Alpha Therapeutic Corporation

Baxter International Inc.

Plasma Technologies, LLC

Baxalta Gmbh

Charles M Heldebrant

Andrew J Conrad

Lorraine B Peddada

H Edward Matveld

John J Whalen, Iii

Peter Schmid

Charles H Davis, Jr

Kim C Crowe

George R Groveman

Michael E Chlebowski

David P Nowotnik

Dennis Curtin

Eugene J Zurlo

Shawn D Latham

Methods of producing multiple protein products from blood-based materials including alpha-1-proteinase inhibitor, gamma globulin, albumin, and other proteins are described herein. The inventive methods include steps of: salt fractionation, chromatography, ultrafiltration, diafiltration, solvent-detergent treatment, and sterile filtration. Advantageously, the inventive methods are simple and produce alpha-1-proteinase inhibitor, gamma globulin, albumin, and other proteins in high yields. The sequence of process steps can be selected to obtain multiple products from various in-process materials, such as supernatants, pastes, chromatography flow-though, and chromatography washes.

Methods for extracting proteins from a blood-based material

A method is provided for identifying viral positive biological fluid donations in the fewest number of test cycles. The method comprises providing biological fluid donations and defining an n-dimensional matrix comprising a multiplicity of elements, each element being identified by a matrix notation comprising an index for each dimension of the array. Samples are taken from each fluid donation and mapped to a matrix element with each sample identified by its corresponding element's notation; n aliquots being taken from each sample and subpools formed from the aliquots with each subpool containing an aliquot from all samples mapped to elements in which one of the dimensional indices is fixed. Subpools are tested for viral indication and the dimensional index of each subpool that returns a positive viral indication is determined. The dimensional indices are combined to identify a subset of matrix elements that contain a viral positive sample.

Efficient algorithm for PCR testing of blood samples

Systems, processes, and devices are provided which are useful for testing blood or plasma donations to detect those specific donations which are contaminated by a virus above a predetermined level. An apparatus and process is described which forms individual, separately sealed and connected sample containers from a flexible hollow tubing segment connected to a fluid donation container. The tubing segment is sealed at spaced-apart intervals along its length, with tubing segment portions in the intervals between the seals defining containers, each of which holds a portion of a plasma sample. The contents of the containers are formed into pools which are subsequently tested for virus contamination by a high-sensitivity test such as PCR. The pools are tested in accordance with an algorithm by which a sample from each donation is mapped to each element of an N-dimensional matrix or grid. Each element of the matrix is identified by a matrix identifier, X , where rcs defines the dimensional index. An aliquot is taken from each sample, and subpools are formed, each subpool comprising aliquots of samples in which one dimensional index is fixed. All of the subpools are tested in one PCR test cycle. The dimensional indicia of each positive subpool is evaluated mathematically in accordance with a reduction by the method of minors, thereby unambiguously identifying a unique element in the grid, thereby unambiguously identifying a uniquely positive blood or plasma donation.

A process is provided for preparing samples of blood, blood plasma, blood serum, or plasma proteins, including blood factor products, for PCR testing which minimizes contaminants which may interfere with the analysis. The process includes centrifugation of the initial sample to form a sample pellet, removing at least a portion of the supernatant from the pellet, and washing the pellet with an aqueous buffer. The buffer and washed pellet are then centrifuged, and a portion of the remaining supernatant is removed along with any contaminants contained therein. The clean, substantially contaminant-free pellet is then processed for PCR analysis.

Process for purification of PCR test samples

An automated system and process is provided for pooling samples from a multiplicity of blood or plasma donations for subsequent testing to uniquely identify any such blood or plasma donations which may be infected with a particular virus. The system includes an autosampler needle which is directly inserted into a blood or plasma sample aliquot container in order to withdraw an aliquot portion of the contents for forming a sample pool with aliquot portions of other blood or plasma samples. The autosampler comprises a tubular piercing member having a hollow interior bore and a tubular shroud surrounding the piercing member.

Automated method and system for testing blood samples

Systems, processes, and devices are provided which are useful for testing blood or plasma donations to detect those specific donations which are contaminated by a virus above a predetermined level. An apparatus and process is described which forms individual, separately sealed and connected sample containers from a flexible hollow tubing segment connected to a fluid donation container. The tubing segment is sealed at spaced-apart intervals along its length, with tubing segment portions in the intervals between the seals defining containers, each of which holds a portion of a plasma sample. The contents of the containers are formed into pools which are subsequently tested for virus contamination by a high-sensitivity test such as PCR The pools are tested in accordance with an algorithm by which a sample from each donation is mapped to each element of an N-dimensional matrix or grid. Each element of the matrix is identified by a matrix identifier, X.sub.rcs, where rcs defines the dimensional index. An aliquot is taken from each sample, and subpools are formed, each subpool comprising aliquots of samples in which one dimensional index is fixed. All of the subpools are tested in one PCR test cycle. The dimensional indicia of each positive subpool is evaluated mathematically in accordance with a reduction by the method of minors, thereby unambiguously identifying a unique element in the grid, thereby unambiguously identifying a uniquely positive blood or plasma donation.

Method of PCR testing of pooled blood samples

Systems, processes and devices are provided which are useful for testing blood or plasma donations to detect those specific donations which are contaminated by virus above a predetermined level. An apparatus and process is described which forms individual, separately sealed, and connected sample-containing pouches from a flexible hollow tubing segment connected to a fluid donation container. The tubing segment is sealed at spaced-apart intervals along its length, with tubing segment portions in the intervals between the seals defining pouches, each of which contains a portion of a plasma sample. The contents of the pouches are formed into pools which are subsequently tested for virus contamination by a high sensitivity test such as PCR. When a pool tests positive, indicating it is contaminated by a virus, a further pouch is removed from each of the tubing segments used to form the initial pool. Subsequent pouches are divided into approximately equal sized subgroups and their contents separately formed into subpools. A selected one of the subgroup pools is then tested for virus contamination. The test process is iterated, with each pool that tests positive being further subdivided into two successively smaller subgroups, until two final subgroups are formed, each comprising a single pouch corresponding to a single plasma donation. The final two pouches are subsequently PCR tested in order to determine and uniquely identify the corresponding contaminated donation.

Method and system for testing blood samples

Systems, processes, and devices are provided which are useful for testing blood or plasma donations to detect those specific donations which are contaminated by a virus above a predetermined level. An apparatus and process is described which forms individual, separately sealed and connected sample containers from a flexible hollow tubing segment connected to a fluid donation container. The tubing segment is sealed at spaced-apart intervals along its length, with tubing segment portions in the intervals between the seals defining containers, each of which holds a portion of a plasma sample. The contents of the containers are formed into pools which are subsequently tested for virus contamination by a high-sensitivity test such as PCR. The pools are tested in accordance with an algorithm by which a sample from each donation is mapped to each element of an N-dimensional matrix or grid. Each element of the matrix is identified by a matrix identifier, X.sub.rcs, where rcs defines the dimensional index. An aliquot is taken from each sample, and subpools are formed, each subpool comprising aliquots of samples in which one dimensional index is fixed. All of the subpools are tested in one PCR test cycle. The dimensional indicia of each positive subpool is evaluated mathematically in accordance with a reduction by the method of minors, thereby unambiguously identifying a unique element in the grid, thereby unambiguously identifying a uniquely positive blood or plasma donation.

A stable perfluorochemical emulsion is provided which comprises perfluorochemical particles in stabilized vesicles. The vesicles comprise a biocompatible polymer formed by coating the perfluorochemical particles with one or more phospholipid monomer(s) and polymerizing the monomer(s).

Perfluorochemical emulsion with stabilized vesicles

Perfluorocarbon emulsion formulations are oxygenated prior to use by means of a portable oxygenation system. The blood substitute is in a closed container or bag. An oxygen-containing gas is introduced into the bag from a separate container. The bag is continuously agitated for a sufficient time to increase the pO.sub.2 of the perfluorocarbon emulsion formulations to a desired pressure, e.g., to at least 600 mmHg. In one embodiment, the system used for oxygenation of the perfluorocarbon emulsion formulations comprises a small tank for gas having an inlet port and an outlet port fitted with shut-off valves. The outlet port is adapted to be connected to a filter which, in turn, is adapted to be connected to the inlet port of a three-way valve. The primary outlet of the three-way valve is adapted to mount a hypodermic needle which is adapted to be pushed through a rubber septum in a port of the bag to communicate with the interior of the bag. The tank is adapted to be filled with oxygen-containing gas, such as carbogen, from a main gas source under pressure. The tank, filter, three-way valve and needle arrangement are connected in series, and the oxygen-containing gas is permitted to flow from the tank into the bag holding the emulsion formulation. After the gas is introduced into the bag, the three-way valve is closed to prevent leakage of the gas from the container. The container is then agitated to oxygenate the emulsion formulation.

Apparatus for oxygenation of liquid state dissolved oxygen-carrying

Apparatus and process for oxygenation of liquid state dissolved

A process is provided for heat treating a protein powder that includes mixing the powder into an organic liquid to form a suspension and heating the suspension for a selected time at a selected temperature. Such heat treatment inactiviates any virus associated with the protein while not substantially impairing the biological activity of the protein.

Growing community of inventors

Arcadia, CA, United States of America

Charles M Heldebrant