The present invention provides novel human sequence antibodies against human CTLA-4 and methods of treating human diseases, infections and other conditions using these antibodies.

Human ctla-4 antibodies and their uses

Formulation and delivery issues for monoclonal antibody therapeutics

Heterogeneity of Monoclonal Antibodies

N-glycosylation is critical to the function of monoclonal antibodies (mAbs) and distinguishes various systems used for their production. We expressed human mAbs in the small aquatic plant Lemna minor, which offers several advantages for manufacturing therapeutic proteins free of zoonotic pathogens. Glycosylation of a mAb against human CD30 was optimized by co-expressing the heavy and light chains of the mAb with an RNA interference construct targeting expression of the endogenous alpha-1,3-fucosyltransferase and beta-1,2-xylosyltransferase genes. The resultant mAbs contained a single major N-glycan species without detectable plant-specific N-glycans and had better antibody-dependent cell-mediated cytotoxicity and effector cell receptor binding activities than mAbs expressed in cultured Chinese hamster ovary (CHO) cells.

Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor

Primordial germ cells (PGCs) are the precursors of sperm and eggs. In most animals, segregation of the germ line from the somatic lineages is one of the earliest events in development; in avian embryos, PGCs are first identified in an extra-embryonic region, the germinal crescent, after approximately 18 h of incubation. After 50-55 h of development, PGCs migrate to the gonad and subsequently produce functional sperm and oocytes. So far, cultures of PGCs that remain restricted to the germ line have not been reported in any species. Here we show that chicken PGCs can be isolated, cultured and genetically modified while maintaining their commitment to the germ line. Furthermore, we show that chicken PGCs can be induced in vitro to differentiate into embryonic germ cells that contribute to somatic tissues. Retention of the commitment of PGCs to the germ line after extended periods in culture and after genetic modification combined with their capacity to acquire somatic competence in vitro provides a new model for developmental biology. The utility of the model is enhanced by the accessibility of the avian embryo, which facilitates access to the earliest stages of development and supplies a facile route for the reintroduction of PGCs into the embryonic vasculature. In addition, these attributes create new opportunities to manipulate the genome of chickens for agricultural and pharmaceutical applications.

Germline transmission of genetically modified primordial germ cells.

The present invention provides human sequence antibodies against CTLA-4 and methods of treating human diseases, infections and other conditions using these antibodies.

Human CTLA-4 antibodies

The tubular gland of the chicken oviduct is an attractive system for protein expression as large quantities of proteins are deposited in the egg, the production of eggs is easily scalable and good manufacturing practices for therapeutics from eggs have been established. Here we examined the ability of upstream and downstream DNA sequences of ovalbumin, a protein produced exclusively in very high quantities in chicken egg white, to drive tissue-specific expression of human mAb in chicken eggs. To accommodate these large regulatory regions, we established and transfected lines of chicken embryonic stem (cES) cells and formed chimeras that express mAb from cES cell-derived tubular gland cells. Eggs from high-grade chimeras contained up to 3 mg of mAb that possesses enhanced antibody-dependent cellular cytotoxicity (ADCC), nonantigenic glycosylation, acceptable half-life, excellent antigen recognition and good rates of internalization.

Production of human monoclonal antibody in eggs of chimeric chickens

The present invention relates to binding compounds specific for BTLA and uses thereof. More specifically, the invention relates to fully human antibodies that recognize human BTLA and modulate its activity in cancer, inflammatory, and autoimmune disorders.

Fully human antibodies to BTLA

The present disclosure provides isolated monoclonal antibodies, particula rly human monoclonal antibodies that specifically bind to BTLA with high aff inity. Nucleic acid molecules encoding the antibodies of the disclosure, exp ression vectors, host cells and methods for expressing the antibodies of the disclosure are also provided. Immunoconjugates, bispecific molecules and ph armaceutical compositions comprising the antibodies of the disclosure are al so provided. The disclosure also provides methods for detecting BTLA, as wel l as methods for treating various diseases, including cancer and infectious diseases, using anti- BTLA antibodies.

Human monoclonal antibodies to btla and methods of use

PROBLEM TO BE SOLVED: To provide new human sequence antibodies against human CTLA-4 and a method of treating human diseases, infections and other conditions by using these antibodies. SOLUTION: Provided are new human sequence antibodies against human CTLA-4, and a method for treating human diseases, infections and other conditions by using these antibodies. The therapeutically effective human sequence antibody is bonded to the CTLA-4 on the cell surface of a normal human cell. Also provided is a composition of a polyclonal antibody containing a number of human sequence antibodies specifically bonding to human CTLA-4. The composition of the antibody may contain at least about 2-1,000 different human sequence antibodies specifically bonding to human CTLA-4. COPYRIGHT: (C)2009,JPO&INPIT

Edward L. Halk

Papers

Human CTLA-4 antibodies

Production of human monoclonal antibody in eggs of chimeric chickens

Fully human antibodies to BTLA

Human monoclonal antibodies to btla and methods of use

Human CTLA-4 antibody and use thereof