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Ganesan A.,University of Glasgow | Watkinson A.,PharmAthene | Moore B.D.,University of Glasgow | Moore B.D.,University of Strathclyde
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2012

Insoluble aggregation or precipitation is one of the most common degradation pathways observed for biotherapeutics; despite this, the structural mechanisms by which this occurs remain poorly understood due to difficulties associated with biophysical characterisation of protein particulates. To address this knowledge gap, we developed a solid-state circular dichroism (CD) technique, which allows in situ measurements of the secondary and tertiary structural changes associated with the formation of visible therapeutic protein aggregates. We demonstrate how solid-state CD, in conjunction with other biophysical and computational methods can aid in gaining valuable insights into the mechanisms and pathways of thermal-induced precipitation of Bacillus anthracis recombinant protective antigen (rPA), the primary immunogen of anthrax subunit vaccine. Using these methods, we show the domains d3 and d4 are the most labile of the four structurally distinct domains of rPA and play the critical role in nucleating the cascade of unfolding and aggregation. During the assembly process, the domains d1 and d2 become kinetically trapped within the insoluble aggregate and reveal previously intractable distinct tertiary structural elements of the rPA native structure. These findings reveal a uniquely detailed insight into the role of rPA domains on protein stability and provide a mechanistic framework for thermal-induced unfolding and precipitation. It also shows that solid-state CD provides a novel approach in characterising protein precipitation that may facilitate rational improvements to the stability of biopharmaceuticals. © 2012 Elsevier B.V. All rights reserved. Source


News Article | December 2, 2013
Site: www.xconomy.com

Theraclone Sciences tried to merge with PharmAthene for a couple of months, but the deal is off. Annapolis, MD-based PharmAthene (NYSE MKT: PIP) chose to pull the plug on a pending merger with Seattle-based Theraclone on the day before a special meeting of shareholders, and Theraclone said today it has agreed. PharmAthene will now pay Theraclone a $1 million breakup fee, and both companies will go back to operating independently. Neither company explained in their respective statements why the deal collapsed. The two companies announced in August that they planned to an all-stock “merger of equals,” with the combined operation named PharmAthene, but with a headquarters in Seattle led by Theraclone CEO Cliff Stocks. The idea was to merge PharmAthene’s government contracting business for anthrax-related product candidates with Theraclone’s antibody drug discovery platform. Theraclone has a couple of drug candidates in clinical trials—one for flu, and another for cytomegalovirus. But Theraclone suffered a setback last week when it said it was unable to secure funding from the Biomedical Advanced Research and Development Authority (BARDA) to help advance its pandemic flu program. The failed merger marks the second time that a graduate of the Seattle-based Accelerator has been unable to complete a pending merger. Allozyne tried, unsuccessfully, to close a merger with Poniard Pharmaceuticals in 2011 which was aimed to get the company traded on a public exchange, at least partly so the initial venture investors could see some liquid returns on their investment. The company was founded in 2005 at Accelerator, and has raised more than $50 million since its start. Theraclone’s most recent financing was a $14 million equity-and-debt deal in March.


News Article | September 16, 2014
Site: www.fiercebiotech.com

A court ruling has saddled biodefense specialist Siga Technologies ($SIGA) with debts it cannot pay, the company said, and the biotech is filing for bankruptcy in an effort to keep its doors open long enough for an appeal. The issue revolves around Tecovirimat, an investigational smallpox treatment Siga provides to the U.S. under contract. Back in 2006, PharmAthene ($PIP) filed suit over Tecovirimat, claiming a share of the drug's proceeds, and, last month, a federal court found in its favor, ordering Siga to hand over as-yet-undecided damages in a lump sum. That figure is likely to be substantial, Siga said, so the company is fleeing for the protection of bankruptcy to stop PharmAthene from taking any enforcement action. In the meantime, the company is gearing up to mount an appeal, and CEO Eric Rose said Siga has enough cash to keep things moving until it can get back in court. More


News Article | November 3, 2014
Site: www.bloomberg.com

Nov. 3 (Bloomberg) -- China will set up its first specialized court to handle intellectual property cases in Beijing within two weeks as it seeks to answer criticisms the country is lax in protecting such rights. Courts dedicated to handling such trials on patents, trademarks and computer software issues will also be set up before the end of the year in two other major Chinese cities, Shanghai and southern Guangzhou, Wang Chuang, the deputy presiding judge with the IP division of China’s Supreme Court, said at a briefing today. “This will be an important revolution of the country’s judicial system to deal with IP-related cases,” Wang said. It’s also “a step to promote the development of China’s emerging industries,” he said. Foreign brands have complained about Chinese companies’ violations of intellectual property. China has made the watch list of countries needing to improve intellectual property rights protection in all 25 years that the Office of the United States Trade Representative has published an annual special report on the issue. The Supreme Court today also said it will set up an intellectual property protection research center and train technical investigation officers to help judges who need professional expertise, Wang said. The establishment of the dedicated court shows the strong desire of China to improve its international image, according to Feng Xiaoqing, a law professor specializing in intellectual property at the China University of Political Science and Law in Beijing. Dealing with such cases remains a fairly recent development in China, he said. For more, click here. Lex Machina, the legal data analytics firm, has compiled the “Hatch-Waxman/ANDA Litigation Report” on 1,671 cases filed from 2009 through September, involving more than 1,100 patents and more than 400 applications to the U.S. Food and Drug Administration. The report found that litigation involving abbreviated new-drug applications has been increasing since 2012, with 2014 likely to be “a record year,” according to a statement from the firm. The median age of patents being litigated in 2014 is five years, a 50 percent decline since 2010, according to the report. It said that “ANDA cases are less likely to settle than non-ANDA cases and more than twice as likely to reach judgment.” Oxycontin, as a trade name, had the most cases. Most ANDA cases are filed in Delaware and New Jersey. The number filed in New York has dropped, according to the report. Litigation stemming from a 2011 patent-licensing agreement between Samsung Electronics Co. and Microsoft Corp. is escalating. On Oct. 30, Samsung filed claims alleging that Microsoft triggered a termination right when it “merged with a major Samsung competitor -- Nokia’s devices and services business” and as a result “began manufacturing its own smartphones.” After the Microsoft-Nokia agreement, Samsung, it alleges, “has been put in the untenable position of being asked to provide” information that is “highly confidential and competitively sensitive” to a rival. Samsung also said sharing information with Microsoft may give rise to antitrust claims. If the agreement isn’t terminated, Samsung alleged, there could be accusations that the companies “are engaged in market allocations in terms of how and when products are developed and distributed to the market.” Microsoft initially claimed in the Aug. 1 suit that Samsung breached an agreement to share patents. The seven-year accord required Samsung to pay Microsoft royalties for phones and tablets that use the software maker’s patented technology, according to Microsoft. Samsung has refused to pay $6.9 million in interest owed under the agreement, Microsoft said. Microsoft claims Samsung is using the acquisition of Nokia Oyj’s phone business as an excuse to stop complying with the contract. The case is Microsoft Corp. v. Samsung Electronics Co., 14-cv-06039, U.S. District Court, Southern District of New York (Manhattan). GT Advanced Technologies Inc. lost a bid to keep an executive’s description of the circumstances surrounding its bankruptcy secret, putting a settlement with Apple Inc. in danger. The company and Apple, with which it had an agreement to supply the synthetic sapphire used in screens of mobile devices, asked to keep the executive’s statement under wraps. U.S. Bankruptcy Judge Henry Boroff on Oct. 30 said he intended to unseal it, while letting some pricing information remain confidential. Boroff said he will go through the statement by GT Advanced Chief Operating Officer Daniel Squiller, as well as other documents the parties want sealed, and probably issue an unsealing order this week. A public statement by Squiller was filed Oct. 28. GT Advanced in November 2013 announced a multiyear agreement to supply Apple with sapphire. The company lined up $578 million in prepayment loans from Apple to buy equipment to make the material, which wasn’t included in the latest version of the iPhone. The settlement would free GT Advanced from exclusivity agreements with Apple, give it control of its sapphire-manufacturing patents, and let it retain ownership and sales rights for more than 2,000 production furnaces in Mesa, Arizona, according to the court papers. The case is In re GT Advanced Technologies Inc., 14-bk-11916, U.S. Bankruptcy Court, District of New Hampshire (Manchester). For more, click here. Siga Technologies Inc., the biological-warfare defense firm supplying the only smallpox drug for the U.S. strategic stockpile, got court permission to mediate a damages award in a licensing dispute that drove it into bankruptcy. Siga and competitor PharmAthene Inc., which won a 2006 lawsuit, agreed to mediate a final resolution over the amount of damages Siga must pay, U.S. Bankruptcy Judge Sean Lane said in a ruling Oct. 30 in Manhattan. A creditor committee that includes PharmAthene supported mediation, according to court papers. The litigation, pending in Delaware state court, will continue during mediation, and any accord over a possible $232 million in damages reached by the companies will require bankruptcy court approval, Lane said. Delaware’s highest court last year upheld a judge’s 2011 finding that Siga violated promises to negotiate in good faith with Annapolis, Maryland-based PharmAthene over a license for Tecovirimat when it was being developed. Siga may have walked away from the talks after realizing the drug’s potential value, the court ruled. Tecovirimat, an antiviral drug, is intended for use during a possible biological terrorist attack and the U.S. needs the product, New York-based Siga said. The company filed for court protection from creditors on Sept. 16, saying the damages award in the lawsuit may imperil its operations. The case is Siga Technologies Inc., 14-bk-12623, U.S. Bankruptcy Court, Southern District of New York (Manhattan). For more patent news, click here. A federal court in Chicago held that U.S. copyright law governs a dispute between six members of the 1985 championship Chicago Bears and a recording label. “The Shufflin’ Crew” are six ex-Bears who recorded the “Super Bowl Shuffle,” a music video trumpeting the success of the National Football League team. The players sued, claiming the defendants weren’t parties to the original agreement with Red Label Records and as a result didn’t have marketing, distribution and licensing rights. Although they filed in state court, the defendants had the case removed to the federal court. U.S. District Judge Edmond Chang ruled that the case was governed by the federal Copyright Act. The case is Dent v. Renaissance Marketing Corp., 14-cv-02999, U.S. District Court, Northern District of Illinois (Chicago). For more copyright news, click here. To contact the reporter on this story: Ellen Rosen in New York at erosen14@bloomberg.net To contact the editors responsible for this story: Michael Hytha at mhytha@bloomberg.net Charles Carter, Joe Schneider


Soliakov A.,Northumbria University | Harris J.R.,Northumbria University | Harris J.R.,University of Mainz | Watkinson A.,PharmAthene | Lakey J.H.,Northumbria University
Vaccine | Year: 2010

Caf1 of the plague bacterium, . Yersinia pestis is a polymeric virulence factor and vaccine component, formed from monomers by a donor strand exchange (DSE) mechanism. Here, EM images of Caf1 reveal flexible polymers up to 1.5 μm long (4. MDa). The bead-like structures along the polymer are 5.8 ± 1. nm long and correspond to single Caf1 proteins. Short polymers often form circles, presumably by DSE. We also provide the first images of proteins bound to alhydrogel adjuvant. Caf1, hemocyanin and anthrax PA are all resolved clearly and Caf1 exhibits adjuvant bound stretches with long intervening loops draped from the edges. © 2010 Elsevier Ltd. Source

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