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US 12,447,207 B2Granted
Human cytomegalovirus gB polypeptide
AssigneePfizer Inc.
InventorsYuhang Liu, Ye Che, Xiaoyuan Sherry Chi, Philip Ralph Dormitzer, Jennifer Anne Nicki, Xiaojie Yao
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Abstract
Polypeptides and cytomegalovirus (CMV) antigens that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). For example, polypeptides stabilized in a conformation alternative to the gB postfusion conformation. Compositions including the polypeptides and uses thereof.
Claims20
A human cytomegalovirus (HCMV) immunogenic composition comprising:
- RNA formulated in a lipid nanoparticle,
- wherein the RNA encodes an amino acid sequence for a glycoprotein B (gB) protein comprising at least one engineered disulfide mutation, wherein the gB protein comprises a cysteine mutation selected from the group consisting of:
- D217C, Y589C, M371C, W506C, N524C, and M684C, numbered according to SEQ ID NO:1.
A human cytomegalovirus (HCMV) immunogenic composition comprising:
- RNA formulated in a lipid nanoparticle,
- wherein the RNA encodes an amino acid sequence for a glycoprotein B (gB) protein comprising at least two amino acid mutations, and wherein said at least two amino acid mutations comprise:
- a) at least one engineered disulfide mutation selected from the group consisting of:
- D217C and Y589C, and M371C and W506C, numbered according to SEQ ID NO:1;
- and
- b) at least one additional mutation selected from the group consisting of:
- i) substitution of YIH at positions 155-157 with GHR;
- ii) substitution of W at position 240 with A;
- iii) substitution of C at position 246 with S;
- iv) substitution of P at position 655 with S;
- v) substitution of F at position 678 with S;
- vi) substitution of L at position 680 with T;
- vii) substitution of R at position 685 with A;
- viii) substitution of MIALDI (SEQ ID NO:
- 275) at positions 648-653 with GSGKDG (SEQ ID NO:
- 276);
- ix) substitution of R at position 693 with V;
- x) substitution of I at positions 767 and 768 with C;
- xi) substitution of D at position 703 and P at position 704 with C;
- and
- xii) substitution of Y at position 696 and V at position 697 with C,
- wherein the positions are numbered according to SEQ ID NO:
- 1.
20 more elements
A human cytomegalovirus (HCMV) immunogenic composition comprising:
- RNA formulated in a lipid nanoparticle,
- wherein the RNA encodes an amino acid sequence for a glycoprotein B (gB) protein comprising at least one engineered disulfide mutation selected from the group consisting of:
- D217C and Y589C, and M371C and W506C, numbered according to SEQ ID NO:1.
Dependencies are inferred from the claim text.