Anti-INSR ADCC Enhanced Antibody (AGT-182) is an ADCC enhanced antibody produced by our Afuco™ platform. AGT‑182 is an investigational enzyme replacement therapy (ERT) for the treatment of neurological complications in patients with Hunter syndrome. Currently approved treatments for Hunter syndrome do not penetrate the BBB and therefore do not address the severe and progressive neurological complications of the disease. AGT-182 is a fusion protein of iduronate-2-sulfatase (IDS), engineered to cross the BBB by binding to insulin receptors located on the BBB. AGT‑182 crosses the BBB safely at unprecedented levels.
Figure 1 Immunocytochemistry of Rhesus monkey brain stained with 15 ug/mL of either the biotinylated HIRMAb-IDS fusion protein (A) or the biotinylated human IgG1k isotype control antibody (B).
The slides are counter-stained with hematoxylin. Both sections were developed under identical conditions. Magnification bar in panel B is 22 microns.
Boado, R. J., Ka-Wai Hui, E., Zhiqiang Lu, J., & Pardridge, W. M. (2014). Insulin receptor antibody-iduronate 2-sulfatase fusion protein: Pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys.Biotechnology and bioengineering, 111(11), 2317-2325.
Figure 2 The plasma IDS enzyme activity profiles generated the PK parameters of plasma clearance of IDS enzyme activity.
Plasma profile of immunoreactive HIRMAb-IDS fusion protein (open squares) and IDS enzyme activity (closed squares) at week 1 for 3 mg/kg (A), 10 mg/kg (B), and 30 mg/kg (C) infusion doses of the HIRMAb-IDS fusion protein. Mean ± SD (N=6–9).
Boado, R. J., Ka-Wai Hui, E., Zhiqiang Lu, J., & Pardridge, W. M. (2014). Insulin receptor antibody-iduronate 2-sulfatase fusion protein: Pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys.Biotechnology and bioengineering, 111(11), 2317-2325.
Figure 3 The parallel proportionality between the plasma AUC, of either the immunoreactive HIRMAb-IDS fusion protein, or the plasma IDS enzyme activity, vs. the infusion dose is shown by the plot.
Plasma area under the concentration curve (AUC) of immunoreactive HIRMAb-IDS fusion protein (open squares), in µg•min/mL, and AUC of plasma IDS enzyme activity (closed squares), in kilounits•min/mL, is plotted vs dose of HIRMAb-IDS fusion protein at week 1. Mean ± SD.
Boado, R. J., Ka-Wai Hui, E., Zhiqiang Lu, J., & Pardridge, W. M. (2014). Insulin receptor antibody-iduronate 2-sulfatase fusion protein: Pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys.Biotechnology and bioengineering, 111(11), 2317-2325.
Figure 4 There is a 1:1 correlation between the PK of plasma clearance of the immunoreactive HIRMAb-IDS fusion protein, and the plasma IDS enzyme activity.
(A) Comparison of plasma area under the concentration curve (AUC) for the IDS enzyme activity vs the plasma AUC of immunoreactive HIRMAb-IDS fusion protein at week 1. Mean ± SD. (B) Comparison of the in vivo specific activity (closed bar) of the HIRMAb-IDS fusion protein in plasma in monkeys over 23 hours after infusion vs the in vitro IDS specific activity (open bar) of the infused HIRMAb-IDS fusion protein. Mean ± SD. The in vivo specific activity was determined from the slope of the plot in panel A.
Boado, R. J., Ka-Wai Hui, E., Zhiqiang Lu, J., & Pardridge, W. M. (2014). Insulin receptor antibody-iduronate 2-sulfatase fusion protein: Pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys.Biotechnology and bioengineering, 111(11), 2317-2325.
Figure 5 The plasma IDS enzyme activity profile was measured following IV infusion of the HIRMAb-IDS fusion protein at the end (week 25) of the study.
Plasma profile of IDS enzyme activity at week 25 for 3 mg/kg (A), 10 mg/kg (B), and 30 mg/kg (C) infusion doses of the HIRMAb-IDS fusion protein. Mean ± SD (N=6–9).
Boado, R. J., Ka-Wai Hui, E., Zhiqiang Lu, J., & Pardridge, W. M. (2014). Insulin receptor antibody-iduronate 2-sulfatase fusion protein: Pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys.Biotechnology and bioengineering, 111(11), 2317-2325.
Figure 6 The ADA response increased after 4 weeks of treatment and reached a maximum by 16–20 weeks of treatment.
Time course of ADA formation against the HIRMAb-IDS fusion protein. Data are mean ± SE (n=6–9 monkeys per time point). All plasma samples were diluted 1:50 in PBS. The dose of each group of monkeys is given in the inset of the figure.
Boado, R. J., Ka-Wai Hui, E., Zhiqiang Lu, J., & Pardridge, W. M. (2014). Insulin receptor antibody-iduronate 2-sulfatase fusion protein: Pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys.Biotechnology and bioengineering, 111(11), 2317-2325.
Figure 7 The titer is 0.2, 1.0, and 2.1, at 3, 10, and 30 mg/kg doses, respectively, when the capture agent is the human IgG1κ isotype control antibody.
Absorbance (A490) is plotted against dilution of pools of primate plasma from 1:50 to 1:10,000 in PBS for monkeys administered the HIRMAb-IDS fusion protein at weekly doses of 3 mg/kg (panel A), 10 mg/kg (panel B), and 30 mg/kg (panel C). The pool was produced from the week 24 blood samples. The capture reagent in the sandwich ELISA is the HIRMAb-IDS fusion protein (open circles), the HIRMAb alone (closed squares), or the human IgG1,κ isotype control (closed triangles). Data are mean ± SD (N=3 replicates).
Boado, R. J., Ka-Wai Hui, E., Zhiqiang Lu, J., & Pardridge, W. M. (2014). Insulin receptor antibody-iduronate 2-sulfatase fusion protein: Pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys.Biotechnology and bioengineering, 111(11), 2317-2325.
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• Confirmed specificity
• High repeatability
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• Animal-free production
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CAT | Product Name | Application | Type |
---|---|---|---|
TAB-441CL | Human Anti-INSR Recombinant Antibody (TAB-441CL) | ELISA | Human IgG |
CAT | Product Name | Application | Type |
---|---|---|---|
TAB-711LC-S(P) | Human Anti-INSR Recombinant Antibody; scFv Fragment (TAB-711LC-S(P)) | ELISA, FC | Human scFv |
TAB-712LC-S(P) | Human Anti-INSR Recombinant Antibody; scFv Fragment (TAB-712LC-S(P)) | ELISA, FC | Human scFv |
TAB-711LC-F(E) | Human Anti-INSR Recombinant Antibody; Fab Fragment (TAB-711LC-F(E)) | ELISA, FC | Human Fab |
PABX-124-S (P) | Recombinant Mouse Anti-IR Antibody scFv Fragment (Fab83-14) | Neut, FuncS | scFv |
PABX-125-S (P) | Recombinant Mouse Anti-IR Antibody scFv Fragment (Fab83-7) | WB, ELISA, FuncS | scFv |
CAT | Product Name | Application | Type |
---|---|---|---|
PABX-124 | Recombinant Mouse Anti-IR Antibody (Fab83-14) | Neut, FuncS | IgG |
PABX-125 | Recombinant Mouse Anti-IR Antibody (Fab83-7) | WB, ELISA, FuncS | IgG |
PABX-124-F (E) | Recombinant Mouse Anti-IR Antibody Fab Fragment (Fab83-14 ) | Neut, FuncS | Fab |
PABX-125-F (E) | Recombinant Mouse Anti-IR Antibody Fab Fragment (Fab83-7 ) | WB, ELISA, FuncS | Fab |
CAT | Product Name | Application | Type |
---|---|---|---|
MHC-LC1205 | PE-H-2Kb/Mouse Insr (GNYSFYAL) MHC Tetramer | FCM | |
MHC-LC1206 | APC-H-2Kb/Mouse Insr (GNYSFYAL) MHC Tetramer | FCM | |
MHC-LC1207 | BV421-H-2Kb/Mouse Insr (GNYSFYAL) MHC Tetramer | FCM |
CAT | Product Name | Application | Type |
---|---|---|---|
NEUT-1533CQ | Mouse Anti-INSR Recombinant Antibody (clone 1.B.109) | Inhib, IP | Mouse IgG2a |
NEUT-1535CQ | Mouse Anti-INSR Recombinant Antibody (clone 47-9) | FC, Block, WB | Mouse IgG1 |
NEUT-1536CQ | Mouse Anti-INSR Recombinant Antibody (clone 18-44) | FC, ICC, IF, Block, FuncS, IP, WB | Mouse IgG2b |
CAT | Product Name | Application | Type |
---|---|---|---|
NEUT-1534CQ | Mouse Anti-INSR Recombinant Antibody (clone 29B4) | IP, Neut | Mouse IgG1 |
CAT | Product Name | Application | Type |
---|---|---|---|
MOR-1844 | Rabbit Anti-INSR Recombinant Antibody (clone DS1844AB) | ICC, IP, WB | Rabbit IgG |
MOR-4630 | Rabbit Anti-INSR Recombinant Antibody (clone TH143DS) | WB | Rabbit IgG |
MOR-4688 | Rabbit Anti-INSR Recombinant Antibody (clone TH202DS) | WB, FC | Rabbit IgG |
CAT | Product Name | Application | Type |
---|---|---|---|
HPAB-0129-YC-S(P) | Mouse Anti-INSR Recombinant Antibody; scFv Fragment (HPAB-0129-YC-S(P)) | ELISA, FC | Mouse scFv |
HPAB-2351LY-S(P) | Human Anti-INSR Recombinant Antibody; scFv Fragment (HPAB-2351LY-S(P)) | ELISA, WB | Humanized scfv |
HPAB-2352LY-S(P) | Human Anti-INSR Recombinant Antibody; scFv Fragment (HPAB-2352LY-S(P)) | ELISA, WB | Humanized scfv |
HPAB-2353LY-S(P) | Human Anti-INSR Recombinant Antibody; scFv Fragment (HPAB-2353LY-S(P)) | ELISA, WB | Humanized scfv |
HPAB-2354LY-S(P) | Human Anti-INSR Recombinant Antibody; scFv Fragment (HPAB-2354LY-S(P)) | ELISA, WB | Humanized scfv |
CAT | Product Name | Application | Type |
---|---|---|---|
HPAB-2351LY-F(E) | Human Anti-INSR Recombinant Antibody; Fab Fragment (HPAB-2351LY-F(E)) | ELISA, WB | Humanized Fab |
HPAB-2352LY-F(E) | Human Anti-INSR Recombinant Antibody; Fab Fragment (HPAB-2352LY-F(E)) | ELISA, WB | Humanized Fab |
HPAB-2353LY-F(E) | Human Anti-INSR Recombinant Antibody; Fab Fragment (HPAB-2353LY-F(E)) | ELISA, WB | Humanized Fab |
HPAB-2354LY-F(E) | Human Anti-INSR Recombinant Antibody; Fab Fragment (HPAB-2354LY-F(E)) | ELISA, WB | Humanized Fab |
HPAB-2355LY-F(E) | Human Anti-INSR Recombinant Antibody; Fab Fragment (HPAB-2355LY-F(E)) | ELISA, WB | Humanized Fab |
CAT | Product Name | Application | Type |
---|---|---|---|
HPAB-2351LY | Human Anti-INSR Recombinant Antibody (HPAB-2351LY) | ELISA, WB, FC, FuncS | Humanized IgG |
HPAB-2352LY | Human Anti-INSR Recombinant Antibody (HPAB-2352LY) | ELISA, WB, FC, FuncS | Humanized IgG |
HPAB-2353LY | Human Anti-INSR Recombinant Antibody (HPAB-2353LY) | ELISA, WB | Humanized IgG |
HPAB-2354LY | Human Anti-INSR Recombinant Antibody (HPAB-2354LY) | ELISA, WB | Humanized IgG |
HPAB-2355LY | Human Anti-INSR Recombinant Antibody (HPAB-2355LY) | ELISA, WB | Humanized IgG |
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