Cell Genesys, Inc.

Genentech, Inc.

Stephen A Sherwin

Sue Klapholz

Arthur I Skoultchi

Robert B Dubridge

Michael A Palladino

Expression of mammalian target genes is achieved by employing chromosomal target DNA, either native primary cells or YACs in a yeast host, where the YACs include a fragment of a mammalian chromosome, the fragment comprising the target gene. Employing homologous recombination, an amplifiable gene is integrated into the mammalian fragment at a site to allow for amplification. In the same step, or one or more steps, as desired, the mammalian gene and/or the transcriptional system may be modified by in vivo mutagenesis. The resulting construct from homologous recombination may then be transformed into a mammalian expression host and integrated into the host genome, either randomly or by homologous recombination. The amplifiable gene may then be amplified by an appropriate agent providing for multiple copies of the target gene and the expression host grown to provide for high yields of the desired wild-type or modified protein.

Gene manipulation and expression using genomic elements

Novel regimens are provided for administering foreign genetically modified allogeneic cells to a host by combining the administration of the cells with a reduced regimen of an immunosuppressive agent. Particularly, cells having a reduced level of Class I MHC antigens may be employed in a variety of cellular therapy situations, where foreign cells are engrafted to treat diseased states.

Combined cellular and immunosuppressive therapies

Methods and compositions are provided for the treatment or prophylaxis of septic shock caused by bacteremic infection. Therapeutically and prophylactically effective doses of transforming growth factor-beta are administered to patients, either alone or in combination with another therapeutic or prophylactic agent for treating this pathologic condition. Preferably, the transforming growth factor-beta is human transforming growth factor-beta, and most preferably TGF-.beta..sub.1, TGF-.beta..sub.2, or TGF-.beta..sub.3.

Method and compositions for the treatment and prevention of septic shock

Gamma interferon is employed in the treatment of chronic myelogenous leukemia. Patients treated in the benign stage exhibit partial and, in some cases, complete responses to gamma interferon. Successful results have also been obtained with some patients in the blast stage of the disease as well as patients who had been found to be refractory to treatment with alpha interferon.

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San Francisco, CA, United States of America

Stephen A Sherwin