WO2001044282A2 - Bcl-g polypeptides, encoding nucleic acids and methods of use - Google Patents
Bcl-g polypeptides, encoding nucleic acids and methods of use Download PDFInfo
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- WO2001044282A2 WO2001044282A2 PCT/US2000/033793 US0033793W WO0144282A2 WO 2001044282 A2 WO2001044282 A2 WO 2001044282A2 US 0033793 W US0033793 W US 0033793W WO 0144282 A2 WO0144282 A2 WO 0144282A2
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- bcl
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4747—Apoptosis related proteins
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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- 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
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/136—Screening for pharmacological compounds
Definitions
- Bcl-G is also contemplated herein as having the ability to function as an ion channel. Additionally, Bcl-G is contemplated herein as having the ability to function target to mitochondria, for example, for example, by 'binding directly to mitochondria or via binding to a protein that is associated with mitochondria such as Bcl-2 or Bcl-X L . Bcl-G can also function to bind adenine nucleotide transporter (ANT) and to other proteins such as voltage-dependent anion channel (VDAC) . Because Bcl-G is located on chromosome 12 in a region that is frequently deleted in cancer cells (Example II) it is contemplated herein that Bcl-G functions as a tumor suppressor.
- ANT adenine nucleotide transporter
- VDAC voltage-dependent anion channel
- Bcl-2 family proteins are central regulators of apoptosis (reviewed in Reed, J. C, Nature, 387:773-776 (1997); Adams & Cory, Science, 281:1322-1326 (1998);
- the invention additionally provides a nucleic acid that hybridizes under high stringency conditions to the Bcl-G coding portion of any of SEQ ID NOS:l, 3 or 41.
- the invention also provides a nucleic acid having a nucleotide sequence the same or substantially the same as set that forth in any of SEQ ID NOS:l, 3 or 41.
- optionally labeled Bcl-G-encoding nucleic acids, or fragments thereof can be employed to probe a library, for example, a cDNA or genomic library, and the like for additional nucleic acid sequences encoding novel Bcl-G polypeptides. Construction of suitable cDNA libraries is well-known in the art.
- a Bcl-G nucleic acid molecule specifically excludes nucleic acid molecules consisting of any of the nucleotide sequences having the Genbank (gb) , EMBL (emb) or DDBJ (dbj) accession numbers described below.
- a Bcl-G polypeptide fragment specifically excludes the amino acid fragments encoded by the nucleotide sequences having the GenBank accession numbers described below.
- GenBank accession numbers specifically excluded include AC005903, AC007439, AW000827, AA399486, AW001213, AI478889, AA400686, AA398276, AI240211, and AA536718.
- GenBank accession numbers specifically excluded include AC005903, AC007439, AW000827, AA399486, AW001213, AI478889, AA400686, AA398276, AI240211, and AA536718.
- the invention thus provides methods for detecting Bcl-G nucleic acid in a sample.
- the methods of detecting Bcl-G nucleic acid in a sample can be either qualitative or quantitative, as desired. For example, the presence, abundance, integrity or structure of a Bcl- G can be determined, as desired, depending on the assay format and the probe used for hybridization or primer pair chosen for application.
- the Bid protein contains a N-terminal domain of -56 amino-acids that masks its BH3 domain, reducing its ability to dimerize with other Bcl-2 family proteins.
- the N-terminal domain exposes the BH3 domain and is associated with translocation of Bid from the cytosol to mitochondria, where it induces cytochrome c release and apoptosis (Li et al., Cell, 94:491-501 (1998); Luo et al., Cell, 94:481-490 (1998)).
- the amino acid length of functional fragments or polypeptide anlogs of the present invention can range from about 5 amino acids up to the full-length protein sequence of an invention Bcl-G.
- the amino acid lengths include, for example, at least about 10 amino acids, at least about 15, at least about 20, at least about 25, at least about 30, at least about 35, at least about 40, at least about 45, at least about 50, at least about 75, at least about 100, at least about 150, at least about 200, at least about 250 or more amino acids in length up to the full-length Bcl-G protein sequence.
- the functional fragments can be contiguous amino acid sequences of a Bcl-G polypeptide, including contiguous amino acid sequences of SEQ ID NOS: 2, 4 or 42.
- Bcl-G polypeptides or a functional portion thereof, can be directly administered to an individual.
- Methods of administering therapeutic polypeptides are well known to those skilled in the art, for example, as a pharmaceutical composition.
- a Bcl-G polypeptide, or functional fragment thereof can be administered to an individual so that the Bcl-G polypeptide or functional fragment is targeted to a tumor to induce apoptosis or otherwise function as a tumor suppressor.
- One method of delivering a Bcl-G polypeptide to an intracellular target is to fuse a Bcl-G polypeptide or functional fragment to an intracellular-targeting peptide that can penetrate the cell membrane or otherwise deliver a polypeptide to the intracellular environment such as via internalization, thereby causing the fused Bcl-G polypeptide to enter the cell.
- Vectors useful for expression in eukaryotic cells can include, for example, regulatory elements including the SV40 early promoter, the cytomegalovirus (CMV) promoter, the mouse mammary tumor virus (MMTV) steroid-inducible promoter, Moloney murine leukemia virus (MMLV) promoter, and the like.
- CMV cytomegalovirus
- MMTV mouse mammary tumor virus
- MMLV Moloney murine leukemia virus
- An anti-Bcl-G antibody, or antigen binding fragment of such an antibody is characterized by having specific binding activity for a Bcl-G polypeptide or a peptide portion thereof of at least about 1 x 10 5 M "1 .
- Fab, F(ab') 2 , Fd and Fv fragments of an anti-Bcl-G antibody, which retain specific binding activity for a Bcl-G polypeptide are included within the definition of an antibody.
- antibody as used herein includes naturally occurring antibodies as well as non-naturally occurring antibodies, including, for example, single chain antibodies, chimeric, bifunctional and humanized antibodies, as well as antigen-binding fragments thereof.
- non-naturally occurring antibodies can be constructed using solid phase peptide synthesis, can be produced recombinantly or can be obtained, for example, by screening combinatorial libraries consisting of variable heavy chains and variable light chains as described by Huse et al .
- the labeling means can be a fluorescent labeling agent that chemically binds to antibodies or antigens without denaturation to form a fluorochrome (dye) that is a useful immunofluorescent tracer.
- a fluorochrome a fluorochrome that is a useful immunofluorescent tracer.
- a description of immunofluorescent analytic techniques is found in DeLuca, "Immunofluorescence Analysis", in Antibody As a Tool, Marchalonis et al . , eds., John Wiley & Sons, Ltd., pp. 189-231 (1982), which is incorporated herein by reference.
- diagnostic systems preferably in kit form, comprising at least one invention nucleic acid or antibody in a suitable packaging material.
- the diagnostic kits containing nucleic acids are derived from the Bcl-G-encoding nucleic acids described herein.
- the diagnostic nucleic acids are derived from any of SEQ ID NOS:l, 3 or 41 and can be oligonucleotides of the invention.
- Invention diagnostic systems are useful for assaying for the presence or absence of nucleic acid encoding Bcl-G in either genomic DNA or mRNA.
- Bcl-G is located in a 600 kb region that has been previously determined to be frequently deleted in childhood ALL and other solid tumors (Baens et al . , supra , 1999) . Therefore, Bcl-G is located in a region deleted in ALL and can function as a tumor suppressor or as a marker for tumor suppressor activity.
- Bcl-2 family proteins such as Bcl-2, Bcl-X L , and Bak, contain a hydrophobic stretch of amino- acids near their carboxyl-terminus that anchors them in intracellular membranes of mitochondria, endoplasmic reticulum, or nuclear envelope (reviewed in Reed, J. C, Nature, 387:773-776 (1997); Adams & Cory, Science, 281:1322-1326 (1998); Gross et al . , Genes Dev., 13:1899- 1911 (1999)).
- This example describes loss of heterozygosity (LOH) associated with Bcl-G in ovarian cancer tissue.
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
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AU25784/01A AU2578401A (en) | 1999-12-14 | 2000-12-13 | Bcl-g polypeptides, encoding nucleic acids and methods of use |
JP2001544771A JP2003516744A (ja) | 1999-12-14 | 2000-12-13 | Bcl−gポリペプチド、それをコードする核酸および使用方法 |
EP00989249A EP1238080A2 (en) | 1999-12-14 | 2000-12-13 | Bcl-g polypeptides, encoding nucleic acids and methods of use |
CA002390662A CA2390662A1 (en) | 1999-12-14 | 2000-12-13 | Bcl-g polypeptides, encoding nucleic acids and methods of use |
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US46164199A | 1999-12-14 | 1999-12-14 | |
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WO2001044282A3 WO2001044282A3 (en) | 2002-02-21 |
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WO (1) | WO2001044282A2 (ja) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001057213A2 (en) * | 2000-02-04 | 2001-08-09 | Lexicon Genetics Incorporated | Human bcl-x-like proteins and polynucleotides encoding the same |
WO2005042582A1 (ja) * | 2003-11-04 | 2005-05-12 | Chugai Seiyaku Kabushiki Kaisha | 抗体の製造方法 |
WO2008023841A1 (en) * | 2006-08-25 | 2008-02-28 | Oncotherapy Science, Inc. | Breast cancer-associated gene, melk, and its interactions with bcl-g |
EP1691824B1 (en) * | 2003-11-19 | 2009-03-11 | Survac ApS | Proteins belonging to the bcl-2 family and fragments thereof, and their use in cancer patients |
US7687465B2 (en) | 2003-04-11 | 2010-03-30 | Kraeftens Bekaempelse | Therapeutic cancer vaccine |
US8030461B2 (en) | 2002-04-15 | 2011-10-04 | Chugai Seiyaku Kabushiki Kaisha | Methods for constructing scDb libraries |
US8337841B2 (en) | 2003-01-21 | 2012-12-25 | Chugai Seiyaku Kabushiki Kaisha | Methods of screening for antibody light chains |
US8597911B2 (en) | 2003-06-11 | 2013-12-03 | Chugai Seiyaku Kabushiki Kaisha | Process for producing antibodies |
US9670269B2 (en) | 2006-03-31 | 2017-06-06 | Chugai Seiyaku Kabushiki Kaisha | Methods of modifying antibodies for purification of bispecific antibodies |
US9777066B2 (en) | 2005-06-10 | 2017-10-03 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical compositions containing sc(Fv)2 |
US10011858B2 (en) | 2005-03-31 | 2018-07-03 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing polypeptides by regulating polypeptide association |
US11124576B2 (en) | 2013-09-27 | 2021-09-21 | Chungai Seiyaku Kabushiki Kaisha | Method for producing polypeptide heteromultimer |
US11649262B2 (en) | 2015-12-28 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for promoting efficiency of purification of Fc region-containing polypeptide |
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US9493569B2 (en) | 2005-03-31 | 2016-11-15 | Chugai Seiyaku Kabushiki Kaisha | Structural isomers of sc(Fv)2 |
EP1908482B1 (en) | 2005-06-10 | 2017-09-06 | Chugai Seiyaku Kabushiki Kaisha | Stabilizer for protein preparation comprising meglumine and use thereof |
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- 2000-12-13 CA CA002390662A patent/CA2390662A1/en not_active Abandoned
- 2000-12-13 WO PCT/US2000/033793 patent/WO2001044282A2/en not_active Application Discontinuation
- 2000-12-13 AU AU25784/01A patent/AU2578401A/en not_active Abandoned
- 2000-12-13 JP JP2001544771A patent/JP2003516744A/ja active Pending
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WO2001057213A3 (en) * | 2000-02-04 | 2002-02-21 | Lexicon Genetics Inc | Human bcl-x-like proteins and polynucleotides encoding the same |
WO2001057213A2 (en) * | 2000-02-04 | 2001-08-09 | Lexicon Genetics Incorporated | Human bcl-x-like proteins and polynucleotides encoding the same |
US8030461B2 (en) | 2002-04-15 | 2011-10-04 | Chugai Seiyaku Kabushiki Kaisha | Methods for constructing scDb libraries |
US8337841B2 (en) | 2003-01-21 | 2012-12-25 | Chugai Seiyaku Kabushiki Kaisha | Methods of screening for antibody light chains |
US7687465B2 (en) | 2003-04-11 | 2010-03-30 | Kraeftens Bekaempelse | Therapeutic cancer vaccine |
US8597911B2 (en) | 2003-06-11 | 2013-12-03 | Chugai Seiyaku Kabushiki Kaisha | Process for producing antibodies |
WO2005042582A1 (ja) * | 2003-11-04 | 2005-05-12 | Chugai Seiyaku Kabushiki Kaisha | 抗体の製造方法 |
EP1691824B1 (en) * | 2003-11-19 | 2009-03-11 | Survac ApS | Proteins belonging to the bcl-2 family and fragments thereof, and their use in cancer patients |
US7842294B2 (en) | 2003-11-19 | 2010-11-30 | Survac Aps | Proteins belonging to the Bcl-2 family and fragments thereof, and their use in cancer patients |
US10011858B2 (en) | 2005-03-31 | 2018-07-03 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing polypeptides by regulating polypeptide association |
US11168344B2 (en) | 2005-03-31 | 2021-11-09 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing polypeptides by regulating polypeptide association |
US9777066B2 (en) | 2005-06-10 | 2017-10-03 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical compositions containing sc(Fv)2 |
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US10934344B2 (en) | 2006-03-31 | 2021-03-02 | Chugai Seiyaku Kabushiki Kaisha | Methods of modifying antibodies for purification of bispecific antibodies |
WO2008023841A1 (en) * | 2006-08-25 | 2008-02-28 | Oncotherapy Science, Inc. | Breast cancer-associated gene, melk, and its interactions with bcl-g |
US11124576B2 (en) | 2013-09-27 | 2021-09-21 | Chungai Seiyaku Kabushiki Kaisha | Method for producing polypeptide heteromultimer |
US11649262B2 (en) | 2015-12-28 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for promoting efficiency of purification of Fc region-containing polypeptide |
Also Published As
Publication number | Publication date |
---|---|
EP1238080A2 (en) | 2002-09-11 |
CA2390662A1 (en) | 2001-06-21 |
JP2003516744A (ja) | 2003-05-20 |
WO2001044282A3 (en) | 2002-02-21 |
AU2578401A (en) | 2001-06-25 |
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