SANTA CRUZ, CA, United States
SANTA CRUZ, CA, United States

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Patent
Transderm, Inc. | Date: 2014-01-24

The present invention is drawn to formulations for the transdermal delivery of rapamycin or other related compounds. Specifically, in one embodiment a formulation for transdermally delivering rapamycin includes an mTOR inhibitor, such as rapamycin, water, a polymer having surfactant properties, a polymer having thickening properties, a solvent for solubilizing the mTOR inhibitor, a glycol, a C_(10)-C_(20 )fatty acid; and a base.


A method for keratin hyperproliferation disorders such as corns, calluses, or keratosis pilaris (KP) by administering to a subject experiencing the disorder a therapeutically effective amount of an RNA sequence which inhibits expression of a gene encoding for a keratin selected from the group consisting of K6a, K6b, K16, K17, and combinations thereof.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2014

DESCRIPTION (provided by applicant): We discovered that the inducible keratins 6a and 6b, mutations in which can result in the skin and nail disorder pachyonychia congenita (PC), contain regulatory motifs in their 5'-untranslated regions that make them susceptible to mTOR inhibitors, including rapamycin. Using RNA profiling and immunohistochemistry of foot sole biopsies taken from PC lesions or adjacent unaffected skin, we found evidence to support that mTOR signaling in PC lesions is activated as indicatedby hyperphosphorylated ribosomal protein S6. Based on the preclinical data, we completed a small off- label study of orally-administered Rapamune(R) in three PC patients in which improvement of PC symptoms was observed, with dramatic reduction of painfulneurovascular structures. However, the study was prematurely terminated due to the adverse events associated with systemic oral rapamycin administration. A recent off-label study with topical rapamycin led to marked improvement of PC symptoms, includi


Patent
Transderm, Inc. | Date: 2015-06-30

The present invention provides for microneedle arrays and related systems and methods. Particularly, microneedle arrays that are configured to deliver active agents, including nucleic acids and vaccines, are provided. Additional related methods of vaccinating and minimizing the amount of vaccine necessary for effective inoculation are also provided.


A method of treating or preventing keratin hyperproliferation skin disorders is set forth. The method includes the administration of an mTOR inhibitor to a subject afflicted with the hyperproliferation disorder. The mTOR inhibitor can be administered to the subject via any means known in the art including oral, topical, and transdermal administration.


Patent
Transderm, Inc. | Date: 2013-02-04

The present invention provides for transdermal delivery devices having microneedle arrays, as well as methods for their manufacture and use. In one embodiment, a transdermal delivery device is provided. The transdermal delivery device includes a polymer layer which has microneedles projecting from one of its surfaces. The microneedles are compositionally homogenous with the polymer base layer.


Patent
Transderm, Inc. and Samyang Biopharmaceuticals Corporation | Date: 2014-07-30

Disclosed is a transdermal preparation, comprising sequentially-stacked layers of a backing layer, a barrier layer, a drug adhesive layer and a release layer, wherein the drug adhesive layer contains a drug selected from the group consisting of fentanyl, an analogue thereof and a pharmaceutically-acceptable salt thereof, a skin permeation enhancer of the drug, and a polyacrylate adhesive, which shows a high skin permeation with a low drug dosage, equivalent to one with high drug dosage, by increasing the skin permeation rate of drug.


Methods of treating pain and/or itch in a targeted region of a subject and compositions and dosage forms therefor are described herein. Such methods can include topically administering a therapeutically effective amount of an mTOR pathway inhibitor to the subject.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 224.66K | Year: 2016

ABSTRACT The rare genetic disorder pachyonychia congenita PC results from dominant mutations in the inducible keratins K including K a K b K and K While disabling painful plantar keratoderma is commonly accepted as the primary symptom affecting patient quality of life hyperhidrosis appears to contribute to blister formation and pain Supporting the involvement of hyperhidrosis to PC pain several teams worldwide have shown that multiple intradermal injections of botulinum toxin BTX known to effectively treat hyperhidrosis substantially reduce pain and blistering in PC patients similar results were observed with the related genodermatosis epidermolysis bullosa simplex Unfortunately the number of dermal injections associated with the current treatment protocol makes this procedure costly and difficult on the patient regional nerve blocks or general anesthesia are used We propose to use TransDermandapos s proprietary Flex PAD delivery system to administer BTX to the skin in a patient friendly manner with little or no pain and with no requirement for anesthetic In Phase we aim to demonstrate that BTX can be effectively and efficiently loaded on Flex PADs and that the resulting drug product has sufficient stability to be evaluated in mouse models and for future clinical trial use The ability of the Flex PADs to delivery BTX will be evaluated in head to head studies with intradermal injection of BTX and scored for its ability to block pilocarpine induced sweating in mouse paws In Phase we refine and streamline manufacture and loading of the Flex PADs with BTX and perform IND enabling stability and toxicity studies in mice and minipig models in preparation for human studies !NARRATIVE Much progress has been made over the past two decades in identifying the underlying genes and mutations responsible for a large number of genodematoses with over disorders identified from mutations in intermediate filament genes alone Despite these discoveries few clinical treatments have emerged that modulate these molecular targets In the skin disorder pachyonychia congenita PC the causative genes for PC are expressed in sweat glands and the structure of the sweat gland is grossly altered and malformed Preliminary human studies suggest that botulinum toxin is effective in reducing hyperhidrosis and pain in PC Although injected botulinum toxin reduced PC symptoms administration is cumbersome and costly with regional nerve blocks or general anesthesia required This project seeks to exploit the ability of TransDermandapos s Flex PAD delivery platform to deliver large charged proteins such as botulinum toxin in a patient friendly i e little or no pain fashion Patient friendly delivery of botulinum toxin by Flex PADs has potential applicability to benefit not only PC patients but also other patients with hyperhidrosis and associated pain including psoriasis such as epidermolysis bullosa simplex


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 4.11M | Year: 2011

DESCRIPTION (provided by applicant): RNA interference (RNAi) has the potential to revolutionize treatment of dominant genetic disorders. Small inhibitory RNAs (siRNAs) are highly potent and selective, demonstrating remarkable single-nucleotide specificity.Clinical trials using siRNAs are currently underway for a number of indications including skin. Facilitated by Phase 1 funding, a small one patient phase 1b clinical trial was undertaken for pachyonychia congenita (PC). This ultrarare skin disorder is caused by mutations, including single nucleotide changes, in the genes encoding keratins 6, 16, and 17. The major complaint of PC patients is the debilitating painful callusing and blistering which occurs on or near the pressure points of the feet. These defined regions on the soles of the feet were targeted for local siRNA treatment by intralesional injection of siRNA (TD101) with encouraging results. Unfortunately, the pain associated with injections into lesions (oral pain medication and regional nerve blocks were required to allow treatment), prevents widespread use of this mode of administration. This observation has led to intense efforts to identify patient-friendly (i.e., little or no pain) delivery options. This clinical trial was the first human use of siRNA in skin and also the first siRNA to target a mutated gene. In Phase 2 of this proposal, we extend the progress of Phase 1 and the Phase 1b clinical trial. We have found that unmodified or stabilized siRNAs are not taken up readily by skin keratinocytes but that modified, so-called self-delivery (sd) siRNAs are. Additional optimization of the sd-siRNA will be undertaken in mouse and human skin models followed by synthesis of GMP material for mouse and rabbit toxicology studies and clinical trialsin which the siRNA will be delivered by dissolvable microneedle arrays or a topical GeneCream formulation, both developed and manufactured at TransDerm. GeneCream and microneedle arrays are both designed to effectively deliver sd-siRNA with little or no pain (microneedle protrusions are designed to only penetrate to the non-innervated epidermis). Although PC is a rare disease, the nature of the disorder makes it an ideal prototype skin disorder (defined mutations with expression in limited, defined areas)for first-in-man siRNA skin clinical trials, and we fully expect the lessons learned will be readily generalized to other skin disorders. PUBLIC HEALTH RELEVANCE: Despite the discovery of the underlying mutations responsible for many inherited skindiseases, few effective treatments have emerged. The discovery that siRNAs can be developed to target specific disease-related mutations portends the advent of a new treatment paradigm. We have identified a potent and selective siRNA that targets a singlenucleotide mutation in the keratin 6a gene that is responsible for the rare skin disorder pachyonychia congenita and blocks its expression. This siRNA (known to the FDA as TD101) was successfully tested in a Phase 1b clinical trial. Despite signs of efficacy, the painful nature of the administration route (intradermal injection of large volumes) required that we develop a more patient-friendly delivery system. Phase 2 of this proposal allows preclinical studies enabling a second clinical trial using microneedles loaded with a self-delivery version of TD101 siRNA. The lessons learned in applying siRNA technology for treatment of PC should be readily generalizable to a host of other dominant skin disorders and likely to other disorders resulting from mutated or overexpressed disease-causing genes.

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