Bayer Corporation

Genetic Therapy, Inc.

Bayer Pharmaceuticals Corporation

Molecular Therapeutics, Inc.

Alan McClelland

Jeffrey M Greve

Gary Davis

Susan C Stevenson

Method of inhibiting human rhinovirus (HRV) Infection by contacting said HRV with a polypeptide comprising a fragment of human rhinovirus major receptor (HRR), said fragment comprising the HRV binding site and being selected from a specific group consisting of HRR domains.

Antiviral methods using human rhinovirus receptor (ICAM-1)

A method for substantially inhibiting initiation or spread of infection by rhinovirus or Coxsackie A virus of host cells expressing the major human rhinovirus receptor (ICAM-1), comprising the step of contacting the virus with a soluble polypeptide comprising the HRV binding site in domains I and II of ICAM-1; which polypeptide is capable of binding to the virus and reducing infectivity thereof; the contact being under conditions which permit the virus to bind to the polypeptide.

Antiviral methods comprising contacting human rhinovirus with tICAM(453).

Antiviral methods using fragments of human rhinovirus receptor (ICAM-1)

Novel analogs of ICAM-1 and methods of using same for reducing human rhinovirus infection.

Soluble truncated forms of ICAM-1

Methods for inhibiting infectivity and reducing infection by human rhinovirus (HRV) of host cells susceptible to infection by HRV and methods of inhibiting initiation and spread of the common cold, said methods comprising contacting HRV under conditions favorable for binding with a multimeric antiviral agent comprising two or more units wherein said units may be the same or different and are each independently selected from the group consisting of transmembrane intercellular adhesion molecule-1 (tmICAM-1) and truncated forms of intercellular adhesion molecule-1 (tICAMs), each of said units containing at least one unpaired cysteine residue at a position selected from the group consisting of 307 and 309, wherein each of said units is linked to at least one other of said units via a disulfide bridge, and wherein said multimeric antiviral agent binds to HRV and reduces infectivity thereof.

Antiviral methods

Multimers comprising two or more monomers, wherein said monomers may be the same or different and are each independently selected from the group consisting of transmembrane intercellular adhesion molecule-1 (tmICAM-1) and fragments thereof, with the proviso that said monomers must comprise domains I and II of ICAM-1 and with the proviso that when said multimer is a dimer, the monomers cannot both be tmICAM-1, wherein said multimer binds to a ligand that binds to the human rhinovirus (HRV) binding site on ICAM-1, and wherein at least two of said monomers are oriented so that relative to each other they mimic the multimeric configuration of native tmICAM-1, such that said multimer exhibits enhanced binding to said ligand relative to at least one of its constituent monomers, and methods of use.

Multimeric forms of human rhinovirus receptor and fragments thereof, and

Multimeric antiviral agents comprising two or more monomers selected from the group consisting of monomers of transmembrane intracellular adhesion molecule-1 (tmICAM-1) and truncated intercellular adhesion molecule-1 (tICAMs), with the proviso that when said multimer is a dimer said monomers cannot both be tmICAM-1, wherein each of said monomers comprises the human rhinovirus (HRV) binding site and retains the ability to bind to HRV and reduce infectivity thereof, and wherein said multimeric antiviral agent mimics the multimeric configuration of tmICAM-1 and exhibits enhanced binding to said HRV relative to at least one of the constituent monomers.

Multimeric antiviral agent

Methods for reducing the infection by human rhinovirus (HRV) of host cells susceptible to infection by HRV, comprising contacting the virus under conditions favorable for binding with an antiviral agent comprising a fragment of human rhinovirus major receptor protein (HRR) in a form that exhibits the ability to bind to HRV capsids and reduce infectivity of the virus, and an intranasal spray comprising HRR or a fragment thereof suitable for use in said method. Human rhinovirus receptor has subsequently been discovered by Greve et al. to be intercellular adhesion molecule-1.

Antiviral methods and prepations

The present invention relates to novel forms and configurations of intercellular adhesion molecule (ICAM) including multimeric configurations that effectively bind to human rhinovirus and can effectively reduce HRV infectivity. When in a multimeric configuration, preferably as dimers, these proteins display enhanced binding of HRV and are able to reduce HRV infectivity as well as the infectivity of other viruses known to bind to the 'major' group human rhinovirus receptor (HRR). The multimerized proteins may also be used to block tICAM interaction with lymphocyte function-associated antigen-1 (LFA-1).

Multimeric forms of human rhinovirus receptor protein

The present invention relates to a soluble form of-intercellular adhesion molecule (sICAM-1) and purified and isolated human sICAM-1. This invention also relates to a purified and isolated DNA sequence encoding sICAM-1. The extracellular domain of sICAM-1 and insoluble ICAM-1 are substantially the same. ICAM-1 is involved in the process through which lymphocytes attach to cellular substrates during inflammation and serves as the major human rhinovirus receptor (HRR). sICAM-1 therefore has both the property of reducing immune inflammation and inhibiting infection of rhinovirus and Coxsackie A virus.

Method of isolating and purifying sICAM-1

The present invention relates to a soluble form of intercellular adhesion molecule (sICAM-1) and purified and isolated human sICAM-1. This invention also relates to a purified and isolated DNA sequence encoding sICAM-1. The extracellular domain of sICAM-1 and insoluble ICAM-1 are substantially the same. ICAM-1 is involved in the process through which lymphocytes attach to cellular substrates during inflammation and serves as the major human rhinovirus receptor (HRR). sICAM-1 therefore has both the property of reducing immune inflammation and inhibiting infection of rhinovirus and Coxsackie A virus.

Soluble molecule related to but distinct from ICAM-1

The present invention relates to a soluble form of intercellular adhesion molecule (sICAM-1) and purified and isolated human sICAM-1, and antibodies thereto. This invention also relates to a purified and isolated DNA sequence encoding sICAM-1. The extracellular domain of sICAM-1 and insoluble ICAM-1 are substantially the same. ICAM-1 is involved in the process through which lymphocytes attach to cellular substrates during inflammation and serves as the major human rhinovirus receptor (HRR). sICAM-1 therefore has both the property of reducing immune inflammation and inhibiting infection of rhinovirus and Coxsackie A virus.

Growing community of inventors

Old Saybrook, CT, United States of America

Alan McClelland