Non-neurotoxic plasminogen activating factors for treating of stroke

Inactive Publication Date: 2006-06-29
PAION GMBH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0045] An increase of the fibrin dependency of plasminogen activators can also be achieved by the introduction of point mutations in the so called “autolysis loop”. This element is known from trypsine; it can also be found as a homologous region in serine proteases and is especially characterized by three hydrophobic amino acids (Leu, Pro and Phe). The autolysis loop in plasminogen activators is responsible for the interaction with plasminogen. Point mutations in this area can have the effect that the protein-protein in

Problems solved by technology

Once in the brain, it activates t-PA that indirectly activates the g

Method used

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  • Non-neurotoxic plasminogen activating factors for treating of stroke
  • Non-neurotoxic plasminogen activating factors for treating of stroke
  • Non-neurotoxic plasminogen activating factors for treating of stroke

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Embodiment Construction

[0056] In a preferred embodiment t-PA is used showing point mutations in the positions 420 to 423. If these residues are substituted by directed mutagenesis the fibrin dependency of t-PA is increased by a factor up to 61,000 (K Song-Hua et al.). Song-Hua et al. examined the point mutations L420A, L420E, S421G, S421E, P422A, P422G, P422E, F423A and F423E. These publications are fully incorporated by reference for disclosure of the use according to the invention.

[0057] According to a further advantageous embodiment a modified tissue plasminogen activator with an amino acid sequence according to SEQ ID No. 1 (FIG. 10) is used. This modified t-PA differs from the wild type t-PA by the exchange of the hydrophobic amino acids in the position 420 to 423 in the autolysis loop as follows: His420, Asp421, Ala422 and Cys423. This t-PA preferentially contains a phenyl alanine at the position 194. Further the position 275 can be occupied by glutamate. Advantageously the position 194 is occupied...

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Abstract

The invention pertains to the use and production of non-neurotoxic plasminogen activating factors e.g. of Desmodus rotundus (DSPA) for the therapeutic treatment of stroke in humans in order to provide a new therapeutic concept for treating stroke in humans.

Description

RELATED APPLICATION [0001] This is a continuation of application Ser. No. 10 / 184,01 filed Jun. 28, 2002, which claims the benefit of priority to German Patent Application No. 101 53 601.1, filed on Nov. 2, 2001, and European Patent Application No. 01 130 006.8 filed on Dec. 17, 2001, all of which are incorporated herein by reference.FIELD OF THE INVENTION [0002] The invention pertains to the therapeutic use of non-neurotoxic plasminogen activators especially from the saliva of Desmodus rotundus (DSPA) preferentially for the treatment of stroke. BACKGROUND OF THE INVENTION [0003] The term “stroke” is a general term that covers conditions having different clinical symptoms. For example, a stroke may be caused by an ischaemic or haemorrhagic insult. [0004] Ischaemic insults (ischaemia) are characterized in a reduction or interruption of the blood circulation in the brain due to a lack of arterial blood supply. Often this is caused by thrombosis of an arteriosclerotic stenosed vessel or...

Claims

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Application Information

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IPC IPC(8): A61K38/18A61K38/00A61K38/46A61K38/49A61P7/02A61P9/00A61P9/10C07K14/47C12N9/72
CPCA61K38/49C12N9/6459C12Y304/21069A61K31/7068A61K45/06C12Y304/21068A61P25/00A61P25/28A61P29/00A61P31/00A61P43/00A61P7/02A61P9/00A61P9/10A61K38/28
Inventor MEDCALF, ROBERT
Owner PAION GMBH
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