Duke University

Regado Biosciences, Inc.

Vitrisa Therapeutics, Inc.

Albert Einstein College of Medicine

396419 B.c. Ltd.

Tobira Therapeutics, Inc.

Christopher P Rusconi

Bruce A Sullenger

Carl Erickson

Kevin G McLure

Juliana Layzer

Douglas Brooks

Steven Zelenkofske

Matthew Levy

Arijit Bhowmick

Sabah Oney

Nanette L S Que-Gewirth

Rebekah R White

Renta Hutabarat

Juliana M Layzer

Steven L Zelenkofske

The application discloses methods and compositions for the inhibition of the alternative complement pathway. The methods and compositions involve the use of aptamers for inhibiting complement Factor D. The application further provides anti-Factor D aptamers for the treatment of dry age-related macular degeneration, geographic atrophy, wet age-related macular degeneration or Stargardt disease. In some cases, stem-loop aptamers are provided for the inhibition of Factor D.

Stem-loop compositions and methods for inhibiting factor D

The application discloses methods and compositions for the inhibition of the alternative complement pathway. The methods and compositions involve the use of aptamers for inhibiting complement Factor D. The application further provides anti-Factor D aptamers for the treatment of dry age-related macular degeneration, geographic atrophy, wet age-related macular degeneration or Stargardt disease.

Compositions and methods for inhibiting factor D

Provided herein are compositions and methods for the treatment of retinal diseases. The compositions and methods include a therapeutic agent conjugated to a vitreous component binding moiety. The vitreous component binding moiety may be an aptamer or a small molecule that binds to a structural component of the vitreous humor (e.g., hyaluronic acid, collagen or vitronectin).

Compositions with improved intravitreal half-life and uses thereof

Compositions and methods for inhibiting Factor D

The present invention relates, in general, to a pharmacologic system to modulate the biology of platelets based upon a nucleic acid ligand that can interact with and modulate the activity of platelet glycoprotein GPVI to regulate platelet function. These nucleic acid ligands are also actively reversible using a modulator that inhibits the activity of the nucleic acid ligand to neutralize this pharmacologic effect and thereby restore GPVI function, including collagen binding, platelet adhesion, collagen-induced platelet activation, and collagen-induced platelet aggregation. The invention further relates to compositions comprising the nucleic acid ligand, the ligand and a modulator, methods to generate the nucleic acid ligand and its modulator, as well as methods of using these agents and compositions in medical therapeutic and diagnostic procedures.

Nucleic acid modulators of glycoprotein VI

The invention provides improved nucleic acid ligands that inhibit coagulation and improved modulators of the nucleic acid ligands to provide ideal modulators of coagulation. These improved nucleic acid ligands and modulators are particularly useful for inhibiting coagulation in a host undergoing a therapeutic regime such as surgery or coronary artery bypass.

Modulators of coagulation factors

The biological activity of nucleic acid ligand is regulated (i.e. enhanced or inhibited) in vivo to produce a desired biological effect. This is accomplished through the administration of a modulator, or regulator, that changes the binding of the nucleic acid ligand for its target or that degrades or otherwise cleaves, metabolizes or breaks down the nucleic acid ligand while the ligand is still exerting its effect. Modulators of the present invention can be administered in real time as needed based on various factors, including the progress of the patient, as well as the physician's discretion in how to achieve optimal therapy. Thus, this invention provides for the first time a regulatable therapeutic regime in the course of nucleic acid ligand therapy.

Modulators of pharmacological agents

Focused aptamer libraries are constructed in accordance with a proteome (i.e., complex mixture of native biomolecules). The libraries may be screened to identify one or more candidate aptamers with desired biological activities other than specific binding to a target. Aptamers which are selected or derivatives thereof may be used for those specific activities in biological systems. Any combination of deconvoluting a focused library (functional profiling), increasing frequencies of particular aptamers in a focused library (Laser SELEX), and decreasing frequencies of particular aptamers in a focused library (DeSELEX) may be performed prior to assaying biological activity.

Focused libraries, functional profiling, laser SELEX, and DESELEX

RNA aptamers and methods for identifying the same are disclosed. The RNA aptamers selectively bind coagulation factors, E2F family members, Ang1 or Ang2, and therapeutic and other uses for the RNA aptamers are also disclosed.

Growing community of inventors

Durham, NC, United States of America

Christopher P Rusconi