IP Library › Granted Patent US 12,673,102
Granted Patent B2
US 12,673,102 · App. 17/922,335 · Granted Jul 7, 2026

Method for improving immunogenicity of protein/peptide antigen

Inventors: Liangzhi Xie (Beijing, CN); Yanjing Zhang (Beijing, CN); Jiandong Zhang (Beijing, CN)
Assignee: SinoCellTech Ltd.
A61K39/385A61K39/092A61K39/12A61K39/145A61K39/215A61K39/29A61K2039/55505A61K2039/55566A61K2039/55572A61K2039/6037A61K2039/6087A61K2039/70
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Quick Facts
Patent No.
US 12,673,102
App. No.
17/922,335
Filed
Oct 28, 2022
Granted
Jul 7, 2026
Kind
B2
Art Unit
1672
USPC
424/186.1
Abstract

Disclosed is a method for improving the immunogenicity of a protein/peptide antigen, the method comprising conjugating a protein/peptide antigen with a sugar to form a sugar-protein/peptide antigen conjugate, which has improved immunogenicity compared to an unconjugated protein/peptide antigen. In particular, the method involves conjugating a pathogen, such as a viral surface protein antigen or a fragment thereof, with a polysaccharide, in particular a capsular polysaccharide of Streptococcus pneumonia . The conjugate with improved immunogenicity can be used to prevent or treat diseases caused by pathogens, in particular diseases caused by coronaviruses.

Claims (65)

1 . A method for improving the immunogenicity of a protein/peptide antigen, comprising forming a glyco-protein/peptide antigen conjugate by conjugating the protein/peptide antigen with a saccharide,

wherein the saccharide is capsular polysaccharide of Streptococcus pneumonia,

wherein the protein/peptide antigen is a virus pathogen-associated protein/peptide antigen selected from human respiratory syncytial virus glycoprotein G (RSV-gpG), hepatitis C virus envelope glycoprotein E1 protein (ECV-E1), hepatitis C virus envelope E2 protein (HCV-E2), influenza B hemagglutinin protein (FLU-B-HA1), influenza A H5N1 hemagglutinin (H5N1-HA), ebola virus glycoprotein (Ebola-GP), ebola virus glycoprotein GP1 (Ebola-GP1), zika virus envelope protein (ZIKV-E), and/or coronavirus spike protein.

2 . The method as claimed in claim 1 , wherein the saccharide is

capsular polysaccharide of Streptococcus pneumoniae serotype 14, 6B or 7F.

3 . The method as claimed in claim 1 , wherein the protein/peptide antigen is a protein/peptide comprising

viral antigen of

coronavirus spike protein receptor binding region RBD.

4 . The method as claimed in claim 3 , wherein the coronavirus is SARS-COV-2 or Middle East respiratory syndrome coronavirus.

5 . The method as claimed in claim 3 , wherein the protein/peptide antigen is a fusion protein

which is SARS-COV-2 RBD-mFc; SARS-COV-2 RBD-his; or MERS-COV RBD-his; and

the Fc fragment is a human or murine IgG Fc fragment.

6 . The method as claimed in claim 4 , wherein the protein/peptide antigen comprises the sequence as set forth as any one of SEQ ID NO:1, SEQ ID NO: 2 or SEQ ID NO:3.

7 . The method as claimed in claim 1 , wherein the molecular weight of the conjugate is 400-14000 KDa.

8 . The method as claimed in claim 1 , wherein the protein/peptide antigen is a fusion protein

which is RSV-gpG-his.

9 . The method as claimed in claim 1 , wherein the protein/peptide antigen comprises the sequence as set forth as SEQ ID NO:4 or SEQ ID NO:12.

10 . The method as claimed in claim 1 , wherein the protein/peptide antigen is a fusion protein

which is Flu-B-HA1-his or H5N1-HA-his.

11 . The method as claimed in claim 1 , wherein the protein/peptide antigen comprises the sequence as set forth as any one of SEQ ID NO:7, SEQ ID NO: 15, SEQ ID NO: 8 or SEQ ID NO: 16.

12 . The method as claimed in claim 1 , wherein the protein/peptide antigen is a fusion protein

which is Ebola-GP-Fc or Ebola-GP1-his;

wherein the Fc is a human or murine IgG Fc fragment.

13 . The method as claimed in claim 1 , wherein the protein/peptide antigen comprises the sequence as set forth as any one of SEQ ID NO: 9, SEQ ID NO: 17, SEQ ID NO: 10 or SEQ ID NO: 18.

14 . The method as claimed in claim 1 , wherein the protein/peptide antigen is a fusion protein

which is ZIKV-E-Fc; wherein

Fc is a human or murine IgG Fc fragment; or

the fusion protein is HCV-E2-his and/or HCV-E1-his.

15 . The method as claimed in claim 1 , wherein the protein/peptide antigen comprises the sequence as set forth as any one of SEQ ID NO:11, SEQ ID NO: 19, SEQ ID NO: 6, SEQ ID NO:14, SEQ ID NO:5 or SEQ ID NO: 13.

16 . The method as claimed in claim 1 , wherein the glyco-protein/peptide antigen is further conjugated with a protein carrier.

17 . The method as claimed in claim 16 , wherein the protein carrier is a tetanus toxoid, a tetanus toxoid fragment C, a tetanus toxoid non-toxic mutant, a diphtheria toxoid, CRM197, or other non-toxic mutants of diphtheria toxoid.

18 . A glyco-protein/peptide antigen conjugate with a saccharide increased immunogenicity compared to an unconjugated protein/peptide antigen;

wherein the saccharide is capsular polysaccharide of Streptococcus pneumonia,

wherein the protein/peptide antigen is a virus pathogen-associated protein/peptide antigen selected from human respiratory syncytial virus glycoprotein G (RSV-gpG), hepatitis C virus envelope glycoprotein E1 protein (ECV-E1), hepatitis C virus envelope E2 protein (HCV-E2), influenza B hemagglutinin protein (FLU-B-HA1), influenza A H5N1 hemagglutinin (H5N1-HA), ebola virus glycoprotein (Ebola-GP), ebola virus glycoprotein GP1 (Ebola-GP1), zika virus envelope protein (ZIKV-E), and/or coronavirus spike protein.

19 . The conjugate as claimed in claim 18 , wherein the saccharide is

capsular polysaccharide of Streptococcus pneumoniae serotype 14, 6B

or 7F.

20 . The conjugate as claimed in claim 18 , wherein the protein/peptide antigen is a protein/peptide comprising

viral antigens of

the coronavirus spike protein receptor binding region RBD.

21 . The conjugate as claimed in claim 20 , wherein the coronavirus is SARS-CoV-2 or Middle East respiratory syndrome coronavirus.

22 . The conjugate as claimed in claim 20 , wherein the protein/peptide antigen is a fusion protein

which is SARS-COV-2 RBD-mFc; SARS-COV-2 RBD-his; or MERS-COV RBD-his; and

the Fc fragment is a human or murine IgG Fc fragment.

23 . The conjugate as claimed in claim 21 , wherein the protein/peptide antigen comprises the sequence as set forth as any one of SEQ ID NO:1, SEQ ID NO: 2 or SEQ ID NO:3.

24 . The conjugate as claimed in claim 18 , wherein the protein/peptide antigen is a fusion protein

which is RSV-gpG-his.

25 . The conjugate as defined in claim 18 , wherein the protein/peptide antigen comprises the sequence as set forth as SEQ ID NO: 4 or SEQ ID NO:12.

26 . The conjugate as claimed in claim 18 , wherein the protein/peptide antigen is a fusion protein which is Flu-B-HA1-his or H5N1-HA-his.

27 . The conjugate as claimed in claim 18 , wherein the protein/peptide antigen comprises the sequence as set forth as any one of SEQ ID NO:7, SEQ ID NO:15, SEQ ID NO:8, or SEQ ID NO: 16.

28 . The conjugate as claimed in claim 18 , wherein the protein/peptide antigen is a fusion protein

which is Ebola-GP-Fc or Ebola-GP1-his; and

wherein the Fc is a human or murine IgG Fc fragment.

29 . The conjugate as claimed in claim 18 , wherein the protein/peptide antigen comprises the sequence as set forth as any one of SEQ ID NO:9, SEQ ID NO: 17, SEQ ID NO: 10, or SEQ ID NO: 18.

30 . The conjugate as claimed in claim 18 , wherein the protein/peptide antigen is a fusion protein

which is HCV-E2-his and/or HCV-E1-his.

31 . The conjugate as claimed in claim 18 , wherein the protein/peptide antigen comprises the sequence as set forth as any one of SEQ ID NO:11, SEQ ID NO: 19, SEQ ID NO: 6, SEQ ID NO:14, SEQ ID NO:5, or SEQ ID NO:13.

32 . The glyco-protein/peptide antigen conjugate as claimed in claim 18 , wherein the glyco-protein/peptide antigen is further conjugated to a protein carrier.

33 . The glyco-protein/peptide antigen conjugate as claimed in claim 32 , wherein the protein carrier is tetanus toxoid, tetanus toxoid fragment C, tetanus toxoid non-toxic mutant, diphtheria toxoid, CRM197, other non-toxic mutants of diphtheria toxoid.

34 . An immunogenic composition comprising the glyco-protein/peptide antigen conjugate of claim 18 , immune adjuvant and excipient.

35 . The immunogenic composition as claimed in claim 34 , the adjuvant selected from aluminium adjuvant, oil-in-water emulsion adjuvant, MF59, QS-21 and lipid monophosphate A.

36 . A method of preventing or treating disease caused by a pathogen-associated protein/peptide antigen, the method comprising administering the glyco-protein/peptide antigen conjugate of claim 18 to a subject in need thereof.

37 . A method of preventing or treating a disease caused by a pathogen-associated protein/peptide antigen, the method comprising preparing a vaccine or drug comprising the glyco-protein/peptide antigen conjugate of 18 and administering said vaccine or drug to a subject in need thereof.

38 . A method of preventing or treating a disease caused by a pathogen-associated protein/peptide antigen, the method comprising administering the immunogenic composition of claim 34 to a subject in need thereof.

39 . A method of preventing or treating a disease caused by a pathogen-associated protein/peptide antigen, the method comprising preparing a vaccine or drug comprising the immunogenic composition of claim 34 , and administering said vaccine or drug to a subject in need thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 28, 2022
From: XIE, LIANGZHI; ZHANG, YANJING; ZHANG, JIANDONG
To: SINOCELLTECH LTD.
Reel/Frame 061586/0124 →
Priority Claims (1)
CN 202010369100.7 · May 1, 2020 · national
Continuity (1)
Related Publication 20230330220A1 · Oct 19, 2023
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