Abstract: Methods of generating conditionally active proteins that target senescent cells and which are conditionally active in an extracellular environment of a senescent cell. The methods include discovery methods using libraries of evolved proteins and assays employing physiological concentrations of components of bodily fluids. Also disclosed are conditionally active proteins for killing or removing senescent cells, pharmaceutical compositions employing these conditionally active proteins and methods for treatment of age-related diseases, conditions or disorders using same. The conditionally active proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety.

Abstract: A non-naturally occurring polypeptide or isolated polypeptide having a ratio of at least 1.3 of an activity in an assay at a first pH in the presence of at least one species having a molecular weight of less than 900 a.m.u. and a pKa up to 4 pH units away from said first pH, to an activity in an assay at a second pH in the presence of the same at least one species. The species has a pKa between said first pH and said second pH and can be a small molecule. Also disclosed are pharmaceutical formulations including the polypeptide and uses thereof. Methods of producing conditionally active polypeptides are also disclosed.

Abstract: The present invention is relevant to proteins and novel methods of protein evolution. The present invention further relates to methods of identifying and mapping mutant polypeptides formed from, or based upon, a template polypeptide.

Abstract: Provided herein are, inter alia, humanized 1E9 antibodies capable of binding CD73. The humanized antibodies are useful for the treatment of cancer. Further provided are nucleic acids encoding humanized 1E9 antibodies and methods of inhibiting cell proliferation using the humanized antibodies provided herein.

Abstract: The present invention relates to methods for efficiently generating recombinant monoclonal antibodies derived from B cells of a non-human host which has been immunochallenged with one or more target antigens. The methods comprise the steps of identifying and isolating B cell that bind to the antigen by FACS, and recombining and enriching for thousands of cells to create a B cell library. Related products and methods, such as methods of producing expression libraries, are also disclosed.

Abstract: A method of preparing a conditionally active biologic protein by selecting a wild-type biologic protein, evolving the DNA which encodes the wild-type biologic protein using one or more evolutionary techniques to create mutant DNAs, expressing the mutant DNAs in a eukaryotic cell production host to obtain a mutant protein, subjecting the mutant protein and the wild-type protein to an assay under a normal physiological condition and to an assay under an aberrant condition, selecting a conditionally active mutant protein which exhibits at least one of: (a) a decrease in activity in the assay at the normal physiological condition compared to the wild-type protein, and (b) an increase in activity in the assay under the aberrant condition compared to the wild-type protein; and producing the conditionally active biologic protein in the same eukaryotic cell production host used in the expression step.

Abstract: The present invention is relevant to the generation of multi-specific antibodies, antibodies that are distinguished by their ability to bind to multiple antigens with specificity and with affinity. In particular, the present invention is related to bi-specific antibodies.

Abstract: A method of detecting tumor cells in a sample containing cells. In the method, a sample is encapsulated to produce a capsule with the sample encapsulated therein. The capsule containing the sample encapsulated therein is incubated under cell culture conditions suitable for supporting cell activity and growth of tumor cells and the encapsulated sample from the incubated capsule is contacted with a conditionally active antibody that has a higher binding affinity to a cell surface protein of a tumor cell under a first value of a condition of a tumor microenvironment, in comparison with the binding affinity of the conditionally active antibody to the same cell surface protein under a second value of the condition.

Abstract: Methods of generating conditionally active biologic proteins, in particular therapeutic or diagnostic proteins, which are more active at an aberrant condition than at a normal physiological condition. The methods include discovery methods using libraries of proteins and assays employing physiological concentrations of components of bodily fluids. The conditionally active biologic proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety. Criteria for selecting starting proteins for the discovery methods, as well as formats of the proteins are also disclosed.

Abstract: A method of preparing a conditionally active polypeptide from a parent polypeptide, comprising steps of evolving a DNA encoding the parent polypeptide by increasing a net charge of the parent polypeptide using one or more techniques selected from increasing a total number of codons of charged amino acid residues in the DNA and decreasing a total number of codons of uncharged amino acid residues in the DNA to create mutant DNAs; expressing the mutant DNAs to obtain mutant polypeptides; and selecting the conditionally active polypeptide from the mutant polypeptides which exhibits a decrease in activity in a first assay at a first value of a condition compared to the same activity in a second assay at a second value of the same condition. The conditionally active polypeptide, pharmaceutical compositions containing same, nanoparticle and drug conjugates thereof and uses thereof are also provided.

Abstract: The present invention relates to methods for efficiently generating recombinant monoclonal antibodies derived from B cells of a non-human host which has been immunochallenged with one or more target antigens. The methods comprise the steps of identifying and isolating B cell that bind to the antigen by FACS, and recombining and enriching for thousands of cells to create a B cell library. Related products and methods, such as methods of producing expression libraries, are also disclosed.

Abstract: The disclosure provides a method for generation of humanized full length antibodies in mammalian cells. A library of humanized variants is provided with high, validated human framework diversity without requiring back-mutations to retain original affinity. Synthetic CDR encoding fragment libraries derived from a template antibody are ligated to human framework region encoding fragments from a human framework pool limited only to germline sequences from a functionally expressed antibodies. The vector comprises a nucleic acid sequence encoding HC framework region 4. No CDR grafting or phage display is required.

Abstract: The disclosure provides a method for generation of humanized full length antibodies in mammalian cells. A library of humanized variants is provided with high, validated human framework diversity without requiring back-mutations to retain original affinity. Synthetic CDR encoding fragment libraries derived from a template antibody are ligated to human framework region encoding fragments from a human framework pool limited only to germline sequences from a functionally expressed antibodies. The vector comprises a nucleic acid sequence encoding HC framework region 4. No CDR grafting or phage display is required.

Abstract: A polypeptide having a heavy chain variable region and/or light chain variable region that specifically binds to Ror2 protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to Ror2 protein.

Abstract: A method of preparing a conditionally active biologic protein by selecting a wild-type biologic protein, evolving the DNA which encodes the wild-type biologic protein using one or more evolutionary techniques to create mutant DNAs, expressing the mutant DNAs in a eukaryotic cell production host to obtain a mutant protein, subjecting the mutant protein and the wild-type protein to an assay under a normal physiological condition and to an assay under an aberrant condition, selecting a conditionally active mutant protein which exhibits at least one of: (a) a decrease in activity in the assay at the normal physiological condition compared to the wild-type protein, and (b) an increase in activity in the assay under the aberrant condition compared to the wild-type protein; and producing the conditionally active biologic protein in the same eukaryotic cell production host used in the expression step.

Abstract: This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at some physiological conditions. For example, conditionally active biologic proteins are active in tumors, but virtually inactive at other body parts, or conditionally active antibodies capable of crossing blood-brain-barrier.

Abstract: This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at some physiological conditions. For example, conditionally active biologic proteins are active in tumors, but virtually inactive at other body parts, or conditionally active antibodies cap able of crossing blood-brain-barrier.

Abstract: A polypeptide having a heavy chain variable region and/or light chain variable region that specifically binds to Axl protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to Axl protein. Pharmaceutical compositions and kits comprising the polypeptide or antibodies and antibody fragments containing the polypeptide are also provided.

Abstract: The present invention is relevant to the generation of multi-specific antibodies, antibodies that are distinguished by their ability to bind to multiple antigens with specificity and with affinity. In particular, the present invention is related to bi-specific antibodies.

Abstract: Methods of generating conditionally active biologic proteins, in particular therapeutic or diagnostic proteins, which are more active at an aberrant condition than at a normal physiological condition. The methods include discovery methods using libraries of proteins and assays employing physiological concentrations of components of bodily fluids. The conditionally active biologic proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety. Criteria for selecting starting proteins for the discovery methods, as well as formats of the proteins are also disclosed.