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Anti-staphylococcus antibodies and uses thereof

A staphylococcus, antibody technology, applied in the direction of antibodies, antibacterial drugs, antibody medical components, etc.

Pending Publication Date: 2021-05-28
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Antibiotic administration is standard treatment for S. aureus infections, but depending on the type of infection (eg, skin infections are proportionally antibiotic-resistant) and the region, antibiotic-resistant infections may be more prevalent

Method used

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  • Anti-staphylococcus antibodies and uses thereof
  • Anti-staphylococcus antibodies and uses thereof
  • Anti-staphylococcus antibodies and uses thereof

Examples

Experimental program
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preparation example Construction

[0209] Production of Human Antibodies

[0210] Methods for producing human antibodies in transgenic mice are known in the art. Any such known method may be used in the context of the present invention to prepare human antibodies that specifically bind to S. aureus antigens. Immunogens comprising any S. aureus antigen such as protein A, IsdA and IsdB can be used to raise antibodies. In certain embodiments, antibodies of the invention are obtained from mice immunized with S. aureus antigens or with DNA encoding the antigens or fragments thereof. Alternatively, the antigen or fragment thereof can be produced using standard biochemical techniques, modified and used as an immunogen. In one embodiment, the immunogen is recombinantly produced protein A, IsdA or IsdB or a fragment thereof. In certain embodiments of the invention, the immunogen may be a commercially available antigen. In certain embodiments, one or more booster injections may be administered. In certain embodiment...

example

[0278] The following examples are set forth to provide those of ordinary skill in the art with a complete disclosure and describe how to make and use the methods and compositions of the invention and are not intended to limit the scope of what the inventors believe to be their invention. Efforts have been made to ensure accuracy with respect to numbers used (eg, amounts, temperature, etc.), but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees Centigrade and pressure is at or near atmospheric.

[0279] For all positions discussed in the present invention, numbering is according to eg Kabat (Kabat et al., 1991, Sequences of Proteins of Immunological Interest), 5th edition, United States Public Health Service ), the EU Index in National Institutes of Health, Bethesda, which is incorporated by reference in its entirety). Those skilled in t...

example 1

[0280] Example 1. Production of Anti-IsdA Antibodies, Anti-IsdB Antibodies, and Anti-Protein A Antibodies The original, namely IsdA-6xHis and IsdB-6xHis immunization to obtain anti-IsdA antibody and anti-IsdB antibody. By genetically engineering mice containing DNA encoding the variable regions of human immunoglobulin heavy and kappa light chains with proteins containing wild-type protein A or mutant protein A (the mutant version does not bind Fc and is called "SpAkkaa") (PMID: 23982075)) to obtain anti-Protein A antibodies.

[0281] Antibody immune responses were monitored by antigen-specific immunoassays, ie, immunoassays specific for IsdA, IsdB, or protein A. When the desired immune response is achieved, splenocytes can be harvested and fused with mouse myeloma cells to maintain their viability and form hybridoma cell lines. Hybridoma cell lines can be screened and selected to identify cell lines that produce IsdA-specific antibodies, IsdB-specific antibodies, or Protein ...

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Abstract

Speciated antibodies or antigen-binding fragments that bind staphylococcal antigens are provided, where the antibodies and antigen-binding fragments have attenuated Fc binding to Protein A or homologous protein. Compositions comprising the antibodies and methods of use are also provided. The antibodies and compositions are useful for treating staphylococcal infection, reducing serum or kidney bacterial titers, and treating symptoms associated with staphylococcal infection. The antibodies may also prevent the severity and / or duration of the primary disease.

Description

technical field [0001] The present invention relates to human antibodies and antigen-binding fragments of human antibodies that specifically bind to Staphylococcus aureus (S. aureus) antigens but exhibit reduced Fc binding to protein A, compositions comprising these antibodies, and treatments using these antibodies method. [0002] sequence listing [0003] The official copy of the sequence listing is submitted electronically through EFS-Web at the same time as the sequence listing in ASCII format and the description, the file name is "10495WO01_SEQ_LIST_ST25.txt", the date of creation is November 20, 2019, and the size is about 96KB. The sequence listing contained in this ASCII formatted file is part of the specification and is incorporated herein by reference in its entirety. Background technique [0004] Staphylococcus aureus is an aerobic gram-positive coccus that commonly colonizes the nose and skin of healthy humans. The Staphylococcus aureus bacterium, sometimes c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/12A61K39/00
CPCC07K16/1271A61K2039/505C07K2317/76C07K2317/92A61K39/40A61K45/06A61K2039/572A61P31/04C07K2317/20C07K2317/21C07K2317/33C07K2317/52C07K2317/565C07K2317/732C07K2317/94C07K2317/55
Inventor A·祖姆斯泰格C·基拉索斯B·普拉萨德A·科皮
Owner REGENERON PHARM INC
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