US 11,744,876 B2
Immunomodulator antibody drug conjugates and uses thereof
Alice Yam, Tiburon, CA (US); Andreas Maderna, Escondido, CA (US); Cristina Abrahams, Burlingame, CA (US); Willy Solis, San Mateo, CA (US); Xiaofan Li, Fremont, CA (US); Ryan Stafford, Emeryville, CA (US); Gang Yin, South San Francisco, CA (US); Venita De Almeida, San Carlos, CA (US); Krishna Bajjuri, Union City, CA (US); and Adam A. Galan, Alameda, CA (US)
Assigned to SUTRO BIOPHARMA, INC., South San Francisco, CA (US)
Filed by Sutro Biopharma, Inc., South San Francisco, CA (US)
Filed on Jun. 10, 2020, as Appl. No. 16/898,233.
Claims priority of provisional application 62/859,629, filed on Jun. 10, 2019.
Claims priority of provisional application 62/984,758, filed on Mar. 3, 2020.
Prior Publication US 2020/0405813 A1, Dec. 31, 2020
Int. Cl. A61K 47/64 (2017.01); A61K 47/68 (2017.01); A61K 38/18 (2006.01); A61K 47/65 (2017.01); A61P 35/00 (2006.01); A61K 39/00 (2006.01)
CPC A61K 38/1866 (2013.01) [A61K 47/65 (2017.08); A61K 47/6803 (2017.08); A61K 47/6835 (2017.08); A61K 47/6889 (2017.08); A61P 35/00 (2018.01); A61K 2039/572 (2013.01)] 47 Claims
 
1. An antibody conjugate comprising an antibody, or an antigen-binding fragment thereof, covalently linked to a drug payload (PA) and further covalently linked to an immunomodulatory payload (IM) wherein
the drug payload is a residue of a cytotoxic compound selected from the group consisting of an alkylating agent, a DNA-crosslinking agent, an anti-tumor antibiotic, an anti-metabolite, an anti-mitotic agent, a histone-deacetylase (HDAC) inhibitor, a telomerase inhibitor, and an immunogenic cell death agent; and
the immunomodulatory payload is a residue of an immunomodulatory compound selected from the group consisting of a kinase inhibitor, a growth factor inhibitor, a Calcineurin inhibitor, a CRAC inhibitor, a PARPl antagonist, a PPARγ agonist, a Kvl.3 antagonist, a PP2A agonist, a MYD88 inhibitor, a BCL-2 inhibitor, an Adenosine A2A receptor (A2ar) agonist, a Toll-like receptor 7/8 (TLR7/8) agonist, a Toll-like receptor 4 (TLR4) agonist, a Toll-like receptor 9 (TLR9) agonist, a calcium-activated potassium channel (Kca3.1) agonist, a TGF˜R1 inhibitor, a TGF-R2 inhibitor, a GLi 1 inhibitor, a tankyrase (TNKS) antagonist, a Traf2 and Nck-interacting kinase (TNIK) antagonist, an imide, and a vitamin D receptor (VDR) agonist; and wherein
(i) the antibody or antigen-binding fragment thereof comprises a non-natural amino acid at position K42 and at least one non-natural amino acid at position Y180 or F404 that are covalently linked to the immunomodulatory payload or to the drug payload; and/or
(ii) the antibody or antigen-binding fragment thereof comprises one or more glutamine (Q) residues that is covalently linked to the immunomodulatory payload or to the drug payload; and/or wherein
(iii) the drug payload or the immunomodulatory payload is linked to the antibody, or antigen-binding fragment, via one or more linkers and the one or more linkers comprise a release trigger group, wherein the release trigger group is a β-glucuronidase-cleavable β-glucuronide according to the structure

OG Complex Work Unit Chemistry
wherein

OG Complex Work Unit Chemistry
indicates the atoms in the antibody drug conjugate to which the β-glucuronidase-cleavable β-glucuronide is bonded.