Achillion Pharmaceuticals, Inc.

Other

National Institutes of Health, a Component of the US Dept. of Health & Human Services

University System of Maryland

Mingjun Huang

Ettore Appella

William G Rice

John K Inman

David Covell

James A Turpin

Steven D Podos

Yongsheng Song

Anders Wallqvist

Andrew Maynard

Michael F Summers

Yongnian Sun

Wengang Yang

Chun Tang

Dharaben Patel

The dosages and methods described herein provide desirable pharmacokinetic (PK) and pharmacodynamics (PD) characteristics which inhibit alternative pathway complement activity, for example at least 85% or more inhibition of AP activity in vivo at dosages from about 120 mg to 200 mg BID that provides a plasma level Cat least about 65 ng/ml, which provides sufficient AP inhibition to reduce the risk of complement breakthrough. In addition, the dosage form described herein provides a significantly low C, providing additional safety margin and better dosing flexibility.

Targeted dosing for the treatment of complement mediated disorders

Provided herein are methods for treating a subject with PNH comprising administering to a subject a therapeutically effective amount of complement component C5 (C5) inhibitor, complement component C3 (C3) inhibitor, or complement factor B (CFB) inhibitor in combination with a therapeutically effective amount of small molecule complement factor D (CFD) inhibitor of Formula I or Formula II, or a pharmaceutically acceptable salt thereof.

Therapeutic regimens for treatment of paroxysmal nocturnal hemoglobinuria

Methods for detecting populations of newly synthesized and newly initiated RNAs in a cell-free system are described. Suitable templates for the populations of newly synthesized and newly initiated RNAs are viral replicon RNAs, particularly HCV viral replicon RNA. The newly synthesized and newly initiated RNAs may be formed in the presence of a labeled nucleotide analog suitable for detection and/or quantitation of the RNAs. The assay may be employed to identify small molecule inhibitors of RNA synthesis of positive strand RNA viruses such as Hepatitis C Virus.

Quantitative assay for detection of newly synthesized RNA in a cell-free system and identification of RNA synthesis inhibitors

This invention pertains to the discovery of a novel family of thiolesters and uses thereof. Also provided for are viricidal compounds and pharmaceutical formulations comprising these novel thiolesters. The invention also provides thiolester-inactivated viruses and thiolester-complexed viral proteins.

Thiolesters and uses thereof

Methods for evaluating the antiviral activity of test compounds are provided. Further aspects of the methods involve the retroviral capsid protein of HIV-1. In another aspect, methods of reducing mortality associated with AIDS with a compound that binds to the apical cleft near the C-terminal end of the N-terminal domain of the HIV-1 capsid protein are provided. Derivatives of CAP-1, CAP-2, CAP-3, CAP-4, CAP-5, CAP-6 and CAP-7 are described that bind to the apical cleft of the N-terminal domain of the HIV-1 capsid protein and inhibit proper assembly of the core particle.

Antiviral inhibition of capsid proteins

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Rockville, MD, United States of America

Mingjun Huang