Alexander Schwarz - Plainsboro NJ Guerard W. Byrne - Allentown NJ Thomas A. Davis - Newtown PA Lisa E. Diamond - Princeton NJ John S. Logan - Robbinsville NJ
One aspect of the present invention relates to methods and compositions for attenuating xenograft rejection by administering, to an animal receiving the xenograft, an amount of a polymer-derivatized xenoantigen (hereinafter âxenopolymerâ) effective for inhibiting or lessening the severity of hyperacute rejection response (HAR), or other immunological response to the graft, that is dependent on the presence of the xenoantigen on the grafted tissues or cells. In certain embodiments, the xenopolymer is administered in an amount sufficient to neutralize host antibodies (âxenoreactive antibodiesâ or âXNAâ) immunoreactive with the xenoantigen. The xenopolymer may additionally, or alternatively, be used as a tolerogen (or anergen) for the xenoantigen, e. g. , able to suppress, to some degree, the production/secretion of XNAs by the immune system of the host.
Alexander Schwarz - Plainsboro NJ, US Guerard Byrne - Allentown NJ, US Thomas Davis - Newtown PA, US Lisa Diamond - Princeton NJ, US John Logan - Robbinsville NJ, US
International Classification:
A61K039/00 C08G063/48 C08G063/91
US Classification:
424/078270, 424/078290, 525/054100
Abstract:
One aspect of the present invention relates to methods and compositions for attenuating xenograft rejection by administering, to an animal receiving the xenograft, an amount of a polymer-derivatized xenoantigen (hereinafter “xenopolymer”) effective for inhibiting or lessening the severity of hyperacute rejection response (HAR), or other immunological response to the graft, that is dependent on the presence of the xenoantigen on the grafted tissues or cells. In certain embodiments, the xenopolymer is administered in an amount sufficient to neutralize host antibodies (“xenoreactive antibodies” or “XNA”) immunoreactive with the xenoantigen. The xenopolymer may additionally, or alternatively, be used as a tolerogen (or anergen) for the xenoantigen, e.g., able to suppress, to some degree, the production/secretion of XNAs by the immune system of the host.
Alexander Schwarz - Plainsboro NJ, US Guerard W. Byrne - Allentown NJ, US Thomas A. Davis - Newtown PA, US Lisa E. Diamond - Princeton NJ, US John S. Logan - Robbinsville NJ, US
Assignee:
Mayo Foundation for Medical Education and Research - Rochester MN
One aspect of the present invention relates to methods and compositions for attenuating xenograft rejection by administering, to an animal receiving the xenograft, an amount of a polymer-derivatized xenoantigen (hereinafter “xenopolymer”) effective for inhibiting or lessening the severity of hyperacute rejection response (HAR), or other immunological response to the graft, that is dependent on the presence of the xenoantigen on the grafted tissues or cells. In certain embodiments, the xenopolymer is administered in an amount sufficient to neutralize host antibodies (“xenoreactive antibodies” or “XNA”) immunoreactive with the xenoantigen. The xenopolymer may additionally, or alternatively, be used as a tolerogen (or anergen) for the xenoantigen, e.g., able to suppress, to some degree, the production/secretion of XNAs by the immune system of the host.
Christopher G.A. McGregor - Rochester MN, US Guerard W. Byrne - Rochester MN, US William R. Davies - Cambridgeshire, GB John S. Logan - Robbinsville NJ, US
Assignee:
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH - Rochester MN
International Classification:
A61F 2/24
US Classification:
623 242, 600 36
Abstract:
The invention relates to heart valve xenografts from transgenic pigs having a disruption of an α1-3 galactosyl transferase nucleic acid sequence and use of the xenografts for treating a patient.
Methods And Materials For Reducing Cardiac Xenograft Rejection
Christopher G.A. McGregor - Rochester MN, US Guerard W. Byrne - Rochester MN, US
Assignee:
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH - Rochester MN
International Classification:
A61K 39/00 A61K 35/34
US Classification:
800 17, 4241851, 424 937, 435 721
Abstract:
This document provides methods and materials involved in reducing cardiac xenograft rejection. For example, methods and materials for preparing transgenic pigs expressing reduced or no endogenous Sdor SDa-like glycans derived from the porcine β1,4 N-acetyl-galactosaminyl transferase 2 (B4GALNT2) glycosyltransferase and/or reduced or no endogenous α-Gal antigens, methods and materials for modifying the xenograft recipient's immunological response to non-Gal antigens (e.g. CD46, CD59, CD9, PROCR, and ANXA2) to reduce cardiac xenograft rejection, and methods and materials for monitoring the progress of xenotransplant immunologic rejection are provided.
Tetracycline Repressor-Mediated Binary Regulation System For Control Of Gene Expression In Transgenic Mice
The present invention relates to a tetracycline repressor-mediated binary regulation system for the control of gene expression in transgenic mice. It is based, at least in part, on the discovery that, in a transgenic mouse that carries a first transgene under the control of a modified promoter comprising a tetR operator sequence and a second transgene encoding the tetR protein, expression of the first transgene may be efficiently induced by administering tetracycline to the mouse.
Methods And Materials For Reducing Cardiac Xenograft Rejection
This document provides methods and materials involved in reducing cardiac xenograft rejection. For example, methods and materials for preparing transgenic pigs expressing reduced or no endogenous Sdor SDa-like glycans derived from the porcine β1,4 N-acetyl-galactosaminyl transferase 2 (B4GALNT2) glycosyltransferase and/or reduced or no endogenous α-Gal antigens, methods and materials for modifying the xenograft recipient's immunological response to non-Gal antigens (e.g. CD46, CD59, CD9, PROCR, and ANXA2) to reduce cardiac xenograft rejection, and methods and materials for monitoring the progress of xenotransplant immunologic rejection are provided.
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