CA2378866A1 - Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens - Google Patents
Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens Download PDFInfo
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- CA2378866A1 CA2378866A1 CA002378866A CA2378866A CA2378866A1 CA 2378866 A1 CA2378866 A1 CA 2378866A1 CA 002378866 A CA002378866 A CA 002378866A CA 2378866 A CA2378866 A CA 2378866A CA 2378866 A1 CA2378866 A1 CA 2378866A1
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- chain constant
- constant region
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- 239000000427 antigen Substances 0.000 title claims abstract 41
- 102000036639 antigens Human genes 0.000 title claims abstract 40
- 108091007433 antigens Proteins 0.000 title claims abstract 40
- 102000004169 proteins and genes Human genes 0.000 title claims abstract 21
- 108090000623 proteins and genes Proteins 0.000 title claims abstract 21
- 230000002708 enhancing effect Effects 0.000 title claims abstract 6
- 230000005847 immunogenicity Effects 0.000 title claims abstract 6
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract 2
- 108091006020 Fc-tagged proteins Proteins 0.000 title 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims abstract 34
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims abstract 34
- 238000000034 method Methods 0.000 claims abstract 28
- 239000002671 adjuvant Substances 0.000 claims abstract 27
- 239000000203 mixture Substances 0.000 claims abstract 25
- 102000037865 fusion proteins Human genes 0.000 claims abstract 24
- 108020001507 fusion proteins Proteins 0.000 claims abstract 24
- 241000124008 Mammalia Species 0.000 claims abstract 20
- 230000028993 immune response Effects 0.000 claims abstract 9
- 150000007523 nucleic acids Chemical group 0.000 claims 12
- 102000004127 Cytokines Human genes 0.000 claims 9
- 108090000695 Cytokines Proteins 0.000 claims 9
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims 7
- 229920001184 polypeptide Polymers 0.000 claims 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims 6
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims 4
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims 4
- 108060003951 Immunoglobulin Proteins 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 108010067390 Viral Proteins Proteins 0.000 claims 4
- 102000003675 cytokine receptors Human genes 0.000 claims 4
- 108010057085 cytokine receptors Proteins 0.000 claims 4
- 102000018358 immunoglobulin Human genes 0.000 claims 4
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 102000039446 nucleic acids Human genes 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 210000000987 immune system Anatomy 0.000 claims 2
- 241000894007 species Species 0.000 claims 2
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 claims 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- 230000004927 fusion Effects 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 210000000612 antigen-presenting cell Anatomy 0.000 abstract 2
- 102000009109 Fc receptors Human genes 0.000 abstract 1
- 108010087819 Fc receptors Proteins 0.000 abstract 1
- 241000027294 Fusi Species 0.000 abstract 1
- 230000008685 targeting Effects 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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- A—HUMAN NECESSITIES
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- A61K39/12—Viral antigens
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- A—HUMAN NECESSITIES
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- A61K39/21—Retroviridae, e.g. equine infectious anemia virus
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
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- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
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- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
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- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
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- A—HUMAN NECESSITIES
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- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6056—Antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
- C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/14—Lymphokine; related peptides
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Abstract
Disclosed herein are methods and compositions for enhancing the immunogenici ty of a preselected protein or peptide antigen in a mammal. Immunogenicity is enhanced by fusing the preselected antigen to an immunoglobulin heavy chain constant region to produce an Fc-antigen fusion protein. The Fc-antigen fusi on proteins bind Fc receptors on the surface of antigen presenting cells, there by targeting the antigen to the antigen presenting cells in the mammal. In addition, disclosed is a family of adjuvants, for example, an Fc-adjuvant fusion protein, for use in combination with the Fc-antigen fusion proteins t o enhance or modulate a particular immune response against the preselected antigen.
Claims (45)
1. A method of enhancing the immunogenicity of a preselected antigen in a mammal, the method comprising:
administering to the mammal intramuscularly, intravenously, transdermally or subcutaneously, a fusion protein comprising an immunoglobulin heavy chain constant region linked by a polypeptide bond to the preselected antigen thereby to elicit an immune response against the preselected antigen, wherein the preselected antigen in the fusion protein elicits a stronger immune response in the mammal than the preselected antigen alone.
administering to the mammal intramuscularly, intravenously, transdermally or subcutaneously, a fusion protein comprising an immunoglobulin heavy chain constant region linked by a polypeptide bond to the preselected antigen thereby to elicit an immune response against the preselected antigen, wherein the preselected antigen in the fusion protein elicits a stronger immune response in the mammal than the preselected antigen alone.
2. The method of claim 1, further comprising administering the fusion protein in combination with an adjuvant in an amount sufficient to enhance the immune response against the preselected antigen of the fusion protein relative to the immune response against the preselected antigen of the fusion protein administered without the adjuvant.
3. The method of claim 2, wherein the fusion protein and adjuvant are administered simultaneously.
4. The method of claim 2, wherein the adjuvant comprises a fusion protein comprising an immunoglobulin heavy chain constant region linked by a polypeptide bond to an adjuvant protein.
5. The method of claim 1 or 4, wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin hinge region.
6. The method of claim 5, wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin heavy chain constant region domain selected from the group consisting of a CH2 domain, a CH3 domain, and a CH4 domain.
7. The method of claim 5, wherein the immunoglobulin heavy chain constant region comprises a CH2 domain and a CH3 domain.
8. The method of claim 1 or 4, wherein the immunoglobulin heavy chain constant region is defined by an amino acid sequence corresponding to an amino acid sequence defining an immunoglobulin heavy chain constant region present in the same species as the mammal.
9. The method of claim 8, wherein the amino acid sequence defining the immunoglobulin heavy chain constant region corresponds to a human immunoglobulin heavy chain constant region.
10. The method of claim 1, wherein the preselected antigen is selected from the group consisting of a prostate-specific membrane antigen, an ectodomain of a cytokine receptor, a viral protein and a tumor-specific protein.
11. The method of claim 4, wherein the adjuvant protein is a cytokine.
12. The method of claim 11, wherein the cytokine is defined by an amino acid sequence corresponding to an amino acid sequence defining a cytokine present in the same species as the mammal.
13. The method of claim 12, wherein the cytokine is a human cytokine.
14. The method of claim 1, wherein the mammal is a human.
15. A composition for eliciting an immune response against a preselected antigen in a mammal, the composition comprising an admixture for intramuscular, intravenous, transdermal or subcutaneous administration selected from the group consisting of:
(a) an antigen fusion protein comprising an immunoglobulin heavy chain constant region linked by a polypeptide bond to the preselected antigen admixed with an adjuvant; and (b) a preselected antigen admixed with an adjuvant fusion protein comprising an immunoglobulin heavy chain constant region linked by a polypeptide bond to an adjuvant protein.
(a) an antigen fusion protein comprising an immunoglobulin heavy chain constant region linked by a polypeptide bond to the preselected antigen admixed with an adjuvant; and (b) a preselected antigen admixed with an adjuvant fusion protein comprising an immunoglobulin heavy chain constant region linked by a polypeptide bond to an adjuvant protein.
16. The composition of claim 15, wherein the adjuvant of clause (a) comprises a fusion protein comprising an immunoglobulin constant region linked by a polypeptide bond to an adjuvant protein.
17. The composition of claim 15, wherein the preselected antigen of clause (b) is linked by a polypeptide bond to an immunoglobulin heavy chain constant region.
18. The composition of claim 15, 16 or 17, wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin hinge region.
19. The composition of claim 18, wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin heavy chain constant region domain selected from the group consisting of a CH2 domain, a CH3 domain, and a CH4 domain.
20. The composition of claim 18, wherein the immunoglobulin heavy chain constant region comprises a CH2 domain and a CH3 domain.
21. The composition of claim 15, wherein the adjuvant of clause (a) comprises an oligonucleotide CpG sequence.
22. The composition of claim 15, wherein the preselected antigen is selected from the group consisting of a prostate-specific membrane antigen, an ectodomain of a cytokine receptor, a viral protein and a tumor-specific protein.
23. The composition of claim 15, wherein the antigen fusion protein of clause (a) or the adjuvant fusion of clause (b) is linked by a disulfide bond to a second immunoglobulin heavy chain constant region.
24. The composition of claim 15, wherein the adjuvant of clause (a) or the adjuvant protein of clause (b) is a cytokine.
25. The composition of claim 24, wherein the cytokine is a human cytokine.
26. The composition of claim 15, 16 or 17, wherein the immunoglobulin heavy chain constant region is defined by a amino acid sequence corresponding to an amino acid sequence defining a human immunoglobulin heavy chain constant region.
27. A method of enhancing the immunogenicity of a preselected antigen in a mammal, the method comprising:
administering to the mammal a nucleic acid sequence encoding a fusion protein comprising an immunoglobulin heavy chain constant region linked to the preselected antigen, whereupon expression of the nucleic acid sequence in the mammal results in the production of the fusion protein, the preselected antigen of which elicits a stronger immune response than the preselected antigen expressed from a nucleic acid encoding the preselected antigen alone.
administering to the mammal a nucleic acid sequence encoding a fusion protein comprising an immunoglobulin heavy chain constant region linked to the preselected antigen, whereupon expression of the nucleic acid sequence in the mammal results in the production of the fusion protein, the preselected antigen of which elicits a stronger immune response than the preselected antigen expressed from a nucleic acid encoding the preselected antigen alone.
28. The method of claim 27, wherein the nucleic acid encodes in a 5' to 3' direction the immunoglobulin heavy chain constant region and the preselected antigen.
29. The method of claim 28, wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin hinge region.
30. The method of claim 27 or 29, wherein the immunoglobulin heavy chain constant region comprises a heavy chain domain selected from the group consisting of a domain, a CH3 domain, and a CH4 domain.
31. The method of claim 29, wherein the immunoglobulin heavy chain constant region comprises a CH2 domain and a CH3 domain.
32. The method of claim 27, wherein the preselected antigen is selected from the group consisting of a prostate-specific membrane antigen, an ectodomain of a cytokine receptor, a viral protein and an cancer-specific antigen.
33. The composition of claim 27, further comprising administering the nucleic acid sequence in combination with an adjuvant.
34. The method of claim 33, wherein the adjuvant comprises a nucleic acid sequence encoding an fusion protein comprising an immunoglobulin heavy chain constant region linked to an adjuvant protein.
35. A composition for eliciting an immune response against a preselected antigen in a mammal, the composition comprising:
(a) a first nucleic acid sequence encoding a fusion protein comprising an immunoglobulin heavy chain constant region and the preselected antigen, whereupon expression of the nucleic acid sequence in the mammal results in production of the fusion protein, the preselected antigen of which elicits a stronger immune response than the preselected antigen expressed from a nucleic acid encoding the preselected antigen alone;
and (b) an adjuvant.
(a) a first nucleic acid sequence encoding a fusion protein comprising an immunoglobulin heavy chain constant region and the preselected antigen, whereupon expression of the nucleic acid sequence in the mammal results in production of the fusion protein, the preselected antigen of which elicits a stronger immune response than the preselected antigen expressed from a nucleic acid encoding the preselected antigen alone;
and (b) an adjuvant.
36. The composition of claim 35, wherein the adjuvant comprises a second nucleic acid sequence encoding a fusion protein comprising an immunoglobulin heavy chain constant region linked by a peptide bond to an adjuvant protein.
37. The composition of claim 35 or 36, wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin hinge region.
38. The composition of claim 35 or 36, wherein the immunoglobulin heavy chain constant comprises an immunoglobulin heavy chain domain selected from the group consisting of a CH2 domain, a CH3 domain, and a CH4 domain.
39. The composition of claim 37, wherein the immunoglobulin heavy chain constant comprises an immunoglobulin heavy chain domain selected from the group consisting of a CH2 domain, a CH3 domain, and a CH4 domain.
40. The composition of claim 35, wherein the preselected antigen is selected from the group consisting of a prostate-specific membrane antigen, an ectodomain of a cytokine receptor, a viral protein and a cancer-specific antigen.
41. The composition of claim 36, wherein the adjuvant protein is a cytokine.
42. The composition of claim 35, wherein the first nucleic acid sequence is operably disposed within a replicable expression vector.
43. The composition of claim 36, wherein the second nucleic acid sequence is operably disposed within a replicable expression vector.
44. A method for enhancing the immunogenicity of a preselected antigen in a mammal, the method comprising:
administering to a mammal, either simultaneously or sequentially, a first fusion protein comprising an antigen protein with a localizing protein, and a second fusion protein comprising an adjuvant protein and said localizing protein, said localizing protein causing an increase in concentration of said first and second fusion proteins in a region of the mammal accessible to the immune system.
administering to a mammal, either simultaneously or sequentially, a first fusion protein comprising an antigen protein with a localizing protein, and a second fusion protein comprising an adjuvant protein and said localizing protein, said localizing protein causing an increase in concentration of said first and second fusion proteins in a region of the mammal accessible to the immune system.
45. A method for enhancing the immunogenicity of a preselected antigen in a mammal, the method comprising:
administering to a mammal a fusion protein comprising an antigen protein, an adjuvant protein and a localizing protein, said localizing protein causing an increase in concentration of said antigen and adjuvant proteins in a region of the mammal accessible to the immune system.
administering to a mammal a fusion protein comprising an antigen protein, an adjuvant protein and a localizing protein, said localizing protein causing an increase in concentration of said antigen and adjuvant proteins in a region of the mammal accessible to the immune system.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14496599P | 1999-07-21 | 1999-07-21 | |
US60/144,965 | 1999-07-21 | ||
PCT/US2000/019816 WO2001007081A1 (en) | 1999-07-21 | 2000-07-21 | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
Publications (2)
Publication Number | Publication Date |
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CA2378866A1 true CA2378866A1 (en) | 2001-02-01 |
CA2378866C CA2378866C (en) | 2011-06-07 |
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Application Number | Title | Priority Date | Filing Date |
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CA2378866A Expired - Fee Related CA2378866C (en) | 1999-07-21 | 2000-07-21 | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
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Country | Link |
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US (2) | US7955590B2 (en) |
EP (1) | EP1198250B8 (en) |
JP (1) | JP4764585B2 (en) |
KR (1) | KR100689739B1 (en) |
CN (1) | CN1308037C (en) |
AT (1) | ATE374042T1 (en) |
AU (1) | AU779388B2 (en) |
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