Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Bispecific antibodies for factor ix and factor x

A bispecific, antibody technology, applied in the field of bispecific antigen binding molecules, can solve problems such as increased patient deaths and safety issues

Pending Publication Date: 2020-02-04
KIMAB LTD
View PDF18 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Thus, the efficacy data on embilizumab are encouraging, but the death of a patient in the HAVEN 1 study raises safety concerns

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Bispecific antibodies for factor ix and factor x
  • Bispecific antibodies for factor ix and factor x
  • Bispecific antibodies for factor ix and factor x

Examples

Experimental program
Comparison scheme
Effect test

example

[0561] The following examples describe the generation, characterization and performance of anti-FIXa antibodies, anti-FX antibodies and bispecific antibodies generated from combinations of the FIXa-binding and FX-binding polypeptide arms of anti-FIXa and anti-FX antibodies, respectively. Using Kymouse TM (a transgenic mouse platform capable of producing antibodies with human variable domains) to produce antibodies. Antibodies from Kymouse have human variable domains and mouse constant domains generated from human v(d) and j fragments. Endogenous mouse variable genes have been silenced and represent only a small fraction of the antibody repertoire (less than 0.5% of all heavy chain variable regions are of mouse origin). The Kymouse system was described in Lee et al. 2014 [ 11 ], described in WO2011 / 004192, WO2011 / 158009 and WO2013 / 061098. This project employed the Kymouse HK strain in which the heavy chain locus and the light chain kappa locus were humanized, and the Kymouse...

example 1

[0562] Example 1. Production of Antibodies Against Factor IXa (FIXa)

[0563] Four Kymouse HK mice (male, 4 months old at the start of immunization) and four Kymouse HL mice (male, 3 months old at the start of immunization) were directed against human Factor IXa (Enzyme Research Laboratories , Inc.)) immunity.

[0564] Spleen tissue was collected from immunized mice, and splenocytes were suspended and sorted by FACS to isolate antigen-specific B cells. A total of 2,460 Factor IXa-specific B cells were sorted from 8 immunized animals. Coupled antibody heavy and light chain variable domain sequences are recovered from B cells by reverse transcription of RNA and PCR amplification of the variable regions.

[0565] Nucleic acid encoding the antibody was transfected into the human cell line Expi293F for expression, and the supernatant collected.

example 2

[0566] Example 2. Production of Factor IXa Antibodies (Homogeneous Time-Resolved Fluorescence) Screening

[0567] The HTRF assay was used to screen for anti-FIXa antibodies that bind to FIXa. FIXa and antibody were labeled with two different fluorophores (donor and acceptor). When the two entities are close enough to each other, excitation of the donor by the energy source triggers energy transfer towards the acceptor, which in turn emits a specific fluorescence at a given wavelength. Therefore, the binding of FIXa to its specific antibody can be detected by detection at the emission wavelength of the receptor.

[0568] Serial dilutions of the anti-human Factor IX reference antibody AbN and the CM7 isotype control antibody were prepared using Expi293 expression medium (Invitrogen). 5 μL of supernatant from each of the 2,460 antibody-secreting human cells generated in Example 1 was transferred to the assay plate. Transfer 5 μL of AbN and CM7 isotype control antibodies to e...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
solubility (mass)aaaaaaaaaa
Login to View More

Abstract

Bispecific antigen binding molecules (e.g., antibodies) that bind blood clotting factors, factor IXa (FIXa) and factor X (FX), and enhance the FIXa-catalysed activation of FX to FXa. Use of the bispecific antigen binding molecules is to control bleeding, by replacing natural cofactor FVIIIa which is deficient in patients with haemophilia A.

Description

technical field [0001] The present invention relates to bispecific antigen binding molecules (eg, antibodies) that bind Factor IXa and Factor X coagulation factors in the coagulation cascade. Such bispecifics functionally displace factor VIII by activating factor X, thereby restoring coagulation in patients deficient in FVIII (ie, patients with hemophilia A). Background technique [0002] Hemophilia is an inherited disorder in which the blood's ability to clot is reduced due to the loss (partial or complete) of one of the various clotting factors. Hemophilia A is a deficiency of clotting factor VIII (FVIII). The disease has mild, moderate and severe forms, depending on the extent to which the patient retains any residual FVIII function and the balance of other components in the coagulation cascade. If left untreated, hemophilia A causes uncontrolled bleeding, which can lead to severe dysfunction, especially because of the damage to the joints caused by the hemarthrosis eve...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/36C07K16/40C07K16/46A61K39/00
CPCC07K16/36C07K16/40C07K2317/31C07K2317/76C07K2317/21C07K2317/55C07K2317/56C07K2317/64C07K2317/70C07K2317/75C07K2317/92A61P7/04
Inventor 汪玮E-C·李J·K·布莱克伍德R·马廖齐
Owner KIMAB LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com