US 12,215,143 B2Granted

Anti-polyubiquitin multispecific antibodies

AssigneeGenentech, Inc.

InventorsVishva Dixit, Marissa Matsumoto, Erick Castellanos

Life of this patent

Estimating the term…

Abstract

The invention provides antibodies that bind mixed-topology polyubiquitin and multispecific anti-polyubiquitin antibodies, and methods of using the same.

Claims15

Dependent claims

A nucleic acid encoding a multispecific antibody that binds a mixed-topology polyubiquitin comprising a first linkage and a second linkage, the antibody comprising a first VH/VL unit specific for the first linkage, and a second VH/VL unit specific for the second linkage, wherein the first linkage and the second linkage are a K11 linkage, and a K48 linkage, or a K48 linkage and a K11 linkage, respectively, wherein the multispecific-antibody comprises first and second half antibodies, wherein,

a) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
28;
b) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
42;
c) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
56;
d) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
28, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
42;
e) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
28, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
56;
or
f) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
42, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
56.

154 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/576,344Filed 14 Jan 2022 · division
Priority: 24 Jun 2016
Published: US 2022/0242938 A14 Aug 2022
Granted: 4 Feb 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07K 16/18
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material from animals or humans
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C12N 15/62
DNA or RNA fragments; Modified forms thereof ; Non-coding nucleic acids having a biological activity: dNA sequences coding for fusion proteins

Family

Application62/354,305Us provisional application · filed 24 Jun 2016
PCT/US2017/038940Parent of this continuation · filed 23 Jun 2017
Application16/211,669Parent of this division · filed 6 Dec 2018
US 2022/0242938 A1Pre-grant publication · published 4 Aug 2022
US 11,274,145 B2Parent of this division
Application16/211,669Parent of this continuation
US 2019/0169278 A1Published application
US 12,215,143 B2This patent

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

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Abstract

The invention provides antibodies that bind mixed-topology polyubiquitin and multispecific anti-polyubiquitin antibodies, and methods of using the same.

a) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
28;
b) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
42;
c) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
56;
d) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
28, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
42;
e) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
28, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
56;
or
f) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
42, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
56.

154 more elements

Facts

Application

17/576,344Filed 14 Jan 2022 · division

Priority

24 Jun 2016

Published

US 2022/0242938 A14 Aug 2022

Granted

4 Feb 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07K 16/18
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material from animals or humans
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C12N 15/62
DNA or RNA fragments; Modified forms thereof ; Non-coding nucleic acids having a biological activity: dNA sequences coding for fusion proteins

Family

Application62/354,305Us provisional application · filed 24 Jun 2016

PCT/US2017/038940Parent of this continuation · filed 23 Jun 2017

Application16/211,669Parent of this division · filed 6 Dec 2018

US 2022/0242938 A1Pre-grant publication · published 4 Aug 2022

US 11,274,145 B2Parent of this division

Application16/211,669Parent of this continuation

US 2019/0169278 A1Published application

US 12,215,143 B2This patent

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