Merck Sharp + Dohme Corp.

Merck + Co., Inc.

Medimmune Limited

Merk & Co., Inc.

Istitute Di Ricerche Di Biologia Molecolare P. Angeletti S.p.a.

Whitehead Insitute of Biomedical Research

Daria Hazuda

Michael D Miller

Jay A Grobler

Deborah Anne Nicoll-Griffith

Sheo B Singh

Anne W Dombrowski

Ming-Tain Lai

Deborah L Zink

Elisabetta Bianchi

Fernando Pelaez

Russell B Lingham

Peter S Kim

Keith C Silverman

John W Shiver

Debra Muir Eckert

Yueming Li

Jon D Polishook

Ana M Teran

Michael J Root

Min Xu

Romas Geleziunas

Hiranthi Jayasuriya

Adam J Simon

Elizabeth Chen Dodson

Xiao-Ping Shi

Guoxin Wu

Bruce Register

Ziqiang Guan

Simon N Lennard

The present invention is directed to methods for inhibition of HIV reverse transcriptase, treatment of infection by HIV, prophylaxis of infection by HIV, and the treatment, prophylaxis and/or delay in the onset or progression of AIDS or ARC by administering a compound of structural Formula I or a pharmaceutically acceptable salt or co-crystal thereof, wherein X is —F or —Cl, less frequently than once daily.

Methods for treatment and prophylaxis of HIV and AIDS

The instant invention relates to a method for reducing the risk for development of anti-viral treatment resistance due to an HIV mutation in a human subject infected with HIV, comprising administering EFdA in combination with one or more anti-viral agents.

HIV drug combination for increasing barrier against resistance

The present invention is directed to methods for inhibition of HIV reverse transcriptase, treatment of infection by HIV, prophylaxis of infection by HIV, and the treatment, prophylaxis and/or delay in the onset or progression of AIDS or ARC by administering a compound of structural Formula I or a pharmaceutically acceptable salt or co-crystal thereof, wherein X is &#x2014;F or &#x2014;Cl, less frequently than once daily.

Methods for the treatment and prophylaxis of HIV and AIDS

Human scFvs are disclosed which interact with a conformational epitope along the pre-hairpin, N-helix coiled coil structure within the heptad repeat 1 (HR1) region of gp41 of HIV. These antibodies, as well as IgG conversions, are shown to neutralize diverse HIV isolates. Isolated nucleic acid molecules are also disclosed which encode relevant portions of these antibodies, as well as the purified forms of the expressed antibodies or relevant antibody fragments, such as Vand Vchains. The antibody compositions disclosed within this specification may provide for a therapeutic treatment against HIV infection by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV infection. These antibodies will also be useful in assays to identify HIV antiviral compounds as well as allowing for the identification of candidate HIV vaccines, such as HIV peptide vaccines.

Human antibodies interacting with HIV gp41

Provided are methods of identifying inhibitors of &#x3b2;-secretase that employ modified &#x3b2;-secretase substrates. The modified &#x3b2;-secretase substrates have &#x3b2;-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered &#x3b2;-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1'-P2&#x2032; of the &#x3b2;-secretase cleavage site. Many of the modified &#x3b2;-secretase substrates are more efficient substrates for &#x3b2;-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by &#x3b2;-secretase. Recombinant polynucleotide molecules encoding the modified &#x3b2;-secretase substrates are provided. Antibodies that recognize cleavage products of the modified &#x3b2;-secretase substrates are provided. Stable cell lines expressing the modified &#x3b2;-secretase substrates are provided. Transgenic animals expressing the modified &#x3b2;-secretase substrates are provided.

Assays using amyloid precursor proteins with modified &#x3b2;-secretase cleavage sites to monitor &#x3b2;-secretase activity

Compounds useful in the inhibition of HIV integrase, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines are described. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. The culture Cytospora sp. MF 6608 (ATCC PTA-1691) is also disclosed, as well as processes for making a compound of the present invention employing the culture.

HIV integrase inhibitors

Novel tetracyclic aromatic ketones are natural product compounds useful in the inhibition of HIV integrase, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. Further, the novel fungal cultures MF6388 (ATCC 74478), Sterile Fungus, and MF6591 (ATCC 74477), Ascochyta sp. are also disclosed. Further, the cultures Sterile Fungus MF6388 (ATCC 74478) and Ascochyta sp. MF6591 (ATCC 74477) are also disclosed, as well as processes for making compounds of the present invention employing the cultures.

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Doylestown, PA, United States of America

Daria Hazuda