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

Human Anti-OPGL Neutralizing Antibodies As Selective OPGL Pathway Inhibitors

a technology of opgl pathway inhibitors and neutralizing antibodies, which is applied in the field of antibodies, can solve the problems of reduced bone mass and strength, slow or incomplete repair of broken bones, and increased risk of fractures

Inactive Publication Date: 2010-08-19
AMGEN INC +1
View PDF99 Cites 29 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides monoclonal antibodies that specifically bind to osteoprotegerin ligand (OPGL), which is a protein involved in low bone density disorders. These antibodies can inhibit the binding of OPGL to its receptor, osteoclast differentiation and activation receptor (ODAR), and can be used to treat disorders associated with low bone density. The antibodies are human and are produced by a hybridoma cell line. The invention also provides methods for making and using these antibodies.

Problems solved by technology

In certain individuals, such as post-menopausal women, the rate of resorption can exceed the rate of deposition, which may result in reduced bone mass and strength, increased risk of fractures, and slow or incomplete repair of broken bones.

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
  • Human Anti-OPGL Neutralizing Antibodies As Selective OPGL Pathway Inhibitors
  • Human Anti-OPGL Neutralizing Antibodies As Selective OPGL Pathway Inhibitors
  • Human Anti-OPGL Neutralizing Antibodies As Selective OPGL Pathway Inhibitors

Examples

Experimental program
Comparison scheme
Effect test

example 1

Production of Human Monoclonal Antibodies Against OPGL

Transgenic HuMab Mice

[0231]Fully human monoclonal antibodies to OPGL were prepared using HCo7, HCo12, and HCo7+HCo12 strains of transgenic mice, each of which expresses human antibody genes. In each of these mouse strains, the endogenous mouse kappa light chain gene has been homozygously disrupted (as described in Chen et al., 1993, EMBO J. 12: 811-820) and the endogenous mouse heavy chain gene has been homozygously disrupted as described in Example 1 of PCT Publication WO 01 / 09187 (incorporated by reference). Each of these mouse strains carries a human kappa light chain transgene, KCo5 (as described in Fishwild et al., 1996, Nature Biotechnology 14: 845-851). The HCo7 strain carries the HCo7 human heavy chain transgene as described in U.S. Pat. Nos. 5,545,806; 5,625,825; and 5,545,807 (incorporated by reference). The HCo12 strain carries the HCo12 human heavy chain transgene as described in Example 2 of PCT Publication WO 01 / 091...

example 2

Cloning the 9H7 Anti-OPGL Heavy and Light Chains

[0241]Cloning of the 9H7 anti-OPGL MAb light chain

[0242]Three anti-OPGL hybridoma light chain cDNAs (9H7, 16E1 and 18B2) were cloned into pDSR19 mammalian cell expression vector. The construction of a plasmid encoding the 9H7 kappa light chain is explicitly described; cloning of the other light chain species was performed using similar procedures. The anti-OPGL-9H7 kappa light chain variable region was obtained using polymerase chain reaction (PCR) amplification methods from first strand cDNA prepared from hybridoma 9H7 total RNA. First strand cDNA was prepared from 9H7 total RNA using a random primer with an extended 5′-adapter (5′-GGCCGGATAGGCCTCACNNNNNNT-3′, SEQ ID NO: 53) and the materials and methods provided by the Gibco SuperScript II™ Preamplification System for First Strand cDNA Synthesis kit (Catalogue No. 18089-011). The oligonucleotides below were used for the PCR:

5′ GeneRacer™ (Invitrogen) primer(SEQ ID NO: 54):5′-GGA CAC ...

example 3

9H7 Anti-OPGL MAb Expression in CHO Cells

[0251]Recombinant anti-OPGL antibodies are produced by Chinese hamster ovary cells, specifically CHO AM-1 / D, as disclosed in U.S. Pat. No. 6,210,924 (incorporated by reference). DNA sequences encoding the complete heavy or light chains of each anti-OPGL antibody of the invention are cloned into expression vectors such as those described above. CHO AM-1 / D cells are co-transfected with an expression vector capable of expressing a complete heavy chain and an expression vector expressing the complete light chain of the appropriate anti-OPGL antibody. For example, to generate the 22B3 antibody, cells are co-transfected with a vector capable of expressing a complete heavy chain comprising the amino acid sequence as set forth in SEQ ID NO: 30 and a vector capable of expressing a complete light chain comprising the amino acid sequence set forth in SEQ ID NO: 32. To generate the 2E11 antibody, cells are co-transfected with a vector capable of expressi...

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
dissociation constantaaaaaaaaaa
dissociation constantaaaaaaaaaa
dissociation constantaaaaaaaaaa
Login to View More

Abstract

Monoclonal antibodies and hybridomas producing them that interact with osteoprotegerin ligand (OPGL) are provided. Methods of treating osteopenic disorders by administering a pharmaceutically effective amount of antibodies to OPGL are also provided. Methods of detecting the amount of OPGL in a sample using antibodies to OPGL are further provided.

Description

[0001]This application is a continuation application of U.S. application Ser. No. 10 / 408,901, filed Apr. 7, 2003; which is a non-provisional application of, and claims priority, to U.S. Provisional Patent Application No. 60 / 370,407 filed on Apr. 5, 2002. The disclosure of each application is herein incorporated by reference.[0002]The sequence listing is filed with this application in electronic format only and is incorporated herein by reference. The computer readable sequence listing text file “01—1145_A_CONSeqList.txt” was created on Feb. 15, 2010, and is 87,784 bytes in size.FIELD OF THE INVENTION[0003]The invention relates to antibodies that bind osteoprotegerin ligand (OPGL). Compositions and methods for the treatment of bone diseases, such as osteoporosis, bone loss from arthritis, Paget's disease, and osteopenia, are also provided.BACKGROUND OF THE INVENTION[0004]Living bone tissue exhibits a dynamic equilibrium between formation of bone, known as deposition, and breakdown of...

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(United States)
IPC IPC(8): A61K39/395C07K16/24C07H21/04C12N15/63C12N5/10C12P21/02A61P19/10A61P19/08C12N15/09A61P19/00A61P19/02A61P43/00C07K16/28
CPCA61K2039/505C07K16/2875C07K2317/21C07K2317/34C07K16/18C07K16/241C07K2317/56A61P19/00A61P19/02A61P19/08A61P19/10A61P29/00A61P35/04A61P43/00
Inventor BOYLE, WILLIAM J.MEDLOCK, EUGENESULLIVAN, JOHN K.ELLIOTT, ROBIN L.MARTIN, FRANKHUANG, HAICHUN
Owner AMGEN INC
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