CMC of Peptide Formulation for the Treatment of ARDS
用于治疗 ARDS 的肽制剂的 CMC
基本信息
- 批准号:10379771
- 负责人:
- 金额:$ 100万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcetatesAcuteAcute Lung InjuryAcute Respiratory Distress SyndromeAnimalsAnti-Inflammatory AgentsAntibodiesAntigensAtrial Natriuretic FactorAttenuatedBacterial PneumoniaBiological AssayBloodBlood PressureC-Type Natriuretic PeptideCOVID-19COVID-19 pandemicCanis familiarisCellsCessation of lifeChemicalsChemistryChemotactic FactorsChronicCicatrixClinicalClinical TrialsCommunicable DiseasesCyclic GMPDataDevelopmentDoseEmergency SituationEquipmentEventExcipientsFDA approvedFatty AcidsFormulationFundingHealth PersonnelHealthcare SystemsHomeHospitalsIn VitroIncidenceIndividualInfectionInflammationInflammatoryInfluenzaInjectableInterleukin-1 betaInterleukin-6Length of StayLifeLiquid substanceLungLung Lavage FluidMaximum Tolerated DoseMeasuresMethodsMiddle East Respiratory SyndromeMusOrphan DrugsPathologyPathology ReportPatientsPeptidesPharmaceutical PreparationsPharmacodynamicsPhasePhase I Clinical TrialsPolymersPopulationPrevalencePrivatizationProductionProteinsPulmonary InflammationPulmonary PathologyPulmonary alveolar structureQuarantineRattusRegulatory AffairsSafetySavingsSecureSelf AdministrationSevere Acute Respiratory SyndromeSmall Business Innovation Research GrantSolidSterilityStructure of parenchyma of lungSyndromeSystemTNF geneTestingTimeTissuesToxicologyUp-RegulationVentilatorWorkbasecopolymercytokineexperimental studyfactor Afibrotic lungimprovedinhibitormacrophagemortalitynecrotic tissueneutrophilnovelnovel therapeuticspandemic diseasepeptide Bpeptide drugreceptorrespiratorysafety studyscreeningside effectsubcutaneoussuccess
项目摘要
ABSTRACT: Without a pandemic such as COVID-19, the prevalence of Acute Respiratory Syndrome (ARDS)
associated with Acute Lung Injury (ALI) is estimated to be ~200-240K patients/year in the US, accounting for
3.6-million hospital days per year and with 30-40% mortality. Considering that US represent only 4.23 % of
world population, the likely incidence of ARDS and commercially addressable needs will be over 4 million
patients/year. This application is seeking funding for Chemistry, Manufacturing, and Control (CMC) for
production of a novel drug product containing a very long-acting anti-inflammatory C-type natriuretic peptide
derivative for use in the treatment of ALI and ARDS characterized by overwhelmingly lung inflammation.
Coronavirus disease 2019 (COVID-19) or any other trigger of a severe lung inflammatory event (such as
SARS, MERS, deadly influenza, bacterial pneumonia, or chemical/antigen) leads to ARDS that compromises
blood oxygenation. ARDS requires a ventilator in a hospital ICU and ARDS caused by very contagious
infectious diseases can cause in spike in ARDS cases and overwhelm the health care system capacity and
equipment that can further be diminished by healthcare provider becoming infected or scared to work. The
present proposal, if successful, can alleviate that by providing a safe injectable formulation that can be self-
administered at home by an infected individual under strict home quarantine. We have completed proof of
efficacy of our novel formulation in mice. The present proposal will develop a formulation with long shelf
stability by evaluating various excipients. This will provide needed shelf stability for commercial product, during
a planned GLP toxicology study and clinical trial and additionally allow field deployment during a pandemic
emergency. We will, establish, qualify, and validate all the analytical assays needed for product release. The
same set of assays will measure stability over time, as required by the FDA. The assays will establish Quality,
Integrity, Purity, Potency and Sterility (QIPPS) of the drug product formulation and its other components.
Additionally, we will determine a) the chronic maximum tolerated dose (MTD, 28-day daily SC dosing in rats) of
the drug product along with its excipients, b) the minimum dose required for sustained elevation (at least 2-
fold) of blood cyclic-GMP level for 24h for QD formulation, 84h for BIW formulation, and potentially 168h for
QW formulation, and c) in vitro toxicology screening for potential off-target receptor side effects. The result of
this will guide us in the execution a full GLP-Tox study in rats and dogs for IND document submission. We will
make 200g API and enough protected graft copolymer (PGC) excipient with well-defined QIPPS (at
PharmaIN). We will formulate the drug product at a cGMP fill and finish facility. This will provide enough
formulation to complete IND-enabling GLP-toxicology testing and Phase 1 clinical safety study.
摘要:如果没有像COVID-19这样的大流行,急性呼吸综合征(ARDS)的患病率
据估计,美国每年约有20 - 24万例患者与急性肺损伤(ALI)相关,
3.6-每年有100万个住院日,死亡率为30-40%。考虑到美国仅占4.23%,
世界人口中,ARDS的可能发病率和商业上可解决的需求将超过400万
患者/年该申请正在寻求化学,制造和控制(CMC)的资金,
含有非常长效的抗炎C型利钠肽的新药物产品的生产
本发明提供了用于治疗以压倒性的肺部炎症为特征的ALI和ARDS的衍生物。
2019冠状病毒病(COVID-19)或任何其他严重肺部炎症事件的触发因素(如
SARS、MERS、致命流感、细菌性肺炎或化学/抗原)导致危害健康的ARDS
血液氧合。ARDS需要在医院ICU使用呼吸机,而ARDS是由非常具有传染性的
传染病可导致ARDS病例激增,并使卫生保健系统不堪重负,
设备,可以进一步减少医疗保健提供者被感染或害怕工作。的
本发明的建议如果成功的话,可以通过提供一种安全的可注射制剂来缓解这种情况,
在严格的家庭隔离下由受感染的个人在家中施用。我们已经完成了
我们的新制剂在小鼠中的功效。本提案将开发一种具有长货架期的制剂
通过评估各种辅料的稳定性。这将为商业产品提供所需的货架稳定性,
计划的GLP毒理学研究和临床试验,并允许在大流行期间进行现场部署
紧急情况我们将建立、鉴定和验证产品放行所需的所有分析测定。的
根据FDA的要求,同一组试验将测量随时间推移的稳定性。试验将确定质量,
制剂处方及其其他组分的完整性、纯度、效价和无菌性(QIPPS)。
此外,我们将确定a)以下的慢性最大耐受剂量(MTD,大鼠中28天每日SC给药):
药物产品沿着其赋形剂,B)持续升高所需的最小剂量(至少2-
QD制剂的血液循环GMP水平为24小时,BIW制剂为84小时,
QW制剂,和c)潜在脱靶受体副作用的体外毒理学筛选。的结果
这将指导我们在大鼠和犬中进行完整的GLP-Tox研究,以提交IND文件。我们将
制备200 g API和足够的具有明确定义的QIPPS的受保护的接枝共聚物(PGC)赋形剂(在
PharmaIN)。我们将在cGMP灌装和成品设施中配制制剂。这将提供足够的
完成IND使能GLP毒理学试验和I期临床安全性研究。
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 }}
Gerardo M. Castillo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
Gerardo M. Castillo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('Gerardo M. Castillo', 18)}}的其他基金
CMC of Peptide Formulation for the Treatment of ARDS
用于治疗 ARDS 的肽制剂的 CMC
- 批准号:
10839580 - 财政年份:2022
- 资助金额:
$ 100万 - 项目类别:
Subcutaneous Drug Development for Portal Hypertension Ascites
门静脉高压腹水的皮下药物开发
- 批准号:
10469005 - 财政年份:2014
- 资助金额:
$ 100万 - 项目类别:
Subcutaneous Drug Development for Portal Hypertension Ascites
门静脉高压腹水的皮下注射药物开发
- 批准号:
8930140 - 财政年份:2014
- 资助金额:
$ 100万 - 项目类别:
Subcutaneous Drug Development for Portal Hypertension Ascites
门静脉高压腹水的皮下注射药物开发
- 批准号:
8776220 - 财政年份:2014
- 资助金额:
$ 100万 - 项目类别:
Subcutaneous Drug Development for Portal Hypertension Ascites
门静脉高压腹水的皮下药物开发
- 批准号:
10320316 - 财政年份:2014
- 资助金额:
$ 100万 - 项目类别:
Nanocarrier-formulated NF-kB inhibitors for Inflammatory diseases
纳米载体配制的用于炎症疾病的 NF-kB 抑制剂
- 批准号:
8300786 - 财政年份:2011
- 资助金额:
$ 100万 - 项目类别:
Nanocarrier-formulated NF-kB inhibitors for Inflammatory diseases
纳米载体配制的用于炎症疾病的 NF-kB 抑制剂
- 批准号:
8196005 - 财政年份:2011
- 资助金额:
$ 100万 - 项目类别:
相似海外基金
Development of palladium-catalyzed novel organic transformations of silylated allyl acetates
钯催化的硅烷化乙酸烯丙酯新型有机转化的开发
- 批准号:
18K05101 - 财政年份:2018
- 资助金额:
$ 100万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Biosynthesis of Methylketones and 2-Alkany l Acetates
甲基酮和 2-烷酰基乙酸酯的生物合成
- 批准号:
9118188 - 财政年份:1992
- 资助金额:
$ 100万 - 项目类别:
Standard Grant