Merck + Co., Inc.

Christopher A Salvatore

Robert G Johnson

Marlene A Jacobson

Christopher J Luneau

Kenneth S Koblan

Stefanie A Kane

John J Mallee

Kevin R Oliver

Disclosed herein are isolated nucleic acid molecules encoding a humanized version of a calcitonin gene-related peptide (CGRP) receptor, which comprises the G-protein coupled receptor calcitonin-receptor-like receptor (CRLR) and the receptor-activity-modifying protein 1 (RAMP1). The humanized CGRP receptors of the present invention attain pharmacological profiles similar to the wild type human receptor via modifications to the respective mammalian RAMP1 nucleotide sequence, specifically at amino acid 74. Also described are related recombinant vectors, recombinant hosts and associated methods for generating such humanized CGRP receptors. Also presented are non-human transgenic animals which express humanized RAMP1. Such animals have been engineered to provide for a CGRP pharmacological profile similar to human CGRP.

Isolated DNA molecules encoding humanized calcitonin gene-related peptide receptor, related non-human transgenic animals and assay methods

The invention concerns recombinant human adenosine receptors A1, A2a, A2b and A3 which have been prepared by cDNA cloning and polymerase chain reaction techniques. The invention also concerns expression systems for these receptors and an assay using the expression systems. The recombinant adenosine receptors comprising the invention can be utililized in an assay to identify and evaluate entities that bind to or enhance binding to adenosine receptors.

Human adenosine receptors

Human A3 adenosine receptors

The invention concerns the identification on eosinophils of the A3 adenosine receptor subtype and the blockade of said receptor in order to achieve inhibition of eosinophil activation and degranulation.

Inhibition of eosinophil activation through A3 adenosine receptor

The invention concerns recombinant human adenosine receptors A1, A2a, A2b and A3 which have been prepared by cDNA cloning and polymerase chain reaction techniques. The invention also concerns expression systems for these receptors and an assay using the expression systems. The recombinant adenosine receptors comprising the invention can be utilized in an assay to identify and evaluate entities that bind to or enhance binding to adenosine receptors.

Growing community of inventors

North Wales, PA, United States of America

Christopher A Salvatore