(19)

(11)

EP 0 456 640 A1

(12)

(43) Date of publication: 21.11.1991 Bulletin 1991/47 (21) Application number: 90900691.0 (22) Date of filing: 08.12.1989

(51) International Patent Classification (IPC):  A61K 48/ 00( . ) C12N 15/ 09( . ) C12P 21/ 02( . ) A61F 2/ 06( . ) C12N 5/ 10( . ) C12N 15/ 867( . ) A61F 2/ 00( . ) (86) International application number: PCT/US1989/005575 (87) International publication number: WO 1990/006997 (28.06.1990 Gazette 1990/15)

(84) Designated Contracting States: AT BE CH DE ES FR GB IT LI LU NL SE (30) Priority: 13.12.1988 US 19880283586 (71) Applicants: UNITED STATES GOVERNMENT as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES Bethesda, MD 20892 (US) UNIVERSITY OF MIAMI Miami, Florida 33101 (US)

(72) Inventors: ANDERSON, W., French Bethesda, MD 20817 (US) FREEMAN, Scott, M. Rockville, MD 20854 (US) ZWEIBEL, James, A. Bethesda, MD 20817 (US) ANTHONY, Thompson, J. Myersville, MD 21773 (US) RYAN, Una, S. Miami, FL 33133 (US) KANTOFF, Philip Needham, MA 02912 (US) DICHEK, David Rockville, MD 20854 (US) (74) Representative: LOUIS, PÖHLAU, LOHRENTZ & SEGETH  Postfach 3055 D-90014 Nürnberg D-90014 Nürnberg (DE)