Peter Vas Dias, Age 462751 W Victor Loop, Coeur D Alene, ID 83815

2002002, Mar 7, 2002

Jun 18, 2001

09/884579

Sujay Singh - San Diego CA, US
Peter Dias - Carlsbad CA, US

A01K067/027
C12P021/04
C07K016/00

435/070210, 800/019000, 530/388100

The present invention provides methods for producing exogenous and chimeric antibodies in avians. One aspect of the present invention is a method of producing avians or avian cells lacking endogenous immunoglobulin light chain and heavy chain loci, or portions thereof, and having at least a portion of at least one exogenous immunoglobulin locus. The present invention provides a method for obtaining an avian cell with a deletion in an endogenous immunoglobulin locus by by introducing a targeting construct comprising two regions of sequences which are homologous to the 5′ and 3′ flanking sequences of the region to be deleted in the wild-type locus. In addition, the invention provides methods for inserting exogenous immunoglobulin gene loci into the genome of an avian cell. A second aspect of the invention is the generation of transgenic avian species or transgenic avian cells for producing chimeric antibodies. The avian host is characterized by: (1) being incapable of producing endogenous immunoglobulin; and (2) having at least a portion of an exogenous immunoglobulin locus comprising at least one immunoglobulin constant region or portion thereof. Specific binding proteins with xenogenic regions can be produced in a viable avian host by immunization of the avian host with an appropriate immunogen. Another aspect of the invention is the isolation of antibody-producing cells from a transgenic avian of the present invention that has been immunized with an antigen of interest. The cells can be immortalized for the production of antibody in culture. The immortalized cells can be used for the isolation of cDNAs encoding immunoglobulin heavy and light chains or portions thereof. The cDNAs can be reintroduced to cell lines, including mammalian cell lines for efficient production of monoclonal antibodies. The cDNAs can optionally be mutated or altered, for example, such that they encode higher avidity antibodies or chimeric immunoglobulin molecules, prior to reintroduction into cell lines.

2004025, Dec 9, 2004

Dec 9, 2003

10/731073

Sujay Singh - San Diego CA, US
Peter Dias - Carlsbad CA, US

A01K067/027

800/019000, 119/300000

The present invention provides methods for producing exogenous and chimeric antibodies in avians. One aspect of the present invention is a method of producing avians or avian cells lacking endogenous immunoglobulin light chain and heavy chain loci, or portions thereof, and having at least a portion of at least one exogenous immunoglobulin locus. The present invention provides a method for obtaining an avian cell with a deletion in an endogenous immunoglobulin locus by by introducing a targeting construct comprising two regions of sequences which are homologous to the 5′ and 3′ flanking sequences of the region to be deleted in the wild-type locus. In addition, the invention provides methods for inserting exogenous immunoglobulin gene loci into the genome of an avian cell. A second aspect of the invention is the generation of transgenic avian species or transgenic avian cells for producing chimeric antibodies. The avian host is characterized by: (1) being incapable of producing endogenous immunoglobulin; and (2) having at least a portion of an exogenous immunoglobulin locus comprising at least one immunoglobulin constant region or portion thereof. Specific binding proteins with xenogenic regions can be produced in a viable avian host by immunization of the avian host with an appropriate immunogen. Another aspect of the invention is the isolation of antibody-producing cells from a transgenic avian of the present invention that has been immunized with an antigen of interest. The cells can be immortalized for the production of antibody in culture. The immortalized cells can be used for the isolation of cDNAs encoding immunoglobulin heavy and light chains or portions thereof. The cDNAs can be reintroduced to cell lines, including mammalian cell lines for efficient production of monoclonal antibodies. The cDNAs can optionally be mutated or altered, for example, such that they encode higher avidity antibodies or chimeric immunoglobulin molecules, prior to reintroduction into cell lines.

6623936, Sep 23, 2003

Feb 7, 2000

09/499559

Peter Dias - San Diego CA
Sujay Singh - San Diego CA

Imgenex - San Diego CA

G01N 3353

435 72, 435 6, 435 71, 435 79, 435 791, 435 793, 435 795, 530350, 5303871

A method for diagnosing clinically distinct embryonal and alveolar subtypes of rhabdomyosarcoma, including contacting a reagent including an antibody that specifically binds myogenin with a sample that includes at least one rhabdomyosarcoma cell or at least one extract of at least one rhabdomyosarcoma cell, detecting the binding of the antibody to the sample to determine the presence, absence, or amount of myogenin in the sample, and diagnosing clinically distinct embryonal and alveolar subtypes of rhabdomyosarcoma, alveolar rhabdomyosarcoma having an increased amount of binding as compared to embryonal rhabdomyosarcoma.