Human Genome Sciences Research Articles

Pharmaceuticals: GSK clinches $3.6 billion deal for Human Genome Sciences

RETURN TO ISSUEPREVNewsNEXTPharmaceuticals: GSK clinches $3.6 billion deal for Human Genome SciencesCite this: Chem. Eng. News 2012, 90, 30, 7Publication Date (Print):July 23, 2012Publication History Published online29 March 2013Published inissue 23 July 2012https://doi.org/10.1021/cen-09030-notw5Copyright © 2012 Chemical & Engineering NewsArticle Views6Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (212 KB) SUBJECTS:Biopolymers,Diseases and disorders,Genomics,Immunology,Pharmaceuticals Get e-Alerts

Eli Lilly & Co v Human Genome Sciences Inc: [2011] UKSC 51: Supreme Court (England and Wales): Lord Hope of Craighead DPSC, Lord Walker of Gestingthorpe JSC, Lord Neuberger of Abbotsbury MR, Lord Clarke of Stone-cum-Ebony JSC, Lord Collins of Mapesbury: (Lord Hope of Craighead DPSC, Lord Walker of Gestingthorpe and Lord Clarke of Stone-cum-Ebony JJSC delivered concurring judgments and

Eli Lilly & Co v Human Genome Sciences Inc: [2011] UKSC 51: Supreme Court (England and Wales): Lord Hope of Craighead DPSC, Lord Walker of Gestingthorpe JSC, Lord Neuberger of Abbotsbury MR, Lord Clarke of Stone-cum-Ebony JSC, Lord Collins of Mapesbury: (Lord Hope of Craighead DPSC, Lord Walker of Gestingthorpe and Lord Clarke of Stone-cum-Ebony JJSC delivered concurring judgments and

Straight talk with...Joseph Schwartz

On 17 May, Human Genome Sciences (HGS) formally rejected a $2.6 billion unsolicited takeover offer by GlaxoSmithKline. The Maryland-based biotech firm had long partnered with the UK drug giant to develop drugs including Benlysta (belimumab), HGS's first drug on the market and the first new medicine approved to fight lupus in 50 years. But, at $13 a share, GSK's bid was deemed "inadequate" by the HGS board. Recent history in the biotech sector shows how high the stakes are in such negotiations. Since last November, six biopharma buyouts have exceeded $1 billion each, with Gilead Sciences' purchase last year of the hepatitis C specialist Pharmasset topping the charts at a whopping $11.2 billion, the highest ever paid for a clinical-stage biotech and an 89% premium to its share price at the time. More recently, in April AstraZeneca paid $1.3 billion for Ardea Biosciences, a company with cancer and gout drugs in the pipeline but nothing on the market.One person watching the upward clime of such deals is biopharma analyst Joseph Schwartz, a managing director at Leerink Swann in Boston. Mark Ratner sought out Schwartz, who was named the top stock picker for pharmaceuticals in the last year's FT/StarMine Analyst Awards, for his views on what's behind the recent buyout spending.

BAFF/BLyS inhibitors: A new prospect for treatment of systemic lupus erythematosus

In November 2009, Human Genome Sciences and Glaxo-Smith Kline [HGS (Rockville, Maryland) and GSK, respectively] announced that Belimumab, a neutralizing antibody to the tumour necrosis factor (TNF)-like ligand, B-cell activating factor (BAFF belonging to the TNF family, also named BLyS), met the primary endpoints in two phase III clinical trials in systemic lupus erythematosus (SLE, lupus). In March 2011, Belimumab was approved by the US Federal Drug Agency for treatment of SLE patients; this was followed in May with approval by the European Medicines Agency for use in the European Union. This is an exciting development as it is the first successful late-stage clinical trial in SLE in over 40 years. In the light of this breakthrough, we review the key data and research outcomes and examine how blocking BAFF in patients with SLE significantly improves clinical outcomes.

Harmony and BLyS in Europe and the UK

*Marks & Clerk LLP, 62–68 Hills Road, Cambridge, CB2 1LA, UK Tel.: +44 1223 345 520 Fax: +44 1223 365 560 E-mail: gwilliams@marks-clerk.com Photograph © Marks & Clerk LLP What level of disclosure is required to obtain a patent? When asserting a physiological or therapeutic function of a molecule, how concrete must these functions be? The first patents case before the UK Supreme Court recently ruled on these issues, as well as considering the often vexed question surrounding the relationship between UK and European courts and whether the UK is bound to follow European case law. European patent law requires, among other things, that an invention be “susceptible of industrial application” (Article 57 EPC glosses this as “An invention shall be considered as susceptible of industrial application if it can be made or used in any kind of industry, including agriculture.”) [1]. The race to the patent office to establish priority for an invention can conflict with the need to ensure that a use for the invention is disclosed. Often, such a use is self-evident; however, in the biotechnology sector this can be more doubtful, with in silico or expression data often hinting at a possible use for a gene or peptide, but final confirmation of this not coming for some time afterwards. This is the case with the recently approved lupus treatment Benlysta (belimumab), an antibody to the B-cell survival factor BLyS, the scientific development of which is summarised in [2]. The patent portfolio surrounding belimumab ultimately reaches back to early patent filings directed to BLyS and led to the first judgment on a patents case from the UK Supreme Court [201]. In 1996, Human Genome Sciences (HGS) filed a patent application disclosing the sequence of a novel peptide termed neutrokine-a [101]. The application indicated that the peptide is a member of the TNF superfamily, based on sequence homology and, as a consequence of this family membership, predicted various uses for the peptide, including inhibition of T-cell proliferation and treatment of autoimmune diseases. These predictions were made on little more evidence than membership of the TNF superfamily and were accompanied by what some might term typical patent verbiage. In the words of Lord Neuberger, “The specification, or description, of the Patent ... is confusingly long, diffuse, and widely expressed, running to over 25 closely typed pages, and nearly 200 paragraphs of descriptive text, and a further 12 pages of sequences of polypeptide amino acids and DNA nucleotides ...The specification ‘contains extravagant and sometimes contradictory claims...” Perhaps rather more tolerantly, the Technical Board of Appeal of the European Patent Office (‘the Board’) referred to the patent as having been drafted on a ‘boiler plate’ basis, which it described as ‘a practice used by patentees’” [201]. As an example of these contradictory claims, the judge noted that the patent suggests that both neutrokine-a and its antagonists inhibit immune-cell

Pharmaceuticals: GlaxoSmithKline offers $2.6 billion to buy Human Genome Sciences

GlaxoSmithKline has made an unsolicited $2.6 billion bid for its long-standing partner Human Genome Sciences. The biotech firm has rejected the bid as too low and has hired Goldman Sachs and Credit Suisse to explore its options, including a sale to GSK or another firm. GSK and HGS have been drug development and marketing partners since 1993, just two years after HGS was founded. To date, only one product has emerged from the pact: Benlysta, a monoclonal antibody approved last year to treat lupus. However, the companies have two other drug candidates in Phase III clinical trials: albiglutide, to treat type 2 diabetes, and darapladib, to treat heart disease. Buying HGS outright, GSK says, would simplify R&D, manufacturing, and sales operations for all three products, yielding some $200 million in cost savings by 2015. The question now, Bernstein Research stock analyst Timothy Anderson says in a note to clients, is ...

Appeal to Be Heard in Human Genome Sciences v. Eli LillyDOCUMENT: Judgment in Human Genome Sciences Inc. (Appellant) v. Eli Lilly and Company (Respondent) Before Lord Hope, Deputy President, Lord Walker, Lord Neuberger, Lord Clarke, and Lord Collins [extract

Appeal to Be Heard in <i>Human Genome Sciences v. Eli Lilly</i>DOCUMENT: Judgment in <i>Human Genome Sciences Inc. (Appellant) v. Eli Lilly and Company (Respondent)</i> Before Lord Hope, Deputy President, Lord Walker, Lord Neuberger, Lord Clarke, and Lord Collins [extract

Judgment in Human Genome Sciences Inc. (Appellant) v. Eli Lilly and Company (Respondent) Before Lord Hope, Deputy President, Lord Walker, Lord Neuberger, Lord Clarke, and Lord Collins [extract

Judgment in <i>Human Genome Sciences Inc. (Appellant) v. Eli Lilly and Company (Respondent)</i> Before Lord Hope, Deputy President, Lord Walker, Lord Neuberger, Lord Clarke, and Lord Collins [extract

Long-Term Follow-Up of an HIV-Infected Patient With Reactive Arthritis Treated With Infliximab

From Arthritis & Rheumatic Disease Specialties, Aventura, FL. The author is a member of the Speakers’ Bureau for and received a grant for the development of this paper from Centocor. He also receives funding for clinical research from Bristol Myers Squibb, Eli Lily, AstraZeneca, UCB, Roche, Genentech, Celgene, Human Genome Sciences, and Cephalon. The author declares no conflict of interest. Correspondence: Norman B. Gaylis, MD, Arthritis & Rheumatic Disease Specialties, 21097 NE 27th Court, Suite 200, Aventura, FL 33180. E-mail: [email protected].

Antibodies 2.0

Antibodies 2.0

Interview: Commercial Translation of Cell-Based Therapies and Regenerative Medicine: Learning by Experience

Dr Haseltine speaks to Emily Culme-Seymour, Assistant Commissioning Editor William A Haseltine, PhD has an active career in both Science and Business. He was a professor at Harvard Medical School and Harvard School of Public Health (MA, USA) from 1976 to 1993, where he was Founder and Chair of two academic research departments. He is well known for his pioneering work on cancer, HIV/AIDS and genomics. He has authored more than 200 manuscripts in peer-reviewed journals and is the author of several books. He is the founder of Human Genome Sciences, Inc. and served as the Chairman and CEO of the company until 2004. He is also the founder of several other successful biotechnology companies. William Haseltine is currently Chairman and President of ACCESS Health International, Inc., which supports access to affordable, high-quality health services in low, middle and high income countries, and Chairman of the Haseltine Foundation for Science and the Arts, which fosters a dialog between sciences and the arts. He is an Adjunct Professor at the Scripps Institute for Medical Research and the Institute of Chemical Engineering, the University of Mumbai, India. He is a member of the Advisory Board of the IE University, Madrid, the President's Council of the Cold Spring Harbor Laboratory, the Advisory Council for the Koch Institute of MIT, a member of the University Council Committee on technology transfer, Yale University, and is a Lifetime Governor of the New York Academy of Science (NY, USA). He is an honorary member of the Board of Trustees of the Brookings Institution, a member of the Board of Trustees of the Center for Emerging Markets of the Indian School of Business, a member of the Council on Foreign Relations, a member of the Board of AID for AIDS International, and a member of the Chairman's Circle of the Asia Society. He is a member of the Advisory Board of the Metropolitan Opera (NY, USA), the Chairman's Council of the Metropolitan Museum (NY, USA), the International Council of the Guggenheim Museum, the International Council of the Tate Modern, the Board of Directors of the Young Concert Artists, Inc. and the Youth Orchestra of the Americas.

Belimumab Efficacy is ‘Mild’ but Market Potential Still Great†

Speaking for the inThought Expert Discussion Series in February, Dr George Tsokos mirrored the opinion of many lupus thought leaders: Human Genome Sciences (HGS) and GlaxoSmithKline's (GSK) belimumab (Benlysta®) was likely to be approved by the US FDA and, despite modest efficacy, will be used by a large proportion of lupus patients. Dr Tsokos praised HGS and GSK's clinical trial program for belimumab, noting that huge trials and unique trial endpoints were needed to demonstrate the drug's efficacy, allowing it to succeed where so many other lupus drugs have failed. Still, belimumab's trial design may not become standard in future lupus trials - questions about identification of appropriate lupus patients with active disease, trial endpoints, and subgrouping lupus patients remain. Although Dr Tsokos does not expect other agents currently being tested in lupus trials to be significantly more efficacious than belimumab, his research suggests that significantly better results could be obtained using agents targeting interleukin-17, spleen tyrosine kinase (SYK), and calcium/calmodulin-dependent protein kinase type IV (CaMKIV). In line with Dr Tsokos' comments and consistent with inThought's outlook for belimumab, the US FDA granted approval for belimumab in March 2011, making it the first new lupus drug to be approved in more than 50 years. inThought projects US sales of $1.1 billion for belimumab by 2017. † Adapted and reproduced from Weintraub B. Benlysta Efficacy is "Mild" but Market Potential Still Great: Anticipating U.S. Approval of the First Lupus Drug Since 1957. inThought Research, 2011 Feb 24.

B cell activating factor is elevated in acute idiopathic thrombotic thrombocytopenic purpura

B cell activating factor is elevated in acute idiopathic thrombotic thrombocytopenic purpura

Industry Update: the Latest Developments in Therapeutic Delivery

This month’s article covers the time frame 16 February–15 March 2011, a period which saw the conclusion of the hard-fought-for takeover of Genzyme by Sanofi-aventis and the purchase of ProStrakan by Kyowa Hakko Kirin. There was good news for GlaxoSmithKline, Human Genome Sciences and sufferers of systemic lupus erythematosus with the US approval of Benlysta®, the first new treatment for this serious and difficult-to-treat condition for more than 50 years. There was bad news for SkyePharma when AstraZeneca decided to discontinue production of Pulmicort® (budesonide) hydrofluoroalkane pressurized metered dose inhaler, developed by SkyePharma, due to unsolved, complex manufacturing issues. Finally, progress towards an EU-wide single patent took a massive leap forward when proposals were approved by the European Parliament and the Council of the EU, only to be knocked back when the European Court of Justice ruled that plans to create an EU-wide patent court structure were not compatible with EU law. As ever, the material for this article has been sourced mainly from company websites and press releases.

First new lupus drug approved in half-century

FDA, Human Genome Sciences Inc., and GlaxoSmithKline PLC on March 9 announced the approval of belimumab, or Benlysta, as add-on therapy in the treatment of adults with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy. The agency said belimumab is

Epididymal Protein Targets: A Brief History of the Development of Epididymal Protease Inhibitor as a Contraceptive

The Laboratories for Reproductive Biology at the University of North Carolina at Chapel Hill began collaboration with Human Genome Sciences (Rockville, Maryland) to sequence a human epididymal library and identify epididymal-specific genes. Among the first clones obtained from Human Genome Sciences was a clone for EPPIN (official symbol, SPINLW1). Our laboratory has described EPPIN (epididymal protease inhibitor) as a novel gene on human chromosome 20q12-13.2 that encodes a cysteine-rich protein containing both Kunitz-type and WAP-type 4-disulfide core consensus sequences that characterize it as a protease inhibitor. EPPIN expresses 3 mRNA splice variants that encode 2 protein isoforms found in the testis and epididymis. Of the 2 isoforms, 1 is secreted and 1 lacks a secretory signal piece. EPPIN is predominantly a dimer, although multiples often exist, and in its native form, EPPIN is found on the sperm surface complexed with lactotransferrin and clusterin. During ejaculation, semenogelin from the seminal vesicles is bound to the EPPIN protein complex, initiating a series of events that define EPPIN's function: modulating prostate-specific antigen (PSA) activity, providing antimicrobial protection, and binding semenogelin, thereby inhibiting sperm motility. As PSA hydrolyzes semenogelin in the ejaculate coagulum, spermatozoa gain progressive motility. Using immunization as a tool to study antigen function, we demonstrated that EPPIN is essential for fertility because immunization of male monkeys with recombinant EPPIN results in complete, but reversible, contraception. To exploit our understanding of EPPIN's function, we have developed a high-throughput screen to look for compounds that inhibit EPPIN-semenogelin interaction and mimic anti-EPPIN, inhibiting sperm motility. These compounds are now being developed into a nonhormonal male contraceptive.

A Multicenter Randomized Phase II Trial of Mapatumumab, a TRAIL-R1 Agonist Monoclonal Antibody, In Combination with Bortezomib In Patients with Relapsed/Refractory Multiple Myeloma (MM)

AbstractAbstract 5031Mapatumumab, a fully human monoclonal antibody, targets and activates the TRAIL-R1 receptor. We conducted this randomized, controlled phase II trial to evaluate the efficacy and safety of mapatumumab in combination with bortezomib in subjects with relapsed/refractory MM. Response was evaluated using the Bladé criteria. Patients were required to have a measurable serum and/or urine M-protein and have failed 1 or 2 prior therapies for MM. Patients were excluded if they had received prior bortezomib. Patients were randomly assigned to Arm A, 1.3 mg/m2 bortezomib (days 1, 4, 8, 11) every 21 days; Arm B10, bortezomib + 10 mg/kg mapatumumab (day 1) every 21 days; or Arm B20, bortezomib + 20 mg/kg mapatumumab (day 1) every 21 days. Cycles were repeated every 21 days for a maximum of 17 cycles (1 year), progressive disease or unacceptable toxicity. Subjects with complete response (CR) were treated for an additional 2 cycles after documentation of CR (not to exceed 17) and then followed. A total of 104 subjects from 4 countries were randomly assigned to the treatment arms. The addition of mapatumumab to bortezomib did not increase the response rate, progression-free survival (PFS) or duration of response compared to bortezomib alone. Adverse events were generally balanced across treatment groups; there was no evidence that mapatumumab exacerbated toxicities associated with bortezomib. As expected, the most common toxicities were hematological and peripheral neuropathies. The results do not support further evaluation of mapatumumab in combination with bortezomib in patients with advanced MM. Additional trials of mapatumumab in other indications are on-going. Disclosures:Gallant:Human Genome Sciences, Inc.: Employment, Equity Ownership. Kumm:Human Genome Sciences, Inc.: Employment, Equity Ownership. Klein:Human Genome Sciences, Inc.: Employment, Equity Ownership.

Phospholipid Scramblase 1 Is Secreted by a Lipid Raft-dependent Pathway and Interacts with the Extracellular Matrix Protein 1 in the Dermal Epidermal Junction Zone of Human Skin

We examined the interaction of ECM1 (extracellular matrix protein 1) using yeast two-hybrid screening and identified the type II transmembrane protein, PLSCR1 (phospholipid scramblase 1), as a binding partner. This interaction was then confirmed by in vitro and in vivo co-immunoprecipitation experiments, and additional pull-down experiments with GST-tagged ECM1a fragments localized this interaction to occur within the tandem repeat region of ECM1a. Furthermore, immunohistochemical staining revealed a partial overlap of ECM1 and PLSCR1 in human skin at the basal epidermal cell layer. Moreover, in human skin equivalents, both proteins are expressed at the basal membrane in a dermal fibroblast-dependent manner. Next, immunogold electron microscopy of ultrathin human skin sections showed that ECM1 and PLSCR1 co-localize in the extracellular matrix, and using antibodies against ECM1 or PLSCR1 cross-linked to magnetic immunobeads, we were able to demonstrate PLSCR1-ECM1 interaction in human skin extracts. Furthermore, whereas ECM1 is secreted by the endoplasmic/Golgi-dependent pathway, PLSCR1 release from HaCaT keratinocytes occurs via a lipid raft-dependent mechanism, and is deposited in the extracellular matrix. In summary, we here demonstrate that PLSCR1 interacts with the tandem repeat region of ECM1a in the dermal epidermal junction zone of human skin and provide for the first time experimental evidence that PLSCR1 is secreted by an unconventional secretion pathway. These data suggest that PLSCR1 is a multifunctional protein that can function both inside and outside of the cell and together with ECM1 may play a regulatory role in human skin.

Belimumab for the treatment of systemic lupus erythematosus

Over the last several years, there has been marked interest regarding the role of B cells in the pathogenesis of systemic lupus erythematosus (SLE) as well as multiple other autoimmune diseases. Owing to the multitude of evidence showing B-cell dysfunction in SLE, targeting B cells has been investigated as a modality for treating the disease. There are a number of strategies that can be used for B-cell-directed therapy. In this article, we focus on the use of B-lymphocyte stimulator (BLyS) inhibition. BLyS has been found to be an important cytokine in B-cell development and activity and is strongly implicated in SLE pathogenesis. Belimumab (Benlysta®, Human Genome Sciences Inc., MD, USA) is a drug that inhibits BLyS and is thus a prime candidate to treat disorders with B-cell dysfunction and SLE in particular. Belimumab has now gone through numerous clinical trials, including an extensive Phase II trial and two Phase III trials. The drug looks very promising and in this paper we review the relevant data, ...

Who owns your genes?

The attempt to break the hold that Myriad has on key patents for cancer genes has reopened the debate on who can own rights to biology. At the press conference held to announce success in transplanting a synthetic genome into a living cell, scientist and cofounder of Synthetic Genomics J Craig Venter claimed: 'I have never been quite comfortable claiming patents on discoveries.' Yet Venter's name was prominent on the bundle of patents filed during his work on the Human Genome Project. In his autobiography, Venter claims he became the scapegoat for the patents filed in the 1990s patents on fragments of DNA uncovered during the sequencing work as part of a plan by the National Institute of Health to secure rights over the DNA before private researchers. But the company he founded and later left, Celera Genomics, sought patents on hundreds of potentially significant human genes despite not knowing what most of the DNA did. Even after Celera, Venter went on to help put together a wide-ranging patent to support his synthetic biology based on subsets of a natural bacterium. Celera was not alone. Incyte Genomics and Human Genome Sciences did the same. But it was Monsanto, already widely criticised for its approach to intellectual property (IP) in the biosciences, who triggered a lawsuit that changed the way that agencies such as the US Patent and Trademark Office viewed DNA patents in the mid-2000s. After that case, the USPTO decided that only genes with a known function could be patented, not just fragments of DNA that seem to come from individual genes found during mass sequencing efforts. Even that view could change again if another biotechnology company, Myriad Genetics, fails in its appeal to put its name against sequences of DNA that have existed in humans for millennia. It is the latest battle in the war to gain control over chunks of the genome, most of which is taking place in the United States of America but which has seen skirmishes in Europe and, more recently, in Australia.