Appeal No. 2000-0827
Application 08/466,104
developed by Dr. Feinstein, which are not described as involving
encapsulation:
Dr. Feinstein . . . found that by sonication of a heat-
sensitive protein, such as albumin, microbubbles of
improved stability were obtained. (See Feinstein, PCT
Application WO 84/02838, corresponding to allowed U.S.
application Serial No. 805,975, filed December 5,
1985)[now Patent 4,718,433 (copy enclosed) 6].
Concentrations of microbubbles of 10 to 14 x 10 6
microbubbles per millimeter were obtained with bubble
sizes from 2 to 9 microns (Keller, Feinstein, and
Watson, 1987). The microbubbles persisted for 24 to 48
hours.
EPO application at 2, ll. 38-43. Furthermore, the EPO
application describes the Widder et al. contrast agents as
achieving encapsulation by following Feinstein's sonication step
with a second, different sonication step:
The imaging agents of this invention are
preferably produced from a heat-denaturable
biocompatible protein by a stepwise sonication
procedure. As with the Feinstein method, an aqueous
solution of protein is subjected to sonication to form
gas microbubbles while concurrently heating the
solution to insolubilize small portions of the protein.
However, the improved sonication procedure, which
results in the increased concentration of highly stable
microbubbles utilizes a novel sequential sonication.
In the initial sonication phase, the sonicator horn is
directly contacted with the solution (viz. by immersion
just below the upper surface of the solution). This
initial sonication is carried out without appreciable
foaming of the solution. In the next phase of the
sonication, foaming is promoted. The sonicator horn is
withdrawn to a position in the ambient atmosphere above
but proximate to the surface of the solution. Intense
6 The abstract of this patent explains that Feinstein used
human serum albumin.
- 17 -
Page: Previous 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Next
Last modified: November 3, 2007