CA2274803A1 - Receptor activator of nf-kappa b, receptor is member of tnf receptor superfamily - Google Patents
Receptor activator of nf-kappa b, receptor is member of tnf receptor superfamily Download PDFInfo
- Publication number
- CA2274803A1 CA2274803A1 CA002274803A CA2274803A CA2274803A1 CA 2274803 A1 CA2274803 A1 CA 2274803A1 CA 002274803 A CA002274803 A CA 002274803A CA 2274803 A CA2274803 A CA 2274803A CA 2274803 A1 CA2274803 A1 CA 2274803A1
- Authority
- CA
- Canada
- Prior art keywords
- rank
- amino acid
- dna
- protein
- host cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 102000010498 Receptor Activator of Nuclear Factor-kappa B Human genes 0.000 title claims 8
- 108010038036 Receptor Activator of Nuclear Factor-kappa B Proteins 0.000 title claims 8
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 title 1
- 102000005962 receptors Human genes 0.000 title 1
- 108020003175 receptors Proteins 0.000 title 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 title 1
- 108020004414 DNA Proteins 0.000 claims abstract 18
- 230000028993 immune response Effects 0.000 claims abstract 3
- 150000001413 amino acids Chemical group 0.000 claims 20
- 108090000765 processed proteins & peptides Proteins 0.000 claims 16
- 210000004027 cell Anatomy 0.000 claims 15
- 229920001184 polypeptide Polymers 0.000 claims 12
- 102000004196 processed proteins & peptides Human genes 0.000 claims 12
- 239000013604 expression vector Substances 0.000 claims 11
- 102000004169 proteins and genes Human genes 0.000 claims 8
- 108090000623 proteins and genes Proteins 0.000 claims 8
- 108060003951 Immunoglobulin Proteins 0.000 claims 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 6
- 238000012258 culturing Methods 0.000 claims 6
- 239000012634 fragment Substances 0.000 claims 6
- 102000018358 immunoglobulin Human genes 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 claims 6
- 230000001737 promoting effect Effects 0.000 claims 6
- 238000003259 recombinant expression Methods 0.000 claims 6
- 125000003729 nucleotide group Chemical group 0.000 claims 5
- 239000002773 nucleotide Substances 0.000 claims 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 3
- 108091034117 Oligonucleotide Proteins 0.000 claims 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 3
- 102000014128 RANK Ligand Human genes 0.000 claims 2
- 108010025832 RANK Ligand Proteins 0.000 claims 2
- 210000004899 c-terminal region Anatomy 0.000 claims 2
- 238000009396 hybridization Methods 0.000 claims 2
- 230000028709 inflammatory response Effects 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 239000012528 membrane Substances 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 238000012216 screening Methods 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
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Isolated receptors, DNAs encoding such receptors, and pharmaceutical compositions made therefrom, are disclosed. The isolated receptors can be used to regulate an immune response. The receptors are also useful in screening for inhibitors thereof.
Claims (34)
1. An isolated DNA selected from the group consisting of:
(a) a DNA encoding a protein having an amino acid sequence as set forth in SEQ
ID
NO:6, wherein the protein has an amino terminus selected from the group consisting of an amino acid between amino acid 1 and amino acid 33, inclusive, of SEQ ID NO:6, and a carboxy terminus selected from the group consisting an amino acid between amino acid 196 and amino acid 616, inclusive;
(b) a DNA encoding a protein having an amino acid sequence as set forth in SEQ
ID NO:15, wherein the protein hay an amino terminus selected from the group consisting of an amino acid between amino acid 1 and amino acid 31, inclusive, of SEQ ID
NO:15, and a carboxy terminus selected from the group consisting an amino acid between amino acid 197 and amino acid 625, inclusive;
(c) DNA molecules capable of hybridization to the DNA of (a) or (b) under stringent conditions, that include 50°C, 5X SSC, overnight, and which encode biologically active RANK; and (d) DNA molecules encoding fragments of proteins encoded by the DNA of (a), (b) or (c), wherein the fragments are biologically active.
(a) a DNA encoding a protein having an amino acid sequence as set forth in SEQ
ID
NO:6, wherein the protein has an amino terminus selected from the group consisting of an amino acid between amino acid 1 and amino acid 33, inclusive, of SEQ ID NO:6, and a carboxy terminus selected from the group consisting an amino acid between amino acid 196 and amino acid 616, inclusive;
(b) a DNA encoding a protein having an amino acid sequence as set forth in SEQ
ID NO:15, wherein the protein hay an amino terminus selected from the group consisting of an amino acid between amino acid 1 and amino acid 31, inclusive, of SEQ ID
NO:15, and a carboxy terminus selected from the group consisting an amino acid between amino acid 197 and amino acid 625, inclusive;
(c) DNA molecules capable of hybridization to the DNA of (a) or (b) under stringent conditions, that include 50°C, 5X SSC, overnight, and which encode biologically active RANK; and (d) DNA molecules encoding fragments of proteins encoded by the DNA of (a), (b) or (c), wherein the fragments are biologically active.
2. The isolated DNA of claim 1, which encodes a RANK polypeptide that is at least about 80% identical in amino acid sequence to the nature form of RANK.
3. The isolated DNA of claim 1, which encodes a soluble RANK polypeptide.
4. The isolated DNA of claim 2, which encodes a soluble RANK polypeptide.
5. The isolated DNA of claim 3, which further comprises a DNA encoding a polypeptide selected from the gourp consisting of an immunoglobulin Fc domain, an immunoglobulin Fc mutein, a FLAG TM tag, a peptide comprising at least about 6 His residues, a leucine zipper, and combinations thereof.
6. The isolated DNA of claim 4, which further comprises a DNA encoding a polypeptide selected from the gourp consisting of an immunoglobulin Fc domain, an immunoglobulin Fc mutein, a FLAG TM tag, a peptide comprising at least about 6 His residues, a leucine zipper, and combinations thereof.
7. A recombinant expression vector comprising a DNA sequence according to claim 1.
8. A recombinant expression vector comprising a DNA sequence according to claim 2.
9. A recombinant expression vector composing a DNA sequence according to claim 3.
10. A recombinant expression vector comprising a DNA sequence according to claim 4.
11. A recombinant expression. sector comprising a DNA sequence according to claim 5.
12. A recombinant expression vector comprising a DNA sequence according to claim 6.
13. A host cell transformed or transfected with an expression vector according to claim 7.
14. A host cell transformed or transfected with an expression vector according to claim 8.
15. A host cell transformed or transfected with an expression vector according to claim 9.
16. A host cell transformed or transfected with an expression vector according to claim 10.
17. A host cell transformed or transfected with an expression vector according to claim 11.
18. A host cell transformed or transfected with an expression vector according to claim 12.
19. A process for preparing a RANK protein, comprising culturing a host cell according to claim 13 under conditions promoting expression and recovering the RANK.
20. A process for preparing a RANK protein, comprising culturing a host cell according to claim 14 under conditions promoting expression and recovering the RANK.
21. A process for preparing a RANK protein, comprising culturing a host cell according to claim 15 under conditions promoting expression and recovering the RANK.
22. A process for preparing a RANK protein, comprising culturing a host cell according to claim 16 under conditions promoting expression and recovering the RANK.
23. A process for preparing a RANK protein, comprising culturing a host cell according to claim 17 under conditions promoting expression and recovering the RANK.
24. A process for preparing a RANK protein, comprising culturing a host cell according to claim 18 under conditions promoting expression and recovering the RANK.
25. An isolated DNA selected from the group consisting of oligonucleotides of at least about 17 nucleotides in length, oligonucleotides of at least about 25 nucleotides in length, and oligonucleotides of at least about 30 nucleotides in length, wherein the fragment is a fragment of nucleotide residues 39-1886 of SEQ ID
NO:5 or a fragment of nucleotides residues 1-1878 of SEQ ID NO:14.
NO:5 or a fragment of nucleotides residues 1-1878 of SEQ ID NO:14.
26. An isolated RANK polypeptide selected from the group consisting of:
(a) a polypeptide having an amino acid sequence of amino acids 33 through 196 of SEQ ID NO: 6;
(b) a polypeptide having an amino acid sequence of amino acids 31 through 197 of SEQ ID NO: 15;
(c) a RANK polypeptide encoded by a DNA capable of hybridization to a DNA
encoding the protein of (a) or (b) under stringent conditions, and which is biologically active; and (d) fragments of the polypeptide of (a), (b) or (c) which are biologically active.
(a) a polypeptide having an amino acid sequence of amino acids 33 through 196 of SEQ ID NO: 6;
(b) a polypeptide having an amino acid sequence of amino acids 31 through 197 of SEQ ID NO: 15;
(c) a RANK polypeptide encoded by a DNA capable of hybridization to a DNA
encoding the protein of (a) or (b) under stringent conditions, and which is biologically active; and (d) fragments of the polypeptide of (a), (b) or (c) which are biologically active.
27. The protein according to claim 26, having an amino acid sequence at least about 80% identical to SEQ ID NO:6 or SEQ ID NO:15.
28. The protein according to claim 27, which is a soluble RANK.
29. The protein according to claim 26, which is a soluble RANK.
30. A soluble RANK protein which further comprises a peptide selected from the group consisting of an immunoglobulin Fc domain, an immunoglobulin Fc mutein, a FLAG TM tag, a peptide comprising at least about 6 His residues, a leucine zipper, and combinations thereof.
31. An antibody immunoreactive with RANK polypeptide according to claim 26.
32. The antibody according to claim 31, which is a monoclonal antitbody.
33. A method of inhibiting activation of NF-B, comprising contacting a cell that expresses membrane-associated RANK with a soluble RANK and allowing the soluble RANK to bind RANKL and inhibit binding thertof to the cell.
34. A method of regulating an immune or inflammatory response, comprising administering a soluble RANK polypeptide composition to an individual at risk for an immune or inflammatory response, and allowing the soluble RANK to hind RANKL
and inhibit binding thereof to cells expressing RANK.
and inhibit binding thereof to cells expressing RANK.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5997896P | 1996-12-23 | 1996-12-23 | |
| US60/059,978 | 1996-12-23 | ||
| US81350997A | 1997-03-07 | 1997-03-07 | |
| US08/813,509 | 1997-03-07 | ||
| US6467197P | 1997-10-14 | 1997-10-14 | |
| US60/064,671 | 1997-10-14 | ||
| PCT/US1997/023866 WO1998028424A2 (en) | 1996-12-23 | 1997-12-22 | Receptor activator of nf-kappa b, receptor is member of tnf receptor superfamily |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2274803A1 true CA2274803A1 (en) | 1998-07-02 |
| CA2274803C CA2274803C (en) | 2012-05-22 |
Family
ID=43981413
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2274803A Expired - Fee Related CA2274803C (en) | 1996-12-23 | 1997-12-22 | Receptor activator of nf-kappa b, receptor is member of tnf receptor superfamily |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2013005802A (en) |
| CA (1) | CA2274803C (en) |
| IL (3) | IL130491A (en) |
| PT (1) | PT946725E (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4138013B2 (en) * | 1996-12-23 | 2008-08-20 | イミュネックス・コーポレーション | Ligand for receptor activator of NF-KAPPA B, a member of TNF superfamily |
-
1997
- 1997-12-22 PT PT97953438T patent/PT946725E/en unknown
- 1997-12-22 CA CA2274803A patent/CA2274803C/en not_active Expired - Fee Related
- 1997-12-22 IL IL130491A patent/IL130491A/en not_active IP Right Cessation
-
2011
- 2011-09-07 IL IL215021A patent/IL215021A0/en unknown
- 2011-09-07 IL IL215020A patent/IL215020A0/en unknown
-
2012
- 2012-08-06 JP JP2012173637A patent/JP2013005802A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL130491A (en) | 2011-10-31 |
| IL215020A0 (en) | 2011-10-31 |
| JP2013005802A (en) | 2013-01-10 |
| IL215021A0 (en) | 2011-10-31 |
| IL130491A0 (en) | 2000-06-01 |
| PT946725E (en) | 2011-04-20 |
| CA2274803C (en) | 2012-05-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20151222 |