Anti-p-selectin antibodies and methods of their use and identification
a technology of antipselectin and antibodies, applied in the field of antipselectin antibodies and methods of their use and identification, can solve the problems of limited ability to predict disease course from birth, limited clinical severities, and serious and sometimes deadly complications, and achieves the effects of reducing vasoocciusion, reducing the number of rolling and adhesion leukocytes, and reducing the number of vasoocciusion
a technology of antipselectin and antibodies, applied in the field of antipselectin antibodies and methods of their use and identification, can solve the problems of limited ability to predict disease course from birth, limited clinical severities, and serious and sometimes deadly complications, and achieves the effects of reducing vasoocciusion, reducing the number of rolling and adhesion leukocytes, and reducing the number of vasoocciusion
US20110212096A1Inactive Publication Date: 2011-09-01SELEXYS PHARMA CORP +1
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[0042]As indicated above, the presently disclosed and claimed inventive concepts, in one embodiment, are directed to antibodies which bind specifically to P-selectin and which block the binding of PSGL-1 to P-selectin (and are referred to herein as “function-blocking” antibodies). In some embodiments, these anti-P-selectin antibodies may also cause dissociation of preformed P-selectin / PSGL-1 complexes. The disclosure describes a heretofore unrecognized antibody binding domain (a conformational epitope) within the lectin domain (e.g., carbohydrate recognition domain, CRD) of P-selectin to which the function-blocking antibodies (which may be chimeric, human or humanized antibodies, or fragments thereof for example) bind. The presently disclosed and claimed inventive concepts also directed to anti-P-selectin antibodies which bind to the conformational epitope described herein and which have a dual function in (1) blocking binding of PSGL-1 to P-selectin and (2) causing dissociation of ...
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Abstract
Antibodies are disclosed which bind specifically to P-selectin and which block the binding of PSGL-1 to P-selectin. These anti-P-selectin antibodies may also 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 function-blocking 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 single and dual function anti-P-selectin antibodies and binding fragments thereof may be used in the treatment of a variety of inflammatory and thrombotic disorders and conditions. Screening methods for identifying such antibodies are also disclosed.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of U.S. Ser. No. 12 / 516,987, filed May 29, 2009, which claims priority under 35 U.S.C. 371 from International Application No. PCT / US2007 / 024692, filed Nov. 30, 2007, which claims benefit of U.S. Provisional Application No. 60 / 872,170, filed Dec. 1, 2006. Each of the above applications is hereby expressly incorporated herein by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]Not applicable.BACKGROUND[0003]The present invention relates to antibodies and antibody fragments which bind to specific conformational epitopes of P-selectin, and to methods of their use and identification.[0004]In normal hemostasis and immune surveillance, leukocytes circulate freely in the blood and respond to injury and infection in a sequential process of adhesion signaling mediated by cell adhesion molecules (1-3). In inflammatory and thrombotic disease, this process is dysr...
Claims
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Patent Timeline
01 Sep 2011
Publication
US20110212096A1
- IPC
- A61K39/395; C07K16/28; C07K16/46; C07H21/04; C12N1/00; C12N5/00; A61P29/00; A61P17/06; A61P35/00; A61P7/02; A61P11/06; A61P9/10
- CPC
- C07K16/2854; C07K2317/76; C07K2317/34; C07K2317/33; A61P7/02; A61P9/10; A61P11/06; A61P17/06
- Inventors
- ROLLINS, SCOTT; ALVAREZ, RICHARD