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Start Preamble
AGENCY:
National Institutes of Health, Public Health Service, HHS.
ACTION:
Notice.
SUMMARY:
The inventions listed below are owned by agencies of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.
ADDRESSES:
Licensing information and copies of the U.S. patent applications listed below may be obtained by writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will Start Printed Page 37851be required to receive copies of the patent applications.
Transgenic Mouse Model of Human B-cell Neoplasia Based on Myc Insertion into IgH (IgH-Mycm)
Siegfried Janz, M.D. (NCI)
DHHS Reference No. E-160-2003/0
Licensing Contact: Jeffrey Walenta; 301/435-4633; walentaj@mail.nih.gov.
Some types of cancers are caused by the translocation of genes between two different chromosomes. When a translocation occurs near a highly active promoter, uncontrolled cell growth can be the result if the translocated chromosome piece contains an oncogene. For example, in some types of B cell neoplasias the Myc oncogene from chromosome 8 is translocated into the highly transcribed region of the IgH locus in chromosome 14.
This invention is a transgenic mouse model that mimics the t(8;14)(q24;q32) translocation commonly found in human sporadic Burkitt's Lymphoma. Specifically, this model has the Myc gene inserted into the IgH locus just upstream of the constant region Cm.
Since the Myc translocation can occur at various regions within the IgH locus, several mouse models of Myc-IgH translocations have been developed. Two of these, the IgH-MycEmIgH-MycCa, have been made available previously. The present specific translocation (IgH-MycCm) animal model will deepen the understanding of the pathogenesis of B-cell neoplasia, uncover new targets for treatment, and serve as a pre-clinical model for innovative intervention approaches.
Inducing a T-Cell Response With Recombinant Pestivirus Replicons or Recombinant Pestivirus Replicon-Transfected Dendritic Cells
Barbara Rehermann et al. (NIDDK) Serial No. 60/462,165 filed 11 Apr 2003 (DHHS Reference No. E-098-2003); Serial No. 60/463,097 filed 14 Apr 2003 (DHHS Reference No. E-230-2003),
Licensing Contact: Jeffrey Walenta; 301/435-4633; walentaj@mail.nih.gov.
Cancer and diseases such as Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Respiratory Syncytial Virus (RSV), Mycobacterium tuberculosis, Plasmodium falciparum infection, are not effectively prevented by the humoral immune response initiated by standard antigen vaccinations. The neutralizing antibody response created by these types of vaccinations is not effective enough to prevent the progression of the disease. In these cases, a cellular, T-Cell mediated immune response is a much more effective vaccination strategy.
This invention describes the use of recombinant pestivirus replicons or recombinant pestivirus replicon transfected dendritic cells to induce and/or enhance a T-cell mediated immune response by exploiting the cross-priming ability of endogenous antigen-presenting cells (APCs). These recombinant pestivirus replicons contain an antigen specific to a disease requiring a T-cell response. This antigen is presented to APCs in the lymphatic system by the apoptotic transfected dendritic cells that initiate cross-priming.
This invention generates a stronger immune response than current dendritic cell/APC methods. Because dendritic cells transfected with the recombinant pestivirus replicons survive longer than dendritic cells transfected with other viral replicons, more transfected dendritic cells enter the lymphatic system and undergo apoptosis there. This results in a greater amount of cross-priming and a stronger T-Cell response.
Inhibition of Ubiquitin-Mediated Process by UBA Domain Peptides
Stan Lipkowitz et al. (NCI)
Serial No. 60/464,658 filed 23 Apr 2003 (DHHS Reference No. E-324-2002/0)
Licensing Contact: Jeffrey Walenta; 301/435-4633; walentaj@mail.nih.gov.
Ubiquitin is a protein tag that targets cellular proteins for degradation by the multicatalytic protease, the proteasome. A three-component system of ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin protein ligase (E3) promotes the covalent attachment of ubiquitin to a protein to be degraded. Of the three components, the E3 component confers the specificity to the ubiquitination.
This invention describes isolated peptides comprising an ubiquitin-associated (UBA) domain that inhibits ubiquitin-mediated protein degradation by binding ubiquitin and polyubiquitin. The series of UBA domain peptides contain a structurally conserved core and a characteristic set of three alpha helices. Specifically, these studies centered on the UBA domain of the proto-oncogene, cbl-b. Expression of the cbl-b UBA-domain peptide in a cell inhibits the degradation of epithelial growth factor (EGFR), murine double minute 2 (Mdm2), and seven in absentia homologue-1 (Siah-1).
UBA domain peptides will be useful in treating conditions associated with an unusually high level of an ubiquitin-mediated process. Defects in the functioning of the ubiquitin/proteasome system can have severe consequences on biological homeostasis, causing a multitude of pathological conditions. The most obvious treatment options using the UBA-domain peptides could be for cancer, developmental disorders, and inflammatory conditions. In addition, UBA domain peptides can be used to inhibit ubiquitin mediated processes to further the understanding of the cell biological and development roles of these processes.
Use of Discoidin Domain Receptor 1 (DDR1) and Agents That Affect the DDR1/Collagen Pathway
Teizo Yoshimura (NCI)
PCT/US02/39793 filed 11 Dec 2002 (DHHS Reference No. E-083-2002/2-PCT-01),
Licensing Contact: Jeffrey Walenta; 301/435-4633; walentaj@mail.nih.gov.
Dendritic cells (DCs) are pivotal antigen-presenting cells for initiation of an immune response. Indeed, dendritic cells provide the basis for the production of an effective immune response to a vaccine, particularly for antigens wherein conventional vaccination is inadequate. DCs are also important in the production on an immune response to tumor antigens.
The present invention discloses methods of using the receptor tyrosine kinase discoidin domain receptor 1 (DDR1) to facilitate the maturation/differentiation of DCs or macrophages. Activating agents of DDR1 may be useful in the induction of a highly potent, mature DCs or highly differentiated macrophages from DC precursors, such as monocytes. Use of this method may enhance the antigen presenting capabilities of the immune system, leading to a more effective overall immune response.
This research is further described in Kamohara et al., FASEB J. 10.1096/fj.01-0359fje (published online October 15, 2001) and Matsuyama et al., FASEB J. 10.1096/fj.02-0320fje (published online May 8, 2003).
Production of Adeno-Associated Viruses in Insect Cells
Robert Kotin et al. (NHLBI)
Serial No. 09/986,618 filed 09 Nov 2001 (DHHS Reference No. E-325-2001/0); Serial No. 10/216,870 filed 13 Aug 2002 (DHHS Reference No. E-325-2001/1); PCT/US02/35829 filed 08 Nov 2002 (DHHS Reference No. E-325-2001/2),
Licensing Contact: Jeffrey Walenta; 301/435-4633; walentaj@mail.nih.gov.
Currently, adeno-associated virus (AAV) is being developed for gene therapy applications. This virus type presents several advantages over alternate vectors for therapeutic gene Start Printed Page 37852delivery. AAV is not considered pathogenic and transduces stably dividing and non-dividing cells; and shows good serotype specificity to various cell types for targeted gene delivery.
This invention is a highly scalable AAV vector production method in insect cells. This production method produces virus particles much more efficiently than the standard mammalian cell culture system. For example, to produce 1015 rAAV particles may require 5,000 175cm2 flasks. With this new production method, 10 to 50 liters of Sf9 insect cells are required to produce the same quantity of AAV particles. This is a striking improvement in production efficiency. In addition, all serotypes of AAV can be produced, with the respective AAV serotype vectors available for the immediate scale up of AAV production.
This invention coupled with NIH invention E-308-2001, titled “Scalable Purification of AAV2, AAV4 or AAV5 Using Ion-Exchange Chromatography,” gives a licensee a highly scalable production and purification system for efficient clinical trial development and commercialization of AAV.
Scalable Purification of AAV2, AAV4 or AAV5 Using Ion-Exchange Chromatography
Nikola Kaludov (NIDCR)
John Chiorini (NIDCR)
Serial No. 60/381,180 filed 17 May 2002; Serial No. 10/166,347 filed 17 May 2003 (DHHS Reference No. E-308-2001/0),
Licensing Contact: Jeffrey Walenta; 301/435-4633; walentaj@mail.nih.gov.
Adeno-associated viruses (AAVs) constitute, as a group, the vehicle of choice for gene therapy because of several attractive features. Among others, AAVs are less pathogenic than other viruses, and they can be used for the long-term expression of therapeutic genes.
This invention describes a simple ion-exchange (HPLC) methodology to purify different AAV serotypes. The protocol, which can be readily scaled up, details the efficient concentration of fully infective AAV particles, and is applicable to a number of promising serotypes for which efficient purification methodologies are currently lacking. Significantly, the method consistently produces higher infectivity per particle ratios than standard methods.
This invention, coupled with NIH invention E-325-2001, entitled “Highly Scalable Production of AAV in Insect Cells,” would give a licensee a purification system that can be readily scaled-up to efficiently produce recombinant adeno-associated viruses for clinical trial development.
This work is further described in Kaludov et al., Hum. Gene Ther. (2002) 13:1235-43.
Start SignatureDated: June 16, 2003.
Steven M. Ferguson,
Acting Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. 03-15971 Filed 6-24-03; 8:45 am]
BILLING CODE 4140-01-P
Document Information
- Published:
- 06/25/2003
- Department:
- National Institutes of Health
- Entry Type:
- Notice
- Action:
- Notice.
- Document Number:
- 03-15971
- Pages:
- 37850-37852 (3 pages)
- PDF File:
- 03-15971.pdf