Nektar Therapeutics

Nektar Therapeutics Al, Corporation

Shearwater Corporation

Shearwater Polymers, Inc.

Naktar Therapeutics

Antoni Kozlowski

Samuel P McManus

Xiaoming Shen

J Milton Harris

Michael David Bentley

Sean M Culbertson

Remy F Gross, Iii

Brian Bray

Jennifer A Riggs-Sauthier

Stephen A Charles

Tony L Sander

Timothy A Riley

Wen Zhang

Jon McKannan

Zhihao Fang

Tracy L Hutchison

Anthony G Schaefer

John R Handley

Michael James Roberts

Lihong Guo

Tony Drew Vinson

Ryan Odom

Xuejun Yuan

YongQi Mu

Neel Kumar Anand

Bo-Liang Deng

Zhongxu Ren

Pankaj Sharma

Natalia Aurrecoechea

Donogh John Roger O'Mahony

Xuyuan Gu

Yuan Song

Dennis G Fry

Mark A Wilson

Seoju Lee

Bhalchandra V Joshi

Patrick Spence

Vijay Kumar Khatri

Michael Lixin Shen

Patrick D Youso

Daniel C Cook

Greg Lavaty

Sachin Tipnis

Aleksandrs Odinecs

David Swallow

Dawei Sheng

Patrick L Spence

Shaoyong Nie

Anthony O Chong

Vidula R Dixit

Venkata Ravidnranadh Somu

John McKannan

Samual Mcmanus

Jon Mckannan

Remy F Iii Gross

Vidula Dixit

Samuel Mcmanus

Milton J Harris

Xioaming Shen

Remy F Gross

Samuel P Mcmanus

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-sunitinib conjugates and related compounds. A compound of the invention, when administered by any of a number of administration routes, exhibits advantages over sunitinib in unconjugated form.

Polymer-sunitinib conjugates

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

Methods for preparing water soluble, non-peptidic polymers carrying carboxyl functional groups, particularly carboxylic acid functionalized poly(ethylene glycol) (PEG) polymers are disclosed, as are the products of these methods. In general, an ester reagent R(C&#x2550;O)OR', wherein R&#x2032; is a tertiary group and R comprises a functional group X, is reacted with a water soluble, non-peptidic polymer POLY-Y, where Y is a functional group which reacts with X to form a covalent bond, to form a tertiary ester of the polymer, which is then treated with a strong base in aqueous solution, to form a carboxylate salt of the polymer. Typically, this carboxylate salt is then treated with an inorganic acid in aqueous solution, to convert the carboxylate salt to a carboxylic acid, thereby forming a carboxylic acid functionalized polymer.

Method of preparing carboxylic acid functionalized polymers

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

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

Multi-arm polymeric prodrug conjugates of cabazitaxel-based compounds

The instant disclosure relates to (among other things) compounds that are derivatives of 6-(2,3-dichlorophenyl)-1,2,4-triazin-5-amine. The compounds provided possess unique effects and differences over other phenyltriazines known in the art.

Derivatives of 6-(2,3-dichlorophenyl)-1,2,4-triazin-5-amine

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Huntsville, AL, United States of America

Antoni Kozlowski