Abstract: A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two "sub-monomers" directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amine bound to the support with an acylating agent comprising a leaving group capable of nucleophilic displacement by --NH.sub.2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a solid support-bound .alpha.-haloacetamide) with a sufficient amount of a second sub-monomer comprising an --NH.sub.2 group, such as a primary amine, alkoxyamine, semicarbazide, acyl hydrazide, carbazate or the like.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
March 2, 1999
Assignee:
Chiron Corporation
Inventors:
Ronald N. Zuckermann, Dane A. Goff, Simon Ng, Kerry Spear, Barbara O. Scott, Aaron C. Sigmund, Richard A. Goldsmith, Charles K. Marlowe, Yazhong Pei, Lutz Richter, Reyna Simon
Abstract: Methods for preventing or treating an antibody-mediated disease in patient are presented, the methods comprising administration of a humanized monoclonal antibody or fragment thereof that is capable of binding to a human CD40 antigen located on the surface of a human B cell, wherein the binding of the antibody to the CD40 antigen prevents the growth or differentiation of the B cell. Humanized monoclonal antibodies and fragments useful in these methods are also presented.
Abstract: Tumor Infiltrating Lymphocyte (TIL) cells transformed with exogenous DNA encoding tumor necrosis factor (TNF) prohormone variants are disclosed. Among such variants are the TNF .gamma. sig construct, which facilitates expression of the mature TNF polypeptide, and the noncleavable cytotoxic prohormone variants TNF.DELTA.(1.fwdarw.12) and TNF(1+12). The transformed TIL cells are useful in antitumor therapy.
Abstract: The present invention is directed to DNA, host cells and a vector encoding a protein with cytokine inhibitory activity, particularly IL-1 inhibitory activity. The protein encoded by the DNA of the present invention is particularly useful as an IL-1 antagonist.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
February 23, 1999
Assignee:
Chiron Corporation/Chapel Hill North Carolina
Inventors:
John Stephen Haskill, George Martin, Peter Ralph
Abstract: Medicaments and methods of using the same are disclosed for treating or preventing diseases resulting from undesirable cell adhesion of IL-1 receptor positive cells to biological materials, particular to endothelial cells, or autoimmune related diseases, preferably graft versus host disease, or IL-1 dependent cancers.
Abstract: Two new isolates of the Hepatitis C virus (HCV), J1 and J7, are disclosed. These new isolates comprise nucleotide and amino acid sequences which are distinct from the prototype HCV isolate, HCV1. Thus, J1 and J7 provide new polynucleotides and polypeptides for use, inter alia, in diagnostics, recombinant protein production and vaccine development.
Type:
Grant
Filed:
May 8, 1995
Date of Patent:
February 16, 1999
Assignees:
Chiron Corporation, The Director General of the National Institute of Health of Japan
Abstract: Methods for causing T cell anergy, treating allograft transplant rejection, treating graft versus host disease, and preventing or treating rheumatoid arthritis are presented, the methods comprising co-administration of a molecule that binds to the B7 antigen and an immunosuppressive agent.
Abstract: The present invention is directed to methods for crystallizing macrophage colony stimulating factor (M-CSF) and to a crystalline M-CSF produced thereby. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.
Type:
Grant
Filed:
May 25, 1995
Date of Patent:
February 2, 1999
Assignee:
Chiron Corporation
Inventors:
Jayvardhan Pandit, Jarmila Jancarik, Sung-Hou Kim, Kirston Koths, Robert Halenbeck, Anna Lisa Fear, Eric Taylor, Ralph Yamamoto, Andrew Bohm
Abstract: Protein aggregates obtained by a process comprising culturing a host cell that expresses a desired protein in a medium comprising an effective amount of Cu.sup.++ and wherein the desired protein forms inclusion bodies in the host cell.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
February 2, 1999
Assignee:
Chiron Corporation
Inventors:
Lawrence S. Cousens, Patricia Tekamp-Olson
Abstract: Chimeric proteins containing sequences from MCP and DAF and further containing peptide sequences capable of binding glycosaminoglycans. Nucleotide sequences encoding the chimeric proteins, expression vectors containing the nucleotide sequences, as well as transformed host cells capable of producing the chimeric proteins are claimed.
Type:
Grant
Filed:
May 5, 1995
Date of Patent:
February 2, 1999
Assignee:
Chiron Corporation
Inventors:
Michael A. Innis, Isabel Zaror, Abla A. Creasey
Abstract: The present invention relates to a keratinocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGF.sub.des1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF.sub.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
January 26, 1999
Assignee:
Chiron Corporation
Inventors:
Denis J. Gospodarowicz, Frank R. Masiarz
Abstract: Compositions and methods are provided for endopeptidases and their production, and for enhanced efficiencies of processing heterologous precursor polypeptides to mature polypeptides. These compositions and methods utilize recombinant PACE 4 and 4.1, mammalian endopeptidases that are specific for dibasic amino acid sites. Therapeutic compositions and methods employing PACE 4 or 4.1 or their inhibitors are also provided.
Abstract: A method of inhibiting proteolytic degradation of a thermally-stable intracellular protein is described. The method involves adding 1 or more denaturing agents to a sample which contains the protease and the protein of interest and heating the resulting solution at a temperature and for period of time sufficient to denature the protease. The method optionally includes a step for lysing the cell if the protein of interest is contained in a cell in order to release said protein. Additionally, a method of determining Mx protein induced by interferon in a blood sample is described. The method involves adding to a blood sample a lysing agent, a denaturing agent, and a detergent selected to solubilize Mx protein. The sample containing Mx protein is then heated at a temperature of from about 50.degree. C. to about 60.degree. C. for a period of time of from about 1 minute to about 30 minutes, and the Mx protein in the solution then is determined.
Abstract: A polymeric sensing membrane having a Stern-Volmer constant within a pre-determined range of Stern-Volmer constants. The membrane includes a polymeric material having a fluorescent dye molecule dispersed therein. The dye molecule is capable of having its fluorescence collisionally quenched by a gas to be detected by the membrane. In one embodiment, the membrane includes a fluorescent dye molecule which has a relaxation time and a polymeric material having a permeability within a range of permeabilities defined by a mathematical function of the pre-determined range of Stern-Volmer constants. In another embodiment, the membrane includes a polymeric having a permeability and a fluorescent dye molecule having a relaxation time within a range of relaxation times defined by a mathematical function of the pre-determined range of Stern-Volmer constants.
Abstract: A new virus, Hepatitis C virus (HCV), which has proven to be the major etiologic agent of blood-borne NANBH, was discovered by Applicant. Reagents for isolating, amplifying, and detecting HCV polynucleotides are provided. These reagents are oligomers containing polynucleotide sequences which are capable of forming hybrid structures with HCV target polynucleotide sequences.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
January 26, 1999
Assignee:
Chiron Corporation
Inventors:
Michael Houghton, Qui-Lim Choo, George Kuo
Abstract: A virion expression system for a desired protein packaged in an envelope derived from a retrovirus useful in administering proteins which cross cell membranes in order to serve their function. Preferred virions are those that carry an RNA sequence that encodes cytokines or lymphokines, and includes IL-2, multiple drug resistance protein, and TNF.
Abstract: Composition, comprising in homogeneous distribution A) at least one salt containing a lipophilic anion, B) a plasticiser-free thermoplastic randomly segmented polyurethane which is soluble in organic solvents, a polyurea or a polyurethane urea, which components are formed from a) 5-45% by weight of an aromatic, cycloaliphatic or linear aliphatic dilsocyanate, b) 0-20% by weight of a linear or branched C2-C12alkylenediol or C2-C12alkylenediamine, c) 0-75% by weight of a polytetrahydrofuran or aminopropyl-terminated polytetrahydrofuran, d) 0-10% by weight of a polyethylene glycol or aminopropyl-terminated polyethylene glycol, e) 0-75% by weight of a polypropylene glycol or aminopropyl-terminated polypropylene glycol, which composition contains f) 15-95% by weight of a hydroxy-, hydroxypropyl- or aminopropyl-terminated polydimethylsiloxane, the percentages relating to the amount of polymer, and the sum of components a) to f) being 100, and C) a nonionic ionophore which forms a complex with Ca++ ions.
Abstract: Methods for solid phase synthesis of N-alkyl amides comprise reductive amination of carbonyl compounds using a reducing agent and an amine-containing linker bound to a solid support. The methods afford high yields of linker-bound, monoalkylated amines, and subsequent coupling with acid derivatives provide derivatized N-substituted amides in excellent yields after cleavage from the solid-phase. Compositions useful in solid phase synthesis are also described.
Abstract: The present invention is directed to a biologically active CSF-1 dimer comprising a first CSF-1 monomer and a second CSF-1 monomer, wherein at least one of the monomers is truncated at the C-terminus after residue position 223. The dimers also include point mutations in one or both of the CSF-1 monomer. The invention also includes pharmaceutical compositions that comprise the CSF-1 dimer in a pharmaceutical excipient.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
January 19, 1999
Assignee:
Chiron Corporation
Inventors:
Robert Halenbeck, Kirston Koths, Cynthia Cowgill, Walter J. Laird
Abstract: Host cells may be treated for an infection or a hyperproliferative disorder which is characterized by the presence, in the affected cells, of a trans-acting factor capable of regulating gene expression by inserting into the cells a polynucleotide construct having a cis-acting regulatory sequence which is regulated by the trans-acting factor and an effector gene which renders said cell susceptible to protection or destruction. For example, the cis-acting region may be homologous to the HIV tar region, and the effector gene may encode ricin A or HSV-1 thymidine kinase. Upon infection with HIV, the HIV tat protein activates the tar region, and induces transcription and expression of ricin A, resulting in cell death, or of HSV-1 tk, resulting in cell death upon treatment with dideoxynucleoside agents such as acyclovir and gancyclovir.