Marder V.J.,University of California at Los Angeles |
Novokhatny V.,Talecris Biotherapeutics
Journal of Thrombosis and Haemostasis | Year: 2010
Direct fibrinolytics are proteolytic enzymes that degrade fibrin without requiring an intermediate step of plasminogen activation. This review summarizes the current information available for five such agents, namely, plasmin (the prototypical form), three derivatives of plasmin (mini-plasmin, micro-plasmin, and delta-plasmin), and alfimeprase, a recombinant variant of a snake venom α-fibrinogenase, fibrolase. Biochemical attributes of molecular size, fibrin binding and inhibitor neutralization are compared. Preclinical investigations that assess the potential for thrombolytic efficacy in vitro and in animal models of vascular occlusion and for hemostatic safety in animal models of bleeding are detailed. Clinical potential has been assessed in patients with peripheral arterial and graft occlusion, acute ischemic stroke, and access catheter and hemodialysis shunt occlusions. The direct fibrinolytic agents have impressive biochemical and preclinical foundations for ultimate clinical application. However, clinical trial results for micro-plasmin and alfimeprase have not measured up to their anticipated benefit. Plasmin has thus far shown encouraging hemostatic safety, but efficacy data await completion of clinical trials. Whether direct fibrinolytics will provide clinical superiority in major thrombotic disorders over currently utilized indirect fibrinolytics such as tissue plasminogen activator remains to be determined. © 2009 International Society on Thrombosis and Haemostasis.
Marder V.J.,University of California at Los Angeles |
Jahan R.,University of California at Los Angeles |
Gruber T.,University of California at Los Angeles |
Goyal A.,University of California at Los Angeles |
Arora V.,Talecris Biotherapeutics
Stroke | Year: 2010
Plasmin is a direct-acting thrombolytic agent with a striking hemostatic safety advantage over plasminogen activators in animal models of thrombolysis and bleeding. In contradistinction to plasminogen activators, which risk bleeding at any effective thrombolytic dose, plasmin is tolerated without bleeding at several-fold higher amounts than those needed for thrombolysis. Plasmin has been safe in a current trial in patients with peripheral arterial or graft occlusion, and efforts are now directed toward therapy of stroke caused by cerebral artery occlusion. A rabbit (4 kg body weight) model of 2-hour, thrombin-induced middle cerebral artery occlusion using angiographic documentation of vascular patency and recanalization was used to perform a dose-ranging study of plasmin, delivered by catheter over a median duration of 10 minutes. Plasmin induced early recanalization in all animals (3 per group) within 10 minutes after discontinuation of 3, 2, or 1 mg of agent infusion. Control saline infusion failed to induce recanalization in 3 of 3 subjects. Plasmin rapidly induces middle cerebral artery recanalization, as determined in an angiogram-based animal model of arterial occlusion. Based on these data and other information, a phase I/IIa clinical trial of plasmin in human middle cerebral artery ischemic stroke has been initiated. © 2010 American Heart Association, Inc.
Stern L.D.,Talecris Biotherapeutics
COPD: Journal of Chronic Obstructive Pulmonary Disease | Year: 2013
Best-in-class systems have evolved among alpha-1 antitrypsin (AAT) producers, specialty pharmacies and the Alpha-1 Foundation and AlphaNet patient groups. The Genetic Alliance, NORD and other independent parties have recognized the benefits regarding public policy, patient advocacy, medical research, medication adherence, patient identification and health outcomes. Driving the next quantum leap in disease state management for Alpha-1 patients will require strong leadership from both industry and patient groups. Six initiatives are suggested that will sustain best-in-class approaches to identify, treat and even cure Alpha-1 patients. © 2013 Informa Healthcare USA, Inc.
Loladze V.V.,Rensselaer Polytechnic Institute |
Loladze V.V.,Talecris Biotherapeutics |
Makhatadze G.I.,Rensselaer Polytechnic Institute
Proteins: Structure, Function and Bioinformatics | Year: 2011
Statistical analysis of the residue separation between a pair of ionizable side chains within 4 Å of each other was performed on a set of 1560 non-homologous PDB structures. We found that the frequency of pairs of like charges (i.e., pairs consisting of acidic residues Asp and Glu or pairs consisting of basic residues Arg and Lys) is two orders of magnitude lower than the pairs of oppositely charged residues (salt-bridges). We also found that for pairs of like charges the distribution is skewed dramatically towards short residue separation (<3). On the basis of these observations, we hypothesize that at short residue separation the repulsion between charges does not contribute much to the protein stability and the effects are largely dominated by the long range charge-charge interactions with other ionizable groups in the protein molecule. To test this hypothesis, we incorporated various pairs of charged residues at position 63 and 64 of ubiquitin and compared the stabilities of these variants. We also performed calculations of the expected changes in the charge-charge interactions. A very good correlation between experimental changes in the stability of ubiquitin variants, and changes in the energy of charge-charge interactions provides support for the hypothesis that a pair of ionizable residues next to each other in sequence modulates protein stability via long range charge-charge interactions with the rest of the protein. © 2011 Wiley-Liss, Inc.
Talecris Biotherapeutics | Date: 2010-02-05
Compositions, kits, and methods for determining plasmin activity using a fluorogenic peptide substrate are provided.
Talecris Biotherapeutics | Date: 2010-11-03
The present invention relates to a polynucleotide comprising a nucleotide sequence encoding a polypeptide having a single N-terminal kringle domain homologous to a kringle domain of native human plasminogen; and a C-terminal domain activation site and serine protease domain homologous to the corresponding domains in human plasminogen; wherein the polypeptide binds to immobilized lysine.
Talecris Biotherapeutics | Date: 2010-03-02
Compositions and methods for preparing plasminogen, in particular recombinant plasminogen, and compositions and methods of utilizing same for preparing plasmin are provided.
News Article | October 2, 2009
Omeros Teed Up for IPO Next Week, Seeking to Rake In More Than $80M Seattle-based Omeros is on the docket to go public next week, and will attempt to become the first pure-play biotechnology company to take the plunge since February 2008, according to Renaissance Capital, an IPO analysis firm. Omeros, which is developing an anti-inflammatory treatment to help people recover from arthroscopic knee surgery, has set a goal of selling 6.8 million shares of common stock at a price range of $10 to $12 apiece, as we reported here a couple weeks ago. Deutsche Bank and Wedbush PacGrow Life Sciences are the lead underwriters of the prospective deal, which could raise as much as $81.8 million for the company, if it can gin up demand for shares at the high end of its range. If Omeros can pull this off, and end up trading under the ticker “OMER,” it will be the first true biotech company to do an IPO since Sunrise, FL-based Bioheart (OTC BB: BHRT) did it in February 2008. That comparison has to give any biotech investor the creeps, since BioHeart, a stem cell company, only traded a year on the NASDAQ and has seen its stock crash from an opening of $5.25 to $1.80 as of today on the bulletin board. Biotech-related IPOs have looked a little better lately. Last month, Nashville, TN-based Cumberland Pharmaceuticals (NASDAQ: CPIX), a specialty pharma company, went public at $17 and has traded down to $15.84 as of mid-day trading today. This week, a former unit of Bayer in Research Triangle Park, NC, that makes plasma-derived protein therapies, Talecris Biotherapeutics (NASDAQ: TLCR), raised $950 million by selling shares at $19 apiece. Its stock is now up over $22. Omeros clearly needs the cash from an IPO to pursue its goals, according to its updated prospectus. It has been around since 1994, and has spent $108.8 million of investors’ money through June 30. The company’s cash reserves dwindled from $20 million at the start of the year, to about $10.4 million at the last reported date, June 30. Assuming it can rake in the new IPO money, Omeros should have enough cash to operate at least through September 2011, according to the prospectus. But without that money, Omeros will need to “significantly modify our operational plans for us to continue as a going concern,” the company stated.
News Article | November 29, 2011
From iOS and Android to BlackBerry and Windows Phone, the app store model has become the main way mobile device users find, download, and update their software. And with employees increasingly begging for access to corporate resources from smartphones and tablets, IT departments are starting to wonder whether they should jump into the app store business themselves. "The public app store is kind of the wild, wild West," Forrester analyst Jeffrey Hammond tells Ars. Private app stores, hosted for the employees of a single business, are receiving “a lot of interest from the clients I talk to. Folks realize that self-provisioning is the long-term trend." Private app stores are both a concession to the consumerization of IT, giving employees what they need in handsets they like, and a technology that can help IT administrators take control over how employee-owned devices are used for work. Corporate app stores are in their nascent stages today, but some big companies (notably IBM) have already built mobile stores for their own employees. Other vendors want to make private app stores accessible to businesses that don't have the staff and resources to build their own. "One thing we don't see a lot today that will be commonplace within the next three years is just about every company [with at least 100 employees] will have their own corporate app store," predicts Dan Croft, CEO of Mission Critical Wireless, which helps businesses manage mobile deployments. Croft likens the emergence of private app stores today to intranets in the 1990s. Private app stores won't address all the security and management concerns caused by the consumerization of IT. Nor will they, by themselves, unlock the full potential of employee-owned devices to improve productivity. But they could become an important tool for businesses that have enough employees and use cases to make the app store model a justifiable expense. Private app stores look and function much as you might expect. End users see an app store, separate from those run by smartphone backers like Apple or Google or Microsoft, from which they can download applications that their employers have developed or purchased. On the back end, IT administrators manage which employees get access to particular apps, ensure that updates are pushed out in a timely fashion, take advantage of built-in analytics tools, and even remotely delete apps from user devices when necessary. Granting employee-owned smartphones more access to company data does carry some risk. Although a business controls what it puts in its own app store, employees can still visit malware-infected websites or download malicious applications from the regular app stores, which has particularly been a problem with the Android Market. Expanding access to corporate resources from phones and tablets also increases the chance of an employee leaking confidential data, intentionally or otherwise. Businesses will naturally want to impose restrictions, but employees may bristle if these are too onerous. To take just a single example, the question of whether it is legal (and appropriate) for businesses to remotely wipe employee phones remains unsettled. But there is hope. New technologies can isolate the corporate and personal components of a smartphone. BlackBerry's Balance technology lets IT shops keep a user's personal information isolated from business information with separate partitions for each, for instance. Similarly, VMware has developed a hypervisor for Android phones that creates a virtual machine in which corporate data and applications are stored separately from a user's personal data and applications. If businesses get the security model right, employee-owned mobile devices can move from being treated as a threat to being treated as a valuable resource. IBM is a great example. The 400,000-employee company built its own app store called WhirlWind. It was initially just for BlackBerry phones but is now being rolled out to iOS and Android devices in pilot trials. So far, 35,000 IBMers use WhirlWind, the vast majority of them from BlackBerrys. IBM started developing the concept late in 2009 and the app store, a Java-based application running on IBM's WebSphere application server and DB2 database software, was in production by late 2010. While users on different mobile platforms see their own IBM app store, with some apps being available on only one platform, the IT folks on the back end can manage them all from a single console. And each app undergoes a code review before distribution. The store connects users both to IBM-specific Web applications and to native apps that can be downloaded onto a user's device, some of which were developed by IBM itself and others by vendors who contract with IBM. Widely used programs available through WhirlWind include "Blue Pages"—a Web-based app that works a bit like a private version of Facebook—and a version of the Sametime IM app customized for IBM employees and available as a download. In the future, the WhirlWind app store will provide more tools for performing common business tasks, like managing travel and submitting expense reports, says Bill Bodin, IBM's CTO for mobility. The store isn't just for phones, either. IBM has rolled out WhirlWind to the iPad and plans to produce a version optimized for Android tablets, too. Naturally, the highly technical workforce at IBM has contributed numerous applications to WhirlWind. "It's really been a great melting pot for internal applications," Bodin says. "We have dozens of applications that have been submitted by developers and our brands [vendors] alike. It's not just a grass-roots effort anymore." IBM has moved slowly from the locked-down BlackBerry environment to one that welcomes iOS and Android. Bodin says IBM worries especially about devices being jailbroken or compromised. "You run the risk of having a rogue application on there that accesses private data and reports and broadcasts information as it sees fit," he says. IBM is using VPNs, password requirements, and endpoint management tools for its own workforce, and is launching a hosted service for IBM customers that ensures personal devices comply with corporate security policies.