Abstract: Methods and compositions directed to improved universal antibody libraries that rationally exploit human diversity information contained within reference antibody libraries, such as universal antibody libraries, are disclosed. The disclosed processes involve use of a query CDR sequence to guide incorporation of human antibody diversity present within the reference library into cohort libraries of the invention. Methods for making and screening such cohort libraries for isolating therapeutics suitable for treating disease are also disclosed.

Abstract: A composition comprising individual single-stranded oligonucleotides capable of self assembling to form a pair of complementary, substantially contiguous single strands of a double-stranded nucleic acid filament, and a method for forming such filaments are disclosed.

Abstract: A method for generating human IgG1 antibodies with enhanced Fc effector function is disclosed. In practicing the method, an IgG1 Fc look-through mutagenesis (LTM) coding library directed at four receptor-contact regions of the Fc CH2 portion of in human IgG1 Fc is expressed in a system in which the mutated Fc fragments are displayed on the surfaces of the expression cells. The fragments are then screened for altered binding affinity to a selected Fc receptor or other Fc-binding protein. The selected mutations may be used, in turn, to guide the selection of multiple substitutions in the construction of a walk-through mutation (WTM) library, for generating additional Fc fragment mutations with desired binding properties. The antibodies so produced have a variety of therapeutic and diagnostic applications.

Abstract: Walk-through mutagenesis and natural-variant combinatorial fibronectin Type III (FN3) polypeptide libraries are described, along with their method of construction and use. Also disclosed are a number of high binding affinity polypeptides selected by screening the libraries against a variety of selected antigens.

Abstract: The invention provides a combinatorial influenza vaccine composition for use in providing prophylactic protection in humans against influenza viruses or animals, and a method of producing the vaccine.

Abstract: A method of mutagenesis by which a predetermined amino acid is introduced into each and every position of a selected set of positions in a preselected region (or several different regions) of a polypeptide to produce a library of polypeptide analogs is disclosed. The method is based on the premise that certain amino acids play a crucial role in the structure and function of proteins and thus is capable of identifying and distinguishing functional amino acid residues (“hot spots”) from non-functional amino acids residues (“cold spots”) within a polypeptide or portion thereof. Libraries can be generated which contain only desired polypeptide analogs and are of reasonable size for screening. The libraries can be used to study the role of specific amino acids in polypeptide structure and function and to develop new or improved polypeptides such as antibodies, antibody fragments, single chain antibodies, enzymes, and ligands.

Abstract: Libraries of immunoglobulins of interest are described, the libraries containing mutated immunoglobulins of interest in which a single predetermined amino acid has been substituted in one or more positions in one or more complementarity-determining regions of the immunoglobulin of interest. The libraries comprise a series of subset libraries, in which the predetermined amino acid is “walked through” each of the six complementarity-determining regions (CDRs) of the immunoglobulin of interest not only individually but also for each of the possible combinatorial variations of the CDRs, resulting in subset libraries that include mutated immunoglobulins having the predetermined amino acid at one or more positions in each CDR, and collectively having the predetermined amino acid at each position in each CDR.

Abstract: The invention provides olive-derived hydroxytyrosol. According to one aspect of the invention, vegetation water is collected from olives. Acid is added to stabilize the vegetation water and prevent fermentation. The mixture is incubated to allow oleoeuropein to convert to hydroxytyrosol, and then fractionated to separate hydroxytyrosol from other components. The hydroxytyrosol is useful as a natural anti-bacterial, anti-viral and fungicidal product for agricultural and pest control applications. In addition, it is useful as a therapeutic and anti-oxidant for a variety of health purposes.

Abstract: The invention provides olive-derived hydroxytyrosol. According to one aspect of the invention, vegetation water is collected from olives. Acid is added to stabilize the vegetation water and prevent fermentation. The mixture is incubated to allow oleoeuropein to convert to hydroxytyrosol, and then fractionated to separate hydroxytyrosol from other components. The hydroxytyrosol is useful as a natural anti-bacterial, anti-viral and fungicidal product for agricultural and pest control applications. In addition, it is useful as a therapeutic and anti-oxidant for a variety of health purposes.

Abstract: Compositions obtained from vegetation water from olives and methods for treating patients suffering from an inflammatory skin disease with the compositions are described. Included are hydroxytyrosol rich compounds obtained from olive vegetation water.

Abstract: Disclosed is a method for the isolation and purification of polypeptides expressed in host cells by recombinant DNA techniques. A fused polypeptide is produced containing a desired polypeptide fused to additional amino acids. The additional amino acids define a leader sequence having properties exploitable in purification, a hinge region, and a cleavage site. The hinge region is cysteine-free and has a secondary structure which serves to expose the cleavage site to a selected endopeptidase. The method of the invention involves the production of a fused polypeptide which may be efficiently isolated by exploiting the properties of the leader sequence, and then efficiently cleaved at the cleavage site in an appropriate aqueous environment by virtue of the influence of the hinge on the cleavage agent/cleavage site reaction and other properties of the fused polypeptide.

Abstract: A method of treating early diabetic neuropathy includes administering a composition comprising an aqueous extract of olives is disclosed. A method of treating patients with Cfiber neuropathy includes administering a composition comprising an aqueous extract of olives. A method of treating patients with large fiber and C-fiber neuropathy includes administering a composition comprising an aqueous extract of olives. Preferably the aqueous extract of olives contains a weight ratio of hydroxytyrosol to oleuropein of between about 1:1 and about 400:1. More preferably, the weight ratio is between about 3:1 and about 200:1. Most preferably, the weight ratio is between about 5:1 and about 50:1. Alternately, an extract from grape leaves can be used to treat patients with large fiber and Cfiber neuropathy.

Abstract: An isolated human anti-TNF-? antibody, or antigen-binding portion thereof, containing at least one high-affinity VL or VH antibody chain that is effective, when substituted for the corresponding VL or VH chain of the anti-TNF-? scFv antibody having sequence SEQ ID NO: 1, to bind to human TNF-? with a Koff rate constant that is at least 1.5 fold lower than that of the antibody having SEQ ID NO: 1, when determined under identical conditions.

Abstract: The invention provides olive-derived vegetation water substantially free of monophenolic compounds (e.g., tyrosol and its derivatives) from olive pits. According to one aspect of the invention, the pits or seeds are removed from the olives prior to pressing. The pitless pulp or meat is then pressed to obtain a liquid-phase mixture including olive oil, vegetation water, and solid by-products. The vegetation water is separated from the rest of the liquid-phase mixture and collected. The vegetation water is useful as a source of oleuropein.

Abstract: A method of mutagenesis by which a predetermined amino acid is introduced into each and every position of a selected set of positions in a preselected region (or several different regions) of a polypeptide to produce a library of polypeptide analogs. The method is based on the premise that certain amino acids play crucial role in the structure and function of proteins. Libraries can be generated which contain only desired polypeptide analogs and are of reasonable size for screening. The libraries can be used to study the role of specific amino acids in polypeptide structure and function and to develop new or improved polypeptides such as antibodies, antibody fragments, single chain antibodies, enzymes, and ligands.

Abstract: A composition includes acetyl-L-carnitine or its pharmacologically acceptable salt and a mixture of polyphenols containing hydroxytyrosol in an effective weight ratio. Carnitine can be L-carnitine, propionyl-L-carnitine, valeryl-L-carnitine, isovaleryl-L-carnitine or mixtures thereof. The composition has a weight ratio of carnitine:hydroxytyrosol of from 100:1 to 1:10. Also disclosed is a method of preventing tissue damage caused by the presence of free radicals due to environmental pollution; of preventing brain or myocardial lesions induced by free radicals following cerebral or myocardial ischemia and reperfusion; of preventing diabetic or toxic neuropathies and metabolic disorders of glucose utilization, which includes administering the composition.

Abstract: A method of treating inflammation, an inflammatory condition, or AIDS-associated neurological disorder in a subject in need of such treatment is disclosed. The method includes administering to said subject a pharmaceutically effective amount of substantially purified hydroxytyrosol or a substantially purified mixture of hydroxytyrosol and oleuropein. Also disclosed are compositions for use in practicing the method.

Abstract: A method of walk-through mutagenesis of a nucleic acid encoding a prototype polypeptide of interest, is described, the method comprising selecting a predetermined amino acid and one or more target regions of the polypeptide, and synthesizing a mixture of oligonucleotides containing at each sequence position in the target region, either a prototype nucleotide that is required for synthesis of the prototype amino acid of the polypeptide, or a predetermined nucleotide that is required for synthesis of the predetermined amino acid, in which during the synthesis, the ratio of available prototype nucleotides, to available predetermined nucleotides, is greater than 1:1.

Abstract: Libraries of immunoglobulins of interest are described, the libraries containing mutated immunoglobulins of interest in which a single predetermined amino acid has been substituted in one or more positions in one or more complementarity-determining regions of the immunoglobulin of interest. The libraries comprises a series of subset libraries, in which the predetermined amino acid is “walked through” each of the six complementarity-determining regions (CDRs) of the immunoglobulin of interest not only individually but also for each of the possible combinatorial variations of the CDRs, resulting in subset libraries that include mutated immunoglobulins having the predetermined amino acid at one or more positions in each CDR, and collectively having the predetermined amino acid at each position in each CDR.

Abstract: A method of mutagenesis by which a predetermined amino acid is introduced into each and every position of a selected set of positions in a preselected region (or several different regions) of a protein to produce library of mutants. The method is based on the premise that certain amino acids play crucial role in the structure and fuction of proteins. Libraries can be generated which contain a high proportion of the desired mutants and are of reasonable size for screening. This libraries can be used to study the role of specific amino acids in protein structure and function and to develop new or improved proteins and polypeptides such as enzymes, antibodies, single chain antibodies and catalytic antibodies.