4959463 intermediates

1
PATENT ABSTRACTS into the lacZ gene, which codes for E. coli beta- galactosidase, carried by the plasmids. Large amounts of the preS- beta-galactosidase fusion proteins can be isolated from microbial cultures carrying the recombinant plasmids. Antigenic determinants of fusion protein so produced are recognized by antibodies to the preS deter- minants of native hepatitis B virus. The beta- galactosidase activity of such fusion protein is detected by a suitable chromogenic or fluorogenic substrate. PreS- beta-galactosidase fusion proteins so produced can be used in an enzyme-linked immunosorbent assay (ELISA) to diagnose the presence of hepatitis B virus in- fection. Additionally, the fusion proteins can be cleaved to release preS polypeptides which can be further purified. PreS polypeptides obtained from these fusion proteins can be used to im- munize patients against hepatitis B virus. 4959327 VECTORS AND METHOD OF PENICILLIUM CHRYSOGENUM TRANSFORMATION Florentina S Sanchez, Victor R Susan, Miguei A Soto, Agustin P A Ortega, Madrid, Spain as- signed to Antibiotics S A Disclosed is a method for transforming Penicil- lium chrysogenum. More particularly, the method includes obtaining an auxotrophic mutant of P. chrysogenum and employing an ex- ogeneous segment of P. chrysogenum DNA capable of complementing said auxotorph so as to restore prototrophy. The exogeneous DNA segment thus comprises a phenotypic marker in- dicating successful transformation of the mutant. The exogeneous complementary DNA segment may further be prepared in a recom- binant plasmid vector. These plasmid vectors in- clude, by way of example, the pPctrpCL and pPctrpC6 plasmids developed by Applicants. These transforming plasmid vectors and those having identifying characteristics thereof are suitable for use in the subject transformation process. The exogeneous complementary DNA segment comprises a gene encoding a selected biosynthetic enzyme. By way of example, these genes include trpC, pyr4, argB and NO- reductase, as well as other genes which encode metabolically required enzymes. The most pre- ferred of these is trpC. 75 4959~3 PROMOTION OF CORNEAL STROMA WOUND HEALING WITH HUMAN EPIDERMAL GROWTH FACTOR PREPARED FROM RECOMBINANT DNA Gregory Brown, Richar Eiferman, Gregory Schultz, Pablo D T Valenzueia assigned to University of Louisville Foundation; Chiron Corporati A method for treating corneal stromal wounds to promote regeneration of the affected tissue is provided. This method employs recombinant human epidermal growth factor. 4959462 DESOXYRIBONUCLEIC ACID; MICROORGANISMS; DIAGNOSTIC AGENT FOR DELTA INFECTION AND THE USE THEREOF Reinder Dijkema, Antonides Kos, Oss, Nether- lands assigned to Nederlandse Centrale Or- ganisatie voor Toegepast Natuurwetenschappelij k Onderzoek This invention relates to DNA having at least 60~ homology relative to gamma-RNA or a portion thereof and the capacity of selective hybridization with delta-RNA. Such DNA, if provided with a detectable label, such as 32P can be used as a diagnostic agent to diagnose delta infection. 4959463 INTERMEDIATES Brian C Froehler, Mark D Matteucci assigned to Genentech Inc A method is provided for the high fidelity, rapid and economical in vitro synthesis of oligonucleotides. Nucleoside H-phosphonates are condensed in seriatim using a dehydrating a- gent to produce a poly (nucleoside H- phosphonate). The produce is oxidized to yield the desired olignnucleotide. A novel reagent is provided for multiple nucleoside additions in single cycles.

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Page 1: 4959463 Intermediates

PATENT ABSTRACTS

into the lacZ gene, which codes for E. coli beta- galactosidase, carried by the plasmids. Large amounts of the preS- beta-galactosidase fusion proteins can be isolated from microbial cultures carrying the recombinant plasmids. Antigenic determinants of fusion protein so produced are recognized by antibodies to the preS deter- minants of native hepatitis B virus. The beta- galactosidase activity of such fusion protein is detected by a suitable chromogenic or fluorogenic substrate. PreS- beta-galactosidase fusion proteins so produced can be used in an enzyme-linked immunosorbent assay (ELISA) to diagnose the presence of hepatitis B virus in- fection. Additionally, the fusion proteins can be cleaved to release preS polypeptides which can be further purified. PreS polypeptides obtained from these fusion proteins can be used to im- munize patients against hepatitis B virus.

4959327

V E C T O R S A N D M E T H O D O F P E N I C I L L I U M C H R Y S O G E N U M

T R A N S F O R M A T I O N

Florentina S Sanchez, Victor R Susan, Miguei A Soto, Agustin P A Ortega, Madrid, Spain as- signed to Antibiotics S A

Disclosed is a method for transforming Penicil- lium chrysogenum. More particularly, the method includes obtaining an auxotrophic mutant of P. chrysogenum and employing an ex- ogeneous segment of P. chrysogenum DNA capable of complementing said auxotorph so as to restore prototrophy. The exogeneous DNA segment thus comprises a phenotypic marker in- dicating successful transformation of the mutant. The exogeneous complementary DNA segment may further be prepared in a recom- binant plasmid vector. These plasmid vectors in- clude, by way of example, the pPctrpCL and pPctrpC6 plasmids developed by Applicants. These transforming plasmid vectors and those having identifying characteristics thereof are suitable for use in the subject transformation process. The exogeneous complementary DNA segment comprises a gene encoding a selected biosynthetic enzyme. By way of example, these genes include trpC, pyr4, argB and NO- reductase, as well as other genes which encode metabolically required enzymes. The most pre- ferred of these is trpC.

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4 9 5 9 ~ 3

P R O M O T I O N O F C O R N E A L S T R O M A W O U N D H E A L I N G W I T H H U M A N E P I D E R M A L

G R O W T H F A C T O R P R E P A R E D F R O M R E C O M B I N A N T D N A

Gregory Brown, Richar Eiferman, Gregory Schultz, Pablo D T Valenzueia assigned to University of Louisville Foundation; Chiron Corporati

A method for treating corneal stromal wounds to promote regeneration of the affected tissue is provided. This method employs recombinant human epidermal growth factor.

4959462

D E S O X Y R I B O N U C L E I C A C I D ; M I C R O O R G A N I S M S ;

D I A G N O S T I C A G E N T F O R D E L T A I N F E C T I O N A N D T H E U S E

T H E R E O F

Reinder Dijkema, Antonides Kos, Oss, Nether- lands assigned to Nederlandse Centrale Or- ganisatie voor Toegepast Natuurwetenschappelij k Onderzoek

This invention relates to DNA having at least 60~ homology relative to gamma-RNA or a portion thereof and the capacity of selective hybridization with delta-RNA. Such DNA, if provided with a detectable label, such as 32P can be used as a diagnostic agent to diagnose delta infection.

4959463

I N T E R M E D I A T E S

Brian C Froehler, Mark D Matteucci assigned to Genentech Inc

A method is provided for the high fidelity, rapid and economical in vitro synthesis of oligonucleotides. Nucleoside H-phosphonates are condensed in seriatim using a dehydrating a- gent to produce a poly (nucleoside H- phosphonate). The produce is oxidized to yield the desired olignnucleotide. A novel reagent is provided for multiple nucleoside additions in single cycles.