Methods, systems, and devices are described for creating a negative bias pressure within a liquid reservoir. Embodiments may include providing a liquid reservoir coupled with an aerosol generator. The liquid reservoir may be sealed to create the sealed reservoir. An ambient pressure may be maintained while the liqui...

The invention provides conjugates wherein the opioid agonists, hydroxycodone (oxycodone) and hydrocodone (di-hydrocodeinone) are covalently attached to poly(ethylene glycol) oligomers. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are diffe...

Various methods, devices, and systems are described for aerosolizing a liquid. Embodiments may include sealing the liquid within a reservoir. An output waveform signal may be generated. A nebulizer element may be vibrated to aerosolize the liquid. A negative pressure may be produced within the reservoir as the liqui...

ABSTRACT COMBINATION OF AN IL-2RBETA-SELECTIVE AGONIST AND A LONG-ACTING IL-15 AGONIST In one or more embodiments of the invention, a method is provided, the method comprising the steps of administering to a cancer patient: (a) an IL-2Rβ-activating amount of a long-acting, IL-2Rβ-selective agonist; and (b) an IL-1...

Various arrangements for determining an atomization element of a nebulizer is dry are presented. The vibratable element of the nebulizer may be energized with an electrical signal that sweeps from a first frequency to a second frequency. While energizing the vibratable element of the nebulizer with the electrical si...

Among other aspects, provided herein are multi-armed polymer conjugates comprising an alkanoate-linker, compositions comprising such conjugates, and related methods of making and administering the same. Methods of treatment employing such conjugates and related uses are also provided. The conjugates are prepared wit...

The present invention provides hydmoxyapatite-targetiing, multiarm polymer reagents suitable for reaction with biologically active agents to form conjugates, the polymeric reagents comprising one or more polymer chains and a plurality of hydroxyapatile-targeting moieties located at the terminus of one or more of the...

The invention provides opioid agonists covalently bound to a water-soluble oligomer having reduced potential for bstance abuse and uses thereof. The compounds of the invention possess altered pharmacokinetic profiles relative to the opioid agonists alone, but are not subject to the risk of physical tampering that al...

The invention provides small molecule drugs that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the small molecule drug not...

Among other aspects, provided herein is a hydrohalide salt of a multi-arm water-soluble polyethylene glycol-drug conjugate, along with related methods of making and using the same. The hydrohalide salt is stably formed, and appears to tbe more resistant to hydrolytic degradation than the corresponding free base form...

The invention relates to (among other things) method of administering to a patient suffering from a cancer the method comprising the steps of: (a) an IL 2Rß activating amount of a long acting IL 2Rß selective agonist; and (b) a CTLA 4 pathway inhibiting amount of an anti CTLA 4 antibody or a PD 1 pathway inhibitin...

Conjugates of an IL 15 moiety and one or more nonpeptidic water soluble polymers are provided. Typically the nonpeptidic water soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided among other things are compositions comprising conjugates methods of making conjugates and methods of administ...

The invention relates to (among other things) oligomer-phenothiazine conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over un-conjugated phenothiazine compounds.

The invention relates to (among other things) oligomer- aryloxy-substituted propanamine conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over un-conjugated aryloxy-substituted propanamine compounds. ...

Conjugates of a cholinesteiase moiety and one or more nonpeptidic, water soluble polymers are provided. Typically, the nonpeptidic, water soluble polymer is poly(ethvylene glycol) or a derivative thereof. Also provided, among other things, are compositions comprising conjugates, methods of making conjugates, and met...

The invention relates to (among other things) oligomer-containing substituted aromatic triazine compounds.A compound of the invention, when administered by any of a number of administration routes, exhibits one or more advantages over corresponding compounds lacking the oligomer.

This invention relates to the use of a dry powder insulin in the manufacture of a medicament for pulmonary delivery wherein the total dose of said dry powder insulin for a single respiratory administration is in the range from 0.5 to 15 mg and is effective by a human patient taking one to four breaths. The said dry ...

A method for preparing a stable, dry powder insulin composition, said method comprising: dissolving insulin in an aqueous buffer at a concentration in the range from 0,01% to 1% to form a solution; and spray drying the solution to produce substantially amorphous particles having an average size in the range fro...

A powdered, dispersible composition having stable dispersibility over time is provided. The composition exhibits a characteristic glass transition temperature (T,) and a recommended storage temperature (T,), wherein the difference between Tg and T, is at least about 10°C (i.e. Tg-Ts is greater than 10"C). The compos...

Among other aspects, provided herein is a mixed-acid salt of a water-soluble polymer-drug conjugate, along with related methods of making and using the same. The mixed-sail acid salt is stably formed, and appears to be more resistant to hydrolytic degradation than the corresponding predominantly pure acid salt or fr...

Various arrangements for determining whether a liquid is in contact with a nebulizer element are disclosed. A nebulizer element may be energized with an electrical signal at a measurement frequency. An impedance of the nebulizer element may be measured thereby obtaining a measured impedance value. The impedance valu...

ALKOXYLATION METHODS The present invention relates to a method comprising the step of alkoxylating in a suitable solvent a previously isolated alkoxylatable oligomer to form an alkoxylated polymeric material, wherein the previously isolated alkoxylatable oligomer has a known and defined weight-average molecular wei...

The invention provides antihistamine drugs that are chemically modified by covalent attachment of a water-solub oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the antihistamine drug not att...

The invention provides compounds that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from those of the compound not attached to the water-soluble oligom...

A pharmaceutical formulation for pulmonary administration comprises particulatcs comprising an active agent particle in a lipid matrix, the active agent having a solubility in water of less than 1.0 mg/ml. In one version, at least 90% of the active agent particles in the pharmaceutical formulation have a geometric d...

The invention provides small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the small molecule drug not attached to the water-...

Abstract COMPOSITIONS AND METHODS FOR ACHIEVING SUSTAINED THERAPEUTIC DRUG CONCENTRATIONS IN A SUBJECT Provided herein are compounds and methods for achieving a sustained therapeutic effect of small molecule anti-cancer agents when administered in vivo.

The invention relates to a conjugate comprising a calcimetic  including cinacalcet  covalently attached via a linkage to a water-soluble  non-peptidic oligomer or polymer  preferably to poly (ethylene glycol).

Conjugates of an IL 7 moiety and one or more nonpeptidic water soluble polymers are provided. Typically the nonpeptidic water soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided among other things are compositions comprising conjugates methods of making conjugates and methods of administe...

Provided are multi-arm polymer conjugates of Toll-Like Receptor ("TLR") agonists such as TLR 7/8 agonists as well as related compositions and methods of making and using such conjugates. Exemplary conjugates are encompassed by Formula I: (I) or a pharmaceutically acceptable salt form thereof where R taken together w...

The instant disclosure provides a long acting IL-15 receptor agonist, related compositions and methods of preparation and use, for example, in the treatment of conditions responsive to therapy effective to provide, for example, sustained immune activation and/or anti-tumor activity.

The instant disclosure provides a combination treatment, composition and kit comprising (a) a long-acting IL-15 receptor agonist and (b) one or more antibodies (mAb) targeting a tumor antigen, related methods of preparation and use, for example, in the treatment of conditions responsive to therapy effective to provi...

The instant disclosure provides (among other things) improved methods of preparing fluorenyl-based polymeric reagents, methods of recovering and purifying such polymeric reagents, methods of reducing unwanted impurities in a fluorenyl-based polymeric reagent, fluorenyl-based polymeric reagents prepared by the method...

The instant disclosure provides (among other things) improved methods of preparing fluorenyl- based polymeric reagents, methods of recovering and purifying such polymeric reagents, methods of reducing unwanted impurities in a fluorenyl-based polymeric reagent, fluorenyl- based polymeric reagents prepared by the m...