Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

Abstract: The present invention describes methods of generating single VL domain antibodies, including chimeric single chain antibodies that comprise of a variable region of a human immunoglobulin ? or ? light chain and a non-human constant region. The non-human constant region is devoid of a first constant domain CH1, and the variable region is devoid of a heavy chain variable domain.

Abstract: The invention provides methods and compositions for generating non-human transgenic cells and organisms that are transgenic at one or more gene sequences by separately recombining fragments of a complete gene in temporal sequence. According to the methods of the invention, a set of DNA constructs containing a non-endogenous DNA sequence flanked and/or operably linked at its ends by sequences from the non-human organism are generated by recombination in a bacterial cell, for example, in E. coli. The DNA constructs that are produced can then be introduced into a non-human homologous recombination competent cell where successive cells will contain recombined segments of a target gene, with the ultimate cell in a line containing an endogenous target gene completely replaced by genomic DNA of another species.

Abstract: Methods are provided for the rapid identification of essential or conditionally essential DNA segments in any species of haploid cell (one copy chromosome per cell) that is capable of being transformed by artificial means and is capable of undergoing DNA recombination. This system offers an enhanced means of identifying essential function genes in diploid pathogens, such as gram-negative and gram-positive bacteria.

Abstract: The invention provides methods and compositions for generating non-human transgenic animals that are humanized at one or more gene sequences. According to the methods of the invention, a DNA construct containing a human DNA sequence flanked by sequences from the non-human animal is generated by recombination in a bacterial cell, for example, in E. coli. The DNA construct that is produced can then be introduced into a non-human embryogenic stem cell where it can recombine with the genomic DNA of the non-human animal.

Abstract: Methods are provided for the rapid identification of essential or conditionally essential DNA segments in any species of haploid cell (one copy chromosome per cell) that is capable of being transformed by artificial means and is capable of undergoing DNA recombination. The BAC system is used to provide to the prokaryotic host cell an additional copy of a known segment of DNA of the host cell (or of another prokaryotic cell whose genome is known) to construct merodiploid test cells wherein the chromosomal region of the host cell that is homologous to the DNA contained in the BAC becomes diploid. Alternatively, due to the high homology in essential genes of prokaryotes, the DNA contained in the BAC can be derived from a prokaryote other than the host cell. A transposon is then delivered randomly to the merodiploid cell.

Abstract: A fragment, synthetic or natural, DNA or RNA, may be attached to a non-radiological label such as a fluorescent compound, a luminescent compound or a color reflective compound, by a linker. The linker is an aminoalkylphosphoramide. The linker may contain a number of methyl units selected to adjust the mobility of the arrangement of the tagged fragment in a polyacrylamide gel during electro-phoresis. A unique color may be attached to each for the four bases. The color coded bases may be separated in a single lane of the ployacrylamide gel. Because the mobility of each arrangement has been adjusted the normal one base spacing will be produced. The sequence of the target may be read directly by manually observing the color sequence or by an automatic reader. The tagging of natural fragments may be used to tag a preselected gene, in the application of Southern and Northern bloting diagnostic procedures, as a diagnostic tool to hunt/detect selected DNA and to label probes to detect ribosonal RNA of pathogens.

Abstract: This invention discloses a newly discovered enzyme and a method of producing said enzyme wherein said enzyme is completely inactivated by treatment with temperatures of 50.degree. or higher for 10 minutes or longer. The alkaline phosphatase is isolated from the psychrophilic bacteria, particularly bacteria from certain areas of the oceans surrounding Antarctica. The preferred alkaline phosphatase is derived from the bacteria HK-47 (ATCC 39469).

Abstract: Composition and methods of production of the compound P.sup.1 -adenosine, P.sup.2 -(3' nucleotide monophosphate)-5' pyrophosphate (AppNp) are disclosed. AppNp is useful in the synthesis of a predetermined sequence of RNA using the enzyme T4 RNA ligase. The use of this invention in the field of recombinant DNA will greatly enhance the ability to synthesize genes of known composition.