Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The present invention provides analytical methods for detecting anti-polymer antibody in an individual. The methods involve contacting a sample from the individual with a water soluble polymer-modified carrier and detecting binding of antibody to the water soluble polymer on the water soluble polymer-modified carrier wherein binding is indicative of the presence of antibody to the water polymer-modified polypeptide. Antibody may be detected to water soluble polymers such as polyethylene glycol, polysialic acid, dextran, hydroxyalkyl starch, or hydroxyethyl starch. When antibody to the water soluble polymer polyethylene glycol is to be detected, the carrier is modified with a non-linear polyethylene glycol derivative.

Abstract: The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF.

Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a blood coagulation 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 linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer. In one embodiment of the invention the conjugation is carried out in the presence of the nucleophilic catalyst aniline. In addition the generated oxime linkage can be stabilized by reduction with NaCNBH3 to form an alkoxyamine linkage.

Abstract: A water soluble polymer, in particular polysialic acid (PSA) or a modified PSA (mPSA), is conjugated to an oxidized carbohydrate moiety of a glycoprotein other than a blood coagulation protein or to a ganglioside or drug delivery system by contacting the oxidized carbohydrate moiety with the water soluble polymer, wherein said water soluble polymer contains an aminooxy group and an oxime linkage is formed between the oxidized carbohydrate moiety and the aminooxy group on the water soluble polymer or wherein said water soluble polymer contains a hydrazide group and a hydrazone linkage is formed between the oxidized carbohydrate moiety and the hydrazide group on the water soluble polymer. Conjugates of aminooxy- or hydrazide-water soluble polymer, such as PSA and mPSA, are thus obtained in which the PSA or mPSA is attached via a carbohydrate moiety.

Abstract: 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.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule having at least a portion of the B domain intact, which is conjugated to a water-soluble polymer such as polyethylene glycol having a molecular weight of greater than 10,000 Daltons. The construct has a biological activity of at least 80% of the biological activity of native Factor VIII, and the in vivo half-life of the construct is increased by at least 1.5 fold as compared to the in vivo half-life of native factor FVIII.

Abstract: The present invention relates, in general, to methods for detecting the amount of a polymer on a protein using near-infrared spectroscopy. Measurement of the number of polymer moieties per protein molecule allows for production of molecules having a uniform number of polymer moieties, which is useful in the production of pharmaceutical compositions.

Abstract: Disclosed herein are methods of determining polydispersity (PDI) and molecular mass distribution (MMD) of reactive PEG samples using mass spectrometry. More specifically, a mass spectrometry method called GEMMA is used to determine PDI and MMD of PEG samples which provides more accurate measurements for high molecular weight PEG samples than prior known MALDI-TOF analysis.

Abstract: The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs.

Abstract: The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs.

Abstract: 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.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The present invention relates, in general, to materials and methods for the preparation of modified blood factors which have low levels of water soluble polymer molecules conjugated to the blood factor but exhibit biological activity similar to or better than molecules having a higher number of water soluble polymer moieties.

Abstract: The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs.