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

Antigen-binding protein specific for serum amyloid P component

A serum starch, specific technology, used in peptide/protein components, drug combinations, immunoglobulins, etc., can solve the problem of not removing SAP

Inactive Publication Date: 2017-03-01
GLAXO GRP LTD
View PDF42 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In a preliminary clinical study (Gillmore et al., (2010) Brit.J.Haematol., doi: 10.1111 / j.1365-2141.2009.08036.x), administration of CPHPC appeared to prevent amyloid accumulation, but it did not produce Amyloid regression, and because CPHPC does not completely remove all SAP from amyloid deposits, an alternative protocol is required

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
  • Antigen-binding protein specific for serum amyloid P component
  • Antigen-binding protein specific for serum amyloid P component
  • Antigen-binding protein specific for serum amyloid P component

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0276] Example 1 - Sequencing of hybridoma variable domains: SAP-E and SAP-K

[0277] SAP-E and SAP-K are derived from 2 panels of anti-SAP monoclonal antibodies, each of which has been individually tested for in vitro binding to SAP. Within their group, SAP-E and SAP-K showed the strongest binding to SAP and they were compared with each other in different experiments.

[0278] The first panel of antibodies comprised antibodies from 7 hybridomas and was named SAP-A to SAP-G, using purified human SAP (SEQ ID NO: 43 shown below) (details of the method for purifying human SAP , see Hawkins et al. (1991) Clin. Exp. Immunol. 84, 308-316) and fusion protocols are produced in a single routine immunization. Two of these antibodies (SAP-E and SAP-B) were of the IgG2a isotype, whereas the others were of the IgGl isotype (see Example 13, Table 11).

[0279] The second panel of antibodies comprised six different IgG2a monoclonal antibodies (SAP-H to SAP-M) derived from immunization by...

Embodiment 2

[0328] Example 2: Construction of Chimeric Antibody

[0329] Chimeric antibodies were constructed by PCR cloning of SAP-E and SAP-K, comprising parental murine variable domains grafted onto human IgGl / κ wild-type constant regions. Based on the consensus sequence, primers for the amplification of the murine variable domains were designed incorporating the restriction sites required to facilitate cloning into mammalian expression vectors. The VH amino acid sequence in SAP-E was changed from that shown in SEQ ID NO: 7 by introducing restriction sites in FR4 (framework region 4 (V-region sequence behind CDR3 and in front of the first constant domain)) TTLTVSS was changed to TLVTVSS, and the VH amino acid sequence in SAP-K was changed from TTVTVSS shown in SEQ ID NO: 17 to TLVTVSS. In the SAP-K variable light chain, an internal EcoRI site exists in CDRL1, and mutagenic primers were designed to remove this unwanted internal EcoRI site by changing one base pair (which does not cha...

Embodiment 3

[0347] Embodiment 3: humanization strategy

[0348] Humanized antibodies are prepared by grafting CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 from murine antibodies onto appropriate human framework sequences.

[0349] SAP-E humanization strategy

[0350] SAP-E heavy chain humanization

[0351] For the SAP-E mouse variable heavy chain sequence, the human germline acceptor framework (IGHV1-69, SEQ ID NO:25) was chosen, which is identical to the mouse SAP-E variable heavy chain sequence (SEQ ID NO:7) and the JH1 minigene (Kabat: AEYFQHWGQGTLVTVSS (SEQ ID NO: 26)) with 60% identity (including CDRs). The first 6 residues of the JH1 minigene residues fell within the CDR3 region and were replaced by importing CDRs from the donor antibody.

[0352] Based on sequence alignment and possible impact on antibody function, five humanized variants were prepared. Construct H0 is a linear graft of murine CDRs (defined using Kabat) into the human acceptor framework selected above. C...

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

No PUM Login to View More

Abstract

The present invention relates to antigen-binding proteins (such as antibodies) that bind serum amyloid P component (SAP), polynucleotides encoding such antigen-binding proteins, pharmaceutical compositions comprising the antigen-binding proteins, and production methods. The invention also relates to the use of such antigen binding proteins in the treatment or prevention of diseases associated with amyloidosis, including systemic amyloidosis, localized amyloidosis, Alzheimer's disease and type II diabetes.

Description

technical field [0001] The present invention relates to antigen-binding proteins (such as antibodies) that bind serum amyloid P component (SAP), polynucleotides encoding such antigen-binding proteins, pharmaceutical compositions comprising the antigen-binding proteins, and production methods. The invention also relates to the use of such antigen-binding proteins in the treatment or prevention of diseases associated with amyloid deposition, including systemic amyloidosis, localized amyloidosis, Alzheimer's disease and type II diabetes. Background technique [0002] Amyloidosis is a serious and often fatal disease caused by the extracellular accumulation in tissues of abnormal insoluble protein fibers called amyloid fibrils. These are derived from more than 20 different proteins in different forms of disease, but all amyloid fibrils share a common cross-beta core structure and are all derived by misfolding of a usually soluble precursor protein (Pepys, M.B. (2006) Annu. Rev....

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 Patents(China)
IPC IPC(8): A61K39/395A61P25/28C07K16/18
CPCA61K2039/505A61K2039/545C07K16/18C07K2317/24C07K2317/34C07K2317/54C07K2317/56C07K2317/565C07K2317/92A61P25/00A61P25/28A61P3/10A61K38/17A61K38/18A61K39/395A61K48/00C07K14/435C07K14/475C07K14/54C07K16/22C07K16/24C07K16/28
Inventor T·K·布欣德S·K·福特V·格马舍夫斯基A·P·路维斯M·B·佩皮斯
Owner GLAXO GRP 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