CHIMERIC OSPA GENES, PROTEINS AND METHODS OF USE THEREOF (Fri, 23 May 2014)
<p id="p-0001" num="0000">The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of <i>Borrelia </i>genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.</p>
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CHIMERIC OSPA GENES, PROTEINS AND METHODS OF USE THEREOF (Fri, 23 May 2014)
<p id="p-0001" num="0000">The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of <i>Borrelia </i>genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.</p>
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POLYMERIC BENZYL CARBONATE-DERIVATIVES (Fri, 09 May 2014)
<p id="p-0001" num="0000">The present invention relates to polymeric derivatives, which can be conjugated to an amino-containing drug to improve its in vivo properties. The polymeric derivative can subsequently be released to yield the drug in its native form. Methods of preparing and using these polymeric derivatives and drug conjugates are described.</p>
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METHODS AND SYSTEMS FOR SCREENING COMPOSITIONS COMPRISING NON-ANTICOAGULANT SULFATED POLYSACCHARIDES (Fri, 21 Feb 2014)
<p id="p-0001" num="0000">Aspects of the invention include methods for identifying one or more NASP (non-anticoagulant sulfated polysaccharide) compositions that are suitable for treating a subject having a blood coagulation disorder. In practicing methods according to certain embodiments, NASP compositions are evaluated by determining the coagulation activity and chemical makeup of the NASP composition and the molecular structure of the NASP. Systems for practicing methods of the invention as well as compositions suitable for treating a subject having a blood coagulation disorder are also described.</p>
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METHODS AND SYSTEMS FOR SCREENING COMPOSITIONS COMPRISING NON-ANTICOAGULANT SULFATED POLYSACCHARIDES (Fri, 21 Feb 2014)
Aspects of the invention include methods for identifying one or more NASP (non-anticoagulant sulfated polysaccharide) compositions that are suitable for treating a subject having a blood coagulation disorder. In practicing methods according to certain embodiments, NASP compositions are evaluated by determining the coagulation activity and chemical makeup of the NASP composition and the molecular structure of the NASP. Systems for practicing methods of the invention as well as compositions suitable for treating a subject having a blood coagulation disorder are also described.
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COMPOSITIONS COMPRISING CHIMERIC OSPA MOLECULES AND METHODS OF USE THEREOF (Fri, 31 Jan 2014)
<p id="p-0001" num="0000">The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of <i>Borrelia </i>genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.</p>
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COMPOSITIONS COMPRISING CHIMERIC OSPA MOLECULES AND METHODS OF USE THEREOF (Fri, 31 Jan 2014)
The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.
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NUCLEOPHILIC CATALYSTS FOR OXIME LINKAGE AND USE OF NMR ANALYSES OF THE SAME (Fri, 22 Nov 2013)
<p id="p-0001" num="0000">The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation and analyzing the conjugation using 2D NMR analysis. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.</p>
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NUCLEOPHILIC CATALYSTS FOR OXIME LINKAGE AND USE OF NMR ANALYSES OF THE SAME (Fri, 22 Nov 2013)
The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation and analyzing the conjugation using 2D NMR analysis. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.
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NUCLEOPHILIC CATALYSTS FOR OXIME LINKAGE (Fri, 22 Nov 2013)
The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.
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Methods and Compositions for Treating Bleeding Disorders (Fri, 15 Nov 2013)
<p id="p-0001" num="0000">Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.</p>
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TFPI INHIBITORS AND METHODS OF USE (Fri, 18 Oct 2013)
<p id="p-0001" num="0000">The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and/or treat a blood coagulation disorder in a subject.</p>
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TFPI INHIBITORS AND METHODS OF USE (Fri, 04 Oct 2013)
<p id="p-0001" num="0000">The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.</p>
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TFPI INHIBITORS AND METHODS OF USE (Fri, 27 Sep 2013)
<p id="p-0001" num="0000">The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. Peptide complexes also are provided. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.</p>
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TFPI INHIBITORS AND METHODS OF USE (Fri, 27 Sep 2013)
The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. Peptide complexes also are provided. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.
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NON-ANTICOAGULANT SULFATED OR SULFONATED POLYSACCHARIDES (Fri, 16 Aug 2013)
<p id="p-0001" num="0000">The present invention provides non-anticoagulant sulfated or sulfonated polysaccharides (NASPs), which accelerate the blood clotting process. Also provided are pharmaceutical formulations comprising a NASP of the invention in conjunction with a pharmaceutically acceptable excipient and, in various embodiments, these formulations are unit dosage formulations. The invention provides a NASP formulation, which is orally bioavailable. Also provided are methods for utilizing the compounds and formulations of the invention to promote blood clotting in vivo as therapeutic and prophylactic agents and in vitro as an aid to studies of the blood clotting process.</p>
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NON-ANTICOAGULANT SULFATED OR SULFONATED POLYSACCHARIDES (Fri, 09 Aug 2013)
The present invention provides non-anticoagulant sulfated or sulfonated polysaccharides (NASPs), which accelerate the blood clotting process. Also provided are pharmaceutical formulations comprising a NASP of the invention in conjunction with a pharmaceutically acceptable excipient and, in various embodiments, these formulations are unit dosage formulations. The invention provides a NASP formulation, which is orally bioavailable. Also provided are methods for utilizing the compounds and formulations of the invention to promote blood clotting in vivo as therapeutic and prophylactic agents and in vitro as an aid to studies of the blood clotting process.
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Modified Polysaccharides for Conjugate Vaccines (Fri, 02 Aug 2013)
<p id="p-0001" num="0000">The present invention relates to methods of manufacture of immunogenic glycoconjugates, in particular for use in pharmaceutical compositions for inducing a therapeutic immune response in a subject. The immunogenic glycoconjugates of the invention comprise one or more oligosaccharides or polysaccharides that are conjugated to one or more carrier proteins via an active aldehyde group. Accordingly, the invention provides methods of making (i) unsaturated microbial N-acyl derivative oligosaccharides or polysaccharides; (ii) novel conjugates of unsaturated N-acyl derivatives; and (iii) glycoconjugate compositions comprising conjugate molecules of fragments of microbial unsaturated N-acyl derivatives that serve as a covalent linker to one or more proteins. The invention further encompasses the use of the immunogenic glycoconjugates pharmaceutical compositions for the prevention or treatment of an infectious disease.</p>
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METHOD FOR THE PRODUCTION OF A POLYMERIZED PRODUCT (Fri, 14 Jun 2013)
<p id="p-0001" num="0000">The invention discloses a method for the production of a polymerized product comprising the following steps: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">providing a polymerization device to which a polymerization mixture and a separation medium can be applied and wherein flow of said mixture and medium can be conducted in appropriate ducts for said mixture and medium,</li> <li id="ul0002-0002" num="0000">transporting said polymerization mixture in a duct of said polymerization device thereby allowing the polymerization reaction,</li> <li id="ul0002-0003" num="0000">transporting said mixture in a duct of said polymerization device in a continuous flow,</li> <li id="ul0002-0004" num="0000">interrupting said continuous flow of said mixture with said separation medium so as to obtain consecutive volumes of said mixture and volumes of said separation medium,</li> <li id="ul0002-0005" num="0000">further transporting said consecutive volumes of said mixture and volumes of said separation medium in a duct of said polymerization device wherein said mixture further polymerizes to obtain a discontinuous polymerized product, and <br/> removing said discontinuous polymerized product from said polymerization device. </li> </ul> </li> </ul> </p>
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HEMOSTATIC COMPOSITIONS (Fri, 19 Apr 2013)
<p id="p-0001" num="0000">The invention discloses a hemostatic composition composing chitin or a water insoluble chitin derivative, especially water insoluble chitosan, in particulate form, wherein the composition is present in paste form.</p>
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HEMOSTATIC COMPOSITIONS (Fri, 19 Apr 2013)
The invention discloses a hemostatic composition comprising chitin or a water insoluble chitin derivative, especially water insoluble chitosan, in particulate form, wherein the composition is present in paste form.
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METHOD FOR THE PRODUCTION OF A POLYMERIZED PRODUCT (Fri, 21 Dec 2012)
The invention discloses a method for the production of a polymerized product comprising the following steps: - providing a polymerization device to which a polymerization mixture and a separation medium can be applied and wherein flow of said mixture and medium can be conducted in appropriate ducts for said mixture and medium, - transporting said polymerization mixture in a duct of said polymerization device thereby allowing the polymerization reaction, - transporting said mixture in a duct of said polymerization device in a continuous flow, - interrupting said continuous flow of said mixture with said separation medium so as to obtain consecutive volumes of said mixture and volumes of said separation medium, - further transporting said consecutive volumes of said mixture and volumes of said separation medium in a duct of said polymerization device wherein said mixture further polymerizes to obtain a discontinuous polymerized product, and removing said discontinuous polymerized product from said polymerization device.
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Von Willebrand factor- and factor VIII-polymer conjugates having a releasable linkage (Fri, 08 Jun 2012)
<p id="p-0001" num="0000">The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.</p>
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TFPI inhibitors and methods of use (Fri, 03 Feb 2012)
<p id="p-0001" num="0000">The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.</p>
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Chimeric OspA genes, proteins, and methods of use thereof (Fri, 27 Jan 2012)
<p id="p-0001" num="0000">The invention relates to the development of chimeric OpsA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of <i>Borrelia </i>genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.</p>
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Chimeric OspA genes, proteins, and methods of use thereof (Fri, 02 Dec 2011)
<p id="p-0001" num="0000">The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of <i>Borrelia </i>genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.</p>
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OSPA CHIMERAS AND USE THEREOF IN VACCINES (Fri, 18 Nov 2011)
The invention relates to the development of chimeric OspA molecules for use in against Lyme disease or borreliosis vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies.
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CHIMERIC OSPA GENES, PROTEINS, AND METHODS OF USE THEREOF (Fri, 18 Nov 2011)
The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.
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OSPA CHIMERAS AND USE THEREOF IN VACCINES (Fri, 18 Nov 2011)
The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.</p>
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OSPA CHIMERAS AND USE THEREOF IN VACCINES (Fri, 18 Nov 2011)
The invention relates to the development of chimeric OspA molecules for use in against Lyme disease or borreliosis vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies.</p>
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Methods and compositions for treating bleeding disorders (Fri, 07 Oct 2011)
<p id="p-0001" num="0000">Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.</p>
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Stabilized liquid and lyophilized ADAMTS13 formulations (Fri, 23 Sep 2011)
<p id="p-0001" num="0000">The present invention relates to formulations of ADAMTS13 with enhanced or desirable properties. As such, the invention provides liquid and lyophilized formulations of ADAMTS13 that are suitable for pharmaceutical administration. Among other aspects, the present invention also provides methods of treating various diseases and conditions related to VWF and/or ADAMTS13 dysfunction in a subject. Also provided herein are kits comprising ADAMTS13 formulations useful for the treatment of various diseases and conditions.</p>
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TFPI INHIBITORS AND METHODS OF USE (Fri, 23 Sep 2011)
The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.
>> read more

TFPI INHIBITORS AND METHODS OF USE (Fri, 23 Sep 2011)
The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.</p>
>> read more

METHODS AND COMPOSITIONS FOR TREATING BLEEDING DISORDERS (Fri, 22 Jul 2011)
Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.
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METHODS AND COMPOSITIONS FOR TREATING BLEEDING DISORDERS (Fri, 22 Jul 2011)
Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.</p>
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Methods and compositions for treating bleeding disorders (Fri, 15 Jul 2011)
<p id="p-0001" num="0000">Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.</p>
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STABILIZED LIQUID AND LYOPHILIZED ADAMTS13 FORMULATIONS (Fri, 25 Mar 2011)
The present invention relates to formulations of ADAMTS13 with enhanced or desirable properties. As such, the invention provides liquid and lyophilized formulations of ADAMTS13 that are suitable for pharmaceutical administration. Among other aspects, the present invention also provides methods of treating various diseases and conditions related to VWF and/or ADAMTS13 dysfunction in a subject. Also provided herein are kits comprising ADAMTS13 formulations useful for the treatment of various diseases and conditions.
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STABLE CO-FORMULATION OF HYALURONIDASE AND IMMUNOGLOBULIN, AND METHODS OF USE THEREOF (Fri, 25 Mar 2011)
Provided herein are stable co-formulations of immunoglobulin and hyaluronidase that are stable to storage in liquid form at room temperature for at least 6 months and at standard refrigerator temperatures for 1-2 years. Such co-formulations can be used in methods of treating IG-treatable diseases or conditions by subcutaneous administration.
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STABLE CO-FORMULATION OF HYALURONIDASE AND IMMUNOGLOBULIN, AND METHODS OF USE THEREOF (Fri, 25 Mar 2011)
Provided herein are stable co-formulations of immunoglobulin and hyaluronidase that are stable to storage in liquid form at room temperature for at least 6 months and at standard refrigerator temperatures for 1-2 years. Such co-formulations can be used in methods of treating IG-treatable diseases or conditions by subcutaneous administration.</p>
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STABILIZED LIQUID AND LYOPHILIZED ADAMTS13 FORMULATIONS (Fri, 25 Mar 2011)
The present invention relates to formulations of ADAMTS13 with enhanced or desirable properties. As such, the invention provides liquid and lyophilized formulations of ADAMTS13 that are suitable for pharmaceutical administration. Among other aspects, the present invention also provides methods of treating various diseases and conditions related to VWF and/or ADAMTS13 dysfunction in a subject. Also provided herein are kits comprising ADAMTS13 formulations useful for the treatment of various diseases and conditions.</p>
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METHODS FOR PREPARING FLUORINATED VINYL ETHERS (Fri, 29 Oct 2010)
A method for preparing a fluorinated vinyl ether compound comprising reacting a fluorinated ether substrate having (i) a hydrogen atom on a carbon atom that is alpha to an etheric oxygen and (ii) a fluorine atom on a carbon atom that is beta to the etheric oxygen, with an organolithium base to provide a reaction product comprising a fluorinated vinyl ether compound.
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METHODS FOR PREPARING FLUORINATED VINYL ETHERS (Fri, 22 Oct 2010)
<p id="p-0001-en" num="0000">A method for preparing a fluorinated vinyl ether compound comprising reacting a fluorinated ether substrate having (i) a hydrogen atom on a carbon atom that is alpha to an etheric oxygen and (ii) a fluorine atom on a carbon atom that is beta to the etheric oxygen, with an organolithium base to provide a reaction product comprising a fluorinated vinyl ether compound.</p>
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Method for Preparing FMOC-Based Hydrolysable Linkers (Fri, 06 Aug 2010)
<p id="p-0001-en" num="0000">A novel process for the production of Fmoc (9H-fluoren-9-ylmethoxycarbonyl)-based compounds is provided, wherein a protecting group for the 9-hydroxymethyl group of the fluorene ring system is utilized. These compounds are useful for the modification of protein and peptide drugs.</p>
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TFPI inhibitors and methods of use (Fri, 09 Jul 2010)
<p id="p-0001" num="0000">The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and/or treat a blood coagulation disorder in a subject.</p>
>> read more

TFPI INHIBITORS AND METHODS OF USE (Fri, 25 Jun 2010)
The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and/or treat a blood coagulation disorder in a subject. </p>
>> read more

Polymeric benzyl carbonate-derivatives (Fri, 26 Feb 2010)
<p id="p-0001" num="0000">The present invention relates to polymeric derivatives, which can be conjugated to an amino-containing drug to improve its in vivo properties. The polymeric derivative can subsequently be released to yield the drug in its native form. Methods of preparing and using these polymeric derivatives and drug conjugates are described.</p>
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POLYMERIC BENZYL CARBONATE-DERIVATIVES (Fri, 26 Feb 2010)
The present invention relates to polymeric derivatives, which can be conjugated to an amino-containing drug to improve its in vivo properties. The polymeric derivative can subsequently be released to yield the drug in its native form. Methods of preparing and using these polymeric derivatives and drug conjugates are described.
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POLYMERIC BENZYL CARBONATE-DERIVATIVES (Fri, 26 Feb 2010)
The present invention relates to polymeric derivatives, which can be conjugated to an amino-containing drug to improve its in vivo properties. The polymeric derivative can subsequently be released to yield the drug in its native form. Methods of preparing and using these polymeric derivatives and drug conjugates are described. </p>
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METHODS AND ASSAYS FOR OVERSULFATED GLYCOSAMINOGLYCANS (Thu, 24 Dec 2009)
Methods and assays for oversulfated glycosaminoglycans are provided. In an embodiment, the present disclosure provides a method for detecting oversulfated glycosaminoglycan (OS-GAG) in a heparin sample. The method comprises placing the heparin sample onto a support comprising immobilized heparin and contacting the heparin sample on the support with a binding compound that attaches to the heparin and forms a heparin-binding compound complex. The binding compound also has a greater affinity for attaching to the OS-GAG than to the heparin in the heparin sample and forms an OS-GAG-binding compound complex. The method can further comprise detecting an amount of the heparin-binding compound complex on the support, and determining an amount of OS-GAG in the heparin sample based on the amount of the heparin-binding compound complex on the support.
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METHODS AND ASSAYS FOR OVERSULFATED GLYCOSAMINOGLYCANS (Fri, 04 Dec 2009)
<p id="p-0001-en" num="0000">Methods and assays for oversulfated glycosaminoglycans are provided. In an embodiment, the present disclosure provides a method for detecting oversulfated glycosaminoglycan (OS-GAG) in a heparin sample. The method comprises placing the heparin sample onto a support comprising immobilized heparin and contacting the heparin sample on the support with a binding compound that attaches to the heparin and forms a heparin-binding compound complex. The binding compound also has a greater affinity for attaching to the OS-GAG than to the heparin in the heparin sample and forms an OS-GAG-binding compound complex. The method can further comprise detecting an amount of the heparin-binding compound complex on the support, and determining an amount of OS-GAG in the heparin sample based on the amount of the heparin-binding compound complex on the support.</p>
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IMMOBILIZATION OF DYES AND ANTIMICROBIAL AGENTS ON A MEDICAL DEVICE (Fri, 30 Jan 2009)
A method for immobilizing dyes and antimicrobial agents on a porous surface is disclosed and described. The surface may be that of a medical device, such as a catheter, a connector, a drug vial spike, a bag spike, a prosthetic device, an endoscope, and surfaces of an infusion pump. The surfaces may also be one or more of those associated with a dialysis treatment, such as peritoneal dialysis or hemodialysis, where it is important that working surface for the dialysis fluid be sterile. These surfaces include connectors for peritoneal dialysis sets or for hemodialysis sets, bag spikes, dialysis catheters, and so forth. A method for determining whether a surface has been sterilized, and a dye useful in so indicating, is also disclosed.
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IMMOBILIZATION OF DYES AND ANTIMICROBIAL AGENTS ON A MEDICAL DEVICE (Fri, 30 Jan 2009)
A method for immobilizing dyes and antimicrobial agents on a porous surface is disclosed and described. The surface may be that of a medical device, such as a catheter, a connector, a drug vial spike, a bag spike, a prosthetic device, an endoscope, and surfaces of an infusion pump. The surfaces may also be one or more of those associated with a dialysis treatment, such as peritoneal dialysis or hemodialysis, where it is important that working surface for the dialysis fluid be sterile. These surfaces include connectors for peritoneal dialysis sets or for hemodialysis sets, bag spikes, dialysis catheters, and so forth. A method for determining whether a surface has been sterilized, and a dye useful in so indicating, is also disclosed. </p>
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IMMOBILIZATION OF DYES AND ANTIMICROBIAL AGENTS ON A MEDICAL DEVICE (Fri, 23 Jan 2009)
<p id="p-0001-en" num="0000">A method for immobilizing dyes and antimicrobial agents on a porous surface is disclosed and described. The surface may be that of a medical device, such as a catheter, a connector, a drug vial spike, a bag spike, a prosthetic device, an endoscope, and surfaces of an infusion pump. The surfaces may also be one or more of those associated with a dialysis treatment, such as peritoneal dialysis or hemodialysis, where it is important that working surface for the dialysis fluid be sterile. These surfaces include connectors for peritoneal dialysis sets or for hemodialysis sets, bag spikes, dialysis catheters, and so forth. A method for determining whether a surface has been sterilized, and a dye useful in so indicating, is also disclosed.</p>
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Method for preparing Fmoc-based hydrolysable linkers (Fri, 02 Jan 2009)
<p id="p-0001-en" num="0000">A novel process for the production of Fmoc (9H-fluoren-9-ylmethoxycarbonyl)-based compounds is provided, wherein a protecting group for the 9-hydroxymethyl group of the fluorene ring system is utilized. These compounds are useful for the modification of protein and peptide drugs.</p>
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METHOD FOR PREPARING FMOC-BASED HYDROLYSABLE LINKERS (Thu, 01 Jan 2009)
A novel process for the production of Fmoc (9H-fluoren-9-ylmethoxycarbonyl)-based compounds is provided, wherein a protecting group for the 9-hydroxymethyl group of the fluorene ring system is utilized. These compounds are useful for the modification of protein and peptide drugs.
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METHOD FOR PREPARING FMOC - BASED HYDROLYSABLE LINKERS (Thu, 01 Jan 2009)
A novel process for the production of Fmoc (9H-fluoren-9-ylmethoxycarbonyl)- based compounds is provided, wherein a protecting group for the 9-hydroxymethyl group of the fluorene ring system is utilized. These compounds are useful for the modification of protein and peptide drugs. </p>
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MODIFIED POLYSACCHARIDES FOR CONJUGATE VACCINES (Thu, 25 Dec 2008)
The present invention relates to methods of manufacture of immunogenic glycoconjugates, in particular for use in pharmaceutical compositions for inducing a therapeutic immune response in a subject. The immunogenic glycoconjugates of the invention comprise one or more oligosaccharides or polysaccharides that are conjugated to one or more carrier proteins via an active aldehyde group. Accordingly, the invention provides methods of making (i) unsaturated microbial N-acyl derivative oligosaccharides or polysaccharides; (ii) novel conjugates of unsaturated N-acyl derivatives; and (iii) glycoconjugate compositions comprising conjugate molecules of fragments of microbial unsaturated N-acyl derivatives that serve as a covalent linker to one or more proteins. The invention further encompasses the use of the immunogenic glycoconjugates pharmaceutical compositions for the prevention or treatment of an infectious disease.
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MODIFIED POLYSACCHARIDES FOR CONJUGATE VACCINES (Thu, 25 Dec 2008)
The present invention relates to methods of manufacture of immunogenic glycoconjugates, in particular for use in pharmaceutical compositions for inducing a therapeutic immune response in a subject. The immunogenic glycoconjugates of the invention comprise one or more oligosaccharides or polysaccharides that are conjugated to one or more carrier proteins via an active aldehyde group. Accordingly, the invention provides methods of making (i) unsaturated microbial N-acyl derivative oligosaccharides or polysaccharides; (ii) novel conjugates of unsaturated N-acyl derivatives; and (iii) glycoconjugate compositions comprising conjugate molecules of fragments of microbial unsaturated N-acyl derivatives that serve as a covalent linker to one or more proteins. The invention further encompasses the use of the immunogenic glycoconjugates pharmaceutical compositions for the prevention or treatment of an infectious disease. </p>
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von Willebrand factor- and factor VIII-polymer conjugates having a releasable linkage (Fri, 26 Sep 2008)
<p id="p-0001" num="0000">The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.</p>
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VON WILLEBRAND FACTOR- AND FACTOR VIII-POLYMER CONJUGATES HAVING A RELEASABLE LINKAGE (Fri, 11 Jul 2008)
The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.
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VON WILLEBRAND FACTOR-AND FACTOR VIII-POLYMER CONJUGATES HAVING A RELEASABLE LINKAGE (Fri, 11 Jul 2008)
The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.</p>
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MICROPARTICLES AND METHODS FOR PRODUCTION THEREOF (Fri, 14 Dec 2007)
An active agent and a non-polymeric polyanionic compound are allowed to be associated with a microparticle containing an anionic macromolecule and an anionic polymer in the presence of a crosslink activator. In a non-limiting example, the non-polymeric polyanionic compound is a polyanionic amino acid such as aspartic acid or glutamic acid. The microparticle can be used for modified release of the active agent in vitro and/or in vivo.
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MULTIPLE CHAMBER CONTAINER WITH MISTAKE PROOF ADMINISTRATION SYSTEM (Fri, 16 Nov 2007)
The present disclosure provides a multiple chamber container (10) that includes a container body sealed around a peripheral edge (14) and having an outlet (16). The container also includes a first peel seal (18) having a projecting portion (42) and a second peel seal (20) that isolates the outlet (16). The second peel seal may also include a projecting portion (44). The first and second peel seals (18,20) may be configured to define a symmeterical chamber. The chamber may include an axis of symmetry extending between the first and second projecting portions (42,44). The chamber geometry of the container ensures a correct sequential opening of the first and second peel seals (18,20).</p>
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METHOD FOR PURIFYING POLYSACCHARIDES (Fri, 27 Jul 2007)
This invention relates to improved methods for purifying polysaccharides from cellular components, such as a cell wall. The method relates to hydrolyzing and separating the polysaccharides, thereby resulting in purified polysaccharides useful for producing antigens, antibodies, and vaccines comprising the polysaccharides alone or conjugated to carrier molecules. This method is simple, rapid, efficient, scalable, and reproducible.
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METHOD FOR PURIFYING POLYSACCHARIDES (Fri, 27 Jul 2007)
This invention relates to improved methods for purifying polysaccharides from cellular components, such as a cell wall. The method relates to hydrolyzing and separating the polysaccharides, thereby resulting in purified polysaccharides useful for producing antigens, antibodies, and vaccines comprising the polysaccharides alone or conjugated to carrier molecules. This method is simple, rapid, efficient, scalable, and reproducible. </p>
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Method for purifying polysaccharides (Fri, 06 Jul 2007)
<p id="p-0001" num="0000">This invention relates to improved methods for purifying polysaccharides from cellular components, such as a cell wall. The method relates to hydrolyzing and separating the polysaccharides, thereby resulting in purified polysaccharides useful for producing antigens, antibodies, and vaccines comprising the polysaccharides alone or conjugated to carrier molecules. This method is simple, rapid, efficient, scalable, and reproducible.</p>
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(POLYALKOXY)SULFONATE SURFACE MODIFIERS (Fri, 04 Aug 2006)
The present invention is directed to novel compounds, methods of manufacture and methods of use. The present invention is also directed to solid drug/active agent particles having one or more of the compounds of the present invention associated with the surface thereof. The compounds of the present invention are comprised of a non-polar polyether covalently linked to an anionic sulfonate group. The compounds have an amphipathic quality and preferably, are surface active. Such compounds are preferably useful as surface-active agents to coat and stabilize dispersions of particles in a continuous liquid medium. These surface-active agents may be applied in the stabilization of suspensions, emulsions, or liposome formulations intended for pharmaceutical, medical, cosmetic, or agricultural use. The particles that can be prepared by a variety of methods and will preferably comprise a pharmaceutical agent. Pharmaceutical compositions of the present invention can be used to treat amyriad of conditions and can be administered by many routes, including intravenous, intramuscular, subcutaneous, intrathecal, subdural, intracameral, intracerebral, intralesional, topical, oral, buccal, rectal, pulmonary, and nasal.
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(POLYALKOXY)SULFONATE SURFACE MODIFIERS (Fri, 04 Aug 2006)
The present invention is directed to novel compounds, methods of manufacture and methods of use. The present invention is also directed to solid drug/active agent particles having one or more of the compounds of the present invention associated with the surface thereof. The compounds of the present invention are comprised of a non-polar polyether covalently linked to an anionic sulfonate group. The compounds have an amphipathic quality and preferably, are surface active. Such compounds are preferably useful as surface-active agents to coat and stabilize dispersions of particles in a continuous liquid medium. These surface-active agents may be applied in the stabilization of suspensions, emulsions, or liposome formulations intended for pharmaceutical, medical, cosmetic, or agricultural use. The particles that can be prepared by a variety of methods and will preferably comprise a pharmaceutical agent. Pharmaceutical compositions of the present invention can be used to treat amyriad of conditions and can be administered by many routes, including intravenous, intramuscular, subcutaneous, intrathecal, subdural, intracameral, intracerebral, intralesional, topical, oral, buccal, rectal, pulmonary, and nasal. </p>
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(Polyalkoxy)sulfonate surface modifiers (Fri, 30 Jun 2006)
<p id="p-0001-en" num="0000">The present invention is directed to novel compounds, methods of manufacture and methods of use. The present invention is also directed to solid drug/active agent particles having one or more of the compounds of the present invention associated with the surface thereof.</p> <p id="p-0002-en" num="0000">The compounds of the present invention are comprised of a non-polar polyether covalently linked to an anionic sulfonate group. The compounds have an amphipathic quality and preferably, are surface active. Such compounds are preferably useful as surface-active agents to coat and stabilize dispersions of particles in a continuous liquid medium. These surface-active agents may be applied in the stabilization of suspensions, emulsions, or liposome formulations intended for pharmaceutical, medical, cosmetic, or agricultural use.</p> <p id="p-0003-en" num="0000">The particles that can be prepared by a variety of methods and will preferably comprise a pharmaceutical agent. Pharmaceutical compositions of the present invention can be used to treat a myriad of conditions and can be administered by many routes, including intravenous, intramuscular, subcutaneous, intrathecal, subdural, intracameral, intracerebral, intralesional, topical, oral, buccal, rectal, transcutaneous, pulmonary, and nasal.</p>
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COMPOSITIONS CAPABLE OF INHIBITING REACTIVE OXYGEN AND CARBONYL SPECIES (Fri, 24 Feb 2006)
Therapeutic compositions are provided. The compositions include a single molecule that can display both antioxidant and carbonyl trapping properties. This can effectively reduce inflammation, oxidative stress and carbonyl stress, such as to prevent and/or treat cardiovascular disease and inflammatory diseases in kidney disease patients.
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Compositions capable of inhibiting reactive oxygen and carbonyl species (Fri, 27 Jan 2006)
<p id="p-0001-en" num="0000">Therapeutic compositions are provided. The compositions include a single molecule that can display both antioxidant and carbonyl trapping properties. This can effectively reduce inflammation, oxidative stress and carbonyl stress, such as to prevent and/or treat cardiovascular disease and inflammatory diseases in kidney disease patients.</p>
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Process for recovery of 1,1,1,3,3,3-hexafluoroisopropanol from the waste stream of sevoflurane synthesis (Fri, 07 Oct 2005)
<p id="p-0001-en" num="0000">Provided is a process of obtaining 1,1,1,3,3,3-hexafluoro-2-propanol (“HFIP”) from a composition comprising an HFIP hydrolyzable precursor. The HFIP hydrolyzable precursor is a compound, other than sevoflurane itself, that has an intact 1,1,1,3,3,3-hexafluoroisopropoxy moiety[(CF<sub>3</sub>)<sub>2</sub>CHO—], and contains one or more moieties susceptible to acidic hydrolysis, such that HFIP is released upon such treatment. The process is useful, among other things, for recovering HFIP from waste streams associated with the synthesis of the inhalation anesthetic, fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (“sevoflurane”). The process includes heating the composition with a strong protic acid to a temperature effective to hydrolyze at least some of the HFIP hydrolyzable precursor to HFIP, and then isolating the HFIP from the heated composition.</p>
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VACCINES AGAINST GROUP Y NEISSERIA MENINGITIDIS AND MENINGOCOCCAL COMBINATIONS THEREOF (Fri, 07 Jan 2005)
This invention relates to modified meningococcal Y polysaccharides (GYMP), conjugates comprising the modified polysaccharides and a carrier, vaccines for the immunisation of warm-blooded animals, including humans, against Group Y Neisseria meningitidis, and to methods for producing these modified polysaccharides, conjugates and vaccines.
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VACCINES AGAINST GROUP Y NEISSERIA MENINGITIDIS AND MENINGOCOCCAL COMBINATIONS THEREOF (Fri, 07 Jan 2005)
<br/><br/><br/>This invention relates to modified meningococcal Y polysaccharides (GYMP), <br/>conjugates comprising the modified polysaccharides and a carrier, vaccines for <br/>the immunisation of warm-blooded animals, including humans, against Group Y <br/>Neisseria meningitidis, and to methods for producing these modified <br/>polysaccharides, conjugates and vaccines.<br/></p>
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Process for preparing pharmaceutical formulations using supercritical fluids (Fri, 15 Oct 2004)
<p id="p-a-0001-en">The invention is directed to a process for preparing a pharmaceutical formulation containing two or more active pharmaceutical ingredients comprising: (a) contacting two or more active pharmaceutical ingredients with a supercritical fluid to form a supercritical fluid solution; and (b) separating the active ingredients from the supercritical solution to yield a powder precipitate. Preferably, the pharmaceutical formulation prepared according to the invention contains a combination of two anti-infective agents or two anticancer agents. The invention is further directed to a process for preparing a pharmaceutical formulation containing two or more active pharmaceutical ingredients comprising: (a) combining two or more active ingredients with a cosolvent to form a solution; (b) contacting the solution with a supercritical fluid; and (c) recovering the precipitate in a powder form. </p>
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Peritoneal dialysis solution containing modified icodextrins (Fri, 01 Oct 2004)
<p id="p-0001-en" num="0000">The present invention provides a peritoneal dialysis solution that contains heat stable osmotic agents such as D-glucitols, gluconic acids and alkylglycosides produced the reduction, oxidation or glycosylation of icodextrins respectively. As a result, osmotic agents that are stable under autoclaving or heat sterilization conditions are provided which reduces the amount of bioincompatible materials in the sterilized peritoneal dialysis solutions. Methods of preparing the D-glucitols, gluconic acids and alkylglycosides are disclosed.</p>
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PROCESS FOR RECOVERY OF 1,1,1,3,3,3-HEXAFLUOROISOPROPANOL FROM THE WASTE STREAM OF SEVOFLURANE SYNTHESIS (Fri, 06 Aug 2004)
Provided is a process of obtaining 1,1,1,3,3,3-hexafluoro-2-propanol ('HFIP') from a composition comprising an HFIP hydrolyzable precursor. The HFIP hydrolyzable precursor is a compound, other than sevoflurane itself, that has an intact 1,1,1,3,3,3-hexafluoroisopropoxy moiety[(CF3)2CHO―], and contains one or more moieties susceptible to acidic hydrolysis, such that HFIP is released upon such treatment. The process is useful, among other things, for recovering HFIP from waste streams associated with the synthesis of the inhalation anesthetic, fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether ('sevoflurane'). The process includes heating the composition with a strong protic acid to a temperature effective to hydrolyze at least some of the HFIP hydrolyzable precursor to HFIP, and then isolating the HFIP from the heated composition.
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PROCESS FOR RECOVERY OF 1,1,1,3,3,3-HEXAFLUOROISOPROPANOL FROM THE WASTE STREAM OF SEVOFLURANE SYNTHESIS (Fri, 06 Aug 2004)
Provided is a process of obtaining 1,1,1,3,3,3-hexafluoro-2-propanol ("HFIP") from a composition comprising an HFIP hydrolyzable precursor. The HFIP hydrolyzable precursor is a compound, other than sevoflurane itself, that has an intact 1,1,1,3,3,3-hexafluoroisopropoxy moiety[(CF3)2CHO~], and contains one or more moieties susceptible to acidic hydrolysis, such that HFIP is released upon such treatment. The process is useful, among other things, for recovering HFIP from waste streams associated with the synthesis of the inhalation anesthetic, fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether ("sevoflurane"). The process includes heating the composition with a strong protic acid to a temperature effective to hydrolyze at least some of the HFIP hydrolyzable precursor to HFIP, and then isolating the HFIP from the heated composition. </p>
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Peritoneal dialysis solution containing modified icodextrins (Wed, 04 Aug 2004)
<p id="p-00001-en">The present invention provides a peritoneal dialysis solution that contains heat stable osmotic agents such as D-glucitols, gluconic acids and alkylglycosides produced the reduction, oxidation or glycosylation of icodextrins respectively. As a result, osmotic agents that are stable under autoclaving or heat sterilization conditions are provided which reduces the amount of bioincompatible materials in the sterilized peritoneal dialysis solutions. Methods of preparing the D-glucitols, gluconic acids and alkylglycosides are disclosed.</p>
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Process for recovery of 1,1,1,3,3,3-hexafluoroisopropanol from the waste stream of sevoflurane synthesis (Fri, 30 Jul 2004)
<p id="p-0001-en" num="0000">Provided is a process of obtaining 1,1,1,3,3,3-hexafluoro-2-propanol (“HFIP”) from a composition comprising an HFIP hydrolyzable precursor. The HFIP hydrolyzable precursor is a compound, other than sevoflurane itself, that has an intact 1,1,1,3,3,3-hexafluoroisopropoxy moiety[(CF<sub>3</sub>)<sub>2</sub>CHO—], and contains one or more moieties susceptible to acidic hydrolysis, such that HFIP is released upon such treatment. The process is useful, among other things, for recovering HFIP from waste streams associated with the synthesis of the inhalation anesthetic, fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (“sevoflurane”). The process includes heating the composition with a strong protic acid to a temperature effective to hydrolyze at least some of the HFIP hydrolyzable precursor to HFIP, and then isolating the HFIP from the heated composition.</p>
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PROCESS FOR PREPARING COMBINATION PHARMACEUTICAL FORMULATIONS USING SUPERCRITICAL FLUIDS (Fri, 09 Jul 2004)
The invention is directed to a process for preparing a pharmaceutical formulation containing two or more active pharmaceutical ingredients comprising: (a) contacting two or more active pharmaceutical ingredients with a supercritical fluid to form a supercritical fluid solution; and (b) separating the active ingredients from the supercritical solution to yield a powder precipitate. Preferably, the pharmaceutical formulation prepared according to the invention contains a combination of two anti-infective agents or two anticancer agents. The invention is further directed to a process for preparing a pharmaceutical formulation containing two or more active pharmaceutical ingredients comprising: (a) combining two or more active ingredients with a cosolvent to form a solution; (b) contacting the solution with a supercritical fluid; and (c) recovering the precipitate in a powder form.
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PROCESS FOR PREPARING COMBINATION PHARMACEUTICAL FORMULATIONS USING SUPERCRITICAL FLUIDS (Fri, 09 Jul 2004)
The invention is directed to a process for preparing a pharmaceutical formulation containing two or more active pharmaceutical ingredients comprising: (a) contacting two or more active pharmaceutical ingredients with a supercritical fluid to form a supercritical fluid solution; and (b) separating the active ingredients from the supercritical solution to yield a powder precipitate. Preferably, the pharmaceutical formulation prepared according to the invention contains a combination of two anti-infective agents or two anticancer agents. The invention is further directed to a process for preparing a pharmaceutical formulation containing two or more active pharmaceutical ingredients comprising: (a) combining two or more active ingredients with a cosolvent to form a solution; (b) contacting the solution with a supercritical fluid; and (c) recovering the precipitate in a powder form. </p>
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PROCESS FOR THE PREPARATION OF POLYETHYLENE GLYCOL BIS AMINE (Fri, 30 Apr 2004)
A two-step process for the preparation of polyethylene glycol-bis amine comprising a first step of reacting the terminal hydroxy groups of polyethylene glycol with a halogen substituted aromatic sulfonyl halide in a solvent to form a disubstituted sulfonyl activated polyethylene glycol intermediate. In a second step the intermediate is directly aminated with ammonia to give polyethylene glycol-bis amine.
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Process for the preparation of polyethylene glycol bis amine (Fri, 08 Aug 2003)
<p id="p-a-0001-en">A two step process for the preparation of polyethylene glycol-bis amine comprising a first step of reacting the terminal hydroxy groups of polyethylene glycol with a halogen substituted aromatic sulfonyl halide in a solvent to form a disubstituted sulfonyl activated polyethylene glycol intermediate. In a second step the intermediate is directly aminated with ammonia to give polyethylene glycol-bis amine. </p>
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PROCESS FOR REMOVAL OF DIMETHYL ETHER IN THE SYNTHESIS OF SEVOFLURANE (Fri, 13 Dec 2002)
The invention provides a process for purifying methyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether, comprising; passing a composition comprising methyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether and dimethyl ether through an evaporation zone; evaporating dimethyl ether by passing a gas stream through the composition; and removing the gas comprising dimethyl ether from the composition.
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IMMUNOGENIC CONJUGATES OF LOW MOLECULAR WEIGHT HYALURONIC ACID WITH POLYPEPTIDE TOXINS (Fri, 22 Nov 2002)
The present invention provides antigenic compositions and methods for treatment and prevention of infection and disease caused by group A and group C streptococci. In particular, the invention provides low molecular weight hyaluronic acid, low molecular weight hyaluronic acid linked to a carrier and compositions comprising them. The compositions elicit antibodies to low molecular weight hyaluronic acid which are cross-reactive with group A and C streptococci and which are minimally cross-reactive with native hyaluronic acid. The invention is particularly useful for providing both active and passive immunogenic protection for those infected wiht or at risk infection with group A and group C streptococci. Additionally, the present invention provides methods and compositions useful for diagnosing infections and diseases caused by group A and group C streptococci.
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IMMUNOGENIC CONJUGATES OF LOW MOLECULAR WEIGHT HYALURONIC ACID WITH POLYPEPTIDE TOXINS (Fri, 22 Nov 2002)
The present invention provides antigenic compositions and methods for treatment and prevention of infection and disease caused by group A and group C streptococci. In particular, the invention provides low molecular weight hyaluronic acid, low molecular weight hyaluronic acid linked to a carrier and compositions comprising them. The compositions elicit antibodies to low molecular weight hyaluronic acid which are cross-reactive with group A and C streptococci and which are minimally cross-reactive with native hyaluronic acid. The invention is particularly useful for providing both active and passive immunogenic protection for those infected wiht or at risk infection with group A and group C streptococci. Additionally, the present invention provides methods and compositions useful for diagnosing infections and diseases caused by group A and group C streptococci. </p>
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Process for removal of dimethyl ether in the synthesis of sevoflurane (Wed, 11 Sep 2002)
<p id="p-00001-en">The invention provides a process for purifying methyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether, comprising: passing a composition comprising methyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether and dimethyl ether through an evaporation zone; evaporating dimethyl ether by passing a gas stream through the composition; and removing the gas comprising dimethyl ether from the composition.</p>
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Antigenic group B Streptococcus type II and type III polysaccharide fragments having a 2, 5-anhydro-D-mannose terminal structure and conjugate vaccine thereof (Wed, 17 Apr 2002)
<p id="p-00001-en">The process for depolymerizing Group B Types II and III Streptococcal Polysaccharide is disclosed which results in polysaccharide fragments having a reducing end suitable for conjugating to protein. Conjugate molecules, vaccines and their use to immunize mammals including humans are also disclosed.</p>
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Method of immunization using a Group B Streptococcus type II and type III polysaccharide conjugate vaccine (Fri, 15 Mar 2002)
<p id="p-00001-en">The process for depolymerizing Group B Types II and III streptococcal polysaccharide is disclosed which results in polysaccharide fragments having a reducing end suitable for conjugating to protein. Conjugate molecules, vaccines and their use to immunize mammals including humans are also disclosed.</p>
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Antibodies to meningococcal polysaccharide conjugate vaccines (Wed, 27 Feb 2002)
<p id="p-00001-en">The invention relates to chemically-modified group B polysaccharides of<i>Neisseria meningitidis</i>. The invention also provides vaccines in which the respective modified polysaccharides are conjugated to a protein carrier, and the like, as well as antibodies to these conjugate vaccines. More specifically, the present invention provides novel group B meningococcal unsaturated N-acyl derivative polysaccharides, novel conjugates of the group B meningococcal unsaturated N-acyl derivative polysaccharides, pharmaceutical compositions comprising conjugate molecules of group B meningococcal unsaturated N-acyl derivative polysaccharide fragments covalently bound to proteins, and the use of these compositions as vaccines.</p>
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Enantiomerically-enhanced nutritional energy substrates (Wed, 24 Oct 2001)
<p id="p-00001-en">Synthetic enantiomeric esters are employed as energy substrates for parenteral or enteral nutritional formulations. The substrates are provided in substantially monoisomeric or anomeric forms readily utilized in patient metabolism.</p>
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Direct methods for molar-mass determination of fragments of Haemophilus influenzae type b capsular polysaccharides and vaccine preparation (Wed, 01 Aug 2001)
<p id="p-00001-en">The invention relates to the accurate and precise direct molar-mass measurement of low-molar-mass fragments of polysaccharides such as<i>Haemophilus influenzae</i>Type b. The methods for obtaining such determinations for polysaccharides use size-exclusion chromatography (SEC) with detection by multi-angle laser-light-scattering photometry (MALLS) and differential refractometry (RI) and/or (2) determination of polysaccharide fragments and direct measurement of average chain length by quantitative<sup>1</sup>H NMR, from which molar masses may be derived. Variation between the molar masses obtained by the two methods ranged from 5 to 7%.</p>
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Procedures for the extraction and isolation of bacterial capsular polysaccharides for use as vaccines or linked to proteins as conjugate vaccines (Wed, 20 Jun 2001)
<p id="p-00001-en">A procedure to isolate large quantities of capsular poly saccharides (CPS) from culture supernatants as well as bacterial cells of gram-negative and gram-positive bacteria using base extraction is described. The procedure is simple, rapid, reproducible and applicable to a variety of bacterial species. The method also yields novel CPS characterized by their lack of covalent attachment to extraneous peptidoglycan. Vaccines and methods of immunization against bacterial infection using the CPS obtained by the process of the invention are also disclosed.</p>
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Method of inactivation of viral and bacterial blood contaminants (Wed, 14 Feb 2001)
<p id="p-00001-en">A method is provided for inactivating viral and/or bacterial contamination in blood cellular matter, such as erythrocytes and platelets, or protein fractions. The cells or protein fractions are mixed with chemical sensitizers, frozen or freeze-dried, and irradiated with, for example, UV, visible, gamma or X-ray radiation while in the solid state.</p>
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PERITONEAL DIALYSIS SOLUTION CONTAINING MODIFIED ICODEXTRINS (Fri, 16 Jun 2000)
The present invention provides a peritoneal dialysis solution that contains heat stable osmotic agents such as D-glucitols, gluconic acids and alkylglycosides produced the reduction, oxidation or glycosylation of icodextrine respectively. As a result, osmotic agents that are stable under autoclaving or heat sterilization conditions are provided which reduces the amount of bioincompatible materials in the sterilized peritoneal dialysis solutions. Methods of preparing the D-glucitols, gluconic acids and alkylglycosides are disclosed.
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PERITONEAL DIALYSIS SOLUTION CONTAINING MODIFIED ICODEXTRINS (Fri, 16 Jun 2000)
The present invention provides a peritoneal dialysis solution that contains heat stable osmotic agents such as D-glucitols, gluconic acids and alkylglycosides produced the reduction, oxidation or glycosylation of icodextrine respectively. As a result, osmotic agents that are stable under autoclaving or heat sterilization conditions are provided which reduces the amount of bioincompatible materials in the sterilized peritoneal dialysis solutions. Methods of preparing the D-glucitols, gluconic acids and alkylglycosides are disclosed. </p>
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Reagents for isotropic size enhancement of a peptide, protein, nucleotide or other substrate (Wed, 26 Jan 2000)
<p>Novel polysaccharide compounds are disclosed for decorating biomolecular surfaces to increase isotropic size and mask antigenicity. The oligosaccharides may be synthesized as repeating disaccharide units, or may be derived by acid hydrolysis of naturally occurring polysaccharides. Such natural sources include chondroitins obtained from shark cartilage, or hyaluronic acid. The polyanionic sulfate groups contained in the sugar moieties impart negative charges which repel the molecules from the negatively charged wall of capillaries, to lengthen retention times of decorated drug molecules, such as crosslinked hemoglobin, in the peripheral circulation.</p>
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Therapeutic hemoglobin composition having isotropically increased size (Wed, 10 Nov 1999)
<p>Novel polysaccharide compounds are disclosed for decorating biomolecular surfaces to increase isotropic size and mask antigenicity. The oligosaccharides may be synthesized as repeating disaccharide units, or may be derived by acid hydrolysis of naturally occurring polysaccharides. Such natural sources include chondroitins obtained from shark cartilage, or hyaluronic acid. The polyanionic sulfate groups contained in the sugar moieties impart negative charges which repel the molecules from the negatively charged wall of capillaries, to lengthen retention times of decorated drug molecules, such as crosslinked hemoglobin, in the peripheral circulation.</p>
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METHOD OF PREPARING MONOFLUOROMETHYL ETHERS (Fri, 04 Jun 1999)
A method of preparing fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) and structurally related monofluormethyl ethers in which the monochloromethyl ether precursor thereof is reacted with a sterically hindered tertiary amine hydrofluoride salt.
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METHOD OF PREPARING MONOFLUOROMETHYL ETHERS (Fri, 04 Jun 1999)
8A method of preparing fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) and structurally related monofluo- methyl ethers in which the monochloromethyl ether precursor thereof is reacted with a sterically hindered tertiary amine hydrofluoride salt. </p>
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Method of preparing monofluoromethyl ethers (Wed, 24 Mar 1999)
<p>A method of preparing fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) and structurally related monofluoromethyl ethers in which the monochloromethyl ether precursor thereof is reacted with a sterically hindered tertiary amine hydrofluoride salt.</p>
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THERAPEUTIC HEMOGLOBIN COMPOSITION HAVING ISOTROPICALLY INCREASED SIZE (Fri, 29 Jan 1999)
Novel polysaccharide compounds are disclosed for decorating biomolecular surfaces to increase isotropic size and mask antigenicity. The oligosaccharides may by synthesized as repeating disaccharide units, or may be derived by acid hydrolysis of naturally occurring polysaccharides. Such natural sources include chondroitins obtained from shark cartilage, or hyaluronic acid. The polyanionic sulfate groups contained in the sugar moieties impart negative charges which repel the molecules from the negatively charged wall of capillaries, to lengthen retention times of decorated drug molecules, such as cross-linked hemoglobin, in the peripheral circulation.
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THERAPEUTIC HEMOGLOBIN COMPOSITION HAVING ISOTROPICALLY INCREASED SIZE (Fri, 29 Jan 1999)
Novel polysaccharide compounds are disclosed for decorating biomolecular surfaces to increase isotropic size and mask antigenicity. The oligosaccharides may by synthesized as repeating disaccharide units, or may be derived by acid hydrolysis of naturally occurring polysaccharides. Such natural sources include chondroitins obtained from shark cartilage, or hyaluronic acid. The polyanionic sulfate groups contained in the sugar moieties impart negative charges which repel the molecules from the negatively charged wall of capillaries, to lengthen retention times of decorated drug molecules, such as cross-linked hemoglobin, in the peripheral circulation. </p>
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PHOSPHINE LIGANDS (Fri, 27 Mar 1998)
Compounds of Formula (I) wherein R, R?1, R2 and R9¿ are as herein defined, processes for their preparation and transition metal complexes comprising such compounds are disclosed. The complexes may be attached to insoluble supports and are useful as asymetric catalysts.
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FLUORESCENT POLY(ARYLPYRIDINE)RARE EATH CHELATES (Wed, 18 Mar 1998)
A class of fluorescent rare earth chelates and the ligands upon which they are based whose molecular structure incorporates a plurality of substituted arylpyridine diacid units attached to a central template structure is disclosed. These ligands function as efficient energy transfer groups in fluorescent tagging reagents and tracers. The present fluorescent chelates contain a plurality of aryl-substituted pyridines arranged structurally within a single molecule such that each optimally binds to a single metal ion. Each pyridine group is structurally insulated from the others so that, in the unchelated form, each retains to some degree the properties of the single pyridine. </p>
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WATER SOLUBLE NON-IMMUNOGENIC POLYAMIDE CROSS-LINKING AGENTS (Fri, 07 Jul 1995)
The present invention relates to water-soluble nonimmunogenic polyamide cross-linking agents and their use to cross-link, polymerize, decorate, and conjugate proteins, polynucleotides and other biological substrates to form substantially nonimmunogenic water-soluble products. The present invention also relates to proteins, polynucleotides and other biological substrates which are cross-linked, conjugated, polymerized or decorated with water-soluble polyamides to form substantially nonimmunogenic products.
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WATER SOLUBLE NON-IMMUNOGENIC POLYAMIDE CROSS-LINKING AGENTS (Fri, 10 Jun 1994)
The present invention relates to water-soluble nonimmunogenic polyamide cross-linking agents and their use to cross-link, polymerize, decorate, and conjugate proteins, polynucleotides and other biological substrates to form substantially nonimmunogenic water-soluble products. The present invention also relates to proteins, polynucleotides and other biological substrates which are cross-linked, conjugated, polymerized or decorated with water-soluble polyamides to form substantially nonimmunogenic products.
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Preparation of bis(salicyl) diesters (Wed, 21 Aug 1991)
<p>Bis(salicyl) diesters useful as cross-linking agents for hemoglobin are prepared in high yield and purity by reacting salicylic acid or a derivative thereof with a lower aliphatic dicarboxylic acid halide in a lower aliphatic ketone or nitrile solvent in the presence of a pyridine derivative. The desired diester is recovered from the resulting insoluble pyridine derivative salt.</p>
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Fluorescent poly(arylpyridine) rare earth chelates (Wed, 17 Jul 1991)
<p>A class of fluorescent rare earth chelates and the ligands upon which they are based whose molecular structure incorporates a plurality of substituted arylpyridine diacid units attached to a central template structure is disclosed. These ligands function as efficient energy transfer groups in fluorescent tagging reagents and tracers. ##STR1##</p>
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Interligand metal transfer assay (Wed, 16 May 1990)
<p>A new reporter mechanism for biospecific reactions is disclosed. This mechanism involves interligand metal ion transfer in which a metal ion is directly transferred from one chelate complex to another following the occurance of the biospecific reaction. The second chelate complex is separate from and detectably different than the first chelate complex. This invention can take the form of methods of chemical analysis and kits for conducting such methods. In preferred embodiments of this invention the detectable difference is a difference in fluorescence, such as an increase or decrease which occurs as a result of the formation of the second chelate. In further preferred embodiments the difference in fluorescence is detected using fluorescent background rejection methods.</p>
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FLUORESCENT POLY(ARYLPYRIDINE) RARE EARTH CHELATES (Fri, 02 Jun 1989)
A class of fluorescent rare earth chelates and the ligands upon which they are based whose molecular structure incorporates a plurality of substituted arylpyridine diacid units attached to a central template structure is disclosed. These ligands function as efficient energy transfer groups in fluorescent tagging reagents and tracers.
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