WO2000002897B1 - Delta cleavage products and methods based thereon - Google Patents
Delta cleavage products and methods based thereonInfo
- Publication number
- WO2000002897B1 WO2000002897B1 PCT/US1999/015817 US9915817W WO0002897B1 WO 2000002897 B1 WO2000002897 B1 WO 2000002897B1 US 9915817 W US9915817 W US 9915817W WO 0002897 B1 WO0002897 B1 WO 0002897B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- amino acid
- delta
- terminating
- present
- seq
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract 5
- 238000003776 cleavage reaction Methods 0.000 title abstract 5
- 230000007017 scission Effects 0.000 title abstract 5
- 239000012634 fragment Substances 0.000 claims abstract 7
- 101800001148 Delta-peptide Proteins 0.000 claims abstract 5
- 108020004707 nucleic acids Proteins 0.000 claims abstract 3
- 102000039446 nucleic acids Human genes 0.000 claims abstract 3
- 150000007523 nucleic acids Chemical class 0.000 claims abstract 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 2
- 150000001413 amino acids Chemical class 0.000 claims 18
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 239000006143 cell culture medium Substances 0.000 claims 3
- 101000914947 Bungarus multicinctus Long neurotoxin homolog TA-bm16 Proteins 0.000 claims 1
- 102000005650 Notch Receptors Human genes 0.000 claims 1
- 108010070047 Notch Receptors Proteins 0.000 claims 1
- 108700041965 Xenopus PSMB6 Proteins 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 108700041286 delta Proteins 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 230000004913 activation Effects 0.000 abstract 5
- 102000007474 Multiprotein Complexes Human genes 0.000 abstract 1
- 108010085220 Multiprotein Complexes Proteins 0.000 abstract 1
- 230000019491 signal transduction Effects 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention is directed to a Delta cleavage peptide and fragments, derivative and analogs thereof, and its encoding nucleic acids. The present invention is also directed to a soluble Delta peptide and fragments, derivative and analogs thereof, and its encoding nucleic acids. The present invention is also directed to protein complexes of Delta and Kuz. The present invention is also directed to methods for detecting or measuring Delta activation by observing or measuring Delta cleavage products that are indicative of Delta activation. The present invention is also directed to methods for detecting or measuring Kuz activation by observing or measuring Delta cleavage products that are indicative of Kuz activation. The present invention is also directed to methods for detecting a molecule that modulates Delta activation or Kuz function by observing or measuring a change in the amount of or pattern of Delta cleavage products. The present invention is based, at least in part, on the discovery that Delta in its active form, i.e., the form that mediates signal transduction and that binds Notch, is a soluble fragment consisting of the extracellular domain.
Claims
AMENDED CLAIMS
[received by the International Bureau on 17 March 2000 (17.03.00); new claims 125 and 126 added; remaining claims unchanged (1 page)]
124. A nucleic acid comprising a nucleotide sequence encoding a fragment of a Delta protein, the amino acid sequence of said fragment consisting of an amino acid sequence beginning at amino acid Ser23 and terminating between amino acid CysS64 and amino acid Gln594 in Drosophila Delta (SEQ ID NO: 9) .
125. A fragment of the soluble Delta peptide, which peptide consists of the amino acid sequence beginning at amino acid Ser22 and terminating between amino acid Cys51s and amino acid PheS4J in human Delta (SEQ ID NO: 10); beginning at amino acid Ser22 and terminating between amino acid Cys515 and amino acid Phe543 in mouse Delta (SEQ ID NO: 6) ; beginning at amino acid Ser24 and terminating between amino acid CysS23 and amino acid PheS51 in chick Delta (SEQ ID NO: 7); beginning at amino acid Ser2z and terminating between amino acid Cyssιa and amino acid Phe544 in Xenopus Delta (SEQ ID NO: 8) ; and the sequence beginning at amino acid Ser23 and terminating between amino acid Cyss64 and amino acid Ala593 in Droβophila Delta (SEQ ID NO: 9) , which fragment is able to bind a Notch protein.
126. An isolated soluble Delta peptide isolated by a process comprising:
(a) culturing a Delta-expressing cell in cell culture medium, such that the cell secretes a soluble Delta peptide into the cell culture medium; and
(b) isolating the soluble Delta peptide from the cell culture medium.
- 160 -
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99935534A EP1096946A2 (en) | 1998-07-13 | 1999-07-13 | Delta cleavage products and methods based thereon |
| CA002333893A CA2333893A1 (en) | 1998-07-13 | 1999-07-13 | Delta cleavage products and methods based thereon |
| AU50994/99A AU5099499A (en) | 1998-07-13 | 1999-07-13 | Delta cleavage products and methods based thereon |
| JP2000559126A JP2002520007A (en) | 1998-07-13 | 1999-07-13 | Delta cleavage products and methods based thereon |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9251398P | 1998-07-13 | 1998-07-13 | |
| US10483498P | 1998-10-19 | 1998-10-19 | |
| US60/104,834 | 1998-10-19 | ||
| US60/092,513 | 1998-10-19 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| WO2000002897A2 WO2000002897A2 (en) | 2000-01-20 |
| WO2000002897A3 WO2000002897A3 (en) | 2000-03-16 |
| WO2000002897B1 true WO2000002897B1 (en) | 2000-05-04 |
| WO2000002897A9 WO2000002897A9 (en) | 2000-07-20 |
Family
ID=26785768
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1999/015817 WO2000002897A2 (en) | 1998-07-13 | 1999-07-13 | Delta cleavage products and methods based thereon |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1096946A2 (en) |
| JP (1) | JP2002520007A (en) |
| AU (1) | AU5099499A (en) |
| CA (1) | CA2333893A1 (en) |
| WO (1) | WO2000002897A2 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0861261B9 (en) | 1995-06-28 | 2010-02-24 | Imperial Cancer Research Technology Limited | Nucleotide and protein sequences of vertebrate delta genes and methods based thereon |
| US6692919B1 (en) | 1997-07-23 | 2004-02-17 | Yale University | Activated forms of notch and methods based thereon |
| US6649346B2 (en) | 2001-03-30 | 2003-11-18 | Board Of Regents, The University Of Texas | Methods of identifying agents that affect cleavage of amyloid-β precursor protein |
| CA2454937A1 (en) * | 2001-07-25 | 2003-02-13 | Lorantis Limited | Modulators of notch signalling for use in immunotherapy |
| GB0300428D0 (en) * | 2003-01-09 | 2003-02-05 | Lorantis Ltd | Medical treatment |
| GB0307472D0 (en) * | 2003-04-01 | 2003-05-07 | Lorantis Ltd | Medical treatment |
| AU2005209909B8 (en) * | 2004-02-03 | 2009-01-15 | The Regents Of The University Of Michigan | Compositions and methods for characterizing, regulating, diagnosing, and treating cancer |
| EA029958B1 (en) | 2011-09-23 | 2018-06-29 | Онкомед Фармасьютикалс, Инк. | Antibodies that bind vascular endothelial growth factor (vegf)/delta-like 4 ligand (dll4) and use thereof |
| AU2016326609B2 (en) | 2015-09-23 | 2023-03-09 | Mereo Biopharma 5, Inc. | Methods and compositions for treatment of cancer |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0861261B9 (en) * | 1995-06-28 | 2010-02-24 | Imperial Cancer Research Technology Limited | Nucleotide and protein sequences of vertebrate delta genes and methods based thereon |
| JP2000517185A (en) * | 1996-08-29 | 2000-12-26 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Novel metalloprotease family KUZ |
| US6664098B1 (en) * | 1997-05-14 | 2003-12-16 | Asahi Kasei Kabushiki Kaisha | Differentiation inhibitory agent |
-
1999
- 1999-07-13 EP EP99935534A patent/EP1096946A2/en not_active Withdrawn
- 1999-07-13 AU AU50994/99A patent/AU5099499A/en not_active Abandoned
- 1999-07-13 CA CA002333893A patent/CA2333893A1/en not_active Abandoned
- 1999-07-13 JP JP2000559126A patent/JP2002520007A/en active Pending
- 1999-07-13 WO PCT/US1999/015817 patent/WO2000002897A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000002897A9 (en) | 2000-07-20 |
| AU5099499A (en) | 2000-02-01 |
| EP1096946A2 (en) | 2001-05-09 |
| WO2000002897A2 (en) | 2000-01-20 |
| WO2000002897A3 (en) | 2000-03-16 |
| CA2333893A1 (en) | 2000-01-20 |
| JP2002520007A (en) | 2002-07-09 |
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