Anti-tissue factor antibodies and antibody conjugates, compositions comprising anti-tissue factor antibodies or antibody conjugates, and methods of making and using anti-tissue factor antibodies and antibody conjugates

Patent metadata

Field	Value
Publication number	US-12540197-B2
Application number	US-202418914023-A
Country	US
Kind code	B2
Filing date	Oct 11, 2024
Priority date	Oct 13, 2023
Publication date	Feb 3, 2026
Grant date	Feb 3, 2026

Abstract

The present disclosure relates to antibodies and antibody conjugates that selectively bind to tissue factor and its isoforms and homologs, and compositions comprising the antibodies. Also provided are methods of using the antibodies and antibody conjugates, such as therapeutic and diagnostic methods.

First claim

What is claimed is:

1 . An antibody conjugate comprising an antibody that specifically binds to tissue factor (TF) linked site-specifically to at least one payload moiety, wherein the antibody comprises one or more non-natural amino acids, and wherein the antibody comprises
(a) a V H comprising: a CDR-H1 comprising SEQ ID NO: 130; a CDR-H2 comprising SEQ ID NO: 780; and a CDR-H3 comprising SEQ ID NO: 1430; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2064; a CDR-L2 comprising SEQ ID NO: 2288; and a CDR-L3 comprising SEQ ID NO: 2512; (b) a V H comprising: a CDR-H1 comprising SEQ ID NO: 455; a CDR-H2 comprising SEQ ID NO: 1105; and a CDR-H3 comprising SEQ ID NO: 1755; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2176; a CDR-L2 comprising SEQ ID NO: 2400; and a CDR-L3 comprising SEQ ID NO: 2624; (c) a V H comprising: a CDR-H1 comprising SEQ ID NO: 214; a CDR-H2 comprising SEQ ID NO: 864; and a CDR-H3 comprising SEQ ID NO: 1514; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2064; a CDR-L2 comprising SEQ ID NO: 2288; and a CDR-L3 comprising SEQ ID NO: 2512; (d) a V H comprising: a CDR-H1 comprising SEQ ID NO: 539; a CDR-H2 comprising SEQ ID NO: 1189; and a CDR-H3 comprising SEQ ID NO: 1839; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2176; a CDR-L2 comprising SEQ ID NO: 2400; and a CDR-L3 comprising SEQ ID NO: 2624; (e) a V H comprising: a CDR-H1 comprising SEQ ID NO: 192; a CDR-12 comprising SEQ ID NO: 842; and a CDR-H3 comprising SEQ ID NO: 1492; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2064; a CDR-L2 comprising SEQ ID NO: 2288; and a CDR-L3 comprising SEQ ID NO: 2512; or (f) a V H comprising: a CDR-H1 comprising SEQ ID NO: 517; a CDR-H2 comprising SEQ ID NO: 1167; and a CDR-H3 comprising SEQ ID NO: 1817; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2176; a CDR-L2 comprising SEQ ID NO: 2400; and a CDR-L3 comprising SEQ ID NO: 2624.

2 . A kit comprising the antibody conjugate of claim 1 and instructions for use of the antibody conjugate.

3 . A polynucleotide encoding the antibody of the antibody conjugate of claim 1 .

4 . A vector comprising the polynucleotide of claim 3 .

5 . A recombinant host cell comprising the vector of claim 4 .

6 . A pharmaceutical composition comprising the antibody conjugate of claim 1 and a pharmaceutically acceptable carrier.

7 . A pharmaceutical composition comprising the antibody conjugate of claim 1 , (b) one or more additional active agents, and (c) a pharmaceutically acceptable carrier.

8 . A method for reducing cell proliferation in a subject in need thereof, comprising administering to the subject an effective amount of an antibody conjugate of claim 1 .

9 . A method for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of an antibody conjugate of claim 1 .

10 . The method of claim 9 , further comprising administering to the subject one or more additional active agents.

11 . A method of diagnosing and treating cancer in subject in need thereof, comprising
(a) detecting the expression of tissue factor in a cell or tissue of the subject to diagnose the cancer; and (b) administering to the subject an effective amount of a pharmaceutical composition of claim 6 .

12 . The antibody conjugate of claim 1 , wherein the antibody comprises one or more non-natural amino acid selected from the group consisting of: HC-F404, HC-K121, HC-Y180, HC-F241, HC-221, HC-Y391, LC-T22, LC-S7, LC-N152, LC-K42, LC-E161, LC-D170, HC-S136, HC-S25, HC-A40, HC-S119, HC-S190, HC-K222, HC-R19, HC-Y52, and HC-S70, according to the Kabat, Chothia, or EU numbering scheme.

13 . The antibody conjugate of claim 1 , wherein a residue of the one or more non-natural amino acids is linked to the payload moiety via a linker that is cleavable.

14 . The antibody conjugate of claim 1 , wherein the one or more non-natural amino acids is selected from the group consisting of p-acetyl-L-phenylalanine, O-methyl-L-tyrosine, an -3-(2-naphthyl) alanine, 3-methyl-phenylalanine, O-4-allyl-L-tyrosine, 4-propyl-L-tyrosine, a tri-O-acetyl-GlcNAcβ-serine, L-Dopa, fluorinated phenylalanine, isopropyl-L-phenylalanine, p-azido-L-phenylalanine, p-azido-methyl-L-phenylalanine, compound 56, p-acyl-L-phenylalanine, p-benzoyl-L-phenylalanine, L-phosphoserine, phosphonoserine, phosphonotyrosine, p-iodo-phenylalanine, p-bromophenylalanine, p-amino-L-phenylalanine, isopropyl-L-phenylalanine, and p-propargyloxy-phenylalanine.

15 . The antibody conjugate of claim 1 , wherein the payload moiety is selected from the group consisting of maytansines, hemiasterlins, amanitins, camptothecins, exatecans, anthracyclines, pyrrolobenzodiazepines, and auristatins.

16 . The antibody conjugate of claim 1 , wherein the antibody comprises a V H comprising: a CDR-H1 comprising SEQ ID NO: 130; a CDR-H2 comprising SEQ ID NO: 780; and a CDR-H3 comprising SEQ ID NO: 1430; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2064; a CDR-L2 comprising SEQ ID NO: 2288; and a CDR-L3 comprising SEQ ID NO: 2512.

17 . The antibody conjugate of claim 1 , wherein the antibody comprises three heavy chain CDRs and three light chain CDRs from a V H /V L pair, selected from the group consisting of SEQ ID NOs: 2752/3061, 2814/3061, and 2836/3061.

18 . The antibody conjugate of claim 1 , wherein the antibody comprises a V H /V L pair, selected from the group consisting of SEQ ID NOs: 2752/3061, and 2836/3061.

19 . The antibody conjugate of claim 1 , wherein the antibody conjugate comprises:
(a) an antibody comprising a V H comprising: a CDR-H1 comprising SEQ ID NO: 130; a CDR-H2 comprising SEQ ID NO: 780; and a CDR-H3 comprising SEQ ID NO: 1430; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2064; a CDR-L2 comprising SEQ ID NO: 2288; and a CDR-L3 comprising SEQ ID NO: 2512; (b) para-azidomethylphenylalanine residues at antibody sites HC241, HC404, HC180, and HC391; and (c) the following linker-payload, wherein n2 is 8 and each linker-payload is bonded to one of the para-azidomethylphenylalanine residue side chains:

20 . The antibody conjugate of claim 1 , wherein the antibody comprises a V H comprising: a CDR-H1 comprising SEQ ID NO: 455; a CDR-H2 comprising SEQ ID NO: 1105; and a CDR-H3 comprising SEQ ID NO: 1755; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2176; a CDR-L2 comprising SEQ ID NO: 2400; and a CDR-L3 comprising SEQ ID NO: 2624.

21 . The antibody conjugate of claim 1 , wherein the antibody comprises a V H comprising: a CDR-H1 comprising SEQ ID NO: 214; a CDR-H2 comprising SEQ ID NO: 864; and a CDR-H3 comprising SEQ ID NO: 1514; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2064; a CDR-L2 comprising SEQ ID NO: 2288; and a CDR-L3 comprising SEQ ID NO: 2512.

22 . The antibody conjugate of claim 1 , wherein the antibody comprises a V H comprising: a CDR-H1 comprising SEQ ID NO: 539; a CDR-H2 comprising SEQ ID NO: 1189; and a CDR-H3 comprising SEQ ID NO: 1839; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 2176; a CDR-L2 comprising SEQ ID NO: 2400; and a CDR-L3 comprising SEQ ID NO: 2624.

23 . The antibody conjugate of claim 1 , wherein the antibody comprises a V H comprising: a CDR-H1 comprising SEQ ID NO: 192; a CDR-H2 comprising SEQ ID NO: 842; and a CDR-H3 comprising SEQ ID NO: 1492; and a V L comprising: a CDR-L1

Assignees

• Sutro Biopharma Inc

Inventors

• Lee Grace Jungeun
• Gakhal Amandeep Kaur
• Calarese Daniel
• Yang Junhao
• Bajjuri Krishna
• Li Xiaofan
• Zhou Sihong
• Kiefel Helena
• Yuan Robert Tian-Xuan
• Mcgeehan Andrew James
• Wen Miao
• Yin Gang
• Yam Alice

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title