DK2040740T3 - COMPOSITIONS AND PROCEDURES FOR DELIVERING NITROGEN MONOXIDE - Google Patents
COMPOSITIONS AND PROCEDURES FOR DELIVERING NITROGEN MONOXIDE Download PDFInfo
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- C07K14/43563—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
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| PCT/US2007/012133 WO2007139767A2 (en) | 2006-05-22 | 2007-05-21 | Compositions and methods for the delivery of nitric oxide |
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| DK11189807.8T DK2463294T3 (en) | 2006-05-22 | 2007-05-21 | Compositions and Methods for Delivery of Nitric Oxide |
| DK11189814.4T DK2463297T3 (en) | 2006-05-22 | 2007-05-21 | Oxygen Compositions and Methods |
| DK07795174.7T DK2032156T3 (da) | 2006-05-22 | 2007-05-21 | Sammensætninger og fremgangsmåder til levering af oxygen |
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| DK07795174.7T DK2032156T3 (da) | 2006-05-22 | 2007-05-21 | Sammensætninger og fremgangsmåder til levering af oxygen |
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| EP2463294B1 (en) | 2006-05-22 | 2016-10-19 | The Regents of The University of California | Compositions and methods for the delivery of nitric oxide |
| US20110243849A1 (en) * | 2010-04-02 | 2011-10-06 | Marletta Michael A | Heme-binding photoactive polypeptides and methods of use thereof |
| CA2897018C (en) * | 2013-01-07 | 2021-07-27 | Omniox, Inc. | Polymeric forms of h-nox proteins |
| JP7049832B2 (ja) | 2015-03-17 | 2022-04-07 | オムニオクス， インコーポレイテッド | タンパク質媒介性ｏ２送達による腫瘍免疫のモジュレーション |
| SG10202007517TA (en) * | 2016-02-16 | 2020-09-29 | Omniox Inc | Modulation of hypoxia associated with stroke |
| JP6467073B2 (ja) * | 2018-01-04 | 2019-02-06 | オムニオクス， インコーポレイテッド | Ｈ−ｎｏｘタンパク質の重合体形態 |
| EP3836911A1 (en) | 2018-08-15 | 2021-06-23 | Omniox, Inc. | H-nox proteins for treating cardiovascular and pulmonary conditions |
| CA3100035A1 (en) | 2018-08-27 | 2020-03-05 | Regeneron Pharmaceuticals, Inc. | Use of raman spectroscopy in downstream purification |
| NZ783169A (en) | 2019-06-25 | 2024-12-20 | Gilead Sciences Inc | Flt3l-fc fusion proteins and methods of use |
| CN118178645A (zh) | 2019-10-18 | 2024-06-14 | 四十七公司 | 用于治疗骨髓增生异常综合征和急性髓系白血病的联合疗法 |
| US20210147568A1 (en) | 2019-10-31 | 2021-05-20 | Forty Seven, Inc. | Anti-cd47 based treatment of blood cancer |
| TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
| LT4081305T (lt) | 2019-12-24 | 2024-11-25 | Carna Biosciences, Inc. | Diacilglicerolio kinazę moduliuojantys junginiai |
| TWI832035B (zh) | 2020-02-14 | 2024-02-11 | 美商基利科學股份有限公司 | 結合ccr8之抗體及融合蛋白及其用途 |
| WO2021222522A1 (en) | 2020-05-01 | 2021-11-04 | Gilead Sciences, Inc. | Cd73 inhibiting 2,4-dioxopyrimidine compounds |
| TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | ＣＤ４７／ＳＩＲＰα結合及ＮＥＤＤ８活化酶Ｅ１調節次單元之共抑制以用於治療癌症 |
| US20220389394A1 (en) | 2021-05-18 | 2022-12-08 | Gilead Sciences, Inc. | METHODS OF USING FLT3L-Fc FUSION PROTEINS |
| AU2022298639C1 (en) | 2021-06-23 | 2025-07-17 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| CA3222595A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2022271684A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2022271677A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| KR20240091056A (ko) | 2021-10-28 | 2024-06-21 | 길리애드 사이언시즈, 인코포레이티드 | 피리디진-3(2h)-온 유도체 |
| WO2023077030A1 (en) | 2021-10-29 | 2023-05-04 | Gilead Sciences, Inc. | Cd73 compounds |
| EP4452414A2 (en) | 2021-12-22 | 2024-10-30 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| JP2024545193A (ja) | 2021-12-22 | 2024-12-05 | ギリアード サイエンシーズ， インコーポレイテッド | Ｉｋａｒｏｓジンクフィンガーファミリー分解剤及びその使用 |
| TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Ｐａｒｐ７抑制劑 |
| US12358887B2 (en) | 2022-03-17 | 2025-07-15 | Gilead Sciences, Inc. | IKAROS Zinc Finger Family degraders and uses thereof |
| KR20240165995A (ko) | 2022-03-24 | 2024-11-25 | 길리애드 사이언시즈, 인코포레이티드 | Trop-2 발현 암의 치료를 위한 병용요법 |
| TWI876305B (zh) | 2022-04-05 | 2025-03-11 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
| CN119487038A (zh) | 2022-04-21 | 2025-02-18 | 吉利德科学公司 | Kras g12d调节化合物 |
| WO2024006929A1 (en) | 2022-07-01 | 2024-01-04 | Gilead Sciences, Inc. | Cd73 compounds |
| US20240091351A1 (en) | 2022-09-21 | 2024-03-21 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPa DISRUPTION ANTICANCER COMBINATION THERAPY |
| EP4638436A1 (en) | 2022-12-22 | 2025-10-29 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| WO2024215754A1 (en) | 2023-04-11 | 2024-10-17 | Gilead Sciences, Inc. | Kras modulating compounds |
| CN121079300A (zh) | 2023-04-21 | 2025-12-05 | 吉利德科学公司 | Prmt5抑制剂及其用途 |
| US20250042922A1 (en) | 2023-06-30 | 2025-02-06 | Gilead Sciences, Inc. | Kras modulating compounds |
| US20250066328A1 (en) | 2023-07-26 | 2025-02-27 | Gilead Sciences, Inc. | Parp7 inhibitors |
| WO2025024811A1 (en) | 2023-07-26 | 2025-01-30 | Gilead Sciences, Inc. | Parp7 inhibitors |
| WO2025054530A1 (en) | 2023-09-08 | 2025-03-13 | Gilead Sciences, Inc. | Pyrimidine-containing polycyclic derivatives as kras g12d modulating compounds |
| WO2025054347A1 (en) | 2023-09-08 | 2025-03-13 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| US20250154172A1 (en) | 2023-11-03 | 2025-05-15 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| US20250230168A1 (en) | 2023-12-22 | 2025-07-17 | Gilead Sciences, Inc. | Azaspiro wrn inhibitors |
| WO2025245003A1 (en) | 2024-05-21 | 2025-11-27 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4873192A (en) | 1987-02-17 | 1989-10-10 | The United States Of America As Represented By The Department Of Health And Human Services | Process for site specific mutagenesis without phenotypic selection |
| US6022849A (en) | 1987-05-16 | 2000-02-08 | Baxter Biotech Technology Saarl | Mutant recombinant hemoglobins containing heme pocket mutations |
| US5731454A (en) | 1990-02-12 | 1998-03-24 | Virginia Commonwealth University | Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored blood |
| AU6766994A (en) | 1994-04-01 | 1995-10-23 | Unisyn Technologies, Inc. | Culture media additives for hollow fiber bioreactors |
| AU735799C (en) * | 1997-02-28 | 2005-04-28 | Regents Of The University Of California, The | Methods and compositions for optimisation of oxygen transport by cell-free systems |
| US6455676B1 (en) | 1997-05-02 | 2002-09-24 | Baxter Biotech Technology Sarl | Hemoglobin mutants with increased soluble expression and/or reduced nitric oxide scavenging |
| DE19837015C2 (de) * | 1998-08-14 | 2003-03-20 | Vasopharm Biotech Gmbh | Isolierte und gereinigte humane lösliche Guanylylcyclase alpha1/beta1 (hsGCalpha1/beta1) |
| US6773613B1 (en) | 1998-10-15 | 2004-08-10 | Sangart, Inc. | Method for production of stroma-free hemoglobin |
| PL356815A1 (en) * | 1999-12-22 | 2004-07-12 | The Scripps Research Institute | Angiogenesis and vascular permeability modulators and inhibitors |
| EP1294868A2 (en) | 2000-06-29 | 2003-03-26 | Incyte Genomics, Inc. | Adenylyl and guanylyl cyclases |
| US20030096240A1 (en) * | 2000-09-19 | 2003-05-22 | Ferid Murad | Genomic organization of mouse and human sGC |
| US6780849B2 (en) * | 2000-12-21 | 2004-08-24 | Scimed Life Systems, Inc. | Lipid-based nitric oxide donors |
| US20030153491A1 (en) | 2002-01-11 | 2003-08-14 | Winslow Robert M. | Methods and compositions for oxygen transport comprising a high oxygen affinity modified hemoglobin |
| US20060130158A1 (en) * | 2002-08-30 | 2006-06-15 | Turner Andrew J | Modified transferrin fusion proteins comprising duplicate transferrin amino or carboxy terminal domains |
| CN1660100A (zh) * | 2002-12-09 | 2005-08-31 | 上海倍艺医药科技有限公司 | 一种治疗糖尿病及其并发症的药物 |
| EP2463294B1 (en) | 2006-05-22 | 2016-10-19 | The Regents of The University of California | Compositions and methods for the delivery of nitric oxide |
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