Schering Aktiengesellschaft

Berlex Laboratories, Inc.

Codon

Codon Genetic Engineering Laboratories

Michael John Morser

David Richard Light

Mariko Nagashima

Charles B Glaser

William H Andrews

Marc A Shuman

Peter A Donner

Charles Glaser

Gang Deng

Kathi Begley

Linda Cashion

Wendy Colby

Jiing-Huey Lin

Craig Rice

Laura R Vilander

The present invention relates to the design, production and use of analogs of thrombomodulin (TM) that have the ability to enhance the thrombin-mediated activation of protein C but which have a significantly reduced ability to promote activation of thrombin-activatable fibrinolysis inhibitor (TAFI). These analogs are useful in, for example, antithrombotic therapy.

Thrombomodulin analogs for pharmaceutical use

The present invention relates to novel human inhibitor-of-apoptosis polypeptides, designated HIAP3, polynucleotides encoding the polypeptides, methods for producing the polypeptides, expression vectors and genetically engineered host cells for expression of the polypeptides. The invention further relates to methods for utilizing the polynucleotides and polypeptides in research, diagnosis, and therapeutic applications.

DNA encoding a novel human inhibitor-of-apoptosis protein

Polymorphisms within a plasma carboxypeptidase designated plasma carboxypeptidase B (PCPB) have been identified. The relative distribution of these polymorphs in a patient's blood can be used to assess an individual's risk toward thrombotic disease.

Method of detecting thrombotic disease risk associated with plasma

It is a general object of the present invention to provide compositions that specifically interact with advanced glycosylation end products (AGEs) or their receptors. Such compositions may be used in a variety of applications including therapeutic applications, e.g., as blocking agents to inhibit or otherwise reduce the AGE/RAGE interaction, screening applications, e.g., as models of the AGE/RAGE interaction, and diagnostic applications, e.g., to identify abnormal levels of AGE or RAGE in a given system.

Antibodies to advanced glycosylation end-product receptor polypeptides

Mutagenesis methods and compositions

The present invention relates to the use of analogs of thrombomodulin ('TM') that have the ability to enhance the thrombin-mediated activation of protein C but which have a significantly reduced ability to inhibit the direct procoagulant activities of thrombin, such as, for example, thrombin-mediated conversion of fibrinogen to fibrin. These analogs are useful in, for example, antithrombotic therapy. Novel proteins, nucleic acid gene sequences, pharmaceuticals and methods of inhibiting thrombotic activity are disclosed. Included are methods for increasing the circulating half life of the proteins.

Superior thrombomodulin analogs for pharmaceutical use

Novel soluble oxidation resistant thrombomodulin analogs are produced for various therapeutic and other uses, such as in thrombotic and vascular disease therapies. These analogs exhibit the characteristic therapeutic properties of native thrombomodulin, yet they are soluble and are not inactivated after they have been exposed to oxidants. Some of the analogs disclosed are multifunctional fusion proteins having both antithrombotic activity and some additional bioactivity.

Oxidation resistant thrombomodulin analogs

This invention relates generally to recombinant DNA techniques and to the expression of mammalian polypeptides in genetically engineered eukaryotic cells. Specifically, the invention relates to preferred plasmid constructs and methods that increase levels of expression of a cloned gene product. These preferred plasmids have selectable and nonselected gene cassettes adjacent to each other and oriented in the opposite direction for transcription. Such an orientation enhances overall levels of expression for the nonselected gene. Further, this invention relates to gene products expressed at these very high levels by the herein described method, and to the eukaryotic cells derived thereby.

Transfected cells containing plasmids having genes oriented in opposing

Methods for recovering t-PA from a liquid medium are disclosed. The methods comprise contacting a liquid medium with at least one substrate capable of effecting a separation of intact t-PA from degraded t-PA thereafter recovering the intact t-PA free from other unrelated protein. The present invention also provides compounds produced by this method, compounds comprising intact one-chain t-PA and pharmaceutical compositions containing them and methods for using such compositions.

Methods for recovery of tissue plasminogen activator

Methods for detecting fibrin or fibrin clots in a host suspected of producing fibrin by: introducing labeled tissue plasminogen activator or a binding site fragment derived therefrom into the host's bloodstream and assaying for the presence of concentrations of labeled tissue plasminogen activator in said host. Also provided are kits for practicing the invention.

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San Francisco, CA, United States of America

Michael John Morser