Abstract: The present invention relates to TNF-&agr; binding molecules and nucleic acid sequences encoding TNF-&agr; binding molecules. In particular, the present invention relates to TNF-&agr; binding molecules with a high binding affinity, a high association rate, a low dissociation rate with regard to human TNF-&agr; and that are capable of neutralizing TNF-&agr; at low concentrations. Preferably, the TNF-&agr; binding molecules of the present invention comprise light and/or heavy chain variable regions with fully human frameworks (e.g. human germline frameworks).

Abstract: Ultra high affinity antibodies with binding affinities in the range of 1010 M−1, and even 1011 M−1 are disclosed. Such antibodies include antibodies having novel high affinity complementarity determining regions (CDRs), especially those with framework and constant regions derived from either humans or mice. Methods of preparing and screening such antibodies, as well as methods of using them to prevent and/or treat disease, especially virus-induced diseases, are also disclosed.

Abstract: The present invention relates to TNF-&agr; binding molecules and nucleic acid sequences encoding TNF-&agr; binding molecules. In particular, the present invention relates to TNF-&agr; binding molecules with a high binding affinity, a high association rate, a low dissociation rate with regard to human TNF-&agr; and that are capable of neutralizing TNF-&agr; at low concentrations. Preferably, the TNF-&agr; binding molecules of the present invention comprise light and/or heavy chain variable regions with fully human frameworks (e.g. human germline frameworks).

Abstract: The invention provides a grafted antibody, or functional fragment thereof, comprising one or more complementarity determining regions (CDRs) having at least one amino acid substitution in one or more CDRs of a heavy chain CDR, where the grafted antibody or functional fragment thereof has specific binding activity for a cryptic collagen epitope. The invention also provides methods of using an antibody having specific binding activity for a cryptic collagen epitope, including methods of inhibiting angiogenesis, tumor growth, and metastasis.

Abstract: The invention provides a cell composition comprising a population of non-yeast eukaryotic cells containing a diverse population of variant nucleic acids, each of the variant nucleic acids being expressed in a different cell and located within each cell at an identical site in the genome. The invention also provides a method of identifying a polypeptide exhibiting optimized activity by screening a population of non-yeast eukaryotic cells containing a diverse population of variant nucleic acids for an activity associated with a parent polypeptide of a diverse population of variant polypeptides encoded by the variant nucleic acids; and identifying a variant polypeptide exhibiting an optimized activity relative to the parent polypeptide.

Abstract: The invention provides a Vitaxin antibody and a LM609 grafted antibody exhibiting selective binding affinity &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: Ultra high affinity antibodies with binding affinities in the range of 1010 M−1, and even 1011 M−1 are disclosed. Such antibodies include antibodies having novel high affinity complementarity determining regions (CDRs), especially those with framework and constant regions derived from either humans or mice. Methods of preparing and screening such antibodies, as well as methods of using them to prevent and/or treat disease, especially virus-induced diseases, are also disclosed.

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: 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 enhanced LM609 grafted antibodies exhibiting selective binding affinity to &agr;V&bgr;3, or a functional fragment thereof. The invention also provides nucleic acid molecules encoding the enhanced LM609 grafted antibodies. Additionally provided are methods of inhibiting a function of &agr;V&bgr;3 by contacting &agr;V&bgr;3 with an enhanced LM609 grafted antibody.

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 method of conferring donor CDR binding affinity onto an antibody acceptor variable region framework. The invention also provides a method of simultaneously grafting and optimizing the binding affinity of a variable region binding fragment. A method of optimizing the binding affinity of an antibody variable region is also provided.

Abstract: The invention provides a grafted antibody, or functional fragment thereof, comprising one or more complementarity determining regions (CDRs) having at least one amino acid substitution in one or more CDRs of a heavy chain CDR, where the grafted antibody or functional fragment thereof has specific binding activity for a cryptic collagen epitope. The invention also provides methods of using an antibody having specific binding activity for a cryptic collagen epitope, including methods of inhibiting angiogenesis, tumor growth, and metastasis.

Abstract: The invention provides a cell composition comprising a population of non-yeast eukaryotic cells containing a diverse population of variant nucleic acids, each of the variant nucleic acids being expressed in a different cell and located within each cell at an identical site in the genome. The invention also provides a method of identifying a polypeptide exhibiting optimized activity by screening a population of non-yeast eukaryotic cells containing a diverse population of variant nucleic acids for an activity associated with a parent polypeptide of a diverse population of variant polypeptides encoded by the variant nucleic acids; and identifying a variant polypeptide exhibiting an optimized activity relative to the parent polypeptide.

Abstract: The invention provides enhanced LM609 grafted antibodies exhibiting selective binding affinity to &agr;V&bgr;3, or a functional fragment thereof. The invention also provides nucleic acid molecules encoding the enhanced LM609 grafted antibodies. Additionally provided are methods of inhibiting a function of &agr;V&bgr;3 by contacting &agr;V&bgr;3 with an enhanced LM609 grafted antibody.

Abstract: The present invention provides a method for identifying a binding molecule having selective affinity for a ligand. The method consists of selectively immobilizing a diverse population of binding molecules to a solid support, simultaneously contacting the diverse population immobilized on the solid support with two or more ligands and determining at least one binding molecule which selectively binds to one or more of the ligands. The invention additionally provides a method for identifying an antibody having selective affinity for a tumor antigen. The method consists of selectively immobilizing a diverse population of antibodies to a solid support, simultaneously contacting the diverse population immobilized on the solid support with two or more tumor antigens and determining at least one antibody which selectively binds to one or more of the tumor antigens. The invention also provides an isolated binding polypeptide selective for a tumor antigen.

Abstract: The invention provides a binding polypeptide, or functional fragment thereof, comprising a kon of at least about 9×107 M−1s−1 for associating with a ligand and having therapeutic potency. The invention also provides a method of determining the therapeutic potency of a binding polypeptide. The methods consist of (a) contacting a binding polypeptide with a ligand; (b) measuring association rate for binding between the binding polypeptide and the ligand, and (c) comparing the association rate for the binding polypeptide to an association rate for a therapeutic control, the relative association rate for the binding polypeptide compared to the association rate for the therapeutic control indicating that the binding polypeptide will exhibit a difference in therapeutic potency correlative with the difference between the association rates.

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.