Ciba-Geigy Corporation

Novartis Corporation

Other

Albert Schmitz

Bernd Meyhack

Nico Cerletti

Walter Marki

Gino Van Heeke

Jan Van Oostrum

David Cox

Gary Kent McMaster

William C Boyar

Nicholas G Galakatos

Hans Rink

Markus G Grutter

Hans Hofstetter

Derek E Brundish

Bruno Suri

John Peter Priestle

Erich Kilchherr

The invention relates to a process for the production of biologically active, dimeric TGF-.beta., to novel TGF-.beta.s and pharmaceutical compositions comprising it. TGF-.beta. produced by this process can be used in various therapeutic modalities.

Process for refolding recombinantly produced TGF-.beta.-like proteins

Disclosed are polypeptide analogues of human C5a which are C5a receptor antagonists that exhibit substantially no analphylatoxin or agonist activity, and derivatives of the analogues, and dimeric forms of the analogues or derivatives. DNA molecules encoding the polypeptides and methods of making the analogues are also provided. Pharmaceutical formulations containing a C5a analogue, are used therapeutically in the treatment of C5a-mediated diseases and inflammatory conditions in mammals, and prophylactically to prevent or reduce inflammation caused by an event which causes inflammation or aggravates an existing inflammatory condition, respectively. Further disclosed are antibodies specific to the C5a analogues, derivatives thereof, and dimers of the analogues and derivatives which exhibit substantially no cross-reactivity with human C5a. The antibodies are used to detect or quantify circulating C5a analogue or derivative, as well as to modify, e.g., neutralize, the activity of the C5a receptor antagonist in vivo.

DNA encoding C5A receptor antagonists having substantially no agonist

C5A receptor antagonists having substantially no agonist activity

A process for the preparation of a recombinant IGF-II (rIGF-II) without a covalently attached foreign protein moiety and without N-terminal attached methionine or a derivative of methionine or of a salt of said IGF-II, rIGF-II produced by said method, hybrid vectors comprising DNA encoding said rIGF-II, hosts transformed with said vectors, and a process for the isolation of said rIGF-II from the host cell and refolding it into a biologically active form.

Process for the production and refolding of unfused IGF-II protein in E.

Peptide derivatives corresponding to the carboxy terminal sequence of

The process for the production of a dimeric, biologically active Transforming Growth Factor type .beta. (TGF-.beta.)-like protein or a salt thereof, comprising refolding the denatured monomeric form of the protein in the presence of a mild detergent that permits folding of the monomeric protein into a spatial conformation, which after dimerization, is the conformation associated with the biological activity, while retaining the monomeric protein in soluble form. Mild detergents include sulfobetaines, 3-(3-chlolamidopropyl)dimethylammonio-1-propanesulfonate, 3-(3-chlolamidopropyl)dimethylammonio-2-hydroxy-1-propane-sulfonate, digitonin, cholate and deoxycholate at a concentration of about 1 to 100 mM. Compositions containing a TGF-.beta.-like protein produced according the invention can be used for the promotion and acceleration of wound healing and bone and tissue repair, cancer treatment, bone marrow protective agent, as a mediator of cardio-protection, as an anti-inflammatory or immunosuppressive agent, or as a growth regulator in mammalian cell cultures.

The invention relates to the field of genetic engineering and provides novel DNA molecules which comprise multifunctional origins of replication and/or a DNA sequence coding for the most abundant protein in the supernatant of cultures of Lactococcus Spec., named Major Secretion Product (MSP), for its signal peptide and/or the promoter of the MSP gene. The novel DNA molecules are used for the production of novel shuttle vectors for cloning of DNA in at least E. coli and Lactococcus spec. or novel vectors for the expression of homologous or heterologous genes and the production of secreted gene products in gram positive bacteria such as Lactococcus spec. and Bacillus Spec.

Bacterial shuttle vectors

Process for the production of unfused IGF-II protein in E. coli

The invention concerns polypeptides related to human immunoglobulin E binding factors (IgE-Bfs), mRNa, DNAs and hybrid vectors coding for said polypeptides, hosts containing said hydrid vectors, processes for the preparation of said polypepties, mRNAs, DNAs, hybrid vectors, and hosts. The polypeptides can be used for the prevention and/or the treatment of allergic diseases, and accordingly the invention concerns also pharmaceutical preparations containing them.

Preparation of transformed hosts which express binding factor related

Growing community of inventors

Basel, Switzerland

Albert Schmitz