Abstract: A process for preparing .alpha.-interferon-polymer conjugates having high levels of retained interferon activity and relatively long circulating lives in vivo is disclosed. The process includes forming substantially non-antigenic .alpha.-interferon-polymer conjugates, combining the .alpha.-interferon-polymer conjugates with a sufficient amount of an acid to reduce the pH of the conjugates to a level which is sufficient to cleave the polymer linkages in an active site area of the interferon and thereafter adjusting the .alpha.-interferon-polymer conjugates to a physiologically-acceptable pH. Methods of treating interferon-susceptible conditions with the compositions of the present invention are also disclosed.

Abstract: The present invention is directed to double prodrugs containing polymeric-based transport forms. These polymeric prodrugs are preferably of the formula: ##STR1## wherein: B is a leaving group or a residue of an amine-containing target moiety;G is ##STR2## or CH.sub.2 ; Y.sub.1-2 are independently O or S;M is X or Q; where X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(.dbd.Y.sub.2);R.sub.1, R.sub.4, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.13 are independently selected from the group consisting of hydrogen, C.sub.1-6 alkyls, C.sub.3-12 branched alkyls, C.sub.3-8 cycloalkyls, C.sub.1-6 substituted alkyls, C.sub.3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C.sub.1-6 heteroalkyls, substituted C.sub.1-6 heteroalkyls;R.sub.2, R.sub.3, R.sub.5 and R.sub.6 are independently selected from the group consisting of hydrogen, C.sub.1-6 alkyls, C.sub.1-6 alkoxy, phenoxy, C.sub.1-8 heteroalkyls, C.sub.

Abstract: Compositions containing alpha interferon conjugated to a substantially non-antigenic polymer are disclosed in which at least about 30% of the conjugates include covalent attachment of the alpha interferon to the substantially non-antigenic polymer at a histidine. Also disclosed is a process for preparing the conjugates. The process includes contacting an alpha interferon with a succinimidyl carbonate-activated substantially non-antigenic polymer at a pH which is sufficient to facilitate covalent attachment of the polymer on a histidine of the alpha interferon.

Abstract: A computing assembly which comprises a hand held computer or PDA that contains a housing, a processor in said housing and an input/output arrangement in said housing coupled to said processor for inputting data to, and outputting data from the processor and a foldable keyboard electrically connected to the PDA. The foldable keyboard has first and second planar keyboard halves having a plurality of depressable keys arranged on a surface. The keyboard halves have complementary curved outer peripheral edges and are attached to one another by an intermediate hinge. When in the open position, the first keyboard half is substantially coplanar with the second keyboard half, and the peripheral edges of the first and second keyboard halves form a substantially continuous curvilinear path. When in the closed position, the first keyboard half is folded over, substantially congruent in shape with, and in a plane parallel to the plane of the second keyboard half.

Abstract: An apparatus (1) for supporting and guiding a conveyor belt (2), comprising a series of supporting assemblies (9) arranged one behind the other, each supporting assembly (9) comprising at least two juxtaposed carrying axles (10), including an angle relative to each other, at least one of the carrying axles carrying a conveyor roller (15), whilst in each case, two carrying axles are interconnected by facing ends for pivoting at least in approximately the plane defined by the carrying axles (10) to form a garland-shaped supporting assembly (9) suspended by its free ends (13) in a supporting frame (5), at least a number of the supporting assemblies within the supporting frame being interconnected by connecting rods (18).

Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Abstract: A purified arginine deiminase (ADI) obtained from Mycoplasma arthritidis having the amino acid sequence of SEQ ID NO:2 as well as an isolated nucleic acid molecule containing a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO:1 are disclosed. Other aspects of the invention include an expression vector, a cloned gene for expressing the Mycoplasma arthritidis derived ADI, (recombinant) host cells useful in expressing the ADI of the present invention and substantially non-antigenic polymer conjugates containing the ADI of the present invention as well as methods of treating arginine deiminase susceptible conditions in mammals. The arginine deiminase-polymer conjugates have high levels of retained enzyme activity and relatively long circulating lives.

Abstract: Substantially non-antigenic polymers containing pI and/or pH optimum modulating moieties are disclosed. The polymers are useful as intermediates for synthesis of amine-based polymers and in the formation of activated polymers for conjugation with nucleophiles. Conjugates and methods of preparation and treatment with the conjugates are also disclosed.

Abstract: The present invention discloses an article orienting apparatus for use in a printing process. The apparatus includes a power roller inclined at an acute angle to the article path for wrappingly receiving an article. The article is moved from a first orientation to a second orientation. The apparatus further includes a second drum for inverting the moving articles.

Abstract: High molecular weight, water-soluble prodrugs of the formula: ##STR1## wherein: D is a biologically active moiety;M is X or Q;X is an electron withdrawing group;Q is a moiety containing a free electron pair positioned five or six atoms from Y';Y and Y' are oxygen or sulfur;R is a polyalkylene oxide; andZ is OH, C.sub.1-4 all moieties or ##STR2## are disclosed. In preferred embodiments, the prodrugs contain a polyethylene glycol having a molecular weight of at least about 20,000.

Abstract: Apparatus for heating water intended for the preparation of hot beverages, comprising a cold-water reservoir (2) for storing unheated water and a hot-water reservoir (3) for storing heated water, wherein a heat-maintaining element (4) is accommodated in the hot-water reservoir (3), wherein the hot-water reservoir (3) comprises a draw-off tap (5), and wherein a conduit (6) is connected to the cold-water reservoir (2) which conduit opens into the hot-water reservoir (3), wherein a through-flow heating element (7) is accommodated in this conduit (6).

Abstract: Corrugated box constructions suitable for packaging, storing and transporting flat rectangular objects such as books and the like. The box has an upper member and a lower member, each with a generally rectangular central panel, a pair of side panels, one of which is hingedly joined to each of the opposite ends of the central panel. Attached to each side panel of the upper member is an underlying panel and attached each side panel of the lower member is an overhanging panel. The side panels of the lower member fold upward, then the overhanging panel folds parallel to the central panel. The side panels of the upper member fold perpendicularly downward, then underlying panel folds under the central panel of the lower member. The upper member is attached to the lower member with an optional adhesive or strap. Preferably an adhesive is situated on the overhanging and underlying panels. The construction allows for packaging products of various sizes and hence greatly reduces waste.

Abstract: Taxane-based compositions of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of aryls, substituted aryls, aralkyls, substituted aralkyls, alkyls and substituted alkyls;R.sub.2 is an aryl or substituted aryl, preferably phenyl;R.sub.3 is H, a C.sub.1-10 alkoxy, SiEt.sub.3 or ##STR2## Y is O or S; (n) is zero or a positive integer;X is oxygen, S, SO.sub.2 or NL, where L is selected from the group consisting of H, C.sub.1-8 alkyls, aryls and aralkyls;R.sub.4 is H or an aroyl of the formula: ##STR3## wherein Ar is an aromatic, substituted aromatic or heteroaromatic group; R.sub.5 is H, CH.sub.3 CO or a substituted acetic acid derivative;Z is H or OR.sub.6 where R.sub.6 is selected from the group consisting of H, C.sub.1-8 alkyls, C.sub.1-8 substituted alkyls, C.sub.1-8 aralkyls, substituted aryls, aralkyls, substituted aralkyls, C.sub.1-10 alkoxy, SiEt.sub.3, ##STR4## P is O or OH; R.sub.8 is one of H, S(CH.sub.3).sub.3, Si(C.sub.2 H.sub.5).sub.3, CH.sub.

Abstract: A purified arginine deiminase (ADI) obtained from Mycoplasma arthritidis having the amino acid sequence of SEQ ID NO:2 as well as an isolated nucleic acid molecule containing a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO:1 are disclosed. Other aspects of the invention include an expression vector, a cloned gene for expressing the Mycoplasma arthritidis derived ADI, (recombinant) host cells useful in expressing the ADI of the present invention and substantially non-antigenic polymer conjugates containing the ADI of the present invention as well as methods of treating arginine deiminase susceptible conditions in mammals. The arginine deiminase-polymer conjugates have high levels of retained enzyme activity and relatively long circulating lives.

Abstract: Kits and methods for measuring enzyme activities and metabolites using NADH and NADPH analogs are disclosed. The analogs have extended stability in aqueous solutions and can used as replacements for NADH or NADPH cofactors in analytical procedures. Preferred aspects of the invention include kits containing the NADH and NADPH analogs for use in the measurement of ALT activity, AST activity, Urea, Ammonia, Salicylate, Triglycerides, Pyruvic Acid, Sorbitol Dehydrogenase activity, 5'-Nucleotidase activity, Creatine Kinase activity, 2,3-Diphosphoglyceric Acid, Adenosine 5'-triphosphate, .alpha.-Hydroxybutyrate Dehydrogenase activity, Lactate Dehydrogenase activity and the Carbon Dioxide content in analytical samples.

Abstract: The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifloroacetic acid. The resultant polymer carboxylic acids are of sufficient plurty so that expensive and time consuming purification steps required for pharmaceutical grade polymers are avoided.

Abstract: Substantially non-antigenic polymers containing pI and/or pH optimum modulating moieties are disclosed. The polymers are useful as intermediates for synthesis of amine-based polymers and in the formation of activated polymers for conjugation with nucleophiles. Conjugates and methods of preparation and treatment with the conjugates are also disclosed.

Abstract: The present invention is directed to methods of treating CD4+ T cell lymphopenia in HIV-infected patients. The methods include administering an effective mount of adenosine deaminase or related enzymatic material to a patient in need thereof. In preferred aspects of the invention, the method is employed in conjunction with HIV-infected patients having CD4+ T cell levels of less than about 200/.mu.l. Effective amounts of the enzyme range from about 5 to about 50 IU/kg/week. In one particularly preferred aspect of the invention, the adenosine deaminase is conjugated to one or more strands of polyethylene glycol to prolonged activity in vivo.