La Jolla Cancer Research Foundation

Phillips Petroleum Company

Research Corporation Technologies, Inc.

Craig, William S.

William S Craig

Michael D Pierschbacher

Soan Cheng

Juerg F Tschopp

David S Lukeman

Daniel G Mullen

Thomas S Vedvick

John R Harper

Jonathan R Parker

Paul J Kostel

Erkki I Ruoslahti

Robert Steven Siegel

James W Polarek

Lin-Shu Liu

James R Glass

Kenneth T Dickerson

Sam D Hernandez

Jose Cardenas

The invention provides cyclic peptides which inhibit platelet aggregation without causing prolonged bleeding time. The invention provides RGD or KGD containing peptides which are cyclized and contain hydrophobic amino acids adjacent to the carboxy terminus of the RGD sequence. Peptides of this nature are also provided which contain in addition to the hydrophobic amino acid an adjacent positively charged amino acid. Such peptides have a high affinity for the receptor IIb/IIIa and a low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.

Method and composition for treating thrombosis

The invention provides cyclic peptides which inhibit platelet aggregation without causing prolonged bleeding time. The invention provides RGD or KGD containing peptides which are cyclized and contain hydrophobic moieties adjacent to the carboxy terminus of the RGD sequence. Peptides of this nature are also provided which contain in addition to the hydrophobic. moiety an adjacent positively charged moiety. Such peptides have a high affinity for the receptor IIb/IIIa and a low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.

The invention provides RGD containing peptides which are cyclized and contain hydrophobic moieties adjacent the carboxy terminus of the RGD sequence. Such peptides have an high affinity for the receptor IIb/IIIa and low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.

A method for identifying a peptide useful for inhibiting platelet aggregation activity without substantially prolonging bleeding time comprising determining the IC.sub.50 value of the peptide in both a heparin assay and a citrate assay and then comparing the value of the IC.sub.50 from each assay.

The invention provides a process for detecting the presence of guanidinium ions in a sample solution. The detection process involves contacting a sample solution suspected of containing guanidinium ions with a cation exchange resin and eluting the guanidinium ions present in the sample solution with an aqueous buffer solution having a pH of about 1.5 to about 2. This is followed by contacting the eluant with a cation suppressor column and simultaneously flowing a suppressor regenerate solution in the opposite direction on the opposite side of the permeable membrane of the column, and finally, detecting the presence of guanidinium ions in the eluant from the ion exchange column which was contacted with the suppressor column by use of a conductivity detector.

Processes for the purification of human recombinant decorin and the

The present invention provides a method of inhibiting an activity of a cell regulatory factor comprising contacting the cell regulatory factor with a purified polypeptide, wherein the polypeptide comprises a cell regulatory factor binding domain of a protein. The protein is characterized by a leucine-rich repeat of about 24 amino acids. In a specific embodiment, the present invention relates to the ability of decorin, a 40,000 dalton protein that usually carries a glycosaminoglycan chain, and more specifically to active fragments of decorin or its functional equivalents to bind TGF.beta.. The invention also provides a novel cell regulatory factor designated MRF. Also provided are methods of identifying, detecting and purifying cell regulatory factors and proteins which bind and affect the activity of cell regulatory factors.

Decorin fragments inhibiting cell regulatory factors

The present invention provides novel conjugates of a synthetic polypeptide containing RGD or (dR)GD and a biodegradable polymer, hyaluronate. The conjugates are prepared by any one of three different methods provided by the present invention: (1) an epoxide method (2) a sodium periodate method, and (3) a tresyl chloride method. The conjugates prepared by these methods are useful to aid in wound healing and tissue regeneration by providing a temporary matrix for tissue repair. The invention also provides novel RGD-peptides.

Immobilization of peptides to hyaluronate

Method and composition for treating vascular graft occlusion

The invention provides cyclic peptides which inhibit platelet aggregation without causing prolonged bleeding time. The invention provides RGD or KGD containing peptides which are cyclized and contain hydrophobic moieties adjacent to the carboxy terminus of the RGD sequence. Peptides of this nature are also provided which contain in addition to the hydrophobic moiety an adjacent positively charged moiety. Such peptides have a high affinity for the receptor IIb/IIIa and a low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.

The present invention is directed to a process for the production of substantially pure human recombinant decorin which involves the combination of three separate stages characterized by contacting decorin-containing cell culture medium with (1) a first strong anionic exchange resin; then with (2) a hydrophobic interactive chromatographic resin; and finally with (3) a second strong anionic exchange resin. By using a combination of steps, and certain reagents, in particular a 2.4 to 3 molar GuHCl solution to elute decorin from a hydrophobic interactive column, the process of this invention provides a more convenient and reproducible process for purifying human recombinant decorin. The invention also provides a process for detecting the presence of guanidinium ions in a sample solution. The detection process involves contacting a sample solution suspected of containing guanidinium ions with a cation exchange resin and eluting the guanidinium ions present in tire sample solution with an aqueous buffer solution having a pH of about 1.5 to about 2. This is followed by contacting the eluant with a cation suppressor columns and simultaneously flowing a suppressor regenerate solution in the opposite direction on the opposite side of the permeable membrane of the column, and finally, detecting the presence of guanidinium ions in the eluant from the ion exchange column which was contacted with the suppressor column by use of a conductivity detector.

The present invention pertains to a process for recovering hepatitis B surface antigen from recombinant Pichia pastoris cells comprising:

Purification of hepatitis proteins

Method for the selective extraction of desired lipophilic proteins from transformed cells of the genus Pichia by cell lysis in the presence of chaotrophic salts is disclosed. The total protein extracted under the invention cell lysis conditions is reduced while the recovery of desired lipophilic proteins remains relatively constant, thereby producing a cell extract with enhanced concentration of the desired lipophilic protein relative to a control cell extract.

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San Diego, CA, United States of America

William S Craig