RU2012120863A - Способы и композиции для модуляции гепсином стимулирующего макрофаги белка - Google Patents

Способы и композиции для модуляции гепсином стимулирующего макрофаги белка Download PDF

Info

Publication number
RU2012120863A
RU2012120863A RU2012120863/10A RU2012120863A RU2012120863A RU 2012120863 A RU2012120863 A RU 2012120863A RU 2012120863/10 A RU2012120863/10 A RU 2012120863/10A RU 2012120863 A RU2012120863 A RU 2012120863A RU 2012120863 A RU2012120863 A RU 2012120863A
Authority
RU
Russia
Prior art keywords
msp
molecule
pro
hepsin
activation
Prior art date
Application number
RU2012120863/10A
Other languages
English (en)
Other versions
RU2539772C2 (ru
Inventor
Раджкумар ГАНЕЗАН
Дэниэль КИРХХОФЕР
Original Assignee
Дженентек, Инк.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Дженентек, Инк. filed Critical Дженентек, Инк.
Publication of RU2012120863A publication Critical patent/RU2012120863A/ru
Application granted granted Critical
Publication of RU2539772C2 publication Critical patent/RU2539772C2/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • 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
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • 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
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
    • G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
    • G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
    • G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
    • G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
    • G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
    • G01N2333/96433—Serine endopeptidases (3.4.21)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Urology & Nephrology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Physics & Mathematics (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Food Science & Technology (AREA)
  • Veterinary Medicine (AREA)
  • Analytical Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

1. Способ идентификации вещества-кандидата, ингибирующего активацию гепсином стимулирующего макрофаги пробелка (про-MSP), где указанный способ включает: (a) контакт вещества-кандидата с первым образцом, содержащим гепсин и субстрат про-MSP, и (b) сравнение уровня активации субстрата про-MSP в образце с уровнем активации про-MSP в контрольном образце, содержащем сходные количества гепсина и субстрата про-MSP, как и в первом образце, но не подвергавшемся контакту с указанным веществом-кандидатом, при этом уменьшение уровня активации субстрата про-MSP в первом образце по сравнению с контрольным образцом указывает на то, что вещество-кандидат способно ингибировать активацию одноцепочечного MSP (про-MSP) гепсином.2. Способ по п.1, где гепсин в образце присутствует в эффективном количестве для активации указанного про-MSP.3. Способ по п.1, где субстрат про-MSP представляет собой полипептид, содержащий про-MSP или его фрагмент, содержащий форму дикого типа пептидной связи Arg-Val.4. Молекула антагониста, ингибирующая взаимодействие гепсина и про-MSP.5. Молекула антагониста по п.4, где молекула содержит антитело или его фрагмент.6. Молекула антагониста по п.4, где молекула содержит полипептид, содержащий последовательность домена Кунитца 1.7. Антагонист по п.4, где молекула содержит малую органическую молекулу.8. Молекула по п.6, где молекула содержит полипептид, содержащий последовательность домена Кунитца (KD), способную ингибировать активацию про-MSP гепсином.9. Молекула по п.8, где последовательность домена Кунитца (KD) содержит последовательность домена Кунитца 1 (KD-1).10. Молекула по п.9, где последовательность KD-1 представляет собой последовательность из

Claims (34)

1. Способ идентификации вещества-кандидата, ингибирующего активацию гепсином стимулирующего макрофаги пробелка (про-MSP), где указанный способ включает: (a) контакт вещества-кандидата с первым образцом, содержащим гепсин и субстрат про-MSP, и (b) сравнение уровня активации субстрата про-MSP в образце с уровнем активации про-MSP в контрольном образце, содержащем сходные количества гепсина и субстрата про-MSP, как и в первом образце, но не подвергавшемся контакту с указанным веществом-кандидатом, при этом уменьшение уровня активации субстрата про-MSP в первом образце по сравнению с контрольным образцом указывает на то, что вещество-кандидат способно ингибировать активацию одноцепочечного MSP (про-MSP) гепсином.
2. Способ по п.1, где гепсин в образце присутствует в эффективном количестве для активации указанного про-MSP.
3. Способ по п.1, где субстрат про-MSP представляет собой полипептид, содержащий про-MSP или его фрагмент, содержащий форму дикого типа пептидной связи Arg483-Val484.
4. Молекула антагониста, ингибирующая взаимодействие гепсина и про-MSP.
5. Молекула антагониста по п.4, где молекула содержит антитело или его фрагмент.
6. Молекула антагониста по п.4, где молекула содержит полипептид, содержащий последовательность домена Кунитца 1.
7. Антагонист по п.4, где молекула содержит малую органическую молекулу.
8. Молекула по п.6, где молекула содержит полипептид, содержащий последовательность домена Кунитца (KD), способную ингибировать активацию про-MSP гепсином.
9. Молекула по п.8, где последовательность домена Кунитца (KD) содержит последовательность домена Кунитца 1 (KD-1).
10. Молекула по п.9, где последовательность KD-1 представляет собой последовательность из ингибитора активатора фактора роста гепатоцитов человека-1, -1B (HAI-1, HAI-1B), или его варианта.
11. Молекула по п.8, где последовательность домена Кунитца (KD) представляет собой один или оба из доменов Кунитца ингибитора активатора фактора роста гепатоцитов человека-2 (HAI-2) или его варианта.
12. Молекула по п.6, где молекула содержит по меньшей мере часть ингибитора активатора фактора роста гепатоцитов человека-1, -1B, или -2 (HAI-1, HAI-1B или HAI-2), или его варианта.
13. Молекула по п.12, где часть содержит последовательность домена Кунитца (KD), способную ингибировать активацию про-MSP гепсином.
14. Молекула по п.13, где последовательность домена Кунитца (KD) представляет собой:
(i) последовательность домена Кунитца 1 (KD-1) ингибитора активатора фактора роста гепатоцитов человека-1, -1B (HAI-1, HAI-1B), или его варианта; или
(ii) один или оба из доменов Кунитца ингибитора активатора фактора роста гепатоцитов человека-2 (HAI-2), или его варианта.
15. Молекула по п.6, где молекула конкурирует с гепсином за связывание с Ron.
16. Молекула по п.6, где молекула конкурирует с про-MSP за связывание с гепсином.
17. Молекула по п.16, где молекула содержит мутантный MSP, способный связывать гепсин и обладающий сниженной активностью активации Ron по сравнению с MSP дикого типа.
18. Молекула по п.17, где мутантный MSP лишен по меньшей мере части β-цепи MSP.
19. Молекула по любому из пп.6-18, где молекула связана с токсином.
20. Выделенная нуклеиновая кислота, кодирующая молекулу по любому из пп.6-18.
21. Вектор, содержащий нуклеиновую кислоту по п.20.
22. Клетка-хозяин, содержащая нуклеиновую кислоту по п.20 или вектор по п.21.
23. Способ получения молекулы по любому из пп.6-18, включающий экспрессию вектора по п.21 в клетке-хозяине, способной экспрессировать молекулу.
24. Композиция, содержащая молекулу по любому из пп.6-18 и носитель.
25. Композиция по п.24, где носитель представляет собой фармацевтически приемлемый носитель.
26. Изделие, содержащее контейнер и композицию, присутствующую внутри контейнера, где композиция содержит молекулу по любому из пп.6-18.
27. Молекула по любому из пп.6-18 или 20 для лечения патологического состояния, ассоциированного с активацией Ron у субъекта.
28. Композиция, содержащая очищенные белки про-MSP и гепсин.
29. Способ ингибирования биологической активности, ассоциированной с активацией про-MSP/Ron, где указанный способ включает контакт клетки или ткани с эффективным количеством молекулы антагониста по любому из предшествующих пунктов.
30. Способ лечения патологического состояния, ассоциированного с активацией про-MSP/Ron у субъекта, где указанный способ включает введение субъекту эффективного количества молекулы антагониста по любому из предшествующих пунктов.
31. Способ по п.29 или 30, где состояние представляет собой злокачественную опухоль, опухоль, нарушение пролиферации клеток или иммунное нарушение.
32. Способ по п.31, где злокачественная опухоль представляет собой рак молочной железы, колоректальный рак, рак легкого, папиллярную карциному, рак толстого кишечника, рак поджелудочной железы, рак яичника, рак шейки матки, злокачественную опухоль центральной нервной системы, рак предстательной железы, остеогенную саркому, карциному почек, печеночно-клеточную карциному, рак мочевого пузыря, карциному желудка, плоскоклеточную карциному головы и шеи, меланому или лейкоз.
33. Способ детекции MSP в образце, включающий (a) контакт образца с гепсином в условиях, позволяющих протеолитический процессинг MSP гепсином, и (b) детекцию присутствия активированного гепсином MSP.
34. Способ детекции гепсина в образце, включающий (a) контакт образца с MSP в условиях, позволяющих протеолитический процессинг MSP гепсином, и (b) детекцию присутствия активированного гепсином MSP.
RU2012120863/10A 2009-10-22 2010-10-21 Способы и композиции для модуляции гепсином стимулирующего макрофаги белка RU2539772C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US25399009P 2009-10-22 2009-10-22
US61/253,990 2009-10-22
PCT/US2010/053600 WO2011050194A1 (en) 2009-10-22 2010-10-21 Methods and compositions for modulating hepsin activation of macrophage-stimulating protein

Publications (2)

Publication Number Publication Date
RU2012120863A true RU2012120863A (ru) 2013-11-27
RU2539772C2 RU2539772C2 (ru) 2015-01-27

Family

ID=43532896

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2012120863/10A RU2539772C2 (ru) 2009-10-22 2010-10-21 Способы и композиции для модуляции гепсином стимулирующего макрофаги белка

Country Status (11)

Country Link
US (1) US8697386B2 (ru)
EP (1) EP2490718B1 (ru)
JP (1) JP5819308B2 (ru)
KR (1) KR20120105446A (ru)
CN (1) CN102711826B (ru)
BR (1) BR112012009409A2 (ru)
CA (1) CA2778442A1 (ru)
ES (1) ES2564207T3 (ru)
MX (1) MX2012004617A (ru)
RU (1) RU2539772C2 (ru)
WO (1) WO2011050194A1 (ru)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102993615B (zh) * 2012-09-29 2015-07-01 北京东方雨虹防水技术股份有限公司 一种防灭火胶体材料、制备方法和用途
CN109072242A (zh) * 2016-02-23 2018-12-21 科罗拉多州立大学董事会法人团体 用于治疗神经损伤的基于肽的方法
WO2017162659A1 (en) 2016-03-24 2017-09-28 Bayer Pharma Aktiengesellschaft Intracellular hepsin as therapeutic target for the treatment of cancer with centrosome amplification

Family Cites Families (337)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US3896111A (en) 1973-02-20 1975-07-22 Research Corp Ansa macrolides
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
US4151042A (en) 1977-03-31 1979-04-24 Takeda Chemical Industries, Ltd. Method for producing maytansinol and its derivatives
US4137230A (en) 1977-11-14 1979-01-30 Takeda Chemical Industries, Ltd. Method for the production of maytansinoids
USRE30985E (en) 1978-01-01 1982-06-29 Serum-free cell culture media
FR2413974A1 (fr) 1978-01-06 1979-08-03 David Bernard Sechoir pour feuilles imprimees par serigraphie
US4265814A (en) 1978-03-24 1981-05-05 Takeda Chemical Industries Matansinol 3-n-hexadecanoate
US4307016A (en) 1978-03-24 1981-12-22 Takeda Chemical Industries, Ltd. Demethyl maytansinoids
JPS5562090A (en) 1978-10-27 1980-05-10 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
US4256746A (en) 1978-11-14 1981-03-17 Takeda Chemical Industries Dechloromaytansinoids, their pharmaceutical compositions and method of use
JPS5566585A (en) 1978-11-14 1980-05-20 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS55164687A (en) 1979-06-11 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS55102583A (en) 1979-01-31 1980-08-05 Takeda Chem Ind Ltd 20-acyloxy-20-demethylmaytansinoid compound
JPS55162791A (en) 1979-06-05 1980-12-18 Takeda Chem Ind Ltd Antibiotic c-15003pnd and its preparation
JPS55164685A (en) 1979-06-08 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS55164686A (en) 1979-06-11 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS6023084B2 (ja) 1979-07-11 1985-06-05 味の素株式会社 代用血液
US4309428A (en) 1979-07-30 1982-01-05 Takeda Chemical Industries, Ltd. Maytansinoids
JPS5645483A (en) 1979-09-19 1981-04-25 Takeda Chem Ind Ltd C-15003phm and its preparation
EP0028683A1 (en) 1979-09-21 1981-05-20 Takeda Chemical Industries, Ltd. Antibiotic C-15003 PHO and production thereof
JPS5645485A (en) 1979-09-21 1981-04-25 Takeda Chem Ind Ltd Production of c-15003pnd
WO1981001145A1 (en) 1979-10-18 1981-04-30 Univ Illinois Hydrolytic enzyme-activatible pro-drugs
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
ZA811368B (en) 1980-03-24 1982-04-28 Genentech Inc Bacterial polypedtide expression employing tryptophan promoter-operator
WO1982001188A1 (en) 1980-10-08 1982-04-15 Takeda Chemical Industries Ltd 4,5-deoxymaytansinoide compounds and process for preparing same
US4450254A (en) 1980-11-03 1984-05-22 Standard Oil Company Impact improvement of high nitrile resins
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4313946A (en) 1981-01-27 1982-02-02 The United States Of America As Represented By The Secretary Of Agriculture Chemotherapeutically active maytansinoids from Trewia nudiflora
US4315929A (en) 1981-01-27 1982-02-16 The United States Of America As Represented By The Secretary Of Agriculture Method of controlling the European corn borer with trewiasine
JPS57192389A (en) 1981-05-20 1982-11-26 Takeda Chem Ind Ltd Novel maytansinoid
US4485045A (en) 1981-07-06 1984-11-27 Research Corporation Synthetic phosphatidyl cholines useful in forming liposomes
US4426330A (en) 1981-07-20 1984-01-17 Lipid Specialties, Inc. Synthetic phospholipid compounds
US4534899A (en) 1981-07-20 1985-08-13 Lipid Specialties, Inc. Synthetic phospholipid compounds
NZ201705A (en) 1981-08-31 1986-03-14 Genentech Inc Recombinant dna method for production of hepatitis b surface antigen in yeast
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4640835A (en) 1981-10-30 1987-02-03 Nippon Chemiphar Company, Ltd. Plasminogen activator derivatives
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
US4943529A (en) 1982-05-19 1990-07-24 Gist-Brocades Nv Kluyveromyces as a host strain
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
US4870009A (en) 1982-11-22 1989-09-26 The Salk Institute For Biological Studies Method of obtaining gene product through the generation of transgenic animals
US4560655A (en) 1982-12-16 1985-12-24 Immunex Corporation Serum-free cell culture medium and process for making same
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
US4713339A (en) 1983-01-19 1987-12-15 Genentech, Inc. Polycistronic expression vector construction
AU2353384A (en) 1983-01-19 1984-07-26 Genentech Inc. Amplification in eukaryotic host cells
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
CA1247080A (en) 1983-03-08 1988-12-20 Commonwealth Serum Laboratories Commission Antigenically active amino acid sequences
NZ207394A (en) 1983-03-08 1987-03-06 Commw Serum Lab Commission Detecting or determining sequence of amino acids
WO1984003506A1 (en) 1983-03-08 1984-09-13 Commw Serum Lab Commission Antigenically active amino acid sequences
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
DD266710A3 (de) 1983-06-06 1989-04-12 Ve Forschungszentrum Biotechnologie Verfahren zur biotechnischen Herstellung van alkalischer Phosphatase
US4544545A (en) 1983-06-20 1985-10-01 Trustees University Of Massachusetts Liposomes containing modified cholesterol for organ targeting
AU3145184A (en) 1983-08-16 1985-02-21 Zymogenetics Inc. High expression of foreign genes in schizosaccharomyces pombe
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US4767704A (en) 1983-10-07 1988-08-30 Columbia University In The City Of New York Protein-free culture medium
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US4496689A (en) 1983-12-27 1985-01-29 Miles Laboratories, Inc. Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer
US4736866A (en) 1984-06-22 1988-04-12 President And Fellows Of Harvard College Transgenic non-human mammals
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US4879231A (en) 1984-10-30 1989-11-07 Phillips Petroleum Company Transformation of yeasts of the genus pichia
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
US4970198A (en) 1985-10-17 1990-11-13 American Cyanamid Company Antitumor antibiotics (LL-E33288 complex)
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
EP1186660A3 (fr) 1985-03-30 2002-03-20 KAUFFMAN, Stuart A. Procédé d'obtension d'ADN, ARN, peptides, polypeptides ou protéines, par une technique de recombination d'ADN
NZ215865A (en) 1985-04-22 1988-10-28 Commw Serum Lab Commission Method of determining the active site of a receptor-binding analogue
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
DE3675588D1 (de) 1985-06-19 1990-12-20 Ajinomoto Kk Haemoglobin, das an ein poly(alkenylenoxid) gebunden ist.
GB8516415D0 (en) 1985-06-28 1985-07-31 Celltech Ltd Culture of animal cells
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
JPS63502716A (ja) 1986-03-07 1988-10-13 マサチューセッツ・インステチュート・オブ・テクノロジー 糖タンパク安定性の強化方法
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
US4927762A (en) 1986-04-01 1990-05-22 Cell Enterprises, Inc. Cell culture medium with antioxidant
GB8610600D0 (en) 1986-04-30 1986-06-04 Novo Industri As Transformation of trichoderma
US4791192A (en) 1986-06-26 1988-12-13 Takeda Chemical Industries, Ltd. Chemically modified protein with polyethyleneglycol
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US5567610A (en) 1986-09-04 1996-10-22 Bioinvent International Ab Method of producing human monoclonal antibodies and kit therefor
DE3788914T2 (de) 1986-09-08 1994-08-25 Ajinomoto Kk Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere.
US5763192A (en) 1986-11-20 1998-06-09 Ixsys, Incorporated Process for obtaining DNA, RNA, peptides, polypeptides, or protein, by recombinant DNA technique
US5079233A (en) 1987-01-30 1992-01-07 American Cyanamid Company N-acyl derivatives of the LL-E33288 antitumor antibiotics, composition and methods for using the same
US4946783A (en) 1987-01-30 1990-08-07 President And Fellows Of Harvard College Periplasmic protease mutants of Escherichia coli
GB8705477D0 (en) 1987-03-09 1987-04-15 Carlton Med Prod Drug delivery systems
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
AU598946B2 (en) 1987-06-24 1990-07-05 Howard Florey Institute Of Experimental Physiology And Medicine Nucleoside derivatives
US5010182A (en) 1987-07-28 1991-04-23 Chiron Corporation DNA constructs containing a Kluyveromyces alpha factor leader sequence for directing secretion of heterologous polypeptides
US4975278A (en) 1988-02-26 1990-12-04 Bristol-Myers Company Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
GB8724885D0 (en) 1987-10-23 1987-11-25 Binns M M Fowlpox virus promotors
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
US5606040A (en) 1987-10-30 1997-02-25 American Cyanamid Company Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group
US5053394A (en) 1988-09-21 1991-10-01 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
US5770701A (en) 1987-10-30 1998-06-23 American Cyanamid Company Process for preparing targeted forms of methyltrithio antitumor agents
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
US5283187A (en) 1987-11-17 1994-02-01 Brown University Research Foundation Cell culture-containing tubular capsule produced by co-extrusion
US4892538A (en) 1987-11-17 1990-01-09 Brown University Research Foundation In vivo delivery of neurotransmitters by implanted, encapsulated cells
WO1989005358A1 (en) 1987-11-30 1989-06-15 University Of Iowa Research Foundation Dna and rna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
WO1989005859A1 (en) 1987-12-21 1989-06-29 The Upjohn Company Agrobacterium mediated transformation of germinating plant seeds
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
EP0406309A4 (en) 1988-03-25 1992-08-19 The University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
US5266684A (en) 1988-05-02 1993-11-30 The Reagents Of The University Of California Peptide mixtures
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5571689A (en) 1988-06-16 1996-11-05 Washington University Method of N-acylating peptide and proteins with diheteroatom substituted analogs of myristic acid
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
AU4005289A (en) 1988-08-25 1990-03-01 Smithkline Beecham Corporation Recombinant saccharomyces
US5663143A (en) 1988-09-02 1997-09-02 Dyax Corp. Engineered human-derived kunitz domains that inhibit human neutrophil elastase
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
DE68925971T2 (de) 1988-09-23 1996-09-05 Cetus Oncology Corp Zellenzuchtmedium für erhöhtes zellenwachstum, zur erhöhung der langlebigkeit und expression der produkte
US5194599A (en) 1988-09-23 1993-03-16 Gilead Sciences, Inc. Hydrogen phosphonodithioate compositions
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US5750373A (en) 1990-12-03 1998-05-12 Genentech, Inc. Enrichment method for variant proteins having altered binding properties, M13 phagemids, and growth hormone variants
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5175384A (en) 1988-12-05 1992-12-29 Genpharm International Transgenic mice depleted in mature t-cells and methods for making transgenic mice
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5225538A (en) 1989-02-23 1993-07-06 Genentech, Inc. Lymphocyte homing receptor/immunoglobulin fusion proteins
US5009772A (en) 1989-02-27 1991-04-23 Kerr-Mcgee Corporation Solvent extraction process
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
WO1990010448A2 (en) 1989-03-07 1990-09-20 Genentech, Inc. Covalent conjugates of lipid and oligonucleotide
US5354844A (en) 1989-03-16 1994-10-11 Boehringer Ingelheim International Gmbh Protein-polycation conjugates
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
FR2646437B1 (fr) 1989-04-28 1991-08-30 Transgene Sa Nouvelles sequences d'adn, leur application en tant que sequence codant pour un peptide signal pour la secretion de proteines matures par des levures recombinantes, cassettes d'expression, levures transformees et procede de preparation de proteines correspondant
DE68927344T2 (de) 1989-04-28 1997-02-20 Rhein Biotech Proz & Prod Gmbh Hefezellen der Gattung-Schwanniomyces
EP0471796A4 (en) 1989-05-10 1993-05-05 Sloan Kettering Institute For Cancer Research Stably transformed eucaryotic cells comprising a foreign transcribable dna under the control of a pol iii promoter
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
EP0402226A1 (en) 1989-06-06 1990-12-12 Institut National De La Recherche Agronomique Transformation vectors for yeast yarrowia
US5227170A (en) 1989-06-22 1993-07-13 Vestar, Inc. Encapsulation process
AU641673B2 (en) 1989-06-29 1993-09-30 Medarex, Inc. Bispecific reagents for aids therapy
FR2649120B1 (fr) 1989-06-30 1994-01-28 Cayla Nouvelle souche et ses mutants de champignons filamenteux, procede de production de proteines recombinantes a l'aide de ladite souche et souches et proteines obtenues selon ce procede
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
WO1991004753A1 (en) 1989-10-02 1991-04-18 Cetus Corporation Conjugates of antisense oligonucleotides and therapeutic uses thereof
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5356633A (en) 1989-10-20 1994-10-18 Liposome Technology, Inc. Method of treatment of inflamed tissues
US5527528A (en) 1989-10-20 1996-06-18 Sequus Pharmaceuticals, Inc. Solid-tumor treatment method
US5721218A (en) 1989-10-23 1998-02-24 Gilead Sciences, Inc. Oligonucleotides with inverted polarity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
DE69027443T2 (de) 1989-10-24 1998-03-19 Gilead Sciences, Inc., Foster City, Calif. Oligonukleotidanaloga mit neuartigen bindungen
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
WO1991006556A1 (en) 1989-10-24 1991-05-16 Gilead Sciences, Inc. 2' modified oligonucleotides
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
CA2026147C (en) 1989-10-25 2006-02-07 Ravi J. Chari Cytotoxic agents comprising maytansinoids and their therapeutic use
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5580575A (en) 1989-12-22 1996-12-03 Imarx Pharmaceutical Corp. Therapeutic drug delivery systems
US5469854A (en) 1989-12-22 1995-11-28 Imarx Pharmaceutical Corp. Methods of preparing gas-filled liposomes
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5498538A (en) 1990-02-15 1996-03-12 The University Of North Carolina At Chapel Hill Totally synthetic affinity reagents
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
US5229275A (en) 1990-04-26 1993-07-20 Akzo N.V. In-vitro method for producing antigen-specific human monoclonal antibodies
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
DE69032425T2 (de) 1990-05-11 1998-11-26 Microprobe Corp., Bothell, Wash. Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden
US5723286A (en) 1990-06-20 1998-03-03 Affymax Technologies N.V. Peptide library and screening systems
JPH06500011A (ja) 1990-06-29 1994-01-06 ラージ　スケール　バイオロジー　コーポレイション 形質転換された微生物によるメラニンの製造
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
ATE154246T1 (de) 1990-07-27 1997-06-15 Isis Pharmaceuticals Inc Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
HU217036B (hu) 1990-08-03 1999-11-29 Sanofi Eljárás génexpresszió gátlására alkalmas vegyületek előállítására
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
WO1992003918A1 (en) 1990-08-29 1992-03-19 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
EP0549686A4 (en) 1990-09-20 1995-01-18 Gilead Sciences Inc Modified internucleoside linkages
US5698426A (en) 1990-09-28 1997-12-16 Ixsys, Incorporated Surface expression libraries of heteromeric receptors
US5770434A (en) 1990-09-28 1998-06-23 Ixsys Incorporated Soluble peptides having constrained, secondary conformation in solution and method of making same
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
WO1992008728A1 (en) 1990-11-08 1992-05-29 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
WO1992009300A1 (en) 1990-11-21 1992-06-11 Iterex Pharmaceuticals Ltd. Partnership Synthesis of equimolar multiple oligomer mixtures, especially of oligopeptide mixtures
US5206161A (en) 1991-02-01 1993-04-27 Genentech, Inc. Human plasma carboxypeptidase B
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
JPH06507398A (ja) 1991-05-14 1994-08-25 リプリジェン　コーポレーション Ｈｉｖ感染治療のための異種複合抗体
JP3220180B2 (ja) 1991-05-23 2001-10-22 三菱化学株式会社 薬剤含有タンパク質結合リポソーム
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
EP1400536A1 (en) 1991-06-14 2004-03-24 Genentech Inc. Method for making humanized antibodies
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
EP0861893A3 (en) 1991-09-19 1999-11-10 Genentech, Inc. High level expression of immunoglobulin polypeptides
US5565332A (en) 1991-09-23 1996-10-15 Medical Research Council Production of chimeric antibodies - a combinatorial approach
US5362852A (en) 1991-09-27 1994-11-08 Pfizer Inc. Modified peptide derivatives conjugated at 2-hydroxyethylamine moieties
US5521291A (en) 1991-09-30 1996-05-28 Boehringer Ingelheim International, Gmbh Conjugates for introducing nucleic acid into higher eucaryotic cells
NZ244306A (en) 1991-09-30 1995-07-26 Boehringer Ingelheim Int Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation
US5587458A (en) 1991-10-07 1996-12-24 Aronex Pharmaceuticals, Inc. Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof
US5270170A (en) 1991-10-16 1993-12-14 Affymax Technologies N.V. Peptide library and screening method
ES2103918T3 (es) 1991-10-17 1997-10-01 Ciba Geigy Ag Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios.
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
DE69232816T2 (de) 1991-11-26 2003-06-18 Isis Pharmaceuticals Inc Gesteigerte bildung von triple- und doppelhelices aus oligomeren mit modifizierten pyrimidinen
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5792608A (en) 1991-12-12 1998-08-11 Gilead Sciences, Inc. Nuclease stable and binding competent oligomers and methods for their use
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
AU675929B2 (en) 1992-02-06 1997-02-27 Curis, Inc. Biosynthetic binding protein for cancer marker
US5573905A (en) 1992-03-30 1996-11-12 The Scripps Research Institute Encoded combinatorial chemical libraries
ZA932522B (en) 1992-04-10 1993-12-20 Res Dev Foundation Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
CA2134773A1 (en) 1992-06-04 1993-12-09 Robert J. Debs Methods and compositions for in vivo gene therapy
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
AU668423B2 (en) 1992-08-17 1996-05-02 Genentech Inc. Bispecific immunoadhesins
EP0752248B1 (en) 1992-11-13 2000-09-27 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US5583020A (en) 1992-11-24 1996-12-10 Ribozyme Pharmaceuticals, Inc. Permeability enhancers for negatively charged polynucleotides
CA2109861C (en) 1992-12-04 1999-03-16 Shu-Hui Chen 6,7-modified paclitaxels
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
JP3351476B2 (ja) 1993-01-22 2002-11-25 三菱化学株式会社 リン脂質誘導体及びそれを含有するリポソーム
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
US5395619A (en) 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
PT616812E (pt) 1993-03-24 2000-04-28 Berlex Biosciences Combinacao de compostos anti-hormonais e moleculas de ligacao no tratamento do cancro
AU6449394A (en) 1993-03-30 1994-10-24 Sterling Winthrop Inc. Acyclic nucleoside analogs and oligonucleotide sequences containing them
HU9501974D0 (en) 1993-03-31 1995-09-28 Sterling Winthrop Inc Oligonucleotides with amide linkages replacing phosphodiester linkages
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
US5462854A (en) 1993-04-19 1995-10-31 Beckman Instruments, Inc. Inverse linkage oligonucleotides for chemical and enzymatic processes
US5534259A (en) 1993-07-08 1996-07-09 Liposome Technology, Inc. Polymer compound and coated particle composition
US5543158A (en) 1993-07-23 1996-08-06 Massachusetts Institute Of Technology Biodegradable injectable nanoparticles
US5417978A (en) 1993-07-29 1995-05-23 Board Of Regents, The University Of Texas System Liposomal antisense methyl phosphonate oligonucleotides and methods for their preparation and use
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
CN1048254C (zh) 1993-12-09 2000-01-12 托马斯杰弗逊大学 用于将预定的改变引入靶基因中的化合物
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5595756A (en) 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5646269A (en) 1994-04-28 1997-07-08 Gilead Sciences, Inc. Method for oligonucleotide analog synthesis
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
WO1995034683A1 (en) 1994-06-10 1995-12-21 Symbiotech, Inc. Method of detecting compounds utilizing genetically modified lambdoid bacteriophage
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5627024A (en) 1994-08-05 1997-05-06 The Scripps Research Institute Lambdoid bacteriophage vectors for expression and display of foreign proteins
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5910486A (en) 1994-09-06 1999-06-08 Uab Research Foundation Methods for modulating protein function in cells using, intracellular antibody homologues
US5591721A (en) 1994-10-25 1997-01-07 Hybridon, Inc. Method of down-regulating gene expression
US5789199A (en) 1994-11-03 1998-08-04 Genentech, Inc. Process for bacterial production of polypeptides
US6214388B1 (en) 1994-11-09 2001-04-10 The Regents Of The University Of California Immunoliposomes that optimize internalization into target cells
US5512295A (en) 1994-11-10 1996-04-30 The Board Of Trustees Of The Leland Stanford Junior University Synthetic liposomes for enhanced uptake and delivery
AU4289496A (en) 1994-12-02 1996-06-19 Chiron Corporation Method of promoting an immune response with a bispecific antibody
US5792747A (en) 1995-01-24 1998-08-11 The Administrators Of The Tulane Educational Fund Highly potent agonists of growth hormone releasing hormone
US5840523A (en) 1995-03-01 1998-11-24 Genetech, Inc. Methods and compositions for secretion of heterologous polypeptides
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
US5739277A (en) 1995-04-14 1998-04-14 Genentech Inc. Altered polypeptides with increased half-life
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US5712374A (en) 1995-06-07 1998-01-27 American Cyanamid Company Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates
US5837234A (en) 1995-06-07 1998-11-17 Cytotherapeutics, Inc. Bioartificial organ containing cells encapsulated in a permselective polyether suflfone membrane
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
AU6785496A (en) 1995-09-07 1997-03-27 Novo Nordisk A/S Phage display for detergent enzyme activity
DE19544393A1 (de) 1995-11-15 1997-05-22 Hoechst Schering Agrevo Gmbh Synergistische herbizide Mischungen
AU2582897A (en) 1996-03-15 1997-10-01 Millennium Pharmaceuticals, Inc. Compositions and methods for the diagnosis, prevention, and treatment of neoplastic cell growth and proliferation
IL126045A0 (en) 1996-03-20 1999-05-09 Dyax Corp Purification of tissue plasminogen activator (tpa)
CA2256449A1 (en) 1996-06-06 1997-12-11 Lajolla Pharmaceutical Company Apl immunoreactive peptides, conjugates thereof and methods of treatment for apl antibody-mediated pathologies
ATE279203T1 (de) 1996-06-10 2004-10-15 Scripps Research Inst Verwendung von substrat-subtraktionsbibliotheken zur unterscheidung von enzymspezifitäten
US5766905A (en) 1996-06-14 1998-06-16 Associated Universities Inc. Cytoplasmic bacteriophage display system
US5922845A (en) 1996-07-11 1999-07-13 Medarex, Inc. Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies
WO1998014277A1 (en) 1996-10-04 1998-04-09 Whatman, Inc. Device and method for simultaneous multiple chemical syntheses
DE69718341T2 (de) 1996-10-08 2003-10-30 Bisys B V U Verfahren und mittel zur auswahl von peptiden und proteinen mit spezifischer affinität zu einem zielmolekül
EP0938497B1 (en) 1996-11-06 2007-02-28 Genentech, Inc. Constrained helical peptides and methods of making same
IL119587A (en) 1996-11-07 2000-12-06 Univ Ramot Method of preparing and for obtaining bimolecular interactions
IL119586A (en) 1996-11-07 2001-09-13 Univ Ramot Discontinuous library of a single biological unit and a method for its preparation
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
EP2341058A3 (en) 1997-09-12 2011-11-23 Exiqon A/S Oligonucleotide Analogues
US20030054400A1 (en) 1997-09-17 2003-03-20 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
US6335155B1 (en) 1998-06-26 2002-01-01 Sunesis Pharmaceuticals, Inc. Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules
EP1141708A1 (en) 1998-12-28 2001-10-10 Sunesis Pharmaceuticals Inc. Identifying small organic molecule ligands for binding
US20030113762A1 (en) 2001-08-17 2003-06-19 Warrington Janet A. Gleason grade 4/5 prostate cancer genes
EP1391213A1 (en) 2002-08-21 2004-02-25 Boehringer Ingelheim International GmbH Compositions and methods for treating cancer using maytansinoid CD44 antibody immunoconjugates and chemotherapeutic agents
AU2003279754A1 (en) 2002-10-04 2004-05-04 Schering Aktiengesellschaft Modified hepsin molecules having a substitute activation sequence and uses thereof
US7432044B2 (en) * 2004-07-26 2008-10-07 Genentech, Inc. Methods and compositions for modulating hepatocyte growth factor activation
WO2007149935A2 (en) * 2006-06-22 2007-12-27 Genentech, Inc. Methods and compositions for modulating hepsin activation of urokinase-type plasminogen activator
ZA200810225B (en) 2006-06-22 2010-03-31 Genentech Inc Methods and compositions for targeting hepsin
EP2491059B1 (en) 2009-10-22 2015-02-25 F.Hoffmann-La Roche Ag Anti-hepsin antibodies and methods using same

Also Published As

Publication number Publication date
EP2490718A1 (en) 2012-08-29
RU2539772C2 (ru) 2015-01-27
WO2011050194A1 (en) 2011-04-28
MX2012004617A (es) 2012-05-08
JP5819308B2 (ja) 2015-11-24
CN102711826A (zh) 2012-10-03
US20120282271A1 (en) 2012-11-08
JP2013507967A (ja) 2013-03-07
KR20120105446A (ko) 2012-09-25
CN102711826B (zh) 2017-03-29
ES2564207T3 (es) 2016-03-18
CA2778442A1 (en) 2011-04-28
BR112012009409A2 (pt) 2017-02-21
US8697386B2 (en) 2014-04-15
EP2490718B1 (en) 2016-01-13

Similar Documents

Publication Publication Date Title
Rousselle et al. Laminin 332 in cancer: When the extracellular matrix turns signals from cell anchorage to cell movement
Pouliot et al. Laminin-511: a multi-functional adhesion protein regulating cell migration, tumor invasion and metastasis
RU2006124743A (ru) СПОСОБЫ И КОМПОЗИЦИИ ДЛЯ ИНГИБИРОВАНИЯ ДИМЕРИЗАЦИИ И АКТИВАЦИИ с-Мет
Yoshida et al. Tenascin-C and integrins in cancer
Gandellini et al. Complexity in the tumour microenvironment: Cancer associated fibroblast gene expression patterns identify both common and unique features of tumour-stroma crosstalk across cancer types
Benvenuti et al. The MET receptor tyrosine kinase in invasion and metastasis
Maulik et al. Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition
To et al. The roles of hepatocyte growth factor/scatter factor and met receptor in human cancers
Schenk et al. Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution
Resnick et al. Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study
Kamimura et al. Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence
Hara et al. Hypoxia enhances c-Met/HGF receptor expression and signaling by activating HIF-1α in human salivary gland cancer cells
JP2019511904A5 (ru)
JP2008507295A5 (ru)
Fukamachi et al. CD49fhigh cells retain sphere-forming and tumor-initiating activities in human gastric tumors
Damdinsuren et al. Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation
CA2486252A1 (en) Methods for screening for agents that modulate hepatocellular carcinoma development
Ziober et al. The extracellular matrix in oral squamous cell carcinoma: friend or foe?
DE69833572D1 (de) Verfahren zur bestimmung des metastasierungspotentials unter verwendung des asp1 gens
Han et al. α‐Ketobenzothiazole serine protease inhibitors of aberrant HGF/c‐MET and MSP/RON kinase pathway signaling in cancer
Würth et al. Expression of CXCR7 chemokine receptor in human meningioma cells and in intratumoral microvasculature
Pelosi et al. High‐affinity monomeric 67‐kd laminin receptors and prognosis in pancreatic endocrine tumours
Ding et al. Induction of epithelial-mesenchymal transition with O-glycosylated oncofetal fibronectin
Rajarajan et al. CD44 expression in oro-pharyngeal carcinoma tissues and cell lines
RU2012120863A (ru) Способы и композиции для модуляции гепсином стимулирующего макрофаги белка

Legal Events

Date Code Title Description
MM4A The patent is invalid due to non-payment of fees

Effective date: 20171022