Engineering cells for concurrent protein drug biosynthesis and polysialylation
Engineering cells for concurrent protein drug biosynthesis and polysialylation
批准号:
8645308
负责人:
Christoph Geisler
金额:
$14.82万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-03-01 至 2016-08-31
关键词:
AddressAnabolismAntibodiesBaculovirusesBiocompatibleBiologyCell LineCellsChemicalsChemistryDataDoseDrug KineticsErythropoietinEscherichia coliFutureGlycoproteinsGoalsGrowthHalf-LifeHealthHeterogeneityHormonesHumanHuman bodyIn VitroInsectaIntellectual PropertyLengthLettersLicensingMammalian CellManufacturer NameMarketingMeasuresMedicineMetabolic Clearance RateMethodsNatureParentsPathway interactionsPharmaceutical PreparationsPhasePolymersPolysaccharidesPolysialic AcidPositioning AttributePrivate SectorProcessProductionProductivityProteinsQualifyingRecombinant ProteinsRecombinantsResearchSialic AcidsSiteSmall Business Innovation Research GrantStagingTechnologyTestingTherapeuticUniversitiesWyomingalpha 1-Antitrypsinbiocompatible polymerbiodegradable polymercell typecellular engineeringclinical efficacycommercializationcostdesigndosageexperienceglycosyltransferaseimprovedin vivoinnovationmeetingsnext generationprototypepublic health relevanceresearch and developmentscaffoldsuccesstherapeutic protein
中文摘要
项目摘要/摘要
治疗性蛋白质或生物制品代表着1000亿美元的市场,其中包括药物
例如抗体、荷尔蒙和许多其他物质。生物制品的临床疗效至关重要
由它们的循环半衰期决定。因此,已经开发了各种方法来
通过降低清关率来增加它们的循环半衰期。这通常通过以下方式实现
在体外将生物制品与生物相容聚合物化学偶联。然而,化学物质
结合是昂贵的,复杂的,并且经常导致比活性的大量损失
以及不同种类的产品混合物。这些严重的缺点催生了一种需求
这项技术可以在不需要体外化学的情况下将生物兼容聚合物添加到生物制品中。
为了满足这种需求,GlycoBac提出了一种新的创新方法来添加聚唾液酸
在生物制品的生物合成过程中。聚唾液酸(PSA)天然存在于人体内,
是一种完全生物相容、可生物降解、无免疫原性的聚合物。体外化学
与之相比,多唾液酸化生物制剂已经显示出更好的耐受性和药代动力学。
成为毒品的母公司。此外,唾液酸生物学经过半个多世纪的研究已经得到了很好的理解。
研究。因此,PSA是添加到生物制品中的极佳选择,目的是增加它们的
半衰期。我们的新方法使用糖蛋白生物制品上现有的N-葡聚糖作为支架
PSA添加。用于生物生产的细胞已经将N-糖链添加到明确的位置。
我们建议在生物过程中以酶法将PSA添加到这些预先存在的N-糖链中
生物合成(体内)。与化学偶联不同的是,我们的方法是特异的,而不是
需要额外的处理步骤,并且不会带来额外的成本和复杂性。
该SBIR项目旨在证明体内聚唾液酸化作为下一步的可行性。
一代平台技术。我们将通过专注于生产原型的目标来实现这一点
具有多唾液酸化途径的细胞系。这些电池将被用来生产两种聚唾液酸化,
与商业相关的糖蛋白生物制品。对于第一阶段,我们将使用糖工程昆虫
细胞,因为GlycoBac在这类细胞方面有丰富的经验。我们的聚唾液分析技术是
也兼容哺乳动物细胞系,如CHO和PerC.6,这是常用的
生产生物制品。第一阶段的成功将为更大的第二阶段项目奠定基础,该项目的重点是
展示了体内聚唾液酸化生物制品的药代动力学和活性。第三阶段
我们的体内聚唾液酸化技术与私营部门合作伙伴的商业化是
预计将通过生产更有效的
糖蛋白生物制剂,需要较少的剂量和/或减少的剂量。
英文摘要
Project Summary / Abstract
Therapeutic proteins, or biologics, represent a $100 billion market that includes drugs
such as antibodies, hormones, and many others. The clinical efficacy of biologics is critically
determined by their circulating half-lives. Hence, various methods have been developed to
increase their circulating half-lives by reducing clearance rates. This is commonly achieved by
chemically conjugating biologics with biocompatible polymers in vitro. However, chemical
conjugation is expensive, complicated, and often results in substantial losses of specific activity
as well as a heterogeneous product mixture. These serious drawbacks have created a demand
for a technology that can add biocompatible polymers to biologics without in vitro chemistry.
To meet this demand, GlycoBac proposes a new, innovative method to add polysialic acid
to biologics during their biosynthesis. Polysialic acid is (PSA) naturally found in the human body,
and is a fully biocompatible, biodegradable and non-immunogenic polymer. In vitro chemically
polysialylated biologics have already shown improved tolerance and pharmacokinetics compared
to parent drugs. Moreover, sialic acid biology is well-understood through over half a century of
research. Thus, PSA is an excellent choice to add to biologics with the goal of increasing their
half-lives. Our new method uses existing N-glycans on glycoprotein biologics as a scaffold for
PSA addition. Cells used for biologic production already add N-glycans to well-defined positions.
We propose to enzymatically add PSA to these pre-existing N-glycans during biologic
biosynthesis (in vivo). In contrast to chemical conjugation, our method is site-specific, does not
require additional processing steps, and does not introduce additional cost and complexity.
This SBIR project is designed to prove the feasibility of in vivo polysialylation as a next-
generation platform technology. We will achieve this by Aims focused on producing a prototype
cell line with a polysialylation pathway. These cells will be used to produce two polysialylated,
commercially relevant glycoprotein biologics. For Phase I, we will use glycoengineered insect
cells, as GlycoBac has extensive experience with this cell type. Our polysialylation technology is
also compatible with mammalian cell lines such as CHO and PerC.6, which are commonly used
to produce biologics. Phase I success will set the stage for a larger Phase II project focused on
demonstrating the pharmacokinetics and activity of in vivo polysialylated biologics. Phase III
commercialization of our in vivo polysialylation technology with private-sector partners is
expected to significantly impact human health by enabling production of more efficacious
glycoprotein biologics that require less-frequent dosing and/or reduced dosages.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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依托单位:
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批准号:8589209
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资助金额:$30.24万
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批准号:9140154
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财政年份:2013
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负责人:Christoph Geisler
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依托单位:
海外基金