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PULMONARY GENE TRANSFER DELIVERY SYSTEMS

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
39016
Program Year/Program:
1998 / SBIR
Agency Tracking Number:
39016
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
ARADIGM CORPORATION
3929 POINT EDEN WAY HAYWARD, CA 94545-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 1998
Title: PULMONARY GENE TRANSFER DELIVERY SYSTEMS
Agency: HHS
Contract: N/A
Award Amount: $750,000.00
 

Abstract:

DESCRIPTION: (Adapted from the Applicant's Abstract). Inhaled gene products are desirable for chronic respiratory diseases with high morbidity and mortality, e.g. cystic fibrosis, emphysema, asthma, lung cancer, and tuberculosis. Aerosolization of DNA (plasmids) using conventional flow-through aerosol devices may cause breaking of plasmid strands due to extensive shearing. The investigators developed a prototype aerosol system (AERxTM) that generates a cloud of respirable aerosol by single extrusion of liquid through an array of precise micron- size holes. Nozzle and drug reservoir form an integral disposable part that avoids potentially toxic or incompatible stabilizers. Because the medicament is in its native form and enters the nozzle only once, the probability of damage to gene vectors is vastly reduced. The aerosol 'bolus' is released with a predetermined inspired volume to optimize delivery to desired parts of the respiratory system. Studies with normal volunteers showed that combining suitable particle size with breath and aerosol actuation control results in a desirable and reproducible pattern of drug deposition in the lung. Comprehensive in vitro evaluation of the aerosol properties and the quality of the aerosolized DNA/vector will be done in Phase I. In Phase II, the investigators plan to commence on clinical scale product development and pre clinical studies in a primate model. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 428 --PROJECT NUMBER......1 R43 HL58263-01 INVESTIGATOR NAME/ADDRESS FY 97 OGATA, LYNN C IRG/INTRAMURAL UNIT..ZRG2 MEDINOX, INC AWARD AMOUNT......... $66,696 11555 SORRENTO VALLEY RD SAN DIEGO, CA 92121 PERFORMING ORGANIZATION: MEDINOX, INC. TITLE IMMUNOLOGIC METHODS FOR IN VIVO NITRIC OXIDE DETECTION ABSTRACT: DESCRIPTION: (Adapted from applicant s abstract) The major objective of this research is to develop a simple, sensitive, and accurate assay method for detection of nitric oxide levels. Nitric oxide is produced in the human body and is important for vasodilation, neurotransmission, and immunity. Although several disease states are associated with abnormal levels of nitric oxide including septic shock, stroke, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, pre-eclampsia, and impotence, there are no diagnostic tools available for the in vivo detection of nitric oxide. For this project, rats will be immunized with a novel metal chelating complex capable of scavenging nitric oxide (a Medinox proprietary compound). Monoclonal antibodies capable of recognizing the nitric oxide-scavenger complex will be isolated. These antibodies will be utilized to develop a new immunoassay for nitric oxide levels. If successful, Phase II of this project will adapt the assay for use in detecting nitric oxide levels in patients suffering from many nitric oxide-related inflammatory and infectious diseases. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 429 --PROJECT NUMBER......1 R43 HL58272-01 INVESTIGATOR NAME/ADDRESS FY 97 SOUTHAN, GARRY J IRG/INTRAMURAL UNIT..ZRG7 INOTEK CORPORATION AWARD AMOUNT......... $98,975 8280 KUGLER MILL RD CINCINNATI, OH 45243 PERFORMING ORGANIZATION: INOTEK CORPORATION TITLE NOVEL SCAVENGER FOR TREATMENT OF MYOCARDIAL INFARCTION ABSTRACT: DESCRIPTION (Adapted from applicant's abstract): Reperfusion injury of the ischemic myocardium is characterized by overproduction of oxygen and nitrogen derived free radicals and oxidants. Some of the final common pathways of reperfusion injury include the production of the toxic oxidant peroxynitrite, the free radical nitric oxide, and the prostaglandin thromboxane. Inotek, Inc. has developed an agent, mercaptoethylguanidine (MEG), which interferes with all 3 pathways simultaneously, acting as a potent scavenger of peroxynitrite, inhibitor of cyclooxygenase, and selective inhibitor of the inducible nitric oxide synthase. The overall goal of this Phase I SBIR proposal is to establish whether MEG prevents cellular injury in an experimental model of myocardial infarction and reperfusion. This hypothesis will be tested using well-established rat models of myocardial ischemia- reperfusion. Demonstration that MEG prevents tissue injury in this model would represent a breakthrough in the design of novel therapeutic regimens for reperfusion injury and would justify continued commercial development of MEG. Phase II SBIR funding would be used to support pre-clinical toxicology, pathology and clinical studies. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 430 --PROJECT NUMBER......1 R43 HL58285-01A1 INVESTIGATOR NAME/ADDRESS FY 97 HILD, GABOR IRG/INTRAMURAL UNIT..ZRG7 ELGAVISH PHARMAGNETICS AWARD AMOUNT......... $99,279 1737 VALPAR DRIVE BIRMINGHAM, AL 35226-2343 PERFORMING ORGANIZATION: ELGAVISH PARAMAGNETICS TITLE ELGAVIST, AN MRI CONTRAST AGENT FOR DIAGNOSIS OF IHD ABSTRACT: DESCRIPTION: Ischemic heart disease (IHD) is the number one cause of death in western societies. A rapid and noninvasive method of early detection of myocardial underperfusion would be important for the timely institution of therapy, but no method to date has provided reliable, high-resolution detection MRI is a noninvasive technique with excellent soft tissue resolution. For IHD, however, it is hampered by the lack of sufficient intrinsic contrast. With specific contrast agents MRI would enable the early detection of perfusion abnormalities. Existing agents, however, are not specific enough nor are retained long enough to allow stress-coupled MRI of perfusion. We have designed and synthesized effective new agents. Three have passed the in vitro tests Gd(BME-DTTA), Gd(MHE-DTTA), and "ELGAVIST." We have shown that Gd(BME- DTTA) creates detectable MRI contrast of underperfused myocardium in images of LAD- occluded ferrets and dogs, in vivo, but it requires liposomic dispersion. Its best water-soluble analog, "ELGAVIST," is the most likely to gain commercial success. Thus the goal of the present proposal is the small- scale study (Phase I) of "ELGAVIST" efficacy in the in vivo experimental dog model of acute myocardial ischemia followed by reperfusion, with and without dobutamine-induced pharmacologic stress. The results would likely lead to a more detailed Phase II which should establish the clinical potential of "ELGAVIST" for early diagnosis of IHD with a market potential larger than that of Thallium or Cardiolite. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 431 --PROJECT NUMBER......1 R43 HL58288-01A1 INVESTIGATOR NAME/ADDRESS FY 97 PURDUM, HOWARD E IRG/INTRAMURAL UNIT..ZRG7 SIMUTECH INC AWARD AMOUNT......... $99,700 2660 HAMPTONS CHASE ALPHARETTA, GA 30202 PERFORMING ORGANIZATION: SIMUTECH TITLE IMPROVED INTRAOPERATIVE BLOOD COLLECTION SYSTEM ABSTRACT: DESCRIPTION (Adapted from applicant's abstract): Intraoperative blood salvage (IBS) is a procedure to collect, process and return the patient's own blood during a surgical operation. Compared to transfusion from even a carefully selected donor, the main advantages of IBS include the elimination of the risk of disease transmission, the prevention of immune reactions, and the avoidance of hemolytic, febrile and allergic problems. IBS also provides ready availability, which is particularly important for rare blood types. IBS also follows directly from the need to provide a clear field for the surgeon. In addition, IBS is cost effective, and reduces the demands of the blood bank industry for its limited resources. The proposed technology is oriented toward improvements in the collection phase of IBS. The new technology is thus designed to work with the conventional blood salvage systems that already provide significant benefits. The additional components of the proposed system are relatively inexpensive, compared to the cost of cell washers or units of transfused blood. These components are also quite simple to use, resulting in minimum requirements of technician training and cost. Finally, the prospect of improved patient care, resulting in shortened hospital stays, makes the proposed system quite promising in terms of net cost effectiveness. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 432 --PROJECT NUMBER......1 R43 HL58297-01 INVESTIGATOR NAME/ADDRESS FY 97 PACHENCE, JAMES M IRG/INTRAMURAL UNIT..ZRG3 VERITAS MEDICAL TECHNOLOGIES I AWARD AMOUNT......... $100,000 116 VILLAGE BOULEVARD, SUITE 2 PRINCETON, NJ 08540-5799 PERFORMING ORGANIZATION: VERITAS MEDICAL TECHNOLOGIES, INC. TITLE NOVEL APPROACH FOR TREATMENT OF PULMONARY HYPERTENSION ABSTRACT: DESCRIPTION: (adapted from applicant's abstract) The principal aim of this proposal is to deliver a sustained release, polymeric agent to prevent collagen accumulation in hypertensive blood vessels. The polymer, a backbone of alternating PEG2000 and lysine with the proline analogue cis-4-hydroxy-L-prol ine (cHyp) attached to the lysine group, has sustained, specific antifibrotic activity. It is proposed to redesign the polymer by using PEG1000 in place of PEG2000 to increase drug "loading" of the polymer. Because of the size of the p olymer (Mr=21,000d), liposomes are required for uptake by endothelial cells and a polysaccharide -coated liposome will be employed to enhance cell uptake. Retention of the polymer/liposome delivery system will be tested using an endothelial cell/smooth muscle cell (SMC) coculture system. Uptake of the delivery system by endothelial cells, stability of the polymer in cells and release of the active agent to SMCs to inhibit collagen synthesis will be studied. Another experiment will evaluate the effects of i.v. infused polymer in polysaccharide-coated liposomes on vascular collagen accumulation and pulmonary hypertension in rats exposed to hypoxia (10% O2). Results will be compared to treatment with nonbioactive trans-Hyp polymer. The strategy to locally deliver a sustained release collagen inhibitor may be applied to various fibrosing disorders. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 433 --PROJECT NUMBER......1 R43 HL58326-01 INVESTIGATOR NAME/ADDRESS FY 97 SOUTHAN, GARRY J IRG/INTRAMURAL UNIT..ZRG2 INOTEK INC AWARD AMOUNT......... $93,946 3130 HIGHLAND AVE/THIRD FLOOR CINCINNATI, OH 45219-2374 PERFORMING ORGANIZATION: INOTEK CORPORATION TITLE NOVEL IMMUNOSUPPRESSIVE AGENT FOR TRANSPLANT REJECTION ABSTRACT: DESCRIPTION: (Adapted from the applicant's abstract) Immune-mediated rejection is the principal obstacle to the use of heart transplantation for the treatment of end-stage cardiac failure. Current immunosuppressive regimens have limited efficacy and are associated with substantial toxicity. The key final common pathways of transplant rejection include the production of the toxic oxidant peroxynitrite, the free radical nitric oxide, and the prostaglandin thromboxane. Inotek, Inc. has developed a revolutionary immunosuppressive agent, mercaptoethylguanidine (MEG), which interferes with all 3 pathways simultaneously, acting as a potent scavenger of peroxynitrite, an inhibitor of cyclooxygenase, and a selective inhibitor of the inducible nitric oxide synthase. The Specific Aim of this Phase I SBIR proposal is to establish whether MEG prevents organ dysfunction and cellular injury in an experimental model of transplant rejection. This hypothesis will be tested using a well- established rat heterotopic cardiac transplantation system. Demonstration that MEG prevents tissue injury and prolongs graft survival in this model would represent a breakthrough in the design of novel immunosuppressive regimes for transplant rejection and would justify continued commercial development of MEG. Phase II SBIR funding would be used to support pre- clinical toxicology/pathology and Phase I clinical studies. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 434 --PROJECT NUMBER......1 R43 HL58332-01 INVESTIGATOR NAME/ADDRESS FY 97 GIBIAN, GARY L IRG/INTRAMURAL UNIT..ZRG7 PLANNING SYSTEMS INC AWARD AMOUNT......... $99,008 7923 JONES BRANCH DRIVE MC LEAN, VA 22102 PERFORMING ORGANIZATION: PLANNING SYSTEMS, INC. TITLE ANALYSIS, STORAGE, AND TRANSMISSION OF LUNG SOUNDS ABSTRACT: DESCRIPTION: (Adapted from the applicant's abstract) Listening to lung sounds (auscultation) is used in the diagnosis of pulmonary problems. Although X-rays and pulmonary function test are normally used as well, neither is adequate by itself for diagnosing all types of lung diseases. There is recent evidence that differences in lung sounds among common pulmonary conditions allow good predictions of diagnostic categories. The application of high-resolution acoustic analytical techniques to develop methods for the remote monitoring of lung function by analyzing breath sounds through a computerized telephone network could make detection and more frequent assessment of pulmonary problems more convenient and more affordable. The goal of the proposed research is to develop a clinically useful system on a common desktop personal computer. This Phase I proposal addresses (1) wavelet based processing techniques to provide enhancements in auscultation for diagnosing lung diseases, data compression and storage, and automatic detection of adventitious sounds by a single system; and (2) a preliminary design study for a remote monitoring system based on transmission of lung sounds between computers on a telephone network. The affordable nature of such a system makes it suitable for widespread use. The system would find commercial application in hospitals, clinics, schools and industrial sites, and doctors' offices. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 435 --PROJECT NUMBER......1 R43 HL58338-01 INVESTIGATOR NAME/ADDRESS FY 97 ANDERSON, D MICHAEL IRG/INTRAMURAL UNIT..ZRG2 MILLENNIUM HEALTH AWARD AMOUNT......... $100,000 2734 CORTLAND PLACE, NW WASHINGTON, DC 20008 PERFORMING ORGANIZATION: MILLENNIUM HEALTH TITLE MULTIMEDIA FITNESS PROMOTION FOR SEDENTARY ADULTS ABSTRACT: This project will develop and evaluate a multimedia exercise promotion program to meet adult learning characteristics by: 1) structuring the program into modules that can be used individually or sequentially; 2) allowing users to select their own path through the program, based on time, need, and learning style; 3) ensuring that the focus of the program is on the application of skills and concepts through use of scenario-based learning experiences; and 4) ensuring that the feedback component of the program is a constructive learning experience providing users with response- specific feedback, remedial branching when needed, and a complete, printed, personal exercise prescription. Video models of basically healthy but inactive adults overcoming barriers to exercise will be available as part of the program. Exercise activities and programs will be selected by the computer to match user characteristics entered at the beginning of the program. For users with modems, an on-line connection will be made possible with online fitness support groups. In the Phase I prototype we will design and evaluate a prototype of one module of the envisioned product. All efforts will be directed toward development of an evaluated and commercially feasible multimedia product in Phase II and for its distribution thereafter.

Principal Investigator:

Gonda, igor
0

Business Contact:


5107830100
Small Business Information at Submission:

Aradigm Corporation
26219 EDEN LANDING RD Hayward, CA 94545

EIN/Tax ID:
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No