US 10,472,422 B2Granted

Tetravalent anti-PSGL-1 antibodies and uses thereof

AssigneesAbGenomics International Inc., BioAlliance C.V.

InventorsRong-Hwa Lin, Shih-Yao Lin, Yu-Ying Tsai

Life of this patent

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Abstract

Provided herein are tetravalent antibodies that specifically bind to human PSGL-1. Unlike bivalent antibodies, these tetravalent antibodies contain a dimer of two monomers, with each monomer comprising two light chain variable (VL) domains and two heavy chain variable (VH) domains. This format allows for cross-linker/FcR-expressing cell-independent tetravalent antibodies against PSGL-1 that show enhanced efficacy as compared to bivalent PSGL-1 antibodies. These tetravalent antibodies can be used in a variety of diagnostic and therapeutic methods, including without limitation treating T-cell mediated inflammatory diseases, transplantations, and transfusions.

Claims150

Dependent claims

A tetravalent antibody that specifically binds to human PSGL-1, the tetravalent antibody comprising a dimer of two monomers, wherein each monomer of the dimer comprises a single-chain polypeptide comprising, from N-terminus to C-terminus:

(a) a first light chain variable (VL) domain;
(b) a first linker sequence, wherein the first linker sequence has 5-12 amino acids;
(c) a first heavy chain variable (VH) domain;
(d) a second linker sequence, wherein the second linker sequence has two, three, four, or five repeats of the amino acid sequence of GGGGS (SEQ ID NO:25);
(e) a second VL domain;
(f) a third linker sequence, wherein the third linker sequence has 5-12 amino acids;
(g) a second VH domain;
(h) a fourth linker sequence, wherein the fourth linker sequence has 5-12 amino acids;
and
(i) an antibody Fc domain,
wherein each of the first and the second VL domains comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:20;
(ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:21;
and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:22;
wherein each of the first and the second VH domains comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:17;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:18;
and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:19;
wherein the first VL domain forms a VH-VL binding unit with the second VH domain, and the first VH domain forms a VH-VL binding unit with the second VL domain;
and wherein each of the two VH-VL binding units is specific for human PSGL-1.

15 more elements

(a) a first heavy chain variable (VH) domain;
(b) a first linker sequence, wherein the first linker sequence has two, three, four, or five repeats of the amino acid sequence of GGGGS (SEQ ID NO:25);
(c) a first light chain variable (VL) domain;
(d) a second linker sequence, wherein the second linker sequence has 5-12 amino acids;
(e) a second VL domain;
(f) a third linker sequence, wherein the third linker sequence has two, three, four, or five repeats of the amino acid sequence of GGGGS (SEQ ID NO:25);
(g) a second VH domain;
(h) a fourth linker sequence, wherein the fourth linker sequence has 5-12 amino acids;
and
(i) an antibody Fc domain,
wherein each of the first and the second VL domains comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:20;
(ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:21;
and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:22;
wherein each of the first and the second VH domains comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:17;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:18;
and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:19;
wherein each of the first and the second VL domains forms a VH-VL binding unit with a corresponding VH domain of the first and the second VH domains;
and wherein each of the two VH-VL binding units is specific for human PSGL-1.

15 more elements

A tetravalent antibody that specifically binds to human PSGL-1, the tetravalent antibody comprising a dimer of two monomers, wherein each monomer of the dimer comprises an antibody heavy chain and an antibody light chain;

wherein the antibody light chain comprises, from N-terminus to C-terminus:
(i) a first heavy chain variable (VH) domain,
(ii) a first linker sequence, wherein the first linker sequence has two, three, four, or five repeats of the amino acid sequence of GGGGS (SEQ ID NO:25),
(iii) a first light chain variable (VL) domain,
(iv) a second linker sequence, wherein the second linker sequence has 5-12 amino acids,
(v) a second VL domain, and
(vi) a light chain constant (CL) domain;
wherein the antibody heavy chain comprises:
(i) a second VH domain, and
(ii) a heavy chain constant region comprising a first heavy chain constant region (CH1) domain, an antibody hinge region, an second heavy chain constant region (CH2) domain, and a third heavy chain constant region (CH3) domain;
wherein each of the first and the second VL domains comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:20;
(ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:21;
and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:22;
wherein each of the first and the second VH domains comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:17;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:18;
and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:19;
wherein each of the first and the second VL domains forms a VH-VL binding unit with a corresponding VH domain of the first and the second VH domains;
and wherein each of the two VH-VL binding units is specific for human PSGL-1.

15 more elements

(a) a first light chain variable (VL) domain;
(b) a first linker sequence, wherein the first linker sequence has 5-12 amino acids;
(c) a first heavy chain variable (VH) domain;
(d) a second linker sequence, wherein the second linker sequence has two, three, four, or five repeats of the amino acid sequence of GGGGS (SEQ ID NO:25);
(e) a second VL domain;
(f) a third linker sequence, wherein the third linker sequence has 5-12 amino acids;
(g) a second VH domain;
(h) a fourth linker sequence, wherein the fourth linker sequence has 5-12 amino acids;
and
(i) an antibody Fc domain,
wherein each of the first and the second VL domains comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:24 or SEQ ID NO:30;
wherein each of the first and the second VH domains comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:23 or SEQ ID NO:29;
wherein the first VL domain forms a VH-VL binding unit with the second VH domain, and the first VH domain forms a VH-VL binding unit with the second VL domain;
and wherein each of the two VH-VL binding units is specific for human PSGL-1.

11 more elements

(a) a first heavy chain variable (VH) domain;
(b) a first linker sequence, wherein the first linker sequence has two, three, four, or five repeats of the amino acid sequence of GGGGS (SEQ ID NO:25);
(c) a first light chain variable (VL) domain;
(d) a second linker sequence, wherein the second linker sequence has 5-12 amino acids;
(e) a second VL domain;
(f) a third linker sequence, wherein the third linker sequence has two, three, four, or five repeats of the amino acid sequence of GGGGS (SEQ ID NO:25);
(g) a second VH domain;
(h) a fourth linker sequence, wherein the fourth linker sequence has 5-12 amino acids;
and
(i) an antibody Fc domain,
wherein each of the first and the second VL domains comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:24 or SEQ ID NO:30;
wherein each of the first and the second VH domains comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:23 or SEQ ID NO:29;
wherein each of the first and the second VL domains forms a VH-VL binding unit with a corresponding VH domain of the first and the second VH domains;
and wherein each of the two VH-VL binding units is specific for human PSGL-1.

11 more elements

wherein the antibody light chain comprises, from N-terminus to C-terminus:
(i) a first heavy chain variable (VH) domain,
(ii) a first linker sequence, wherein the first linker sequence has two, three, four, or five repeats of the amino acid sequence of GGGGS (SEQ ID NO:25),
(iii) a first light chain variable (VL) domain,
(iv) a second linker sequence, wherein the second linker sequence has 5-12 amino acids,
(v) a second VL domain, and
(vi) a light chain constant (CL) domain;
wherein the antibody heavy chain comprises:
(i) a second VH domain, and
(ii) a heavy chain constant region comprising a first heavy chain constant region (CH1) domain, an antibody hinge region, an second heavy chain constant region (CH2) domain, and a third heavy chain constant region (CH3) domain;
wherein each of the first and the second VL domains comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:24 or SEQ ID NO:30;
wherein each of the first and the second VH domains comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:23 or SEQ ID NO:29;
wherein each of the first and the second VL domains forms a VH-VL binding unit with a corresponding VH domain of the first and the second VH domains;
and wherein each of the two VH-VL binding units is specific for human PSGL-1.

11 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/400,888Filed 6 Jan 2017 · us provisional application
Priority: 8 Jan 2016
Published: US 2017/0198052 A113 Jul 2017
Granted: 12 Nov 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 16/2896
Against receptors, cell surface antigens or cell surface determinants: against molecules with a "CD"-designation, not provided for elsewhere
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
C07K 2317/21
Characterized by taxonomic origin: from primates, e.g. man

Family

Application62/276,806Us provisional application · filed 8 Jan 2016
US 2017/0198052 A1Pre-grant publication · published 13 Jul 2017
US 10,472,422 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

15/400,888Filed 6 Jan 2017 · us provisional application

Priority

8 Jan 2016

Published

US 2017/0198052 A113 Jul 2017

Granted

12 Nov 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 16/2896
Against receptors, cell surface antigens or cell surface determinants: against molecules with a "CD"-designation, not provided for elsewhere
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
C07K 2317/21
Characterized by taxonomic origin: from primates, e.g. man