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

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. Pharmaceutical compositions and kits comprising the polypeptide or antibodies and antibody fragments containing the polypeptide are also provided.

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: Provided are monoclonal antibodies and antigen-binding fragments thereof that bind to, and inhibit the activity of, CD47, as well as monoclonal antibodies and antigen binding fragments thereof that compete with the former for binding to CD47. Also provided are combinations of any of the foregoing. Such antibody compounds are variously effective in 1) treating tissue ischemia and ischemic-reperfusion injury (IRI) in the setting of organ preservation and transplantation, pulmonary hypertension, sickle cell disease, myocardial infarction, stroke, and other instances of surgery and/or trauma in which IRI is a component of pathogenesis; 2) in treating autoimmune and inflammatory diseases; and 3) as anti-cancer agents that are toxic to susceptible cancer cells, promoting their phagocytic uptake and clearance, or directly killing such cells.

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: 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 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. Pharmaceutical compositions and kits comprising the polypeptide or antibodies and antibody fragments containing the polypeptide are also provided.

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: A polypeptide having a heavy chain variable region and/or light chain variable region that specifically binds to CTLA4 protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to CTLA4 protein. Pharmaceutical compositions and kits comprising the polypeptide or antibodies and antibody fragments containing the polypeptide are also provided.

Abstract: An antibody or antibody fragment having a heavy chain variable region and/or light chain variable region that specifically binds to Axl protein. Immuoconjugages, pharmaceutical compositions and kits comprising the antibodies and antibody fragments are also provided. Also disclosed are methods of treating Axl-expressing cancers using the antibodies, antibody fragments, immunoconjugates and pharmaceutical compositions of the present invention.

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 invention relates to a belt deflector with a main element (100) that can be attached to the structure of a vehicle, and with a belt support element (200) that is movable relative to the main element (100) and forms a support surface (231) or support edge for a safety belt (20) to be deflected. According to the invention, the belt deflector comprises an intermediate element (300, 400) that is deformed when the movable belt support element (200) is moved relative to the main element (100), in the direction of the intermediate element (300, 400), and because of this deformation is pressed against the safety belt (20).

Abstract: This disclosure relates to a chimeric antigen receptor for binding with a tumor specific target antigen. The chimeric antigen receptor comprises at least one antigen specific targeting region evolved from a parent protein or a fragment thereof and having a decrease in activity in the assay at the normal physiological condition compared to the activity in the assay under the aberrant condition. A method for producing the chimeric antigen receptor is also provided.

Abstract: A multi-specific antibody contains at least one binding site for a cell specific antigen and at least one binding site for a tumor-reactive lymphocyte antigen and a multi-specific antibody including an IgG antibody or fragment thereof that binds to a first antigen; and at least one scFv antibody that binds to a second antigen that is different from the first antigen and is linked to a C terminus of at least one light chain or heavy chain of said IgG antibody or fragment. The multi-specific antibody reversibly binds to at least one of the cell specific antigen and tumor-reactive lymphocyte antigen or the first antigen and the second antigen with a greater affinity at an aberrant condition than at a normal physiological condition. Conjugates of the multi-specific antibodies and methods for generating the multi-specific antibody are also provided.

Abstract: An anti-IL-22 antibody or antibody fragment that binds to both human IL-22 and a mammalian IL-22 as well as modified anti-IL-22 antibodies and antibody fragments. Pharmaceutical compositions and kits comprising the antibody or antibody fragment are also provided. Also provided are methods for treatment of various IL-22 mediated conditions and diseases.

Abstract: The invention relates to a belt deflector (10) having a main element (20) which is fastenable to a vehicle structure, and a belt contact element (30) which is movable in relation to the main element (20) and forms a belt contact face (SA30) or belt contact edge for a seat belt (40) that is to be deflected, wherein the belt deflector (10) has a deformable intermediate element (50) which, during a relative movement of the movable belt contact element (30) relative to the main element (20) in the direction of the intermediate element (50), is deformed and is pressed against the seat belt (40) by this deformation. According to the invention, provision is made that the belt contact element (30) forms a mating clamping face (G30), and a belt strap portion (41) of the seat belt (40) is arranged between the intermediate element (50) and the mating clamping face (G30), and, during said relative movement, the intermediate element (50) presses the belt strap portion (41) onto the mating clamping face (G30).

Abstract: The present invention relates to modified Fc regions of antibodies, and uses thereof, such as in antibodies that contain an Fc region of the present invention.

Abstract: A labelling system includes a labelling plate being adapted to be removably connected with a sterile container, wherein the labelling plate includes interfaces for at least one label (e.g. barcode) and at least one identification tag (e.g. RFID). The interfaces can removably hold the at least one identification tag and/or the at least one label at the separate labelling plate.

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.