US 11,530,271 B2 · CD70 combination therapy

Abstract

The present invention relates to combination therapies for the treatment of malignancy, particularly myeloid malignancy such as acute myeloid leukemia (AML). The combination therapies may include an antibody molecule that binds to CD70 and at least one antibody molecule that binds to a leukemic stem cell target. Preferred leukemic stem cell targets are TIM-3, IL1R3/IL1RAP and CD47.

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Claims24

Dependent claims

A combination comprising a first antibody molecule that specifically binds to CD70 and a second antibody molecule that specifically binds to TIM-3,

wherein the first antibody molecule comprises a first variable heavy chain domain (VH) comprising HCDR1, HCDR2 and HCDR3 regions, and a first variable light chain domain (VL) comprising LCDR1, LCDR2 and LCDR3 regions, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 regions of the first VH and the first VL comprise the amino acid sequences set forth in SEQ ID NOs:
1 2, 3, 5, 6, and 7, respectively, and
wherein the second antibody molecule comprises a second VH comprising HCDR1, HCDR2 and HCDR3 regions, and a second VL comprising LCDR1, LCDR2 and LCDR3 regions, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 regions of the second VH and the second VL comprise:
(i) SEQ ID NOs:
39, 40, 41, 78, 79, and 80, respectively;
(ii) SEQ ID NOs:
39, 42, 43, 81, 82, and 83, respectively;
(iii) SEQ ID NOs:
44, 45, 46, 84, 85, and 86, respectively;
(iv) SEQ ID NOs:
47, 48, 49, 87, 82, and 88, respectively;
(v) SEQ ID NOs:
50, 51, 52, 89, 90, and 91, respectively;
(vi) SEQ ID NOs:
53, 54, 55, 92, 93, and 94, respectively;
(vii) SEQ ID NOs:
56, 57, 58, 95, 96, and 97, respectively;
(viii) SEQ ID NOs:
50, 59, 60, 98, 99, and 100, respectively;
(ix) SEQ ID NOs:
61, 62, 63, 101, 102, and 103, respectively;
(x) SEQ ID NOs:
39, 64, 65, 104, 105, and 106, respectively;
(xi) SEQ ID NOs:
50, 66, 67, 107, 108, and 109, respectively;
(xii) SEQ ID NOs:
50, 68, 69, 110, 111, and 112, respectively;
(xiii) SEQ ID NOs:
70, 71, 72, 113, 114, and 115, respectively;
(xiv) SEQ ID NOs:
50, 73, 74, 116, 111, and 117, respectively;
or
(xv) SEQ ID NOs:
75, 76, 77, 118, 119, and 120, respectively.

31 more elements

Dependencies are inferred from the claim text.

Description22,372 words

Summary2,909 words

#This application claims benefit of Great Britain Patent Application No. 1800649.4, filed Jan. 16, 2018, the entire contents of which are incorporated herein by reference.

#The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jan. 16, 2019, is named 608245_AGX5-038_Sequence_Listing.txt and is 59,685 bytes in size.

#The present invention relates to combination therapies for the treatment of malignancy, particularly myeloid malignancy such as acute myeloid leukemia (AML). The combination therapies may include an antibody molecule that binds to CD70 and at least one antibody molecule that binds to a leukemic stem cell (LSC) target. Preferred leukemic stem cell targets are TIM-3, IL1R3/IL1RAP and CD47. Alternatively or in addition, the combination therapies may include an antibody molecule that binds to CD70 and an agent that inhibits SIRPα signaling. The combination therapies may further include an additional anti-cancer agent, for example an agent used for the treatment of AML such as azacitidine or decitabine.

Brief description of the drawings9 figures

#FIG. 1 shows the combined efficacy of an anti-CD70 antibody (ARGX-110) and anti-TIM-3 antibodies (1A11 and 2B10) in mediating antibody-dependent cellular phagocytosis (ADCP) against BDCM cell line.

#FIG. 2 shows the combined efficacy of an anti-CD70 antibody (ARGX-110) and anti-IL1RAP antibodies (1F10, 1C1, 7E4G1E8 and 89412) in mediating antibody-dependent cellular phagocytosis (ADCP) against AML cell lines (MV4-11, THP1 and U937).

#FIGS. 3A and 3B show the combined efficacy of an anti-CD70 antibody (ARGX-110) and anti-CD47 antibodies (B6H12, CC2C6 and BRIC126) in mediating antibody-dependent cellular phagocytosis (ADCP) against AML cell lines (MC1010, MV4-11, THP1, GDM1 and U937).

Detailed description19,179 words

#A. Definitions

#Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one skilled in the art in the technical field of the invention.

#“Combination therapy”—As used herein, the term “combination therapy” refers to a treatment in which a subject, for example a human subject, is given two or more therapeutic agents. The “combinations” described herein are for use in combination therapy. The two or more therapeutic agents are typically administered so as to treat a single disease, herein a malignancy. In certain embodiments, the combination therapies of the present invention utilize antibody molecules binding to different targets, specifically CD70 and a leukemic stem cell target, for example TIM-3, CD47 or IL1RAP. As described elsewhere herein, the antibody molecules included in the combination therapies may be comprised within a single antibody (for example, a multispecific antibody), may be co-formulated or may be provided separately, for example as separate compositions, for administration to a subject or patient in need thereof. In certain embodiments, the combination therapies of the present invention utilize an antibody molecule that binds to CD70 in combination with at least one agent that inhibits SIRPα signaling. The antibody molecule that binds to CD70 may be combined with the agent that inhibits SIRPα signaling into a single SIRPα-antibody molecule fusion protein. Alternatively, the antibody molecule that binds to CD70 and the agent that inhibits SIRPαsignaling may be provided separately, for example as separate compositions, for administration to a subject or patient in need thereof.

Facts

Application

16/249,480Filed 16 Jan 2019

Priority

GB 180064916 Jan 2018

Published

US 2019/0241668 A18 Aug 2019

Granted

20 Dec 2022

Term ends

28 Oct 2039

Estimated · how

20 years from earliest known nonprovisional domestic filing plus recorded patent term adjustment, including 285 days of adjustment. Maintenance-fee lapses, terminal disclaimers and statutory extensions have not been checked. The continuity chain may be incomplete; this is not an enforceability determination.

Classification14 codes

C07K 16/2875
Against receptors, cell surface antigens or cell surface determinants: against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61P 35/02
Antineoplastic agents: specific for leukemia
C07K 16/2803
Against receptors, cell surface antigens or cell surface determinants: against the immunoglobulin superfamily

Timeline

16 Jan 2018Priority claimedGB 1800649
16 Jan 2019Application filedUS 16/249,480
17 May 2019Assigned to Argenx Bvbaassignment of assignor's interest
8 Aug 2019PublishedUS 2019/0241668 A1
25 Jan 2021Assigned to Argenx Bvbaassignment of assignor's interest
8 Apr 2022Assigned to Argenx BVchange of name
20 Dec 2022GrantedUS 11,530,271 B2
12 Oct 2026TodayWithin its term
28 Oct 2039Term endsEstimated, includes 285 days of adjustment

CD70 combination therapy

Life of this patent

CD70 combination therapy

Life of this patent

Life of this patent

Abstract

Drawings

Drawings

Claims24

Description22,372 words

Drawings

Classification14 codes

Life of this patent

Description22,372 words