05650492 is referenced by 65 patents and cites 4 patents.

Analysis of the culture media of p40-transfected COS cells indicated the presence of 40 kDa monomers and 80 kDa disulfide-linked homodimers. Examination of partially purified p40 recombinant proteins demonstrated that only the homodimer but not the monomer binds to the IL-12 receptor. Partially purified 80 kDa homodimer inhibited [.sup.125 I]IL-12 binding to PHA-activated human lymphoblasts with an IC.sub.50 of 80 ng/ml, which is similar to the IC.sub.50 value (20 ng/ml) for the human IL-12 heterodimer. Although neither the 40 kDa monomer nor the 80 kDa dimer could stimulate human PHA-blast proliferation, the 80 kDa dimer inhibited IL-12-induced proliferation in a dose-dependent manner with an IC.sub.50 of 1 .mu.g/ml. The IL-12 p40 subunit contains the essential epitopes for receptor binding, but they are only active when p40 is covalently associated with a second protein such as p35 or p40. When p40 is associated with the p35 subunit, the heterodimer acts as an agonist mediating biologic activity. When p40 associates with itself, the homodimer behaves as an antagonist.

Title
P-40 homodimer of interleukin-12
Application Number
87832
Publication Number
5650492
Application Date
April 18, 1995
Publication Date
July 22, 1997
Inventor
Ping Ling
Nutley
NJ, US
John Hakimi
Scarsdale
NY, US
Maurice Kent Gately
Pine Brook
NJ, US
Agent
Alan P Kass
Dennis P Tramaloni
George W Johnston
Assignee
Hoffmann La Roche
NJ, US
IPC
A61K 38/20
C07K 14/54
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