Protein Polymer Technologies, Inc.

University of Utah Research Foundation

Genelux Corporation

Protein Polymer

Protien Polymer Technologies, Inc.

Joseph Cappello

Franco A Ferrari

Erwin R Stedronsky

John W Crissman

Charles Richardson

Thomas J Pollock

James Chambers

Hamidreza Ghandehari

Stuart C Causey

Mark Martin Jensen

Azadeh Poursaid

Aladar A Szalay

Glenn D Prestwich

Nanhai G Chen

Boris Minev

Wanjian Jia

Siam Oottamasathien

Garret Textor

Joshua Gustafson

Robert Andrew Price

Hamid Ghandehari

Richard J Aguilar

Jordan Frandsen

Tina L Buerkle

Mary A Dorman

Khaled Greish

Described herein are in situ gelling compositions. The compositions include an anti-inflammatory polysaccharide and a gelling polymer, wherein the composition is a liquid prior to administration to a subject but converts to a gel upon administration to the subject. The compositions described herein have numerous applications with respect to the local treatment (reduction or prevention) of inflammation and/or tissue damage.

In situ gelling compositions for the treatment or prevention of inflammation and tissue damage

Methods for producing viruses from adherent cells are provided. The methods include releasing virus from adherent host cells grown in a bioreactor, and purifying released virus by ultrafiltration and/or diafiltration. The methods can be used to manufacture viruses, including for clinical use, at reduced cost relative to conventional virus manufacturing methods.

Bioreactor production of virus from adherent cells

Described herein are chemoembolic compositions and agents. The compositions include one or more anti-cancer agents and a silk-elastinlike protein polymer, wherein the compositions are liquids prior to administration to a subject but convert to hydrogels upon administration to the subject. Administration of the chemoembolic compositions to tumor and/or tumor vasculature in a subject having cancer can result in reduced or inhibited blood flow to the tumor as well as localized, sustained release of the anti-cancer agent in the vicinity of the tumor. Reduction in blood flow, in turn, results in a reduction of tumor volume and/or inhibition of tumor growth, while localized release of the anti-cancer agent results in reduced systemic effects and lower overall toxicity of treatment with the compositions.

Methods for producing chemoembolic agents for the delivery of anti-cancer agents

A delivery system that includes a recombinantly synthesized protein polymer with protease cleavage sites such as matrix metalloproteinase responsive sequences engineered within the protein polymer. The system may be used to treat cancer, wounds, or pathological conditions in other tissues that express excess protease relative to healthy tissue.

Matrix metalloproteinase cleavable protein polymers for cancer gene therapy

Provided are adjunct therapies for use in combinations and compositions with an oncolytic virus, such as a vaccinia virus. The adjunct therapies include co-administration and co-formulation of a complement inhibitor and/or a lipid emulsion composition with the oncolytic virus. Also provided herein are therapeutic methods using the adjunct therapies for treatment of disease and conditions employing an oncolytic therapeutic virus, such as for the treatment of hyperproliferative diseases or conditions including tumors or cancers.

Oncolytic virus adjunct therapy with agents that increase virus infectivity

A chemoembolic agent is disclosed that includes an injectable, recombinantly synthesized silk-elastin like protein copolymer and one or more chemotherapeutic agents. Upon injection, the chemoembolic agent blocks the tumor vasculature, including the capillary bed, and may optionally release chemotherapeutic agents. The chemoembolic agent may be used to treat cancer, including hepatocellular carcinoma.

Silk-elastin like protein polymers for embolization and chemoembolization to treat cancer

Novel polypeptides comprising repetitive units of amino acids, as well as synthetic genes encoding the subject polypeptides are provided. The subject polypeptides are characterized by comprising repetitive units of amino acids, where the repetitive units are present in naturally occurring proteins, particularly naturally occurring structural proteins. The subject polypeptides find use in a variety of applications, such as structural components of prosthetic devices, synthetic fibers, and the like.

Peptides comprising repetitive units of amino acids and DNA sequences encoding the same

Proteinaceous polymers having repetitive units from naturally occurring structural proteins are employed as backbones for functionalities for crosslinking to provide strongly adherent tissue adhesives and sealants. Particularly, block copolymers of elastin and fibroin are employed having lysine substitutions in spaced apart units, where the amino group can be crosslinked using difunctional crosslinking agents.

Adhesion and sealing of tissue with compositions containing polyfunctional crosslinking agents and protein polymers

Proteinaceous polymers having repetitive units from naturally occurring structural proteins are employed as backbones for functionalities for crosslinking to provide strongly adherent tissue adhesive compositions for bonding together separated tissue, and for sealing or filling tissue defects by injecting the compositions into the defects. Particularly, block copolymers having repeating units of elastin and fibroin are employed having lysine substitutions in spaced apart units, where the amino group can be crosslinked using difunctional crosslinking agents such as glutaraldehyde, activated diolefins, diisocyanates, acid anhydrides or diamines. The protein polymer contains at least 40 weight percent of repetitive units of 3 to 30 amino acids, preferably 3 to 15 amino acids, of at least one naturally occurring structural protein and at least two amino acids containing a functional group capable of reacting with the crosslinking agent. The protein polymer generally has a molecular weight of at least about 30 kD and not more than 250 kD. A preferred protein polymer contains at least 70 weight percent of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser and Gly-Val-Gly-Val-Pro, where in at least two units an amino acid is substituted with one of lysine or arginine, and the protein polymer has a lysine and arginine equivalent weight in the range of 1 to 20 kD and contains at least two amino acids having a functional group capable of reacting with at least one of aldehyde, isocyanate, thioisocyanate and activated carboxy. The protein polymer is produced by recombinant DNA technology, and a kit may be formed containing the crosslinking agent and protein polymer.

Sealing or filling tissue defects using polyfunctional crosslinking agents and protein polymers

Method and compositions are provided which are useful for delivering a biologically active substance to a localized site in vivo and for altering the physical dimensions of a body tissue. These method and compositions employ protein polymers having varying ratios of elastin-like collagen-like, keratin-like repeating units and repeating units which promote protein crystallization such as silk-like repeating units. By varying the length of segments of the repeating units and/or the concentration of the protein polymers in the composition, the rate of delivery of a biologically active substance to a localized site can be greatly varied. Moreover, because the compositions are capable of acquiring a non-liquid form under normal physiological conditions, they find use as biocompatible tissue augmentation products.

Synthetic proteins for in vivo drug delivery and tissue augmentation

Novel polymers are provided which are produced by recombinant techniques. The polymers are characterized by having a small repeating sequence which provides for strands capable of associating, resulting in useful structural characteristics, where the strands are joined by turns or loops which are flexible and available for interaction with the environment. Specifically, repeating groups of naturally occurring proteins such as silk are modified by introduction of an amino-acid sequence at a site which provides for a turn between strands to provide for readily available oligopeptides capable of interacting with molecules in the environment.

Functional recombinantly prepared synthetic protein polymer

Proteinaceous polymers having repetitive units from naturally occurring structural proteins are employed as backbones for functionalities for crosslinking to provide strongly adherent tissue adhesives and sealants. Particularly, block copolymers having repeating units of elastin and fibroin are employed having lysine substitutions in spaced apart units, where the amino group can be crosslinked using difunctional crosslinking agents. The protein polymer contains at least 40 weight percent of repetitive units of 3 to 30 amino acids of at least one naturally occurring structural protein and at least two functional groups capable of reacting with a crosslinking agent to form a strongly adherent adhesive composition for bonding together separated tissue or for sealing tissue defects. A preferred adhesive composition contains glutaraldehyde or polymethylene diisocyanate and a protein block copolymer of at least 30 kD containing at least 70 weight percent of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser and Gly-Val-Gly-Val-Pro, where in at least two units an amino acid is substituted with one of lysine or arginine, and the copolymer has a lysine and arginine equivalent weight in the range of 3 to 15 kD. The protein polymer is produced by recombinant DNA technology, and a kit may be formed containing the crosslinking agent and protein polymer.

Bonding together tissue with adhesive containing polyfunctional

Polypeptides comprising repetitive units of amino acids, as well as synthetic genes encoding the subject polypeptides are provided. The subject polypeptides are characterized by comprising repetitive units of amino acids, where the repetitive units are present in naturally occurring proteins, particularly naturally occurring structural proteins. The subject polypeptides find use in a variety of applications, such as structural components of prosthetic devices, synthetic fibers, and the like.

Growing community of inventors

San Diego, CA, United States of America

Joseph Cappello