final IPR Biotech _August 2010_

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					WISTA                                                                                                            AUGUST 2010

  From the Desk of Chairman                                                         IPR Biotechnology :          Part 8 - 64
       Epigenome is a set of chemical switches that control gene expression within a cell. It works as a second layer
  of information that directs select cells to become brain, hair or other cells. The chemical changes affecting the gene
  expression include methylation, ie, additon of a methyl group to certain nitrogen bases. Epigenetics being an emerging
  scientific field, has generated interest of researchers for studying gene expression patterns, as well as the way
  environmental factors change the manner genes are expressed. It is increasingly considered that a wide variety
  of illnesses and behaviors are linked to epigenetic mechanisms. Therefore, epigenetic research could be expected
  to help realize the potential of stem cells for medical applications.
       The 'Special Feature' in the current issue of WISTA: IPR Biotechnology deals with epigenetics and its role
  in heredity and normal fucntioning. It covers the internal factors that determine the gene expression profile and the
  epigenetic mechanism. This feature also gives gist of some pertinent patents granted recently in this field, particularly
  in the USA.
       The feature 'Perspective' relates to nanosensors, whose medicinal use revolves around the potential these have
  in accurately identifying particular cells or places in the body. Nanosensors have the potential to distinguish between
  and recongnize cerntain cells, notably those of cancer, by measuring changes in volume, concentration, displacement,
  pressure or temperature of cells in a body. This write-up also covers the significance of nanosensor and their likely
  applications in the field of healthcare and other fields.
       'On to Excellence' profiles Generex Biotechnology Corporation, that focuses on developing proprietary vaccine
  formulations that work by stimulating immune system. It also lists the Corporation's key acheivements over the
      Other features covered include: Scan Around the Globe; Watch-Out IPR; In Focus, Strategic Alliances,
  Clinical Trials; Awards; Fine Tuning; and Legal Scene.
      We welcome comments and suggestions.
                                                                                  Dr K V Swaminathan

  CONTENTS                                                                                   RESEARCH & ANALYSIS TEAM
  • From the Desk of Chairman [P 2 ]                                                        Dr Shelley Lahiri        Consultant
  • Scan Around the Globe: Breast Cancer Gene Patent (Australia); AccuDial Drug(Canada);
    Biofuels form Straw (Germany); Notice of Allowance for OXIGON (Israeli); E Keppra       Mr B K Wadhawan          Director
    Receives Regulatoral Approval (Japan); Healthcare Industry of Singapore(Singapore);
    Vitamin E Reduces Alzheimer’s Risk (Sweden). [P 3 - 4]                                  Mr S S Kalra             Director
  • Watch-Out IPR: Influenza Patent; Notice of Allowance for Diabetes Drug; Novel Hip
    Implant; Patent for Cell Proliferative Disorders; Patent for Digital Forensics;         This     publication  aims   at
    PRTT Acquires of Multipantents; Stem Cell Industry Report; UK Patent for TLE3           disseminating information on
    Biomarker [P 5 - 6]                                                                     pertinent developments in its
  • Perspective: Nanosensor. [P 7]                                                          specific field of coverage. The
                                                                                            information published does not,
  • In Focus: Cardiac–Specific Gene; Genetic Regulatory Materials; Hepcidin Affected
                                                                                            therefore, imply endorsement of
    Lymphocytes; Immune Regulatory Single Protein; Oncogene’s Secret Growth Formula;
    Nuclear Receptors for Heart; Synthetic Enzymes. [P 8 - 9]                               any product/process/producer or
                                                                                            technology by WITT.
  • Strategic Alliances: Agreement for Drug Formulation; Co-Development of siRNA
    Therapeutics; Combining Technologies for Chromatography; Merger Agreement;
    Partnership to Develop Prophylactic Vaccine; Phileps-Dako Collaboration; Research       Editor : Dr K V Swaminathan
    and Development Agreement. [P 10 - 11]                                                  Printed and Published by
  • On To Excellence: Generex Biotechnolgy Corporation. [ P 12 ]                            Dr K V Swaminathan, on behalf of
  • Special Feature: Epigenetics. [P 13 - 15]                                               Waterfalls Institute of Technology
                                                                                            Transfer, J-29 South Extension Part I,
  • Clinical Trials: Preventive Malaria Treatment; Side Efects of Increasing Dose. [P 16]
                                                                                            New Delhi - 110 049.
  • Awards: AACR Award ; Vaccine Industry Excellence Award. [P 16]
  • Fine Tuning: PRC 1 Protein. [P 17]
                                                                                             Printed at Sagar Printers,
  • Legal Scene: Action Closing Prosecution; Counterclaims to Declaratory Judgment;          1880 Udaichand Marg,
    Drug Marketing Lawsuit; Endovascular Technology; New Defence in Infringement             Kotla Mubarakpur,
    Case; Settlement of OPANA ER Litigation; Validity of Haemonetics' Patent;
                                                                                             New Delhi -110 003.
    ZETIA Patent Litigation. [P 18 - 19]

 VOL 12 ISSUE 2                                                   1                                IPR BIOTECHNOLOGY
 SEC 2
WISTA                                                                                                   AUGUST 2010

                                                                 label. A parent simply rotates the label until their
        SCAN AROUND THE GLOBE                                    child’s weight appears in the viewing window and
                                                                 the correct dose is shown below the weight. A dosing
                                                                 spoon is included in each package so parents can
 Breast Cancer Gene Patent                                       easily measure and administer the medication.

     BRCA1 and BRCA2 are two susceptible genes                                  (Canada – Marketwire, Jul 27, 2010)
 for women’s breast or ovarian cancer. Changes of
 these two genes, known as mutations, are significant            Biofuels from Straw
 in women who go to develop breast or ovarian
 cancer. Melbourne based company Genetic                             Süd-Chemie is to build Germany’s largest
 Technologies Ltd. (GTL) has the exclusive license               plant for the biotechnolgcial production of
 from American biotechnology company Myriad                      climate friendly, second generation bioethanol,
 Genetics to carry out testing for the genes in Australia.       so called cellulose ethanol, based on biotechnological
    Myriad holds a patent for these genes. After many
 women complained of the cost of the genetic tests                   The total project has a volume of altogether
 which could be done only by the patent holding                  •28 million and comprises an investment volume
 company, many law firms came forth to argue that                of some •16 million and accompanying research
 genes occur in nature and could not be patented.                projects amounting to approximately •12 million.
                                                                 These and additional related research projects will
     According to patent law expert at the                       be subsidized by the Bavarian state government and
 Australian National University, this lawsuit is very            Germany’s federal ministry of education and
 significant, because for the first time in Australian           research (BMBF) with approximately •5
 legal history, the Australian courts are going to rule          million respectively. As from the end of 2011, this
 on whether an isolated biological material, such as             large-scale demonstration plant, located in the
 the human gene which has been removed from the                  immediate vicinity of the new Bavarian BioCampus
 human body, is an invention. For the last 20-odd                in Straubing, will produce up to 2,000 tonnes
 years the Australian patent office [IP Australia]               per year of bioethnol fuel from agricultural waste,
 has been granting patents on all manner of                      such as cereal straw.
 biological material, such as plants, plant genes, viral
 genes, etc.                                                         The sunliquid® process, which Süd-Chemie
                                                                 has been testing in the pilot plant since the beginning
     (Australia – Medical Patent News, Jun 7, 2010)              of 2009, is an innovative method of producing
                                                                 second-generation bioehtanol in a cost-effective
 AccuDial Drug                                                   and energy-efficient manner. To this end,
                                                                 cellulose-based plant residue, such as wheat straw
     Canadian Sales & Marketing Company,                         or maize straw, bagasse from sugar cane or
 AccuDial® Pharmaceutical, Inc. has developed                    so-called energy crops, are initially converted into
 a revolutionary way to better dose childern. This               sugar constituents with the aid of enzymes
 drug from the company’s over-the-counter (OTC)                  generated using biotechnology.
 division offer the only rotating labeling system
 for weight-specific dosing of childern’s over-                      Bioethnol is subsequently extracted from these
 the-counter medications to treat children's pain                constituents and used as fuel. In the case of Süd-
 and fever, allergy, cough and cold.                             Chemie’s process, not only the cellulose contained
                                                                 in plants, but also the co-called hemicellulose can be
     Children’s AccuDial is the only medication                  converted into ethanol, making it possible to
 that provides weight-specific dosing using a rotating           increase ethanol production by up to 50 percent

IPR BIOTECHNOLOGY                                            2
WISTA                                                                                        AUGUST 2010

 compared with conventional technology.                  Healthcare Industry of Singapore
 Furthermore, the enzymes needed to convert the
 cellulose can be optimized depending on the original        Singapore Pharmaceuticals and Healthcare
 raw materials used and produced directly on             Report provides industry professionals and
 the spot in each production plant. This guarantees      strategists, corporate analysts, pharmaceutical
 an optimal enzyme supply, being both highly efficient   associations, government department and
 and cost-effective.                                     regulatory bodies with independent forecasts
                                                         and competitive intelligence on Singapore’s
              (Germany – Bionity .com, Jul 23, 2010)     pharmaceuticals and healthcare industry.

 Notice of Allowance for OXIGON                              In BMIs Business Environment Ratings (BER)
                                                         table for Q3 10, Singapore is ranked fifth of the
    Intellect Neurosciences, Inc has received a          16 markets assessed in the Asia Pacific region, up
 Notice of Allowance from the Israeli Patent and         from the previous quarter and improving further
 Trademark Office for a new patent related to the        upon its rise from eighth in Q4 09 to seventh in
 company’s clinical-stage drug candidate                 Q1 10. Globally, Singapore ranks 22nd of the 82
 OX1 (OXIGON™), which has disease-modifying              pharmaceutical markets surveyed by BMI.
 potential for Alzheimer’s and other
 neurodegenerative disorders.                                  (Singapore – Singapore Pharmaceuticals and
                                                                 Healthcare Report Q3 2010, Jun 29, 2010)
    OX1, which has been successfully tested by the
 company in human Phase I safety trials, is an orally-   Vitamin E Reduces Alzheimer’s Risk
 administered, brain-penetrating, naturally-occurring
 copper-binding small molecule targeting multiple            The Aging Research Centre (ARC), Karolinska
 mechanisms that contribute significantly to the         Institute, Stockholm, Sweden, conducted a
 underlying pathology of Alzheimer’s disease.            research study of Alzheimer’s disease (AD) in
                                                         collaboration with the Institute of Gerontology
     The Notice of Allowance is a written                and Geriatrics, University of Perugia, Italy. The
 communication from the patent office of Israel          study included a sample of 232 participants from
 stating that the application has been allowed and       the Kungsholmen Project, a population-based
 will be granted an Israeli patent after payment         longitudinal study on aging and dementia in
 of the government issue fee.                            Stockholm (Kungsholmen parish). All participants
                                                         were aged 80+ years and were dementia-free at
                               (Israeli - Jun 9, 2010)   the beginning of the study (baseline). After 6 years
                                                         of follow-up, 57 AD cases were identified.
 E Keppra Receives Regulatory Approval
                                                             In the study, high levels of several vitamin E
     Two Japanese companies, Otsuka Pharmaceutical       (which is a family of eight natural components)
 Co. Ltd. and UCB are co-promoting a drug called         components in the blood were found to be
 E Keppra. The two companies have received               associated with a decreased risk for Alzheimer’s
 manufacturing and marketing approval from               disease in advanced age. But most studies related
 the Japanese Ministry of Health, Labour and             to Alzheimer’s disease investigate only one of
 Welfare (MHLW) for E Keppra, as an adjunctive           these components, ±-tocopherol. Yet according to
 therapy in the treatment of partial onset of epilepsy   the leading research investigator, all the vitamin E
 in adults.                                              family members could be important in protecting
                                                         against AD. This study was published in the July
      (Japan - Otsuka Pharmaceutical Co., Ltd. and       2010 issue of the Journal of Alzheimer’s Disease.
                              UBC, Jul 26, 2010)                       (Sweden – ScienceDaily, Jul 2, 2010)

                                                     3                           IPR BIOTECHNOLOGY
WISTA                                                                                                        AUGUST 2010

                                                                      Novel Hip Implant
                  WATCH-OUT IPR
                                                                          A spinal and orthopaedic implant and instrument
                                                                      manufacturer, Amedica Corporation focusing
 Influenza Patent                                                     on unique silicon nitride (SiN) ceramic technologies,
                                                                      has been granted United States Patent (No.
    NexBio, Inc.has announced the grant of US                         7,695,521) covering its novel hip implant that
 patent (No. 7,645,448) entitled “Class of                            features a monoblock ceramic acetabular cup for
 Therapeutic Protein Based Molecules”.                                use in articulating joints for total joint replacement.
                                                                       Currently under development, Amedica’s cup
     The patent covers NexBio’s sialidase                             covered under this and other pending patents
 pharmaceutical compositions, including its lead                      will be used as an ultralow- wear-bearing component
 compound DAS181 (Fludase(®)), and methods of                         for motion-preserving implants.
 treating or preventing viral infection by influenza
 and parainfluenza with such compositions.                                According to CEO of the company, the
                                                                      unique ceramic manufacturing capability of the
      DAS181 is a broad spectrum drug candidate
                                                                      technology will help surgeons to achieve more
 in Phase II human clinical development, being
                                                                      successful outcomes in restoring patient function,
 studied for the treatment and prevention of
                                                                      allowing individuals to return to productive and
 influenza-like illness (ILI) caused by any strain of influenza
                                                                      pain-free lives.
 and parainfluenza virus.
                                                                                     (Amedica Corporation, Jun 3, 2010)
     The ‘448 patent is NexBio’s first issued US
 patent. NexBio has several other US and                              Patent for Cell Proliferative Disorders
 international patent applications pending directed to
 DAS181, some of which have issued in foreign                             Oncolytics Biotech Inc. has been granted its
 countries. In addition, the company has numerous                     35th US patent, No. 7,731,951, entitled “Viruses for
 patent applications pending in the US and                            the Treatment of Cellular Proliferative Disorders.”
 foreign countries for TOSAP(®), its technology                       The patent claims cover methods for treating cell
 platform for formulating large molecules, small                      proliferative disorders by administering modified
 molecules, and combinations thereof into dry                         vaccinia virus to proliferating cells having an
 powder, for additional potential products.                           activated Ras-pathway.

                              (NexBio, Inc, Feb 8, 2010)                  According to the vice president of the
                                                                      company, the patent provides further coverage
 Notice of Allowance for Diabetes                                     with respect to the use of a range of modified
                                                                      viruses to treat a variety of different cancers.
     Melior Discovery Inc, anounced that the United
 States Patent and Trademark Office (USPTO) has                                    (Oncolytics Biotech Inc, Jun 19, 2010)
 awarded a Notice of Allowance for a broad
 patent application, covering the company’s use                       Patent for Digital Forensics
 of MLR-1023 for, among other things, the treatment
 of type II diabetes and obesity. The patent will                         The leading provider of forensic triage tools for
 cover use of MLR-1023 for the treatment of also                      computers and peripherals company, ADF
 metabolic syndrome, including its use in combination                 Solutions, Inc. has been granted a US patent on
 with other compounds and as a component in                           methods of searching forensic data. The patent
 other drugs.                                                         has critical applications for forensic triage, cyber-
                                                                      security, cyber-intelligence, digital forensics and
                        (Melior Discovery, Jun 8, 2010)               e-discovery.

IPR BIOTECHNOLOGY                                                 4
WISTA                                                                                                AUGUST 2010

     The patent covers the company’s innovative                 neuropathic pain, fibromyalgia, postherpetic
 SearchPak® technology, which enables an                        neuralgia and epilepsy.
 organization to capture its digital forensic
 investigative strategy and share it across                         (Pro-Tect Pharmaceuticals, Inc., Apr 26, 2010)
 organizations and with other individuals while not
 revealing the actual content. The SearchPak hides              Stem Cell Industry Report
 the complexity of the detailed forensic search
                                                                    Sunlight Research's 'Stem Cell Industry Report'
 definition and stores it in a secure container that
                                                                evaluates 911 issued US patents relating to stem
 can be deployed and used by non-forensically
                                                                cell technologies. The stem cell patents have been
 trained operators. This process allows analysts and
                                                                categorized by stem cell type or origin and by
 forensic examiners to control precisely the job
                                                                the therapeutic methods contemplated in the
 performed by the operators.
                                                                patent claims for treating diseases. The report
                                                                includes patents from over 349 assignees, including
      For law enforcement and intelligence agencies,
                                                                major pharmaceutical companies, academic
 the SearchPak technology allows the agencies to
                                                                research institutions and individual inventors.
 share digital intelligence for investigations while
                                                                    The report analyzes the US stem cell patent
 still maintaining secrecy. This has been a major
                                                                landscape. Stem cells are particularly attractive for
 breakthrough for key agencies, as the inability to
                                                                use as cellular therapies because they self-renew
 share key intelligence was identified as a major
                                                                and have the capacity to produce many different
 issue leading to the 9/11 attacks.
                                                                specialized cell types.
                  (ADF Solutions, Inc, Jun 10, 2010)                        (Sunlight Research, LLC, Apr 16, 2010)
 PRTT Acquires of Multipatents                                  UK Patent for TLE3 Biomarker

     Pro-Tect Pharmaceuticals, Inc. (PRTT) has                      Clarient, Inc., a premier technology and services
 acquisitired multiple patents and patents-                     resource for pathologists, oncologists and the
 pending from Nectid, Inc., that would contribute               pharmaceutical industry, announced that the
 to three revolutionary drug delivery technologies.             United Kingdom Patent Office has granted a
                                                                UK patent on the company’s TLE3 biomarker,
     The acquired patents would enable Pro-Tect to              a marker which may be used to predict which
 provide efficient, effective drug delivery platforms for       cancer patients will respond favourably to taxane
 three essential yet currently unmet needs:                     therapy. In addition, the company has received
                                                                a Notice of Allowance from the United States
 •   A gastro-retentive platform for drugs                      Patent and Trademark Office (USPTO) for a US
     that otherwise have short time windows                     patent on the TLE3 biomarker. Other patents for the
     for absorption;                                            TLE3 biomarker are pending in the US, Canada,
 •   An abuse deterrent platform for prescription               Japan, China, India and elsewhere in Europe. The
     drugs that are prone to abuse, especially                  US patent will cover uses of the TLE3 biomarker
     narcotic pain-killers; and                                 in breast cancer. The UK patent covers uses of
 •   A once-daily platform that allows two or more              TLE3 in breast , lung and ovarian cancers.
     drugs commonly taken in combination to be
     delivered via a single dose with fewer                         Taxanes are important cancer therapeutics which,
     side effects.                                              in combination with other cancer therapies, can
                                                                markedly improve a patient’s response rate
    In the near term, Pro-Tect intends to proceed               to therapy.
 with a comprehensive program to develop and
 commercialize once-daily drugs for diabetic                                   (Medical Patent News, Jun 8, 2010)

                                                            5                            IPR BIOTECHNOLOGY
WISTA                                                                                                   AUGUST 2010

                                                                Existing Nanosensors
                                                                    Currently, the most common mass-produced
                                                                functioning nanosensors exist in the biological
 NANOSENSOR                                                     world as natural receptors of outside stimulation.
 Introduction                                                   One of the first working examples of a synthetic
                                                                nanosensor was built by researchers at the Georgia
     The advancement of biotechnology in the                    Institute of Technology in 1999. It involved
 nanotechnology field mainly concerns the nanosensor            attaching a single particle onto the end of a carbon
 devices based on nanosensor technology. As the                 nanotube and measuring the vibrational frequency
 understanding of physics, chemistry and biology is             of the nanotube both with and without the particle.
 required for the advancement of nanotechnology,                The discrepancy between the two frequencies
 similarly understanding of sensing mechanism in                allowed the researchers to measure the mass of the
 nanodimensions is very important for developing the            attached particle.
 efficient sensors. Researchers are putting their
 efforts to make small and ultrasensitive sensors.              Patents
 Recently, the biosensors have got a lot of attention               Upto June 2010, there were two hundred thirty
 in the field of medical therapy. Materials in the              nine (239) US patents on nanosensor. Some of the
 nanostructured form can achieve high response to               pertinent patents are:
 very small targets in practical conditions. Presently,
                                                                •   US patent (No. 7,754,444) granted on July
 there are several ways proposed to make
 nanosensors, including top-down and bottom-up                  13, 2010, is entitled “Biofunctional magnetic
 design, top-down lithography, bottom-up assembly,              nanoparticles for pathogen detection”. The
 and molecular self-assemby.                                    biofunctional magnetic nanoparticles are preferabley
                                                                a conjugate of vancomycin (a glycopeptide antibiotic)
     A survey was presented by a German Institute               and FePt (Iron-Platinum nanoparticles).
 on the above approaches to the design of
                                                                •  Bright et al. won the US patent, No. 7,750,294
 nanostructured sensors which monitor different
 physical and chemical qualities. Particular emphasis is        on 6th July, 2010 entitled “Photonic sensors,
 given on new materials and transducers for molecular           xerogel-based sensors and nanosensors”.
 recognition by chemical sensors. They convert chemical         •   US scientists Shew, et al, were awarded the
 information into electronic signals by making use of           US patent on June 8, 2010 entitled “Charged
 suitable atomic structure of chemically sensitive              carbon nanotubes for use as sensors”. The charged
 materials under either thermodynamically or                    single wall nanotubes are very sensitive to environmental
 kinetically controlled conditions. This in turn requires       disturbanes and the nanotube's optical properties will
 the molecular understanding of sensor mechanisms               be affected by these perturbations.
 which is deduced from comparative microscopic,                 •   Another group of US scientists Wu, et al won
 spectroscopic and sensor test studies on                       the US patent on June 1, 2010 on “Engineered
 “prototype materials”. Selected examples illustrate            anti-CD20 antibody fragments for in vivo targeting
 typical mechanisms of molecular recognition with               and therapeutics”.
 electron conductors, ion conductors, missed
                                                                •  On May 4, 2010, US scientists Adriaens,
 conductors, molecular cages, polymers, and
 bimolecular function units.                                    et al were awarded with the US patent on
                                                                “DNAzymes and sensors incorporating the same”.
    Nanosensors are any biological, chemical, or
 sugery sensory points used to convey information               •   On April 27, 2010, US scientists Chaton, et al
 about nanoparticles to the macroscopic world.                  won the US patent on “Microsensors and
 Their use mainly include various medicinal purposes            nanosensors for chemical and biological species
 and as gateways to building other nanoproducts,                with surface plasmons”. The invention concerns novel
 such as computer chips that work at the nanoscale              localised surface plasmon sensors for chemical
 and nanorobots.                                                and biological species.

IPR BIOTECHNOLOGY                                           6
WISTA                                                                                                  AUGUST 2010

                                                               the problems in the absorption of iron. Through the
                     IN FOCUS                                  digestive track leading too much iron in the organism
                                                               and to its toxic accumulation in the organs. This
 Cardiac – Specific Genes                                      means that in this form it needs to be “watched” and
                                                               regulated around the clock. In vertebrates, this is done
     A group of doctors and scientists have revealed           through hepcidin, a liver protein that “moves” iron
 a major insight into how heart development is                 between cells and plasma according to the body
 regulated. Researchers at the Texas Heart Institute at        needs. The problem is that the hepcidin liver cells
 St. Luke’s Episcopal Hospital (THI) St. Luke’s                have limited mobility so a complementary for
 presented the results of research which they believe          reaching iron control was needed. Since 1978,
 marks a significant advance in understanding how              Maria de Sousa and her group have been chasing
 cardiac-specific genes are turned on during the               this idea that lymphocytes, with their unique capacity
 development of the heart in mice embryo. For this             to move throughout the body were the perfect
 research job, they had selected the right stem cells.         candidates. Thirty years ago at the beginning of
 Doctors anticipate that the research-findings could           her career, she noticed that lymphocytes were
 lead to better way to differentiate human stem cells          attracted to places with surplus of iron.
 that can be placed into damaged human hearts and
 spur generation of heart muscle and other tissues.                For some years the small groups of scientists
 THI doctors and scientists had conducted the clinical         have been pioneering the revolutionary idea that
 trials in which improved heart functions had                  the vertebrates immune system could have
 demonstrated in patients who had been injected with           a role in the regulation of iron in the body. The
 their own bone-narrow derived stem cells after                work which was published in the journal immunology
                                                               showed that human lymphocytes (white blood
 severe heart failure.
                                                               cells) actually produce hepcidin, the most important
              (Texas Heart Institute, Jul 23, 2010)            protein in the regulation of iron levels in the body.
 Genetic Regulatory Materials                                  They showed that hepcidin affected lymphocyte
                                                               multiplication occurs during an infection. So, the
     Chemical changes in the genetic material, known           lymphocyte multiplication and infection seems to
 as epigenetic modifications, regulate the activity of         be much more interlinked. The discovery of the
 many genes. Thus, attachment of methyl groups to              scientists resumes from new players in both iron
 DNA often inactivates important cellular growth brakes.       metabolism and immunology to a new understanding
 Therefore, this process called methy1ation is believed        of how cell division in itself is controlled (both normal
 to be a major cause of uncontrolled division of               cell division and cancer) to even help us to better
 cancer cells. Specific enzymes, the DNA                       understand the evolution of the immune system. The
 methyltransferases, are responsible for methylation.          scientist team first proposed the idea of a link
     Epigenetic mutations are reversible and, thus,            between the immune system and iron homeostasis.
 cancer cells can be restored to their “normal state”.                          (Medical News Apr 22, 2010)
 Substances causing this re-programming are already            Immune Regulatory Single Protein
 being used as anticancer drugs. Examples are
                                                                   Unchecked, the natural or innate immune system,
 azacytidine and decitabine, which are used in the
                                                               can run out of control like a stuck accelerator on a
 treatment of a specific type of blood cancer called
                                                               car. Eventually, it will kill the host it is supposed
 acute myeloid leukemia. Both substances are
                                                               to protect.
 incorporated into the cell’s genetic material, where
 they act as a trap for methyltransferases.                        Much scientific attention is directed at how
                                                               this innate immune system is turned on, but little is
        (Helmholtz Association of German Research
                                                               known how it is cooled down or regulated. A team
                              Centres, May 7, 2010)
                                                               of researcher led by Baylor College of Medicine
 Hepcidin affected Lymphocytes                                 has identified a protein called NLRC5, a member
    Iron is an essential element for most life forms.          of the NOD like protein family. The two immune
 The iron-related disease hemochromatosis concerns             pathways are NF-KB and type 1 interferon. The

                                                           7                              IPR BIOTECHNOLOGY
WISTA                                                                                                  AUGUST 2010

 above mentioned research protein NLRC5 is                        With this understanding of c-Myc’s role in
 involved in inhibition of protein complexes such as           controlling proliferation genes, the scientists have
 the protein IKK complex in NF-KB pathway, and                 embarked on a search for drugs that could interrupt
 RIG-I and MDA5 as pathogen sensors in type I                  c-Myc’s pause release activity in tumors where it is
 interferon pathways. These two protein complexes              over-impressed.
 act like natural forces to control and direct the             (Whitehead Institute for Biomedical Research, Apr
 cascade of events that result in innate immunity.                                                     30, 2010)
     NLRC5 interacts with the submits of the two               Nuclear Receptors for Heart
 protein complexes to block the innate immune                      The heart is a pump. It needs a steady supply
 response. By knocking down or reducing the                    of energy to function properly. It gets this energy
 amount of the NLRC5 protein, Baylor College of                from different fuels found in the body “glucose or
 Medicine scientists showed the results in increased           fatty acids” depending on availability. A group of
 innate immune responses and antiviral immunity.               researchers recently identifies several genetic
                                                               programs which work together to ensure this energy
        (Bayloy College of Medicine, May 30, 2010)
                                                               is available. They have identified two new
 Oncogene’s Secret Growth Formula                              receptors, ERRa and g receptors, that control the
                                                               whole setup.
      Scientists have long known that DNA-binding
 transcription factors recruit the RNA polymerase                  They explained that the nuclear receptors receive
 Pol II (which prompts copying of DNA into                     signals from different parts of the body. These signals
 RNA protein codes) to promoters in order to kick              “tell the cell what action to take by controlling
 off the transcription process.                                which genetic will be turned on or off in the cell".
                                                                   The two identified receptors had already been
     A comprehensive new gene expression study
                                                               linked to the activity of cellular power plants called
 in embroyic stem cells has uncovered a transcription
                                                               mitochondria. Present researchers discovered that
 control mechanism. That is not only more pervasive
                                                               these two closely related nuclear receptors (ERRa
 than once thought but is also heavily regulated by
                                                               and g) play an essential role in coordinating the
 the cancer-causing gene c-Myc.
                                                               expression of a set of proteins that the heart requires
      In research published in the April 30th edition of       to produce the energy it needs to pump effectively.
 Cell, a team of Whitehead Institute researchers               Using powerful genomic tools, researchers discovered
 describes a pausing step in the transcription process         that the ERRa and g receptors play a key role in
 that serves to regulate expression of as many as 80%          regulating the genes which guide the complex
 of the genes in mammalian cells. Now the researchers          biological processes fuelling the heart. Because of
 have found that additional factors recruited to               this, the two receptors are essential to heart function.
 the promoters serve to stop transcription in its                                     (ScienceDaily, May 10, 2010)
 tracks shortly after it’s begun.
                                                               Synthetic Enzymes
      Scientists said that it is the engine running, but           Using a rare metal that is not utilized by nature,
 the transmission is not engaged in the transcription          Rice University chemists have created a synthetic
 apparatus. There need something to engage the                 enzymes that could help unlock the identities of
 transmission. That “something” is the transcription           thousands of difficult-to-study proteins, including
 factor c-Myc. This transcription factor c-Myc                 many that play key roles in cancer and other
 performs the so-called pause release role which is            diseases. The synthetic enzymes or catalysts enhance
 very significant, as many of c-Myc’s targets are genes        chemical reactions by increasing the rate
 in highly proliferative cells. Over expression of c-Myc       of reaction without being consumed themselves.
 is a hallmark of a number of tumors. And it now               In living things, proteins called enzymes serve the
 appears that c-Myc’s ability to release transcriptional       same purpose.
 pausing is linked with the hyper proliferation that             (Journal of the American Chemical Society, May
 is characteristic of cancer cells.                                                                    3, 2010)

IPR BIOTECHNOLOGY                                          8
WISTA                                                                                                AUGUST 2010

                                                             Instruction® Receptor Phase stationary phases in
           STRATEGIC ALLIANCES                               combination with Novasep’s chromatography and
                                                             purification expertise for the development of
                                                             optimized large-scale chromatography processes
 Agreement for Drug Formulation                              for synthetic and semi-synthetic compounds.
    Bio Nano Consulting (BNC)specialists in bio and              instrAction is commercializing its Instruction®
 nanotechnology partnerships between the academic            Receptor Phases as API-selective resins for
 and industrial sectors, have signed a service               large-scale chromatography processes. The
 level agreement (SLA) with the School of                    technology enables the immobilization of a wide
 Pharmacy, University of London. This latest SLA             variety of functional ligands on a polymer network,
 enables BNC to offer an expanded service offering           coated on different porous backbone materials.
 to life science and pharma companies as it                  Small molecules and high molecular weight
 provides access to an increased pool of academic            molecules are separated by highly selective reversible
 experts skilled in the fields of pharmaceutics,             interactions. The specificity of a particular instrAction
 pharmacology and drug discovery.                            stationary phase is achieved by multivalent-
                                                             multimodal interactions between the target molecule
       Under the terms of the agreement, BNC will
                                                             and the functional ligands of the phase.
 manage a specific project, carried out by scientists
 at the School of Pharmacy, to formulate a phase I               Novasep claims the combination of technologies
 cancer drug with the goal of making the treatment           will result in customers receiving a purification
 orally available, rather than delivered intravenously.      process or service with optimized and cost-effective
 The four month proof of concept project is                  performance guaranteed.
 intended to demonstrate dissolution and oral
                                                                 Novasep offers a range of solutions and services
 availability and, once successful, will progress to a
                                                             for the production of synthetic molecules and
 second project stage with School scientists
                                                             biomolecules including purification processes,
 working closely with the biotechnology company to
                                                             manufacturing, and custom manufacturing services.
 take the formulation through to late-stage development.
                                                             The firm has two complementary business divisions.
                 (Bio Nano Consulting, Jul 27, 2010)         Novasep Synthesis specializes in chemical
                                                             synthesis and purification technologies to develop
 Co-Development of siRNA Therapeutics                        and produce active ingredients and advanced
     RNAi therapeutics firm Quark Pharmaceuticals            intermediates for the pharmaceutical, crop science,
 inked a collaboration and licensing deal with               and other fine chemical industries. Novasep Process
 Japanese materials company Nitto Denko focused              develops and supplies purification processes,
 on the development of siRNA therapeutics against            equipment, and systems for the pharmaceutical,
 fibrotic diseases. The firms aim to have the first          biopharmaceutical, and industrial biotechnology
 product IND-ready by early 2012.                            industries, and it provides contract
                                                             biomanufacturing services.
     The collaboration will combine Quark’s RNAi
 technologies and novel structures with Nitto Denko’s         (Genetic Engineering & Biotechnology News, Jul
 drug-delivery platform and IP in therapeutic strategies.                                          19, 2010)
 The firms say the partnership will have an initial budget   Merger Agreement
 in the double-digit millions of dollars range.                  China PharmaHub Corp. (“PharmaHub”),
                            (GEN News, Jul 15, 2010)         a pharmaceutical hub between Chinese
                                                             pharmaceutical companies and other pharmaceutical
 Combining Technologies for Chromatography
                                                             companies located worldwide, announced that it
     Novasep and instrAction inked a worldwide               has entered into a merger agreement with World
 strategic alliance designed to give pharmaceutical          Wide Relics, Inc. (“WWR”). The merger is expected
 clients access to the latter’s API-selective                to close in August 2010.

                                                         9                              IPR BIOTECHNOLOGY
WISTA                                                                                           AUGUST 2010

      PharmaHub’s business is the identification,         through which pathologists examine tissue sections
 licensing, development and commercialization of          mounted on glass slides and treated with different
 pharmaceutical and healthcare products and               stains. The staining enhances the contrast between,
 technologies between the People’s Republic of            or reveals the presence of, cellular and molecular
 China (“PRC”) and the rest of the world. Its initial     components such as cell nuclei or specific proteins.
 focus is on the US and Europe, with the goal of          Accurate interpretation of the results is critical to
 assisting small biotech companies and individuals in     the diagnosis and staging of each individual
 bringing their projects to market and large biotech      patient’s disease and requires a great deal of skill
 companies in expanding their coverage to the PRC.        and experience. Digitizing the images that
  The merger with WWR will provide PharmaHub              pathologists normally view through a microscope
 with the additional resources and exposure to enhance    may enable the introduction of objective and
 its existing project pipeline.                           quantitative image analysis tools.
                        (PRNewswire, Jul 28, 2010)            A fast pathology slide scanner and an
                                                          associated image management system form the basis
 Partnership to Develop Prophylactic Vaccine              of Philips’ proposed integrated solutions for
     Singapore’s Agency for Science, Technology           digitizing pathology workflows. The Philips-Dako
 and Research (A*Star) announced a partnership            collaboration will initially focus on leveraging
 with Cytos Biotechnology to develop a virus-like         Dako’s image analysis software for tissue-based
 particle (VLP) flu vaccine targeting the viral           breast cancer diagnosis using its reagents for
 hemagglutinin protein.                                   staining HER2, Estrogen Receptor (ER),
                                                          Progesterone Receptor (PR), p53 and Ki-67
     The vaccine collaboration will involve Cytos         proteins. The detection and quantification of these
 working in partnership with A*Star’s Experimental        proteins in biopsy tissue are highly relevant for the
 Therapeutics Centre (ETC) and the Singapore              classification of breast cancers and the selection of
 Immunology Network (SigN) to develop a                   appropriate therapy. Philips and Dako will also
 prophylactic vaccine that will undergo preclinical       explore the possibility of extending the
 development at Singapore’s DSO National                  collaboration to include image analysis software
 Laboratories. Proof-of-concept studies will              for immunohistology-based prostate and colon
 subsequently be carried out by Singapore’s Duke          cancer diagnostics.
 NUS-Graduate Medical School and the Singapore
 Clinical Research Institute.                                                  (Philips & Dako, Jul 23, 2010)

     Cytos will retain worldwide rights to further        Research and Development Agreement
 develop, manufacture, and commercialize the                  EnWave Corporation has signed a R & D
 vaccine, with A*Star subsidiaries retaining the          Agreement with Nestec Ltd. involves EnWave’s
 right to produce the vaccine for Singapore and           nutraREV™ food dehydration technology.
 other ASEAN (Association of Southeast Asian
 Nations) territories.                                        Using proprietary technologies developed
                                                          in conjunction with the University of British
                           (Gen News, Jul 15, 2010)       Columbia, EnWave is commercializing a new
                                                          method for dehydrating food and biological
 Phileps-Dako Collaboration                               materials using Radiant Energy Vacuum technology
     Royal Philips Electronics and Dako, have signed      under its nutraREV™, powderREV™, bioREV™
 an agreement to integrate a selection of Dako’s          and freezeREV™ brands.
 image analysis applications into Philips’ future            EnWave’s nutraREV™ technology offers
 digital pathology solutions.                             continuous high-speed drying in a low temperature
                                                          vacuum environment.
    Currently, anatomic pathology workflows to
 examine tissue samples are based on the microscope,                    (EnWave Corporation - Jul 27, 2010)

IPR BIOTECHNOLOGY                                    10
WISTA                                                                                             AUGUST 2010

             ON TO EXCELLENCE                               •   Commenced preparation for Phase III clinical
                                                                trials for Generex Oral-lyn.
 Generex Biotechnology Corporation                          •   National retail expansion of Glucose RapidSpray
                                                                throughout USA and Canada.
 Introduction                                               2007
     Generex Biotechnology Corporation was                  •   Received Regulatory Approval to Sell Generex
 established in December 2000 in downtown                       Oral-lynTM in India.
 Toronto. The company is engaged in the research,           •   Test Novel RNAi-Based Immune Response
 development and commercialization of drug                      Strategy in Cancer Patients.
 delivery systems and technologies. Generex
                                                            •   Initiated Phase II Clinical Trial in Breast Cancer
 Corporation has developed a proprietary
                                                                Patients in Collaboration With United States
 technology platform for the delivery of drugs into
                                                                Military’s Cancer Institute.
 the human body through the oral cavity. The
 company’s proprietary liquid formulations allow            2006
 drug typically administered by injection to be             •   Being the First Human Clinical Trial of Avian
 absorbed into the body by lining of the inner mouth.           Influenza Vaccine.
 Technology                                                 •   US Distribution of New Glucose RapidSpray™
     Generex has many platform technogies in the
                                                            •   Successful Equipment & Filling Line Installation
 area of drug delivery and immunomedicines.
                                                                for Commencement of Generex Oral-lyn(TM)
 Its drug delivery-Rapid MistTM: is comprised of a
                                                                Commercial Production.
 proprietary device and pharmaceutical agents in
 an aerosolized liquid formulation. The drug is             2004
 delivered through the buccal mucosa (inner check           •   Reported   on   Novel     Mechanism           for
 of mouth) and not the lungs.                                   Immunotherapy Cure of Prostate Cancer.
     Generex’s product pipehine includes: Generex           2003
 Oral-1yn, BaBOOM!TM, Crave-NX TM, Glucose                  •   Awarded a $444,000 Phase I NH SBIR Grant
 RapidSprayTM. Generex is currently conducting                  for Melanoma Peptide Vaccine.
 pre-clinical and human clinical trials using its
 proprietary technology platforms in the areas
 of diabetes, pain management and cancers.                  •   Announces Continued Positive Results of
                                                                Long-Term Safety And Toxicology Study of
 Milestones                                                     Generex Oral-lyn™.
     Generex Biotechnology Corporation has achieved         •   Receives Approval of US IND for Buccal
 numerous milestones over the last 9 years. The                 Morphine.
 timeline below highlights some of the key achievements.    2001
 2009                                                       •   Opens newly expanded manufacturing facility and
                                                                analytical lab.
 •   Successful commercial launch of Generex Oral-Iyn
     in Algeria and Lebanon.                                Conclusion
 •   Successful Phase III Study Data for Generex                Presently the company is well-positioned to
     Oral-LynTM .                                           conduct additional research and development in
 •   Launch of Crave-NXTM 7- Day Diet Aid Spray             various large molecule applications on its own
     and Glucose RapidSpray for Companion Pets.             technology platform.

                                                       11                            IPR BIOTECHNOLOGY
WISTA                                                                                               AUGUST 2010

                                                              code' which researchers believe defines how
                SPECIAL FEATURE                               different genetic programmes can be executed from the
                                                              same genome in different tissues.
 EPIGENETICS                                                      Several chemical groups, such as acetyl
                                                              or methyl groups, that affect gene expression levels
                                                              have been identified. These chemical groups
     Genetics is the study of genes. Epigenetics is a         recruit other proteins that are able to regulate the
 field of biological research that focuses on changes         expression of genes. Either the amount of a specific
 to DNA or chromosomal proteins that affect the               chemical modification or the location on the
 amount produced of a particular gene. The amount             DNA sequence or chromosome where the
 of a gene produced by a cell is referred to as the           modification is made can influence the level of
 expression level. Whereas the field of genetics              gene expression. Nearly every cell in a person’s
 commonly focuses on how changes in the DNA                   body contains DNA with an identical sequence
 sequence affect gene activity, epigenetics focuses           of nucleotide bases. These double stranded
 on changes to the DNA that do not involve changes            molecules carry the genetic instructions that encode
 in the sequence.                                             the proteins and enable cells to reproduce and
                                                              perform specific functions. But the individual
     DNA is located in a compartment of the cell              members of the genome – the sum total of DNA
 called the nucleus and is packaged in structures             contained in an organism – are not self directed.
 called chromosomes. In addition to DNA,                      Like actors in a troupe, they need to be assigned
 chromosomes also contain proteins, such as                   roles before the script can be acted out. The
 histones, which help package the DNA in an orderly           epigenome is a set of chemical switches that control
 way. DNA also contains four different chemical               gene expression within a cell. It’s like a second
 compounds called bases: cytosine, thymine, guanine,          layer of information that tells genes how to act. By
 and adenine. In any given individual, these bases            turning some genes on and leaving some genes
 are found in a particular order along the                    off, it directs certain cells to become brain cells,
 chromosomes, and it is the order, or sequence,               others hair cells, and so on.
 of these bases that stores information for
 making genes.                                                Chromatin Structure and Epigenetic Markers

    Chromosomes contain hundreds of genes, which                  To understand epigenetics requires an
 provide the instructions for making proteins.                understanding of chromatin structure. Chromatin,
 Chromosomes also contain many other regulatory               which is organized into repeating units called
 sequences that control how much of a gene will               nucleosomes, is the complex of DNA, protein, and
 be made, when it will be made, and where in the              RNAs that comprises chromosomes. A nucleosome
 body it will be made.                                        consists of 147 bp of double-stranded DNA
                                                              wrapped around an octamer of histone proteins.
 Epigenetic Code                                              In mammalian cells, most of the chromatin exists
                                                              in a condensed, transcriptionally silent form
     The level of gene expression can be regulated            called heterochromatin. Euchromatin is less
 by cells through chemical modification of DNA or             condensed, and contains most actively transcribed
 the histone proteins. Epigenetic changes include             genes. Histones and DNA are chemically modified
 modification of DNA bases, through addition or               with epigenetic markers that influence chromatin
 removal of simple chemical tags, such as a methyl            structure by altering the electrostatic nature of the
 group, and similar changes of the proteins that are          chromatin or by altering the affinity of chromatin-
 closely entwined with DNA to form chromatin, the             binding proteins. DNA can be modified by
 functional form of the genome. Collectively, these           methylation of cytosine bases. The enzymes that
 modifications are also referred to as the 'epigenetic        methylate DNA are called DNA methyltransferases.

IPR BIOTECHNOLOGY                                        12
WISTA                                                                                              AUGUST 2010

     Histones are subject to several different covalent    fit into the nucleus. The packaging is done by a set
 modifications, including methylation, acetylation,        of proteins called histones. These proteins wrap
 phosphorylation, ubiquitylation, and sumoylation. The     DNA around them and interlink to stabilize the
 best-characterized histone modifications are              packaging. The histones can be modified by the
 acetylation and methylation. Acetylation of histone       addition of an acetyl or methyl group to their tails.
 lysine residues is associated with euchromatin            Different modifications lead to different levels of
 because it weakens the charge attraction between          DNA accessibility around the histones and its
 histone and DNA, serving to decondense chromatin          overall expression levels. Histones modifications
 and facilitate transcription.                             are sometimes used to force a specific gene expression
                                                           profile in a certain tissue or at a certain time.
     Histones are not the only proteins that interact
 with DNA in chromatin. Nucleosome remodeling              Research
 complexes manipulate chromatin structure, thereby
 affecting gene silencing and expression. Chromatin            Now a days extensive research is being conducted
 remodeling proteins affect chromatin structure in         on epigenetics, specifically for accurate diagnosis and
 various ways. They can expose DNA wrapped in              treatment of cancer. Recently (ScienceDaily: Feb 13,
 nucleosomes by sliding histones along the DNA,            2010) researchers from the Institute of Psychiatry (IoP),
 or detach the histone octamer completely from a           King's College London, have identified numerous
 DNA sequence. In recent studies, the reverse              novel regions of the genome where the chemical
 reaction has also been observed for the insertion of      modifications involved in controlling gene expression
 variant histone proteins. Not all nucleosome              are influenced by either genetic variation or the
 remodeling proteins possess the same functions.           parental origin of that particular stretch of DNA.
                                                           This contradicts previous assumptions that epigenetic
 Epigenetic Mechanism                                      signals are generally equal accross both copies of
                                                           a given region of the genome, except at a small
     The DNA organism carries encodes for all              number of known imprinted genes.
 the proteins needed in any tissue at any time (and
 some non protein coding genes). The expression            Patent Scenario
 of each gene should be tightly regulated in time and
 space in order for a specific cell and the entire             Upto June 2010, there were eighty-six (86) US
 organism to function. Mutations in the genes or the       patents on 'Epigenetics'. Some of the these patents
 factors controlling their regulation might lead to        are mentioned below:-
 malfunctioning. For an instance, Prader-Willi
                                                           •   On June 22, 2010 US scientists Shi, et al
 syndrome is caused by genetic and epigenetic errors
                                                               were awarded US patent (No. 7,741,086) on
 to the same part of chromosome 15. Every internal
                                                               “Histone demethylation mediated by the nuclear
 factor determining the gene expression profile can
                                                               amine oxidase homolog LSD1”. This invention is
 be considered as an epigenetic mechanism, two
                                                               related to the area of gene regulation. In
 of which, DNA methylation and histome
                                                               particular, it relates to the area of modification
 modifications, are the major ones.
                                                               of chromosome structure as a means of
     DNA methylation is a modification in which a              regulating transcription. This modification
 small molecule is attached to the DNA bases,                  importantly impacts disease processes as well
 usually cytosine ones. DNA methylation occurs in              as normal physiology and development.
 all vertebrates, as far as scientists know. The
 modification silences the expression of the genes         •   Another US patent was granted to Hoon, et al.
 near he modification site leading to differential             on “DNA markers for management
 gene expression.                                              of cancer” (patent No. 7,718,364). The invention
                                                               is related to the fields of molecular biology and
      Another mechanism utilizes the histones to exert         oncology and provides methods for diagnosis,
 its function. The DNA should be tightly packed to             staging and monitoring of cancer patients.

                                                      13                              IPR BIOTECHNOLOGY
WISTA                                                                                             AUGUST 2010

 •   On April 20, 2010, US scientists McSwiggen,                mass spectrometry to determine the amino acid
     et al won the US patent (No. 7,700,760) on                 positions of the substrate that are enzymatically
     “RNA interference mediated inhibition of                   acetylated or deacetylated.
     vascular cell adhesion molecule (VCAM) gene
                                                            •   On March 2, 2010 US scientists, Minassian,
     expression using short interfering nucleic
                                                                et al. won the US patent (No. 7,670,773) on
     acid (siNA)”. This invention relates to
                                                                “ MECP2E1 gene”. The invention is a novel
     compounds, compositions, and methods
                                                                MECP2E1 splice variant and its corresponding
     useful for modulating vascular cell adhesion
                                                                polypeptide. The invention also includes
     molecule gene expression using short
                                                                methods of using these nucleic acid sequences
     interfering nucleic acid (siNA) molecules. This
                                                                and proteins in medical diagnosis and treatment
     invention also relates to compounds, compositions,
                                                                of neuropsychiatric disorders or development
     and methods useful for modulating the
     expression and activity of other genes involved in
     pathways of vascular cell adhesion molecule            •   A team of US scientists, McSwiggen, et al, on
     gene expression and/or activity by RNA                     February 9, 2010 got the US patent (No.
     interference (RNAi) using small nucleic acid               7,659,390) on “RNA interference mediated
     molecules.                                                 inhibition of muscarinic colinergic receptor gene
                                                                expression using short interfering nucleic acid
 •   Chen, et al. of US were granted on April 6, 2010           (siNA)”. Specifically, the invention relates to
     the US patent (No. 7,691,405) on “Lipid
                                                                small nucleic acid molecules, such as short
     nanoparticle based compositions and methods
                                                                interfering nucleic acid (siNA), short interfering
     for the delivery of biologically active molecules”.
     The invention relates to novel cationic lipids,            RNA (siRNA), double-stranded RNA (dsRNA),
     transfection agents, microparticles, nanoparticles,        micro-RNA (miRNA), and short hairpin RNA
     and short interfering nucleic acid (siNA)                  (shRNA) molecules capable of mediating
     molecules. Specifically, the invention relates             RNA interference (RNAi) against cholinergic
     to novel cationic lipids, microparticles,                  muscarinic receptor gene expression.
     nanoparticles and transfection agents that
                                                            •   Another US patent that, McSwiggen, and
     effectively transfect or deliver short interfering
                                                                colleagues 9th Feb, 2010 were awarded on " RNA
     nucleic acid (siNA). The compositions described
     herein are generally referred to as formulated             interference mediated inhibition of MYC and/or
     molecular compositions (FMC) or lipid                      MYB gene expression using short interfering
     nanoparticles (LNP).                                       nucleic acid (siNA) (No. 7,659,389) . This
                                                                invention relates to compounds, compositions,
 •   On March 2, 2010, another group scientists                 and methods useful for modulating Myc
     were awarded the US patent (No. 7,670,795)                 and/or Myb gene expression using short
     on “Methods for assaying acetyl transferase or             interfering nucleic acid (siNA) molecules.
     deacetylase activity”. The invention provides
     methods and kits for characterizing the activity
     of an acetyl transferase or deacetylase. The               DNA carries the code shaping an organism and
     method involves enzymatically acetylating or           an individual but this code is not complete without
     deacetylating in vitro a substrate that is a           the epigenetic one. Modifications related to DNA
     peptide fragment of a full-length polypeptide,         expression and packaging can alter the organism's
     and then non-enzymatically acylating the peptide       phenotype, taking a crucial role in the evolutionary
     substrate with acyl groups that differ in              process. The epigenetic code can be changed and
     molecular weight from the enzymatically added          endowed to the offspring, counter to the stable
     or removed acetyl groups. Typically,                   genetic one. Epigenetic inheritance can enable
     deuterated acetic anhydride is used to non-            heredity of acquired phenotypes. This kind of
     enzymatically acylate the substrate. The fully         inheritance could be considered as a modern version
     acylated substrate is then characterized by            of Lamarck's Idea.

IPR BIOTECHNOLOGY                                      14
WISTA                                                                                               AUGUST 2010

                 CLINICAL TRIALS                                                    AWARDS

 Preventive Malaria Treatment                                    AACR Award in Cancer Research
     Pfizer Inc. and Medicines for Malaria Venture
 (MMV) entered into an agreement for the                             Genetic Medicine at the Johns Hopkins
 development, access and delivery of a fixed-dose                University School of Medicine, and a Howard
 combination treatment consisting of azithromycin                Hughes Medical Institute Early Career Scientist,
 dihydrate (AZ) and chloroquine phosphate (CQ)                   is the recipient of the 30 th annual American
 for the intermittent preventive treatment of                    Association for Cancer Research award for
 P.falciparum malaria in pregnancy (IPTp). There                 outstanding achievement in cancer research.
 is currently an unmet need for new treatment                    The award is for advancing the understanding
 options and the World Health Organization (WHO)                 of microRNAs (miRNAs), genetic signaling
 estimates that some 30 million pregnant women                   elements involved in gene “silencing,” which are
 are at risk for malaria in endemic areas in Africa              important for normal physiology and diseases
 each year.                                                      such as cancer.
     A product development team comprised
                                                                     The award, which comes with a $5,000 cash
 of representatives from Pfizer, MMV and the
                                                                 prize, was presented during the 101st annual
 London School of Hygiene and Tropical Medicine
                                                                 meeting of the American Association for
 (LSHTM) are coordinating the clinical trials
                                                                 Cancer Research, at which Mendell delivered a
 of AZCQ for treatment of highly vulnerable
                                                                 lecture, “MicroRNA Reprogramming in Cancer:
 patient group. An external independent Data
                                                                 Mechanisms and Therapeutic Opportunities.” His
 Monitoring Committee of malaria experts
                                                                 recent research demonstrates that the delivery of
 oversee them.
                                                                 microRNAs to cancer cells represents a promising
 (Pfizer Inc. and Medicines for Malria Venture, Apr              strategy for cancer therapy.
                                          23, 2010)
 Side Efects of Increasing Dose                                                   (Genetic Medicine, Apr 24, 2010)
     Cancer patients in West Michigan will soon have
                                                                 Vaccine Industry Excellence Award
 the opportunity to access new drugs being developed
 to fight their disease due to a partnership being
                                                                     Inovio Biomedical Corporation, a leader in DNA
 formed in Grand Rapids.
                                                                 vaccine design, development and delivery, was
     Van Andel Research Institute (VARI), Spectrum               awarded a 'Vaccine Industry Excellence Award'
 Health, and Cancer & Hematology Centers of                      in the category of “Best Early Stage Biotech” by a
 Western Michigan have signed agreements to develop              panel of judges comprising a broad selection of
 a Phase I clinical trial program. The program will be the       biotech industry stakeholders. The award was
 link between the lab and clinical research, involving           presented at the World Vaccine Congress being held
 patients, allowing faster, close-to-home enhanced access        April 19 - 22, 2010, in Washington, DC.
 to potentially life-saving diagnostic and treatment
 options for cancer and other clinical conditions.                   The award citation highlights Inovio’s
     Phase I clinical trials are initial studies to determine    pioneering development of a DNA vaccine platform
 the actions of drugs in humans, identify the side               using electroporation delivery and its current
 effects associated with increasing doses, and gain              clinical-stage DNA vaccine programs for influenza,
 early evidence of effectiveness.                                HIV and cancer.
              (Van Andel Research (VARI), Cancer &
                                                                    (Inovio Biomedical Corporation, Apr 21, 2010)
                          Hematology, Jul 27, 2010)

                                                            15                           IPR BIOTECHNOLOGY
WISTA                                                                                                 AUGUST 2010

                                                              to control the formation and size of this important
                   FINE TUNING                                spindle feature. EMBL scientists found that protein
                                                              PRC1 bundles together microtubules coming from
                                                              opposite ends of the cell, attaching them to each
  This section attempts to fine-tune some basic               other. It then recruits a second protein, a molecular
  concepts on a subject of interest about which one           motor from the kinesin-4 subfamily, increasing its
  might have already heard of. The current issue              concentration in the spindle mid-zone. This motor
  features “Importance of "PRC 1 Protein ”.                   walks along the overlapping microtubules like an
                                                              officer on patrol, until it reaches one of the ends.
 PRC 1 Protein                                                When enough kinesin-4 molecules reach the end of
                                                              the overlap, they inhibit the growth of microtubules
      Cell division is an essential and functional process
                                                              there, thus keeping the overlap size constant
 in the organism developmental stage. Mitosis and
                                                              without affecting microtubules elsewhere the cell.
 Meiosis are two divisional stages of development.
 Mitosis is a highly regulated process characterized               The spindle mid-zone plays an important role not
 by dramatic and coordinated morphological changes            only in helping to align the chromosomes in
 to ensure the fidelity of chromosome segregation.            metaphase, but also in the final stages of cell
 According to Cao and Wang (1990), cytokines occur            division, when it drives the physical separation of
 at this final stage of mitosis and is accomplished by        the two daughter-cells. But between these two
 the contraction of an actomyosin ring that leads to          stages, the two ends of the spindle must move away
 daughter cell separation at the mid-body. A number           from each other, to drag half the genetic material to
 of proteins accumulate at the mid-zone of the                each side of the dividing cells. At this point, if PRC1
 mammalian mitotic spindle during late mitosis and            and kinesin-4 had stopped microtubule growth
 have been shown to play a role in cell cleavage              permanently in the central part of the spindle, the
 by antibody suppression, over expression, or                 overlap would become smaller and smaller, until
 mutagenesis.                                                 eventually the spindle itself would collapse,
                                                              jeopardizing cell division. But the German scientists
     Researchers have discovered that among these
                                                              have found that PRC1 and kinesin-4 control the overlap
 proteins are passenger proteins, such as INCENP
 and survivin; protein Kinases, such as polo and              size in an adaptive manner. As the spindle stretches
 aurora B; small G-proteins, such as Rho; and                 and the overlap between microtubules becomes
 microtubule motor proteins, such as CENP-E,                  smaller, the scientists posit, the inhibitory effect of
 Rab6-KIFL, and MKLP. Some interactions                       kinesin-4 diminishes, allowing the microtubule
 among these proteins have been established, but              ends to grow. Their findings help us to understand
 specifically defined functional roles in the cleavage        the fundamentals of cell division.
 process are still largely unknown. Jiang et al (1998)             The PRC1 gene encodes the protein that is
 have described that protein PRC1 accumulates in              involved in cytokinesis. The encoded protein which
 the spindle mid-zone and it has a demonstrated               is called PRC1 is at high level during S and G2/M and
 role in sustaining cell cleavage. During cell                drop dramatically after cells exit mitosis and enter G1.
 division, microtubules emanating from each of                It is located in the nucleus during interphase, and
 the spindle poles meet and overlap in the spindle’s          becomes associated with mitotic spindles in a
 mid zone. On this aspect there is a recent report            highly dynamic manner during mitosis, and localizes
 (August, 2010) of a group of German-scientists.              to the cell mid-body during cytokinesis. The protein
      European Molecular Biology Laboratory (EMBL),           has been shown to be a substrate of several
 scientists identify molecular machinery that                 cyclin-dependent kinases (CDKs).
 maintains important feature of the spindle. They                 So, it can be concluded that the function of
 have uncovered the molecular mechanism that                  PRC1 is necessary for spindle integrity during late
 determines the extent of this overlap and were able          mitosis, particularly to maintain the mid-zone
 to reconstruct such anti-parallel microtubule overlaps       MT (microtubules) bundles that are essential for
 in vitro, and identify two proteins which are sufficient     the completion of all cell cleavage.

IPR BIOTECHNOLOGY                                        16
WISTA                                                                                            AUGUST 2010

                                                           use of romidepsin for injection in T-cell
                  LEGAL SCENE                              lymphomas, declared invalid and not infringed
                                                           by Celgene’s products.
 Action Closing Prosecution                                    (Cyclacel Pharmaceuticals, Inc., Jun 18, 2010)
     Precision BioSciences, Inc, announced
                                                           Drug Marketing Lawsuit
 that the USPTO has issued Actions Closing
 Prosecution in the re-examination proceedings
                                                               AstraZeneca has settled a case and agreed
 for US patent No. 6,610,545 (“the ‘545 patent”)
                                                           to pay $520 million after federal investigations
 and US Patent No. 7,309,605 (“the ‘605 patent”)
                                                           into its marketing practices for a schizophrenia
 that are owned by the Institute Pasteur and
                                                           drug, Seroquel.
 the Universite Pierre et Marie Curie
 (UPMC), and licensed to Cellectis, SA (ALCLS).
                                                               Government officials, including Health and
 The ‘545 patent and the ‘605 patent are the two
                                                           Human Services said the company paid
 patents asserted against Precision in litigation filed
                                                           illegal kickbacks to doctors to promote drugs
 in March 2008 by Cellectis, but the PTO has
                                                           for unapproved uses by children, the elderly,
 now twice rejected all claims asserted against
                                                           veterans and prisoners, which was illegal under
 Precision in the litigation. Significantly, during the
                                                           federal law. AstraZeneca denies those allegations.
 course of the re-examinations, the patent owners
 have filed amendments to each of the original                          (Pharmaceutical News, Apr 29, 2010)
 independent claims asserted in the litigation in an
 effort to overcome the PTO’s rejections.                  Endovascular Technology
 The Actions Closing Prosecution are designated
 “non-final” because the patent owners have the                The United States District Court, Southern
 right to file comments in an effort to persuade the       District of Indiana, has ruled in favor of Cook
 patent examiners to reconsider the rejections             Incorporated in its decision to lift the stay on
 and re-open prosecution.                                  Cook’s patent infringement case against
                                                           Endologix, Inc (Nasdaq: ELGX). With this
               (Precision BioSciences, Jun 18, 2010)       ruling, the case filed by Cook on October 6, 2009,
                                                           will now proceed. The complaint claims infringement
 Counterclaims to Declaratory Judgment
                                                           by Endologix of two Cook patents for endovascular
     Cyclacel Pharmaceuticals, Inc, a biopharmaceutical    technologies, one of Cook’s leading technology
 company developing oral therapies that target             portfolios.
 the various phases of cell cycle control for the
 treatment of cancer and other serious disorders,              The two patents in suit are Cook’s US Patent
 announced that it filed its Answer and                    5,755,777 and 5,035,706. The ‘777 patent is
 Counterclaims to the declaratory judgment                 entitled “Expandable Transluminal Graft Prosthesis
 complaint filed by Celgene Corporation. Cyclacel          for Repair of Aneurysm,” and was granted on
 has filed counterclaims charging Celgene with             May 26, 1998. The ‘706 patent is entitled
 infringement of each of four Cyclacel-owned               “Percutaneous Stent and Method of Retrieval
 patents and seeks damages for Celgene’s                   Thereof,” and was granted on July 30, 1991. The
 infringement as well as injunctive relief. The four       Patent Office has issued a re-examination certificate
 patents directly involve the use and administration       for the ‘706 patent, as well as notice of intent to
 of Celgene’s ISTODAX® (romidepsin for                     issue a re-examination certificate on the ‘777 patent.
 injection) product.                                       As a result, the court ruled that Cook’s case was
                                                           “now poised to move forward.”
    The declaratory judgment complaint seeks to
 have the four Cyclacel patents, which claim the                                  (Cook Medical, Jun 8, 2010)

                                                      17                            IPR BIOTECHNOLOGY
WISTA                                                                                          AUGUST 2010

 New Defence in Infringement Case                         Validity of ‘983 Patent

     Cubist Pharmaceuticals, Inc. opposed a motion            Haemonetics Corporation announced that on
 filed by the Teva defendants to amend their answer       May 28, 2010, the United States Patent and
 to add a new defense in the patent litigation            Trademark Office issued a decision confirming
 between Cubist and Teva pending in the US                the validity of Haemonetics’ ‘983 patent in light
 district court for the district of Delaware. A motion    of numerous prior art references cited by
 for leave to amend the answer is a request to be         Fenwal Inc,.
 permitted to add a new allegation. The Teva
 defendants seek leave to amend their answer to allege         The ‘983 patent was the basis of a judgment
 that US patent Nos. 6,468,967 and 6,852,689 are          entered by the US Federal Court for the District
 unenforceable due to inequitable conduct.                of Massachusetts in June 2009 that found Fenwal
                                                          guilty of patent infringement, and liable to
     Cubist filed a patent infringement lawsuit           Haemonetics for $18 million in damages for past
 against Teva Parenteral Medicines, Inc. (TPM),           sales of the infringing product, and which imposed
 Teva Pharmaceuticals USA, Inc. and Teva                  a 10% royalty for future sales of the infringing
 Pharmaceutical Industries Ltd. The complaint             product until an injunction was to be effective
 alleges infringement of US patent Nos. 6,468,967         December 1, 2010.
 and 6,852,689, which exprie on September 24,
 2019, and US patent RE39,071, which expires                  On June 2, 2010, a three judge panel of the
 on June 15, 2016.                                        United States Court of Appeals for the Federal
                                                          Circuit issued a decision on Fenwal’s appeal,
               (Medical Patent News, Jun 11, 2010)        reversing in part, vacating in part, and remanding
                                                          the case to the trial court for further proceedings.
 Settlement of OPANA ER Litigation
                                                          The Appeals Court ruling did not invalidate
     Endo Pharmaceuticals and Penwest                     Haemonetics’ patent and made no decision about
 Pharmaceuticals have settled litigation with Impax       whether Fenwal’s product infringed, leaving the
 Laboratories, Inc. regarding the production and          question of infringement to be decided after further
 sale of generic formulations of OPANA® ER                proceedings before the district court.
 (oxymorphone hydrochloride) Extended Release
 tablets.                                                           (Haemonetics Corporation, Jun 4, 2010)
                                                          ZETIA Patent Litigation
     Under the terms of the settlement, Endo and
 Penwest have agreed to grant Impax a license to               Merck & Co., Inc. and Gelenmark Pharmaceuticals
 sell a generic of OPANA ER on Jan. 1, 2013.              Inc. USA and Gelenmark Pharmaceuticals, Ltd.
 Impax Laboratories will have 180-days of                 have reached an agreement to settle their patent
 exclusivity for 5, 10, 20, 30 and 40 mg tablets.         litigation involving Glenmark's challenge to Merck'
     Endo and Penwest also announced that                 patent covering ZETIA® (eztimibe). Specifically,
 they have executed an amendment to their                 Glenmark challenged Merck's basic compound
 existing strategic collaboration agreement under         patent, RE37,721 on numerous grounds.
 which the royalty rate on net sales of OPANA ER
                                                             This settlement effectively ends the lawsuit that
 would now be capped at 22 percent during the
                                                          was scheduled to begin on May 12, involving a
 period from April 1, 2010 through December 31,
                                                          challenge by Gelenmark which sought to launch
 2012, subject to adjustment in the fourth
                                                          a generic version to ZETIA drug before the
 quarter of 2012, and 20 percent during
                                                          April 2017 expiration of the patent exclusivity
 calendar 2013, subject to adjustment in the fourth
                                                          covering ZETIA.
 quarter of 2013.
               (Endo Pharmaceuticals, Jun 9, 2010)                         (Merck & Co., Inc, May 11, 2010)

IPR BIOTECHNOLOGY                                    18

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