Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1996-12-27
1999-02-09
Stucker, Jeffrey
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
435 71, 435 79, 435 792, 435974, 530324, 530325, 530326, 530327, 530328, 530329, 530330, 530350, C12Q 170
Patent
active
058692320
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to an antigen/antibody specificity exchanger, which comprises an amino-acid sequence which specifically binds to a certain antigen linked to an amino-acid sequence to which a certain antibody binds. In vitro the antigen/antibody specificity exchanger of the invention can be used as a diagnostic reagent instead of antisera or monoclonal antibodies in testing systems, and in vivo it can be used to redirect antigens or antibodies to other antibodies or antigens, respectively, than they were originally directed to.
BACKGROUND
During the past decade the antigenic structure of several viral proteins have been characterized using synthetic peptides, such as the human immunodeficiency virus-1(HIV-1)gp160, and the hepatitis B virus core/e antigens (HBc/eAg). Recently it has been shown that a synthetic peptide corresponding to the complementarity determining region 3 of the heavy chain (CDRH3) of a monoclonal antibody (mAb; F58), directed to the variable third (V3) domain of HIV-1 gp160, may act as a mini antibody and neutralize HIV-1 in vitro. In the experimental part of the present specification, the construction of synthetic peptides combining the CDRH3 domain of the mAb F58, or CDRH1, CDRH2, CDRH3 domain of Ab C1-5, and antigenic regions derived from the HIV-1 gp41, HBc/e antigen, hepatitis C virus (HCV) core protein or from the poliovirus VP1, is shown. These peptides specifically bound the V3 domain of HIV-1. Thus, it was possible to modify the antigenic surface of HIV-1 V3 peptides. This antigen/antibody specificity exchanger will be used for redirecting the reactivity of circulating antibodies and using already existing antibody specificities for a predetermined purpose. It may also serve to alter the composition of the surface of proteins by the addition of foreign determinants. For example, the widely used poliovirus vaccination, together with the high rate of seropositivity to enteroviral proteins may be a suitable pool of antibodies to redirect against other pathogens, such as HIV.
The complementary determining regions (CDRs) of antibodies are responsible for the specificity of the antibody (1,2). X-ray crystallography has shown that the three CDRs of the variable (V) region of the heavy chain and the three CDRs of the V region of the light chain may all have contact with the epitope in an antigen-antibody complex (3). Single peptides corresponding to the CDRs of mAbs to various antigens have been shown to mimic the recognition capabilities of the respective mAb (4-10). Recently it was shown that a peptide corresponding to CDRH3 of a mAb specific for the V3 region of human immuno deficiency virus-1, holds neutralizing capacity when assayed in vitro (9). It was also observed that the CDRH2 of a mAb to hepatitis B core antigen (HBcAg) is capable of capturing HBcAg (10).
DESCRIPTION OF THE INVENTION
The present invention is, in one aspect, directed to an antigen/antibody specificity exchanger, which comprises
A) an amino-acid sequence corresponding to an amino-acid sequence of an antibody which specifically binds to a certain antigen, including hapten,
B) linked by a link to
C) an amino-acid sequence to which a certain antibody binds.
The amino-acid sequence of A) may comprise additional amino acids or sequences on one or both sides of the amino-acid sequence of an antibody which specifically binds to a certain antigen, including hapten. Such additional amino acids and sequences may be, but are not limited to, the amino acids and sequences naturally occurring in said antibody as extensions to the amino-acid sequence of A). The number of amino-acid residues in the amino-acid sequence of A) is preferably at least 5, and is together with possible extensions preferably less than 35.
Further, the amino-acid sequence of C) may comprise additional amino acids or sequences on one or both sides of the amino-acid sequence to which a certain antibody binds. Such additional amino acids and sequences may be, but are not limited to, the amino acids and sequences naturally occurring as
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patent: 5260189 (1993-11-01), Formoso et al.
A Complementarity-Determining Region Synthetic Peptide Acts As A Miniantibody And Neutralizes Human Immunodeficiency Virus Type 1 in vitro, Proc. National Acad. Sci. vol. 90 May 1993, pp. 4374-4378, Michael Levi et al.
Design and Synthesis Of A Mimetic From An Antibody Complementarity-Determining Region, Science, vol. 253, Aug. 1991, pp. 792-795, Horacio Uri Saragovi et al.
Antigenized Antibodies, Nature vol. 355, Jan. 1992, pp. 476-477, Maurizio Zanetti.
Affinity Purification Of A Difficult-Sequence Protein. Implications For The Inclusion Of Capping In Synthetic Protocols, Int. J. Pept. Protein Res. 1993 Jul.; 42 (1) 93-96, E. Bianchi et al.
Chemical Synthesis Of A Diagnosed Beta-Protein Through The Flow-Polymide Method, Int. J. Pept Protein Res 1993 Apr.; 41(4): 385-93, E. Bianchi et al.
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Stucker Jeffrey
Tripep AB
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