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US005328840A
United States Patent [191
[11]
Patent Number:
5,328,840
Coller
[45]
Date of Patent:
Jul. 12, 1994
Coller et al., 1990, “Thromboerythrocytes: preliminary
[54] METHOD FOR PREPARING TARGETED
CARRIER ERYTHROCYTES
[75]
in vitro attempts to develop a semi-arti?cial, autolo
gous platelet (P) substitute,” Circulation, Suppl. 111.,
Barry S. Coller, Dix Hills, N.Y.
Inventor:
[73] Assignee:
82(4), Abstract 2377.
Coller, 1980 “Interaction of normal, thrombasthenic,
and Bernard-Soulier platelets with immobilized ?brino
gen: defective platelet~?brinogen interaction in throm
basthenia,” Blood 55:169-178.
The Research Foundation of the State
University of New York, Albany,
N.Y.
[211 Appl. No.: 790,851
Nov. 12, 1991
[22] Filed:
Cumber et al., 1985, “Preparation of antibody-toxin
conjugates,” Meth. Enzymol. 112:207-225.
Primary Examiner-Robert J. Hill, Jr.
Related U.S. Application Data
[63]
Assistant Examiner-Gian P. Wang
Attorney, Agent, or Firm-Pennie & Edmonds
Continuation-impart of Ser. No. 611,164, Nov. 9, 1990,
abandoned, which is a continuation-in-part of Ser. No.
[57]
394,018, Aug. 15, 1989, abandoned.
[51]
Int. Cl.5 ..................... .. C12N 5/00; C12N 11/08;
[52]
U.S. Cl. ............................ .. 435/2402; 435/2401;
The present invention provides new compounds and
methods for promoting platelet aggregation, and con
trolling bleeding. The present invention is based on the
A6lK 37/02; A61K 37/00
surprising discovery that erythrocytes conjugated to
435/240.23; 435/240.243; 435/7021; 435/180;
certain peptides and polypeptides containing an R-G-D
(Arg-Gly-Asp) sequence (collectively termed herein
435/181; 514/2; 530/300; 530/350
[5 8]
Field of Search ........... .. 435/2401, 240.2, 240.23,
“RGD peptides”) according to the invention, selec
435/240.243, 4, 180, 181, 300, 70.21; 530/350,
351, 387, 388, 829, 810, 811, 812; 424/858;
tively bind to activated platelets but not to unactivated
platelets. In recognition of the dual nature of the deriva
tized erythrocytes, they are termed herein “thrombo
514/2
[56]
References Cited
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ABSTRACT
erythrocytes”. The thrombo-erythrocytes have no sig
ni?cant change in their rheological properties. In a
preferred aspect, the thrombo-erythrocytes have the
Rivier et al. .
Johnston et a1. .
majority of RGD peptide cross-linked speci?cally to
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Guillemin et a1. .
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erythrocyte. In the thrombo-erythrocytes of the inven
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Angstroms, from the erythrocyte protein to which the
RGD peptide is conjugated. The invention is further
directed to erthrocytes modified by replacement of
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Pierschbacher et a1. .
Ruoslahti et al. .
Ruoslahti et al. .
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Ruoslahti et a1. .
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20 Claims, 23 Drawing Sheets
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ER
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o
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Thromboerythrocytes (TE). A potential analogous
3142452-454.
US. Patent
July 12, 1994
100i
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