Surgery – Means for introducing or removing material from body for... – Material introduced into and removed from body through...
Reexamination Certificate
2000-05-22
2003-07-22
Walberg, Teresa (Department: 3742)
Surgery
Means for introducing or removing material from body for...
Material introduced into and removed from body through...
C604S501000
Reexamination Certificate
active
06595947
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to topical delivery of substances into the skin, particularly by disruption of the stratum corneum and delivery of the substance to the epidermal layer beneath.
BACKGROUND OF THE INVENTION
Delivery of substances to the body through the skin has typically been invasive, involving needles and syringes to facilitate intradermal (ID), intramuscular (AIM) or subcutaneous (SC) injection. These methods are painful for the subject, require the skills of a trained practitioner and often produce bleeding. There have more recently been efforts to overcome these disadvantages by use of devices which disrupt or abrade the stratum corneum, the thin external layer of keratinized cells about 10-20 &mgr;m thick which serves as the skin's outer barrier, with delivery of the desired substance to the exposed epidermis. The substance can then diffuse through the epidermis to the dermis which contains blood vessels and lymphatics for absorption and delivery of the substance throughout the body. For topical delivery of vaccines, the epidermis itself is a particularly desirable target for drug delivery as it is rich in antigen presenting cells. In comparison, the dermis contains fewer antigen presenting cells. The stratum corneum and epidermis do not contain nerves or blood vessels, so this method has the advantage of being essentially painless and blood-free while giving access to the skin layers capable of responding to the antigen.
The prior art reports a variety of devices and methods for disrupting the stratum corneum for the purpose of delivering substances to the body. For example, breach of the stratum corneum may be achieved by puncturing as taught in U.S. Pat. No. 5,679,647 to Carson, et al. This patent teaches that narrow diameter tynes, such as those found on devices used for tuberculin skin tests and allergy tests, can be coated with polynucleotides and used for delivery of such materials into the skin. The method of using such devices involves puncturing the skin with the tynes resulting in intracutaneous injection of the coated substance. This is in contrast to the present invention, where it has been unexpectedly discovered that substances coated onto the surface of narrow diameter micro-protrusions are delivered more effectively by lateral abrasion across the skin surface rather than by puncturing. U.S. Pat. No. 5,003,987; U.S. Pat. No. 5,879,326; and U.S. Pat. No. 3,964,482 teach breaching the stratum corneum by abrasion, however, little is known about how to optimize topical application methods to achieve efficient and efficacious delivery by this route. Such optimization is of particular interest for topical nucleic acid delivery, especially topical delivery of nucleic acid-based vaccines and gene therapies. In this regard, the most commonly suggested method for topical administration is to abrade the skin prior to application of the vaccine. However, it has now been unexpectedly found that delivery of nucleic acids and peptides or polypeptides such as allergens is more efficient and more efficacious when the substance is delivered simultaneously with abrasion.
SUMMARY OF THE INVENTION
The present invention provides optimized methods for topical delivery of substances, particularly nucleic acids, amino acids, amino acid derivatives, peptides or polypeptides. It has been discovered that nucleic acids exhibit enhanced gene expression and produce an enhanced immune response to the expressed protein when they are delivered simultaneously with abrasion of the stratum corneum. Similarly, allergens delivered simultaneously with abrasion produce a more vigorous immune response than conventional allergen testing methods.
REFERENCES:
patent: 3289670 (1966-12-01), Krug et al.
patent: 3556080 (1971-01-01), Hein
patent: 3964482 (1976-06-01), Gerstel et al.
patent: 4270548 (1981-06-01), Brennen
patent: 4483348 (1984-11-01), Sher
patent: 4568343 (1986-02-01), Leeper et al.
patent: 4746515 (1988-05-01), Cheng et al.
patent: 5003987 (1991-04-01), Grinwald
patent: 5273528 (1993-12-01), Skeen et al.
patent: 5380337 (1995-01-01), Romaine
patent: 5501784 (1996-03-01), Lessmollmann et al.
patent: 5611806 (1997-03-01), Jang
patent: 5658515 (1997-08-01), Lee et al.
patent: 5660680 (1997-08-01), Keller
patent: 5679647 (1997-10-01), Carson et al.
patent: 5848991 (1998-12-01), Gross et al.
patent: 5855801 (1999-01-01), Lin et al.
patent: 5879326 (1999-03-01), Godshall et al.
patent: 5885211 (1999-03-01), Eppstein et al.
patent: 5910306 (1999-06-01), Alving et al.
patent: 5919364 (1999-07-01), Lebouitz et al.
patent: 5928207 (1999-07-01), Pisano et al.
patent: 5931794 (1999-08-01), Pitesky
patent: 5958589 (1999-09-01), Glenn et al.
patent: 5970998 (1999-10-01), Talbot et al.
patent: 5980898 (1999-11-01), Glenn et al.
patent: 5983136 (1999-11-01), Kamen
patent: 6015599 (2000-01-01), Keller et al.
patent: 6032060 (2000-02-01), Carim et al.
patent: 6050988 (2000-04-01), Zuck
patent: 6065864 (2000-05-01), Evans et al.
patent: 6106751 (2000-08-01), Talbot et al.
patent: 6132755 (2000-10-01), Eicher et al.
patent: 6173202 (2001-01-01), Eppstein
patent: 6183434 (2001-02-01), Eppstein
patent: 6187210 (2001-02-01), Lebouitz et al.
patent: 6256533 (2001-07-01), Yuzhakov et al.
patent: 6299900 (2001-10-01), Reed et al.
patent: 6312612 (2001-11-01), Sherman et al.
patent: 6331266 (2001-12-01), Powell et al.
patent: 6334856 (2002-01-01), Allen et al.
patent: 6454755 (2002-09-01), Godshall
patent: 2002/0111600 (2002-08-01), Cormier et al.
patent: 195 18 974 (1995-11-01), None
patent: 0 381 410 (1990-08-01), None
patent: 0 509 122 (1996-10-01), None
patent: 1086719 (2000-08-01), None
patent: 1 092 444 (2001-04-01), None
patent: 2 125 280 (1984-03-01), None
patent: 172 4181 (1992-04-01), None
patent: 96 07369 (1996-03-01), None
patent: WO 96/37256 (1996-11-01), None
patent: WO 97/03718 (1997-02-01), None
patent: WO 97/11650 (1997-04-01), None
patent: WO 97/48440 (1997-12-01), None
patent: WO 97/48442 (1997-12-01), None
patent: WO 99/00155 (1999-01-01), None
patent: WO 99/43350 (1999-09-01), None
M.J. McCluskie et al., Molecular Medicine, 5:287, 1999.
Skin Immunization Made Possible by Cholera Toxin, Nature, vol. 391, Feb. 26, 1998, p. 851.
Tuberculin, Old Mono-Vacc Test (O.T.), product information, www.us.aventispasteur.com.
E. Raz et al., Intradermal Gene Immunization: The Possible Role of DNA Uptake in the Induction of Cellular Immunity to Viruses, Proc. Natl. Acad. Sci., USA 91 (1994).
D.A. Greenhalgh et al., Epidermis: An Attractive Target Tissue for Gene Therapy, Journal of Investigative Dermatology, vol. 108, No. 5, May 1997.
M. Yokohama et al., DNA Immunization: Effects of Vehicle and Route of Adminstration on the Induction of Protective Antiviral Immunity, FEMS Immunology and Medical Microbiology 14 (1996) 221-230.
L. Li et al., The Feasibility of Targeted Selective Gene Therapy of the Hair Follicle, Nature Medicine, vol. 1, No. 7, Jul. 1995.
D. Tang, Vaccination onto Bare Skin, Nature, vol. 388, Aug. 21, 1997, p 729.
Wm. C. Brown Publishers, Van De Graff, et al., Concepts of Human Anatomy and Physiology, pp. 197-1999 (1986) USA.
Alarcon Jason
Brittingham John M.
Dekker, III John P.
Mikszta John A.
Pettis Ronald J.
Becton Dickinson and Company
Fastovsky L
Lee Eric M.
Walberg Teresa
LandOfFree
Topical delivery of vaccines does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Topical delivery of vaccines, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Topical delivery of vaccines will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3020100