Nono Inc.

Arbor Vita Corporation

Jonathan David Garman

Michael Tymianski

Peter S Lu

Michael P Belmares

Michael W Salter

Hong Cui

Johannes Schweizer

Chamorro Somoza Diaz-Sarmiento

Xiujun Sun

Rongwen Li

Frieder Hofmann

Albert Frederick Candia, Iii

The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c, as chloride salts. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. The chloride salt of TAT-NR2B9c shows improved stability compared with the acetate salt form of prior formulations. Formulations of the chloride salt of TAT-NR2B9c are stable at ambient temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital.

Chloride salt of TAT-NR2B9C

The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. Such formulations are stable at room temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital.

Prelyophilized, lyophilized and reconstituted formulations comprising TAT-NR2B9C with d-amino acids, histidine and trehalose

Chloride salt of TAT-NR2B9c

The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefiting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

Therapy for subarachnoid hemorrhage and ischemia

Lyophilized formulation comprising tat-NR2B9C, histidine and trehalose

The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c including histidine, trehalose and lysine. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. Such formulations are stable at ambient temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital.

Lyophilized formulation of TAT-NR2B9C with acetylation scavenger

The invention provides methods of delivering pharmacologic agents linked to an internalization peptide, in which an inflammatory response inducible by the internalization peptide is inhibited by co-administration of an anti-inflammatory or by linking the internalization peptide to biotin or similar molecule. Such methods are premised in part on the results described in the examples whereby administration of a pharmacological agent linked to tat at high dosages is closely followed by an inflammatory response, which includes mast cell degranulation, histamine release and the typical sequelae of histamine release, such as redness, heat, swelling, and hypotension.

Co-administration of an agent linked to an internalization peptide with an anti-inflammatory

The invention provides methods of treatment or prophylaxis of damaging effects of penetrative injury to the brain or other part of the central nervous system. The methods are based in part on results in a rodent model of penetrative ballistic injury showing that an inhibitor of PDF-95 NMDAR interaction is effective in inhibiting neurological deficits resulting from such injury. The methods are useful for treating subjects having or at risk of penetrative brain injury, including subjects who have been shot in the head or at risk of such injury (e.g., military or law enforcement personnel).

Treatment of penetrative injury to the brain

The subject invention provides antibodies, including polyclonal and monoclonal antibodies, that bind to E6 proteins from at least three oncogenic strains of HPV. In general, the antibodies bind to amino acids motifs that are conserved between the E6 proteins of different HPV strains, particularly HPV strains 16 and 18. The subject antibodies may be used to detect HPV E6 protein in a sample, and, accordingly, the antibodies find use in a variety of diagnostic applications, including methods of diagnosing cancer. Kits for performing the subject methods and containing the subject antibodies are also provided.

Antibodies for oncogenic strains of HPV and methods of their use

The invention provides animal models and clinical trials for assessing agents for potential use in treating and effecting prophylaxis stroke and other neurological diseases, particularly those mediated at least in part by excitoxitity. The invention also provides preferred dosage and infusion regimes and pharmaceutical compositions for clinical application of such agents.

Model systems and treatment regimes for treatment of neurological disease

This invention relates to methods of screening for modulators of mammalian cell injury cause by TRPM7 gene and protein activity, compounds that modulate TRPM7 gene and protein activity and methods of treatment of mammalian cell injury using modulators of TRPM7 gene and protein activity.

Agents and methods for treating ischemic and other diseases

The invention provides agents useful for treating pain. An exemplary agent comprises or consists of the a portion of a retroviral Tat protein. One such agent is the peptide Tat-NR2B9c. This peptide has previously been described as an agent for inhibiting damaging effects of stroke and similar conditions via inhibition of PSD95 interactions with NMDA receptors and/or NOS. The present application provides data showing that the Tat-NR2B9c peptides is effective in alleviation of pain. The alleviation of pain can be obtained at a dose of the peptide below the dose required to inhibit PSD-95 interactions with NMDAR or NOS.

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Thornhill, Canada

Jonathan David Garman