Abstract: Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R?-subunit and that are incapable of transducing a signal through either the ?- or ?-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the ?- or ?-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.

Abstract: Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R?-subunit and that are incapable of transducing a signal through either the ?- or ?-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the ?- or ?-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.

Abstract: The invention provides formulations of GM-CSF to which a chelating agent has been provided to stabilize the GM-CSF against N-terminal degradation.

Abstract: Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R?-subunit and that are incapable of transducing a signal through either the ?- or ?-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the ?- or ?-subunits of the IL-15 receptor complex.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R?-subunit and that are incapable of transducing a signal through either the ?- or ?-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the ?- or ?-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.

Abstract: Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R?-subunit and that are incapable of transducing a signal through either the ?- or ?-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the ?- or ?-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.

Abstract: Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R&agr;-subunit and that are incapable of transducing a signal through either the &bgr;- or &ggr;-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the &bgr;- or &ggr;-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of protecting one or more sites on the protein, contacting the protected protein with polyethylene glycol under conditions suitable for conjugating the polyethylene glycol to the protein, and deprotecting the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains sterically free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: The invention provides formulations of GM-CSF to which a chelating agent has been provided to stabilize the GM-CSF against N-terminal degradation.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with, polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with, polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Formulations for controlled, prolonged release of GM-CSF have been developed. These are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof with excipients and drug loadings that yield zero order or first order release, or multiphasic release over a period of approximately three to twenty one days, preferably one week, when administered by injection. In the preferred embodiment, the microparticles are microspheres having diameters in the range of 10 to 60 microns, formed of a blend of PLGA having different molecular weights, most preferably 6,000, 30,000 and 41,000. Other embodiments have been developed to alter the release kinetics or the manner in which the drug is distributed in vivo.

Abstract: Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R&agr;-subunit and that are incapable of transducing a signal through either the &bgr;- or &ggr;-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the B- or &ggr;subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed. including treating allograft rejection and graft-versus-host disease.

Abstract: Antagonists of mammalian interleukin-15 (“IL-l5”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R&agr;-subunit and that are incapable of transducing a signal through either the &bgr;- or &ggr;-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the &bgr;- or &ggr;-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.

Abstract: Antagonists of mammalian interleukin-15 ("IL-15") are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R.alpha.-subunit and that are incapable of transducing a signal through either the .beta.- or .gamma.-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the .beta.- or .gamma.-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed including treating allograft rejection and graft-versus-host disease.

Abstract: Antagonists of mammalian interleukin-15 ("IL-15") are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R.alpha.-subunit and that are incapable of transducing a signal through either the .beta.- or .gamma.-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the .beta.- or .gamma.-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.