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Methods for identifying inducers and inhibitors of propteolytic antibodies, compositions and their uses

A technology of antibodies and compounds, applied in the fields of immunology, molecular biology and medicine, can solve problems such as increased catalytic turnover

Inactive Publication Date: 2008-01-02
内布拉斯卡大学评议会 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The ensuing ΔG + 催化 A decrease in leads to an increase in turnover

Method used

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  • Methods for identifying inducers and inhibitors of propteolytic antibodies, compositions and their uses
  • Methods for identifying inducers and inhibitors of propteolytic antibodies, compositions and their uses
  • Methods for identifying inducers and inhibitors of propteolytic antibodies, compositions and their uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment IA

[0085] Catalytic Antibodies for Tumor Immunotherapy

[0086] In this example a method for producing catalytic antibodies (Abs) suitable for the treatment of cancer is described. Such antibodies rely on catalytic functions to provide a superior immunotherapy option for cancer treatment, since cleavage of the target antigen should result in its permanent inactivation. Furthermore, a single antibody molecule can be reused to inactivate multiple antigen molecules. In contrast, non-catalytic antibodies bind antigen stoichiometrically and the binding is reversible. Upon dissociation from the complex, the antigen can resume its biological function.

[0087] A tumor-associated antigen, epidermal growth factor receptor (EGFR), will be used to synthesize an exemplary antigen suitable for stimulating the production of antibodies with enzymatic activity. Previous studies on peptidase antibodies have revealed that 1) certain antibodies are able to combine the ability to bind individual ...

Embodiment IB

[0136] Administration of Catalytic Antibody and Antisense p53 in a Combination Chemotherapy Regimen

[0137] When a cell suffers damage to its genome, there are mechanisms in place in the cell that will determine whether the cell will attempt to repair itself, or whether it will undergo programmed cell death. In order for proliferating cells to efficiently undertake genome repair, they must be taken out of cycle. This can be achieved using so-called "cell cycle checkpoints", which give proliferating cells time to repair genomic damage rather than pass it on to daughter cells.

[0138] Figure 18 illustrates the central role of normal (wild-type) p53 in inducing one or the other of these two possible cellular responses to genomic damage. Damage to the genome results in increased expression of p53, which in turn initiates a variety of other events that produce specific cellular responses to the damage.

[0139] Based on these relationships, it is reasonable to expect that certa...

Embodiment II

[0209] Catalytic antibodies in vaccination against HIV

[0210] Described herein is a vaccine construct useful in the treatment of AIDS comprising model B cell epitopes and T helper cell epitopes derived from gp120. The CRAA of the B cell epitope was used to elicit catalytic antibodies. Canonical B cell epitopes are derived from the CD4 binding site that is generally conserved among different HIV-1 strains. Furthermore, the CD4 binding site of gp120 is a suitable target because, unlike many other epitopes, the CD4 binding site is easily accessible by antibodies on the surface of native viruses [31]. The CD4 binding site is known to be a conformational determinant.

[0211] In the present invention, the preparation of catalytic antibodies recognizing a specific part of the CD4 binding site (as opposed to the complete CD4 binding site) is described. Additional peptide epitopes in gp120 (or other HIV proteins) that may be suitable targets for catalytic antibodies will also be ...

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PUM

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Abstract

Covalently reactive antigen analogs are disclosed herein. The antigens of the invention may be used to stimulate production of catalytic antibodies specific for predetermined antigens associated with particular medical disorders. The antigen analogs may also be used to permanently inactivate endogenously produced catalytic antibodies produced in certain autoimmune diseases as well as in certain lymphoproliferative disorders.

Description

technical field [0001] The present invention relates to the fields of immunology, molecular biology and medicine. More specifically, the present invention provides novel methods and compositions for stimulating the production of novel catalytic antibodies and inhibitors thereof. The invention also provides methods for identifying and isolating naturally occurring catalytic antibodies expressed from germline genes. Finally, the present invention provides methods for the synthesis of covalently reactive antigen analogs that stimulate the production of catalytic antibodies and / or irreversibly inhibit their activity. Background technique [0002] In order to more fully describe the state of the art to which this invention pertains, several publications are cited throughout this application by numbers in parentheses. The specifications of each of these publications are hereby incorporated by reference. [0003] The discovery that antibodies from asthmatic patients cleave vasoa...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/00A61K39/00A61K38/00A61K39/395A61P5/14A61P11/06A61P17/00A61P19/02A61P19/04A61P29/00A61P35/00A61P37/06C07K7/04C07K16/10C07K16/32C12N9/00C12N9/64
CPCC12N9/0002C07K16/1063C07K2317/34C07K16/32A61K2039/505A61P11/06A61P17/00A61P19/02A61P19/04A61P29/00A61P31/00A61P35/00A61P35/02A61P37/02A61P37/06A61P5/14C07K16/00
Inventor S·保尔G·戈洛洛波夫L·史密斯
Owner 内布拉斯卡大学评议会
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