Celsus News

Celsus submits Heparin Lithium Master Access File to the FDA

September 10, 2015 - Cincinnati OH -- Celsus Laboratories, Inc. ("Celsus") recently submitted a Master Access File to the FDA for its Heparin Lithium products used as components in medical devices. The submission was assigned number MAF2648. The source material for subject products, Heparin Sodium, is manufactured by Celsus under controls of FDA Drug Master File 7944 from a porcine raw material, fully traceable to dedicated U.S. or European slaughterhouses that are registered with the FDA. MAF2648 enables Celsus to further support its customers with a cross-reference for medical device applications.

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Celsus Offers Heparin Sodium Ph. Eur. in compliance with new monograph effective January 1, 2015

January 2, 2015 - Celsus Laboratories, Inc., a wholly-owned subsidiary of Celsus Glycoscience, Inc. ("Celsus"), is pleased to offer Heparin Sodium of porcine tissue of U.S..and European origin that it is fully compliant with the revision in European Pharmacopoeia (Ph. Eur.) 8.3 that became effective on January 1, 2015. The new Ph. Eur. monograph includes a revised specification for sodium content, the implementation of chromogenic Anti-Factor IIa and Anti-Factor Xa potency assays, and additional limitations on the presence of likely contaminant species. There were no significant changes required in Celsus’ manufacturing process in order to meet the new Ph. Eur. standard. Heparin Sodium that is certified to conform to the specification of the USP and Ph. Eur. monographs is currently available for purchase from Celsus.

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Celsus Announces Expansion of U.S. Heparin Manufacturing Facility

May 12, 2014 - Cincinnati, OH -- Celsus Laboratories, Inc. ("Celsus") is proud to announce that it has completed an expansion of its facility at 12150 Best Place, Cincinnati, OH 45241, increasing its facility’s size by approximately 40%. The expansion became necessary to keep pace with Celsus' continued growth, resulting from successful partnerships with its diverse pharmaceutical and medical device customer base.

Celsus has been an FDA-inspected manufacturer of bulk-lyophilized Heparin Sodium USP, and derivatives thereof, for more than 25 years. The aforesaid products are offered for direct sale to manufacturers throughout the world for use as a component in biomedical devices and for further manufacture into parenteral drugs, heparin lock flush solutions, and low molecular weight heparins. Celsus does not source any of its crude heparin raw material from China and is one of the few remaining U.S. owned manufacturers of the above mentioned products.

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Celsus Offers Heparin Sodium USP Per New Monograph May 1st 2014

April 28, 2014 - Cincinnati, Ohio -- Celsus Laboratories, Inc. ("Celsus") is pleased to announce that it is prepared for the implementation of the Heparin Sodium USP monograph revision that will become effective in USP 37 NF32, on May 1st, 2014. This revision includes changes to 5 assays, the addition of a molecular weight analysis and a requirement for the manufacturing process to be validated to clear lipid impurities. No significant change in the Celsus manufacturing process is anticipated based on the results of successful validation and verification studies on lipid clearance and the new / revised assays, respectively. All batches tested during said studies met the new established FDA-enforceable standards in USP37-NF32.

Similarly, Celsus is prepared to meet all applicable requirements recently proposed by the FDA in the draft Guidance entitled, 'Medical Devices Containing materials Derived from Animal Sources'. The aforesaid draft Guidance stipulates "that the sum of the log clearance of virus from the selected processing steps and sterilization processes are at least six logs greater than the concentration of virus anticipated in the unprocessed source material". Celsus believes this requirement is quite relevant, especially given the recent challenges associated with the emergence of porcine viruses, such as African Swine Fever (ASF) in Europe, porcine epidemic diarrhea virus (PEDv) and swine delta corona virus (SDCv). It is noteworthy, that PEDv is not zoonotic and therefore poses neither risk to other animals and humans, nor to food safety. However, it may adversely affect future availability of Heparin Sodium USP, and derivatives thereof, by reducing the number of hogs available for slaughter.

Celsus Laboratories, Inc., located in Cincinnati, Ohio, has been an FDA-inspected manufacturer of bulk-lyophilized Heparin Sodium USP and derivatives thereof for more than 25 years. The aforesaid products are offered for direct sale to manufacturers throughout the world for use as a component in biomedical devices and for further manufacture into parenteral drugs, heparin lock flush solutions, and low molecular weight heparins.

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Celsus in full compliance with a new FDA guidance for Industry

June 26, 2013 - Cincinnati OH -- Celsus Laboratories, Inc, ("Celsus") announces that it has been in full compliance with an FDA guidance for industry entitled "Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for Quality" published in the Federal Register on June 25th. Celsus maintains traceability records for each batch of heparin manufactured back to the dedicated porcine slaughterhouses from which the porcine tissue was obtained. Celsus will continue to maintain its vigilance to ensure the sourcing of only the highest integrity raw materials.

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Celsus Submits Two Master Access Files (MAF) for Quaternary Heparins to the FDA

June 8, 2013 - Cincinnati, OH -- Celsus Laboratories, Inc. ("Celsus") is pleased to advise that Master Access Files (MAF) have been submitted to the U.S. Food and Drug Administration ("FDA") for Benzalkonium Heparin (HB-3185/BY-3189), and Stearalkonium Heparin (MS-3175). Celsus quaternary heparins are derivatives of Heparin Sodium USP and alkyldimethylbenzylammonium chlorides and are intended for use as components in medical devices in need of increased hydrophilicity and or antithrombotic and antimicrobial activity. The MAF submissions serve as tangible proof of the products' integrity, activity, and purity, as well as a testament to Celsus' long term commitment to the pharmaceutical and medical device industries.

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Celsus Laboratories Announces Fourth Consecutive Time that No Form 483 issued as a Result of an FDA Inspection

Cincinnati, Ohio - January 3, 2013 -- Celsus Laboratories is pleased to announce that for a fourth consecutive time no Form 483 was issued as a result of an FDA inspection of its heparin manufacturing facility.

Celsus Laboratories, Inc. has been a continuous manufacturer of heparin sodium USP and other related active pharmaceutical ingredients (APIs) for the past 25 years. Its animal raw material feedstock is fully-traceable and is sourced exclusively from FDA registered facilities in countries that are recognized by the World Organization for Animal Health (OIE) as having a negligible or controlled risk of bovine spongiform encephalopathy or "mad cow disease". Celsus' heparin APIs are intended for the further manufacture into parenteral drugs, for use as components in medical devices or as an intermediate in the manufacture of low molecular weight heparins, used clinically. The Company exports more than 50% of its output.

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Celsus Laboratories, Inc. ceases imports of crude heparin feedstock from China

Cincinnati, Ohio – June 5, 2012 -- Celsus Laboratories announces that it will henceforth limit importation of crude heparin to countries that are recognized by the World Organisation of Animal Health (OIE) as having a negligible or controlled risk of bovine spongiform encephalopathy (BSE), commonly referred to as "mad cow disease”. China, the largest supplier of heparin to the United States, does not meet this criterion. Moreover, now that the crude form of heparin has been defined by the U.S. Food and Drug Administration as a drug, sourcing from China becomes even more problematic since China exports significantly more than it currently claims to monitor for safety and integrity.

Celsus Laboratories, a closely-held enterprise located in Cincinnati, has been a continuous manufacturer of heparin active pharmaceutical ingredients (API) for the past 25 years. Celsus' heparin API are intended for further manufacture into parenteral drug products, for use as components in medical devices, and for use as ligands in affinity chromatography. Celsus exports more than 60% of its output.

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Celsus Laboratories, Inc. Limits Future Feedstock to Drug-Listed Crude Heparins from Drug Establishments Registered with the FDA

Cincinnati, Ohio - April 5, 2012 - Celsus Laboratories, Inc. announces an increase in bulklyophilized heparin APIs production capacity to more than 500 billion units to be derived entirely from crude heparins in the form of heparin-on-resin, heparin eluate or crude heparin powder that are drug-listed and manufactured in drug establishments registered with the FDA. Before release at Celsus for further manufacture into heparin APIs, all crude heparins must further test (i) negative for prion antigens by IEA, (ii) positive for porcine and negative for bovine DNA by PCR assay, and (iii) negative for extraneous polyanions by SAX-HPLC. Further manufacture at Celsus Laboratories includes purification steps validated to remove infectious viruses and TSE pursuant to drug master files maintained at regulatory authorities in Australia, Canada, the European Union, Japan, and the United States.

Celsus Laboratories, Inc., an FDA-inspected manufacturer and global distributor of heparin APIs for more than 25 years, underwent an FDA inspection in November and December 2011. No Form 483 was issued for a third consecutive time.

Celsus Announces the Appointment of Dr. Zhenyu Wang as Vice President Research

Cincinnati, Ohio - September, 2011 - Celsus Laboratories, Inc. announced the appointment of Zhenyu Wang, Ph.D. to Vice President, Research. In this position, Dr. Wang will direct Celsus' research and discovery efforts. Dr. Wang will report to Case Van Gorp, the Company's founder, president and chief executive officer.

Dr. Wang received a B.S. in Bioengineering from Shandong University of Jinan, China, and a Ph.D. in Biology from Rensselaer Polytechnic Institute of Troy, NY. His Ph.D. work at RPI included the fermentation, purification, characterization, and scale up prodiuction of E.coli K5 heparosan, and the development of chemo-enzymatic modification processes for a bioengineered heparin.

Celsus Laboratories' Heparin Facility Audited by the FDA - No Form 483 Observations Issued

Cincinnati, Ohio - April 18, 2011 -- Celsus Laboratories Inc. announced today that the U.S. Food & Drug Administration (FDA) completed a current Good Manufacturing Practices (cGMP) compliance inspection of its manufacturing facility on March 28th 2011. The FDA auditors did not issue Form 483 observations at the close out of the inspection.

Celsus Reports New Validation of its Heparin Sodium USP

Cincinnati, Ohio - October 23, 2009 - Celsus Laboratories, Inc. recently completed validation of a bulk-lyophilized Heparin Sodium manufactured to specifications of the new United States Pharmacopeia (USP) monograph for heparin, effective October 1, 2009. The change includes a new USP reference standard that is used to determine the anti-Factor IIa potency of heparin and introduces new test methods for certain impurities that may be present in heparin. The monograph change will also harmonize the USP unit dose with the WHO International Standard (IS) unit dose.

FDA acknowledges Celsus' contribution to development of an analytical method for heparin

Cincinnati, Ohio - June 15, 2009 -- Celsus Laboratories, Inc. was recently recognized by FDA investigators (J. Pharm. Biomed. Anal. 2009; 49:670-673) for its contribution to the analysis for contaminants and impurities in heparin sodium using strong anion exchange high performance liquid chromatography (SAX-HPLC). Celsus announced its development of SAX-HPLC for the quantitative analysis of oversulfated chondroitin sulfate in heparin sodium in an earlier press release.

SAX-HPLC also has demonstrated to be a valuable tool in the composition and structural analysis of Celsus' enoxaparin sodium. Heparin lyase digestion of enoxaparin sodium, manufactured by Celsus pursuant to drug master file 11789, yielded di- and oligosaccharide profiles including fragments with a blocked reducing end bearing the 1,6-anhydro bicyclized ring structure that are virtually indistinguishable from the enoxaparin sodium in Lovenox® of Sanofi-Aventis.

FDA seizes OSCS-contaminated heparin from Celsus

Cincinnati, Ohio -- November 6, 2008 - Twelve lots of bulk-lyophilized heparin sodium and heparin lithium, under quarantine at Celsus since April 2008, were seized today pursuant to an FDA initiated court-ordered action. Bulk-lyophilized heparins manufactured by Celsus Laboratories for more than 20 years are intended only for research, for further manufacture into finished drug products by pharmaceutical manufacturers or for use as a component in the device industry. Celsus neither offers, distributes, nor recommends its products for retail sale or for use directly by patients.

On March 6, 2008 the FDA disclosed on its web site the potential presence of an extraneous polyanion in imported raw heparin (later determined to be oversulfated chondroitin sulfate (OSCS)) and recommended at that time the use of specialized procedures for its detection. Within days of the announcement, Celsus had put into place these procedures and opened an investigation under protocol to ascertain whether the integrity of its heparin had been affected. Suspect heparin batches were identified and quarantined. Customers, that had received heparin from such batches, were informed in late March and early April. Subsequently, having received notice as a result of the customer contacts, the FDA initiated a fact finding inspection of Celsus' Cincinnati facility from April 15 through May 15, 2008. The suspect lot numbers, their quantities and all of Celsus' consignees were disclosed to FDA investigators at that time. The quarantined lots were inspected by the agency, reconciled against company records, and re-inspected by the FDA on May 30th, June 4th and again on September 24th. On November 6, 2008 these lots under number PH-62707, PH-62807, PH-62907, PH-63507, PH- 64107, PH-64507 and HL-31707, HL-31807, HL-32708, HL-32808, HL-32908 and HL-33008, held in quarantine, were seized by United States Marshals under court order filed by the agency.

Since April 2008, a number of safeguards have been in place that prevent OSCS and other impurities from entering the supply chain of finished heparins. Imported heparin raw materials are first tested by the FDA before their release. The same raw materials are again tested by Celsus for OSCS and other impurities before their use in manufacturing. Additionally, Celsus performs all of the tests pursuant to the USP monograph on Heparin Sodium. Heparin Lithium is derived from heparin sodium and is also subject to the current impurity tests for OSCS.

Benzalkonium Heparin Now Available Directly From Celsus Laboratories

Cincinnati, Ohio - May 6, 2008 -- Celsus Laboratories, the leading manufacturer of subject product, announces a change in its distribution of Heparin Benzalkonium solution, also known as H-Bac, intended for use as a bioactive coating of catheters, and guidewires. Celsus found it problematic from a quality system point of view of having an intervening party between the product and the manufacturers of medical devices. Therefore, the Celsus product will no longer be available from NAMSA.

The change only impacts those device manufacturers that have sourced Benzalkonium Heparin Solution or H-Bac from NAMSA or its distributors. Such manufacturers are invited to purchase any future requirements directly from Celsus Laboratories. Benzalkonium heparin solution is being dispatched under UN-rated conditions from inventory in 1 liter or 16 liter quantities. Orders may be placed either by email or by faxing +1 (513) -772-8132.

Both Benzalkonium Heparin (HB-3185) and Benzalkonium Heparin Solution (BY- 3189) are derivatives of Heparin Sodium of porcine tissue manufactured by Celsus Laboratories pursuant to drug master files reviewed by regulatory authorities in Australia, Canada, the European Union, Japan and the United States.

Celsus Laboratories Discloses Its SAX-HPLC Test For Heparin Sodium

Cincinnati OH - April 16, 2008 - - In light of the recent concern about contaminated heparin, Celsus Laboratories is offering for consideration by regulatory agencies and industry, strong anion exchange high performance liquid chromatography (SAXHPLC) as an alternative method for the quantitative analysis of heparin-like glycosaminoglycans in Heparin Sodium USP.

The method, developed by Celsus, is rapid, quantitative, and exhibits high resolution for the discrimination and identification of not only the naturally-occurring glycosaminoglycans, but also oversulfated chondroitin sulfate (OCS). Analysis time is typically 30 minutes from injection. It further offers the advantage that HPLC is available to many more laboratories than 500 MHz nuclear magnetic resonance (NMR) spectroscopy and Capillary Electrophoresis (CE), the current methods of analysis. Presently lacking, unfortunately, is a readily available reference standard. Nonetheless, even without a standard, SAX-HPLC is a high resolution method for quickly determining the quantity of OCS-like species in Heparin Sodium USP and commercial heparin preparations derived thereof.

Celsus Laboratories, Inc., located in Cincinnati, Ohio, has been active as a FDAinspected manufacturer and global distributor of bulk-lyophilized derivatives of crude heparin since 1988.

Celsus First to Manufacture Commercial Quantities of Generic Enoxaparin Sodium in the U.S.

Cincinnati, Ohio - August 8, 2007 -- In anticipation of a generic market, Celsus Laboratories has positioned itself to be the first manufacturer of Enoxaparin Sodium in the U.S. Enoxaparin Sodium is a low molecular weight heparin (LMWH) manufactured and offered by Celsus as an alternative to the active pharmaceutical ingredient (API) in the listed drug Enoxaparin Sodium Injection, the anticoagulant of choice for the treatment and prevention of venous thrombosis.

Venous thrombosis is the third most common cardiovascular disorder, affecting about two million people each year in the US alone. Of these, around 60,000 will develop a pulmonary embolism which will prove fatal in 8-10% of cases. Venous thromboses is commonly treated with heparin sodium, or the low molecular weight heparins (LMWHs), or a synthetic alternative known as fondaparinux. The most commonly prescribed LMWH in the Americas and Europe is Sanofi-Aventis' Lovenox® / Clexane® (enoxaparin sodium) with worldwide sales in 2006 of more than $ 3 billion of which almost $ 2 billion was in the US alone. The large U.S. share of the global market is due to a significantly higher price in the U.S. than in the rest of the world. Not surprisingly, a number of companies are anxiously awaiting a decision on an appeal filed by Sanofi-Aventis to reverse a lower court decision of unenforceability of its LMWH patent due to inequitable conduct in its prosecution of the patent. ANDA applications for a generic enoxaparin have been filed in the U.S. by Amphastar, Teva, and Momenta. The first two procure their API from foreign sources. The latter licensed the manufacture of commercial quantities of its API to Sandoz of Germany.

Celsus to Commence Phase I Clinical Studies of Intimatan™

CINCINNATI, Ohio -- January, 2007-- Celsus, Inc. announced plans to initiate phase I clinical studies of Intimatan™ while considering out-licensing opportunities for the major pharmaceutical markets.

Intimatan™ is an improved anti-inflammatory anticoagulant intended for use in indications dominated by heparin. Among its competitive advantages as a heparincofactor II agonist, Intimatan: (i) inhibits both systemic and clot-bound thrombin, the latter resistant to inhibition by the heparin-antithrombin complex; (ii) imparts an improved therapeutic index as demonstrated in high hurdle models of venous and arterial thrombosis; (iii) restores anticoagulant activity in antithrombin-deficient plasma of patients with both hereditary and acquired heparin resistance; (iv) blocks platelet activation in plasma of patients with heparin-induced thrombocytopenia (HIT) or "white clot syndrome", making Intimatan the first-in-class HIT-antagonist that abates the heparin-induced disease mechanism at its immunological root cause while affording anticoagulant and antithrombotic protection, and (v) reduces infarct size due to ischemia-reperfusion injury. In adjuvant settings, Intimatan shows synergy with glycoprotein IIb/IIIa inhibitors to yield complete myocardial protection in coronary arterial thrombosis models at signficantly reduced doses that diminish hemorrhagic effects, and prevents rethrombosis following successful fibrinolysis with recombinant tissue plasminogen activator. Protamine is an effective antidote for Intimatan as well as unfractionated heparin. There are no specific antidotes for low molecular weight heparin or the direct thrombin inhibitors, hirudin, lepirudin, bivalirudin and argatroban.

European Patent Office Grants Celsus Patent For Intimatan

Cincinnati OH - June 23, 2005 -- Celsus, Inc. announced today that the European Patent Office has granted the company EP 0 983 304 B1 for dermatan disulfate, an inhibitor of thrombin generation and complement activation. With the European Patent Office process completed and the patent granted, Celsus is now seeking "nationalization" of the patent in the major countries of the European Union.

In contrast to heparin and low molecular weight heparin (LMWH), the current anticoagulants of choice, (i) dermatan disulfate, also known as Intimatan™, catalyzes heparin cofactor II-dependent inhibition of both soluble and surface-bound thrombin, thus suppressing the thrombin feedback loop, at doses that pose minimal systemic anticoagulation or bleeding, and (ii) in animal models, Intimatan has shown to be more effective as an inhibitor of venous and arterial thrombisis, to prevent recurrent arterial thrombosis after successul thrombolysis with tissue plasminogen activator and to act synergistically with glycoprotein IIb/IIIa receptor antagonists to inhibit human platelet activation. These properties may position Intimatan™ as a preferred anticoagulant for use in acute thrombosis indications, especially for antithrombin III-deficient patients.

Recent studies have shown that Intimatan™ inhibits the activation of human platelets induced by heparin when incubated with immune serum from patients with heparin-induced thrombocytopenia (HIT), thereby qualifying Intimatan as the first anticoagulant HIT-antagonist. HIT, previously known as white clot syndrome, is a debilitating disease that affects 2 - 5% of the 12 million patients in the U.S. on heparin and LMWH therapy.

Celsus Qualifies for a Third NIH Grant for Drug Development

02/28/03 -- Celsus Laboratories, Inc. (Cincinnati OH) announces it received a $224,000 phase I research grant from the National Heart, Lung, and Blood Institute for a preclinical study of the drug, Intimatan. Included will be research in a revascularization model of ischemic reperfusion injury during cardiopulmonary bypass (CPB) surgery by Emory University. The new study is designed to further test the efficacy of Intimatan as a replacement for heparin in cardiac surgery.

Intimatan is a patented heparin cofactor II agonist, comprising a disaccharide sequence of repeating L-iduronic acid N-acetyl-D-galactosamine 4,6-O-disulfate joined by 1,3 and 1,4 linkages. This naturally-occurring, but rare, disaccharide may be prepared by synthesis or by site-selective 6-O-sulfation of native dermatan sulfate.

Current practice for CPB surgery requires high dose heparin (400 U/kg) to maintain patency of the extracorporeal circuits during flow. However, thrombin bound to the fibrin clot, vessel wall and biomaterial surfaces is typically resistant to inhibition by heparin. In comparison with heparin, using a pig model of CPB, Intimatan maintained extracorporeal patency at one tenth the anticoagulant dose; generated a 4-fold lower activated clotting time (ACT); reduced chest wall bleeding more than 2- fold; and did not induce thrombin rebound or require neutralization post-procedure. In contrast, the use of heparin requires post surgical neutralization which often results in heparin-protamine-complex-induced complement activation contributing to post-operative edema, tissue injury and neural deficits.

Other preclinical pharmacology studies, thus far, have shown Intimatan to be an inhibitor of surface-bound thrombin, complement activation, and neointimal hyperplasia in models of restenosis injury. In the treatment of acute coronary thrombosis, Intimatan reduces the dose of platelet GPIIb/IIIa inhibitors required to block coronary thrombosis in vivo and prevents recurrent coronary artery thrombosis in the canine following adjuvant thrombolysis with tissue plasminogen activator. It completely prevents primary arterial and venous thromboses in the canine model of electrolytic injury. Intimatan also protects against inflammation damage to the isolated perfused rabbit heart and may thus protect against the ravages of ischemicreperfusion injury in myocardial infarction and stroke. Furthermore, Intimatan blocks the activation of platelets of patients with heparin-induced thrombocytopenia (HIT) caused by heparin allergy. As a HIT antagonist, Intimatan may benefit highrisk cardiac patients who experience thrombosis due to heparin exposure.

Combination of Glycoprotein IIb/IIIa Platelet Receptor Antagonist and Heparin Cofactor II Agonist receives Notice of Patent Allowance.

10/02/02 -- Intimax Corporation (Cincinnati OH), a subsidiary of Celsus, Inc., received from the USPTO a notice of allowance for a patent claiming combination of glycoprotein (GP) IIb/IIIa platelet receptor antagonist and heparin cofactor II agonist for use in the treatment of thrombo-embolic disorders arising from platelet- and thrombin-dependent-coagulation processes. Treatment typically addresses the inhibition of platelet aggregation and thrombin generation and activation by use of a GP IIb/IIIa antagonist in combination with various anticoagulants including heparin.

A variety of animal pharmacology studies have shown Intimatan, a heparin cofactor II agonist under development at Celsus, to be a superior anticoagulant to both unfractionated and the low molecular weight heparins in cardiac surgery and in the treatment of thrombosis. In contrast to the heparins, Intimatan blocks both thrombin generation and thrombin activity via a sustained action at the vessel wall that suppresses the thrombin feedback loop, at doses that pose minimal systemic anticoagulation or bleeding. In the patented combination Intimatan has been shown to act synergistically with GPIIb/IIIa antagonists, at sub-therapeutic doses of both, to maintain vessel patency with less bleeding than GPIIb/IIIa antagonists in combination with the heparins. Intimatan also ameliorates the activation of human platelets induced by immune serum of patients with heparin induced thrombocytopenia (HIT). These properties potentially make Intimatan the preferred anticoagulant adjuvant for the treatment of acute myocardial infarction with fibrinolytic agents and GPIIb/IIIa antagonists and/or peri- and post-surgery in the cardiac patient.

Celsus Receives Research Funding To Develop O-Desulfated Heparin

9/3/02 - Celsus Laboratories, Inc. received a phase I Small Business Innovation Research (SBIR) grant from the U.S. Department of Health and Human Services to develop a process for the manufacture of an O-desulfated heparin the use of which has been shown experimentally to prevent ischemic reperfusion injury such as that associated with myocardial infarction, stroke and pulmonary thromboembolism. The research will be done in collaboration with the Carolinas Medical Center of Charlotte NC.

Intimatan™ Prevents Rethrombosis After Successful Thrombolysis

8/12/02 - Celsus Laboratories, Inc. and investigators of the University of Michigan will present the results of a study of Intimatan in the presence and absence of an adjuvant thrombolytic agent in a canine model of deep vessel wall injury on September September 10th 2002 at the 17th Congress of the International Fibrinogen Research Society in Munich Germany.

Intimatan (9 mg/kg plus an infusion of 300 μg/kg/min, i.v.) significantly increased the time to carotid artery (CA) (226 ± 0.4 min) and jugular vein (JV) (240 ± 0.0 min) thrombosis compared with control vessels in the same animal (87.1 ± 7.9 CA and 60.0 ± 7.4 min JV) determined before drug administration. Vessel patency was maintained in 8/8 JV and 7/8 CA during Intimatan treatment. Although dalteparin (400 IU/kg, s.c.) delayed the time to thrombosis in the CA (122 ± 17.5) relative to control CA (64.3 ± 8.2), it had no effect on the time to thrombosis in the JV, whereas only one CA remained patent at the end of the 240 min protocol. After establishing successful thrombolysis with recombinant tissue plasminogen activitator (rt-PA), Intimatan decreased the incidence of rethrombosis in the right CA to 1/7 versus 4/7 in the vehicle-treated groups. After thrombolysis, the quality of right CA blood flow assessed by the patency score (scale 0-3) was 2.6 ± 0.4 for Intimatan and 1.1 ± 0.6 for vehicle control. In the left CA, the incidence of occlusion was 0/7 (Intimatan) versus 2/7 (vehicle control) and the patency score was 2.7 ± 0.6 (Intimatan) vs 1.6 ± 0.5 (vehicle) after thrombolysis. The results demonstrate that Intimatan prevents occlusive arterial and venous thrombosis in an experimental model of deep vessel wall injury and prevents CA rethrombosis after successful thrombolysis with rt-PA. These effects are achieved with minimal increases in the bleeding time and activated partial thromboplastin time. Intimatan is an improved anticoagulant and new drug candidate for the treatment of coronary syndromes in the setting of adjuvant thrombolytic therapy.