Nektar Therapeutics

Serina Therapeutics, Inc.

Serina Therapeutics (al), Inc.

Sarina Therapeutics, Inc.

Tacey Viegas

Michael David Bentley

Zhihao Fang

Kunsang Yoon

Xuan Zhao

Rebecca Weimer

J Milton Harris

Randall Moreadith

Zhongxu Ren

Bekir Dizman

Lin Cheng

Mei-chang Kuo

Richard R Goodin

Randall W Moreadith

Jennifer A Riggs-Sauthier

Mary J Bossard

Wen Zhang

David Lechuga-Ballesteros

Francesco Maria Veronese

Franco J Duarte

Xuyuan Gu

Hema Gursahani

Stewart A Thompson

Chester Leach

Yuan Song

C Simone Jude-Fishburn

Anna Mero

C Simone Fishburn

Robert J Sharpe

Ribecca Weimer

The present disclosure provides for polyoxazoline (POZ) conjugates wherein the conformation of the POZ conjugate and the release rate of an agent from the POZ conjugate can be controlled by selecting one or more characteristics of the POZ polymer. Methods of controlling the conformation of a POZ conjugate and the release rate of an agent prior are provided as well as methods of treatment using such POZ conjugates and methods. Pharmaceutical compositions comprising a POZ conjugate are also provided.

Polyoxazoline-drug conjugates with novel pharmacokinetic properties

Polyoxazoline (POZ) conjugates wherein the conformation of the POZ conjugate and the release rate of an agent from the POZ conjugate can be controlled by selecting one or more characteristics of the POZ polymer and methods of controlling the conformation of a POZ conjugate and the release rate of an agent prior are provided as well as methods of treatment using such POZ conjugates and methods. Pharmaceutical compositions including a POZ conjugate are also provided.

POZ-lipid conjugates and lipid nanoparticles (LNPs) including POZ-lipid conjugates used to facilitate delivery of an encapsulated payload. LNPs including POZ-lipid conjugates and a nucleic acid payload such as, but not limited to, mRNA or modified mRNA are disclosed. Such LNPs have no immunogenicity or reduced immunogenicity as compared to a corresponding LNP containing a PEG-lipid.

Polyoxazoline-lipid conjugates and lipid nanoparticles and pharmaceutical compositions including same

Methods of preparing monodisperse oligomer reagent compositions such as oligo(ethylene glycol) reagent compositions are described herein. The methods involve reacting a halo-terminated oligomer such as an oligo(ethylene oxide) having (m) monomers with a hydroxyl-terminated oligomer such as a hydroxyl-terminated oligo(ethylene oxide) having (n) monomers.

Methods of preparing a monodisperse oligo(ethylene glycol) reagent composition

The present disclosure provides polymer conjugates comprising a polymer and an agent the agent linked to the polymer via a linking group containing a cleavable moiety.

Subcutaneous delivery of polymer conjugates of therapeutic agents

The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.

Multifunctional forms of polyoxazoline copolymers and drug compositions comprising the same

Described are conjugates comprising a water-soluble polymer linked to a compound comprising a catechol moiety via a cleavable linkage, wherein the cleavable linkage is formed between the water-soluble polymer and a first phenolic hydroxyl group of the catechol moiety and a second phenolic hydroxyl group of the catechol moiety is linked to a blocking group wherein the rate of hydrolytic release of the compound comprising the catechol moiety is controlled, at least in part, through structure or design of the blocking group on the second phenolic hydroxyl group of the catechol moiety. Therefore, the rate of hydrolytic release of the compound comprising the catechol moiety can be tuned through structural design of the group on the second phenolic hydroxyl group of the catechol moiety. Compounds used in the synthesis of the described conjugates and methods of using the described conjugate and other compounds in the treatment of dopamine-responsive disorders are also described.

Cleavable conjugates of catechol compounds and water-soluble polymers and methods of treatment using the same

The present disclosure provides polymer conjugates comprising a polymer and an agent, the agent linked to the polymer via a linking group containing a cleavable moiety.

Subcutaneous delivery of polymer conjugates of therapeutics agents

The present disclosure provides polymer conjugates comprising a polymer and an agent, the agent linked to the polymer via a linking group containing a hydrolyzable moiety.

Subcutaneous delivery of poly(oxazoline) polymer conjugates

Methods of modifying the rate of systemic absorption of a drug administered to a subject by a pulmonary route, the method comprising covalently conjugating a hydrophilic polymer to a drug, wherein the drug has a half-life of elimination from the lung of less than about 180 minutes, to form a drug-polymer conjugate, wherein the drug-polymer conjugate has a net hydrophilic character and a weight average molecular weight of from about 50 to about 20,000 Daltons, and wherein the half-life of elimination from the lung of the drug-polymer conjugate is at least about 1.5-fold greater than the half-life of elimination from the lung of the drug, wherein the half-life of elimination from the lung is measured by bronchioalveolar lavage followed by assaying residual lung material.

Chemically modified small molecules

In the present disclosure, polymer conjugates, including polymer-antibody-drug conjugates (polymer ADCs) are described, as well as the use of such conjugates to treat human disease. The polymer conjugates can contain a large number of polymer-bound agents, thus effectively increasing the drug antibody ration (DAR) of the antibody significantly beyond the currently available technology. This may be of particular importance when antibodies to low density antigens are used as target antibodies. The described polymer-ADCs have improved pharmacokinetics and solubility relative to traditional ADCs. The linker between agent and the polymer can be tailored to provide release of toxin at the desired site and under the desired conditions within the tumor. An additional feature of the polymer-ADCs of the current disclosure is that a purification moiety can be attached to the polymer backbone to provide ease of purification of the polymer-ADCs.

Polyoxazoline antibody drug conjugates

The present disclosure provides POZ derivatives having a range of active functional groups allowing conjugation of POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives. In one embodiment, the POZ derivative is a terminally activated monofunctional POZ derivative.

Activated polyoxazolines and conjugates and compositions comprising the same

Provided herein are water-soluble prodrugs, compositions comprising such prodrugs, and related methods of making and administering the same. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are typically covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water-soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.

Growing community of inventors

Madison, AL, United States of America

Tacey Viegas