New York University

University of Massachusetts

Molsoft LLC

Johns Hopkins University

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

The United States Government As Represented by the Department of Veterans Affairs

Timothy J Cardozo

Susan Zolla-Pazner

Maxim Totrov

Shan Lu

Xiang-peng Kong

Abraham Pinter

Michele Pagano

Leslie I Gold

Genoveffa Franchini

Philip A Band

Shixia Wang

Ruben Abagyan

Konstantin Ichtchenko

Miroslaw K Gorny

David Ron

Dan Sherman

Jürgen Bosch

Xiangpeng Kong

Lily Wu

Lawrence B Gardner

Leenus Martin

Hong Wang

Sondra Maureen Nemetski

John C Pui

Mohamed Boutjdir

Manuel Becerra-Flores

Giacomo Gorini

Isabela Silva De Castro

Edwin Vazquez-Cintron

Massimiliano Bissa

Embodiments of recombinant HIV-1 gp120 proteins that contain a V1 deletion are disclosed. Also provided are gp140, gp145, and gp160 proteins containing the V1 deletion, as well as HIV-1 Env ectodomain trimers containing protomers containing the V1 deletion. Nucleic acid molecules encoding these proteins are also provided. In several embodiments, the disclosed recombinant HIV-1 proteins and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

Recombinant gp120 protein with V1-loop deletion

The present invention is directed to a fusion protein comprising a light chain region of a Clostridial neurotoxin and a heavy chain region of a Clostridial neurotoxin, where the light and heavy chain regions are linked by a disulfide bond. The fusion protein also has a single chain antibody positioned upstream of the light chain region, where the single chain antibody possesses antigen-binding activity. Also disclosed are therapeutic agents, treatment methods, propeptide fusions, isolated nucleic acid molecules, expression systems, host cells, and methods of expressing fusion proteins.

Propeptide fusion comprising a mutated clostridium botulinum neurotoxin and a VHH domain

Disclosed herein, are decoy peptides or polypeptides capable of neutralizing and/or inhibiting the binding of anti-Ro antibodies to a hERG potassium channel extracellular pore region, and pharmaceutical compositions containing the decoy peptides or polypeptides and methods of use.

Compositions and methods for treating and preventing autoimmune induced cardiac long QT syndrome

The present disclosure provides compounds suitable for inhibiting CaMKK2. Also provided are compositions and methods of treating diseases associated with CaMKK2.

Inhibitors of CaMKK2 and uses of same

The present invention relates to an isolated immunogenic peptide chimera comprising a first peptide moiety comprising the amino acid sequence of SEQ ID NO: 1, or at least a contiguous 5 amino acid fragment thereof, a second peptide moiety comprising the amino acid sequence of SEQ ID NO: 2, or at least a contiguous 5 amino acid fragment thereof, and a linker joining the first and second peptide moieties, wherein the first peptide moiety is at the immunogenic peptide chimera's N-terminus and the second peptide moiety is at the immunogenic peptide chimera's C-terminus. Also disclosed is an immunogenic peptide including the amino acid sequence corresponding to SEQ ID NO: 6, or at least a contiguous 5 amino acid fragment thereof, having a length sufficient to form &#x3b2;-hairpin structure. A further aspect of the present invention is an immunogenic peptide including the amino acid sequence corresponding to SEQ ID NO: 15, or at least a contiguous 5 amino acid fragment thereof, capable of folding into an alpha-helical structure. These immunogenic peptides can be inserted into an immunogenic scaffold protein to form an immunogenic polypeptide. The immunogenic peptides or immunogenic polypeptides can be used in an immunogenic vaccine composition and in methods of inducing a neutralizing antibody response, or inducing a protective and non-neutralizing antibody response, or protective antibodies, against HIV-1 gp120 in a subject. Isolated antibodies and methods of detecting are also disclosed.

Highly immunogenic peptides derived from the human immunodeficiency virus V2 region

In one aspect, the present invention relates to a method of identifying compounds useful in modifying the activity of Aldolase. The method includes providing a first model comprising Aldolase or residues of the amino acid sequence corresponding to SEQ ID NO: 1 said residues being at amino acid positions selected from the group consisting of 10-13, 26, 27, 29, 30, 31, 32, 33, 37, 39, 40, 41, 43, 44, 47, 48, 51, 52, 60, 63, 66, 79, 84, 85, 92, 93, 103, 106-109, 112-117, 138, 142, 146, 148, 151, 153, 179, 182, 183, 185, 186, 194, 196, 197, 198, 199, 208, 226-228, 231-269, 270, 272, 277-283, 285-289, 294, 295, 297-299, 301-304, 306-310, 312, 313, 316, 317, 319, 321, 323, 326, 330, 344, 345, and 347, providing one or more candidate compounds, evaluating contact between the candidate compounds and the first model to determine which of the one or more candidate compounds have an ability to bind to and/or fit in the first model, and identifying compounds which, based on said evaluating, have the ability to bind to and/or fit in the first model as compounds potentially useful for modifying the activity of Aldolase. The present invention also discloses compounds and compositions which modify the activity of Aldolase, or a complex between Aldolase and TRAP. Methods of treating or preventing malaria, or an infection by apicomplexan organisms are also disclosed.

Small molecule malarial Aldolase-TRAP enhancers and glideosome inhibitors

The present invention relates to an isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120. This peptide binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection, does not react with blood of matched patients who did not receive the vaccine, and can, therefore, elicit anti-HIV-1 antibodies which protect against HIV-1 infection. Other aspects of the present invention relate to an isolated immunogenic polypeptide comprising the peptide inserted into an immunogenic scaffold protein, a vaccine composition comprised of the immunogenic peptide and an immunologically or pharmaceutically acceptable vehicle or excipient as well as methods of inducing an immune response against HIV-1 and methods of detecting HIV-1.

Peptides mimicking HIV-1 viral epitopes in the V2 loop for the GP120 surface envelope glycoprotein

The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.

Immunogenic polypeptides comprising a modified loop peptide presenting the HIV-1 GP120 3074 mAb epitope and scaffold proteins containing said peptide

The present invention relates to pharmaceutical compositions comprising a compound and a pharmaceutically acceptable carrier. The present invention is also directed to a method of treating cancer in a subject. Also disclosed are methods of inhibiting SCF-Skp2 activity and a method of identifying inhibitors of SCF-Skp2 activity.

Method of treating cancer with modulators of SCFSkp2

The present invention relates to pharmaceutical compositions comprising a compound and a pharmaceutically acceptable carrier. The present invention is also directed to a method of treating a genetic disease caused by premature termination codons, or other conditions that render messenger ribonucleic acid (mRNA) susceptible to nonsense mediated RNA decay, in a subject. Also disclosed is a method of inhibiting nonsense mediated RNA decay and/or induction of autophagy. The present invention also relates to a method of identifying inhibitors of nonsense mediated RNA decay and/or inducing autophagy. The present invention further relates to a method of inhibiting nonsense mediated RNA decay and/or induction of autophagy in a subject.

Pharmaceutical compositions and treatment of genetic diseases associated with nonsense mediated RNA decay

The present invention relates to a method of identifying compounds useful in inhibiting protein kinase-like endoplasmic reticulum protein kinase (PERK). The method comprises providing a first model comprising PERK active domains, where the said active domains are selected from the group consisting of the peptide spanning from amino acid residue Asp144 to amino acid residue Ser191 of SEQ ID NO: 1 and a peptide comprising the amino acid residue at position 7 of SEQ ID NO: 1, providing one or more candidate compounds, evaluating contact between the candidate compounds and the first model to determine which of the one or more candidate compounds have an ability to bind to and/or fit in the first model, and identifying the compounds which, based on said evaluating, have the ability to bind to and/or fit in the first model as compounds potentially useful for inhibiting PERK. The present invention further relates to compounds that can be used for inhibition of PERK, for example human PERK, and methods related to treatment of PERK-mediated diseases.

Method of treating cancer by inhibition of protein kinase-like endoplasmic reticulum protein kinase

Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely relatedenterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.

Immunogen comprising the HIV GP120 V3 loop in a conformation that induces broadly neutralizing antibodies

Newly discovered structural characteristic of the gp120 V3 loop have resulted in a 'rule' or algorithm, that is used in a method for determining whether a subject is infected with HIV-1 virus that expresses selectivity for CXCR4 or CCR5 chemokine receptors. A positively charged surface patch defined by V3 loop residues 11 and 24 or 25 at the base of the &#x3b2;-strands in the V3 loop and the homologous &#x3b2;2-&#x3b2;3 chemokine hairpin is responsible for CXCR4 receptor selection. Thus a method for detecting the presence of HIV-1 virus that is selective for X4-co-receptors in a subject infected with HIV-1 or suspected of being infected, from the amino acid sequence of at least a part of the HIV-1 gp120 V3 region peptide that includes residues 11, 24 and 25, or from the nucleotide sequence of a nucleic acid encoding said V3 region peptide, is disclosed.

Method for determining co-receptor selectivity of Human Immunodeficiency Virus-1

The present invention relates to the treatment of inflammatory skin conditions, including psoriasis, with a prodrug of 5-fluorouracil. The invention relates to methods for treatment of psoriasis with capecitabine, an oral prodrug of 5-fluorouracil.

Growing community of inventors

New York, NY, United States of America

Timothy J Cardozo