SOLUBLE PD-1 VARIANTS, FUSION CONSTRUCTS, AND USES THEREOF

• US 20120121634A1
• Filed: 11/11/2011
• Published: 05/17/2012
• Est. Priority Date: 11/11/2010
• Status: Active Grant

• Current Assignee: Versitech Limited (Government of Hong Kong Special Administrative Region)
• Original Assignee: University of Hong Kong (Government of Hong Kong Special Administrative Region)
• Inventors: CHEN, ZHIWEI, Zhou, Jingying
• Granted Patent: US 9,029,315 B2
• Time in Patent Office: Days
• US Class Current: 424/188.1
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/32 fusions with soluble part of a cell surface receptor, "decoy receptors"
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C12N 2740/16034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16222 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

The subject invention provides novel soluble PD-1 (sPD-1) proteins, nucleic acids, and fusion constructs thereof, for enhancing humoral and cell-mediated immunity of a subject. Also provided are therapeutic compositions comprising the sPD-1 proteins, nucleic acids, and fusion constructs of the subject invention. In a preferred embodiment, the therapeutic composition is formulated as a vaccine composition. Advantageously, the sPD-1 proteins, nucleic acids, and therapeutic compositions provide protective immunity against pathogenic infection including HIV infection. In additon, the subject invention can be used in the prevention and/or treatment of tumor or cancer.

Claims

1. A soluble PD-1 protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:

11, SEQ ID NO;

15, and SEQ ID NO;

25.

2. A PD-1 nucleic acid molecule encoding a soluble PD-1 protein of claim 1.

3. A soluble PD-1 fusion protein, comprising a soluble PD-1 protein fragment and an antigenic protein fragment, wherein the soluble PD-1 protein fragment comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

21, SEQ ID NO;

11, SEQ ID NO;

15, and SEQ ID NO;

25.

4. The soluble PD-1 fusion protein of claim 3, wherein the antigenic protein fragment is derived from an immunogenic protein fragment of a viral, bacterial, or fungal pathogen, or cancer or tumor cells.

5. The PD-1 fusion protein of claim 4, wherein the pathogen is selected from human immunodeficiency virus (HIV), HSV, respiratory syncytial virus, rhinovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, hepatitis F virus, hepatitis G virus, oncoviruses, human T-lymphotropic virus Type I (HTLV-1), influenza virus, bovine leukemia virus (BLV), Epstein-Barr virus, rotavirus, anpapillomavirus, pneumococcus, streptococcus, staphylococcus, E. coli, cytomegalovirus (CMV), respiratory syncytial virus, parainfluenza virus, adenovirus, flavivirus, dengue virus, Mycobacteria tuberculosis, or Plasmodium falciparum.

6. The PD-1 fusion protein of claim 4, wherein the antigenic protein fragment is derived from HIV p24.

7. The PD-1 fusion protein of claim 3, further comprising a Fc domain.

8. The PD-1 fusion protein of claim 7, further comprising a linker sequence, wherein the linker sequence links the soluble PD-1 domain and the antigen.

9. The PD-1 fusion protein of claim 3, comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:

13, 17, 19, 23, and 27.

10. A sPD-1 fusion nucleic acid molecule encoding a PD-1 fusion protein of claim 3.

11. The sPD-1 fusion nucleic acid molecule of claim 10, wherein the nucleic acid molecule comprises a sequence selected from the group consisting of SEQ ID NOs:

14, 18, 20, 24, and 28.

12. A vaccine composition comprising the sPD-1 fusion nucleic acid molecule of claim 10.

13. A method for preventing or treating pathogenic infection and/or tumor or cancer, comprising administering, to a subject in need of such prevention or treatment, an effective amount of a fusion nucleic acid of claim 10.

14. The method of claim 13, wherein the pathogenic infection is caused by a pathogen selected from human immunodeficiency virus (HIV), HSV, respiratory syncytial virus, rhinovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, hepatitis F virus, hepatitis G virus, oncoviruses, human T-lymphotropic virus Type I (HTLV-1), influenza virus, bovine leukemia virus (BLV), Epstein-Barr virus, rotavirus, anpapillomavirus, pneumococcus, streptococcus, staphylococcus, E. coli, cytomegalovirus (CMV), respiratory syncytial virus, parainfluenza virus, adenovirus, flavivirus, dengue virus, Mycobacteria tuberculosis, or Plasmodium falciparum.

15. The method of claim 14, wherein the fusion nucleic acid comprises an antigenic nucleic acid fragment encoding HIV p24 and the pathogenic infection is HIV infection.

16. The method of claim 15, wherein the fusion nucleic acid comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

14, 18, 20, 24, and 28.

17. The method of claim 13, wherein the fusion nucleic acid is delivered by injection.

18. The method of claim 17, wherein the fusion nucleic acid is delivered via electroporation.

19. A method for preventing or treating pathogenic infection and/or tumor or cancer, comprising administering, to a subject in need of such prevention or treatment, an effective amount of a fusion protein of claim 3.

20. The method of claim 19, wherein the pathogenic infection is caused by a pathogen selected from human immunodeficiency virus (HIV), HSV, respiratory syncytial virus, rhinovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, hepatitis F virus, hepatitis G virus, oncoviruses, human T-lymphotropic virus Type I (HTLV-1), influenza, bovine leukemia virus (BLV), Epstein-Barr virus, rotavirus, anpapillomavirus, streptococcus, staphylococcus, E. coli, shigella, cytomegalovirus (CMV), respiratory syncytial virus, adenovirus, flavivirus, Mycobacteria tuberculosis, or Plasmodium falciparum.