US 11,932,669 B2
Modified cytomegalovirus proteins and stabilized complexes
Enrico Malito, Rockville, MD (US); Matthew James Bottomley, Rockville, MD (US); Andrea Carfi, Cambridge, MA (US); Sumana Chandramouli, Rockville, MD (US); and Kate Luisi, Rockville, MD (US)
Assigned to GLAXOSMITHKLINE BIOLOGICALS SA, Rixensart (BE)
Filed by GLAXOSMITHKLINE BIOLOGICALS SA, Rixensart (BE)
Filed on Apr. 6, 2021, as Appl. No. 17/223,207.
Application 17/223,207 is a continuation of application No. PCT/IB2019/058777, filed on Oct. 15, 2019.
Claims priority of provisional application 62/746,804, filed on Oct. 17, 2018.
Prior Publication US 2021/0277067 A1, Sep. 9, 2021
Int. Cl. C07K 14/045 (2006.01); A61K 38/00 (2006.01); A61K 39/245 (2006.01)
CPC C07K 14/045 (2013.01) [A61K 39/245 (2013.01); A61K 38/00 (2013.01)] 18 Claims
 
1. 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.