Claims for Patent: 7,790,870

Summary for Patent: 7,790,870

Title:	Membrane-anchored GP41 peptides that inhibit subsequent HIV viral entry
Abstract:	The invention relates to the genetically engineered treatment of an HIV infection by the expression of membrane-anchored gp41 peptides. With this treatment vectors are made available for the first time which code for a fusion protein that contains a peptide derived from gp41 of HIV and a carboxy terminal by means of a trans-membrane anchor tagged to a flexible linker.
Inventor(s):	von Laer; Meike-Dorothee (Hamburg, DE)
Assignee:	Heinrich-Pette-Institut (Hamburg, DE)
Application Number:	10/148,064
Patent Claims:	1. A nucleic acid molecule encoding a fusion protein comprising four linked polypeptides comprising: (a) a first sequence encoding a membrane translocation signal peptide; (b) a second sequence encoding a section of a gp41 protein comprising at least 28 amino acids of a heptad repeat region; (c) a third sequence encoding a transmembrane anchor of a type 1 membrane protein; and (d) a hinge sequence that connects said second sequence and said third sequence, wherein said hinge sequence encodes a flexible linker from a protein selected from the group consisting of immunoglobulin G (IgG), human P-glycoprotein, human replication protein A and parathyroid hormone-related protein. 2. The nucleic acid molecule of claim 1, wherein said signal peptide is a signal peptide from a protein selected from the group consisting of the low affinity nerve growth factor receptor (LNGFR), the interleukin-2 receptor (IL-2R), and the granulocyte macrophage colony-stimulating factor receptor (GM-CSFR). 3. The nucleic acid molecule of claim 2, wherein said transmembrane anchor is selected from a transmembrane anchor of a type 1 membrane protein is selected from the group consisting of LNGFR and CD34. 4. The nucleic acid molecule of claim 1, wherein said heptad repeat region is selected from the group consisting of the amino acid sequence from any HIV type corresponding to positions 539-589 or 622-662 of SEQ ID NO: 4. 5. The nucleic acid molecule of claim 4, wherein said HIV type is HIV-1. 6. A vector comprising the nucleic acid molecule of claim 1. 7. The vector of claim 6, wherein said vector is a retroviral vector. 8. The nucleic acid molecule of claim 1, wherein said second sequence encodes a maximum length of 40 amino acids and said hinge sequence encodes a maximum length of 30 amino acids. 9. The nucleic acid molecule of claim 1, wherein (a) said signal peptide from a protein is selected from the group consisting of the low affinity nerve growth factor receptor (LNGFR), the interleukin-2 receptor (IL-2R), and the granulocyte macrophage colony-stimulating factor receptor (GM-CSFR); (b) said heptad repeat region is selected from the group consisting of the amino acid sequence from any HIV type corresponding to positions 539-589 or 622-662 of SEQ ID NO: 4; and (c) said transmembrane anchor is selected from a transmembrane anchor of a type 1 membrane protein selected from the group consisting of LNGFR and CD34. 10. The nucleic acid molecule of claim 1, wherein said heptad repeat region is selected from the amino acid sequence from any HIV type corresponding to positions 622-662 of SEQ ID NO: 4. 11. The nucleic acid molecule of claim 1, wherein (a) said signal peptide is low affinity nerve growth factor receptor (LNGFR); (b) said heptad repeat region is selected from the group consisting of the amino acid sequence from any HIV type corresponding to positions 622-662 of SEQ ID NO: 4; (c) said transmembrane anchor is CD34; and (d) wherein said hinge sequence encodes a immunoglobulin G (IgG) flexible linker. 12. A vector comprising SEQ ID NO: 1. 13. The vector of claim 12, deposited with the German Collection of Microorganisms and Cell Cultures under the number DSM 13139. 14. A nucleic acid molecule encoding SEQ ID NO: 2. 15. A fusion protein with three linked amino acid sequences comprising: (a) a section of a gp41 protein of HIV comprising at least 28 amino acids from a heptad repeat region; (b) a transmembrane anchor of a type 1 membrane protein; and (c) a flexible linker that connects said section of a gp41 protein of HIV and said trans-membrane anchor of a type 1 membrane protein, wherein said flexible linker is from a protein selected from the group consisting of immunoglobulin G (IgG), human P-glycoprotein, human replication protein A and parathyroid hormone-related protein; wherein said fusion protein, when expressed on the surface of a mammalian cell, inhibits subsequent HIV viral entry. 16. The fusion protein of claim 15, wherein said heptad repeat region is selected from the group consisting of the amino acid sequences from any HIV type corresponding to positions 539-589 or 622-662 of SEQ ID NO: 4. 17. The fusion protein of claim 15, wherein said heptad repeat region corresponds to positions 622-662 of SEQ ID NO: 4. 18. The fusion protein of claim 15, wherein said heptad repeat region corresponds to positions 31-66 of SEQ ID NO: 2. 19. A nucleic acid molecule encoding a fusion protein comprising four linked polypeptides comprising: (a) a first sequence encoding a membrane translocation signal peptide; (b) a second sequence encoding a section of a gp41 protein comprising at least 28 amino acids from any HIV type corresponding to positions 31 to 66 of SEQ ID NO: 2; (c) a third sequence encoding a transmembrane anchor of a type 1 membrane protein; and (d) a hinge sequence that connects said second sequence and said third sequence, wherein said hinge sequence encodes a flexible linker from a protein selected from the group consisting of immunoglobulin G (IgG), human P-glycoprotein, human replication protein A and parathyroid hormone-related protein; and wherein the expressed fusion protein inhibits subsequent HIV viral entry. 20. The nucleic acid molecule of claim 19, wherein (a) said signal peptide is low affinity nerve growth factor receptor (LNGFR); (b) said transmembrane anchor is CD34; and (c) wherein said hinge sequence encodes a immunoglobulin G (IgG) flexible linker.

Details for Patent 7,790,870

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2019-11-25
Octapharma Pharmazeutika Produktionsges.m.b.h.	CUTAQUIG	immune globulin subcutaneous (human)-hipp	Solution	125668	12/12/2018		2019-11-25