Novartis Ag

Wellstat Immunotherapeutics, LLC

Wellstat Ophthalmics Corporation

Pharma Cinq, LLC

Welltat Ophthalmics Corporation

Novartis Pharma Gmbh

Tianci Luo

Michael Kaleko

Robert Berkowitz

Jeffrey Allan Miller

ChangHung Chen

Beibei Li

Ruigong Wang

Ivan Plavec

Janet Lynn Douglas

Peter Anthony Campochiaro

Romulus Kimbro Brazzell

Jun Zhang

Katharine Hilary Dixon

Jeffrey Allen Miller

Gabriel Castille

Rene Molina

Changhung Chen

Robert David Berkowitz

A fusion protein is described, comprising a first N-terminal signal peptide sequence, a second peptide sequence C-terminal to the signal peptide sequence, and a third peptide sequence C-terminal to the second peptide sequence; wherein one of the second peptide sequence and the third peptide sequence is an RdCVF-short peptide sequence and the other is a hydrophilic peptide sequence. After translation the signal peptide is cleaved, leaving a fusion protein comprising the second peptide sequence and the third peptide sequence minus the signal peptide. Also described are nucleic acids and expression vectors encoding the fusion protein, cells comprising the nucleic acid or expression vector, as well as methods of treatment and uses of the fusion protein, nucleic acid, and expression vector. The fusion protein can be produced in vitro by culturing the cells of this invention under conditions allowing for expression and secretion of the encoded fusion protein, and isolating the fusion protein from the cell culture.

Fusion protein between short form rod-derived cone viability factor and a hydrophilic peptide

A recombinant fusion protein is disclosed. The fusion protein comprises: (a) a CD55 peptide sequence, (b) a linker sequence C-terminal to the CD55 sequence, (c) a transmembrane domain C-terminal to the linker sequence, and (d) an intracellular domain C-terminal to the transmembrane domain. The fusion protein does not contain a GPI anchor. The fusion protein can be expressed with an N-terminal secretory signal peptide, which is cleaved to yield the mature protein on the surface of a cell line or an enveloped virus. An oncolytic virus expressing the fusion protein is resistant to complement inactivation and can be used to treat cancer.

Enveloped virus resistant to complement inactivation for the treatment of cancer

The invention provides polypeptides comprising a complement factor B analog. The invention also provides various complement factor B analogs including complement factor B analogs comprising a mutation of a free cysteine amino acid and related methods, nucleic acids and vectors. These complement factor B analogs and related methods, nucleic acids and vectors can be used to modulate a complement pathway or for the study and/or treatment of various conditions or diseases related to a complement pathway.

Complement factor B analogs and their uses

The present invention relates to nucleic acids coding for and capable of expressing a rod-derived cone viability factor (RdCVF) and viral vectors containing these nucleic acids. The invention also relates to compositions and pharmaceutical preparations comprising these nucleic acids or vectors, methods of producing or secreting an RdCVF, and methods of treatment.

Vectors encoding rod-derived cone viability factor

Methods are provided for the treatment of ocular neovascularization by increasing, in an individual afflicted with ocular neovascularization, in vivo concentrations of an endostatin protein in the ocular tissues of the individual to an ocular neovascularization inhibiting effective amount, where the endostatin protein has anti-ocular neovascularization activity in vivo.

Method for treating ocular neovascularization

BIV packaging constructs, BIV packaging cell lines, methods of making BIV packaging cells and methods of making BIV producer cells are described.

Bovine immunodeficiency virus (BIV) based vectors

The present invention provides novel lentiviral packaging constructs that are useful for the establishment of stable packaging cell lines and producer cell lines. In particular, the present invention provides novel packaging cell lines that are capable of constitutively expressing high levels of lentiviral proteins.

Lentiviral packaging constructs

This invention pertains to BIV constructs encompassing BIV combination vectors, BIV vectors and BIV packaging vectors and particularly the invention pertains to a three vector system comprising: a) a BIV vector construct including a DNA segment from a BIV genome, a packaging sequence to package RNA into virions; a promoter operably linked to the DNA segment; and a transgene operably linked to a second promoter; b) a BIV packaging vector construct comprising a BIV DNA sequence fragment comprising at least a gag gene or pol gene of BIV; a promoter operably linked to the BIV DNA fragment; and a polyadenylation sequence located downstream of the BIV DNA fragment; and c) an expression vector construct comprising a gene encoding a viral surface protein. Also provided is a method for transferring a gene of interest into a mammalian cell.

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Clarksville, MD, United States of America

Tianci Luo