(19) United States (12) Reissued Patent

(45) Date of Reissued Patent:

Emanuele et al. (54) POLYOXYPROPYLENE/

4,764,567 4,801,452 4,837,014 4,837,083 4,873,083 4,879,109 4,897,263 4,937,070 4,997,644 5,017,370 5,028,599 5,030,448 5,032,394 5,039,520 5,041,288


(75) Inventors: R. Martin Emanuele, Alpharetta, GA (US); Robert L. Hunter, Bellaire, TX

(US); Paula H. Culbreth, Loganville, GA (US)

(73) Assignee: CytRX Corporation, Los Angeles, CA

(Us) (21) Appl. No.: 09/460,298 (22) Filed:

Dec. 9, 1999




Dec. 9, 1997

Appl. No.:



Jun. 2, 1995

Division of application No. 08/087,136, ?led on Jul. 2, 1993, now Pat. No. 5,523,492, which is a continuation of appli cation No. 07/847,874, ?led on Mar. 13, 1992, now aban

doned, which is a continuation-in-part of application No. 07/673,289, ?led on Mar. 19, 1991, now abandoned.


Int. Cl? ....................... .. c07c 43/02; c07c 43/04;


US. Cl. ...................................... .. 568/623; 568/624


Field of Search ..

covc 43/11



4/1954 9/1958 4/1961 5/1962 5/1963

Lundsted Buckwalter et al. Lundsted Jackson Stone

3,140,232 A

7/1964 Noseworthy

3,228,834 A 3,391,196 A

1/1966 Gans 7/1968 Earing et al.

3,450,502 A 3,577,522 A 3,590,125 A

6/1969 Hymes 5/1971 Hymes 6/1971 Hymes

3,641,240 3,740,421 3,867,521 3,867,533 3,956,259 3,980,772 4,073,886 4,100,271 4,104,455 RE29,909 4,179,337 4,186,253 4,195,167


4,275,244 A

2/1972 6/1973 2/1975 2/1975 5/1976 9/1976 2/1978 7/1978 8/1978 2/1979 12/1979 1/1980 3/1980

Ott Hunter Hunter Hunter Hunter Hunter Hunter Hunter Hunte Hunter Hunter Hunter Hunter Hunter Hunter

et et et et

al. al. al. al.

et al.


0000704 0003399 0049422 0098110

33193/70 5094 206763/88 1183112 WO 87/06831 WO 87/06836 WO 88/06038 WO 90/07336

A1 A3 A3 A3

2/1979 9/1979 4/1982 1/1984

10/1970 1/1979 8/1988 10/1985 11/1987 11/1987 8/1988 7/1990


....... .. 568/623, 624

References Cited

2,674,619 2,854,378 2,979,528 3,036,118 3,089,818

8/1988 1/1989 6/1989 6/1989 10/1989 11/1989 1/1990 6/1990 3/1991 5/1991 7/1991 7/1991 7/1991 8/1991 8/1991


Reissue of:



Jul. 20, 2004

(List continued on neXt page.)

Related US. Patent Documents

(64) Patent No.:

US RE38,558 E

(10) Patent Number:

Hymes et al. Schmolka Miskel et al. Schmolka Garcia et al. Ginger et al. Kehm Krezanoski Nagasawa et al. KurtZ Davis et al. Yokoyama et al. Knopf et al.

6/ 1981 Helfert et al.

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229—236 (1985). (List continued on neXt page.)

Primary Examiner—Paul F. Shaver

(74) Attorney, Agent, or Firm—Andy Arismendi, Jr.



The present invention comprises novel preparations of

polyoXypropylene/polyoXyethylene copolymers which retain the therapeutic activity of the commercial preparations, but are substantially free from the undesirable effects which are inherent in the prior art preparations.

Because the preparations of polyoXypropylene/

polyoXyethylene copolymers which comprise the present

4,305,922 A 4,378,347 A 4,395,393 A

12/1981 Rhodes 3/1983 Franco 7/1983 Schmolka

invention are a less polydisperse population of molecules

4,407,790 4,600,652 4,606,918 4,609,546

10/1983 Oakes et al. 7/1986 Solomon et al. 8/1986 Allison et al.

better de?ned and more predictable.


9/ 1986 Hiratani

than the prior art polyoXypropylene/polyoXyethylene

copolymers, the biological activity of the copolymers is 16 Claims, 20 Drawing Sheets

US RE38,558 E Page 2

5,047,236 5,057,540 5,064,643 5,071,649 5,078,995 5,080,894 5,089,260 5,114,708 5,183,687 5,198,211 5,250,294 5,294,365 5,340,916


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Viscosity”, Arch. Surg., vol. 106, pp. 307—310 (1973). Grover, F.L., et al., “The Effect of Pluronic® F—68 On

Circulatory Dynamics And Renal And Carotid Artery FloW

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* cited by examiner

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U.S. Patent

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Polyoxypropylene/polyoxyethylene copolymers with improved ...

Dec 9, 1999 - tionation”, Transfusion, vol. 28, pp. 375—378 (1987). Lane, T.A., et al., Paralysis of phagocyte migration due to an arti?cial blood substitute, Blood, vol. 64, pp. 400—405. (1984). Spiess, B.D., et al., “Protection from cerebral air emboli. With per?uorocarbons in rabbits”, Stroke, vol. 17, pp. 1146—1149 (1986).

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