Boehringer Ingelheim Pharmaceuticals, Inc.

Dana-Farber-Cancer Institute Inc.

Robert Rothlein

Steven D Marlin

Timothy Alan Springer

Michael L Dustin

Genus J Possanza

Ronald Faanes

Craig D Wegner

Robert H Gundel

Takashi Kei Kishimoto

Rene Marc Lemieux

Karl G Grozinger

John P Devlin

Clara K Miao

Joseph R Woska, Jr

Hans C Reiser

Gary O Caviness

Kathleen Last-Barney

The present invention relates to intercellular adhesion molecules (ICAM-1) which are involved in the process through which lymphocytes recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, screening assays for identifying such molecules and antibodies capable of binding such molecules. The invention also includes uses for adhesion molecules and for the antibodies that are capable of binding them.

Functional derivatives of ICAM-1 with altered ability to bind LFA-1 or HRV

The present invention relates generally to a method for identifying molecules that bind the R7.1 epitope of LFA-1 or bind LFA-1 such that the R7.1 epitope is modified. The present invention further relates to a method for determining occupancy of the LFA-1 receptor by molecules that bind to the R7.1 epitope or bind LFA-1 such that the R7.1 epitope is modified after administration to a subject. The present invention further relates to molecules useful in the methods of the invention.

Methods and molecules useful for identifying molecules that bind LFA-1 and for determining receptor occupancy

ICAM-1 derivatives with altered ability to bind LFA-1

Soluble fragments of human intercellular adhesion molecule-1

The present invention relates to the use of intercellular adhesion molecule-1 (ICAM-1) or fragments thereof, anti-CD18 antibodies or fragments thereof, and members of the CD18 family of proteins or fragments thereof in the treatment of asthma.

Use of intercellular adhesion molecules, and their binding ligands in

Nucleotide sequence encoding intercellular adhesion molecule-1 and

R6-5-D6, an antibody which binds intercellular adhesion molecule-1

A method for the detection of the presence of inflammation in a patient by measuring the amount of circulating intercellular adhesion molecule (cICAM-1) in a sample of one or more bodily fluids of the patient and then comparing the amount of cICAM-1 in the sample to standards normal for the bodily fluid or fluids assayed. The amount of cICAM-1 can be measured using anti-ICAM-1 antibodies. Higher than normal amounts of cICAM-1 indicate the presence of inflammation.

Method for detecting inflammation

Method for detecting pathological pregnancy

The present invention provides a method of reducing the severity of asthma. Specifically, the present invention discloses that anti-adhesion antibodies, such as anti-ICAM-1 or anti-CD18 family member antibodies, when administered to a mammal, are capable of decreasing the hyperresponsive reaction associated with an asthmatic response.

Use of antibodies to intercellular adhesion molecule-1 (ICAM-1) in the

Pharmaceutical compositions comprising antibodies to intercellular adhesion molecule-1 (ICAM-1 or CD54) are useful in methods of decreasing the severity of inflammation associated with the adhesion of leukocytes to cells bearing ICAM-1. Treatment with anti-ICAM-1 antibodies reduced the severity of inflammation associated with acute organ or tissue rejection and prolonged allograft survival time. Such compositions may optionally contain other immunsuppressive agents.

Intercellular adhesion molecules, and their binding ligands

A method for the detection of the presence of inflammation in a patient by measuring the amount of circulating intercellular adhesion molecule (cICAM-1) in a sample of one or more bodily fluids of the patient and then comparing the amount of cICAM-1 in the sample to standards normal for the bodily fluid or fluids assayed. The amount of cICAM-1 can be measured using anti-ICAM-1 antibodies. Higher than normal amounts of cICAM-1 indicate the presence of inflammation. Also contemplated is a method for the detection of organ transplant or tissue graft rejection.

Method for detecting organ transplant rejection

A method for treating inflammation in a patient which comprises administering to the patient a therapeutically effective amount of a compound of the formula: ##STR1## wherein A and R.sub.1 -R.sub.6 are defined herein.

Method for treating inflammation

Novel thienylbenzylamine compounds of the formula ##STR1## wherein A and R.sub.1 -R.sub.5 are defined herein. These compounds are useful for the treatment of inflammation.

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Danbury, CT, United States of America

Robert Rothlein