Abstract: The invention relates to a Kunitz domain peptide, designated DPI-14 herein, for inhibiting human neutrophil elastase. The invention also relates to a method of using a DPI-14 for treating cystic fibrosis or cystic fibrosis-related disease or disorder.

Abstract: In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained.

Abstract: The invention features novel polypeptides homologous to the first Kunitz domain (K1) of lipoprotein associated coagulation inhibitor (LACI) that are capable of inhibiting plasmin, and nucleic acids encoding these proteins. The invention also features the use of such polypeptides in diagnostic, therapeutic and clinical methods.

Abstract: The present invention provides binding moieties for CEA, which have a variety of uses wherever detecting, isolating or localizing CEA, and particularly CEA as opposed to cross-reactive antigens such as NCA, is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding CEA, which is overexpressed in adenocarcinomas of endodermally derived digestive system epithelia and fetal colon. Such polypeptides and disclosed derivatives are useful, e.g., as imaging agents for CEA-expressing tumors.

Abstract: Novel enterokinase cleavage sequences are provided. Also disclosed are methods for the rapid isolation of a protein of interest present in a fusion protein construct including a novel enterokinase cleavage sequence of the present invention and a ligand recognition sequence for capturing the fusion construct on a solid substrate. Preferred embodiments of the present invention show rates of cleavage up to thirty times that of the known enterokinase cleavage substrate (Asp)4-Lys-Ile.

Abstract: Disclosed are methods and compositions useful, e.g., for controlling the valency of display proteins during display library screenings and selections. In one embodiment, they are applicable to phage and phage libraries that are based on bacteriophage, e.g., filamentous bacteriophage.

Abstract: The invention relates to a Kunitz domain peptide, designated DPI-14 herein, for inhibiting human neutrophil elastase. The invention also relates to a method of using a DPI-14 for treating cystic fibrosis or cystic fibrosis-related disease or disorder.

Abstract: The present invention provides binding moieties for CEA, which have a variety of uses wherever detecting, isolating or localizing CEA, and particularly CEA as opposed to cross-reactive antigens such as NCA, is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding CEA, which is overexpressed in adenocarcinomas of endodermally derived digestive system epithelia and fetal colon. Such polypeptides and disclosed derivatives are useful, e.g., as imaging agents for CEA-expressing tumors.

Abstract: In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained.

Abstract: In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained.

Abstract: Novel small proteins which bind cathepsin G have been identified. These are useful as inhibitors of excessive cathepsin G activity in patients.

Abstract: In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained.

Abstract: In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained.

Abstract: The present invention provides binding moieties for CEA, which have a variety of uses wherever detecting, isolating or localizing CEA, and particularly CEA as opposed to cross-reactive antigens such as NCA, is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding CEA, which is overexpressed in adenocarcinomas of endodermally derived digestive system epithelia and fetal colon. Such polypeptides and disclosed derivatives are useful, e.g., as imaging agents for CEA-expressing tumors.

Abstract: Binding polypeptides comprising specific amino acid sequences are disclosed that bind B Lymphocyte Stimulator (BLyS) protein or BLyS-like polypeptides. The binding polypeptides can be used in methods of the invention for detecting or isolating BLyS protein or BLyS-like polypeptides in solutions or mixtures, such as blood, tissue samples, or conditioned media.

Abstract: Mutants of Kunitz domain 1 (ITI-D1) of human inter-&agr;-trypsin inhibitor (ITI), are useful as inhibitors of human neutrophil elastase. Mutants characterized by one or more of the following substitutions (numbered to correspond to bovine pancreatic trypsin inhibitor, the archetypal Kunitz domain) are of particular interest: (a) Val15 or Ile15, (b) Ala16, (c) Phe18, (d) Pro19, (e) Arg1, (f) Pro2, and/or (g) Phe4.

Abstract: This invention provides: novel proteins, which are homologous to the first Kunitz domain (K1) of lipoprotein-associated coagulation inhibitor (LACI), and which are capable of inhibiting plasmin; uses of such novel proteins in therapeutic, diagnostic, and clinical methods; and polynucleotides that encode such novel proteins.

Abstract: A method is disclosed for obtaining affinity ligands for isolating tissue-type plasminogen activator (tPA). Ligands binding tPA with high specificity at pH 7 and releasing tPA at pH 5 or lower are disclosed. Also disclosed are methods whereby additional ligands having desirable preselected binding and release (elution) characteristics may be isolated, permitting the development of tailored ligands to meet the purification problems presented by any particular feed stream containing tPA.

Abstract: Focused libraries of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of antibody peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The libraries have length and sequence diversities that mimic that found in native human antibodies.

Abstract: In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural-signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained.