Other

Valigen (US), Inc.

Dnx Biotherapeutics

Onconova Therapeutics, Inc.

Kimeragen, Inc.

Ramesh Kumar

Ajay K Sharma

Richard A Metz

John S Logan

Sunita Midha

Clara Paulhiac

Anastasia M Khoury-Christianson

Charles Joel Arntzen

Manoj Maniar

Peter B Kipp

Gregory D May

Anastasia P Khoury-Christianson

The present invention provides compositions and methods for promoting rapid healing and/or regeneration of damaged tissue resulting from a wound comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound of (E)-4-carboxystyryl-4-chlorobenzylsulfone, or a functional derivative thereof, and a pharmaceutically acceptable excipient.

Compositions and methods for prevention and treatment of wounds

The invention concerns the use of duplex oligonucleotides about 25 to 30 base pairs to introduce site specific genetic alterations in plant cells. The oligonucleotides can be delivered by mechanical (biolistic) systems or by electrpoporation of plant protoplasts. Thereafter plants having the genetic alteration can be generated from the altered cells. In specific embodiments the invention concerns alteration in the gene that encode acid invertase, UDP-glucose pyrophosphorylase, polyphenol oxidase, O-methyl transferase, cinnamyl alcohol dehydrogenase, ACC synthase and ACC oxidase or etr-1 or a homolog of etr-1, and plants having isolated point mutations in such genes.

Use of mixed duplex oligonucleotides to effect localized genetic changes in plants

The invention is based on the discovery that recombinagenic oligonucleobases are active in prokaryotic cells that contain a strand transfer activity (RecA) and mismatch repair activity (MutS). Using this system a type of Duplex Mutational Vector termed a Heteroduplex Mutational Vector, was shown to be more active in prokaryotic cells than the types of mutational vectors heretofore tested. Further improvements in activity were obtained by replacing the tetrathymidine linker by a nuclease resistant oligonucleotide, such as tetra-2&prime;-O-methyl-uridine, to link the two strands of the recombinagenic oligonucleobase and removing the DNA-containing intervening segment. The claims concern Duplex Mutational Vectors that contain the above improvements. In an alternative embodiment the claims concern the use of Duplex Mutational Vectors in prokaryotic cells.

Chimeric mutational vectors

The present invention relates to the use of transgenic pigs for the production of human hemoglobin. The transgenic pigs of the invention may be used as an efficient and economical source of cell-free human hemoglobin that may be used for transfusions and other medical applications in humans.

Production of human hemoglobin in transgenic pigs

The invention is based on the discovery that Duplex Mutational Vectors are active in prokaryotic cells that contain a strand transfer activity (RecA) and mismatch repair activity (MutS). Using this system a type of Duplex Mutational Vector, termed a Non-Chimeric Mutational Vector, having no RNA:DNA hybrid-duplex, was shown to be active in prokaryotic cells if protected from 3' exonuclease attack. Such protection can be conferred by replacement of a tetrathymidine linker by a nuclease resistant oligonucleotide, such as tetra-2'-O-methyl-uridine, to link the two strands of the recombinagenic oligonucleobase. The claims concern 3'-exonuclease protected Non-Chimeric Mutational Vectors.

Non-chimeric mutational vectors

The present invention concerns a method and compositions of matter useful for the method of making, in transgenic animals, a human hemoglobin that is more stable and more readily purified from the endogenous hemoglobins of the transgenic animal than hemoglobin A. The hemoglobins produced by the invention include hemoglobin A.sub.2, which is an .alpha..sub.2 .delta..sub.2 tetramer, as well as other hemoglobins having similar properties to hemoglobin A.sub.2 and have .beta./.delta. chimeric globins. The specification discloses a chimeric gene, encoding a human .delta.-globin that is expressed in transgenic animals at levels approximating the level of expression of the .alpha. or .beta. globin.

Production of hemoglobin having a .delta.-like globin

The present invention relates to the use of transgenic pigs for the production of human hemoglobin. The transgenic pigs of the invention may be used as an efficient and economical source of cell-free human hemoglobin that may be used for transfusions and other medical applications in humans. Also disclosed are the methods of purifying human hemoglobin from pig red cell lysate, and plasmids contained pig and human nucleic acid sequences for the production of transgenic pigs expressing human globin DNA sequences.

Purifying Human Hemogloblin from transgenic pig red cells and plasmids

The present invention concerns a method and compositions of matter useful for the method of making, in transgenic animals, a human hemoglobin that is more stable and more readily purified from the endogenous hemoglobins of the transgenic animal than hemoglobin A. The hemoglobins produced by the invention include hemoglobin A.sub.2, which is an .beta..sub.2 .delta..sub.2 tetramer, as well as other hemoglobins having similar properties to hemoglobin A.sub.2 and have .beta./.delta.chimeric globins. The specification discloses a chimeric gene, encoding a human .delta.-globin that is expressed in transgenic animals at levels approximating the level of expression of the .alpha. or .beta. globin.

Production of hemoglobin having a delta-like globin

The present invention relates to a novel method for making a predetermined, desired peptide in transgenic animals and can be advantageously used for the production of large quantities of the desired peptide. More particularly, the invention concerns the engineering of a transgenic animal having an artificial gene, which is controlled by globin locus control region (LCR) and which encodes a fusion protein, in which the desired peptide is joined via a cleavable peptide linker to a globin polypeptide. The erythrocytes of the transgenic animal express the fusion globin which is incorporated into hemoglobin produced by the host cell. The desired peptide can be obtained from a hemolysate of the red cells of the transgenic animals by enzymatic or chemical cleavage at the linker.

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Pennington, NJ, United States of America

Ramesh Kumar