The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Department of Health

Karl G Csaky

Robert Nussenblatt

Michael R Robinson

Janine A Smith

Peng Yuan

Cynthia Sung

Hynda K Kleinman

William J Larochelle

Lourdes Ponce

Matthew P Fronheiser

Hyuncheol Kim

Daniel M Sullivan

Eddy Anglade

Unregulated angiogenesis is associated with a variety of pathological conditions. Tumor growth and metastasis is dependent on the development of new blood vessels. The development of new blood vessels in the eye, or ocular neovascularization, has been implicated in a variety of serious ocular diseases. For instance, choroidal neovascularization is linked to age-related macular degeneration, while retinal neovascularization is linked to diabetic retinopathy. The present invention is based on the discovery of a peptide sequence, C16Y, which inhibits ocular neovascularization and tumor growth in vivo. C16Y is a scrambled version of the C16 peptide sequence from the y1 chain of laminin-1. Unlike C16, which is an angiogenic stimulator, C16Y has been shown to inhibit angiogenesis. The present invention discloses methods of treating ocular neovascularization and cancer using both full-length and truncated versions of the C16Y.

Therapeutic administration of the scrambled anti-angiogenic peptide C16Y

Ocular implant devices () for the delivery of a therapeutic agent to an eye () in a controlled and sustained manner. Dual mode and single mode drug delivery devices () are illustrated and described. Implants () suitable for subconjunctival placement are described. Implants () suitable for intravitreal placement also are described. The invention also includes fabrication and implementation techniques associated with the unique ocular implant devices () that are presented herein.

Ocular therapeutic agent delivery devices and methods for making and using such devices

Ocular implant devices for the delivery of a therapeutic agent to an eye in a controlled and sustained manner. Dual mode and single mode drug delivery devices are illustrated and described. Implants suitable for subconjunctival placement are described. Implants suitable for intravitreal placement also are described. The invention also includes fabrication and implementation techniques associated with the unique ocular implant devices that are presented herein.

The invention is directed toward a compound comprising a recombinant nucleic acid encoding an immunoadhesin inserted within an adenoviral nucleic acid, wherein the recombinant nucleic acid can be packaged in an adenovirus particle and wherein expression of the recombinant nucleic acid encoding the immunoadhesin results in production of the immunoadhesin protein. The recombinant nucleic acid encoding the immunoadhesin can be within an adenovirus. The invention further provides methods for delivering an immunoadhesin to a cell or a subject comprising administering to the cell or the subject an adenovirus comprising a recombinant nucleic acid encoding an immunoadhesin; producing an immunoadhesin comprising administering to a cell an adenovirus comprising a recombinant nucleic acid encoding an immunoadhesin inserted within an adenoviral nucleic acid, whereby the cell expresses the recombinant nucleic acid encoding the immunoadhesin, thereby producing the immunoadhesin; treating an inflammatory condition in a subject comprising administering to the subject an adenovirus comprising a recombinant nucleic acid encoding an immunoadhesin inserted within an adenoviral nucleic acid or a recombinant nucleic acid encoding an immunoadhesin inserted within an adenoviral nucleic acid, whereby a cell in the subject expresses the recombinant nucleic acid encoding the immunoadhesin and produces the immunoadhesin, thereby treating the inflammatory condition or administering to the subject a recombinant nucleic acid encoding an immunoadhesin, or an immunoadhesin, wherein the immunoadhesin is selected from the group consisting of vIL-10-IgG, IL-13-IgG, LFA-IgG, IL-2ra-IgG, IL-1ra-IgG, mutant IL-4-IgG, VLA4-IgG, IL-2-IgG, TGF-.beta.1-IgG, TGF-.beta.1.sup.223,225 -IgG, and VCAM-IgG; and methods of screening an immunoadhesin for bioactivity.

Immunoadhesins and methods of production and use thereof

Growing community of inventors

Kensington, MD, United States of America

Karl G Csaky