Bayer Corporation

Molecular Diagnostics, Inc.

Wallace Haigh

William J Knowles

Vincent T Marchesi

John T Letsinger

Donna Guralski

Kevin B Clairmont

John T Hart

An aminopeptidase which is a component of GLUT4-containing vesicles in the natural state, and which cleaves insulin. The claimed protein has an apparent molecular weight of approximately 110 kD in its deglycosylated form and a predicted molecular weight of 117,239 Daltons. It includes the amino acid sequences Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala (SEQ ID NO: 1) and Ile-Leu-Gln-Asn-Gln-Ile-Gln-Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly-Xaa-Pro-Xaa-Me t (SEQ ID NO: 2, and reacts with antibodies produced against the peptide identified as (SEQ ID NO: 1). It is encoded by the cDNA of FIG. 20 (SEQ. ID NOs. 15 and 16) and is essentially the protein sequence therein described. Modulators of the activity of the aminopeptidase and a method for treating syndromes of insulin resistance, including diabetes, by administration of such a modulator are also claimed.

Glucose transporter vesicle aminopeptidase

An aminopeptidase which is a component of GLUT4-containing vesicles in the natural state, and which cleaves insulin. The claimed protein has a molecular weight of approximately 110 kD in its deglycosylated form. It includes the amino acid sequences Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala [SEQ ID NO: 1] and Ile-Leu-Gln-Asn-Gln-Ile-Gln-Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly-Xaa-Pro-Xaa-Me t [SEQ ID NO: 2], and reacts with antibodies produced against the peptide identified as [SEQ ID NO: 1]. Modulators of the activity of the aminopeptidase and a method for treating syndromes of insulin resistance, including diabetes, by administration of such a modulator are also claimed.

Monoclonal antibodies specific for the glucosylated N-terminal peptide residue in Hb A.sub.1c, a method for producing such antibodies, hybridoma cell lines secreting such antibodies and a method for their production, and immunoassay methods and reagent systems using such antibodies for the determination of Hb A.sub.1c in human blood samples. The monoclonal antibodies are secreted by hybridomas obtained from the fusion of a myeloma cell and a lymphocyte which has been taken from an animal, preferably a mouse, immunized with a synthetic peptide immunogen and which produces antibody specific for the glucosylated N-terminal peptide residue in Hb A.sub.1c. The synthetic peptide immunogen comprises an N-terminal plucosylated peptide residue having at least 2 amino acid units corresponding to the N-terminus of the beta-subunit of human hemoglobin and an immunogenic carrier to which the glucosylated peptide residue is linked. The immunoassay involves treatment of the blood sample to expose the glucosylated N-terminal peptide epitope and detection thereof by binding of the specific monoclonal antibody or a fragment thereof.

Antibodies for use in determining hemoglobin A.sub.1c

Monoclonal antibodies specific for the glucosylated N-terminal peptide residue in Hb A.sub.1c, a method for producing such antibodies, hybridoma cell lines secreting such antibodies and a method for their production, and immunoassay methods and reagent systems using such antibodies for the determination of Hb A.sub.1c in human blood samples. The monoclonal antibodies are secreted by hybridomas obtained from the fusion of a myeloma cell and a lymphocyte which has been taken from an animal, preferably a mouse, immunized with a synthetic peptide immunogen and which produces antibody specific for the glucosylated N-terminal peptide residue in Hb A.sub.1c. The synthetic peptide immunogen comprises an N-terminal glucosylated peptide residue having at least 2 amino acid units corresponding to the N-terminus of the beta-subunit of human hemoglobin and an immunogenic carrier to which the glucosylated peptide residue is linked. The immunoassay involves treatment of the blood sample to expose the glucosylated N-terminal peptide epitope and detection thereof by binding of the specific monoclonal antibody or a fragment thereof.

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Madison, CT, United States of America

Wallace Haigh