JP2001500372A - 独特の髄膜炎菌性bエピトープを規定するモノクローナル抗体およびワクチン組成物の調製におけるそれらの使用 - Google Patents
独特の髄膜炎菌性bエピトープを規定するモノクローナル抗体およびワクチン組成物の調製におけるそれらの使用Info
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- JP2001500372A JP2001500372A JP10511915A JP51191598A JP2001500372A JP 2001500372 A JP2001500372 A JP 2001500372A JP 10511915 A JP10511915 A JP 10511915A JP 51191598 A JP51191598 A JP 51191598A JP 2001500372 A JP2001500372 A JP 2001500372A
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Classifications
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- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
- C07K16/1217—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Neisseriaceae (F)
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria
- G01N2333/22—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Neisseriaceae (F), e.g. Acinetobacter
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/807—Hapten conjugated with peptide or protein
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/808—Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products
Landscapes
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- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.Neisseria meningitidis血清型B莢膜ポリサッカライド誘導体に対する単離 された抗体であって、自己反応性ではない、抗体。 2.前記抗体が、ELISAにおいてNeisseria meningitidis血清型B莢膜ポリサッ カライド(MenB PS)と交差反応しない、請求項1に記載の抗体。 3.前記抗体が、Neisseria meningitidis血清型B生物に対する機能活性を示す 、請求項1に記載の抗体。 4.前記抗体が、モノクローナル抗体である、請求項1に記載の抗体。 5.請求項1に記載の抗体によって結合され得る、独特のNeisseria meningitid is血清型Bエピトープ。 6.請求項2に記載の抗体によって結合され得る、独特のNeisseria meningitid is血清型Bエピトープ。 7.請求項3に記載の抗体によって結合され得る、独特のNeisseria meningitid is血清型Bエピトープ。 8.請求項4に記載の抗体によって結合され得る、独特のNeisseria meningitid is血清型Bエピトープ。 9.請求項4に記載のモノクローナル抗体を産生するハイブリドーマ。 10.SEAM-2(ATCC番号CRL-12380)、SEAM-3(ATCC番号HB-12170)、SEAM−12 (ATCC番号HB-12169)、およびSEAM-18(ATCC番号CRL-12381)からなる群から選 択されるハイブリドーマ細胞株を同定する特徴を有する、請求項9に記載のハイ ブリドーマ。 11.Neisseria meningitidis血清型B(MenB)の独特のエピトープの分子模倣 物を単離するための方法であって、以下: (a)MenBの独特のエピトープの推定分子模倣物を含む分子の集団を提供する 工程; (b)該分子模倣物が存在する場合には、請求項1に記載の抗体と該分子模倣 物との間の免疫学的結合を可能にする条件下で、該分子の集団を該抗体と接触さ せて複合体を提供する工程;および (c)非結合分子から該複合体を分離する工程、 を包含する、方法。 12.前記分子の集団が、ペプトイドライブラリーを含む、請求項11に記載の 方法。 13.前記分子の集団が、ペプチドライブラリーを含む、請求項11に記載の方 法。 14.前記分子の集団が、ファージディスプレイライブラリーを含む、請求項1 1に記載の方法。 15.請求項11に記載の方法を用いて単離される、Neisseria meningitidis血 清型B(MenB)の独特のエピトープの分子模倣物。 16.請求項1に記載の抗体分子を用いて産生される抗イディオタイプ抗体分子 から構成される、Neisseria meningitidis血清型B(MenB)の独特のエピトープ の分子模倣物。 17.Neisseria meningitidis血清型B(MenB)の独特のエピトープの分子模倣 物であって、配列番号1〜66、および配列番号67からなる群から選択される配列 に実質的に相同であるアミノ酸配列を有するペプチドから構成される、分子模倣 物。 18.前記模倣物が、配列番号8に実質的に相同であるアミノ酸配列を有するペ プチドから構成される、請求項17に記載の模倣物。 19.Neisseria meningitidis血清型B(MenB)の独特のエピトープを、薬学的 に受容可能な賦形剤と組み合わせて含む、ワクチン組成物。 20.Neisseria meningitidis血清型B(MenB)の独特のエピトープの分子模倣 物を、薬学的に受容可能な賦形剤と組み合わせて含む、ワクチン組成物。 21.前記分子模倣物が、抗イディオタイプ抗体分子を含む、請求項20に記載 のワクチン組成物。 22.前記分子模倣物が、核酸分子を含む、請求項20に記載のワクチン組成物 。 23.前記分子模倣物が、ペプチド分子を含む、請求項20に記載のワクチン組 成物。 24.前記ペプチド分子が、配列番号1〜66、および配列番号67からなる群から 選択される配列に実質的に相同であるアミノ酸配列を有する、請求項23に記載 のワクチン組成物。 25.前記エピトープが、キャリア分子に共有結合している、請求項19に記載 のワクチン組成物。 26.前記分子模倣物が、キャリア分子に共有結合している、請求項20に記載 のワクチン組成物。 27.前記ペプチド分子が、キャリア分子に共有結合している、請求項23に記 載のワクチン組成物。 28.アジュバントをさらに含む、請求項19に記載のワクチン組成物。 29.アジュバントをさらに含む、請求項20に記載のワクチン組成物。 30.哺乳動物被験体において、Neisseria meningitidis血清型Bおよび/また はE.coli K1疾患を予防するための方法であって、該被験体に請求項19に記載 のワクチンの有効量を投与する工程を包含する、方法。 31.哺乳動物被験体において、Neisseria meningitidis血清型Bおよび/また はE.coli K1疾患を予防するための方法であって、該被験体に請求項20に記載 のワクチンの有効量を投与する工程を包含する、方法。 32.哺乳動物被験体において、Neisseria meningitidis血清型Bおよび/また はE.coli K1疾患を予防するための方法であって、該被験体に請求項23に記載 のワクチンの有効量を投与する工程を包含する、方法。 33.請求項1に記載の抗体を、薬学的に受容可能なビヒクルと組み合わせて含 む、薬学的組成物。 34.哺乳動物被験体において、Neisseria meningitidis血清型Bおよび/また はE.coli K1疾患を処置または予防するための方法であって、該被験体に請求項 33に記載の薬学的組成物の有効量を投与する工程を包含する、方法。
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US2579996P | 1996-08-27 | 1996-08-27 | |
US60/025,799 | 1996-08-27 | ||
PCT/US1997/015167 WO1998008874A1 (en) | 1996-08-27 | 1997-08-27 | Monoclonal antibodies that define unique meningococcal b epitopes and their use in the preparation of vaccine compositions |
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JP2007221879A Division JP2008044947A (ja) | 1996-08-27 | 2007-08-28 | 独特の髄膜炎菌性bエピトープを規定するモノクローナル抗体およびワクチン組成物の調製におけるそれらの使用 |
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JP2001500372A true JP2001500372A (ja) | 2001-01-16 |
JP2001500372A5 JP2001500372A5 (ja) | 2005-04-07 |
JP4150082B2 JP4150082B2 (ja) | 2008-09-17 |
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JP51191598A Expired - Fee Related JP4150082B2 (ja) | 1996-08-27 | 1997-08-27 | 独特の髄膜炎菌性bエピトープを規定するモノクローナル抗体およびワクチン組成物の調製におけるそれらの使用 |
JP2007221879A Withdrawn JP2008044947A (ja) | 1996-08-27 | 2007-08-28 | 独特の髄膜炎菌性bエピトープを規定するモノクローナル抗体およびワクチン組成物の調製におけるそれらの使用 |
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US (4) | US6048527A (ja) |
EP (1) | EP0922059B1 (ja) |
JP (2) | JP4150082B2 (ja) |
AT (1) | ATE252602T1 (ja) |
CA (1) | CA2264585C (ja) |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006516186A (ja) * | 2002-10-16 | 2006-06-29 | サントル ナショナル ドゥ ラ ルシェルシュ シアンティフィク | NCAM機能を調節するためのポリ−α2,8−シアル酸模倣ペプチドの使用 |
JP2009525947A (ja) * | 2005-12-23 | 2009-07-16 | チルドレンズ ホスピタル アンド リサーチ センター アット オークランド | 脱アセチル化シアル酸抗原、これに対する抗体、及び癌療法における使用方法。 |
JP2010532389A (ja) * | 2007-07-03 | 2010-10-07 | チルドレンズ ホスピタル アンド リサーチ センター アット オークランド | ポリシアル酸誘導体、製造方法、ならびにがん抗原産生の増強およびターゲティングにおける使用 |
US9089513B2 (en) | 2004-06-23 | 2015-07-28 | Children's Hospital & Research Center Oakland | De-N-acetyl sialic acid antigens, antibodies thereto, and methods of use in cancer therapy |
Families Citing this family (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9422096D0 (en) * | 1994-11-02 | 1994-12-21 | Biocine Spa | Combined meningitis vaccine |
WO2002064091A2 (en) * | 2001-02-13 | 2002-08-22 | Palatin Technologies, Inc. | Melanocortin metallopeptides for treatment of sexual dysfunction |
US5811102A (en) * | 1995-06-07 | 1998-09-22 | National Research Council Of Canada | Modified meningococcal polysaccharide conjugate vaccines |
ATE252602T1 (de) * | 1996-08-27 | 2003-11-15 | Chiron Corp | Meningokokkus b-epitop ausbildende monoklonale antikoerper und deren verwendung zur herstellung von impfstoffzusammenstellungen |
CA2264735C (en) * | 1996-08-27 | 2008-01-29 | Chiron Corporation | Neisseria meningitidis serogroup b glycoconjugates and methods of using the same |
PT1007546E (pt) | 1997-08-27 | 2009-04-24 | Childrens Hosp & Res Ct Oak | Compostos miméticos moleculares de epítopos de meningococos do serogrupo b |
GB9823835D0 (en) * | 1998-10-30 | 1998-12-23 | Univ London | Component for vaccine |
EP1141375A4 (en) * | 1998-12-14 | 2002-06-05 | Palatin Technologies Inc | COMBINATIONAL LIBRARIES OF METAL OPEPTIDES AND THEIR USE |
US7033748B2 (en) * | 1999-08-06 | 2006-04-25 | Ivigene Corporation | Identification of microbial polynucleotides expressed during infection of a host |
EP1238102B1 (en) | 1999-08-06 | 2008-11-12 | Oragenics, Inc. | Microbial polynucleotides expressed during infection of a host |
US7049398B1 (en) * | 1999-08-12 | 2006-05-23 | Palatin Technologies, Inc. | Melanocortin metallopeptide constructs, combinatorial libraries and applications |
US6838553B1 (en) * | 1999-10-05 | 2005-01-04 | Academia Sinica | Peptide repeat immunogens |
US7189405B1 (en) * | 1999-10-29 | 2007-03-13 | Rice Peter A | Peptide mimics of conserved gonococcal epitopes and methods and compositions using them |
WO2001036006A1 (en) * | 1999-11-19 | 2001-05-25 | Palatin Technologies, Inc. | Opioid metallopeptide compositions and methods |
ES2507100T3 (es) * | 2000-01-17 | 2014-10-14 | Novartis Vaccines And Diagnostics S.R.L. | Vacuna OMV suplementada contra meningococo |
GB0024200D0 (en) * | 2000-10-03 | 2000-11-15 | Smithkline Beecham Sa | Component vaccine |
US7385025B2 (en) * | 2000-12-19 | 2008-06-10 | Palatin Technologies, Inc. | Metallopeptide compounds |
US20020131953A1 (en) * | 2001-03-14 | 2002-09-19 | Ut Southwestern Medical Center | In situ langerhans cell vaccine |
JP2004529643A (ja) * | 2001-04-17 | 2004-09-30 | カイロン コーポレイション | 機能活性抗体を誘発する髄膜炎菌性bエピトープの分子模倣物 |
MX339524B (es) | 2001-10-11 | 2016-05-30 | Wyeth Corp | Composiciones inmunogenicas novedosas para la prevencion y tratamiento de enfermedad meningococica. |
WO2003089473A1 (en) * | 2002-04-19 | 2003-10-30 | Yonsei University | Vaccine composition for preventing meningococcal disease |
MXPA05014015A (es) * | 2003-06-23 | 2006-03-17 | Baxter Int | Vacunas contra grupo y nisseria meningitidis y combinaciones meningococales del mismo. |
AR048840A1 (es) * | 2004-05-11 | 2006-05-31 | Boehringer Ingelheim Int | Epitopes inductores de la muerte de las celulas t |
RU2404995C2 (ru) * | 2004-06-23 | 2010-11-27 | Чилдрен'С Хоспитал Энд Рисерч Сентер Эт Окленд | Производные полисахаридов и их применение для индуцирования иммунной реакции |
US8052971B2 (en) * | 2005-11-21 | 2011-11-08 | MG Biologics | Oral use of specific antibodies for intestinal health |
WO2007070372A2 (en) * | 2005-12-09 | 2007-06-21 | Entremed, Inc. | Compositions and methods for inhibiting cellular proliferation |
AR058736A1 (es) * | 2005-12-29 | 2008-02-20 | Ct Ingenieria Genetica Biotech | Peptidos mimeticos de carbohidratos y su empleo en formulaciones farmaceuticas |
WO2007084856A2 (en) * | 2006-01-13 | 2007-07-26 | Baxter International Inc. | Method for purifying polysaccharides |
GB0606155D0 (en) * | 2006-03-28 | 2006-05-10 | Liverpool School Of Tropical M | Bacterial vaccine |
WO2007116409A2 (en) * | 2006-04-11 | 2007-10-18 | Yeda Research And Development Co. Ltd. At The Weizmann Institute Of Science | Improved vaccines comprising multimeric hsp60 peptide carriers |
GB0611914D0 (en) * | 2006-06-15 | 2006-07-26 | Teti Giuseppe | Peptides that mimic non-human cross-reactive protective epitopes of the group Bmeningococcal capsulsar polysaccharide |
AR064642A1 (es) | 2006-12-22 | 2009-04-15 | Wyeth Corp | Polinucleotido vector que lo comprende celula recombinante que comprende el vector polipeptido , anticuerpo , composicion que comprende el polinucleotido , vector , celula recombinante polipeptido o anticuerpo , uso de la composicion y metodo para preparar la composicion misma y preparar una composi |
ES2621359T3 (es) * | 2007-06-20 | 2017-07-03 | Pfizer Ireland Pharmaceuticals | Polisacáridos modificados para vacunas conjugadas |
JP5702600B2 (ja) | 2007-07-03 | 2015-04-15 | チルドレンズ ホスピタル アンド リサーチ センター アット オークランド | オリゴシアル酸誘導体、製造方法および免疫学的使用 |
AU2008272854B2 (en) * | 2007-07-03 | 2014-03-13 | Children's Hospital & Research Center At Oakland | Inhibitors of polysialic acid de-N-acetylase and methods for using the same |
US8067730B2 (en) | 2007-07-20 | 2011-11-29 | The George Washington University | Laser ablation electrospray ionization (LAESI) for atmospheric pressure, In vivo, and imaging mass spectrometry |
US20100285446A1 (en) * | 2007-07-20 | 2010-11-11 | Akos Vertes | Methods for Detecting Metabolic States by Laser Ablation Electrospray Ionization Mass Spectrometry |
US7960336B2 (en) | 2007-08-03 | 2011-06-14 | Pharmain Corporation | Composition for long-acting peptide analogs |
US8563527B2 (en) * | 2007-08-20 | 2013-10-22 | Pharmain Corporation | Oligonucleotide core carrier compositions for delivery of nucleic acid-containing therapeutic agents, methods of making and using the same |
US20090156459A1 (en) * | 2007-11-16 | 2009-06-18 | Pharmain Corporation | Cationic-Core Carrier Compositions for Delivery of Therapeutic Agents, Methods of Making and Using the Same |
US20110014226A1 (en) * | 2008-03-18 | 2011-01-20 | Caulfield Michael J | high throughput protein interaction assay |
AR077636A1 (es) * | 2009-07-08 | 2011-09-14 | Abbott Biologicals Bv | Vacuna viral y uso de la misma |
PT3246044T (pt) | 2010-08-23 | 2021-02-15 | Wyeth Llc | Formulações estáveis de antigénios de rlp2086 de neisseria meningitidis |
NZ607224A (en) | 2010-09-10 | 2014-11-28 | Wyeth Llc | Non-lipidated variants of neisseria meningitidis orf2086 antigens |
WO2012054879A1 (en) * | 2010-10-22 | 2012-04-26 | Duke University | Compositions and methods for the treatment of septic arthritis, osteomyelitis, and bacteremia |
JP2014524121A (ja) | 2011-07-14 | 2014-09-18 | ザ・ジョージ・ワシントン・ユニバーシティ | レーザアブレーション・エレクトロスプレイイオン化質量分析用のプルームコリメーション |
WO2013132040A2 (en) * | 2012-03-08 | 2013-09-12 | Novartis Ag | In vitro potency assay for protein-based meningococcal vaccines |
SA115360586B1 (ar) | 2012-03-09 | 2017-04-12 | فايزر انك | تركيبات لعلاج الالتهاب السحائي البكتيري وطرق لتحضيرها |
NZ628449A (en) | 2012-03-09 | 2016-04-29 | Pfizer | Neisseria meningitidis compositions and methods thereof |
US9802987B2 (en) | 2013-03-08 | 2017-10-31 | Pfizer Inc. | Immunogenic fusion polypeptides |
US9770504B2 (en) * | 2013-05-03 | 2017-09-26 | The Board Of Regents Of The University Of Texas System | Generating peptoid vaccines |
EP4098276A1 (en) | 2013-09-08 | 2022-12-07 | Pfizer Inc. | Neisseria meningitidis compositions and methods thereof |
KR20170103009A (ko) | 2015-02-19 | 2017-09-12 | 화이자 인코포레이티드 | 나이세리아 메닌지티디스 조성물 및 그의 방법 |
CN118021947A (zh) | 2017-01-31 | 2024-05-14 | 辉瑞大药厂 | 脑膜炎奈瑟菌组合物及其使用方法 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4356170A (en) | 1981-05-27 | 1982-10-26 | Canadian Patents & Development Ltd. | Immunogenic polysaccharide-protein conjugates |
DE3483957D1 (de) * | 1983-11-21 | 1991-02-21 | Wellcome Found | Komplexe, verfahren zu ihrer herstellung und dieselben enthaltende formulierungen. |
US4727136A (en) * | 1985-10-01 | 1988-02-23 | Canadian Patents And Development Ltd. | Modified meningococcal group B polysaccharide for conjugate vaccine |
US4970070A (en) * | 1986-02-07 | 1990-11-13 | Genetic Systems Corporation | Protective monoclonal antibody compositions for infections due to group B streptococcus |
AU640118B2 (en) * | 1988-12-19 | 1993-08-19 | De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn, Volksgezonheid En Cultuur | Meningococcal class 1 outer-membrane protein vaccine |
SU1708846A1 (ru) * | 1989-11-22 | 1992-01-30 | Научно-исследовательский институт вакцин и сывороток им.И.И.Мечникова | Штамм бактерий NeISSeRIa меNINGIтIDIS серогруппы В - продуцент капсульного полисахарида и полисахаридно-белкового комплекса |
HU218146B (hu) * | 1989-12-14 | 2000-06-28 | National Research Council Of Canada | Továbbfejlesztett meningokokkusz-poliszacharid-konjugátum vakcina |
GB9422096D0 (en) * | 1994-11-02 | 1994-12-21 | Biocine Spa | Combined meningitis vaccine |
US5811102A (en) | 1995-06-07 | 1998-09-22 | National Research Council Of Canada | Modified meningococcal polysaccharide conjugate vaccines |
CA2264735C (en) | 1996-08-27 | 2008-01-29 | Chiron Corporation | Neisseria meningitidis serogroup b glycoconjugates and methods of using the same |
ATE252602T1 (de) | 1996-08-27 | 2003-11-15 | Chiron Corp | Meningokokkus b-epitop ausbildende monoklonale antikoerper und deren verwendung zur herstellung von impfstoffzusammenstellungen |
PT1007546E (pt) | 1997-08-27 | 2009-04-24 | Childrens Hosp & Res Ct Oak | Compostos miméticos moleculares de epítopos de meningococos do serogrupo b |
-
1997
- 1997-08-27 AT AT97941371T patent/ATE252602T1/de active
- 1997-08-27 US US08/925,002 patent/US6048527A/en not_active Expired - Lifetime
- 1997-08-27 JP JP51191598A patent/JP4150082B2/ja not_active Expired - Fee Related
- 1997-08-27 CA CA002264585A patent/CA2264585C/en not_active Expired - Fee Related
- 1997-08-27 DE DE69725739T patent/DE69725739T2/de not_active Expired - Lifetime
- 1997-08-27 WO PCT/US1997/015167 patent/WO1998008874A1/en active IP Right Grant
- 1997-08-27 EP EP97941371A patent/EP0922059B1/en not_active Expired - Lifetime
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2001
- 2001-07-23 US US09/910,552 patent/US6642354B2/en not_active Expired - Fee Related
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2003
- 2003-08-19 US US10/643,465 patent/US7063949B2/en not_active Expired - Fee Related
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2005
- 2005-10-05 US US11/244,209 patent/US7504254B2/en not_active Expired - Fee Related
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- 2007-08-28 JP JP2007221879A patent/JP2008044947A/ja not_active Withdrawn
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JP2011016810A (ja) * | 2002-10-16 | 2011-01-27 | Centre National De La Recherche Scientifique | NCAM機能を調節するためのポリ−α2,8−シアル酸模倣ペプチドの使用 |
US9089513B2 (en) | 2004-06-23 | 2015-07-28 | Children's Hospital & Research Center Oakland | De-N-acetyl sialic acid antigens, antibodies thereto, and methods of use in cancer therapy |
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JP2010532389A (ja) * | 2007-07-03 | 2010-10-07 | チルドレンズ ホスピタル アンド リサーチ センター アット オークランド | ポリシアル酸誘導体、製造方法、ならびにがん抗原産生の増強およびターゲティングにおける使用 |
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CA2264585C (en) | 2005-06-14 |
JP2008044947A (ja) | 2008-02-28 |
US20040077840A1 (en) | 2004-04-22 |
JP4150082B2 (ja) | 2008-09-17 |
ATE252602T1 (de) | 2003-11-15 |
US6048527A (en) | 2000-04-11 |
US6642354B2 (en) | 2003-11-04 |
WO1998008874A1 (en) | 1998-03-05 |
DE69725739T2 (de) | 2004-08-05 |
US20020197260A1 (en) | 2002-12-26 |
US7063949B2 (en) | 2006-06-20 |
US7504254B2 (en) | 2009-03-17 |
CA2264585A1 (en) | 1998-03-05 |
EP0922059A1 (en) | 1999-06-16 |
EP0922059B1 (en) | 2003-10-22 |
DE69725739D1 (de) | 2003-12-11 |
US20060035284A1 (en) | 2006-02-16 |
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