Cyclodextrin protein drug conjugates
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsAmy Han, William Olson
Life of this patent
Estimating the term…
Abstract
Provided herein are compounds, compositions, conjugates and methods for the treatment of diseases, and/or conditions such as, but not limited to, proliferative diseases. In certain embodiments, compounds, compositions, and conjugates are provided, which include cyclodextrin-based linker-payloads and protein conjugates thereof, and/or in combination with other agents. By administering these compounds, compositions, and conjugates as described herein to specific target cells, side-effects due to non-specific binding phenomena, for example, to non-target cells are reduced.
Claims41
A method for the treatment of a disease or disorder in a patient in need thereof comprising administering a compound or a pharmaceutically acceptable salt thereof to the patient, wherein the disease or disorder is selected from the group consisting of a proliferative disorder, a neurodegenerative disorder, an immunological disorder, an autoimmune disease, an inflammatory disorder, a dermatological disease, a metabolic disease, a cardiovascular disease, and a gastrointestinal disease, and wherein the compound is according to:
- (i) Formula (Ib1), Formula (Ib2), or Formula (Ic1):
- (ii) a Formula selected from the group consisting of:
- wherein BA is an antibody or an antigen binding fragment thereof;
- LL is a trivalent linker;
- SP is, independently in each instance, absent or is a spacer;
- n is an integer from 1 to 30;
- and
- PA is a payload moiety;
- or
- a regioisomer and/or stereoisomer thereof;
- (iii) Formula (Id):
- wherein:
- BA is an antibody or antigen binding fragment thereof;
- RG is a reactive group residue independently selected from the group consisting of
- wherein the
- indicates the atom through which the RG is bonded to the adjacent groups in the formula;
- SP1 and SP2 are each, independently in each instance, a spacer group residue, and wherein SP1 comprises a trivalent linker when attached to -CD, or SP1-CD or SP2 are independently, in each instance, absent;
- AA1 is a trivalent linker comprising an amino acid residue;
- AA2 is a di-peptide residue;
- PEG is a polyethylene glycol residue;
- PAB is
- wherein the
- indicates the atom through which the PAB is bonded to the adjacent groups in the formula;
- CD is, independently in each instance, absent, a cyclodextrin, or a modified cyclodextrin wherein the modified cyclodextrin is -SP3-RG-cyclodextrin;
- and, wherein at least one of CD is present;
- SP3 is, independently in each instance, absent or a spacer group residue;
- cyclodextrin is selected from the group consisting of
- wherein the
- indicates the atom through which the cyclodextrin is bonded to the adjacent groups in the formula;
- subscript n is an integer from 1 to 30;
- subscript m is an integer from 0 to 5;
- subscript p is 0 or 1;
- and
- PA is a payload moiety;
- or
- a regioisomer and/or stereoisomer thereof;
- or
- (iv) Formula (Ie):
- wherein:
- BA is an antibody or antigen binding fragment thereof;
- RG is, independently in each instance, a reactive group residue;
- SP2 is, independently in each instance, absent or a spacer group residue;
- AA1 is a trivalent linker comprising an amino acid residue;
- AA2 is a di-peptide residue;
- PEG is a polyethylene glycol residue;
- PAB is
- wherein the
- indicates the atom through which the PAB is bonded to the adjacent groups in the formula;
- CD is a cyclodextrin residue;
- subscript n is an integer from 1 to 30;
- subscript m is an integer from 0 to 5;
- subscript p is 0 or 1;
- and
- PA is a payload moiety;
- or
- a regioisomer and/or stereoisomer thereof.
Dependencies are inferred from the claim text.