BOULDER, CO, United States

Bolder Biotechnology, Inc.

www.bolderbio.com
BOULDER, CO, United States

Time filter

Source Type

Patent
Bolder Biotechnology, Inc., Indiana University and Medical College of Wisconsin | Date: 2016-09-19

Methods and compositions comprising hematopoietic growth factor proteins and/or protein analogs thereof and/or combinations thereof and angiotensin converting enzyme inhibitors to treat the acute and long term adverse effects of radiation exposure in subjects who have been or will be exposed to radiation are disclosed.


Methods and compositions for the use of long-acting hematopoietic factor protein analogs for accelerating hematopoietic recovery in subjects who have been or will be exposed to radiation are disclosed.


Patent
Bolder Biotechnology, Inc. | Date: 2014-04-25

Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.


Patent
Bolder Biotechnology, Inc. | Date: 2012-02-02

Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.


Patent
Bolder Biotechnology, Inc. | Date: 2013-05-03

The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby. Also disclosed are therapeutic methods for using the cysteine variants of the invention.


Patent
Bolder Biotechnology, Inc. | Date: 2015-01-15

The present invention relates to novel methods of making soluble proteins having free cysteines in which a host cell is exposed to a cysteine blocking agent. The soluble proteins produced by the methods can then be modified to increase their effectiveness. Such modifications include attaching a PEG moiety to form pegylated proteins.


Patent
Bolder Biotechnology, Inc. | Date: 2013-11-25

Disclosed is a method for refolding a protein or peptide that does not contain essential disulfides and that contains at least one free cysteine residue. Also disclosed are polymer IFN- conjugates that have been created by the chemical coupling of polymers such as polyethylene glycol moieties to IFN-, particularly via a free cysteine in the protein. Also disclosed are analogs of bioactive peptides that may be used to create longer acting versions of the peptides, including analogs of glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, Gastric inhibitory peptide (GIP), PYY, exendin, ghrelin, gastrin, amylin, and oxyntomodulin.


Patent
Bolder Biotechnology, Inc. | Date: 2013-11-25

The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby.


Patent
Bolder Biotechnology, Inc. | Date: 2016-02-22

Disclosed is a method for refolding a protein or peptide that does not contain essential disulfides and that contains at least one free cysteine residue. Also disclosed are polymer IFN- conjugates that have been created by the chemical coupling of polymers such as polyethylene glycol moieties to IFN-, particularly via a free cysteine in the protein. Also disclosed are analogs of bioactive peptides that may be used to create longer acting versions of the peptides, including analogs of glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, Gastric inhibitory peptide (GIP), PYY, exendin, ghrelin, gastrin, amylin, and oxyntomodulin.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 3.20M | Year: 2013

DESCRIPTION provided by applicant Development of radiological nuclear medical countermeasures to treat Acute Radiation Syndrome ARS is a high priority research area for NIAID Bone marrow is one of the most sensitive tissues to radiation damage and impaired hematopoiesis is one of the first clinical signs of excessive radiation exposure often resulting i death Granulocyte colony stimulating factor G CSF is a kDa protein that stimulates bone marrow cells to divide and differentiate into neutrophils Recombinant human G CSF is widely used to treat chemotherapy related neutropenia in cancer patients and recent studies indicate that it improves overall survival in animal models of ARS although the drug requires daily administration which may not be possible following a radiological nuclear disaster G CSF has a short half life in humans which necessitates daily dosing for two weeks or more and may not optimize therapeutic benefits of the protein for patients Long acting G CSF analogs that do not require frequent dosing could provide significant treatment advantages in a nuclear emergency setting where healthcare provider time will be at a premium and daily dosing of patients may not be possible We developed a rationally designed long acting G CSF analog through site specific chemical modification of the protein with polyethylene glycol PEG Our long acting PEG G CSF analog has a fold half life than unmodified G CSF and is significantly more effective than G CSF at accelerating neutrophil recovery in chemotherapy treated rats Studies performed during the Phase I SBIR grant demonstrated the utility of this novel long acting G CSF analog for improving survival in a well characterized mouse ARS model In contrast to G CSF our long acting G CSF analog required only a single administration to be effective Notably mice of lethally irradiated mice treated h post irradiation with a single administration of this long acting G CSF analog survived days compared to a mortality rate of mice for vehicle treated mice Our long acting G CSF analog also improved survival compared to placebo following multiple injections into irradiated mice Irradiated mice treated with our long acting G CSF analog showed accelerated recovery of neutrophils red blood cells and platelets compared to vehicle treated mice indicating that the protein positively affected recovery of multiple blood cell types The Phase II grant has three major goals First we will perform additional studies in irradiated mice to determine how long after irradiation the drug can be administered and still improve survival Second we will determine whether the protein improves survival of lethally irradiated non human primates which is the gold standard ARS model adopted by the FDA Third we will measure the safety profile and pharmacokinetic properties of the protein in IND enabling GLP animal pharmacology and toxicology studies in order to identify safe doses of the drug for testing in humans Our novel G CSF analog will provide physicians with an effective and convenient therapy for the treatment of all of the major hematopoietic complications of ARS and improve survival of subjects exposed to high radiation doses as a result of a radiological nuclear disaster The fact that the drug requires only a single administration for effectiveness represents a significance advance in the treatment of ARS and will optimize healthcare provider time in a radiological nuclear emergency setting where patient numbers are expected to overwhelm available healthcare resources The drug should prove useful for treating other diseases for which G CSF is used as a therapy such as neutropenia resulting from chemotherapy use in cancer patients PUBLIC HEALTH RELEVANCE Development of radiological nuclear medical countermeasures to treat Acute Radiation Syndrome ARS is a high priority research area for NIAID The Phase I SBIR studies showed that our long acting G CSF analog significantly improved survival of lethally irradiated mice compared to a placebo Unlike G CSF which is administered daily for days following radiation exposure our long acting G CSF analog was effective when administered only once Improved survival of irradiated mice treated with our long acting G CSF analog correlated with accelerated recovery of multiple blood cell types including neutrophils red blood cells and platelets which is a novel finding The primary goals of this Phase II SBIR grant are to demonstrate the feasibility of using this novel long acting G CSF analog to improve survival in a non human primate ARS model determine how long after radiation exposure the drug can be administered and still provide a survival benefit and complete IND enabling animal toxicology studies required by the FDA to begin testing the protein in human safety studies and pivotal animal ARS studies Our long acting G CSF analog will prove useful for improving survival of humans exposed to an otherwise lethal dose of radiation as a result of a radiological nuclear disaster The long half life of the drug will allow patients to be treated only once with the drug which will optimize healthcare provider time in a radiological nuclear emergency setting The drug should prove useful for treating other diseases for which G CSF is used as a therapy such as neutropenia resulting from chemotherapy use in cancer patients

Loading Bolder Biotechnology, Inc. collaborators
Loading Bolder Biotechnology, Inc. collaborators