摘要:
DNA constructs useful in the production of thrombopoietin are disclosed. In general, the DNA constructs comprise a first DNA segment encoding a fusion of an amino-terminal secretory peptide joined to a thrombopoietin polypeptide and one or more additional DNA segments that provide for the transcription of the first segment. The secretory peptide is a native mammalian t-PA secretory peptide or may be modified to enhance proteolytic cleavage of the fusion. Also disclosed are cultured eukaryotic cells containing these DNA constructs and methods for producing thrombopoietin polypeptides through the use of the DNA constructs and cultured eukaryotic cells.
摘要:
Human protein C molecules are modified to provide increased resistance to inactivation by human plasma factors while retaining substantially the biological activity of human protein C. The modifications are generally to the heavy chain of protein C, which chain may be substituted with a protein C heavy chain of non-human origin, such as bovine, yielding a chimeric protein C molecule. The human protein C heavy chain may also be modified to be human-like, in that at least one amino acid from a non-human sequence may be substituted for the corresponding residue(s) of the human sequence, thereby allowing the molecule to retain substantially human characteristics yet having increased resistance to inactivation. Also included are methods for producing the modified protein C molecules and pharmaceutical compositions thereof. The modified molecules, having an increased half-life in human plasma, are particularly useful for treating coagulation-related disorders, such as protein C deficiency or thrombosis, or for promoting fibrinolysis in a patient.
摘要:
On modifie des molécules de protéine C humaine afin d'obtenir une résistance accrue à l'inactivation par des facteurs de plasma humain, tout en conservant l'activité biologique de la protéine C humaine. Les modifications sont effectuées sur la chaîne lourde de la protéine C, laquelle chaîne peut être remplacée par une chaîne lourde de protéine C d'origine non humaine, par exemple d'origine ovine, produisant une molécule de protéine C chimérique. On peut également modifier la chaîne lourde de la protéine C humaine afin qu'elle ait une apparence humaine, de sorte qu'au moins un acide aminé tiré d'une séquence non humaine peut être remplacé par le/les reste(s) correspondant de la séquence humaine, ce qui permet à la molécule de conserver des caractéristiques humaines tout en ayant une résistance accrue à l'inactivation. L'invention concerne également des procédés de production des molécules de protéine C modifiées ainsi que leurs compositions pharmaceutiques. Les molécules modifiées présentant une demi-vie augmentée dans du plasma humain sont particulièrement utiles pour traiter les troubles relatifs à la coagulation, tels que les carences en protéine C ou la thrombose, ou afin de stimuler la fibrinolyse chez un patient.
摘要:
This present invention is directed to polypeptide and polynucleotide molecules that encode a four-helical bundle cytokine. The cytokine has been designated zsig81, and has restricted expression in primarily heart, lung and liver. zsig81 has been shown to stimulate proliferation of hematopoietic cells and will be useful expansion of these cells, as well as conditions associated with hematopoietic cells. The invention is directed to antibodies and methods of making zsig81 polypeptides, as well.
摘要:
Hematopoietic proteins and polypeptide fragments thereof are provided, including proteins and polypeptides from mice and humans. Also provided are DNA molecules encoding the proteins and polypeptides, as well as vectors and cells useful in their production. Antibodies that bind to an epitope on the proteins are also provided. The proteins and polypeptides are useful for in vivo and ex vivo therapy, and as reagents for cell culture and investigation of cell proliferation and development.
摘要:
Methods for treating cancer by co-administering a therapeutic monoclonal antibody with IL-21 are described. Exemplary monoclonal antibodies that can be used are rituximab, trastuzumab and anti-CTLA-4 antibodies. The enhanced antitumor of the combination therapy is particularly useful for patient populations that are recalcitrant to monoclonal therapy, relapse after treatment with monoclonal antibodies or where the enhanced IL-21 antitumor effect reduces toxicities associated with treatment using the monoclonal antibodies.
摘要:
There is provided an in vitro method for expansion of hematopoietic cells and hematopoietic cell progenitors comprising: culturing bone marrow or peripheral blood cells with a composition comprising an amount of IL-21 sufficient to produce an increase in the number of lymphoid cells in the bone marrow or peripheral blood cells as compared to bone marrow or peripheral blood cells cultured in the absence of IL-21. There are also provided anti-cancer effector cells for use in the treatment of cancer in a patient by adoptive immunotherapy, wherein said anti-cancer effector cells have been obtained from the patient, and wherein the use comprises an initial ex vivo step of expanding the anti-cancer effector cells in culture in the presence of IL-21.
摘要:
Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for soluble zalpha11 receptors that may be used as novel cytokine antagonist, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block zalpha11 Ligand activity in vitro and in vivo, and may be used in conjunction with zalpha11 Ligand and other cytokines to selectively stimulate the immune system. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.
摘要:
DNA constructs useful in the production of thrombopoietin are disclosed. In general, the DNA constructs comprise a first DNA segment encoding a fusion of an amino-terminal secretory peptide joined to a thrombopoietin polypeptide and one or more additional DNA segments that provide for the transcription of the first segment. The secretory peptide is a native mammalian t-PA secretory peptide or may be modified to enhance proteolytic cleavage of the fusion. Also disclosed are cultured eukaryotic cells containing these DNA constructs and methods for producing thrombopoietin polypeptides through the use of the DNA constructs and cultured eukaryotic cells.