CA2692358A1 - Recombinant human interferon-like proteins - Google Patents
Recombinant human interferon-like proteins Download PDFInfo
- Publication number
- CA2692358A1 CA2692358A1 CA002692358A CA2692358A CA2692358A1 CA 2692358 A1 CA2692358 A1 CA 2692358A1 CA 002692358 A CA002692358 A CA 002692358A CA 2692358 A CA2692358 A CA 2692358A CA 2692358 A1 CA2692358 A1 CA 2692358A1
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- Prior art keywords
- protein
- alpha
- huifn
- seq
- polynucleotide
- Prior art date
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Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract 86
- 102000004169 proteins and genes Human genes 0.000 title claims abstract 85
- 239000002157 polynucleotide Substances 0.000 claims abstract 20
- 102000040430 polynucleotide Human genes 0.000 claims abstract 20
- 108091033319 polynucleotide Proteins 0.000 claims abstract 20
- 230000001028 anti-proliverative effect Effects 0.000 claims abstract 14
- 230000000840 anti-viral effect Effects 0.000 claims abstract 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 5
- 238000002560 therapeutic procedure Methods 0.000 claims abstract 5
- 206010028980 Neoplasm Diseases 0.000 claims abstract 4
- 201000011510 cancer Diseases 0.000 claims abstract 4
- 102100040018 Interferon alpha-2 Human genes 0.000 claims abstract 3
- 108010079944 Interferon-alpha2b Proteins 0.000 claims abstract 3
- 108010050904 Interferons Proteins 0.000 claims abstract 3
- 102000014150 Interferons Human genes 0.000 claims abstract 3
- 229940079322 interferon Drugs 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims abstract 3
- 239000013598 vector Substances 0.000 claims abstract 3
- 201000010099 disease Diseases 0.000 claims abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 2
- 230000003612 virological effect Effects 0.000 claims abstract 2
- 230000004071 biological effect Effects 0.000 claims 10
- 238000000034 method Methods 0.000 claims 7
- 150000001413 amino acids Chemical class 0.000 claims 4
- 230000001747 exhibiting effect Effects 0.000 claims 4
- 239000012634 fragment Substances 0.000 claims 3
- 229920001184 polypeptide Polymers 0.000 claims 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 229920000642 polymer Polymers 0.000 claims 2
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 claims 1
- 201000006662 cervical adenocarcinoma Diseases 0.000 claims 1
- 208000019065 cervical carcinoma Diseases 0.000 claims 1
- 201000006585 gastric adenocarcinoma Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 230000002519 immonomodulatory effect Effects 0.000 claims 1
- 238000002372 labelling Methods 0.000 claims 1
- 201000005296 lung carcinoma Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 201000001514 prostate carcinoma Diseases 0.000 claims 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 abstract 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 abstract 1
Classifications
-
- 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
- C07K14/555—Interferons [IFN]
-
- C—CHEMISTRY; METALLURGY
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K14/555—Interferons [IFN]
- C07K14/56—IFN-alpha
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
This application relates to recombinant human interferon-like proteins. In one embodiment a recombinant protein created by gene shuffling technology is described having enhanced anti-viral and anti-proliferative activities in comparison to naturally occurring human interferon alpha 2b (HuIFN-.alpha.2b). The invention encompasses a polynucleotide encoding the protein and recombinant vectors and host cells comprising the polynucleotide.
Preferably the polynucleotide is selected from the group of polynucleotides each having a sequence at least 93% identical to SEQ ID: No. 1 and the protein is selected from the group of proteins each having an amino acid sequence at least 85% identical to SEQ ID No: 2. The proteins and compositions comprising the proteins can be used for treatment of conditions responsive to interferon therapy, such as viral diseases and cancer.
Preferably the polynucleotide is selected from the group of polynucleotides each having a sequence at least 93% identical to SEQ ID: No. 1 and the protein is selected from the group of proteins each having an amino acid sequence at least 85% identical to SEQ ID No: 2. The proteins and compositions comprising the proteins can be used for treatment of conditions responsive to interferon therapy, such as viral diseases and cancer.
Claims (58)
1. An isolated polynucleotide encoding a protein having human interferon-like biological activities, wherein said polynucleotide is selected from the group consisting of polynucleotides each comprising a nucleotide sequence at least 95%
identical to SEQ ID No: 1.
identical to SEQ ID No: 1.
2. The polynucleotide as defined in claim 1, wherein said sequence is at least 97%
identical to SEQ ID No: 1.
identical to SEQ ID No: 1.
3. The polynucleotide as defined in claim 2, wherein said sequence is at least 98%
identical to SEQ ID No: 1.
identical to SEQ ID No: 1.
4. The polynucleotide as defined in any one of claims 1-3, wherein said protein is non-naturally occurring.
5. The polynucleotide as defined in claim 4, wherein said protein has enhanced anti-viral and anti-proliferative activities in comparison to human interferon alpha 2b (HuIFN-.alpha.2b).
6. The polynucleotide as defined in claim 5, wherein said protein has anti-viral activity at least 2 fold greater than HuIFN-.alpha.2b.
7. The polynucleotide as defined in claim 5, wherein said protein has anti-proliferative activity at least 10 fold greater than HuIFN-.alpha.2b.
8. A recombinant vector comprising the polynucleotide of claim 1.
9. A host cell containing the recombinant vector of claim 8.
10. A non-naturally occurring protein exhibiting human interferon-like biological activities, wherein said protein is selected from the group consisting of proteins each comprising an amino acid sequence at least 89% identical to SEQ ID No: 2.
11. The protein as defined in claim 10, wherein said sequence is at least 90%
identical to SEQ ID No: 2.
identical to SEQ ID No: 2.
12. The protein as defined in claim 10, wherein said sequence is at least 95%
identical to SEQ ID No: 2.
identical to SEQ ID No: 2.
13. The protein as defined in any one of claims 10-12, wherein said protein has enhanced anti-viral and anti-proliferative activity in comparison to HuIFN-.alpha.2b.
14. The protein as defined in claim 13, wherein said protein has anti-viral activity at least 2 fold greater than HuIFN-.alpha.2b.
15. The protein as defined in claim 14, wherein said protein has anti-viral activity at least 5 fold greater than HuIFN-.alpha.2b.
16. The protein as defined in claim 15, wherein said protein has anti-viral activity at least 10 fold greater than HuIFN-.alpha.2b.
17. The protein as defined in claim 13, wherein said protein has anti-proliferative activity at least 10 fold greater than HuIFN-.alpha.2b.
18. The protein as defined in claim 17, wherein said protein has anti-proliferative activity at least 50 fold greater than HuIFN-.alpha.2b.
19. The protein as defined in claim 18, wherein said protein has anti-proliferative activity at least 100 fold greater than HuIFN-.alpha.2b.
20. The protein as defined in claim 19, wherein said protein has anti-proliferative activity at least 200 fold greater than HuIFN-.alpha.2b.
21. The protein as defined in claim 10, wherein said protein is recombinant.
22. The protein as defined in claim 10, wherein said protein has a molecular weight of 19315 daltons.
23. The protein as defined in claim 10, optionally comprising a methionine residue at the N terminus.
24. A non-naturally occurring protein comprising a sequence which differs in 0 to 19 amino acids from SEQ ID No: 2, wherein said protein exhibits human interferon-like biological activities.
25. The protein as defined in claim 24, wherein said protein has enhanced anti-viral and anti-proliferative activity in comparison to HuIFN-.alpha.2b.
26. The protein as defined in claim 25, wherein said protein has anti-viral activity at least 2 fold greater than HuIFN-.alpha.2b.
27. The protein as defined in claim 24, wherein said protein has anti-proliferative activity at least 10 fold greater than HuIFN-.alpha.2b.
28. The protein as defined in claim 27, wherein said protein has anti-proliferative activity at least 100 fold greater than HuIFN-.alpha.2b.
29. The protein as defined in claim 24, wherein said protein is recombinant.
30. A polypeptide comprising a fragment of the protein as defined in claim 10, wherein said fragment comprises at least 146 amino acids and exhibits anti-viral and anti-proliferative biological activities at least as active as human interferon alpha 2b.
31. A protein construct comprising the protein as defined in claim 10 coupled to a moiety, wherein said construct exhibits said human interferon-like biological activities.
32. The protein construct as defined in claim 31, wherein said protein is glycosylated.
33. The protein construct as defined in claim 31, wherein said moiety is a polypeptide.
34. The protein construct as defined in claim 31, wherein said moiety is a non-polypeptide.
35. The protein construct as defined in claim 34, wherein said moiety is a polymer molecule.
36. The protein construct as defined in claim 35, wherein said polymer molecule is a linear or branched polyethylene glycol.
37. The protein construct as defined in claim 31, wherein said moiety is a labeling molecule.
38. A composition comprising the protein as defined in claim 10 and a pharmaceutically acceptable carrier, diluent or excipient.
39. A polynucleotide encoding a protein as defined in claim 10.
40. The use of the protein as defined in claim 10 as an anti-viral agent.
41. The use of the protein as defined in claim 10 as an anti-proliferative agent.
42. The use of the protein as defined in claim 10 as an anti-cancer agent.
43. The use of the protein as defined in claim 10 as an immunomodulation agent.
44. A method of treating cancer comprising administering to a subject in need of therapy a therapeutically effective amount of the protein as defined in claim 10.
45. A method of treating a viral disease comprising administering to a subject in need of therapy a therapeutically effective amount of the protein as defined in claim 10.
46. The method as defined in claim 44 or 45, wherein said subject is a human being.
47. The method as defined in claim 44 or 45, wherein said protein is administered together with a pharmaceutically acceptable carrier, diluent or excipient.
48. A method of treating a condition responsive to interferon therapy comprising administering to a subject in need of treatment a therapeutically effective amount of the protein as defined in claim 10.
49. The method as defined in claim 44, wherein said protein is therapeutically effective in respect of a broad range of different types of cancer, said cancer being selected from the group consisting of melanoma, colorectal adenocarcinoma, hepatocellular carcinoma, hepatoma, lymphoma, prostate carcinoma, gastric adenocarcinoma, esophagus carcinoma, lung carcinoma, cervix adenocarcinoma and cervix carcinoma.
50. A non-naturally occurring protein exhibiting human interferon-like biological activities, wherein said protein has an amino acid sequence at least 95%
identical to SEQ ID No: 2 and wherein said protein has enhanced anti-viral and anti-proliferative activities in comparison to HuIFN-.alpha.2b.
identical to SEQ ID No: 2 and wherein said protein has enhanced anti-viral and anti-proliferative activities in comparison to HuIFN-.alpha.2b.
51. A polynucleotide encoding the protein of claim 50.
52. A composition comprising the protein of claim 50.
53. A protein having the amino acid sequence of SEQ ID No: 2 or a fragment thereof comprising at least 146 amino acids exhibiting human interferon-like biological activities.
54. A polynucleotide encoding the protein of claim 53.
55. An isolated polynucleotide encoding a protein having human interferon-like biological activities, wherein said polynucleotide is selected from the group consisting of polynucleotides each comprising a nucleotide sequence at least 97%
identical to SEQ ID No: 1.
identical to SEQ ID No: 1.
56. A protein exhibiting human interferon-like biological activities, wherein said protein is selected from the group consisting of proteins each comprising an amino acid sequence at least 95% identical to SEQ ID No: 2.
57. A protein comprising a sequence which differs in 0 to 8 amino acids from SEQ ID
No: 2, wherein said protein exhibits human interferon-like biological activities.
No: 2, wherein said protein exhibits human interferon-like biological activities.
58. A method of treating a condition responsive to interferon therapy comprising protein as defined in claim 56 or 57.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/764,786 US7625555B2 (en) | 2007-06-18 | 2007-06-18 | Recombinant human interferon-like proteins |
| US11/764,786 | 2007-06-18 | ||
| PCT/CA2007/001123 WO2008154719A1 (en) | 2007-06-18 | 2007-06-22 | Recombinant human interferon-like proteins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2692358A1 true CA2692358A1 (en) | 2008-12-24 |
| CA2692358C CA2692358C (en) | 2012-11-20 |
Family
ID=40132903
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2692358A Active CA2692358C (en) | 2007-06-18 | 2007-06-22 | Recombinant human interferon-like proteins |
Country Status (21)
| Country | Link |
|---|---|
| US (8) | US7625555B2 (en) |
| EP (3) | EP3133161A1 (en) |
| JP (3) | JP5439189B2 (en) |
| KR (2) | KR20130027043A (en) |
| CN (3) | CN102250918A (en) |
| AU (1) | AU2007355415B2 (en) |
| BR (1) | BRPI0716948B1 (en) |
| CA (1) | CA2692358C (en) |
| DK (2) | DK2078082T3 (en) |
| ES (2) | ES2524251T3 (en) |
| HK (2) | HK1129128A1 (en) |
| IL (1) | IL196673A (en) |
| MX (1) | MX2009001366A (en) |
| MY (1) | MY167485A (en) |
| NZ (1) | NZ574306A (en) |
| PL (2) | PL2078082T3 (en) |
| PT (2) | PT2078082E (en) |
| RU (1) | RU2469091C2 (en) |
| TW (1) | TWI375716B (en) |
| WO (1) | WO2008154719A1 (en) |
| ZA (1) | ZA200901680B (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7625555B2 (en) * | 2007-06-18 | 2009-12-01 | Novagen Holding Corporation | Recombinant human interferon-like proteins |
| JP5840148B2 (en) * | 2010-03-04 | 2016-01-06 | フェニックス インク． | Method for producing soluble recombinant interferon protein without denaturation |
| MY178288A (en) * | 2013-09-20 | 2020-10-07 | Nat Inst Biomedical Innovation Health & Nutrition | Complex containing oligonucleotide having immunopotentiating activity and use thereof |
| LT6164B (en) | 2013-10-15 | 2015-06-25 | Uab Biotechnologinės Farmacijos Centras "Biotechpharma" | Fused proteins of interferon alpha 5 with another cytokine and process for production thereof |
| WO2016009451A2 (en) * | 2014-07-14 | 2016-01-21 | Gennova Biopharmaceuticals Limited | A novel process for purification of rhu-gcsf |
| WO2018041973A1 (en) * | 2016-09-01 | 2018-03-08 | Proqr Therapeutics Ii B.V. | Chemically modified single-stranded rna-editing oligonucleotides |
| WO2018101151A1 (en) * | 2016-12-02 | 2018-06-07 | 興人ライフサイエンス株式会社 | Ribose-containing yeast condiment |
| US10780931B2 (en) * | 2018-05-21 | 2020-09-22 | Ronald Siwicki | Kickstand assembly |
| CN109627343A (en) * | 2018-12-27 | 2019-04-16 | 北京美福源生物医药科技有限公司 | Long-acting cytokine gene derivative fusion protein |
| CN113289006A (en) * | 2020-02-24 | 2021-08-24 | 杰华生物技术(青岛)有限公司 | Application of recombinant cytokine gene derived protein or fragment thereof |
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