US 11,932,669 B2Granted

Modified cytomegalovirus proteins and stabilized complexes

AssigneeGlaxosmithkline Biologicals SA

InventorsEnrico Malito, Matthew James Bottomley, Andrea Carfi, Sumana Chandramouli, Kate Luisi

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Abstract

Described are mutant human cytomegalovirus (HCMV) pentamer complex polypeptides, methods of making them, and their use in HCMV protein complexes and compositions. In particular, the use of the modified HCMV polypeptides to stabilize HCMV complexes or unmask a pentamer epitope is described.

Claims18

Dependent claims

A complex comprising one or more mutant Human Cytomegalovirus (HCMV) polypeptides, wherein the one or more mutant HCMV polypeptides are:

(a) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine (C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 140, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cysteine (C) at residue 150, numbered with respect to SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 64, numbered with respect to SEQ ID NO:
17, and a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(b) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine (C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 150, numbered with respect to SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 64, numbered with respect to SEQ ID NO:
17, and a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(c) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine (C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 145, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cysteine (C) at residue 150, numbered with respect to SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 64, numbered with respect to SEQ ID NO:
17, and a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(d) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine
(C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 224, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cysteine (C) at residue 150, numbered with respect to SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 64, numbered with respect to SEQ ID NO:
17, and a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(e) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine
(C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 224, numbered with respect to the wild-type Sequence of SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(f) a pUL128 polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 77, numbered with respect to the wild-type Sequence of SEQ ID NO:
13, and has a cavity filling mutant at residue 103, numbered with respect to the wild-type Sequence of SEQ ID NO:
13;
and
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 140, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cavity filling mutant at residue 145, numbered with respect to the wild-type Sequence of SEQ ID NO:
7;
(g) a pUL128 polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 77, numbered with respect to the wild-type Sequence of SEQ ID NO:
13, and has a cavity filling mutant at residue 103, numbered with respect to the wild-type Sequence of SEQ ID NO:
13;
and
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 140, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, has a cavity filling mutant at residue 145, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cavity filling mutant at residue 224, numbered with respect to the wild-type Sequence of SEQ ID NO:
7;
(h) a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 140, numbered with respect to the wild-type Sequence of SEQ ID NO:
7;
and
a pUL131 polypeptide, or complex-forming fragment thereof, that has a repacking hydrophobic mutant at residue 52, numbered with respect to the wild-type Sequence of SEQ ID NO:
21, and has a repacking hydrophobic mutant at residue 67, numbered with respect to the wild-type Sequence of SEQ ID NO:
21;
(i) a pUL131 polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 86, numbered with respect to the wild-type Sequence of SEQ ID NO:
21;
or
(j) a pUL128 polypeptide, or complex-forming fragment thereof, that has a cysteine
(C) at residue 83, numbered with respect to SEQ ID NO:
13;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine
(C) at residue 167, numbered with respect to SEQ ID NO:
17.

72 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/223,207Filed 6 Apr 2021 · continuation
Priority: 17 Oct 2018
Published: US 2021/0277067 A19 Sep 2021
Granted: 19 Mar 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
C07K 14/045
Herpetoviridae, e.g. pseudorabies virus: cytomegalovirus
A61K 39/245
Viral antigens: herpetoviridae, e.g. herpes simplex virus
C07K 14/005
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from viruses

Family

Application62/746,804Us provisional application · filed 17 Oct 2018
PCT/IB2019/058777Parent of this continuation · filed 15 Oct 2019
US 2021/0277067 A1Pre-grant publication · published 9 Sep 2021
US 11,932,669 B2This patent

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

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Abstract

A complex comprising one or more mutant Human Cytomegalovirus (HCMV) polypeptides, wherein the one or more mutant HCMV polypeptides are:

(a) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine (C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 140, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cysteine (C) at residue 150, numbered with respect to SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 64, numbered with respect to SEQ ID NO:
17, and a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(b) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine (C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 150, numbered with respect to SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 64, numbered with respect to SEQ ID NO:
17, and a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(c) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine (C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 145, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cysteine (C) at residue 150, numbered with respect to SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 64, numbered with respect to SEQ ID NO:
17, and a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(d) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine
(C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 224, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cysteine (C) at residue 150, numbered with respect to SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 64, numbered with respect to SEQ ID NO:
17, and a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(e) a pUL128 polypeptide, or complex-forming fragment thereof, that has cysteine
(C) at residue 142, numbered with respect to SEQ ID NO:
13;
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 224, numbered with respect to the wild-type Sequence of SEQ ID NO:
7;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine (C) at residue 95, numbered with respect to SEQ ID NO:
17;
(f) a pUL128 polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 77, numbered with respect to the wild-type Sequence of SEQ ID NO:
13, and has a cavity filling mutant at residue 103, numbered with respect to the wild-type Sequence of SEQ ID NO:
13;
and
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 140, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cavity filling mutant at residue 145, numbered with respect to the wild-type Sequence of SEQ ID NO:
7;
(g) a pUL128 polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 77, numbered with respect to the wild-type Sequence of SEQ ID NO:
13, and has a cavity filling mutant at residue 103, numbered with respect to the wild-type Sequence of SEQ ID NO:
13;
and
a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 140, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, has a cavity filling mutant at residue 145, numbered with respect to the wild-type Sequence of SEQ ID NO:
7, and has a cavity filling mutant at residue 224, numbered with respect to the wild-type Sequence of SEQ ID NO:
7;
(h) a gL polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 140, numbered with respect to the wild-type Sequence of SEQ ID NO:
7;
and
a pUL131 polypeptide, or complex-forming fragment thereof, that has a repacking hydrophobic mutant at residue 52, numbered with respect to the wild-type Sequence of SEQ ID NO:
21, and has a repacking hydrophobic mutant at residue 67, numbered with respect to the wild-type Sequence of SEQ ID NO:
21;
(i) a pUL131 polypeptide, or complex-forming fragment thereof, that has a cavity filling mutant at residue 86, numbered with respect to the wild-type Sequence of SEQ ID NO:
21;
or
(j) a pUL128 polypeptide, or complex-forming fragment thereof, that has a cysteine
(C) at residue 83, numbered with respect to SEQ ID NO:
13;
and
a pUL130 polypeptide, or complex-forming fragment thereof, that has a cysteine
(C) at residue 167, numbered with respect to SEQ ID NO:
17.

72 more elements

Facts

Application

17/223,207Filed 6 Apr 2021 · continuation

Priority

17 Oct 2018

Published

US 2021/0277067 A19 Sep 2021

Granted

19 Mar 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
C07K 14/045
Herpetoviridae, e.g. pseudorabies virus: cytomegalovirus
A61K 39/245
Viral antigens: herpetoviridae, e.g. herpes simplex virus
C07K 14/005
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from viruses