US 12,428,477 B2
Antibody-drug conjugates comprising anti-TM4SF1 antibodies and methods of using the same
Paul A. Jaminet, Sudbury, MA (US); Shou-Ching S. Jaminet, Sudbury, MA (US); Edward H. Ha, Cambridge, MA (US); Leonard G. Presta, San Francisco, CA (US); and Manish S. Hudlikar, Brookline, MA (US)
Assigned to ANGIEX, INC., Cambridge, MA (US)
Appl. No. 17/434,315
Filed by ANGIEX, INC., Cambridge, MA (US)
PCT Filed Feb. 27, 2020, PCT No. PCT/US2020/020207
§ 371(c)(1), (2) Date Aug. 26, 2021,
PCT Pub. No. WO2020/176794, PCT Pub. Date Sep. 3, 2020.
Claims priority of provisional application 62/811,411, filed on Feb. 27, 2019.
Claims priority of provisional application 62/967,377, filed on Jan. 29, 2020.
Prior Publication US 2023/0096824 A1, Mar. 30, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61K 47/68 (2017.01)
CPC C07K 16/28 (2013.01) [A61K 47/68033 (2023.08); A61K 47/6849 (2017.08); A61K 2039/505 (2013.01); C07K 2317/21 (2013.01); C07K 2317/52 (2013.01)] 7 Claims
 
1. An antibody-drug conjugate comprising (1) an anti-transmembrane 4 L six family member 1 (TM4SF1) antibody or an antigen binding fragment thereof conjugated to (2) a therapeutic molecule via a linker, wherein the anti-TMA4SF1 antibody or the antigen binding fragment thereof comprises a human IgG1 Fc region comprising (1) a cysteine residue at position N297, or (2) a cysteine residue at position N297 and one or more mutations selected from the group consisting of M252Y, S254T, and T256E; as numbered by the EU index as set forth in Kabat, wherein the linker comprises (1) acetamide and (2) a spacer of C6 alkylene, wherein the therapeutic molecule is conjugated to the cysteine at position 297, and wherein the anti-TM4SF1 antibody or the antigen binding fragment thereof comprises:
(a) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 6, 7, and 8, respectively; and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 12, 13, and 14, respectively;
(b) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 18, 19, and 20, respectively; and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 24, 25, and 26, respectively;
(c) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 30, 31, and 32, respectively; and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 36, 37, and 38, respectively;
(d) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 42, 43, and 44, respectively; and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 48, 49, and 50, respectively;
(e) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 54, 55, and 56, respectively; and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 60, 61, and 62, respectively;
(f) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 66, 67, and 68, respectively; and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 72, 73, and 74, respectively;
(g) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 78, 79, and 80, respectively; and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 84, 85, and 86, respectively;
(h) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 94, 95, and 96, respectively; and a light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NOs: 107 or 108, a CDR2 comprising the amino acid sequence of SEQ ID NO: 109, a CDR3 comprising the amino acid sequence of SEQ ID NOs: 110 or 111; or
(i) a heavy chain comprising a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 115, a CDR2 domain comprising the amino acid sequence of SEQ ID NOs: 116 or 117, a CDR3 domain comprising the amino acid sequence of SEQ ID NOs: 118, 119, 120, or 121; and a light chain comprising a CDR1 domain comprising the amino acid sequence of SEQ ID NOs: 124, 125, 126, or 127, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 128, a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 129.