CA2707726C - Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease - Google Patents
Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease Download PDFInfo
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- CA2707726C CA2707726C CA2707726A CA2707726A CA2707726C CA 2707726 C CA2707726 C CA 2707726C CA 2707726 A CA2707726 A CA 2707726A CA 2707726 A CA2707726 A CA 2707726A CA 2707726 C CA2707726 C CA 2707726C
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- 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
- C07K14/525—Tumour necrosis factor [TNF]
-
- 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
- C07K14/525—Tumour necrosis factor [TNF]
- C07K14/5255—Lymphotoxin [LT]
-
- 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
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3214596P | 1996-12-09 | 1996-12-09 | |
| US60/032,145 | 1996-12-09 | ||
| US08/982,272 | 1997-12-01 | ||
| US08/982,272 US7070771B1 (en) | 1996-12-09 | 1997-12-01 | Methods of expressing chimeric mouse and human CD40 ligand in human CD40+ cells |
| CA2274498A CA2274498C (en) | 1996-12-09 | 1997-12-08 | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2274498A Division CA2274498C (en) | 1996-12-09 | 1997-12-08 | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2707726A1 CA2707726A1 (en) | 1998-06-18 |
| CA2707726C true CA2707726C (en) | 2013-10-22 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2707726A Expired - Fee Related CA2707726C (en) | 1996-12-09 | 1997-12-08 | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
| CA2274498A Expired - Fee Related CA2274498C (en) | 1996-12-09 | 1997-12-08 | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2274498A Expired - Fee Related CA2274498C (en) | 1996-12-09 | 1997-12-08 | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
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| Country | Link |
|---|---|
| US (3) | US7070771B1 (https=) |
| EP (4) | EP1806360A3 (https=) |
| JP (1) | JP4015201B2 (https=) |
| CN (1) | CN1221662C (https=) |
| AT (2) | ATE420956T1 (https=) |
| AU (1) | AU5795798A (https=) |
| BR (1) | BR9714004A (https=) |
| CA (2) | CA2707726C (https=) |
| DE (1) | DE69739220D1 (https=) |
| DK (1) | DK0948614T3 (https=) |
| ES (1) | ES2321246T3 (https=) |
| IL (3) | IL130247A0 (https=) |
| NO (2) | NO327411B1 (https=) |
| NZ (1) | NZ336092A (https=) |
| PT (1) | PT948614E (https=) |
| WO (1) | WO1998026061A2 (https=) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7070771B1 (en) * | 1996-12-09 | 2006-07-04 | Regents Of The University Of California | Methods of expressing chimeric mouse and human CD40 ligand in human CD40+ cells |
| JP2003508016A (ja) * | 1999-04-16 | 2003-03-04 | エフ．ホフマン−ラ ロシュ アーゲー | Ｃｄ４０／ｃｄ４０ｌキメラポリペプチドをコードする核酸、それらの生成方法及びそれらの使用 |
| GB9917180D0 (en) * | 1999-07-23 | 1999-09-22 | Univ Sheffield | Cell surface receptor |
| GB0025307D0 (en) * | 2000-10-16 | 2000-11-29 | Celltech Chiroscience Ltd | Biological products |
| AU2002221780A1 (en) * | 2000-10-31 | 2002-05-15 | F.Hoffmann-La Roche Ag | Nucleic acids encoding cd40/cd40l chimeric polypeptides, methods for their production and uses thereof |
| US7786282B2 (en) * | 2001-12-06 | 2010-08-31 | The Regents Of The University Of California | Nucleic acid molecules encoding TNF-α ligand polypeptides having a CD154 domain |
| EP1478390A2 (en) * | 2002-02-25 | 2004-11-24 | Isis Innovation Limited | Novel complexes for inducing an immune response |
| US7495090B2 (en) * | 2002-05-23 | 2009-02-24 | The Regents Of The University Of California | Nucleic acids encoding chimeric CD154 polypeptides |
| US7435596B2 (en) | 2004-11-04 | 2008-10-14 | St. Jude Children's Research Hospital, Inc. | Modified cell line and method for expansion of NK cell |
| US20130266551A1 (en) | 2003-11-05 | 2013-10-10 | St. Jude Children's Research Hospital, Inc. | Chimeric receptors with 4-1bb stimulatory signaling domain |
| US20080044393A1 (en) * | 2004-07-16 | 2008-02-21 | White Robert L | Retinal dystrophin transgene and methods of use thereof |
| WO2008109825A2 (en) * | 2007-03-08 | 2008-09-12 | Mayo Foundation For Medical Education And Research | Inducing immune-mediated tumor cell death |
| US20100050276A1 (en) * | 2008-08-22 | 2010-02-25 | Brown University | Transgenic non-human animal models of apoptosis-mediated conditions |
| WO2013083254A1 (en) | 2011-12-09 | 2013-06-13 | Bavarian Nordic A/S | Poxvirus vector for the expression of bacterial antigens linked to tetanus toxin fragment c |
| PL2908865T3 (pl) * | 2012-10-17 | 2019-08-30 | Vascular Biogenics Ltd. | Adenowirus wykazujący ekspresję chimery Fas i jego zastosowanie w sposobach leczenia raka |
| WO2015148879A1 (en) * | 2014-03-27 | 2015-10-01 | The Regents Of The University Of Michigan | Cancer immunotherapy compositions and methods |
| DK3143134T3 (da) | 2014-05-15 | 2021-01-04 | Nat Univ Singapore | Modificerede, naturlige dræberceller og anvendelser deraf |
| CN105567679B (zh) * | 2014-10-10 | 2019-07-05 | 深圳市北科生物科技有限公司 | 可分泌型trail蛋白构建物和表达载体 |
| US20180244750A1 (en) | 2015-11-02 | 2018-08-30 | Memgen, Llc | Methods for treatment of cancer |
| US11298420B2 (en) | 2016-12-21 | 2022-04-12 | Memgen, Llc | Armed oncolytic viruses |
| BR112019019917A2 (pt) | 2017-03-27 | 2020-04-22 | Nat Univ Singapore | receptores quiméricos nkg2d truncados e seus usos em imunoterapia de células exterminadoras naturais |
| WO2018191369A1 (en) | 2017-04-12 | 2018-10-18 | Memgen, Llc | Methods of cd40 and toll like receptor immune activation |
| EP3749685A4 (en) | 2018-02-09 | 2021-12-22 | National University of Singapore | ACTIVATOR CHEMERIC RECEPTORS AND THEIR USES IN NATURAL KILLING CELL IMMUNOTHERAPY |
| JP7334985B2 (ja) | 2018-04-02 | 2023-08-29 | ナショナル ユニヴァーシティー オブ シンガポール | 免疫細胞で発現される膜結合抗サイトカイン非シグナル伝達バインダーによるヒトサイトカインの中和 |
| EP3844186A4 (en) | 2018-08-29 | 2022-08-17 | National University of Singapore | METHOD OF SPECIFIC STIMULATION OF SURVIVAL AND EXPANSION OF GENETICALLY MODIFIED IMMUNE CELLS |
| CA3120563A1 (en) | 2018-11-26 | 2020-06-04 | Nkarta, Inc. | Methods for the simultaneous expansion of multiple immune cell types, related compositions and uses of same in cancer immunotherapy |
| EP3773918A4 (en) | 2019-03-05 | 2022-01-05 | Nkarta, Inc. | CD19 DIRECTED CHIMERIC ANTIGEN RECEPTORS AND THEIR USES IN IMMUNOTHERAPY |
| CN112725379B (zh) * | 2021-01-27 | 2024-08-13 | 上海南方模式生物科技股份有限公司 | 人源化cd40基因改造动物模型的构建方法及应用 |
| US11585330B1 (en) * | 2021-09-29 | 2023-02-21 | Halliburton Energy Services, Inc. | Flow control for geothermal well |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3750056T2 (de) | 1986-06-20 | 1995-04-06 | Dainippon Pharmaceutical Co | Polypeptid-Mutanten des menschlichen TNF und für diese Mutanten codierende DNS. |
| ATE87007T1 (de) | 1987-05-29 | 1993-04-15 | Sagami Chem Res | Fusionsprotein, enthaltend lymphotoxin. |
| AU5940090A (en) | 1989-08-16 | 1991-04-03 | Cetus Oncology Corporation | Compositions for the inhibition of protein hormone formation and uses thereof |
| US5519119A (en) | 1990-09-21 | 1996-05-21 | Ishihara Sangyo Kaisha Ltd. | Muteins of TNF pharmaceutical compositions and a method of making |
| CA2055168A1 (en) | 1990-11-21 | 1992-05-22 | Walter Fiers | Tnf-muteins |
| ES2198025T3 (es) | 1991-10-25 | 2004-01-16 | Immunex Corporation | Anticuerpos contra cd40-l. |
| ATE242322T1 (de) | 1992-03-30 | 2003-06-15 | Immunex Corp | Fusionsprotein , das zwei rezeptoren des tumornekrose-faktors enthält |
| SK376492A3 (en) | 1992-04-02 | 1995-06-07 | Hoffmann La Roche | Tnf - muteins and method of their production |
| ATE311895T1 (de) | 1992-05-26 | 2005-12-15 | Immunex Corp | Neue zytokine die cd30 binden |
| AU5098493A (en) | 1992-08-21 | 1994-03-15 | Schering Corporation | Cd40 ligand, anti cd40 antibodies, and soluble cd40 |
| WO1994004680A1 (en) | 1992-08-21 | 1994-03-03 | Schering Corporation | Human interleukin-13 |
| US5540926A (en) | 1992-09-04 | 1996-07-30 | Bristol-Myers Squibb Company | Soluble and its use in B cell stimulation |
| US5573924A (en) | 1992-09-08 | 1996-11-12 | Immunex Corporation | CD27 ligand |
| US5565321A (en) | 1993-01-22 | 1996-10-15 | Immunex Corporation | Detection of mutations in a CD40 ligand gene |
| AU677995B2 (en) | 1993-01-22 | 1997-05-15 | Immunex Corporation | Detection and treatment of mutations in a CD40 ligand gene |
| US5830463A (en) | 1993-07-07 | 1998-11-03 | University Technology Corporation | Yeast-based delivery vehicles |
| US5861310A (en) * | 1993-11-03 | 1999-01-19 | Dana-Farber Cancer Institute | Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor |
| JPH08127594A (ja) | 1993-11-10 | 1996-05-21 | Mochida Pharmaceut Co Ltd | Ｆａｓ抗原に結合する新規蛋白質およびそれをコードするＤＮＡ |
| WO1995014487A1 (en) * | 1993-11-24 | 1995-06-01 | The Australian National University | Treatment of viral disease with cd40l peptide |
| ES2222463T3 (es) | 1993-12-23 | 2005-02-01 | Immunex Corporation | Uso de anticuerpos monoclonales o ligandos oligomericos solubles en la fabricacion de un medicamento para la prevencion o tratamiento de trastornos neoplasicos. |
| ATE387458T1 (de) | 1994-01-07 | 2008-03-15 | Mochida Pharm Co Ltd | Fas-antigenbindender ligand |
| ATE309267T1 (de) | 1994-04-28 | 2005-11-15 | Boehringer Ingelheim Pharma | Methode zur proliferation und differenzierung von b-zellen und verwendungen dafür |
| US5606023A (en) | 1994-05-24 | 1997-02-25 | Thomas Jefferson University | Mutant tumor necrosis factor proteins |
| US5759536A (en) | 1994-05-27 | 1998-06-02 | University Technology Corporation | Use of fas ligand to supress T-lymphocyte-mediated immune responses |
| AU3111995A (en) | 1994-07-22 | 1996-02-22 | F. Hoffmann-La Roche Ag | Pharmaceutical compositions comprising a chimaeric tnf binding protein |
| GB9425060D0 (en) | 1994-12-13 | 1995-02-08 | Univ Birmingham | Carcinoma treatment |
| US5888764A (en) * | 1995-01-20 | 1999-03-30 | Uab Research Foundation | Human fas gene promoter region |
| US6017527A (en) * | 1996-07-10 | 2000-01-25 | Immunex Corporation | Activated dendritic cells and methods for their activation |
| US6544523B1 (en) | 1996-11-13 | 2003-04-08 | Chiron Corporation | Mutant forms of Fas ligand and uses thereof |
| US7070771B1 (en) * | 1996-12-09 | 2006-07-04 | Regents Of The University Of California | Methods of expressing chimeric mouse and human CD40 ligand in human CD40+ cells |
| US6016832A (en) * | 1997-04-16 | 2000-01-25 | Woodward Governor Company | Valve for controlling gas mass flow |
| ATE460482T1 (de) | 1997-09-17 | 2010-03-15 | Mochida Pharm Co Ltd | Fas-liganden derivate |
| US7786282B2 (en) * | 2001-12-06 | 2010-08-31 | The Regents Of The University Of California | Nucleic acid molecules encoding TNF-α ligand polypeptides having a CD154 domain |
| US7495090B2 (en) * | 2002-05-23 | 2009-02-24 | The Regents Of The University Of California | Nucleic acids encoding chimeric CD154 polypeptides |
| GB2392158B (en) * | 2002-08-21 | 2005-02-16 | Proimmune Ltd | Chimeric MHC protein and oligomer thereof |
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1997
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- 1997-12-08 EP EP06125424A patent/EP1806360A3/en not_active Ceased
- 1997-12-08 CN CNB971816743A patent/CN1221662C/zh not_active Expired - Fee Related
- 1997-12-08 ES ES97954089T patent/ES2321246T3/es not_active Expired - Lifetime
- 1997-12-08 EP EP09164341A patent/EP2145958B1/en not_active Expired - Lifetime
- 1997-12-08 DE DE69739220T patent/DE69739220D1/de not_active Expired - Lifetime
- 1997-12-08 CA CA2707726A patent/CA2707726C/en not_active Expired - Fee Related
- 1997-12-08 IL IL13024797A patent/IL130247A0/xx active IP Right Grant
- 1997-12-08 PT PT97954089T patent/PT948614E/pt unknown
- 1997-12-08 EP EP97954089A patent/EP0948614B1/en not_active Expired - Lifetime
- 1997-12-08 BR BR9714004-0A patent/BR9714004A/pt not_active IP Right Cessation
- 1997-12-08 AU AU57957/98A patent/AU5795798A/en not_active Abandoned
- 1997-12-08 DK DK97954089T patent/DK0948614T3/da active
- 1997-12-08 NZ NZ336092A patent/NZ336092A/en not_active IP Right Cessation
- 1997-12-08 JP JP52695698A patent/JP4015201B2/ja not_active Expired - Fee Related
- 1997-12-08 WO PCT/US1997/022740 patent/WO1998026061A2/en not_active Ceased
- 1997-12-08 EP EP10184082A patent/EP2287309A1/en not_active Withdrawn
- 1997-12-08 CA CA2274498A patent/CA2274498C/en not_active Expired - Fee Related
- 1997-12-08 AT AT97954089T patent/ATE420956T1/de not_active IP Right Cessation
- 1997-12-08 AT AT09164341T patent/ATE547524T1/de active
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1999
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2004
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2006
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2007
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2009
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