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Anti-P-selectin antibodies and methods of their use and identification

A selectin and screening method technology, applied in chemical instruments and methods, antibody medical components, specific peptides, etc., can solve problems such as vascular occlusion, pain crisis, etc.

Inactive Publication Date: 2014-06-18
瑟莱克斯制药公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0022] As mentioned above, the interaction between sickled RBCs, platelets, leukocytes, and microvasculature in SCD is a P-selectin-dependent process that leads to vascular occlusion and painful crises

Method used

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  • Anti-P-selectin antibodies and methods of their use and identification
  • Anti-P-selectin antibodies and methods of their use and identification
  • Anti-P-selectin antibodies and methods of their use and identification

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Embodiment Construction

[0035] Before at least one embodiment of the inventive concept is explained in detail by means of exemplary drawings, experiments, results and experimental procedures, it should be understood that the inventive concept is not limited to what is set forth in the following description or shown in the drawings, experiments and / or results. Build and setup details in the examples section. The inventive concept is capable of other embodiments or of being practiced or carried out in various ways. The language used herein is intended to give the broadest possible scope and meaning, and the examples are illustrative rather than exhaustive. Also, it is to be understood that the phraseology and terminology used herein are for the purpose of description and should not be regarded as limiting.

[0036]Unless otherwise defined herein, scientific and technical terms related to the inventive concepts shall have the meanings commonly understood by those of ordinary skill in the art. Further,...

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PUM

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Abstract

Antibodies are disclosed which bind specifically to P-selectin, block the binding of PSGL-1 to P-selectin, and cause dissociation of preformed P-selectin / PSGL-1 complexes. The disclosure identifies a heretofore unrecognized, near N-terminal, antibody binding domain (a conformational epitope) of P-selectin to which the antibodies (which may be chimeric, human or humanized antibodies for example) bind. Antibodies are disclosed which bind to the conformational epitope of P-selectin and which have a dual function in blocking binding of PSGL-1 to P-selectin, and in causing dissociation of preformed P-selectin / PSGL-1 complexes. Such dual function anti-P-selectin antibodies and binding fragments thereof may be used in the treatment of a variety of acute and chronic inflammatory and thrombotic disorders and conditions. Screening methods for identifying and characterizing such antibodies are also disclosed.

Description

field of invention [0001] The present invention relates to antibodies and antibody fragments that bind P-selectin-specific conformational epitopes, and methods for their use and identification. Background of the invention [0002] During normal hemostasis and immune surveillance, leukocytes circulate freely in the blood and respond to injury and infection through a continuous adhesion signaling process mediated by cell adhesion molecules (1-3). In inflammatory and thrombotic diseases, dysregulation of this process perpetuates a pathology in which white blood cells attack self-tissue and can cause serious, sometimes fatal complications. It is well known that leukocyte adhesion plays a major role in the pathology of many inflammatory and thrombotic diseases such as sickle cell disease vascular occlusion, reperfusion injury, thrombosis, atherosclerosis, asthma, rheumatoid arthritis, Psoriasis and tumor metastasis (4-15), deep vein thrombosis (DVT). P-selectin is also involved...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00
CPCC07K2317/24C07K2317/71A61K39/00C07K16/2854C07K2317/34C07K2317/76C07K2317/33C07K2317/92A61P1/00A61P1/04A61P3/10A61P5/14A61P7/00A61P7/02A61P7/06A61P9/10A61P11/00A61P11/02A61P11/06A61P13/12A61P17/00A61P17/02A61P17/06A61P19/02A61P25/00A61P29/00A61P31/04A61P35/00A61P35/04A61P37/00A61P37/02A61P37/06A61P37/08
Inventor S·罗林斯R·阿尔瓦雷斯R·洛特Z·S·凯沃R·P·麦凯沃
Owner 瑟莱克斯制药公司
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