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ADC药物研发解决方案

ADC药物研发解决方案
背景
ADC药物的三大元件包括:1、特异性靶向抗体 2、毒素 3、可裂解/不可裂解的连接子。特异性靶点识别及有效的毒素作用使ADC成为名副其实的“生物导弹”。 ADC药物的开发具有较高的技术壁垒,需要综合考虑靶点的合理选择;抗体、连接子、小分子药物及它们之间的合理组合;抗体偶联技术以及ADC药物的耐药性等多个因素。 其中,靶点的选择、连接子的选择、偶联技术以及临床前的药效评价是ADC研发过程中关注的焦点。>>>点击查看“ADC药物开发策略、创新技术及工艺放大质控关键点分享”直播回放
为满足ADC药物研发需求,ACROBiosystems可提供:
多种高质量靶点蛋白;
用于Linker酶切的MMP/Cathepsin/uPA;
ADC定点偶联试剂盒;
抗小分子药物抗体和抗独特型抗体及开发服务便于ADC 耐药性研究;
分子互作及抗独特型抗体开发服务;
这一系列产品可满足ADC从抗体制备、筛选、偶联到后期的生产质控全流程,协助加速ADC药物研发。
ADC结构图
热门产品
ADC热门靶点蛋白
ADC靶点蛋白

产品特点

  1. 50 +ADC热门靶点蛋白全覆盖;
  2. 多种属,多标签;
  3. 高纯度经MALS验证;
  4. 高生物活性经ELISA/SPR/BLI/FACS等验证。

应用场景

  • 免疫、抗体筛选、细胞功能验证、质控

特色产品

  • ✔ 行业鲜有LIV-1系列蛋白,覆盖Human、Mouse、Cynomolgus、Rat等种属,表达区间根据SGN-LIV1A结合表位设计
多肽Linker裂解酶
Cathepsin B等,ADC 多肽Linker裂解酶

产品特点

  1. 产品类型丰富:MMPsCathepsin以及uPA系列
    蛋白产品;
  2. 采用HEK293表达,更接近蛋白天然构象;
  3. 高酶活:酶活> 2,500 pmol/min/µg。

应用场景

  • ✔ 用于酶切验证,以评估Linker的酶切效果,保证payload在胞内高效释放。
ADC定点偶联试剂盒
ADC定点偶联试剂盒

产品特点

  1. 无需对抗体序列做基因改造,具有普适性和高效性;
  2. 偶联产物DAR(Drug to Antibody Ratio)值高度均一;
  3. “一锅法”反应,操作便捷;
  4. 纯水相反应体系,避免引入有机溶剂带来不利影响;
  5. DAR2和DAR4两种偶联选择;
  6. 偶联产物稳定;
  7. 组分齐全,工具酶活性稳定,批间一致性好。

应用场景

  • ✔ 偶联阶段定点偶联,ADC早期偶联研究

特色产品

  • AGlink ADC Conjugation Kit (MMAE, DAR4)(Cat.No. ADC-P001)和AGlink ADC Conjugation Kit (MMAE, DAR2) (Cat.No. ADC-P002),偶联产物高度均一。
PK分析相关抗体
抗MMAE抗体及抗独特型抗体,ADC PK分析相关抗体

产品特点

  1. 产品丰富:抗MMAE抗体和多种抗独特型抗体
  2. 高特异性;
  3. 高灵敏度和高稳定性。

应用场景

  • ✔ ADC药物临床前和临床免疫原性分析的阳性参照
  • ✔ 药代动力学分析
  • ✔ 抗Payload抗体—定性进行DAR值的检测

特色产品

  • 高灵敏度单克隆抗MMAE抗体(Cat.No.MME-M5252),活性经与Disitamab Vedotin (RC-48)结合验证,线性区间为0.1-2 ng/mL。
亲和力检测及抗独特型抗体开发服务
SPR/BLI亲和力检测服务

SPR/BLI亲和力检测服务:

  1. 免费提供检测所需蛋白
  2. CNAS认可的技术服务
  3. 报告支持中美澳多国申报
  • 应用场景
  • ACROBiosystems基于Biacore及ForteBio Octet平台提供专业的抗体筛选、表征,一致性评价以及生物大分子间相互作用等技术服务,以个性化方案设计和报告形式助力生物医药的发展。
抗独特型抗体开发服务

抗独特型抗体(ADA)开发服务:

  1. 专注抗独特型抗体开发
  2. 保证交付灵敏度满足法规要求
  3. 全球交付支持多国临床试验
  • 开发范围:抗独特型单/多克隆抗体、ADA assay / PK assay试剂盒,满足客户多样化需求
  • 应用场景
  • ✔ ADA检测:包括筛选、验证、滴度和中和抗体实验
  • ✔ PK检测:代替抗原包板、bridging ELISA
产品列表
  • ADC靶点蛋白
  • 多肽Linker裂解酶
  • ADC定点偶联试剂盒
  • PK分析相关抗体
分子 货号 产品描述 订购/预购
Cathepsin B CTB-H5222 Human Cathepsin B / CTSB Protein, His Tag (active enzyme, MALS verified)

订购

Plasma Kallikrein/KLKB1 KL1-H52H9 Human Plasma Kallikrein / KLKB1 Protein, His Tag (active enzyme, MALS verified)

订购

MMP-1 MM1-H52H3 Human MMP-1 Protein, His Tag (active enzyme, MALS verified)

订购

MMP-9 MM9-H5221 Human MMP-9 Protein, His Tag (active enzyme)

订购

MMP-9 MM9-H5229 Human MMP-9 Protein, His Tag (active enzyme) (MALS verified)

订购

MMP-9 MM9-H52H9 Human MMP-9 (20-707) Protein, His Tag (active enzyme, MALS verified)

订购

PLAU PLU-H5228 Human PLAU / uPA Protein, His Tag (activated by trypsin) (active enzyme)

订购

PLAU PLU-H5229 Human PLAU / uPA Protein, His Tag

订购

Cathepsin L CAL-M52H3 Mouse Cathepsin L / CTSL1 Protein, His Tag (active enzyme, MALS verified)

订购

Cathepsin B CTB-M52H9 Mouse Cathepsin B / CTSB Protein, His Tag (active enzyme, MALS verified)

订购

Plasma Kallikrein/KLKB1 KL1-M52H9 Mouse Plasma Kallikrein / KLKB1 Protein, His Tag

预购

MMP-2 MM2-M52H9 Mouse MMP-2 (30-460) Protein, His Tag (active enzyme)

订购

MMP-9 MM9-M52H1 Mouse MMP-9 (20-471) Protein, His Tag (active enzyme, MALS verified)

订购

MMP-9 MM9-C52H3 Cynomolgus MMP-9 Protein, His Tag (active enzyme)

订购

分子 货号 产品描述 订购/预购
GDP-Fuc-vc-PAB-MMAE ADC-P001 AGLink® ADC Conjugation Kit (MMAE, DAR4, 2mg)

订购

GDP-Fuc-vc-PAB-MMAE ADC-P002 AGLink® ADC Conjugation Kit (MMAE, DAR2&DAR4, 2mg)

订购

GDP-Fuc-vc-PAB-MMAE ADC-P003 AGLink® ADC Conjugation Kit (MMAE, DAR4, 5mg)

订购

GDP-Fuc-vc-PAB-MMAE ADC-P004 AGLink® ADC Conjugation Kit (MMAE, DAR2&DAR4, 5mg)

订购

> 抗Payload抗体

分子 货号 产品描述 订购/预购
DM-1 DM1-BLY73 Biotinylated Monoclonal Anti-DM-1&DM-4 Antibody, Mouse IgG1 (MALS verified)

订购

DM-1 DM1-PLY73 HRP conjugated Monoclonal Anti-DM-1&DM-4 Antibody,Mouse IgG1

订购

DM-1 DM1-Y73 Monoclonal Anti-DM-1&DM-4 Antibody, Mouse IgG1 (MALS verified)

订购

DXD DXD-BLM684 Biotinylated Mouse Anti-DXD&Exatecan Antibody, Mouse IgG1

订购

DXD DXD-M684 Monoclonal Anti-DXD&Exatecan Antibody, Mouse IgG1 (MALS verified)

订购

DXD DXD-PLM684 HRP conjugated Monoclonal Anti-DXD&Exatecan Antibody, Mouse IgG1

订购

MMAE MME-BLS104 Biotinylated Monoclonal Anti-MMAE&MMAF Antibody, Mouse IgG1 (MALS verified)

订购

MMAE MME-M5252 Monoclonal Anti-MMAE&MMAF Antibody, Mouse IgG1 (MALS verified)

订购

MMAE MME-PLS104 HRP conjugated Monoclonal Anti-MMAE&MMAF Antibody,Mouse IgG1

订购

PTX PTX-S343 Monoclonal Anti-PTX Antibody, Mouse IgG2a (MALS verified)

订购

SN38 SN8-BLS223 Biotinylated Monoclonal Anti-SN38 Antibody, Mouse IgG1

订购

SN38 SN8-M685 Monoclonal Anti-SN38 Antibody, Mouse IgG1 (MALS verified)

订购

SN38 SN8-PLM685 HRP conjugated Monoclonal Anti-SN38 Antibody, Mouse IgG1

订购

SN38 SN8-PLS223 HRP conjugated Monoclonal Anti-SN38 Antibody,Mouse IgG1

订购

SN38 SN8-S223 Monoclonal Anti-SN38 Antibody (MALS verified)

订购

> 抗独特型抗体

分子 货号 产品描述 中和活性 应用
Adalimu*ab ADB-Y19 Anti-Adalimu*ab Antibodies (AY19) Neutralizing Antibody ADA assay; Neutralizing assay; Indirect ELISA
Adalimu*ab ADB-Y23b Anti-Adalimu*ab Antibodies (AY23b) (recommended for PK/PD) Non-Neutralizing Antibody PK bridging ELISA; Indirect ELISA
Bevacizu*ab BEB-Y10 Anti-Bevacizu*ab Antibodies (AY10) (MALS verified, recommended for PK/PD) Neutralizing Antibody PK bridging ELISA; Neutralizing assay; Indirect ELISA
Bevacizu*ab BEB-Y12 Anti-Bevacizu*ab Antibodies (AY12) (recommended for neutralizing assay) Neutralizing Antibody ADA assay; Neutralizing assay; Indirect ELISA
Bevacizu*ab BEB-Y9 Anti-Bevacizu*ab Antibodies (AY9) (recommended for ADA assay) Neutralizing Antibody ADA assay; Neutralizing assay; Indirect ELISA
Bevacizu*ab BEB-BY13 Biotinylated Anti-Bevacizu*ab Antibodies (AY13) (recommended for PK/PD) Neutralizing Antibody PK bridging ELISA;Neutralizing assay; Indirect ELISA
Cetuxi*ab CEB-Y27 Anti-Cetuxi*ab Antibodies (AY27) (recommended for ADA assay) Neutralizing Antibody ADA assay; Neutralizing assay; Indirect ELISA
Cetuxi*ab CEB-Y31 Anti-Cetuxi*ab Antibodies (AY31) (Non-Neutralizing) Non-Neutralizing Antibody ADA assay; Indirect ELISA
Cetuxi*ab CEB-Y28 Anti-Cetuxi*ab Antibodies (AY28) Neutralizing Antibody ADA assay; Neutralizing assay; Indirect ELISA
Cetuxi*ab CEB-BY31 Biotinylated Anti-Cetuxi*ab Antibodies (AY31) (recommended for PK/PD) Non-Neutralizing Antibody PK bridging ELISA; Indirect ELISA
Rituxi*ab RIB-Y36 Anti-Rituxi*ab Antibodies (AY36) (recommended for ADA assay) Neutralizing Antibody ADA assay;Neutralizing assay; Indirect ELISA
Rituxi*ab RIB-Y37 Anti-Rituxi*ab Antibodies (AY37) (recommended for PK/PD) Neutralizing Antibody PK bridging ELISA;Neutralizing assay;Indirect ELISA
Rituxi*ab RIB-Y35c Anti-Rituxi*ab Antibodies (MALS verified) Non-Neutralizing Antibody ADA assay; Indirect ELISA
Trastuzu*ab TRB-Y5b Anti-Trastuzu*ab Antibodies (AY5b) (recommended for PK/PD) Neutralizing Antibody PK bridging ELISA
Trastuzu*ab TRB-Y1b Anti-Trastuzu*ab Antibodies (AY1b) (recommended for PK/PD) Neutralizing Antibody PK bridging ELISA; Neutralizing assay; Indirect ELISA
ADC药物靶点蛋白
靶点蛋白验证数据
高纯度—MALS 验证
HER2 MALS测定结果

The purity of Human Her2, His Tag (Cat. No. HE2-H5225) was more than 90% and the molecular weight of this protein is around 80-95 kDa verified by SEC-MALS.

高亲和力—ELISA验证
HER2 ELISA测定结果

Immobilized Human TROP-2, His Tag (Cat. No. TR2-H5223) at 1 μg/mL (100 μL/well) can bind Mouse Monoclonal Antibody Against Human TROP-2, Mouse IgG1 with a linear range of 0.1-2 ng/mL (QC tested).

申请 Protocol
PSMA ELISA测定结果

Immobilized Human PSMA, His Tag (Cat. No. PSA-H52H3) at 2 μg/mL (100 μL/well) can bind Monoclonal Anti-Human PSMA Antibody, Human IgG1 with a linear range of 0.3-39 ng/mL (Routinely tested).

申请 Protocol
高亲和力—SPR验证
LIV-1 SPR测定结果

Anti-LIV-1 mAb captured on CM5 chip via anti-human IgG Fc antibody can bind Human LIV-1, His Tag (Cat. No. LV1-H5223) with an affinity constant of 5.24 nM as determined in a SPR assay (Biacore T200) (Routinely tested).

申请 Protocol 点击咨询SPR服务
HER2 SPR测定结果

Herceptin (Trastuzumab) captured on CM5 chip via anti-human IgG Fc antibodies surface, can bind Human Her2, His Tag (Cat. No. HE2-H5225) with an affinity constant of 1.07 nM as determined in a SPR assay.

申请 Protocol 点击咨询SPR服务
高亲和力—BLI验证
Nectin-4 BLI测定结果

Loaded Mouse Nectin-4, His Tag (Cat. No. NE4-M52H3) on HIS1K Biosensor, can bind Human Nectin-1, Fc Tag (Cat. No. PV1-H5253) with an affinity constant of 0.12 μM as determined in BLI assay (ForteBio Octet Red96e) (Routinely tested).

申请 Protocol 点击咨询BLI服务
高亲和力—FACS验证
ROR1 BLI测定结果

2e5 of anti-ROR1 CAR-293 cells were stained with 100 μL of 10 μg/mL of Human / Cynomolgus / Rhesus macaque ROR1 (39-151, Ig-like domain), His Tag (Cat. No. RO1-H5221) and negative control protein respectively, washed and then followed by PE-anti-His Tag and analyzed with FACS (Routinely tested).

申请 Protocol
多肽Linker裂解酶
在ADC设计开发中,Linker的结构及化学性质直接影响ADC的稳定性、安全性和特异性。Linker分为可裂解和不可裂解Linker。多肽Linker是目前ADC开发中广泛应用的一种可裂解Linker,在设计时,需综合考虑选择合适的裂解酶用于Linker的裂解。
ACROBiosystems开发了一系列用于裂解酶切Linker的MMPsCathepsin以及uPA蛋白产品。

相关阅读:

不同Linker裂解酶:针对多肽Linker“量体裁衣”

更多anti-payload antibodies(Anti-Dxd antibody/Anti-SN-38 antibody/Anti-MMAF antibody)正在开发中,敬请期待!
ADC作用机理
验证数据
测定产品 货号:CTB-H5222 Human Cathepsin B / CTSB Protein, His Tag (active enzyme) 货号:MM9-H5221 Human MMP-9 Protein, His Tag (active enzyme)
水解底物 荧光标记多肽底物 Z-LR-AMC 荧光标记多肽底物 Mca-PLGL-Dpa-AR-NH2
酶活
(pmol/min/μg)
> 2500 > 2500
ADC定点偶联试剂盒
偶联方式一般分为非定点偶联和定点偶联。非定点偶联会导致ADC的异质性,影响ADC的活性、稳定性、药代动力学及疗效。相比于非定点偶联,采用定点偶联策略能实现抗体与小分子毒素定点、定量偶联,通过该技术获得的ADC DAR值均一,同质性高,稳定性、药代动力学性质更好,治疗窗更宽。很大程度上保证药物批量生产稳定性,也更适用于ADC的大规模生产。因此,定点偶联策略的开发和应用显著增加。
非定点偶联和定点偶联的比较
非定点偶联和定点偶联的比较[1]
ACROBiosystems与岩唐生物科技(杭州)有限责任公司合作推出了AGLink ADC定点偶联试剂盒。该试剂盒基于岩唐生物的YTConju技术平台开发[2],可以对具有Fc结构域的抗体进行位点特异性定量偶联,产生稳定且DAR值均一的抗体偶联物,可用于ADC药物早期科学研究。

相关阅读:

ADC酶定点偶联试剂盒,让你的“魔术子弹”魔力倍增

偶联原理
几乎所有的单克隆抗体在Fc区N297位,都会有糖基化修饰。因而可利用特异性的酶对糖链进行改造,并在改造后的糖基上实现药物的定点偶联。具体示意图如下[2]
AGlink ADC Conjugation Kit (MMAE, DAR4)
AGlink ADC Conjugation Kit (MMAE, DAR4)
AGlink ADC Conjugation Kit (MMAE, DAR2)
AGlink ADC Conjugation Kit (MMAE, DAR2)
验证数据
偶联产物高度均一
ADC(DAR 4 & DAR 2)的HIC-HPLC分析

DAR 4 & DAR 2 ADC的HIC-HPLC分析

偶联后不改变抗原结合能力
ADC(DAR 4 & DAR 2 )的HER2抗原结合力分析

DAR 4 & DAR 2 ADC的HER2抗原结合力分析

偶联过程温和,不易产生聚体
ADC(DAR 4 & DAR 2 )的SEC-HPLC分析

DAR 4 & DAR 2 ADC的SEC-HPLC分析,聚体< 5%

偶联产物具有较高的血浆稳定性
ADC人血浆(体外)稳定性

DAR 4 & DAR 2 ADC的人血浆(体外)稳定性。DAR 4 & DAR 2 ADC在人血浆(体外)中稳定无降解

体外细胞杀伤活性验证
ADC体外细胞杀伤活性验证

DAR 4 & DAR 2 ADC的体外细胞杀伤活性验证

PK分析相关抗体
ACROBiosystems可提供一系列高特异性、高灵敏度和高稳定性抗MMAE抗体抗独特型抗体,用于ADC药物临床前和临床免疫原性分析的阳性参照和药代动力学分析,可以节省客户制备抗体的时间,免费提供完整的方法学protocol。
验证数据:
抗MMAE抗体高特异性结合MMAE
抗MMAE抗体高特异性结合MMAE

The EC50 value of anti-MMAE antibody to MMAE-conjugated hRS7 (MMAE-ADC) was 0.12 μg/ml. The unconjugated hRS7 antibody was used as negative control

抗MMAE抗体高特异性结合MMAE ADC

Immobilized Disitamab Vedotin (RC48) at 0.2 μg/mL (100 μL/well) can bind Mouse Anti-MMAE Antibody, Mouse IgG1 (Cat. No. MME-M5252) with a linear range of 0.1-2 ng/mL (QC tested).

申请 Protocol
特异性检测体内抗体药水平
抗Rituximab抗体特异性检测体内抗体药水平
Detection of rituximab by antigen-capture ELISA (0.1% serum).
抗Rituximab抗体特异性检测体内抗体药水平
Detection of rituximab by anti-idiotypic capture ELISA (0.1% serum).
抗Rituximab抗体特异性检测体内抗体药水平
Detection of rituximab by anti-idiotypic bridging ELISA (10% serum).
检测方法 线性范围
(µg/mL)
灵敏度
(µg/mL)
优势 劣势
Antigen-capture ELISA 方法简单,通用性好 背景值高,无活性
Anti-idiotypic capture ELISA 0.156-10 0.156 解决了CD20获得难的问题,方法简单 背景高,只适用于美罗华biosimilar
Bridging ELISA by anti-idiotypic antibodies 0.012-0.78 0.012 解决了CD20获得难的问题,灵敏度好,背景低 只适用于美罗华biosimilar

相关阅读:

ADC药物PK验证,岂能缺少抗MMAE抗体

SPR/BLI亲和力检测以及抗独特性抗体开发服务
除上述产品外,依托强大专业的技术团队,ACROBiosystems同时也为客户提供高质量一体化的SPR&BLI分子互作检测服务以及多种抗独特型单/多克隆抗体、血药浓度定量检测试剂盒开发的一站式服务,协助客户加快ADC药物研发进程。
SPR&BLI分子互作检测服务
合作工业及科研用户百余家
检测用ADC靶点蛋白免费提供
抗体筛选、表征、一致性评价方法开发免费赠送
最快询单次日即可出具报告
助力多个抗体药物成功申报临床
ADC中SPB/BLI分子互作服务
抗独特型抗体开发服务
抗体筛选所需ACRO蛋白免费提供
响应快,项目组一对一服务,实时跟进实验进度
提供从抗原制备到检测试剂盒开发的一站式服务
保证交付灵敏度满足法规要求的PK/ADA检测试剂
ADC中抗独特型抗体(ADA)开发服务
参考文献
  • [1] Antibody drug conjugate: the “biological missile” for targeted cancer therapy
  • [2] Reducing the Complexity of Fc Glycan Enables the Construction of Antibody Conjugates with Unexpected High Efficiency and Payload Capacity via Glycoengineering
抗Payload抗体试用装申请
ACRO质量管理体系

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