Ciba-geigy Corporation

Jan Van Oostrum

Jutta Heim

Bernd Meyhack

Albert Schmitz

Sefik Alkan

Bhabatosh Chaudhuri

Gino Van Heeke

Fredericus A Asselbergs

William C Boyar

Bhanu Rajput

Nicholas G Galakatos

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

Novel single-chain hybrid plasminogen activators having an amino acid sequence composed of at least two subsequences corresponding in amino acid identity and number to subsequences of human t-PA and of human u-PA, and mutants thereof in which at least one of the N-glycosylation sites is modified such that glycosylation cannot take place at these sites exhibit valuable pharmacological properties. The hybrid plasminogen activators are produced by recombinant DNA technology.

Hybrid plasminogen activator

DNA molecules encoding hybrid proteins of tissue plasminogen activator

Growing community of inventors

Fluh, Switzerland

Jan Van Oostrum