Process for encapsulating biologics using crosslinkable biocompatible ...

[54] PROCESS FOR ENCAPSULATING

BIOLOGICS USING CROSSLINKABLE
BIOCOMPATIBLE ENCAPSULATION
SYSTEM

4,592,998 6/1986 Avrameas et al 435/28

4,663,286 5/1987 Tsang 435/178

4,744,933 5/1988 Rha 264/43

4,749,620 6/1988 Rha 423/402

4,791,061 12/1988 Sumino 435/178

4,798,786 1/1989 Tice 435/177

4,824,916 4/1989 Kershner et al 525/420

5,041,292 8/1991 Feijen 424/484

[75] Inventors: Neil P. Desai; Patrick Soon-Shiong;

Paul A. Sandford; Roswitha E.
Heintz, all of Los Angeles, Calif.

[73] Assignee: VivoRx, Inc., Santa Monica, Calif.

[21] Appl. No.: 258,769
[22] Filed: Jun. 13,1994

Related U.S. Application Data

[62] Division of Ser. No. 866,038, Apr. 8, 1992, Pat. No. 5,334, 640.

[51] Int. CI.6 C08K 5/15; C08L 5/00;

A61K9/14; C12N 11/02

[52] U.S. CI 524/56; 524/54; 524/28;

424/488; 424/499; 435/177; 435/178

[58] Field of Search 524/56, 54, 28;

424/488, 499; 435/177, 178

[56] References Cited

U.S. PATENT DOCUMENTS

4,177,038 12/1979 Biebricher 81/192

4,352,883 10/1982 Lim 435/178

4,391,909 7/1983 Lim 435/178

4,409,331 10/1983 Lim 435/178

FOREIGN PATENT DOCUMENTS

2237574 5/1991 United Kingdom .

9107591 6/1991 WIPO.

9109119 6/1991 WIPO .

9111205 8/1991 WIPO .

Primary Examiner—Paul R. Michl

Assistant Examiner—LaVonda R. DeWitt

Attorney, Agent, or Firm—Pretty, Schroeder, Brueggemann

& Clark; Stephen E. Reiter

[57] ABSTRACT

Crosslinked biocompatible compositions comprising an ionically crosslinked component and a covalently crosslinked component for encapsulating biologies are disclosed. In accordance with the present invention, also disclosed are crosslinkable biocompatible mixtures comprising an ionically crosslinkable component and a covalently crosslinkable component. Methods for encapsulating biologics with the crosslinked and cross-linkable biocompatible compositions are provided. Also, retrievable macrocapsules for encapsulating microcapsules or biologies are disclosed.

40 Claims, 8 Drawing Sheets