US 12,729,243 B2Granted

Dosing for treatment with anti-CD20/anti-CD3 bispecific antibody

AssigneeHoffmann-La Roche Inc.

InventorsLinda Lundberg, Peter N. Morcos, Martin Weisser, Axel Boehnke, David Carlile, Nassim Djebli

Life of this patent

Estimating the term…

Abstract

The present invention relates to methods of treating a B-cell proliferative disorder by administering an anti-CD20/anti-CD3 bispecific antibody, and methods for reduction of adverse effects in response to the administration of the anti-CD20/anti-CD3 bispecific antibody. The present invention further relates to combination treatment methods of treating a B-cell proliferative disorder.

Claims24

Dependent claims

A method of treating a subject having a CD20-positive B cell proliferative disorder comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle, wherein:

(a) the first dosing cycle comprises a first dose (C1D1) and a second dose (C1D2) of the anti-CD20/anti-CD3 bispecific antibody, wherein the C1D1 is 2.5 mg, and the C1D2 is 10 mg;
and (b) the second dosing cycle comprises a single dose (C2D1) of either 16 or 30 mg of the anti-CD20/anti-CD3 bispecific antibody,
wherein the anti-CD20/anti-CD3 bispecific antibody comprises:
(a) at least one antigen binding domain that specifically binds to CD20, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:3;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
and
(b) at least one antigen binding domain that specifically binds to CD3, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
9;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
10;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:11;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
12;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
13;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
14:
wherein
(i) the first dose (C1D1) is administered on day 1 of the first dosing cycle and the second dose (C1D2) is administered on day 8 of the first dosing cycle;
(ii) the single dose of the second dosing cycle (C2D1) is administered on day 1 of the second dosing cycle;
and
(iii) one dosing cycle comprises 14 days or 21 days;
and
wherein the method further comprising administering to the subject obinutuzumab,
wherein:
(iv) obinutuzumab is administered 7 days before the first dose of the anti-CD20/anti-CD3 bispecific antibody (C1D1);
and
(v) obinutuzumab is administered at one single dose of 1000 ma or a first and a second dose of each 1000 ma obinutuzumab.

44 more elements

A method of treating a subject having a non-Hodgkin lymphoma comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle, wherein:

(a) the first dosing cycle comprises a first dose (C1D1) and a second dose (C1D2) of the anti-CD20/anti-CD3 bispecific antibody, wherein the C1D1 is 2.5 mg, and the C1D2 is 10 mg;
and (b) the second dosing cycle comprises a single dose (C2D1) of 30 mg of the anti-CD20/anti-CD3 bispecific antibody,
wherein the anti-CD20/anti-CD3 bispecific antibody comprises:
(a) at least one antigen binding domain that specifically binds to CD20, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:3;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
and
(b) at least one antigen binding domain that specifically binds to CD3, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
9;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
10;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:11;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
12;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
13;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
14;
and
wherein
(i) the first dose (C1D1) is administered on day 1 of the first dosing cycle and the second dose (C1D2) is administered on day 8 of the first dosing cycle;
(ii) the single dose of the second dosing cycle (C2D1) is administered on day 1 of the second dosing cycle;
and
(iii) one dosing cycle comprises 14 days or 21 days;
and
wherein the method further comprising administering to the subject obinutuzumab,
wherein:
(iv) obinutuzumab is administered 7 days before the first dose of the anti-CD20/anti-CD3 bispecific antibody (C1D1);
and
(v) obinutuzumab is administered at one single dose of 1000 mg or a first and a second dose of each 1000 mg obinutuzumab.

45 more elements

A method of treating a subject having a diffuse large B cell lymphoma comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle, wherein:

(a) the first dosing cycle comprises a first dose (C1D1) and a second dose (C1D2) of the anti-CD20/anti-CD3 bispecific antibody, wherein the C1D1 is 2.5 mg, and the C1D2 is 10 mg;
and (b) the second dosing cycle comprises a single dose (C2D1) of 30 mg of the anti-CD20/anti-CD3 bispecific antibody,
wherein the anti-CD20/anti-CD3 bispecific antibody comprises:
(a) a first antigen binding domain that specifically binds to CD20, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:3;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
(b) second antigen binding domain that specifically binds to CD3, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
9;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
10;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:11;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
12;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
13;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
14;
and
(c) a third antigen binding domain that specifically binds to CD20, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:3;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
and
wherein
(i) the first dose (C1D1) is administered on day 1 of the first dosing cycle and the second dose (C1D2) is administered on day 8 of the first dosing cycle;
(ii) the single dose of the second dosing cycle (C2D1) is administered on day 1 of the second dosing cycle;
and
(iii) one dosing cycle comprises 14 days or 21 days;
and
wherein the method further comprising administering to the subject obinutuzumab,
wherein obinutuzumab is administered 7 days before the first dose of the anti-CD20/anti-CD3 bispecific antibody (C1D1);
and obinutuzumab is administered at one single dose of 1000 mg.

59 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/733,909Filed 29 Apr 2022 · us provisional application
Priority: 30 Apr 2021
Published: US 2022/0372156 A124 Nov 2022
Granted: 8 Sep 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification29 codes

A61K 38/1774
Receptors; Cell surface antigens; Cell surface determinants: immunoglobulin superfamily
C07K 16/2887
Against receptors, cell surface antigens or cell surface determinants: against CD20
A61K 31/475
Quinolines; Isoquinolines: having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
A61K 31/573
Substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone: substituted in position 21, e.g. cortisone,…

Family

Application63/182,398Us provisional application · filed 30 Apr 2021
Application63/226,962Us provisional application · filed 29 Jul 2021
US 2022/0372156 A1Pre-grant publication · published 24 Nov 2022
US 12,729,243 B2This patent

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

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Abstract

(a) the first dosing cycle comprises a first dose (C1D1) and a second dose (C1D2) of the anti-CD20/anti-CD3 bispecific antibody, wherein the C1D1 is 2.5 mg, and the C1D2 is 10 mg;
and (b) the second dosing cycle comprises a single dose (C2D1) of either 16 or 30 mg of the anti-CD20/anti-CD3 bispecific antibody,
wherein the anti-CD20/anti-CD3 bispecific antibody comprises:
(a) at least one antigen binding domain that specifically binds to CD20, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:3;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
and
(b) at least one antigen binding domain that specifically binds to CD3, comprising
a heavy chain variable region comprising:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
9;
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
10;
and
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:11;
and a light chain variable region comprising:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
12;
(ii) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
13;
and
(iii) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
14:
wherein
(i) the first dose (C1D1) is administered on day 1 of the first dosing cycle and the second dose (C1D2) is administered on day 8 of the first dosing cycle;
(ii) the single dose of the second dosing cycle (C2D1) is administered on day 1 of the second dosing cycle;
and
(iii) one dosing cycle comprises 14 days or 21 days;
and
wherein the method further comprising administering to the subject obinutuzumab,
wherein:
(iv) obinutuzumab is administered 7 days before the first dose of the anti-CD20/anti-CD3 bispecific antibody (C1D1);
and
(v) obinutuzumab is administered at one single dose of 1000 ma or a first and a second dose of each 1000 ma obinutuzumab.

44 more elements

Facts

Application

17/733,909Filed 29 Apr 2022 · us provisional application

Priority

30 Apr 2021

Published

US 2022/0372156 A124 Nov 2022

Granted

8 Sep 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification29 codes

A61K 38/1774
Receptors; Cell surface antigens; Cell surface determinants: immunoglobulin superfamily
C07K 16/2887
Against receptors, cell surface antigens or cell surface determinants: against CD20
A61K 31/475
Quinolines; Isoquinolines: having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
A61K 31/573
Substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone: substituted in position 21, e.g. cortisone,…