Production and characterization of factor VIII produced by recombinant DNA technology

CONGRESS

ABSTRACTS OF 12TH NATIONAL

Vol. 70,Suppl. 1

s15 THROFiBOLYTIC AND FIBRINOLYTIC THERAPIES: CRITERIA FOR A DIFFERENTATION. F. Laghi Pasini lnSti.tUte of CliniCal Medicine - University of SIENA - ITALY Thrombolytic therapy consists on the administration of pharmacologic agent able to induce lysis of arterial or venous preformed thrombi, by directly converting plasminogen to plasmin. Thrombolytic drugs represent the main treatment of A.M.I., and are also widely employed in the therapy of pulmonary embolism, D.V.T., ischaemic cerebral infarction, P.D.A.D. Conversely, profibrinolytic therapy employes a series of molecules able to enhance endogenous fibrinolytic activity, by tPA release from inducing endothelial cells. Such a therapeutic approach is mainly used for the antithrombotic prophylaxis of those conditions characterized by a poor spontaneous fibrinolysis. Such treatments, while being well defined in terms of therapeutic goals, can be distinguiseed from the pharmacologic point of view on the basis of the different effects produced on circulating cells (platelets, neutrophils, R.B.C.), blood rheology, endothelial cell function. The systemic lytic state induced by thrombolytic treatment, supports a long-lasting procoagulant activity by means of series of mechanisms, not completely identified as yet. Such mechanisms may becorrected by the combined administration of drugs aimed to prevent rethrombosis. Profibrinolytic agents, namely heparansulphates and defibrotide, do not induce high plasmin activity,and they modulate interactions among endothelial cells, platelets, and neutrophils, shifting their functional expression towards antithrombotic activity.

S 16 PROOUCTIOlAID CHARACTERIZATION TECHNOLOGY.

RichardSchuartz,

Advances

in

cDNA encoding active

FVIII

from

As a result inferred

of

complete

biology

of

advantages of

there

over

has

deep

exchange, highly

of

of a

haoster

are of

a

nou

Kogenate

in

R

uill

into

in

1984

of

DNA

of

cell

the

gene

HIV or

cells

transfected

resultant

degree

of

a

with

product

of

large

has

prior

progress. be discussed

to

The in

no

scale

method continuous

human FVIII

steps

a

gene

including

ion in

a

extensive

undergone

caamenceaent

to

multistep

resulting

manufacturing detail.

and

As such

from

ckomatography

Kogenate

years.

important

purity

undergoes

chromatography

ioounoaffinity

the

line.

?? olecular

viruses.

manufactured

the

and the

eight

several

hepatitis

developing is

past

offers

a high

as

the

of

functionally

a xamualian

in

(rFVII1)

(rFVII1)

testing

in

cloning

dramatically

including

preparation.

pre-clinical

the

FVIII. understanding of the

such

series

and

rFVII1 and

The

using

exclusion,

purified

which

kidney

fermenters.

process size

characterization

of

inkerest

Kogenate

RECONBINANT

expression

characterization

DNA technology FVIII

to the

transfected from

sequence

human viruses

strong

baby

tank

characterization studies,

acid

plasma-derived

rFVII1.

purification

derived

recombinant

been

cultivation in

by

transaission

manufacture

led

FYI11moleculehas expanded

the

FVIIIproduced risk

DNA clones

information

BY

CA, USA.

VIII (FVIII)and

Factor

amino

Inc.,

VIII PRODUCED

DNA technology

recoabinant

the

FACTOR

Wiles

recombinant

human

OF

of

clinical

process

and