Claims for Patent: 6,057,298

Summary for Patent: 6,057,298

Title:	Keratin K1 expression vectors and methods of use
Abstract:	A keratin K1 vector for expression of a nucleic acid sequence in an epidermal cell. The vector includes a 5\' flanking region which includes necessary sequences for expression of a nucleic acid cassette, a keratin K1 3\' flanking region which regulates expression of a nucleic acid sequence, predominantly in the epidermis, and a linker which connects the 5\' flanking region to a nucleic acid. The linker has a position for inserting a nucleic acid cassette. The linker does not contain the coding sequence of a gene that the linker is naturally associated with. That is, the linker is not the normal gene associated with the 5\' and 3\' regions.
Inventor(s):	Roop; Dennis R. (Houston, TX), Rothnagel; Joseph A. (Houston, TX), Greenhalgh; David A. (Houston, TX), Yuspa; Stuart H. (Bethesda, MD)
Assignee:	Baylor College of Medicine (Houston, TX) The United States of America as represented by the Department of Health (Washington, DC)
Application Number:	08/452,872
Patent Claims:	1. A method of treating skin cancer in a mammal comprising administering a K-1 keratin expression vector at or directly around the site of a skin cancer cell, wherein said vector comprises in operable association: a nucleic acid sequence encoding a functional p53 protein; a 5' flanking region from a mammalian gene including necessary sequences for expression of said nucleic acid sequence; a 3' flanking region from a mammalian K1 keratin gene which regulates expression predominantly in epidermal tissue; and a linker connecting said 5' flanking region to said nucleic acid sequence, said linker having a position in which said nucleic acid sequence is inserted, wherein expression of said p53 protein by said skin cancer cell results in inhibition of the cell's proliferation. 2. The method of claim 1, wherein said 5' flanking region includes a promoter, a 5' UTR and a first intron and intron/exon boundary in appropriate relationship for expression of said nucleic acid cassette. 3. The method of claim 1, wherein said 3' flanking region includes a 3' UTR and a 3' NCR containing the transcriptional termination region. 4. The method of claim 2, wherein said 5' flanking region is approximately 1.2 kb, said first intron/exon boundary is 1.0 kb, and said 3' flanking region is approximately 3.9 kb of said mammalian keratin K1 gene. 5. The method of claim 2, wherein said 5' flanking region is approximately 1.2 kb, said first intron and intron/exon boundary is 1.0 kb, and said 3' flanking region is approximately 4.3 kb of said mammalian keratin in K1 gene. 6. The method of claim 1, wherein said vector further comprises a modulator sequence in either the 5' flanking region or the 3' flanking region. 7. The method of claim 6, wherein said modulator sequence comprises sequences responsive to calcium, Vitamin D or its metabolite, Vitamin A or its metabolite, or progesterone. 8. The method of claim 6, wherein said 3' flanking region further includes an 18 KB EcoRV fragment from said mammalian keratin K1 gene. 9. The method of claim 2, wherein said 5' flanking region comprises nucleotides 1 to 1246 of Sequence ID No. 1; said 3' flanking region comprises nucleotides 6891 to 10747 of Sequence ID No. 1; and said linker comprises nucleotides 2351 to 2376 of Sequence ID No. 2. 10. The method of claim 2, wherein said 5' flanking region comprises nucleotides 1 to 46 of Sequence ID No. 1; said 3' flanking region comprises nucleotides 7895 to 7921 of Sequence ID No. 1; and said linker comprises nucleotides 2351 to 2376 of Sequence ID No. 2. 11. The method of claim 2, wherein said 5' flanking region comprises nucleotides 1 to 46 of Sequence ID No. 1; said 3' flanking region comprises nucleotides 7924 to 7948 of Sequence ID No. 1; and said linker comprises nucleotides 2351 to 2376 of Sequence ID No. 2. 12. The method of claim 1 wherein said skin cancer cell is a squamous epithelial cell. 13. The method of claim 12, wherein said squamous epithelial cells are selected from a group consisting of epidermis, oral mucosa, esophageal, vaginal, tracheal or corneal epithelia. 14. The method of claim 12, wherein said 5' flanking region includes a promoter, 5' UTR, and a first intron and intron/exon boundary in appropriate relationship for expression of said nucleic acid sequence. 15. The method of claim 12, wherein said 3' flanking region includes a 3' UTR and a 3' NCR containing a transcriptional termination region. 16. The method of claim 14, wherein said 5' flanking region is approximately 1.2 kb, said first intron and intron/exon boundary is 1.0 kb, and said 3' flanking region is approximately 3.9 kb of a keratin K1 gene. 17. The method of claim 14, wherein said 5' flanking region is approximately 1.2 kb, said first intron and intron/exon boundary is 1.0 kb, and said 3' flanking region is approximately 4.3 kb of a keratin K1 gene. 18. The method of claim 14, wherein said 5' flanking region comprises nucleotides 1 to 46 of Sequence ID No. 1; said 3' flanking region comprises nucleotides 6891 to 10747 of Sequence ID No. 1; and said linker comprises nucleotides 2351 to 2376 of Sequence ID No. 2. 19. The method of claim 14, wherein said 5' flanking region comprises nucleotides 1 to 46 of Sequence ID No. 1; said 3' flanking region comprises nucleotides 7895 to 7921 of Sequence ID No. 1; and said linker comprises nucleotides 2351 to 2376 of Sequence ID No. 2. 20. The method of claim 12, wherein said 5' flanking region comprises nucleotides 1 to 46 of Sequence ID No. 1; said 3' flanking region comprises nucleotides 7924 to 7948 of Sequence ID No. 1; and said linker comprises nucleotides 2351 to 2376 of Sequence ID No. 2. 21. The method of claim 12, wherein said vector further comprises a modulator sequence associated with said 3' flanking region or said 5' flanking region. 22. The method of claim 21, wherein said modulator sequence comprises sequences responsive to calcium, Vitamin D or its metabolite, Vitamin A or its metabolite, or progesterone. 23. The method of any of claims 2-11 wherein said skin cancer cell is an epidermal cell.

Details for Patent 6,057,298

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2017-05-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2017-05-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2017-05-02