Recombinant proteins containing shiga-like toxin and vascular endothelial growth factor fragments

• US 20090023649A1
• Filed: 08/14/2007
• Published: 01/22/2009
• Est. Priority Date: 03/22/2000
• Status: Active Grant

• Current Assignee: Sibtech Incorporated
• Original Assignee: Sibtech Incorporated
• Inventors: Backer, Marina V., Backer, Joseph M.
• Granted Patent: US 7,700,557 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 14/245 Escherichia (G)
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The present invention is directed to an isolated polypeptide including: (1) the A subunit of Shiga-like bacterial toxin, wherein said subunit has the nucleic acid sequence of SEQ ID NO:9; and (2) human vascular endothelial growth factor wherein the growth factor has the nucleic acid sequence of SEQ ID NO:10; wherein the isolated polypeptide possesses ribosome inactivating activity. The present invention is also directed to compositions for inhibiting endothelial cell growth in a patient.

Claims

1. An isolated polypeptide comprising:

(1) the A subunit of Shiga-like bacterial toxin, wherein said subunit has the nucleic acid sequence of SEQ ID NO;

9; and

(2) human vascular endothelial growth factor, wherein said growth factor has the nucleic acid sequence of SEQ ID NO;

10;

wherein said isolated polypeptide possesses ribosome inactivating activity.

2. The isolated polypeptide of claim 1, wherein said isolated polypeptide specifically binds vascular endothelial growth factor receptors.

3. The isolated polypeptide of claim 2, wherein said isolated polypeptide is internalized by a cell which expresses said receptors.

4. The isolated polypeptide of claim 1, wherein said internalization occurs by endocytosis.

5. The isolated polypeptide of claim 1, wherein said isolated polypeptide is encoded by the nucleic acid of SEQ ID NO:

11.

6. A composition for inhibiting endothelial cell growth in a patient, comprising:

(A) a fusion protein comprising the A subunit of Shiga-like bacterial toxin; and

human vascular endothelial growth factor, said fusion protein possessing ribosome inactivating activity; and

(B) a pharmaceutically acceptable carrier;

wherein said A subunit of said Shiga-like bacterial toxin, is encoded by the nucleic acid sequence of SEQ ID NO;

9, and wherein said human vascular endothelial growth factor is encoded by the nucleic acid sequence of SEQ ID NO;

11.

7. A fusion protein encoded by a nucleic acid sequence comprising SEQ ID NO:

9 and SEQ ID NO;

11.

8. A fusion protein encoded by a nucleic acid having the nucleic acid sequence of SEQ ID NO:

11.