DEVELOPMENT AND CHARACTERIZATION OF MONOCLONAL-ANTIBODIES SPECIFIC FOR AMYLIN

Highly selective monoclonal antibodies to the peptide hormone human am ylin have been produced and characterized, These antibodies are produc ed by hybridomas resulting from the fusions of BALB/c-derived myelomas and splenocytes from either inbred or outbred mouse strains. Certain of these antibodies recognize epitopes at the amino-terminus or the am idated carboxy-terminus, as well as conformational epitopes within the central region of the 37 amino acid peptide, Several of these antibod ies show less than 0.1% cross-reactivity with related peptide hormones such as calcitonin and calcitonin gene-related peptide (CGRP) and hav e apparent affinities in the low nanomolar range, Antibody pairs were selected for use in two-site assays for the direct measurement of endo genous amylin and the synthetic human amylin analogue, pramlintide (25 , 28, 29 tripro-human amylin), which is presently under clinical inves tigation for improving glucose control in patients with both Type I an d Type II diabetes treated with insulin.