 to 12; y is 1 or 2; p ranges from 1 to 10 and is the average number of -Aa-Ww—
Yy-D units per antibody in the composition; and-D is a Drug unit of the formula - View Dependent Claims (54, 55, 56, 57, 58, 80, 81)
- the drug-linker-antibody conjugates having Formula Ia;
Specification