Abstract: The present invention provides a method for determining binding of a receptor to one or more ligands. The method consists of contacting a collective receptor variant population with one or more ligands and detecting binding of one or more ligands to the collective receptor variant population. The collective receptor variant population can be further divided into two or more subpopulations, one or more of the two or more subpopulations can be contacted with one or more ligands and one or more receptor variant subpopulations having binding activity to one or more ligands can be detected. The steps of dividing, contacting and detecting can be repeated one or more times. The invention also provides methods for identifying a receptor variant having optimal binding activity to one or more ligands. The invention additionally provides a method for determining binding of a ligand to one or more receptors.

Abstract: The invention provides a LM609 grafted antibody comprising one or more CDRs having at least one amino acid substitution, where the LM609 grafted antibody has &agr;v&bgr;3 binding activity. Nucleic acids encoding LM609 grafted heavy and light chains are additionally provided. Functional fragments of such encoding nucleic acids are similarly provided. The invention also provides a method of inhibiting a function of &agr;v&bgr;3. The method consists of contacting &agr;v&bgr;3 with a LM609 grafted antibody or functional fragments thereof under conditions which allow binding to &agr;v&bgr;3. Finally, the invention provides for a method of treating an &agr;v&bgr;3-mediated disease. The method consists of administering an effective amount a LM609 grafted antibody or functional fragment thereof under conditions which allow binding to &agr;v&bgr;3.

Abstract: The invention provides a Vitaxin antibody and a LM609 grafted antibody exhibiting selective binding affinity to &agr;v&bgr;3. The Vitaxin antibody consists of at least one Vitaxin heavy chain polypeptide and at least one Vitaxin light chain polypeptide or functional fragments thereof. Also provided are the Vitaxin heavy and light chain polypeptides and functional fragments. The LM609 grafted antibody consists of at least one CDR grafted heavy chain polypeptide and at least one CDR grafted light chain polypeptide or functional fragment thereof. Nucleic acids encoding Vitaxin and LM609 grafted heavy and light chains as well as nucleic acids encoding the parental non-human antibody LM609 are additionally provided. Functional fragments of such encoding nucleic acids are similarly provided.

Abstract: The invention provides a Vitaxin antibody and a LM609 grafted antibody exhibiting selective binding affinity to &agr;v&bgr;3. The Vitaxin antibody consists of at least one Vitaxin heavy chain polypeptide and at least one Vitaxin light chain polypeptide or functional fragments thereof. Also provided are the Vitaxin heavy and light chain polypeptides and functional fragments. The LM609 grafted antibody consists of at least one CDR grafted heavy chain polypeptide and at least one CDR grafted light chain polypeptide or functional fragment thereof. The invention additionally provides a high affinity LM609 grafted antibody comprising one or more CDRs having at least one amino acid substitution, where the &agr;v&bgr;3 binding activity of the high affinity LM609 grafted antibody is enhanced. Nucleic acids encoding Vitaxin and LM609 grafted heavy and light chains as well as nucleic acids encoding the parental non-human antibody LM609 are additionally provided.

Abstract: The invention provides a method of reducing the proliferation of a neoplastic cell. The method consists of contacting the neoplastic cell with a cytotoxic or cytostatic binding agent specifically reactive with an aberrantly expressed vesicular membrane associated neoplastic cell specific internalizing antigen. The neoplastic cell specific internalizing anitgen can be selected from the group consisting of lamp-2 and limp II families of lysosomal integral membrane proteins. Also provided is a method of intracellular targeting of a cytotoxic or cytostatic agent to a neoplastic cell population.

Abstract: The invention provides a Vitaxin antibody and a LM609 grafted antibody exhibiting selective binding affinity to &agr;v&bgr;3. The Vitaxin antibody consists of at least one Vitaxin heavy chain polypeptide and at least one Vitaxin light chain polypeptide or functional fragments thereof. Also provided are the Vitaxin heavy and light chain polypeptides and functional fragments. The LM609 grafted antibody consists of at least one CDR grafted heavy chain polypeptide and at least one CDR grafted light chain polypeptide or functional fragment thereof. Nucleic acids encoding Vitaxin and LM609 grafted heavy and light chains as well as nucleic acids encoding the parental non-human antibody LM609 are additionally provided. Functional fragments of such encoding nucleic acids are similarly provided. The invention also provides a method of inhibiting a function of &agr;v&bgr;3.

Abstract: A composition of matter comprising a plurality of procaryotic cells containing diverse combinations of first and second DNA sequences encoding first and second polypeptides which form a heteromeric receptor exhibiting binding activity toward a preselected molecule, those heteromeric receptors being expressed on the surface of filamentous bacteriophage.

Abstract: The invention relates to methods for manipulating nucleic acids so as to optimize the binding characteristics of an encoded binding protein by providing two or more nucleic acids encoding binding proteins having at least one set of splicing sites, the set of splicing sites flanking opposite ends of one or more encoded binding domains; mixing the nucleic acids to produce a parent population of mixed nucleic acids encoding binding proteins; and randomly incorporating the binding domains between the nucleic acids through the set of splicing sites to produce a different population of nucleic acids encoding binding proteins wherein at least one binding protein is characterized by substantially different binding characteristics than a member of the parent population.

Abstract: The invention provides a method of synthesizing oligonucleotides having random tuplets using individual monomers. The steps consist of: (1) sequentially coupling monomers on separate supports to form at least two different tuplets, the coupling is performed in separate reaction vessels; (2) mixing the supports from the reaction vessels; (3) dividing the mixed supports into two or more separate reaction vessels; and (4) repeating steps (1) through (3) one or more times in the reaction vessels of step (3), wherein the last step ends at step (2). Additionally, the oligonucleotides can be cleaved from the supports.

Abstract: The present invention includes non-RGD cyclic peptides that inhibit the function of the integrin receptor, .alpha..sub.v .beta..sub.3. The inventive peptides are between five to about thirty amino acids in length and include the sequence (SEQ ID NO:8), Arg-Cys-Asp-Gly-X.sub.i where X.sub.i is any amino acid, and a five-membered cyclic portion. These non-RGD peptides display surprisingly potent antagonist activity despite the lack of the consensus binding sequence Arg-Gly-Asp, and present opportunities for selective targeting to the .alpha..sub.v .beta..sub.3 receptor. Pharmaceutical compositions and methods of use are also disclosed. The therapeutic uses for the inventive peptides include treating diseases involving .alpha..sub.v .beta..sub.3 receptors such as cancer, osteoporosis, restenosis, and angiogenic-based diseases.

Abstract: A method of synthesizing isolated, soluble peptides having constrained secondary structure in solution is described herein. The peptides are encoded by expressible oligonucleotides having a desirable bias of random codon sequences.

Abstract: The present invention includes non-RGD, nine amino acid cyclic peptides that inhibit the function of the integrin receptor, .alpha..sub.v .beta..sub.3. These peptides display surprisingly potent antagonist activity despite the lack of the consensus binding sequence Arg-Gly-Asp, and present opportunities for selective targeting to the .alpha..sub.v .beta..sub.3 receptor. Pharmaceutical compositions and methods of use are also disclosed. The therapeutic uses for the inventive peptides include treating diseases involving .alpha..sub.v .beta..sub.3 receptors such as osteoporosis, restenosis, and angiogenic-based diseases, including cancer, arthritis, and diabetic retinopathy.

Abstract: The present invention is directed to a process for the production of a peptide, polypeptide, or protein having a predetermined property. In accordance with one embodiment, the process begins by producing by way of synthetic polynucleotide coupling, stochastically generated polynucleotide sequences. A library of expression vectors containing such stochastically generated polynucleotide sequences is formed. Next, host cells containing the vectors are cultured so as to produce peptides, polypeptides, or proteins encoded by the stochastically generated polynucleotide sequences. Screening or selection is carried out on such host cells to identify a peptide, polypeptide, or protein produced by the host cells which has the predetermined property. The stochastically generated polynucleotide sequence which encodes the identified peptide, polypeptide, or protein is then isolated and used to produce the peptide, polypeptide, or protein having the predetermined property.

Abstract: A composition of matter comprising a plurality of procaryotic cells containing diverse combinations of first and second DNA sequences encoding first and second polypeptides which form a heteromeric receptor exhibiting binding activity toward a preselected molecule, said heteromeric receptors being expressed on the surface of filamentous bacteriophage.