MA29243B1 - Agonistes de pyy et leurs utilisations - Google Patents

Agonistes de pyy et leurs utilisations

Info

Publication number
MA29243B1
MA29243B1 MA30123A MA30123A MA29243B1 MA 29243 B1 MA29243 B1 MA 29243B1 MA 30123 A MA30123 A MA 30123A MA 30123 A MA30123 A MA 30123A MA 29243 B1 MA29243 B1 MA 29243B1
Authority
MA
Morocco
Prior art keywords
pyy agonists
pyy3
npy
agonist
receptors
Prior art date
Application number
MA30123A
Other languages
English (en)
Inventor
Rory Francis Finn
Ned Roger Siegel
Neena Lynne Summers
Nancy Ann Nardone
Original Assignee
Pfizer Prod Inc
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 Pfizer Prod Inc filed Critical Pfizer Prod Inc
Publication of MA29243B1 publication Critical patent/MA29243B1/fr

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/48Drugs for disorders of the endocrine system of the pancreatic hormones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Diabetes (AREA)
  • Biochemistry (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Toxicology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Immunology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'INVENTION CONCERNE DES VARIANTS DU PYY3-36 ET DES DÉRIVÉS PÉGYLÉS DE CEUX-CI ET DES COMPOSITIONS ET DES PROCÉDÉS UTILES DANS LE TRAITEMENT D'ÉTATS MODULÉS PAR UN AGONISTE DES RÉCEPTEURS NPY Y2.
MA30123A 2005-02-04 2007-08-03 Agonistes de pyy et leurs utilisations MA29243B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US65036605P 2005-02-04 2005-02-04
US73365605P 2005-11-04 2005-11-04

Publications (1)

Publication Number Publication Date
MA29243B1 true MA29243B1 (fr) 2008-02-01

Family

ID=36175074

Family Applications (1)

Application Number Title Priority Date Filing Date
MA30123A MA29243B1 (fr) 2005-02-04 2007-08-03 Agonistes de pyy et leurs utilisations

Country Status (33)

Country Link
US (3) US20060178501A1 (fr)
EP (2) EP2078729A1 (fr)
JP (1) JP4314304B2 (fr)
KR (1) KR100892545B1 (fr)
AP (1) AP2007004069A0 (fr)
AR (1) AR052108A1 (fr)
AT (1) ATE426614T1 (fr)
AU (1) AU2006211039A1 (fr)
BR (1) BRPI0606142A2 (fr)
CA (1) CA2596977C (fr)
CY (1) CY1109054T1 (fr)
DE (1) DE602006005902D1 (fr)
DK (1) DK1846445T3 (fr)
DO (1) DOP2006000025A (fr)
EA (1) EA011882B1 (fr)
ES (1) ES2322293T3 (fr)
GT (1) GT200600038A (fr)
HR (1) HRP20090245T1 (fr)
IL (1) IL184324A0 (fr)
MA (1) MA29243B1 (fr)
MX (1) MX2007009389A (fr)
NL (2) NL1031067C2 (fr)
NO (1) NO20074498L (fr)
PA (1) PA8660701A1 (fr)
PE (1) PE20061412A1 (fr)
PL (1) PL1846445T3 (fr)
PT (1) PT1846445E (fr)
RS (1) RS50966B (fr)
SI (1) SI1846445T1 (fr)
TN (1) TNSN07305A1 (fr)
TW (1) TWI310038B (fr)
UY (1) UY29357A1 (fr)
WO (1) WO2006082517A1 (fr)

Families Citing this family (82)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100350968C (zh) 2001-09-24 2007-11-28 皇家创新有限公司 饮食行为的改进
US7173003B2 (en) 2001-10-10 2007-02-06 Neose Technologies, Inc. Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF
US7214660B2 (en) 2001-10-10 2007-05-08 Neose Technologies, Inc. Erythropoietin: remodeling and glycoconjugation of erythropoietin
MXPA05010773A (es) 2003-04-09 2005-12-12 Neose Technologies Inc Metodos de glicopegilacion y proteinas/peptidos producidos por los metodos.
WO2005012484A2 (fr) 2003-07-25 2005-02-10 Neose Technologies, Inc. Conjugues anticorps-toxines
US8633157B2 (en) 2003-11-24 2014-01-21 Novo Nordisk A/S Glycopegylated erythropoietin
US20080305992A1 (en) 2003-11-24 2008-12-11 Neose Technologies, Inc. Glycopegylated erythropoietin
CN101072789B (zh) 2004-01-08 2013-05-15 生物种属学股份公司 肽的o-连接的糖基化
US20050215710A1 (en) * 2004-03-23 2005-09-29 Gegg Colin V Jr Chemically modified protein compositions and methods
US20080300173A1 (en) 2004-07-13 2008-12-04 Defrees Shawn Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1]
JP5948627B2 (ja) 2004-10-29 2016-07-20 レイショファーム ゲーエムベーハー 線維芽細胞成長因子(fgf)のリモデリングと糖質ペグ化
EP1858543B1 (fr) 2005-01-10 2013-11-27 BioGeneriX AG Facteur de stimulation de colonie de granulocytes glycopegylé
EP2386571B1 (fr) 2005-04-08 2016-06-01 ratiopharm GmbH Compositions et méthodes utilisées pour la préparation de mutants par glycosylation de l'hormone de croissance humaine résistant à la protéase
AU2006257792A1 (en) * 2005-06-13 2006-12-21 Mdrna, Inc. Transmucosal delivery of peptide derivatives
US20070105755A1 (en) 2005-10-26 2007-05-10 Neose Technologies, Inc. One pot desialylation and glycopegylation of therapeutic peptides
EP2380435B1 (fr) * 2005-08-31 2016-05-25 Kaneka Corporation Erythropoiétine féline et son procédé de production
WO2007056191A2 (fr) 2005-11-03 2007-05-18 Neose Technologies, Inc. Purification de sucre de nucleotide en utilisant des membranes
WO2007085887A1 (fr) * 2006-01-27 2007-08-02 Pfizer Products Inc. Agonistes du pyy et leurs utilisations
US9187532B2 (en) 2006-07-21 2015-11-17 Novo Nordisk A/S Glycosylation of peptides via O-linked glycosylation sequences
JP2008069073A (ja) * 2006-09-12 2008-03-27 Yokohama Tlo Co Ltd ラクトフェリン複合体及びその製造方法
JP2010505874A (ja) 2006-10-03 2010-02-25 ノヴォ ノルディスク アー/エス ポリペプチドコンジュゲートの精製方法
CN101600448B (zh) * 2006-10-04 2015-11-25 诺和诺德公司 甘油连接的peg化的糖和糖肽
TWI428346B (zh) 2006-12-13 2014-03-01 Imp Innovations Ltd 新穎化合物及其等對進食行為影響
KR20150064246A (ko) 2007-04-03 2015-06-10 바이오제너릭스 게엠베하 글리코페길화 g―csf를 이용하는 치료 방법
CA2690611C (fr) 2007-06-12 2015-12-08 Novo Nordisk A/S Procede ameliore pour la production de sucres de nucleotide
WO2009108806A1 (fr) 2008-02-27 2009-09-03 Novo Nordisk A/S Molécules de facteur viii conjuguées
WO2010016936A1 (fr) * 2008-08-07 2010-02-11 Ipsen Pharma S.A.S. Compositions pharmaceutiques d'analogues de polypeptide insulinotrope glucose-dépendant
US10040838B2 (en) * 2008-11-04 2018-08-07 Janssen Pharmaceutica Nv CRHR2 peptide agonists and uses thereof
WO2010067233A1 (fr) 2008-12-08 2010-06-17 Pfizer Inc. 1,2,4 triazolo[4,3-a][1,5] benzodiazépin-5(6h)-ones utilisées comme agonistes du récepteur de la cholécystokinine-1 (cck-1r)
JP2012515760A (ja) 2009-01-20 2012-07-12 ファイザー・インク 置換ピラジノンアミド
WO2010086820A1 (fr) 2009-02-02 2010-08-05 Pfizer Inc. Dérivés de 4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazépin-6(5h)-yl)phényle
WO2010089685A1 (fr) 2009-02-03 2010-08-12 Pfizer Inc. Dérivés de 4-amino-7,8-dihydropyrido[4,3-d]pyrimidin-5(6h)-one
JP2012516885A (ja) 2009-02-04 2012-07-26 ファイザー・インク 4−アミノ−7,8−ジヒドロピリド[4,3−d]ピリミジン−5(6H)−オン誘導体
US20110319379A1 (en) 2009-03-11 2011-12-29 Corbett Jeffrey W Substituted Indazole Amides And Their Use As Glucokinase Activators
CA2754681C (fr) 2009-03-11 2014-01-07 Pfizer Inc. Derives de benzofuranyle utilises comme inhibiteurs de la glucokinase
EP2408780A2 (fr) 2009-03-20 2012-01-25 Pfizer Inc. 3-oxa-7-azabicycloý3,3.1¨nonanes
AU2010255422B2 (en) 2009-06-05 2014-04-10 Pfizer Inc. 1- ( piperidin-4-yl) -pyrazole derivatives as GPR 119 modulators
US20130072427A1 (en) 2009-09-23 2013-03-21 Pfizer Inc. Gpr 119 modulators
ES2527179T3 (es) 2009-11-02 2015-01-21 Pfizer Inc. Derivados de dioxa-biciclo[3.2.1]octano-2,3,4-triol
EP2499140A1 (fr) 2009-11-10 2012-09-19 Pfizer Inc. Inhibiteurs de n2-pyrazolospirocétone acétyl-coa carboxylase
CN102695708B (zh) 2009-11-10 2014-10-15 辉瑞大药厂 N1-吡唑并螺酮乙酰辅酶a羧化酶抑制剂
WO2011061679A1 (fr) 2009-11-23 2011-05-26 Pfizer Inc. Imidazo-pyrazoles comme inhibiteurs du gpr119
JP5496409B2 (ja) 2010-03-19 2014-05-21 ファイザー・インク 2,3ジヒドロ−1h−インデン−1−イル−2,7−ジアザスピロ[3.5]ノナン誘導体およびグレリン受容体のアンタゴニストまたは逆アゴニストとしてのそれらの使用
WO2011158149A1 (fr) 2010-06-18 2011-12-22 Pfizer Inc. Dérivés de 2-(3,5-disubstitutedphenyl)pyrimidin-4(3h)-one
US8859577B2 (en) 2010-09-30 2014-10-14 Pfizer Inc. N1-pyrazolospiroketone acetyl-CoA carboxylase inhibitors
CA2815169C (fr) 2010-10-29 2015-10-06 Pfizer Inc. Inhibiteurs de la n1/n2-lactame acetyl-coa carboxylase
MX2013006768A (es) 2010-12-23 2013-07-22 Pfizer Moduladores de receptor de glucagon.
EA023517B1 (ru) 2011-02-08 2016-06-30 Пфайзер Инк. Модуляторы глюкагонового рецептора
MX348860B (es) 2011-04-22 2017-06-30 Pfizer Derivados de pirazoloespirocetona para usarse como inhibidores de acetil-coa carboxilasa.
EP2731944A1 (fr) 2011-07-15 2014-05-21 Pfizer Inc Modulateurs de gpr 119
US8927577B2 (en) 2011-07-22 2015-01-06 Pfizer Inc. Quinolinyl glucagon receptor modulators
JP6043355B2 (ja) 2011-08-31 2016-12-14 ファイザー・インク ヘキサヒドロピラノ[3,4−d][1,3]チアジン−2−アミン化合物
JP6067754B2 (ja) 2012-02-24 2017-01-25 アルテオジェン インコーポレイテッドAlteogen Inc. システイン残基を含むモチーフが結合した修飾抗体、前記修飾抗体を含む修飾抗体−薬物複合体及びその製造方法
KR20140137404A (ko) 2012-04-06 2014-12-02 화이자 인코포레이티드 디아실글리세롤 아실트랜스퍼라제 2 억제제
US8889730B2 (en) 2012-04-10 2014-11-18 Pfizer Inc. Indole and indazole compounds that activate AMPK
WO2013164730A1 (fr) 2012-05-04 2013-11-07 Pfizer Inc. Composés d'hexahydropyrano[3,4-d][1,3]thiazin-2-amine substitués par des hétérocycliques à titre d'inhibiteurs d'app, bace1 et bace2
WO2014045162A1 (fr) 2012-09-20 2014-03-27 Pfizer Inc. Composés d'hexahydropyrano[3,4-d][1,3]thiazine-2-amine alkyl-substitués
EP2931731A1 (fr) 2012-12-11 2015-10-21 Pfizer Inc. Composés d'hexahydropyrano [3,4-d][1,3]thiazin-2-amine en tant qu'inhibiteurs de bace1
CA2893333C (fr) 2012-12-19 2017-10-24 Pfizer Inc. Composes hexahydropyrano[3,4-d][1,3]thiazin-2-amine substitues carbocycliques et heterocycliques
JP2016507551A (ja) 2013-02-13 2016-03-10 ファイザー・インク ヘテロアリール置換ヘキサヒドロピラノ[3,4−d][1,3]チアジン−2−アミン化合物
US9233981B1 (en) 2013-02-15 2016-01-12 Pfizer Inc. Substituted phenyl hexahydropyrano[3,4-d][1,3]thiazin-2-amine compounds
CA2909045C (fr) 2013-05-02 2022-12-06 Glaxosmithkline Intellectual Property Development Limited Peptides therapeutiques
CA2926568C (fr) 2013-10-09 2017-09-05 Pfizer Inc. Antagonistes de recepteur ep3 de prostaglandine
KR20160098278A (ko) * 2013-12-20 2016-08-18 에프. 호프만-라 로슈 아게 C-말단 아미드화를 위한 펩티딜글라이신 알파-아미드화 모노옥시게나제 (pam) 의 용도
HUE039446T2 (hu) 2014-03-17 2018-12-28 Pfizer Diacilglicerol-aciltranszferáz-2 inhibitorok metabolikus rendellenességek és kapcsolódó rendellenességek kezelésében történõ alkalmazásra
MD20160105A2 (ro) 2014-04-10 2017-03-31 Pfizer Inc. 2-Amino-6-metil-4,4a,5,6-tetrahidropirano[3,4-d][1,3]tiazin-8a(8H)-il-1,3-tiazol-4-il amide
WO2016092413A1 (fr) 2014-12-10 2016-06-16 Pfizer Inc. Composés indoliques et indazoliques qui activent l'ampk
EP3237401B1 (fr) 2014-12-22 2019-03-06 Pfizer Inc Antagonistes de récepteur ep3 de prostaglandine
WO2016124687A1 (fr) * 2015-02-04 2016-08-11 Novo Nordisk A/S Composés pyy sélectifs et leurs utilisations
EP3766885B1 (fr) 2015-06-17 2022-05-25 Pfizer Inc. Composés tricycliques comme inhibiteurs de la phosphodiesterase
AU2016325665A1 (en) 2015-09-24 2018-03-08 Pfizer Inc. N-[2-(2-amino-6,6-disubstituted-4, 4a, 5, 6-tetrahydropyrano [3,4-d][1,3] thiazin-8a (8h)-yl) -1, 3-thiazol-4-yl] amides
JP2018534251A (ja) 2015-09-24 2018-11-22 ファイザー・インク Bace阻害剤として有用なn−[2−(3−アミノ−2,5−ジメチル−1,1−ジオキシド−5,6−ジヒドロ−2h−1,2,4−チアジアジン−5−イル)−1,3−チアゾール−4−イル]アミド
JP2018531924A (ja) 2015-09-24 2018-11-01 ファイザー・インク テトラヒドロピラノ[3,4−d][1,3]オキサジン誘導体、およびbace阻害剤としてのその使用
CN108473469B (zh) 2015-12-29 2020-11-03 辉瑞公司 作为己酮糖激酶抑制剂的被取代的3-氮杂双环[3.1.0]己烷
AR109179A1 (es) 2016-08-19 2018-11-07 Pfizer Inhibidores de diacilglicerol aciltransferasa 2
WO2019106193A1 (fr) 2017-12-01 2019-06-06 University Of Copenhagen Hormone peptidique avec un ou plusieurs o-glycanes
WO2019210154A1 (fr) * 2018-04-26 2019-10-31 Colorado State University Research Foundation Méthodes et compositions pour le suivi de produits végétaux
BR112021003039A2 (pt) 2018-08-31 2021-05-18 Pfizer Inc. combinações para o tratamento de nash/nafld e doenças relacionadas
WO2020234726A1 (fr) 2019-05-20 2020-11-26 Pfizer Inc. Combinaisons comprenant du benzodioxol en tant qu'agonistes de glp-1r destinées à être utilisées dans le traitement de la nash/nafld et de maladies associées
WO2023283392A1 (fr) * 2021-07-08 2023-01-12 Gila Therapeutics, Inc. Compositions et procédés d'activation d'un récepteur neuronal
WO2023026180A1 (fr) 2021-08-26 2023-03-02 Pfizer Inc. Forme amorphe de (s)-2-(5-((3-éthoxypyridin-2-yl)oxy)pyridin-3-yl)-n-(tétrahydrofuran-3-yl)pyrimidine-5-carboxamide
WO2024118524A1 (fr) 2022-11-28 2024-06-06 Cerevel Therapeutics, Llc Composés d'azaindole et leur utilisation en tant qu'inhibiteurs de phosphodiestérase

Family Cites Families (145)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US141985A (en) * 1873-08-19 Improvement in sewing-machine tables
US176643A (en) * 1876-04-25 Improvement in ironing-tables
US176630A (en) * 1876-04-25 Improvement in wagon-locks
US244041A (en) * 1881-07-12 Machine for blocking and shaping hats
US2919901A (en) * 1957-01-25 1960-01-05 Thor Power Tool Co Drill system with suction
US5508815A (en) * 1981-12-14 1996-04-16 Smart Vcr Limited Partnership Schedule display system for video recorder programming
US4908713A (en) * 1981-12-14 1990-03-13 Levine Michael R VCR Programmer
US4586158A (en) * 1983-02-22 1986-04-29 International Business Machines Corp. Screen management system
US4708934A (en) 1984-09-27 1987-11-24 Unigene Laboratories, Inc. α-amidation enzyme
US6319685B1 (en) 1984-09-27 2001-11-20 Unigene Laboratories, Inc. Alpha-amidating enzyme compositions and processes for their production and use
US6492107B1 (en) 1986-11-20 2002-12-10 Stuart Kauffman Process for obtaining DNA, RNA, peptides, polypeptides, or protein, by recombinant DNA technique
DE229046T1 (de) 1985-03-30 1987-12-17 Marc Genf/Geneve Ballivet Verfahren zum erhalten von dns, rns, peptiden, polypeptiden oder proteinen durch dns-rekombinant-verfahren.
US4821097A (en) * 1987-03-05 1989-04-11 General Instrument Corporation Apparatus and method for providing digital audio on the sound carrier of a standard television signal
US5789234A (en) 1987-08-14 1998-08-04 Unigene Laboratories, Inc. Expression systems for amidating enzyme
US4930160A (en) * 1987-09-02 1990-05-29 Vogel Peter S Automatic censorship of video programs
US4984152A (en) * 1987-10-06 1991-01-08 Bell Communications Research, Inc. System for controlling computer processing utilizing a multifunctional cursor with decoupling of pointer and image functionalities in space and time
US4827250A (en) * 1987-10-26 1989-05-02 Tektronix, Inc. Graphics display system having data transform circuit
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US4991011A (en) * 1988-12-23 1991-02-05 Scientific-Atlanta, Inc. Interactive television terminal with programmable background audio or video
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
JP2877509B2 (ja) 1989-05-19 1999-03-31 アムジエン・インコーポレーテツド メタロプロテイナーゼ阻害剤
US5727060A (en) * 1989-10-30 1998-03-10 Starsight Telecast, Inc. Television schedule system
DE69133566T2 (de) 1990-01-12 2007-12-06 Amgen Fremont Inc. Bildung von xenogenen Antikörpern
EP0814159B1 (fr) 1990-08-29 2005-07-27 GenPharm International, Inc. Souris transgéniques capables de produire des anticorps hétérologues
US5293357A (en) * 1990-09-10 1994-03-08 The Superguide Corporation Method and apparatus for controlling a television program recording device
US5247347A (en) * 1991-09-27 1993-09-21 Bell Atlantic Network Services, Inc. Pstn architecture for video-on-demand services
JP2654283B2 (ja) * 1991-09-30 1997-09-17 株式会社東芝 アイコン表示方法
US5317391A (en) * 1991-11-29 1994-05-31 Scientific-Atlanta, Inc. Method and apparatus for providing message information to subscribers in a cable television system
US5291554A (en) * 1992-05-28 1994-03-01 Tv Answer, Inc. Shared-price custom video rentals via interactive TV
FR2692575B1 (fr) 1992-06-23 1995-06-30 Sanofi Elf Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant.
EP0652950B1 (fr) 1992-07-24 2007-12-19 Amgen Fremont Inc. Production d'anticorps xenogeniques
JPH06139671A (ja) * 1992-10-27 1994-05-20 Sony Corp 記録再生システム
JP2721751B2 (ja) * 1992-10-30 1998-03-04 ジューキ株式会社 自動封入封緘装置におけるカッタユニット
US5592551A (en) * 1992-12-01 1997-01-07 Scientific-Atlanta, Inc. Method and apparatus for providing interactive electronic programming guide
US5715515A (en) * 1992-12-02 1998-02-03 Scientific-Atlanta, Inc. Method and apparatus for downloading on-screen graphics and captions to a television terminal
US5410326A (en) * 1992-12-04 1995-04-25 Goldstein; Steven W. Programmable remote control device for interacting with a plurality of remotely controlled devices
WO1994014284A1 (fr) * 1992-12-09 1994-06-23 Discovery Communications, Inc. Terminal reprogrammable destine a suggerer des programmes presentes dans un systeme de diffusion de programmes de television
US5600364A (en) * 1992-12-09 1997-02-04 Discovery Communications, Inc. Network controller for cable television delivery systems
US5483277A (en) * 1992-12-15 1996-01-09 Alcatel Network Systems Simplified set-top converter for broadband switched network
US5598524A (en) * 1993-03-03 1997-01-28 Apple Computer, Inc. Method and apparatus for improved manipulation of data between an application program and the files system on a computer-controlled display system
AU685803B2 (en) * 1993-03-29 1998-01-29 University Of Cincinnati, The Analogs of peptide YY and uses thereof
US5594509A (en) * 1993-06-22 1997-01-14 Apple Computer, Inc. Method and apparatus for audio-visual interface for the display of multiple levels of information on a display
US5621456A (en) * 1993-06-22 1997-04-15 Apple Computer, Inc. Methods and apparatus for audio-visual interface for the display of multiple program categories
US5414455A (en) * 1993-07-07 1995-05-09 Digital Equipment Corporation Segmented video on demand system
US5410344A (en) * 1993-09-22 1995-04-25 Arrowsmith Technologies, Inc. Apparatus and method of selecting video programs based on viewers' preferences
US5398071A (en) * 1993-11-02 1995-03-14 Texas Instruments Incorporated Film-to-video format detection for digital television
US5481542A (en) * 1993-11-10 1996-01-02 Scientific-Atlanta, Inc. Interactive information services control system
US5422674A (en) * 1993-12-22 1995-06-06 Digital Equipment Corporation Remote display of an image by transmitting compressed video frames representing background and overlay portions thereof
US5516653A (en) * 1993-12-28 1996-05-14 Synaptic Pharmaceutical Corporation DNA encoding a human neuropeptide Y/peptide YY/pancreatic polypeptide receptor (Y4) and uses thereof
JPH07244781A (ja) * 1994-03-07 1995-09-19 C S K Sogo Kenkyusho:Kk ソフトウェアレンタル方法および装置ならびに流通媒体
US5629732A (en) * 1994-03-29 1997-05-13 The Trustees Of Columbia University In The City Of New York Viewer controllable on-demand multimedia service
US5512958A (en) * 1994-04-29 1996-04-30 Matsushita Electric Corporation Of America System for controlling the effects of noise in television receivers
US5521631A (en) * 1994-05-25 1996-05-28 Spectravision, Inc. Interactive digital video services system with store and forward capabilities
JP3575063B2 (ja) * 1994-07-04 2004-10-06 ソニー株式会社 再生装置、再生方法
US5596106A (en) 1994-07-15 1997-01-21 Eli Lilly And Company Cannabinoid receptor antagonists
EP0699000B1 (fr) * 1994-08-24 2001-06-20 Hyundai Electronics America Serveur vidéo et système l'employant
US5682325A (en) * 1994-09-12 1997-10-28 Bell Atlantic Network Services, Inc. Level 1 gateway for video tone networks
US5619249A (en) * 1994-09-14 1997-04-08 Time Warner Entertainment Company, L.P. Telecasting service for providing video programs on demand with an interactive interface for facilitating viewer selection of video programs
DE4435477A1 (de) 1994-10-04 1996-04-11 Bayer Ag Cycloalkano-indol- und -azaindol-derivate
US5614940A (en) * 1994-10-21 1997-03-25 Intel Corporation Method and apparatus for providing broadcast information with indexing
JP3025907B2 (ja) 1994-10-27 2000-03-27 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ アポリポタンパク質−b合成阻害剤
US5521186A (en) 1994-10-27 1996-05-28 Janssen Pharmaceutica N.V. Apolipoprotein-β synthesis inhibitors
US5724521A (en) * 1994-11-03 1998-03-03 Intel Corporation Method and apparatus for providing electronic advertisements to end users in a consumer best-fit pricing manner
US5623613A (en) * 1994-11-29 1997-04-22 Microsoft Corporation System for displaying programming information
US5912227A (en) * 1995-01-27 1999-06-15 North Carolina State University Method of enhancing nutrient uptake
US5619247A (en) * 1995-02-24 1997-04-08 Smart Vcr Limited Partnership Stored program pay-per-play
US5632681A (en) * 1995-03-07 1997-05-27 International Business Machines Corporation Universal electronic video game renting/distributing system
US5651010A (en) * 1995-03-16 1997-07-22 Bell Atlantic Network Services, Inc. Simultaneous overlapping broadcasting of digital programs
ATE390933T1 (de) 1995-04-27 2008-04-15 Amgen Fremont Inc Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8
US5721829A (en) * 1995-05-05 1998-02-24 Microsoft Corporation System for automatic pause/resume of content delivered on a channel in response to switching to and from that channel and resuming so that a portion of the content is repeated
US6558708B1 (en) * 1995-05-17 2003-05-06 Cedars-Sinai Medical Center Methods for manipulating upper gastrointestinal transit, blood flow, and satiety, and for treating visceral hyperalgesia
US5740549A (en) * 1995-06-12 1998-04-14 Pointcast, Inc. Information and advertising distribution system and method
US5751282A (en) * 1995-06-13 1998-05-12 Microsoft Corporation System and method for calling video on demand using an electronic programming guide
US5724106A (en) * 1995-07-17 1998-03-03 Gateway 2000, Inc. Hand held remote control device with trigger button
US5745837A (en) * 1995-08-25 1998-04-28 Terayon Corporation Apparatus and method for digital data transmission over a CATV system using an ATM transport protocol and SCDMA
US5737028A (en) * 1995-11-01 1998-04-07 International Business Machines Corporation Previous channel listing with cursor controlled user interface for television video displays
US5919901A (en) * 1996-04-08 1999-07-06 Bayer Corporation Neuropeptide Y receptor Y5 and nucleic acid sequences
US5721897A (en) * 1996-04-09 1998-02-24 Rubinstein; Seymour I. Browse by prompted keyword phrases with an improved user interface
US5721827A (en) * 1996-10-02 1998-02-24 James Logan System for electrically distributing personalized information
EP2262243A1 (fr) * 1996-12-10 2010-12-15 United Video Properties, Inc. Appareil pour guide de programme électronique via internet
US6654933B1 (en) * 1999-09-21 2003-11-25 Kasenna, Inc. System and method for media stream indexing
EP2088188B1 (fr) 1997-04-16 2011-08-31 Unigene Laboratories, Inc. Expression directe des peptides dans un milieu de culture
IL121230A (en) * 1997-07-03 2004-05-12 Nds Ltd Intelligent electronic program guide
US6342220B1 (en) 1997-08-25 2002-01-29 Genentech, Inc. Agonist antibodies
BR9812540A (pt) 1997-09-26 2001-12-26 Athersys Inc Expressão de genes endógenos por recombinaçãonão homóloga de uma construção de vetor comdna celular
US6046167A (en) * 1998-03-25 2000-04-04 University Of Cincinnati Peptide YY analogs
US6505348B1 (en) * 1998-07-29 2003-01-07 Starsight Telecast, Inc. Multiple interactive electronic program guide system and methods
US6360053B1 (en) * 1998-08-07 2002-03-19 Replaytv, Inc. Method and apparatus for fast forwarding and rewinding in a video recording device
IL141769A0 (en) 1998-09-11 2002-03-10 Aventis Pharma Sa Azetidine derivatives, preparation and medicines containing them
US20020026638A1 (en) * 2000-08-31 2002-02-28 Eldering Charles A. Internet-based electronic program guide advertisement insertion method and apparatus
FR2789079B3 (fr) 1999-02-01 2001-03-02 Sanofi Synthelabo Derive d'acide pyrazolecarboxylique, sa preparation, les compositions pharmaceutiques en contenant
EP1189629B1 (fr) * 1999-02-10 2010-09-29 Curis, Inc. Peptide yy (pyy) pour traiter des troubles metaboliques du glucose
US7086077B2 (en) * 1999-04-01 2006-08-01 Sedna Patent Services, Llc Service rate change method and apparatus
US7150031B1 (en) * 2000-06-09 2006-12-12 Scientific-Atlanta, Inc. System and method for reminders of upcoming rentable media offerings
US6986156B1 (en) * 1999-06-11 2006-01-10 Scientific Atlanta, Inc Systems and methods for adaptive scheduling and dynamic bandwidth resource allocation management in a digital broadband delivery system
US6832386B1 (en) * 1999-06-11 2004-12-14 Scientific-Atlanta, Inc. System and method for allowing a user to quickly navigate within a program guide to an established reference point
US7010801B1 (en) * 1999-06-11 2006-03-07 Scientific-Atlanta, Inc. Video on demand system with parameter-controlled bandwidth deallocation
US7228556B2 (en) * 1999-12-21 2007-06-05 Tivo Inc. Distributed, interactive television program guide; system and method
US20030030679A1 (en) * 2000-01-06 2003-02-13 Anuj Kumar Jain User-definable images in bookmarks
WO2001075736A1 (fr) * 2000-03-31 2001-10-11 Liquid Engines, Inc. Moteur d'adaptation electronique pour adapter des caracteristiques voulues a des attributs d'articles
ES2400716T3 (es) * 2000-03-31 2013-04-11 United Video Properties, Inc. Sistema y método de medios interactivos para presentar contenido
US20020007485A1 (en) * 2000-04-03 2002-01-17 Rodriguez Arturo A. Television service enhancements
GB0008691D0 (en) * 2000-04-07 2000-05-31 Post Impressions Systems Ltd Input and output systems for data processing
US7934232B1 (en) * 2000-05-04 2011-04-26 Jerding Dean F Navigation paradigm for access to television services
US8069259B2 (en) * 2000-06-09 2011-11-29 Rodriguez Arturo A Managing removal of media titles from a list
US7685520B2 (en) * 2000-06-22 2010-03-23 Intel Corporation Electronic programming guide with selectable categories
US7962370B2 (en) * 2000-06-29 2011-06-14 Rodriguez Arturo A Methods in a media service system for transaction processing
JP4356226B2 (ja) * 2000-09-12 2009-11-04 ソニー株式会社 サーバ装置、配信システム、配信方法、及び端末装置
US8302127B2 (en) * 2000-09-25 2012-10-30 Thomson Licensing System and method for personalized TV
WO2002032120A2 (fr) * 2000-10-11 2002-04-18 United Video Properties, Inc. Systemes et procedes d'elaboration de listes de medias d'utilisateur
US20020049978A1 (en) * 2000-10-20 2002-04-25 Rodriguez Arturo A. System and method for access and placement of media content information items on a screen display with a remote control device
US6924291B2 (en) 2001-01-23 2005-08-02 Merck & Co., Inc. Process for making spiro isobenzofuranone compounds
EP1373216B1 (fr) 2001-03-22 2004-12-15 Solvay Pharmaceuticals B.V. Derives de 4,5-dihydro-1h-pyrazole ayant une activite d'antagoniste de cb 1
MXPA03009566A (es) 2001-04-19 2004-12-06 Scripps Research Inst Metodos y composicion para la produccion de pares trna-aminoaciltrna sintetasa ortogonales.
NZ528752A (en) 2001-06-28 2006-06-30 Pfizer Prod Inc Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (MTP) and/or apolipoprotein B (APO B) secretion
US8006262B2 (en) * 2001-06-29 2011-08-23 Rodriguez Arturo A Graphic user interfaces for purchasable and recordable media (PRM) downloads
CN100350968C (zh) 2001-09-24 2007-11-28 皇家创新有限公司 饮食行为的改进
US7142590B2 (en) * 2001-10-11 2006-11-28 Utstarcom Inc. Method and system for oversubscribing a DSL modem
US20030074257A1 (en) * 2001-10-12 2003-04-17 Michael Saveliev Method and apparatus for advertising adjacent to a beverage dispenser to facilitate advertising income device placement in high traffic venues
US7334251B2 (en) * 2002-02-11 2008-02-19 Scientific-Atlanta, Inc. Management of television advertising
AU2003219934A1 (en) 2002-03-06 2003-09-22 Merck And Co., Inc. Method of treatment or prevention of obesity
US7423067B2 (en) 2002-03-26 2008-09-09 Merck & Co., Inc. Diphenyl cyclopentyl amides as cannabinoid-1 receptor inverse agonists
ES2301833T3 (es) 2002-07-29 2008-07-01 Hoffmann La Roche Derivados de benzodioxol.
EP1558252B1 (fr) 2002-08-02 2007-10-10 Merck & Co., Inc. Derives de furo[2,3-b]pyridine substitues
US7129239B2 (en) 2002-10-28 2006-10-31 Pfizer Inc. Purine compounds and uses thereof
MY134457A (en) 2002-11-22 2007-12-31 Merck & Co Inc Substituted amides
US7186692B2 (en) 2002-12-17 2007-03-06 Nastech Pharmaceutical Company Inc. Compositions and methods for enhanced mucosal delivery and non-infused administration of Y2 receptor-binding peptides and methods for treating and preventing obesity
CA2510199A1 (fr) 2002-12-17 2004-07-08 Nastech Pharmaceutical Company Inc. Compositions et procedes permettant d'ameliorer l'administration aux muqueuses de peptides de liaison du recepteur y2, et procedes pour le traitement et la prevention de l'obesite
AU2003289118A1 (en) * 2002-12-18 2004-07-09 International Business Machines Corporation Web service providing system, server device for the same, control method for controlling computer system as server device for web service providing system, program for executing the control method, and recording medium
US7329658B2 (en) 2003-02-06 2008-02-12 Pfizer Inc Cannabinoid receptor ligands and uses thereof
US20070027073A1 (en) * 2003-04-08 2007-02-01 Menachem Rubinstein Long-acting derivatives of pyy agonists
US7145012B2 (en) 2003-04-23 2006-12-05 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US7141669B2 (en) 2003-04-23 2006-11-28 Pfizer Inc. Cannabiniod receptor ligands and uses thereof
AU2004241242A1 (en) 2003-05-14 2004-12-02 Emisphere Technologies, Inc. Compositions for delivering peptide YY and PYY agonists
US8008255B2 (en) 2003-05-30 2011-08-30 Amylin Pharmaceuticals, Inc. Methods and compositions for enhanced transmucosal delivery of peptides and proteins
US7274740B2 (en) * 2003-06-25 2007-09-25 Sharp Laboratories Of America, Inc. Wireless video transmission system
US20050091693A1 (en) * 2003-10-22 2005-04-28 Rochelle Communications, Inc. Dual mode set-top box that optimizes the delivery and user selection of audio or video programming over data networks
US7151097B2 (en) 2003-11-07 2006-12-19 Pfizer Inc. Bicyclic pyrazolyl and imidazolyl compounds and uses thereof
EA010369B1 (ru) 2004-02-04 2008-08-29 Пфайзер Продактс Инк. Замещенные хинолиновые соединения
JP5638177B2 (ja) * 2004-02-11 2014-12-10 アミリン・ファーマシューティカルズ, リミテッド・ライアビリティ・カンパニーAmylin Pharmaceuticals, Llc 膵臓ポリペプチドファミリーモチーフおよびそのモチーフを含むポリペプチド
EP1718671A2 (fr) * 2004-02-23 2006-11-08 Rheoscience A/S Analogues du peptide yy
US7954129B2 (en) * 2004-09-24 2011-05-31 Smartvue Corporation Wireless video surveillance system and method with remote viewing
US20060088105A1 (en) * 2004-10-27 2006-04-27 Bo Shen Method and system for generating multiple transcoded outputs based on a single input
US7620065B2 (en) * 2005-07-22 2009-11-17 Trellia Networks, Inc. Mobile connectivity solution
US8189472B2 (en) * 2005-09-07 2012-05-29 Mcdonald James F Optimizing bandwidth utilization to a subscriber premises

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US20060178501A1 (en) 2006-08-10
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