JP2021504403A - 骨髄浸潤リンパ球を動員する方法、およびその使用 - Google Patents
骨髄浸潤リンパ球を動員する方法、およびその使用 Download PDFInfo
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
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- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
Description
式(I)の異性体、式(I)の互変異性体、およびこれらのいずれかの薬学的に許容可能な塩から選択され、
ここで、
R1はC1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
R2はH、−M、および−L−Mから選択され;
R3は−OH基、−NH2基、−OC(=O)Y1基、−NHC(=O)Y1基、および−NHC(=O)NHY1基から選択され、ここでY1は、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、C2−C8ハロアルキニル基、C6−C18アリール基、およびC1−C13ヘテロアリール基から選択され;
R4は−OH基、および−NZ1Z2基から選択され、ここで同一または異なってもよい、Z1およびZ2はそれぞれ独立してH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され、ここでZ1およびZ2は一緒に環を形成してもよく;
R5はC3−C8シクロアルキル基から選択され;
R6は−OH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
R7は−CH2OH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
R8はC1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
Lはリンカー基から選択され;および
Mは−C(=O)NH(CH2)1−4NH2基、C1−C8アルキル基、−C(=O)OY2基、およびポリエチレングリコール、チアゾリル、またはクロメニルを含む部分から選択される非糖模倣部分であり、ここでY2はC1−C4アルキル基、C2−C4アルケニル基、およびC2−C4アルキニル基から選択される。
式(II)の異性体、式(II)の互変異性体、およびこれらのいずれかの薬学的に許容可能な塩から選択され、
ここで、
R1はH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
R2は−OH基、−NH2基、−OC(=O)Y1基、−NHC(=O)Y1基、および−NHC(=O)NHY1基から選択され、ここでY1は、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、C2−C8ハロアルキニル基、C6−C18アリール基およびC1−C13ヘテロアリール基から選択され;
R3は−CN基、−CH2CN基および−C(=O)Y2基から選択され、ここでY2は、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、−OZ1基、−NHOH基、−NHOCH3基、−NHCN基および−NZ1Z2基から選択され、ここで同一または異なってもよいZ1およびZ2は、独立してH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され、ここでZ1およびZ2は一緒に環を形成してもよく;
R4はC3−C8シクロアルキル基から選択され;
R5は独立してH基、ハロ基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
nは1から4の範囲の整数から選択され;および
Lはリンカー基から選択される。
から選択される。
である。
から選択される。
である。
である。
から選択され、
ここで、nは1から100の範囲の整数から選択される。いくつかの実施形態において、nは4、8、12、16、20、24、および28から選択される。
から選択される。
から選択される。
(001)
化学物質:GMI−1271(100% 親(parent)、純度97%より上)を白色、結晶性物質として得た。GMI−1271を−20℃で遮光して保存した。化合物を、滅菌リン酸緩衝生理食塩水(PBS)中で処方し、pHの値7.4および4mg/mlの濃度で透明、無色の溶液を得た。投薬溶液を、最初の投与の12時間前に調製し、4℃で治療の間遮光して保存した。
(002)
動物および畜産:メスのEnvigo Balb/cマウス(BALB/cAnNHsd)が、本研究において使用された。それらは、実験の1日目に生後6から7週であった。動物は、照射されたHarlan 2918.15 Rodent Dietおよび水を適宜供給された。動物は、Biobubble(登録商標)クリーンルーム内のトウモロコシの穂軸の寝藁を備えたInnovive使い捨て換気ケージに収容され、H.E.P.Aフィルター処理された空気を1時間あたり100回の完全な空気交換でバブル環境(bubble environment)に供給した。治療、体重決定、および腫瘍測定のすべてが、バブル環境下で行われた。環境は、70°±2°Fの温度範囲、および30から70%の湿度範囲で制御された。
(003)
がん細胞調製:CT26WT細胞を得た。それらは、RPMI1640培地中で培養した。RPMI1640培地は、1%の100mMピルビン酸ナトリウム、1%の1M HEPESバッファー、1%の45%グルコース溶液で改変され、そして10%非熱不活化ウシ胎児血清(FBS)および1%の100Xペニシリン/ストレプトマイシン/L−グルタミン(PSG)が補充された。増殖環境は、5%CO2雰囲気、37℃でインキュベーター中に維持した。増殖が完了した際、細胞(継代数 3)を、0.25%トリプシンEDTA溶液を使用してトリプシン処理し、細胞を剥離し、トリプシンを完全な培養培地で希釈することにより不活性化し、任意の細胞凝集をピペッティングにより分離した。細胞を200rcfで8分間4℃で遠心分離し、上清を吸引し、そしてペレットを冷ダルベッコリン酸緩衝生理食塩水(DPBS)中にピペッティングにより再懸濁させた。均一な細胞懸濁液の分取分をトリパンブルー溶液中に希釈し、Luna自動セルカウンターを使用して数えた。移植前細胞生存率は93%であった。細胞懸濁液は、200rcfで8分間4℃で遠心分離した。上清を吸引し、そして細胞ペレットを冷無血清培地中に再懸濁させ、最終濃度2.50E+06トリパン除去細胞/mLで得た。細胞懸濁液を移植中氷上で維持した。
GMI−1271、GMI−1359、またはG−CSFを投与後、CT26免疫マウス中のCD8+T細胞の分布が、解析された。図1Aから1Cに示されるように、CD8+T細胞の表現型は、抹消血液および骨髄試料で測定された。データは、G−CSFと対照的に、GMI−1271およびGMI−1359での治療が、末梢血液中のナイーブ(図1A)およびセントラルメモリー(CM)CD8+T細胞(図1B)の両方を動員したことを示す。エフェクターメモリー(EM)CD8+T細胞の再分布は、GMI−1271、またはGMI−1359によって影響されない(図1C)。
Claims (20)
- がんを治療する、および/またはがんの再発を予防する方法であって、ここで前記方法が、患者に少なくとも一つのEセレクチン拮抗薬を投与するステップを含み、投与される前記Eセレクチン拮抗薬の量が、前記患者のMILを末梢血液中に動員するのに十分である方法。
- がんを治療する、および/またはがんの再発を予防する方法であって、ここで前記方法が、
ドナー患者に少なくとも一つのEセレクチン拮抗薬を、投与するステップであって、ここで投与される前記Eセレクチン拮抗薬の量が、前記ドナー患者のMILを末梢血液中に動員するのに十分であるステップ;
前記末梢血液からMILを回収するステップ;ならびに
MIL細胞集団の少なくとも一部を、前記ドナー患者または第2の患者に移植するステップ、
を含む方法。 - がんを予防する方法であって、ここで前記方法が、
ドナー患者に少なくとも一つのEセレクチン拮抗薬を投与するステップであって、ここで投与される前記Eセレクチン拮抗薬の量が、前記患者のMILを末梢血液中に動員するのに十分であるステップ;
前記末梢血液からMILを回収するステップ;ならびに
MIL細胞集団の少なくとも一部を、被験体に移植するステップ、
を含む方法。 - 回収したMILを、移植前にex vivoで増殖させる、請求項2または3に記載の前記方法。
- 前記少なくとも一つのEセレクチン拮抗薬が、医薬組成物の形態である、請求項1から4のいずれか一項に記載の前記方法。
- 前記医薬組成物が、少なくとも一つの追加の薬学的に許容可能な成分をさらに含む、請求項5に記載の前記方法。
- 前記少なくとも一つのEセレクチン拮抗薬が、シアリルルイスX(sLex)およびsLex模倣物から選択される、請求項1から4のいずれか一項に記載の前記方法。
- 前記少なくとも一つのEセレクチン拮抗薬が、糖模倣物、抗体、ペプチド、ポリペプチド、ペプチド模倣物、およびアプタマーから選択される、請求項1から4のいずれか一項に記載の前記方法。
- 前記少なくとも一つのEセレクチン拮抗薬が、式(I)の化合物:
式(I)の異性体、式(I)の互変異性体、およびこれらのいずれかの薬学的に許容可能な塩から選択される、請求項1から4のいずれか一項に記載の前記方法であって、
ここで、
R1はC1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
R2はH、−M、および−L−Mから選択され;
R3は−OH基、−NH2基、−OC(=O)Y1基、−NHC(=O)Y1基、および−NHC(=O)NHY1基から選択され、ここでY1は、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、C2−C8ハロアルキニル基、C6−C18アリール基、およびC1−C13ヘテロアリール基から選択され;
R4は−OH基、および−NZ1Z2基から選択され、ここで同一または異なってもよいZ1およびZ2は、それぞれ独立してH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され、ここでZ1およびZ2は一緒に環を形成してもよく;
R5はC3−C8シクロアルキル基から選択され;
R6は−OH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
R7は−CH2OH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
R8はC1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
Lはリンカー基から選択され;および
Mは−C(=O)NH(CH2)1−4NH2基、C1−C8アルキル基、−C(=O)OY2基、およびポリエチレングリコール、チアゾリル、またはクロメニルを含む部分から選択される非糖模倣部分であり、ここでY2はC1−C4アルキル基、C2−C4アルケニル基、およびC2−C4アルキニル基から選択される方法。 - 前記少なくとも一つのEセレクチン拮抗薬が、式(Ia)の化合物
から選択される、請求項1から4のいずれか一項に記載の前記方法であって、ここでnが1から100の範囲の整数から選択される方法。 - 前記少なくとも一つのEセレクチン拮抗薬が、式(II)の化合物:
式(II)の異性体、式(II)の互変異性体、および前記化合物のいずれかの薬学的に許容可能な塩から選択される、請求項1から4のいずれか一項に記載の前記方法であって、
ここで、
R1はH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
R2は−OH基、−NH2基、−OC(=O)Y1基、−NHC(=O)Y1基、および−NHC(=O)NHY1基から選択され、ここでY1は、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、C2−C8ハロアルキニル基、C6−C18アリール基およびC1−C13ヘテロアリール基から選択され;
R3は−CN基、−CH2CN基および−C(=O)Y2基から選択され、ここでY2は、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、−OZ1基、−NHOH基、−NHOCH3基、−NHCN基および−NZ1Z2基から選択され、ここで同一または異なってもよいZ1およびZ2は、独立してH基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され、ここでZ1およびZ2は一緒に環を形成してもよく;
R4はC3−C8シクロアルキル基から選択され;
R5は独立して、H基、ハロ基、C1−C8アルキル基、C2−C8アルケニル基、C2−C8アルキニル基、C1−C8ハロアルキル基、C2−C8ハロアルケニル基、およびC2−C8ハロアルキニル基から選択され;
nは1から4の範囲の整数から選択され;および
Lはリンカー基から選択される方法。 - 前記少なくとも一つのEセレクチン拮抗薬が、式(IIa)の化合物
から選択される、請求項1から4のいずれか一項に記載の前記方法。 - 前記方法がさらに、前記患者へ、前記少なくとも一つのEセレクチン拮抗薬の投与と共に、コロニー刺激因子を投与することを含む、請求項1から12のいずれか一項に記載の前記方法。
- 前記患者が、化学療法および/または放射線療法を受けているか、または受ける予定である、請求項1から13のいずれか一項に記載の前記方法。
- 前記化学療法が、ボルテゾミブおよび/またはゲムシタビンの投与を含む、請求項14に記載の前記方法。
- 前記がんが、血液がんである、請求項1から15のいずれか一項に記載の前記方法。
- 前記がんが、固形がんである、請求項1から15のいずれか一項に記載の前記方法。
- 前記がんが、液性がん(liquid cancer)である、請求項1から15のいずれか一項に記載の前記方法。
- 前記患者が、第1タイプのがんと診断されており、治療および/または予防するために実行する前記方法の対象の前記がんが、第2タイプのがんである、請求項1から15のいずれか一項に記載の前記方法。
- 少なくとも一つのEセレクチン拮抗薬によって骨髄から外に動員された、がん患者由来のMILを含む組成物。
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015500887A (ja) * | 2011-12-22 | 2015-01-08 | グリコミメティクス, インコーポレイテッド | E−セレクチンアンタゴニスト化合物、組成物および使用方法 |
WO2016089872A1 (en) * | 2014-12-03 | 2016-06-09 | Glycomimetics, Inc. | Heterobifunctional inhibitors of e-selectins and cxcr4 chemokine receptors |
Family Cites Families (244)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL7409399A (nl) | 1973-07-19 | 1975-01-21 | Rhone Poulenc Sa | Werkwijze ter bereiding van thermostabiele har- sen en voorwerpen geheel of gedeeltelijk be- staande uit deze harsen. |
US4471057A (en) | 1981-06-30 | 1984-09-11 | The Wistar Institute | Detection of colorectal carcinoma |
DK17885D0 (da) | 1985-01-14 | 1985-01-14 | Karlsson Karl Anders | Antiviralt middel |
US4876199A (en) | 1985-04-04 | 1989-10-24 | Fred Hutchinson Cancer Research Center | Hybridomas producing monoclonal antibodies to mono-, di-, and trifucosylated type 2 chain |
US4851511A (en) | 1986-01-30 | 1989-07-25 | Fred Hutchinson Cancer Research Center | Monoclonal antibody that specifically binds to disialosyl Lea |
US4925796A (en) | 1986-03-07 | 1990-05-15 | Massachusetts Institute Of Technology | Method for enhancing glycoprotein stability |
ATE94395T1 (de) | 1986-05-09 | 1993-10-15 | Pulverer Gerhard | Verwendung von spezifischen monosacchariden zur herstellung eines arzneimittels zur verhinderung von metastasen maligner tumore. |
US5538724A (en) | 1987-08-11 | 1996-07-23 | The Board Of Trustees For The Leland Stanford Junior Univ. | Method of control leukocyte extravasation |
US5079353A (en) | 1987-12-02 | 1992-01-07 | Chembiomed, Ltd. | Sialic acid glycosides, antigens, immunoadsorbents, and methods for their preparation |
US5632991A (en) | 1988-11-14 | 1997-05-27 | Brigham & Women's Hospital | Antibodies specific for E-selectin and the uses thereof |
EP0381310A1 (en) | 1989-01-30 | 1990-08-08 | The Biomembrane Institute | Monoclonal antibodies directed to tumor-associated gangliosides and fucogangliosides and method for production thereof |
US5464778A (en) | 1989-03-08 | 1995-11-07 | Board Of Regents Of The University Of Oklahoma | Glycoprotein ligand for P-selectin and methods of use thereof |
US5272263A (en) | 1989-04-28 | 1993-12-21 | Biogen, Inc. | DNA sequences encoding vascular cell adhesion molecules (VCAMS) |
EP0585963A1 (en) | 1989-05-23 | 1994-03-09 | Otsuka Pharmaceutical Co., Ltd. | Monoclonal antibodies to CMP-170 antigen on activated endothelial cells |
US6033665A (en) | 1989-09-27 | 2000-03-07 | Elan Pharmaceuticals, Inc. | Compositions and methods for modulating leukocyte adhesion to brain endothelial cells |
US6001988A (en) | 1990-06-11 | 1999-12-14 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands to lectins |
US6280932B1 (en) | 1990-06-11 | 2001-08-28 | Gilead Sciences, Inc. | High affinity nucleic acid ligands to lectins |
AU8007791A (en) | 1990-06-15 | 1992-01-07 | Cytel Corporation | Intercellular adhesion mediators |
US5576305A (en) | 1990-06-15 | 1996-11-19 | Cytel Corporation | Intercellular adhesion mediators |
US5753631A (en) | 1990-06-15 | 1998-05-19 | Cytel Corporation | Intercellular adhesion mediators |
US6391857B1 (en) | 1990-06-18 | 2002-05-21 | Stanford University | Methods and compositions for endothelial binding |
US6387884B1 (en) | 1990-06-18 | 2002-05-14 | Stanford University | Leukocyte homing modulation |
ATE224911T1 (de) | 1990-07-17 | 2002-10-15 | Univ Oklahoma | Gmp-140 ligand |
US5648344A (en) | 1990-07-30 | 1997-07-15 | Glycomed Incorporated | Methods of treating inflammation using selection binding compounds |
US5211937A (en) | 1990-07-30 | 1993-05-18 | Glycomed Incorporated | Method of determining a site of inflammation utilizing elam-1 ligands |
US5143712A (en) | 1990-07-30 | 1992-09-01 | Glycomed Incorporated | Method of determining a site of inflammation utilizing elam-1 ligands |
US5789573A (en) | 1990-08-14 | 1998-08-04 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2 |
NZ240316A (en) | 1990-10-25 | 1996-12-20 | Univ Michigan | Compound for treating disease mediated by the elaboration of elam-1 on endothelial cells |
IE914075A1 (en) | 1990-11-23 | 1992-06-03 | Gen Hospital Corp | Inhibition of cell adhesion protein-carbohydrate¹interactions |
US5151360A (en) | 1990-12-31 | 1992-09-29 | Biomembrane Institute | Effect of n,n,n-trimethylsphingosine on protein kinase-c activity, melanoma cell growth in vitro, metastatic potential in vivo and human platelet aggregation |
US6124267A (en) | 1991-02-05 | 2000-09-26 | Southpac Trust Internationals, Inc. | O-glycan inhibitors of selectin mediated inflammation derived from PSGL-1 |
US6309639B1 (en) | 1991-02-05 | 2001-10-30 | The Board Of Regents Of The University Of Oklahoma | Method for inhibiting an inflammatory response using antibodies to P-selectin glycoprotein ligand |
US6121233A (en) | 1991-04-19 | 2000-09-19 | John L. Magnani | Methods for the inhibition of cancer metastasis mediated by endothelial adhesion molecules |
EP0584229B1 (en) | 1991-05-06 | 2003-07-23 | Genentech, Inc. | A selectin ligand |
US5318890A (en) | 1991-05-06 | 1994-06-07 | The Regents Of The University Of California | Assays for inhibitors of leukocyte adhesion |
US5646123A (en) | 1991-06-10 | 1997-07-08 | Alberta Research Council | Time dependent administration of oligosaccharide glycosides related to blood group determinants having a type I or type II core structure in reducing inflammation in a sensitized mammal arising form exposure to an antigen |
US5580858A (en) | 1991-06-10 | 1996-12-03 | Alberta Research Council | Immunosuppressive and tolerogenic modified Lewisx compounds |
US5352670A (en) | 1991-06-10 | 1994-10-04 | Alberta Research Council | Methods for the enzymatic synthesis of alpha-sialylated oligosaccharide glycosides |
JPH07507040A (ja) | 1991-09-10 | 1995-08-03 | セントコー,インコーポレイテッド | セレクチンによって介在される炎症のペプチド阻害剤 |
US5268364A (en) | 1991-12-12 | 1993-12-07 | The Biomembrane Institute | Method for inhibiting selectin-dependent adhesion of leukocytes and platelets by O-glycosylation modification |
JPH07501828A (ja) | 1991-12-18 | 1995-02-23 | セントコー,インコーポレイテッド | セレクチン類で仲介される炎症のペプチド阻害剤 |
US5643873A (en) | 1992-05-06 | 1997-07-01 | Affymax Technologies N.V. | Peptides and compounds that bind selectins including endothelial leukocyte adhesion molecule 1 |
US5591835A (en) | 1992-06-29 | 1997-01-07 | Glycomed Incorporated | Substituted lactose derivatives |
CA2100412A1 (en) | 1992-07-15 | 1994-01-16 | Yutaka Yamada | Glycolipid derivatives |
US5753617A (en) | 1992-09-08 | 1998-05-19 | Centocor, Inc. | Peptide inhibitors of cellular adhesion |
US5519008A (en) | 1992-09-10 | 1996-05-21 | Glycomed Incorporated | Derivatives of triterpenoid acids as inhibitors of cell-adhesion molecules ELAM-1 (E-selectin) and LECAM-1 (L-selectin) |
WO1994006442A1 (en) | 1992-09-11 | 1994-03-31 | The Regents Of The University Of California | Sulfated ligands for l-selectins and use of chlorates and or sulfatases for the treatment of inflammation |
US5695752A (en) | 1992-09-11 | 1997-12-09 | The Regents Of The University Of California | Treating inflammation via the administration of specific sulfatase enzymes and/or sulfation inhibitor |
US6277975B1 (en) | 1992-10-23 | 2001-08-21 | Genetics Institute, Inc. | Fusions of P-selectin ligand protein and polynucleotides encoding same |
US5843707A (en) | 1992-10-23 | 1998-12-01 | Genetics Institute, Inc. | Nucleic acid encoding a novel P-selectin ligand protein |
EP0601417A3 (de) | 1992-12-11 | 1998-07-01 | Hoechst Aktiengesellschaft | Physiologisch verträglicher und physiologisch abbaubarer, Kohlenhydratrezeptorblocker auf Polymerbasis, ein Verfahren zu seiner Herstellung und seine Verwendung |
WO1994014836A1 (en) | 1992-12-18 | 1994-07-07 | Centocor, Inc. | Peptide inhibitors of selectin binding |
DE69322289T2 (de) | 1992-12-29 | 1999-05-20 | Genentech Inc | Behandlung von entzündlichen darmerkrankungen mit interferon-gamma-inhibitoren |
US5412123A (en) | 1993-02-08 | 1995-05-02 | Glycomed Incorporated | Anthraquinone and anthracene derivatives as inhibitors of the cell-adhesion molecules of the immune system |
JP2716657B2 (ja) | 1993-02-26 | 1998-02-18 | 株式会社ディ・ディ・エス研究所 | 接着分子elam‐1に特異的結合能を有する化合物 |
CA2157489A1 (en) | 1993-03-04 | 1994-09-15 | Masaaki Numata | Lewis-associated compound, process for producing the same, and anti-inflammatory |
US5527890A (en) | 1993-04-16 | 1996-06-18 | Glycomed Incorporated | Derivatives of triterpenoid acids and uses thereof |
AU4236393A (en) | 1993-05-05 | 1994-11-21 | Affymax Technologies N.V. | Peptides and compounds that bind to elam-1 |
SE9301677L (sv) | 1993-05-14 | 1994-11-18 | Kurt G I Nilsson | Syntesmetod |
US5854218A (en) | 1993-05-14 | 1998-12-29 | Cytel Corporation | Sialyl Lex analogues as inhibitors of cellular adhesion |
US5811404A (en) | 1993-05-14 | 1998-09-22 | Cytel Corporation | Sialyl Lex analogues as inhibitors of cellular adhesion |
US5527785A (en) | 1993-05-14 | 1996-06-18 | The Regents Of The University Of California | Selectin receptor modulating compositions |
CZ298895A3 (en) | 1993-05-14 | 1996-04-17 | Cytel Corp | Compound analogous to sialyl lex, pharmaceutical composition containing thereof and process for preparing lactosammonium salt |
SG52383A1 (en) | 1993-05-17 | 1998-09-28 | T Cell Sciences Inc | Compositions comprising complement related proteins and carbohydrates and methods for producing and using said compositions |
US5856300A (en) | 1994-05-12 | 1999-01-05 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
US5976540A (en) | 1993-05-17 | 1999-11-02 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
US5646248A (en) | 1993-06-08 | 1997-07-08 | La Jolla Cancer Research Foundation | E-selection binding soluble lamp-1 polypeptide |
US5837689A (en) | 1993-06-16 | 1998-11-17 | Glycomed Incorporated | Sialyl lewis-x mimetics containing naphthyl backbones |
US5658880A (en) | 1993-06-16 | 1997-08-19 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
US5750508A (en) | 1993-06-16 | 1998-05-12 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
US5789385A (en) | 1993-06-16 | 1998-08-04 | Glycomed Incorporated | Sialyl Lewisx mimetics containing phenyl backbones |
US5679321A (en) | 1993-06-17 | 1997-10-21 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
DK76193D0 (da) | 1993-06-25 | 1993-06-25 | Astra Ab | Kulhydratderivater |
US5559103A (en) | 1993-07-21 | 1996-09-24 | Cytel Corporation | Bivalent sialyl X saccharides |
US5508387A (en) | 1993-08-04 | 1996-04-16 | Glycomed Incorporated | Selectin binding glycopeptides |
WO1995005830A1 (en) | 1993-08-20 | 1995-03-02 | The Regents Of The University Of California | Polyanion anti-inflammatory agents |
US5464815A (en) | 1993-09-08 | 1995-11-07 | Genentech, Inc. | Inhibition of heparin-binding |
JPH09504522A (ja) | 1993-10-12 | 1997-05-06 | グリコメド・インコーポレイテッド | 細胞接着インヒビターの同定に有用なグリコ−ペプチドのライブラリー |
US5783693A (en) | 1993-11-19 | 1998-07-21 | The Regents Of The University Of California | Methods for synthesizing sulfated disaccharide inhibitors of selectins |
WO1995014787A1 (en) | 1993-11-22 | 1995-06-01 | Centocor, Inc. | Peptide inhibitors of selecting binding |
US5663151A (en) | 1994-03-04 | 1997-09-02 | Bristol-Myers Squibb Company | Sulfated α-glycolipid derivatives as cell adhesion inhibitors |
EP0671409A3 (de) | 1994-03-11 | 1996-06-12 | Hoechst Ag | Malonsäurederivate mit antiadhäsiven Eigenschaften. |
DE4408248A1 (de) | 1994-03-11 | 1995-09-14 | Hoechst Ag | Physiologisch verträgliche und physiologisch abbaubare Kohlenhydrat-Mimetika, ein Verfahren zur Herstellung und ihre Verwendung |
HUT77345A (hu) | 1994-04-29 | 1998-03-30 | Texas Biotechnology Corporation | E-szelektin, P-szelektin vagy L-szelektin szialil-Lewis x-hez vagy szialil-Lewis a-hoz kapcsolódását gátló mannopiranoziloxi-bifenil származékok és ezeket tartalmazó gyógyszerkészítmények |
US5444050A (en) | 1994-04-29 | 1995-08-22 | Texas Biotechnology Corporation | Binding of E-selectin or P-selectin to sialyl Lewisx or sialyl-Lewisa |
US5486536A (en) | 1994-08-15 | 1996-01-23 | The Regents Of The University Of Michigan | Sulfatides as anti-inflammatory compounds |
JPH0899989A (ja) | 1994-09-30 | 1996-04-16 | Akira Hasegawa | 新規糖脂質誘導体およびその製造用中間体 |
DE4436164A1 (de) | 1994-10-10 | 1996-04-11 | Hoechst Ag | Neue Kohlenhydratkonjugate als Inhibitoren der Zelladhäsion |
US5686426A (en) | 1994-11-17 | 1997-11-11 | Bristol-Myers Squibb Company | Dicarboxymethylated glycolipid derivatives as cell adhesion inhibitors |
US6492332B1 (en) | 1995-12-12 | 2002-12-10 | Omeros Corporation | Irrigation solution and methods for inhibition of tumor cell adhesion, pain and inflammation |
US5639734A (en) | 1994-12-20 | 1997-06-17 | Esko; Jeffrey D. | Disaccharide inflammation inhibitors and uses thereof |
WO1996020204A1 (fr) | 1994-12-28 | 1996-07-04 | Sumitomo Pharmaceuticals Company, Limited | Derive x de lewis et procede de production correspondant |
US20020040008A1 (en) | 1995-01-24 | 2002-04-04 | Wagner Denisa D. | Method for treating and preventing atherosclerosis |
US5527936A (en) | 1995-02-17 | 1996-06-18 | E. I. Du Pont De Nemours And Company | Hydrosilylation of unsaturated compounds |
GB9504065D0 (en) | 1995-03-01 | 1995-04-19 | Pharmacia Spa | Poly-pyrrolecarboxamidonaphthalenic acid derivatives |
US6506770B1 (en) | 1996-06-06 | 2003-01-14 | Anormed, Inc. | Antiviral compounds |
GB9511357D0 (en) | 1995-06-06 | 1995-08-02 | Johnson Matthey Plc | Improved antiviral compounds |
AU6155896A (en) | 1995-06-07 | 1996-12-30 | Cytel Corporation | Humanized antibodies to e-selectin |
US5736533A (en) | 1995-06-07 | 1998-04-07 | Neose Technologies, Inc. | Bacterial inhibition with an oligosaccharide compound |
IT1290779B1 (it) | 1995-06-26 | 1998-12-10 | Antonio Sacchetti | Procedimento per il potenziamento delle attivita' terapeutiche di sostanze naturali (vitamine, minerali, erbe, fitopreparati, alimenti) |
CN1196731A (zh) | 1995-06-29 | 1998-10-21 | 诺瓦蒂斯有限公司 | 二糖基化1,2-二醇作为唾液酰-路易斯x和唾液酰-路易斯a的模拟物 |
US5876715A (en) | 1995-08-17 | 1999-03-02 | The Biomembrane Institute | Antibodies that bind novel carbohydrate ligands (myelorollins) that cause E-selectin dependent cell rolling, and uses thereof |
DE19532902A1 (de) | 1995-09-06 | 1997-03-13 | Hoechst Ag | Neuartige Glycomimetika als Selektin-Antagonisten und daraus hergestellte entzündungshemmend wirkende Arzneimittel |
DE19537334A1 (de) | 1995-10-09 | 1997-04-10 | Hoechst Ag | Antiadhäsive Piperidin- und Pyrrolidin-Carbonsäuren |
WO1997014707A1 (en) | 1995-10-18 | 1997-04-24 | Cytel Corporation | SIALYL Lex ANALOGUES AS INHIBITORS OF CELLULAR ADHESION |
EP0859005A1 (en) | 1995-10-26 | 1998-08-19 | Kanebo, Ltd. | Fucose derivatives, drugs containing the same as active ingredient, and intermediates for producing the same |
US5747463A (en) | 1995-11-13 | 1998-05-05 | Bristol-Myers Squibb Company | Malonate derivatives of glycolipids as cell adhesion inhibitors |
JPH09176047A (ja) | 1995-12-25 | 1997-07-08 | Unitika Ltd | 外用医薬製剤 |
DE19602355A1 (de) | 1996-01-24 | 1997-07-31 | Hoechst Ag | Mehrfach fucosylierte Dicarbonsäuren mit antiadhäsiven Eigenschaften |
DE69737496D1 (de) | 1996-01-30 | 2007-05-03 | Glycomimetics Inc | SIALYL-LEWISa UND SIALYL LEWISx EPITOP-ANALOGE |
WO1997028174A1 (en) | 1996-01-30 | 1997-08-07 | Novartis Ag | SIALYL-LEWISa AND SIALYL-LEWISx EPITOPE ANALOGUES |
JP2001516334A (ja) | 1996-03-01 | 2001-09-25 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | セレクチン結合の阻害 |
US5710023A (en) | 1996-03-01 | 1998-01-20 | Genetics Institute, Inc. | IL-13 cytokine receptor chain |
US6344545B1 (en) | 1996-06-14 | 2002-02-05 | Progenics Pharmaceuticals, Inc. | Method for preventing HIV-1 infection of CD4+ cells |
US5654412A (en) | 1996-05-29 | 1997-08-05 | Glycomed Incorporated | Processes for the synthesis of sialyl Lewisx compounds |
US5994402A (en) | 1996-06-05 | 1999-11-30 | Rotstein; Ori D. | Anti-inflammatory and anti-pyretic method |
US5919768A (en) | 1996-06-26 | 1999-07-06 | Texas Biotechnology Corporation | Di- and trivalent small molecule selectin inhibitors |
NZ334048A (en) | 1996-08-08 | 2000-05-26 | Novartis Ag | Mimetics of natural carbohydrate epitotes as ligands for E and P Selectin |
US5830871A (en) | 1996-10-28 | 1998-11-03 | The Scripps Research Institute | Inhibitors of E-, P- and L-selectin binding |
GB9618520D0 (en) | 1996-09-05 | 1996-10-16 | Chiroscience Ltd | Compounds and their therapeutic use |
US6592872B1 (en) | 1996-09-17 | 2003-07-15 | The United States Of America As Represented By The Department Of Health And Human Services | Targeting antigens to the MHC class I processing pathway with an anthrax toxin fusion protein |
WO1998013058A1 (en) | 1996-09-27 | 1998-04-02 | The Trustees Of Columbia University In The City Of New York | Methods for treating an ischemic disorder and improving stroke outcome |
US6110897A (en) | 1996-10-10 | 2000-08-29 | Glycorex Ab | Antiinflammatory cell adhesion inhibitors |
WO1998021334A2 (en) | 1996-11-13 | 1998-05-22 | Morphogenesis, Inc. | Antibody mg1 recognizing a small subset of human hematopoietic cells |
CA2281684C (en) | 1997-02-28 | 2006-08-29 | The Regents Of The University Of California | Inhibition of cell-cell binding by lipid assemblies |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
SE9701127D0 (sv) | 1997-03-26 | 1997-03-26 | Karolinska Innovations Ab | Antigenic fusionprotein carrying GALal, 3GAL epitopes |
JP3720520B2 (ja) | 1997-03-27 | 2005-11-30 | タカラバイオ株式会社 | 糖と標的物との相互作用の測定方法 |
US6413760B1 (en) | 1997-04-15 | 2002-07-02 | Genetics Institute, Inc. | Highly purified mocarhagin cobra venom protease polynucleotides endcoding same and related proteases and therapeutic uses thereof |
US5916910A (en) | 1997-06-04 | 1999-06-29 | Medinox, Inc. | Conjugates of dithiocarbamates with pharmacologically active agents and uses therefore |
US6193973B1 (en) | 1997-08-22 | 2001-02-27 | B. David Tuttle | Dietary supplement for boosting energy and increasing muscular strength |
US5948628A (en) | 1997-09-05 | 1999-09-07 | The Board Of Regents Of The University Of Oklahoma | Methods of screening for compounds which mimic galectin-1 |
US7018637B2 (en) | 1998-02-23 | 2006-03-28 | Aventis Pasteur, Inc | Multi-oligosaccharide glycoconjugate bacterial meningitis vaccines |
AU8967998A (en) | 1998-02-25 | 1999-09-15 | Hsc Research & Development Limited Partnership | Antibiotic-ligand conjugates and methods of use thereof |
WO1999043353A2 (en) | 1998-02-26 | 1999-09-02 | Boehringer Ingelheim Pharmaceuticals, Inc. | Combination anti-selectin and immunosuppressant therapy |
CA2245224A1 (en) | 1998-08-14 | 2000-02-14 | Jiang-Hong Giong | Chemokine receptor antagonists and chemotherapeutics |
US6458777B1 (en) | 1998-03-13 | 2002-10-01 | Mucosal Therapeutics Llc | Methods and compositions for treating and preventing mucositis |
US6365365B1 (en) | 1998-03-20 | 2002-04-02 | The Regents Of The University Of California | Method of determining whether an agent modulates glycosyl sulfotransferase-3 |
US6265192B1 (en) | 1998-03-20 | 2001-07-24 | The Regents Of The University Of California | Glycosly sulfortransferase-3 |
US6037333A (en) | 1998-05-07 | 2000-03-14 | Trustees Of Tufts College | Microbe-inhibiting compositions |
US6372712B1 (en) | 1998-05-22 | 2002-04-16 | The Board Of Trustees Of The Leland Stanford Jr. University | Synthetic bifunctional molecules containing a drug moiety and presenter protein ligand |
EP1087996B1 (en) | 1998-06-16 | 2007-01-17 | The Board of Regents of The University of Oklahoma | Glycosulfopeptides and methods of synthesis and use thereof |
US6004815A (en) | 1998-08-13 | 1999-12-21 | The Regents Of The University Of California | Bacteria expressing nonsecreted cytolysin as intracellular microbial delivery vehicles to eukaryotic cells |
JP4553488B2 (ja) | 1998-09-21 | 2010-09-29 | 大塚製薬株式会社 | カルボキシメチルガラクトース誘導体 |
US6960566B1 (en) | 1998-11-06 | 2005-11-01 | The Wister Institute of Anatomy and Biology | Compositions and methods for treatment of cancer |
JP2002529521A (ja) | 1998-11-12 | 2002-09-10 | ノヴォリティックス インコーポレイテッド | 血管閉塞を生成する組成物および方法 |
GB9904387D0 (en) | 1999-02-25 | 1999-04-21 | Pharmacia & Upjohn Spa | Antitumour synergistic composition |
EP1189609A4 (en) | 1999-05-03 | 2002-10-30 | Smithkline Beecham Corp | CXCR-4 RECEPTOR ANTAGONISTS AND THROMBOPOIETIN MIMETIKA |
US6515117B2 (en) | 1999-10-12 | 2003-02-04 | Bristol-Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
US6887842B1 (en) | 1999-11-19 | 2005-05-03 | The Board Of Trustees Of The Leland Stanford Junior University | Modulating a pharmacokinetic property of a drug by administering a bifunctional molecule containing the drug |
US7204981B2 (en) | 2000-03-28 | 2007-04-17 | Eli Lilly And Company | Methods of treating diseases with activated protein C |
PT2796553T (pt) | 2000-03-30 | 2019-09-27 | Massachusetts Inst Technology | Mediadores de interferência de arn específicos de sequência de arn |
US6683056B2 (en) | 2000-03-30 | 2004-01-27 | Bristol-Myers Squibb Company | O-aryl glucoside SGLT2 inhibitors and method |
AU2001261735B2 (en) | 2000-05-19 | 2006-09-21 | The Center For Blood Research, Inc. | Methods for diagnosing and treating hemostatic disorders by modulating p-selectin activity |
US20020165178A1 (en) | 2000-06-28 | 2002-11-07 | Christian Schetter | Immunostimulatory nucleic acids for the treatment of anemia, thrombocytopenia, and neutropenia |
AU2000274809A1 (en) | 2000-09-12 | 2002-03-26 | Genetics Institute Llc | Inhibition of stenosis or restenosis by p-selectin antagonists |
JP2004523479A (ja) | 2000-10-18 | 2004-08-05 | マサチューセッツ インスティテュート オブ テクノロジー | 多糖の肺送達に関する方法および産物 |
CA2428721A1 (en) | 2000-11-14 | 2002-05-23 | The General Hospital Corporation | Blockade of t cell migration into epithelial gvhd target tissues |
WO2002062810A2 (en) | 2000-11-29 | 2002-08-15 | Bracco International B.V. | Linkable sialyl lewis x analogs |
US20020132220A1 (en) | 2000-12-27 | 2002-09-19 | Berens Kurt L. | Use of selectin antagonists in organ preservation solutions |
CN101694497B (zh) | 2001-03-28 | 2014-11-26 | 哈佛大学校长及研究员协会 | 将外源蛋白递送到胞质溶胶中的方法,及其用途 |
US20030198639A1 (en) | 2002-04-16 | 2003-10-23 | Frenette Paul S. | Methods of treating sickle cell disease |
US7087212B2 (en) | 2001-08-17 | 2006-08-08 | Mallinckrodt, Inc | Multicomponent assemblies having enhanced binding properties for diagnosis and therapy |
AU2002337913A1 (en) | 2001-10-19 | 2003-04-28 | Richard D. Cummings | Glycosulfopeptide inhibitors and methods of use thereof |
AU2002357072A1 (en) | 2001-12-07 | 2003-06-23 | Centocor, Inc. | Pseudo-antibody constructs |
US20030220341A1 (en) | 2001-12-21 | 2003-11-27 | Gary Bridger | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
US20030186942A1 (en) | 2002-01-16 | 2003-10-02 | Crooks Peter A. | Compounds of use in the treatment of epilepsy, seizure, and electroconvulsive disorders |
WO2003088980A1 (en) | 2002-04-18 | 2003-10-30 | Embury Stephen H | Method and composition for preventing pain in sickle cell patients |
EP1534725A2 (en) | 2002-05-16 | 2005-06-01 | Glycomimetics, Inc. | Compounds and methods for inhibiting selectin-mediated function |
WO2004004636A2 (en) | 2002-07-03 | 2004-01-15 | Glycomimetics, Inc. | Compositions and methods for diagnosis and therapy of medical conditions involving angiogenesis |
CA2504755C (en) | 2002-10-11 | 2010-12-14 | University Of Maryland Biotechnology Institute | Carbohydrate-based synthetic vaccines for hiv |
EP1575619A1 (en) | 2002-12-20 | 2005-09-21 | Glycomimetics, Inc. | Oligosaccharides and conjugates thereof for the treatement of pseudomonas bacteria infection |
US6844125B2 (en) | 2003-03-20 | 2005-01-18 | Kabushiki Kaisha Toshiba | Combination of developing agents, image forming apparatus, and method for forming image |
US7332334B2 (en) | 2003-04-18 | 2008-02-19 | Oklahoma Medical Research Foundation | Hematopoietic stem cells treated by in vitro fucosylation and methods of use |
US20040219158A1 (en) | 2003-05-02 | 2004-11-04 | Glycomimetics, Inc. | Compositions and methods for diagnosis and therapy of medical conditions involving infection with pseudomonas bacteria |
US20050054614A1 (en) | 2003-08-14 | 2005-03-10 | Diacovo Thomas G. | Methods of inhibiting leukocyte accumulation |
US7041226B2 (en) | 2003-11-04 | 2006-05-09 | Lexmark International, Inc. | Methods for improving flow through fluidic channels |
US20050214283A1 (en) | 2003-11-07 | 2005-09-29 | Robert Sackstein | Antibodies to CD44 glycoforms and uses thereof |
US20050187171A1 (en) | 2003-11-19 | 2005-08-25 | Glycomimetics, Inc. | Glycomimetic antagonists for both E-and P-selectins |
DE602004011272T2 (de) | 2003-11-19 | 2008-12-24 | Glycomimetics, Inc. | Spezifischer antagonist sowohl für e- als auch p-selektine |
DE602004011574T2 (de) | 2003-12-18 | 2009-01-29 | Unibioscreen S.A. | Glycosylierte steroidderivate mit antimigratorischer wirkung |
GB0404434D0 (en) | 2004-02-27 | 2004-03-31 | Novartis Ag | Organic compounds |
US7745421B2 (en) | 2004-05-25 | 2010-06-29 | The Johns Hopkins University | Methods and compositions for treating diseases and disorders associated with Siglec-8 expressing cells |
CA2571431A1 (en) | 2004-06-24 | 2006-01-05 | The Scripps Research Institute | Arrays with cleavable linkers |
WO2006017180A2 (en) | 2004-07-09 | 2006-02-16 | Progenics Pharmaceuticals, Inc. | Glycopeptide dimers and uses thereof |
JP5135795B2 (ja) | 2004-08-27 | 2013-02-06 | 小野薬品工業株式会社 | 塩基性基を含有する化合物およびその用途 |
WO2006062946A2 (en) | 2004-12-06 | 2006-06-15 | University Of Florida Research Foundation, Inc. | Incorporation of bone marrow derived stem cells in tumors |
KR20070115879A (ko) | 2005-01-07 | 2007-12-06 | 에모리 유니버시티 | 의학 장애의 치료용 cxcr4 길항제 |
AU2006203826A1 (en) | 2005-01-07 | 2006-07-13 | Emory University | CXCR4 antagonists for the treatment of HIV infection |
US20080287469A1 (en) | 2005-02-17 | 2008-11-20 | Diacovo Thomas G | Phosphoinositide 3-Kinase Inhibitors for Inhibiting Leukocyte Accumulation |
WO2006105019A1 (en) | 2005-03-25 | 2006-10-05 | Wisconsin Alumni Research Foundation | Compounds and methods for treating seizure disorders |
US20090036386A1 (en) | 2005-05-25 | 2009-02-05 | Glycomimetics, Inc | Heterobifunctional compounds for selectin inhibition |
US20060287253A1 (en) | 2005-06-17 | 2006-12-21 | Kriegler Steven M | Compounds and methods for treating seizure disorders |
CN101583273A (zh) | 2005-07-22 | 2009-11-18 | 加利福尼亚大学董事会 | 肝素组合物和选择素抑制 |
CN101291946B (zh) | 2005-08-09 | 2011-06-29 | 糖模拟物有限公司 | 对来自假单胞菌的pa-il凝集素、pa-iil凝集素或其两者的糖模拟物抑制剂 |
US20070059242A1 (en) | 2005-08-15 | 2007-03-15 | Paul Wentworth | Methods to identify therapeutic agents |
EP1924260A2 (en) | 2005-08-18 | 2008-05-28 | Novartis AG | Use of cxcr4 binding molecules for the treatment of whim syndrome |
JP5209476B2 (ja) | 2005-09-02 | 2013-06-12 | グリコミメティクス, インコーポレイテッド | ヘテロ二官能性全セレクチン阻害剤 |
EP1937308A4 (en) | 2005-09-14 | 2010-09-15 | Univ Maryland Biotech Inst | SYNTHETIC ADDED CARBOHYDRATES AS INGREDIENTS OF MICROBICIDES |
WO2007143052A1 (en) | 2006-06-01 | 2007-12-13 | Glycomimetics, Inc. | Galactosides and thiodigalactosides as inhibitors of pa-il lectin from pseudomonas |
EP2029164B1 (en) | 2006-06-07 | 2015-12-23 | The Board of Trustees of the Leland Stanford Junior University | Anti-leukocyte recruitment therapy for the treatment of seizures and epilepsy |
WO2008002449A2 (en) | 2006-06-23 | 2008-01-03 | Glycomimetics, Inc. | Glycomimetic inhibitors of siglec-8 |
WO2008008852A2 (en) | 2006-07-11 | 2008-01-17 | Emory University | Cxcr4 antagonists including heteroatoms for the treatment of medical disorders |
US20080227799A1 (en) | 2006-07-11 | 2008-09-18 | Liotta Dennis C | CXCR4 Antagonists Including Heteroatoms for the Treatment of Medical Disorders |
WO2008008854A2 (en) | 2006-07-11 | 2008-01-17 | Emory University | Cxcr4 antagonists including diazine and triazine structures for the treatment of medical disorders |
WO2008011094A2 (en) | 2006-07-18 | 2008-01-24 | Robert Sackstein | Cytokine induction of selectin ligands on cells |
US7964569B2 (en) | 2006-10-12 | 2011-06-21 | Glycomimetics, Inc. | Glycomimetic replacements for hexoses and N-acetyl hexosamines |
US20080306098A1 (en) | 2006-11-06 | 2008-12-11 | Mutz Mitchell W | Pharmacokinetics of protease inhibitors and other drugs |
US20100145032A1 (en) | 2007-01-18 | 2010-06-10 | Suomen Punainen Risti, Veripalelu | Novel carbohydrate profile compositions from human cells and methods for analysis and modification thereof |
WO2008100453A1 (en) | 2007-02-09 | 2008-08-21 | Glycomimetics, Inc. | Methods of use of glycomimetics with replacements for hexoses and n-acetyl hexosamines |
US20080261978A1 (en) | 2007-03-08 | 2008-10-23 | Clark Michael P | Chemokine receptor modulators |
US20090054334A1 (en) | 2007-05-23 | 2009-02-26 | Mutz Mitchell W | Combinatorial improvement of bifunctional drug properties |
US8039442B2 (en) | 2007-07-18 | 2011-10-18 | Glycomimetics, Inc. | Compounds and methods for treatment of sickle cell disease or complications associated therewith |
KR20100042654A (ko) | 2007-08-08 | 2010-04-26 | 교와 핫꼬 기린 가부시키가이샤 | 단리된 세포 집단 |
JP2011500601A (ja) | 2007-10-12 | 2011-01-06 | トランスモレキュラー, インコーポレイテッド | 腫瘍の診断および処置のためのクロロトキシン薬剤の全身性投与 |
FI20070853A0 (fi) | 2007-11-09 | 2007-11-09 | Glykos Finland Oy | Glykaania sitovat monoklonaaliset vasta-aineet |
US9486497B2 (en) | 2007-12-10 | 2016-11-08 | The University Of Queensland | Treatment of immunocompromised conditions |
US8895510B2 (en) | 2008-04-08 | 2014-11-25 | Glycomimetics, Inc. | Pan-selectin inhibitor with enhanced pharmacokinetic activity |
CA2727788A1 (en) | 2008-06-13 | 2009-12-17 | Glycomimetics, Inc. | Treatment of cancers of the blood using selected glycomimetic compounds |
US20110245265A1 (en) | 2008-08-29 | 2011-10-06 | Genzyme Corporation | Cxcr4 antagonists for kidney injury |
US20100240773A1 (en) | 2009-03-23 | 2010-09-23 | Kenneth Korzekwa | Multifunctional linkers |
FI20095459A0 (fi) | 2009-04-24 | 2009-04-24 | Suomen Punainen Risti Veripalv | Uusia määritysmenetelmiä |
AU2010241807B2 (en) | 2009-05-01 | 2014-08-14 | Glycomimetics, Inc. | Heterobifunctional inhibitors of E-selectins and CXCR4 chemokine receptors |
US20120093782A1 (en) | 2009-05-13 | 2012-04-19 | Grove Robert I | Enhanced Hematopoietic Stem Cell Engraftment |
WO2011127179A1 (en) | 2010-04-07 | 2011-10-13 | Glycomimetics, Inc. | Glycomimetic compounds and methods to inhibit infection by hiv |
WO2012037034A1 (en) | 2010-09-14 | 2012-03-22 | Glycomimetics, Inc. | E-selectin antagonists |
WO2012047918A1 (en) | 2010-10-04 | 2012-04-12 | Glycomimetics, Inc. | Anti-epileptogenic agents |
FI20106031A0 (fi) | 2010-10-06 | 2010-10-06 | Suomen Punainen Risti Veripalv | Menetelmä solujen eristämiseksi ja menetelmällä eristetty solupopulaatio |
WO2012061662A1 (en) | 2010-11-03 | 2012-05-10 | Glycomimetics, Inc. | Glycomimetic-peptidomimetic inhibitors of e-selectins and cxcr4 chemokine receptors |
US8765126B2 (en) * | 2011-05-05 | 2014-07-01 | Robert Sackstein | Methods of treating complications and disorders associated with G-CSF administration |
JP2016501840A (ja) | 2012-10-31 | 2016-01-21 | グリコミメティクス, インコーポレイテッド | E−セレクチンアンタゴニスト化合物および使用方法 |
PT2928476T (pt) | 2012-12-07 | 2018-05-10 | Glycomimetics Inc | Compostos, composições e métodos que utilizam antagonistas de e-selectina para mobilização de células hematopoiéticas |
WO2014149837A1 (en) | 2013-03-15 | 2014-09-25 | Glycomimetics, Inc. | Compounds and methods to enhance the oral availability of glycomimetics |
CA2920377A1 (en) | 2013-08-05 | 2015-02-12 | Cambridge Enterprise Limited | Inhibition of cxcr4 signaling in cancer immunotherapy |
EP3052510A4 (en) | 2013-09-30 | 2017-03-29 | GlycoMimetics, Inc. | Methods and compositions for treating and/or preventing mucositis |
US20160333043A1 (en) | 2014-01-17 | 2016-11-17 | Glycomimetics, Inc. | E-Selectin Antagonists Modified By Macrocycle Formation to the Galactose |
WO2016164394A1 (en) | 2015-04-08 | 2016-10-13 | Glycomimetics, Inc. | 2-halo-galactose-containing selectin antagonists |
JP2018522040A (ja) | 2015-08-03 | 2018-08-09 | グリコミメティクス, インコーポレイテッド | 増強された再構成能および寿命を有するt細胞の動員および使用のための方法 |
EP3383882A1 (en) | 2015-12-02 | 2018-10-10 | GlycoMimetics, Inc. | Heterobifunctional pan-selectin antagonists having a triazole linker |
WO2017151708A1 (en) | 2016-03-02 | 2017-09-08 | Glycomimetics, Inc. | Methods for the treatment and/or prevention of cardiovescular disease by inhibition of e-selectin |
EP3497131B1 (en) | 2016-08-08 | 2022-03-09 | GlycoMimetics, Inc. | Combination of t-cell checkpoint inhibitors with inhibitors of e-selectin or cxcr4, or with heterobifunctional inhibitors of both e-selectin and cxcr4. |
CN117298287A (zh) | 2016-10-07 | 2023-12-29 | 糖模拟物有限公司 | 高效的多聚体e-选择蛋白拮抗剂 |
JP7272956B2 (ja) * | 2017-03-15 | 2023-05-12 | グリコミメティクス, インコーポレイテッド | E-セレクチンアンタゴニストとしてのガラクトピラノシル-シクロヘキシル誘導体 |
CA3146048A1 (en) * | 2019-07-31 | 2021-02-04 | Glycomimetics, Inc. | Use of e-selectin antagonists to enhance the survival of reconstituted, bone marrow-depleted hosts |
-
2018
- 2018-11-29 WO PCT/US2018/062988 patent/WO2019108750A1/en unknown
- 2018-11-29 JP JP2020529351A patent/JP7275131B2/ja active Active
- 2018-11-29 EP EP18822193.1A patent/EP3717013A1/en active Pending
- 2018-11-29 US US16/767,698 patent/US11712446B2/en active Active
-
2023
- 2023-06-01 US US18/327,429 patent/US20230414642A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015500887A (ja) * | 2011-12-22 | 2015-01-08 | グリコミメティクス, インコーポレイテッド | E−セレクチンアンタゴニスト化合物、組成物および使用方法 |
WO2016089872A1 (en) * | 2014-12-03 | 2016-06-09 | Glycomimetics, Inc. | Heterobifunctional inhibitors of e-selectins and cxcr4 chemokine receptors |
Non-Patent Citations (3)
Title |
---|
BLOOD, 2015, VOL.126, NO.23, P.512, JPN6022046490, ISSN: 0004912317 * |
FRONTIERS IN IMMUNOLOGY, 2016, VOL.7, #112, JPN6022046489, ISSN: 0004912318 * |
SCI. TRANSL. MED., 2015, VOL.7, NO.288, #288RA78, AUTHOR MANUSCRIPT, JPN6022046488, ISSN: 0004912316 * |
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