The United States of America As Represented by the Department of Health

Exponential Biotherapies, Inc.

National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Secretary of

Monoclonetics International, Inc.

Panacea Pharmaceuticals, Inc.

The Government of the United States of America, As Represented by the

Other

Virxsys Corporation

Carl R Merril

Sankar L Adhya

Richard M Carlton

Hossein A Ghanbari

Bruce M Cameron, Sr

Dale VanderPutten

Guy J Creed

Mihael Hristos Polymeropoulos

Lloyd G Mitchell

Biswajit Biswas

Mihael H Polymeropoulos

Denis Francois Hochstrasser

Michael G Harrington

David Goldman

Edward Otto

Richard E Warrington

D Carleton Gajdusek

Dean Scholl

Ginger Johnson

Michael H Polymeropoulos

Abbas A Khan

David M Asher

The present invention encompasses a cancer vaccine therapy targeting Aspartyl-[Asparaginyl]-,8-hydroxylase (HAAH). The present invention contemplate bacteriophage expressing HAAH peptide fragments and methods for using said bacteriophage in methods of treating cancer.

Therapeutic cancer vaccine targeted to HAAH (aspartyl-[asparaginyl]-beta-hydroxylase

The present invention encompasses a cancer vaccine therapy targeting Aspartyl-[Asparaginyl]-&#x3b2;-hydroxylase (HAAH). The present invention contemplate bacteriophage expressing HAAH peptide fragments and methods for using said bacteriophage in methods of treating cancer.

Therapeutic cancer vaccine targeted to HAAH (aspartyl-[asparaginyl]-&#x3b2;-hydroxylase)

The invention is related to the treatment of prion-related diseases such as the transmissible spongiform encephalopathies (TSEs) in mammals by administering chaotropic agents to or inducing a hyperthermia state in the affected mammals.

Methods of treating prion disease in mammals

The present invention provides methods and compositions for conferring selective death on cells expressing a specific target precursor messenger RNA (selective target pre-mRNA). The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) expressed within a cell and mediate a trans-splicing reaction resulting in the generation of a novel chimeric mRNA molecule (chimeric mRNA) capable of encoding a light producing protein or enzyme. Cell death is further mediated by the presence of a photosensitizer which upon photoactivation produces cytotoxicity.

Trans-splicing mediated photodynamic therapy

The present invention is directed to bacteriophage therapy, using methods which enable the bacteriophage to delay inactivation by any and all parts of the host defense system (HDS) against foreign objects. The HDS normally reduces the number of bacteriophage in an animal, which decreases the efficiency of the bacteriophage in killing the host bacteria present during an infection. Disclosed is a method of producing bacteriophage modified for anti-HDS purposes by physico-chemical alteration of the bacteriophage surface proteins, so that the altered bacteriophage remain active in the body for longer periods of time than the unmodified bacteriophage.

Antibacterial therapy with bacteriophage physico-chemically altered by pegylation to delay inactivation by the host defense system

The present invention discloses compositions and methods for the prophylaxis and treatment of bacterial infections by the use of polyvalent bacteriophage having multiple host range.

Bacteriophage having multiple host range

The invention relates to a biomolecular complex comprising a target biomolecule; a phage having a phage-expressed binding protein that can bind to the target biomolecule or having joined thereto a linked or un-linked protein or nucleic acid that can bind to the target biomolecule, wherein the phage-expressed binding protein or the linked or unlinked protein or nucleic acid is bound to the target biomolecule to provide a bound phage; and a host bacterial cell that is a host for the phage under conditions that permit the bound phage to infect the host.

High sensitivity phage display biomolecule detection

The invention relates to polymorphic markers (two tetranucleotide, one dinucleotide repeat polymorphisms, 27 markers characterized by primer pairs 1A-27A, and eleven markers characterized by primer pairs 1B-11B that are useful for human individualization. Applications are in forensic medicine and for paternity and prenatal screening as well as genetic mapping. These markers are characterized by sets of oligonucleotide primers according to the invention useful in PCR amplification and DNA segment resolution. The invention further relates to an assay for measuring the subtle differences in genetic material regarding an added or omitted set of dinucleotide or tetranucleotide repeat polymorphisms which comprises obtaining an amount of nucleotide segments effective for testing, amplifying the segments by the PCR procedure using at least one primer nucleotide sequence according to the present invention, resolving the amplified segments using gel electrophoresis, and comparing the resolved segments by autoradiography to observe the differences in migration patterns due to structural differences. The assay according to the invention is easy to perform and results can be obtained within 24 hours. It is not uncommon for results to be available within 3-4 hours. Accordingly, the invention also relates to an improved PCR procedure and a PCR assay kit which comprise nucleotides according to the invention.

Eleven highly informative microsatelite repeat polymorphic DNA markers

Methods of diagnosing peripheral nerve damage, including diagnosing and monitoring chronic back and cervical pain are disclosed. The methods involve subjecting a body fluid sample from a patient suspected of having chronic lumbar or cervical pain and peripheral nerve damage to two-dimensional electrophoresis or an immunoassay and measuring relative amounts of protein or proteins which increase or decrease in concentration as compared to a standard control. A preferred method employs an Apo-E variant as a marker of peripheral nerve damage. Also disclosed are kits for use with the diagnostic methods.

Methods for the diagnosis of peripheral nerve damage

The invention provides a process wherein a biotinylated oligonucleotide primer and an oligonucleotide primer which has not undergone biotinylation are used when amplifying a DNA sequence to facilitate separation of the DNA strands following the polymerase chain reaction process. The biotinylation/PCR product is then exposed to a support which will selectively bind the biotinylated strand to allow selective elution of the product.

Sequencing DNA; a modification of the polymerase chain reaction

The present invention is directed to bacteriophage therapy, using methods that enable the bacteriophage to delay inactivation by any and all parts of the host defense system (HDS) against foreign objects that would tend to reduce the numbers of bacteriophage and/or the efficiency of those phage at killing the host bacteria in an infection. Disclosed is a method of producing bacteriophage modified for anti-HDS purposes, one method being selection by serial passaging of a bacteriophage, and the other method being genetic engineering of a bacteriophage, so that the modified bacteriophage will remain active in the body for longer periods of time than the wild-type phage.

Bacteriophage genotypically modified to delay inactivations by the host

The present invention is directed to bacteriophage therapy, using methods that enable the bacteriophage to delay inactivation by any and all parts of the host defense system (HDS) against foreign objects that would tend to reduce the numbers of bacteriophage and/or the efficiency of those phage at killing the host bacteria in an infection. Disclosed is a method of producing bacteriophage modified for anti-HDS purposes, one method being selection by serial passaging, and the other method being genetic engineering of a bacteriophage, so that the modified bacteriophage will remain active in the body for longer periods of time than the wild-type phage.

Antibacterial therapy with bacteriophage genotypically modified to delay

The invention relates to polymorphic markers (two tetranucleotide and one dinucleotide repeat polymorphisms) that are useful for human individualization. Applications are in forensic medicine and for paternity and prenatal screening as well as genetic mapping. These markers are characterized by sets of oligonucleotide primers according to the invention useful in PCR amplification and DNA segment resolution. The invention further relates to an assay for measuring the subtle differences in genetic material regarding an added or omitted set of dinucleotide or tetranucleotide repeat polymorphisms which comprises obtaining an amount of nucleotide segments effective for testing, amplifying the segments by the PCR procedure using at least one primer nucleotide sequence according to the present invention, resolving the amplified segments using gel electrophoresis, and comparing the resolved segments by autoradiography to observe the differences in migration patterns due to structural differences. The assay according to the invention is easy to perform and results can be obtained within 24 hours. It is not uncommon for results to be available within 3-4 hours. Accordingly, the invention also relates to an improved PCR procedure and a PCR assay kit which comprise nucleotides according to the invention.

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Rockville, MD, United States of America

Carl R Merril