Nanocarrier formulated enzyme for the treatment of S. aureus infection
纳米载体配制的酶用于治疗金黄色葡萄球菌感染
基本信息
- 批准号:8468113
- 负责人:
- 金额:$ 30万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-05-09 至 2015-04-30
- 项目状态:已结题
- 来源:
- 关键词:AffinityAnimalsAntibioticsArea Under CurveBackBacteriaBindingBiodistributionBiological AssayBloodBlood Circulation TimeCell LineCellsClinicalClinical TrialsCloningCommunitiesCoupledCyclic GMPDaptomycinDataDevelopmentDissociationDrug CombinationsDrug FormulationsDrug InteractionsDrug KineticsEffectivenessEndocarditisEndotoxinsEnzyme-Linked Immunosorbent AssayEnzymesEscherichia coliEvaluationFeasibility StudiesFigs - dietaryFreedomFundingFurunculosisGenerationsGoalsHalf-LifeHourIn VitroInfectionInflammationInstructionIntentionLegal patentLettersLicensingLifeLinezolidLysostaphinMeasurableMediatingMetalloendopeptidasesModelingMusOsteomyelitisPeptidesPhasePneumoniaPreparationProductionProteinsRecombinantsRecoveryResistanceResourcesSecureSerumSiteSmall Business Innovation Research GrantSpeedStaphylococcal InfectionsStaphylococcus aureusStructureSystemic TherapyTestingThigh structureTimeToxicologyVancomycinVariantVascular PermeabilitiesWorkcatheter related infectionchemical synthesiscopolymercostdesignimmunogenicityimprovedin vivokillingsmethicillin resistant Staphylococcus aureusnanocarrierphase 2 studypre-clinicalpreventresidencesuccess
项目摘要
DESCRIPTION (provided by applicant): Lyso, a metalloendopeptidase that is bacteriolytic for S. aureus, is a potential systemic therapy for treating methicillin-resistant S. aureus (MRSA) mediated infections including endocarditis, osteomyelitis, catheter related infections, and MRSA-mediated community acquired furunculosis and pneumonia. However, the short half-life of this enzyme in vivo has precluded its development thus far as a systemic therapy, despite positive clinical trial data. Our company, PharmaIN, has developed a nanocarrier, Protected Graft Copolymers (PGC), that can reversibly bind peptides and/or proteins (US patent #7,138,105) with measurable dissociation constant (Kd). Importantly, because of its size, PGC nanocarrier concentrates at sites of increased vascular permeability and thus can potentially concentrate lyso at the site of infection. Our goal is to develop a formulation of lyso to provide life-saving treatment against MRSA and to suppress the emergence of resistance. Our preliminary data demonstrates that PGC can reversibly associate with lyso, increase blood half-life 14-fold, and increase its in vivo efficacy against MRSA by 100-fold. We propose to prepare endotoxin- free lyso and create a "master cell-line bank" (E. coli expressing lyso) that will be used for: 1) this project to supply our lyso needs, and 2) as reference cells for the planned post-SBIR IND filing and clinical trial. We will also optimize the structure of PGC by synthesizing variations (at least 10) of the effective PGC shown in the preliminary data with the intention to further extend the half-life to at least 30 fold. This is important before we put a lot of resource towards IND. To this end, we will continue the development of PGC-lyso formulation by doing binding studies of at least 10 new carrier variations. We will do PKs and biodistribution studies on at least 6 selected lyso formulations. We will determine and compare with commercially available antibiotics the effectiveness of our lyso formulation in vivo against MRSA. PharmaIN Corp. Confidential
描述(由申请人提供):Lyso是一种金属内肽酶,对金黄色葡萄球菌具有溶菌作用,是一种潜在的全身疗法,用于治疗耐甲氧西林金黄色葡萄球菌(MRSA)介导的感染,包括心内膜炎、骨髓炎、导管相关感染和MRSA介导的社区获得性真菌病和肺炎。然而,尽管有积极的临床试验数据,但这种酶在体内的半衰期短阻碍了其作为全身治疗的发展。我们的公司PharmaIN开发了一种纳米载体,保护接枝共聚物(PGC),可以可逆地结合肽和/或蛋白质(美国专利#7,138,105),具有可测量的解离常数(Kd)。重要的是,由于其大小,PGC纳米载体集中在血管通透性增加的部位,因此可能在感染部位集中溶酶。我们的目标是开发一种lyso配方,为MRSA提供挽救生命的治疗,并抑制耐药性的出现。我们的初步数据表明,PGC可以与lyso可逆结合,将血液半衰期延长14倍,将体内抗MRSA的功效提高100倍。我们建议制备无内毒素的溶酶酶并建立一个“主细胞系库”(表达溶酶酶的大肠杆菌),该细胞系库将用于:1)本项目提供我们对溶酶酶的需求,2)作为计划中的sbir后IND申请和临床试验的参考细胞。我们还将通过合成初步数据中显示的有效PGC的变体(至少10种)来优化PGC的结构,目的是将半衰期进一步延长到至少30倍。在我们将大量资源投入到IND之前,这一点很重要。为此,我们将通过对至少10种新的载体变体进行结合研究,继续开发PGC-lyso配方。我们将对至少6种选定的lyso制剂进行PKs和生物分布研究。我们将确定并与市售抗生素比较我们的lyso制剂在体内对抗MRSA的有效性。PharmaIN公司
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Elijah M. Bolotin其他文献
Compositions de supports a noyau hydrophobe pour l'administration d'agents therapeutiques, et procedes de preparation et d'utilisation
支持治疗剂施用、制备和利用过程的疏水性组合物
- DOI:
- 发表时间:
2006 - 期刊:
- 影响因子:0
- 作者:
Gerardo M. Castillo;Elijah M. Bolotin - 通讯作者:
Elijah M. Bolotin
Erratum to: Protected Graft Copolymer Excipient Leads to a Higher Acute Maximum Tolerated Dose and Extends Residence Time of Vasoactive Intestinal Peptide Significantly Better than Sterically Stabilized Micelles
- DOI:
10.1007/s11095-013-1061-0 - 发表时间:
2013-05-09 - 期刊:
- 影响因子:4.300
- 作者:
Sandra Reichstetter;Gerardo M. Castillo;Israel Rubinstein;Akiko Nishimoto-Ashfield;ManShun Lai;Cynthia C. Jones;Aryamitra Banerjee;Alex Lyubimov;Duane C. Bloedow;Alexei Bogdanov;Elijah M. Bolotin - 通讯作者:
Elijah M. Bolotin
Elijah M. Bolotin的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Elijah M. Bolotin', 18)}}的其他基金
Vasoactive Intestinal Peptide for the treatment of Female Sexual Arousal Disorder
血管活性肠肽治疗女性性唤起障碍
- 批准号:
8638840 - 财政年份:2014
- 资助金额:
$ 30万 - 项目类别:
Vasoactive intestinal peptide for the treatment of psoriasis
血管活性肠肽治疗牛皮癣
- 批准号:
8248548 - 财政年份:2012
- 资助金额:
$ 30万 - 项目类别:
Nanocarrier formulated enzyme for the treatment of S. aureus infection
纳米载体配制的酶用于治疗金黄色葡萄球菌感染
- 批准号:
8392195 - 财政年份:2012
- 资助金额:
$ 30万 - 项目类别:
Vasoactive intestinal peptide for the treatment of psoriasis
血管活性肠肽治疗牛皮癣
- 批准号:
8540904 - 财政年份:2012
- 资助金额:
$ 30万 - 项目类别:
Nanocarrier-formulated anti-fibrotic peptides for cirrhosis - Fast Track SBIR
纳米载体配制的抗纤维化肽治疗肝硬化 - Fast Track SBIR
- 批准号:
8102077 - 财政年份:2010
- 资助金额:
$ 30万 - 项目类别:
Nanocarrier-formulated anti-fibrotic peptides for cirrhosis - Fast Track SBIR
纳米载体配制的抗纤维化肽治疗肝硬化 - Fast Track SBIR
- 批准号:
8097148 - 财政年份:2010
- 资助金额:
$ 30万 - 项目类别:
Nanocarrier-formulated anti-fibrotic peptides for cirrhosis - Fast Track SBIR
纳米载体配制的抗纤维化肽治疗肝硬化 - Fast Track SBIR
- 批准号:
7901175 - 财政年份:2010
- 资助金额:
$ 30万 - 项目类别:
Nanocarrier with metal bridge for affinity based delivery of metal binding peptid
具有金属桥的纳米载体,用于基于亲和力的金属结合肽的递送
- 批准号:
7568232 - 财政年份:2008
- 资助金额:
$ 30万 - 项目类别:
Nanocarrier with metal bridge for affinity based delivery of metal binding peptid
具有金属桥的纳米载体,用于基于亲和力的金属结合肽的递送
- 批准号:
7475033 - 财政年份:2008
- 资助金额:
$ 30万 - 项目类别:
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 30万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 30万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 30万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 30万 - 项目类别:
Discovery Early Career Researcher Award
Zootropolis: Multi-species archaeological, ecological and historical approaches to animals in Medieval urban Scotland
Zootropolis:苏格兰中世纪城市动物的多物种考古、生态和历史方法
- 批准号:
2889694 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Studentship
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Training Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Continuing Grant
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)