Abstract: A mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may lower serum calcium levels in a subject by 10, 15 or even 20 percent or more. Moreover, the mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin. The compositions of this invention are useful in the treatment of various bone disorders and pain.

Abstract: A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.

Abstract: Methods of treating diabetes mellitus in a patient in need of such treatment include administering an effective amount of an insulin polypeptide-oligomer conjugate of formula V to the patient in order to treat diabetes mellitus in the patient. Methods according to the present invention may “activate” the liver, potentially restoring normal glucose homeostasis to individuals suffering from diabetes mellitus.

Abstract: Methods of treating diabetes mellitus in a patient in need of such treatment include administering an effective amount of an insulin drug to the patient in order to treat diabetes mellitus in the patient. Methods according to the present invention may “activate” the liver, potentially restoring normal glucose homeostasis to individuals suffering from diabetes mellitus.

Abstract: A mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may lower serum calcium levels in a subject by 10, 15 or even 20 percent or more. Moreover, the mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin. The compositions of this invention are useful in the treatment of various bone disorders and pain.

Abstract: The invention relates to a fuel charging system having pressure pulsation damping. The fuel charging system includes a first side rail connected to a second side rail by a crossover tube. Defined within the crossover tube are first and second passageways; the first passageway including a restricted flow section therein.

Abstract: The present invention provides amphiphilic prodrugs comprising a therapeutic compound conjugated to an PEG-oligomer/polymer and methods for using said prodrugs to enable oral drug delivery and/or delivery of drugs across the blood brain barrier into the central nervous system.

Abstract: Methods of synthesizing a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties include: reacting a substantially monodispersed mixture of compounds having the structure of Formula I: R1(OC2H4)n—O?X+ ??(I) wherein R1 is H or a lipophilic moiety; n is from 1 to 25; and X+ is a positive ion, with a substantially monodispersed mixture of compounds having the structure of Formula II: R2(OC2H4)m—OMs ??(II) wherein R2 is H or a lipophilic moiety; and m is from 1 to 25, under conditions sufficient to provide a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties and having the structure of Formula III: R2(OC2H4)m+n—OR1 . ??(III) Substantially monodispersed mixtures of polymers comprising polyethylene glycol moieties are also disclosed.

Abstract: A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.

Abstract: A mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may lower serum calcium levels in a subject by 10, 15 or even 20 percent or more. Moreover, the mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin.

Abstract: Methods of treating diabetes mellitus in a patient in need of such treatment include administering an effective amount of an insulin drug to the patient in order to treat diabetes mellitus in the patient. Methods according to the present invention may “activate” the liver, potentially restoring normal glucose homeostasis to individuals suffering from diabetes mellitus.

Abstract: The present invention relates to amphiphilic drug-oligomer conjugates capable of traversing the blood-brain barrier (“BBB”) and to methods of making and using such conjugates. An amphiphilic drug-oligomer conjugates comprise a therapeutic compound conjugated to an oligomer, wherein the oligomer comprises a lipophilic moiety coupled to a hydrophilic moiety. The conjugates of the invention further comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, etc., and prodrugs, precursors, derivatives and intermediates thereof, chemically coupled to amphiphilic oligomers.

Abstract: The present invention relates to amphiphilic drug-oligomer conjugates capable of traversing the blood-brain barrier (“BBB”) and to methods of making and using such conjugates. An amphiphilic drug-oligomer conjugates comprise a therapeutic compound conjugated to an oligomer, wherein the oligomer comprises a lipophilic moiety coupled to a hydrophilic moiety. The conjugates of the invention further comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, etc., and prodrugs, precursors, derivatives and intermediates thereof, chemically coupled to amphiphilic oligomers.

Abstract: The present invention relates to amphiphilic drug-oligomer conjugates capable of traversing the blood-brain barrier (“BBB”) and to methods of making and using such conjugates. An amphiphilic drug-oligomer conjugate comprises a therapeutic compound conjugated to an oligomer, wherein the oligomer comprises a lipophilic moiety coupled to a hydrophilic moiety. The conjugates of the invention further comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, etc., and prodrugs, precursors, derivatives and intermediates thereof, chemically coupled to amphiphilic oligomers.

Abstract: A non-polydispersed mixture of conjugates in which each conjugate in the mixture comprises a drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may result in less inter-subject variability than polydispersed mixtures of similar conjugates.

Abstract: Methods of synthesizing a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties include: reacting a substantially monodispersed mixture of compounds having the structure of Formula I: R1(OC2H4)n—O−X+  (I) wherein R1 is H or a lipophilic moiety; n is from 1 to 25; and X+ is a positive ion,  with a substantially monodispersed mixture of compounds having the structure of Formula II: R2(OC2H4)m—OMs  (II) wherein R2 is H or a lipophilic moiety; and m is from 1 to 25, under conditions sufficient to provide a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties and having the structure of Formula III: R2(OC2H4)m+n—OR1  (III).

Abstract: Drug-oligomer conjugates and pharmaceutical compositions prepared therefrom. Methods of making and using the drug-oligomer conjugates and pharmaceutical compositions.

Abstract: Mixtures of conjugates in which each conjugate in the mixture comprises a growth hormone drug coupled to an oligomer that includes a polyalkylene glycol moiety wherein the mixtures have a molecular weight distribution with a standard deviation of less than about 22 Daltons are disclosed. Methods of treating growth hormone deficiency in a subject in need of such treatment and methods of accelerating the growth rate of an animal arc also disclosed. Processes for synthesizing substantially monodispersed mixtures of conjugates wherein each conjugate comprises a growth hormone drug coupled to an oligomer that comprises a polyethylene glycol moiety are further provided.

Abstract: A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.

Abstract: Methods of synthesizing a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties include: reacting a substantially monodispersed mixture of compounds having the structure of Formula I: R1(OC2H4)n—O−X+  (I) wherein R1 is H or a lipophilic moiety; n is from 1 to 25; and X+ is a positive ion, with a substantially monodispersed mixture of compounds having the structure of Formula II: R2(OC2H4)m—OMS  (II) wherein R2 is H or a lipophilic moiety; and m is from 1 to 25, under conditions sufficient to provide a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties and having the structure of Formula III: R2(OC2H4)m+n—OR1  (III). Substantially monodispersed mixtures of polymers comprising polyethylene glycol moieties are also disclosed.