SPECIAL NOTICE
A -- TECHNOLOGY/BUSINESS OPPORTUNITY Selective High Affinity Ligands
- Notice Date
- 2/26/2009
- Notice Type
- Special Notice
- NAICS
- 238990
— All Other Specialty Trade Contractors
- Contracting Office
- Department of Energy, Lawrence Livermore National Laboratory (DOE Contractor), Industrial Partnerships & Commercialization, 7000 East Avenue, L-795, Livermore, California, 94550
- ZIP Code
- 94550
- Solicitation Number
- FBO200-09
- Archive Date
- 3/13/2009
- Point of Contact
- Connie L Pitcock, Phone: 925-422-1072
- E-Mail Address
-
pitcock1@llnl.gov
- Small Business Set-Aside
- N/A
- Description
- TECHNOLOGY/BUSINESS OPPORTUNITY Selective High Affinity Ligands Opportunity : Lawrence Livermore National Laboratory (LLNL), operated by the Lawrence Livermore National Security (LLNS), LLC under contract with the U.S. Department of Energy (DOE), is offering the opportunity to license selective high affinity ligands for treatment of Non-Hodgkin's Lymphoma. Background : Non-Hodgkin's Lymphoma (NHL) is the sixth most common cancer. It is the cancer of lymphoid tissue and lymph nodes of the lymphatic system, derived from B-cell or T-cell lymphocytes, two types of white blood cells. Lymph nodes produce and store lymphocytes as part of a process that generates an immune response against infections. In 2008, an estimated 66,120 new diagnoses were made and 19,160 people died of NHL in the United States. [1] The current treatment of NHL, which varies depending on the progression of the disease, involves radiation, chemotherapy or a combination of chemotherapy and immunotherapy. Recently, radioimmunotherapy using the radionuclide-tagged Lym-1 monoclonal antibody has been used in clinical trials to selectively deliver cytotoxic radiation to the disease. While this approach has shown considerable success, one disadvantage of radioimmunotherapy is the long residence time of the antibody in the body. This leads to the irradiation of sensitive, normal cells. Antibodies have also been observed to provoke a serious immune response in the patient. Description : Lawrence Livermore National Laboratory (LLNL) and University of California, Davis have developed a synthetic ligand 2 with a similar affinity and specificity to the antibody Lym-1, which binds to the HLA-DR10 receptor on the surface of B-cell lymphocytes. The HLA-DR10 marker is present on the lymphoma cells of over eighty percent (80%) of patients diagnosed with NHL. Using small molecule screening techniques and engaging with synthetic chemists to produce the compound, we have created a small molecule that mimics the binding of the Lym-1 antibody to NHL cells. The selective high affinity ligand (SHAL) binds specifically to cells that have the HLA-DR10 cell receptor and exhibits minimal uptake by other organs 3, such as the kidneys and liver. The compound has been shown in animal studies to have improve pharmacokinetic properties when compared to antibodies and is less likely to elicit an immune response. The compound is selectively cytotoxic to cultured cells expressing HLA-DR10 4 and has been shown to induce the regression of xenograft tumors in mice 5. [2] Advantages : Small molecule (less than 4,000 Da) with improved pharmacokinetic properties Synthetic ligand binds selectively to the beta-subunit of HLA-DR10 on NHL cells Contains a chelator for attaching radionuclides to enable its use in radioimmunotherapy Selectively delivers cytotoxic radiation to disease Less likely to elicit immune response Can be synthesized in gram quantities at a fraction of the cost of antibodies Potential Applications : Selective High Affinity Ligands may be used to diagnose and treat Non-Hodgkin's Lymphoma. Development Status : A team of LLNL and UC Davis investigators have developed a series of small molecule therapeutics for non-Hodgkin's Lymphoma. Derivatives of the molecules have been produced with biotin, fluorochrome or metal chelating tags for use in staining cells/tissues or charging with radionuclides for targeted radiotherapy. Modifications have been made to enhance uptake and selective retention of the molecules in tumor cells. Pharmacokinetic studies have revealed the molecules exhibit tissue uptake and blood and body clearance rates characteristic of small molecule therapeutics. Other experiments have been conducted to assess the efficacy of two of the compounds in killing tumor cells. Both compounds are selectively cytotoxic to tumor cell lines expressing HLA-DR10; these molecules have no adverse effect on cell lines lacking HLA-DR10 (normal or tumor). One of these compounds has also been observed to induce the regression of tumor xenografts in mice. Two patent applications have been filed. A published patent application, 20060084115 "Selective High Affinity Polydentate Ligands and Methods of Making Such" is available from the USPTO. (link: http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=/netahtml/PTO/srchnum.html&r=1&f=G&l=50&s1=20060084115.PGNR.&OS=DN/20060084115&RS=DN/20060084115) A recent publication in International Journal of Oncology (2007) 31(4): 729-740 is also available. (link: http://www.spandidos-publications.com/ijo/archive.jsp?journal_id=ijo ) LLNL is seeking industry partners to complete the toxicology studies, shepherd the best of the compounds into a clinical trial, and commercialize the final reagent or therapeutic for use in diagnosing or treating non-Hodgkin's lymphoma and other B-cell lymphocyte derived malignancies. Moving critical technology beyond the Laboratory to the commercial world helps our licensees gain a competitive edge in the marketplace. All licensing activities are conducted under policies relating to the strict nondisclosure of company proprietary information. Please visit the IPO website at http://ipo.llnl.gov/workwithus/partneringprocess.php for more information on working with LLNL and the industrial partnering and technology transfer process. Note: THIS IS NOT A PROCUREMENT. Companies interested in commercializing LLNL's Selective High Affinity Ligands should provide a written statement of interest, which includes the following: 1. Company Name and address. 2. The name, address, and telephone number of a point of contact. •3. A description of corporate expertise and facilities relevant to commercializing this technology. Written responses should be directed to: Lawrence Livermore National Laboratory Industrial Partnerships Office Attn: Ida C. Shum P.O. Box 808, L-795 Livermore, CA 94551-0808 Attention: FBO 200-09 Please provide your written statement within fifteen (15) days from the date this announcement is published to ensure consideration of your interest in LLNL's technology. <hr size="1" /> 1 National Cancer Institute 2 Balhorn, R et al., Selective High Affinity Ligand Antibody Mimics for Cancer Diagnosis and Therapy: Initial Application to Lymphoma/Leukemia. Clin. Cancer Res. (2007) 13: 5621s-5628s. 3 DeNardo, GL et al., Characteristics of Dimeric(bis) Bidentate Selective High Affinity Ligands (SHALs) as HLA-DR10 Beta-Antibody Mimics to Target non-Hodgkin's Lymphoma (NHL). Int. J. Oncol. (2007) 31: 729-740. 4 DeNardo, GL et al., Nanomolecular HLA-DR10 Antibody Mimics: A Potent System for Molecular Targeted Therapy and Imaging. Cancer Biother. & Radiopharm. (2008) 23: 783-795. 5 DeNardo, GL et al., Molecular Specific and Cell Selective Cytotoxicity Induced by a Novel Synthetic HLA-DR Antibody Mimic for Lymphoma and Leukemia. Int. J. Oncol. (2009) 34: 511-516.
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