US 11,597,761 B2Granted

Methods of detecting polyubiquitin using anti-polyubiquitin antibodies

AssigneeGenentech, Inc.

InventorsRobert F. Kelley, Vishva Dixit, Marissa L. Matsumoto

Life of this patent

Estimating the term…

Abstract

The invention provides anti-polyubiquitin antibodies and methods of using the same.

Claims20

Dependent claims

A method of determining the presence of a polyubiquitin or polyubiquitinated protein in a sample suspected of containing a polyubiquitin or polyubiquitinated protein, comprising exposing the sample to at least one antibody and determining the binding of the at least one antibody to a polyubiquitin or polyubiquitinated protein in the sample, wherein the at least one antibody comprises:

a) the hypervariable (HVR)-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
82, and the HVR-H3 sequence of SEQ ID NO:
9;
or
b) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence selected from SEQ ID NO:
2, 58 and 60, the HVR-L3 sequence selected from SEQ ID NO:
3, 65 and 72, the HVR-H1 sequence of SEQ ID NO:
7 or 80, the HVR-H2 sequence of SEQ ID NO:
8 or 82, and the HVR-H3 sequence of SEQ ID NO:
9 or 87;
or
c) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
d) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
82, and the HVR-H3 sequence of SEQ ID NO:
9;
or
e) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
11, and the HVR-H3 sequence of SEQ ID NO:
12;
or
f) the HVR-L1 sequence of SEQ ID NO:
19, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
23, and the HVR-H3 sequence of SEQ ID NO:
12;
or
g) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
20, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
11, and the HVR-H3 sequence of SEQ ID NO:
12;
or
h) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
21, the HVR-H1 sequence of SEQ ID NO:
22, the HVR-H2 sequence of SEQ ID NO:
24, and the HVR-H3 sequence of SEQ ID NO:
12;
or
i) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
j) the HVR-L1 sequence of SEQ ID NO:
4, the HVR-L2 sequence of amino acids 50-56 of SEQ ID NO:
27, the HVR-L3 sequence of SEQ ID NO:
5, the HVR-H1 sequence of SEQ ID NO:
13, the HVR-H2 sequence of amino acids 52-62 of SEQ ID NO:
31, and the HVR-H3 sequence of SEQ ID NO:
15;
or the HVR-L1 sequence of SEQ ID NO:
4, the HVR-L2 sequence of amino acids 50-56 of SEQ ID NO:
28, the HVR-L3 sequence of SEQ ID NO:
6, the HVR-H1 sequence of SEQ ID NO:
16, the HVR-H2 sequence of amino acids 52-62 of SEQ ID NO:
32, and the HVR-H3 sequence of SEQ ID NO:
18;
or
k) the HVR-L1 sequence of SEQ ID NO:
1, 50, 52-57, or 199-218, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
l) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58-62 or 219-239, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
m) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
6, 64-72, or 240-254, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
n) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
73-81 or 255-260, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
o) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
17, 82-86, or 261-264, and the HVR-H3 sequence of SEQ ID NO:
9;
or
p) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
265-282.

131 more elements

A method of separating C-to N-terminal-linked polyubiquitinated protein from non-C-to N-terminal-linked polyubiquitinated protein in a sample, comprising contacting the sample with at least one antibody, wherein the at least one antibody comprises:

a) the hypervariable (HVR)-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
82, and the HVR-H3 sequence of SEQ ID NO:
9;
or
b) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence selected from SEQ ID NO:
2, 58 and 60, the HVR-L3 sequence selected from SEQ ID NO:
3, 65 and 72, the HVR-H1 sequence of SEQ ID NO:
7 or 80, the HVR-H2 sequence of SEQ ID NO:
8 or 82, and the HVR-H3 sequence of SEQ ID NO:
9 or 87;
or
c) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
d) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
82, and the HVR-H3 sequence of SEQ ID NO:
9;
or
e) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
11, and the HVR-H3 sequence of SEQ ID NO:
12;
or
f) the HVR-L1 sequence of SEQ ID NO:
19, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
23, and the HVR-H3 sequence of SEQ ID NO:
12;
or
g) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
20, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
11, and the HVR-H3 sequence of SEQ ID NO:
12;
or
h) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
21, the HVR-H1 sequence of SEQ ID NO:
22, the HVR-H2 sequence of SEQ ID NO:
24, and the HVR-H3 sequence of SEQ ID NO:
12;
or
i) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
j) the HVR-L1 sequence of SEQ ID NO:
4, the HVR-L2 sequence of amino acids 50-56 of SEQ ID NO:
27, the HVR-L3 sequence of SEQ ID NO:
5, the HVR-H1 sequence of SEQ ID NO:
13, the HVR-H2 sequence of amino acids 52-62 of SEQ ID NO:
31, and the HVR-H3 sequence of SEQ ID NO:
15;
or the HVR-L1 sequence of SEQ ID NO:
4, the HVR-L2 sequence of amino acids 50-56 of SEQ ID NO:
28, the HVR-L3 sequence of SEQ ID NO:
6, the HVR-H1 sequence of SEQ ID NO:
16, the HVR-H2 sequence of amino acids 52-62 of SEQ ID NO:
32, and the HVR-H3 sequence of SEQ ID NO:
18;
or
k) the HVR-L1 sequence of SEQ ID NO:
1, 50, 52-57, or 199-218, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
l) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58-62 or 219-239, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
m) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
6, 64-72, or 240-254, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
n) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
73-81 or 255-260, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
o) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
17, 82-86, or 261-264, and the HVR-H3 sequence of SEQ ID NO:
9;
or
p) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
265-282.

131 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/914,996Filed 29 Jun 2020 · division
Priority: 5 Aug 2011
Published: US 2021/0017260 A121 Jan 2021
Granted: 7 Mar 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 16/18
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material from animals or humans
A61P 21/00
Drugs for disorders of the muscular or neuromuscular system
A61P 25/00
Drugs for disorders of the nervous system
A61P 35/00
Antineoplastic agents

Family

Application61/515,729Us provisional application · filed 5 Aug 2011
Application13/567,919Parent of this division · filed 6 Aug 2012
Application15/071,422Parent of this division · filed 16 Mar 2016
US 9,321,844 B2Parent of this division · filed 26 Apr 2016
US 2021/0017260 A1Pre-grant publication · published 21 Jan 2021
US 10,738,106 B2Parent of this division
US 2013/0058955 A1Published application
US 2016/0304591 A1Published application
US 11,597,761 B2This patent

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

Timeline

Citations

Open elsewhere

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a) the hypervariable (HVR)-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
82, and the HVR-H3 sequence of SEQ ID NO:
9;
or
b) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence selected from SEQ ID NO:
2, 58 and 60, the HVR-L3 sequence selected from SEQ ID NO:
3, 65 and 72, the HVR-H1 sequence of SEQ ID NO:
7 or 80, the HVR-H2 sequence of SEQ ID NO:
8 or 82, and the HVR-H3 sequence of SEQ ID NO:
9 or 87;
or
c) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
d) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
82, and the HVR-H3 sequence of SEQ ID NO:
9;
or
e) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
11, and the HVR-H3 sequence of SEQ ID NO:
12;
or
f) the HVR-L1 sequence of SEQ ID NO:
19, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
23, and the HVR-H3 sequence of SEQ ID NO:
12;
or
g) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
20, the HVR-H1 sequence of SEQ ID NO:
10, the HVR-H2 sequence of SEQ ID NO:
11, and the HVR-H3 sequence of SEQ ID NO:
12;
or
h) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
21, the HVR-H1 sequence of SEQ ID NO:
22, the HVR-H2 sequence of SEQ ID NO:
24, and the HVR-H3 sequence of SEQ ID NO:
12;
or
i) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
j) the HVR-L1 sequence of SEQ ID NO:
4, the HVR-L2 sequence of amino acids 50-56 of SEQ ID NO:
27, the HVR-L3 sequence of SEQ ID NO:
5, the HVR-H1 sequence of SEQ ID NO:
13, the HVR-H2 sequence of amino acids 52-62 of SEQ ID NO:
31, and the HVR-H3 sequence of SEQ ID NO:
15;
or the HVR-L1 sequence of SEQ ID NO:
4, the HVR-L2 sequence of amino acids 50-56 of SEQ ID NO:
28, the HVR-L3 sequence of SEQ ID NO:
6, the HVR-H1 sequence of SEQ ID NO:
16, the HVR-H2 sequence of amino acids 52-62 of SEQ ID NO:
32, and the HVR-H3 sequence of SEQ ID NO:
18;
or
k) the HVR-L1 sequence of SEQ ID NO:
1, 50, 52-57, or 199-218, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
l) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
58-62 or 219-239, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
m) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
6, 64-72, or 240-254, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
n) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
73-81 or 255-260, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
9;
or
o) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
17, 82-86, or 261-264, and the HVR-H3 sequence of SEQ ID NO:
9;
or
p) the HVR-L1 sequence of SEQ ID NO:
1, the HVR-L2 sequence of SEQ ID NO:
2, the HVR-L3 sequence of SEQ ID NO:
3, the HVR-H1 sequence of SEQ ID NO:
7, the HVR-H2 sequence of SEQ ID NO:
8, and the HVR-H3 sequence of SEQ ID NO:
265-282.

131 more elements

Facts

Application

16/914,996Filed 29 Jun 2020 · division

Priority

5 Aug 2011

Published

US 2021/0017260 A121 Jan 2021

Granted

7 Mar 2023

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 16/18
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material from animals or humans
A61P 21/00
Drugs for disorders of the muscular or neuromuscular system
A61P 25/00
Drugs for disorders of the nervous system
A61P 35/00
Antineoplastic agents

Family

Application61/515,729Us provisional application · filed 5 Aug 2011

Application13/567,919Parent of this division · filed 6 Aug 2012

Application15/071,422Parent of this division · filed 16 Mar 2016

US 9,321,844 B2Parent of this division · filed 26 Apr 2016

US 2021/0017260 A1Pre-grant publication · published 21 Jan 2021

US 10,738,106 B2Parent of this division

US 2013/0058955 A1Published application

US 2016/0304591 A1Published application

US 11,597,761 B2This patent

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