Proprietary Technologies Available for Licensing

Aequorin

Recombinant aequorin, is a 22,000-molecular weight photoprotein isolated from the jellyfish, Aequorea victoria. Aequorin emits a flash of blue light upon exposure to calcium ions, which produces a direct, ultrasensitive signal that can be measured with a luminometer.  When conjugated to other proteins such as antibodies or streptavidin or to small molecules such as biotin, the conjugates can be used as detection labels in bioluminescence-based assays (BIA). The amount of label present is determined by adding a calcium salt solution and measuring the amount of light produced during the bioluminescent reaction. U.S. Patent numbers 5,422,266, 5,744,579, 5,766,941, 5,798,441 and related foreign patents.

AMPK

AMPK (5’ AMP-activated protein kinase) is a heterotrimeric protein formed by α, β, and γ sub-units and is a key regulatory protein involved in cellular energy homeostasis. Binding of AMP (adenosine monophosphate) to the γ domain induces a conformational change, exposing the catalytic domain of the α sub-unit to phopsphorylation by the upstream kinase AMPKK. Upon phosphorylation by AMPKK, AMPK increases cellular energy levels by downregulating energy-consuming anabolic pathways and upregulating energy-producing catabolic pathways. AMPK is deactivated by increasing levels of ATP. AMPK is protected by U.S. patent number 6,124,125.

Amplifluor

Amplifluor® is a novel amplification and detection methodology that uses fluorescence energy transfer labels to perform quantitative PCR in a closed-tube format. This system consists of energy transfer labeled hairpin primers that produce a fluorescent signal only through incorporation into the amplification product. This technology allows for real-time monitoring of PCR as the fluorescence emitted is proportional to the amount of specific amplicon produced. Endpoint analysis can also be performed using this method. The signal can be detected by a variety of devices including fluorescent microtiter plate readers, spectrofluorometers, fluorescent imaging systems, and real-time instruments. U.S. Patent numbers 5,866,336, 6,090,552, 6,117,635 and related foreign patents.

BRCA1 and BRCA2

BRCA1 and BRCA2 are important gene targets in the investigation and diagnosis of breast and ovarian cancers. Millipore has the exclusive license rights from Myriad Genetics, Inc. to patents covering the BRCA1 and BRCA2 genes including their polypeptides and antibodies in the research field of use. U.S. patent numbers 5,747,282, 5,753,441, 5,837,492, 6,124,104 and 6,162,897.

GST

The Glutathione S-transferase (GST) gene fusion system is an integrated system for the expression, purification and detection of fusion proteins. U.S. Patent numbers 5,654,176 and related foreign patents. *Any commercial applications requires a license (examples include: antibodies against GST fusion proteins, development of commercial products through use of the GST expression system, research using the GST expression system that results in a commercial product). Amersham Pharmacia has exclusive rights for sales of expression vectors for scientific and research purposes only.

ILK

Integrin-linked kinase (ILK) is a serine-threonine kinase that is implicated in cell-to-extracellular matrix interaction, growth factor signaling, cell survival, cell migration, invasion, anchorage-independent growth, and angiogenesis. Increased expression of ILK has been associated with the progression of several tumor types. The ILK nucleic acid sequence, polypeptide, and anti-ILK antibodies are protected by U.S. Patents 6,369,205; 6,013,782; 6,001,622; 6,338,958; 6,699,983; 7,189,802 and related foreign equivalents. Millipore has the exclusive commercial research rights to these ILK patents and the ability to sub-license these patent rights which are owned by the University of Toronto Innovations Foundation.

Kinase Substrates

Protein kinases are a family of enzymes that modify other proteins by phosphorylation. Phosphorylation of the kinase substrate results in a functional change of the substrate protein by changing the enzymatic activity of the substrate, altering the substrate’s cellular location, or the influencing the substrate’s ability to associate with other proteins. Protein kinases regulate the majority of cellular pathways, especially those involved in cellular signal transduction. Aberrant expression and regulation of protein kinases have been implicated in tumorigenesis. Certain kinase substrates are protected by E.U. Patent 1492882. Millipore has the exclusive right to sub-license unique kinase substrates in the research field.

Antibodies to JAK1 and JAK2

JAK kinases are a series of proteins involved in the regulation of the immune system and cell proliferation. Through the phosphorylation of STATS, these enzymes play a critical role in the cytokine and growth factor signal transduction pathways. The antibodies to JAK1 and JAK2 are covered under US patent number 5,658,791, Australian patent #PK3954, and European patent #9290155.9-2105. These antibodies are exclusively licensed by Millipore for use in research applications.

MAP2K/MKK

Mitogen-activated protein (MAP) kinase kinase (MAPKK or MAP2K) mediate unique signal transduction pathways that activate MAP kinases p38 and JNK, which result in downstream activation of activating transcription factor-2 (ATF2) and c-Jun. MAP kinase pathways are activated by a number of factors, including cytokines and environmental stress. MAP2K is protected by U.S. Patent 6,174,676 and related foreign equivalents. Millipore has the exclusive rights to sub-license MAP2K patents rights from the patentee (Mass General) within the research field.

Methylarginine Antibodies

Protein methylation plays an important role in cell signaling. N-methylation, which modifies arginine residues in proteins, has generally been regarded as a constitutive and irreversible post-translational modification. While protein methylation is clearly important in cell signaling mechanisms, its precise role in cellular growth and differentiation remains largely undetermined. Methylarginine-specific antibodies are protected by U.S. Patent 6,699,673. Millipore has the exclusive right to sub-license methylarginine-specific antibodies from The Research Foundation of State University of New York, Buffalo in the research field.

MSK1/MSK2

Mitogen-and-Stress-Activated Protein Kinase 1 and 2 (MSK1, MSK2) are unique nuclear serine/threonine protein kinases containing two kinase domains within a single polypeptide. MSK1 and MSK2 are believed to mediate signal transduction in the inflammatory response and regulate cellular proliferation and differentiation. MSK1 and MSK2 are activated by the MAPK/ERK pathway (mitogen/growth factor signaling) or SAPK2/p38 pathway (stress/oxidation signaling). MSK1 and MSK2 are believed to activate transcription factors CREB and ATF-1. MSK1 and MSK2 are licensed exclusively by Millipore from the University of Dundee and are protected by U.S. 7,122,360 and EP1109918.

P15 and P14

Cyclin-dependent kinase inhibitors p15 and p14 act as tumor suppressor genes and are frequently deleted or mutated in a wide variety of human tumors. Millipore has the exclusive license rights from Myriad Genetics, Inc. to patents covering certain regions of these genes as well as the polypeptides, proteins and antibodies for p15 in the research field of use. U.S. patents 5,739,027, 5,801,236, 5,843,756, 5,994,095, 6,060,301, 6,140,473, 6,180,776, 6,210,949 and 6,218,146.

Photoprotein Conjugation

Millipore has the exclusive rights to a method of conjugating photoproteins. This method allows for the retention of a substantial portion of the luminescent activity of the photoprotein. Bioluminescent proteins conjugated through this technique may be conjugated with a variety of binding reagents including, but not limited to, streptavidin/avidin, lectins, enzymes, glycoproteins, peptides, hormones, receptors, antigens, drugs, antibodies and antigen binding fragments thereof, RNA, DNA, oligonucleotides, or any other selectively bindable molecules or compositions. U.S. patents 5,486,455, 5,648,218 and related foreign patents.

PTEN

PTEN is a tumor suppressor protein located on human chromosome 10 that is often mutated in various types of advanced cancers. The PTEN protein exhibits protein phosphatase activity and can suppress the growth of glioma cells. Millipore has the exclusive license rights from Myriad Genetics, Inc. to patents covering the PTEN gene including its polypeptide and antibodies in the research field of use. U.S. patents 6,262,242, 6,482,795 and 7,217,795.

Renilla Luciferase

Renilla Luciferase is a bioluminescent peptide derived from the sea pansy. The addition of the substrate ceolenterazine catalyzes a long-lasting luminescence or "glow". When conjugated to other proteins these conjugates can be used as detection labels in bioluminescence-based assays. US patents 5,418,155 and related foreign patents.

SGK

Serum and glucocorticoid-induced protein kinase (SGK) is a class of serine/threonine protein kinases induced following cellular exposure to serum or glucocorticoids. SGK is also induced in response to other stimuli, such as follicle stimulating hormone, induced extracellular osmolarity, and transfection of mammary epithelial cells with p53. SGK is activated by IGF-1 or oxidative stress via the PtdIns-3-kinase pathway. Once activated, SGK preferentially inactivates GSK3 via phosphorylation. SGK1, 2, and 3 are licensed exclusively by Millipore from the University of Dundee and are protected by U.S. 7,083,511.

SOCS proteins

The suppressors of cytokine signaling (SOCS) are a family of intracellular protein that regulate cytokine responses. The SOCS proteins regulate signal transduction by combining direct inhibitory interactions with cytokine receptors and signaling proteins (Alexander WS, 2002). Millipore has the right to grant licenses in the research field of use to the SOCs family of patents. U.S. patent 6,323,317.

If you are interested in obtaining a license for any of the listed technologies, please contact roy.millender@merckgroup.com or marie.azzaria@merckgroup.com for further information.