Nektar Therapeutics

Nektar Therapeutics Al, Corporation

United States of America As Represented by the Administrator of Nasa

Naktar Therapeutics

Samuel P McManus

Antoni Kozlowski

Sean M Culbertson

Xiaoming Shen

Michael David Bentley

Remy F Gross, Iii

J Milton Harris

Stephen A Charles

Jennifer A Riggs-Sauthier

Wen Zhang

Brian Bray

Jon McKannan

Tracy L Hutchison

Timothy A Riley

Anthony G Schaefer

John R Handley

Dennis G Fry

Mark A Wilson

Daniel C Cook

Sachin Tipnis

Greg Lavaty

David Swallow

Patrick D Youso

Mary J Bossard

Donald Odell Frazier

Bhalchandra V Joshi

Seoju Lee

Dawei Sheng

Mark S Paley

Xuejun Yuan

Anthony O Chong

Shaoyong Nie

Patrick L Spence

Vidula R Dixit

David N Donovan

John McKannan

Venkata Ravidnranadh Somu

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 methods described herein, and conjugates prepared by reaction with fluorenyl-based polymeric reagents prepared by the methods described herein.

Method of making releasable polymeric reagents

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-salt acid salt is stably formed, and appears to be more resistant to hydrolytic degradation than the corresponding predominantly pure acid salt or free base forms of the polymer-drug conjugate. The mixed acid salt is reproducibly prepared and recovered, and provides surprising advantages over non-mixed acid salt forms of the water-soluble polymer drug conjugate.

Alkoxylation methods

Among other aspects, provided herein are multi-arm polymeric prodrug conjugates of taxane-based compounds and/or fluorinated forms thereof. Methods of preparing such conjugates as well as methods of administering the conjugates are also provided. Upon administration to a patient, release of the taxane-based compound is achieved.

Multi-arm polymeric prodrug conjugates of taxane-based compounds

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 with high drug loading efficiencies.

Multi-arm polymeric alkanoate conjugates

Provided herein are polymeric &#x3b1;-hydroxy aldehyde or &#x3b1;-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the &#x3b1;-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

Polymeric alpha-hydroxy aldehyde and ketone reagents and conjugation method

Polymeric reagents are provided comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

Polymer derivatives having particular atom arrangements

The invention relates to (among other things) polymer-des-ethyl sunitinib conjugates and related compounds. A compound of the invention, when administered by any of a number of administration routes, exhibits advantages over des-ethyl sunitinib in unconjugated form.

Polymer-des-ethyl sunitinib conjugates

The present invention provides conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates. The conjugates as well as the polymeric reagents used to form the conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods of making polymeric reagents and conjugates, as well as methods for administering conjugates and compositions, are also provided.

Conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates

The present invention provides, among other things, compounds that include a water-soluble and non-peptidic polymer as well as a maleimidyl group. The compounds are useful as, among other things, polymeric reagents.

Methods for preparing functionalized polymers from polymer alcohols

Composition comprising a polymeric reagent

Methods for preparing active carbonate esters of water-soluble polymers are provided. Also provided are other methods related to the active carbonate esters of water-soluble polymers, as well as corresponding compositions.

Methods for preparing polymeric reagents and compositions of polymeric reagents

Growing community of inventors

Huntsville, AL, United States of America

Samuel P McManus