Abstract: Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.

Abstract: Humanized anti-CD11a antibodies and various uses therefor are disclosed. The humanized anti-CD11a antibody may bind specifically to human CD11a I-domain, have an IC50(nM) value of no more than about 1 nM for preventing adhesion of Jurkat cells to normal human epidermal keratinocytes expressing ICAM-1, and/or an IC50 (nM) value of no more than about 1 nM in the mixed lymphocyte response assay.

Abstract: A method of treating a human patient via active immunotherapy comprising administrating an effective amount of extracellular portion of human HER2 receptor to the patient wherein the method provokes a cell-mediated immune response to HER2 receptor in the patient treated therewith.

Abstract: The protein tyrosine kinase receptors, designated Rse and HPTK6, have been purified from human and/or murine cell tissues. Rse and HPTK6 have been cloned from a cDNA library of a human liver carcinoma cell line (i.e., Hep 3B) using PCR amplification. Provided herein are nucleic acid sequences encoding Rse and HPTK6 useful as diagnostics and in the recombinant preparation of Rse and HPTK6. Rse and HPTK6 are used in the preparation and purification of antibodies thereto and in diagnostic assays.

Abstract: Agonist antibodies are disclosed which bind to the extracellular domain of the flk2/flt3 receptor and thereby activate the intracellular kinase domain thereof. The labeled antibodies are useful as diagnostics for detecting the presence of the flk2/flt3 receptor in primitive hematopoietic cells for example. The antibodies are able to cause primitive hematopoietic cells to proliferate and/or differentiate and thereby enhance repopulation of mature blood cell lineages in a mammal which has undergone chemo- or radiation therapy or bone marrow transplantation. The antibodies are further useful for treating mammals which have suffered a decrease in blood cells as a consequence of disease or a hemorrhage, for example.

Abstract: Antibodies are disclosed which bind to ErbB3 protein and further possess any one or more of the following properties: an ability to reduce heregulin-induced formation of an ErbB2-ErbB3 protein complex in a cell which expresses ErbB2 and ErbB3; the ability to increase the binding affinity of heregulin for ErbB3 protein; and the characteristic of reducing heregulin-induced ErbB2 activation in a cell which expresses ErbB2 and ErbB3.

Abstract: A method for improving clinical outcome in focal ischemic stroke in a mammal by increasing cerebral blood flow and/or reducing infarct size is described which involves administering an effective amount of an anti-CD18 antibody to the mammal, in the absence of removal of the arterial obstruction.

Abstract: An assay for measuring activation (i.e., autophosphorylation) of a tyrosine kinase receptor of interest is disclosed.(a) A first solid phase is coated with a substantially homogeneous population of cells so that the cells adhere to the first solid phase. The cells have either an endogenous tyrosine kinase receptor or have been transformed with DNA encoding a receptor or "receptor construct" and the DNA has been expressed so that the receptor or receptor construct is presented in the cell membranes of the cells.(b) A ligand is then added to the solid phase having the adhering cells, such that the tyrosine kinase receptor is exposed to the ligand.(c) Following exposure to the ligand, the adherent cells are solubilized, thereby releasing cell lysate.(d) A second solid phase is coated with a capture agent which binds specifically to the tyrosine kinase receptor, or, in the case of a receptor construct, to the flag polypeptide.

Abstract: An assay for measuring activation (i.e., autophosphorylation) of a tyrosine kinase receptor of interest is disclosed.(a) A first solid phase is coated with a substantially homogeneous population of cells so that the cells adhere to the first solid phase. The cells have either an endogenous tyrosine kinase receptor or have been transformed with DNA encoding a receptor or "receptor construct" and the DNA has been expressed so that the receptor or receptor construct is presented in the cell membranes of the cells.(b) A ligand is then added to the solid phase having the adhering cells, such that the tyrosine kinase receptor is exposed to the ligand.(c) Following exposure to the ligand, the adherent cells are solubilized, thereby releasing cell lysate.(d) A second solid phase is coated with a capture agent which binds specifically to the tyrosine kinase receptor, or, in the case of a receptor construct, to the flag polypeptide.

Abstract: Novel polypeptides with binding affinity for the p185.sup.HER2 receptor, designated heregulin 2-.alpha. and heregulin 2-.beta., have been identified and purified from human tissue. The cDNA encoding the novel heregulin 2-.alpha. has been isolated from human tissue and sequenced. Provided herein is nucleic acid sequence of the heregulin 2-.alpha. useful in the production of heregulin 2-.alpha. by recombinant means. Further provided an amino acid sequence of heregulin 2-.alpha. and heregulin 2-.beta.. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.

Abstract: A method of producing a polypeptide in fed batch cell culture is provided which involves an initial cell growth phase and a distinct production phase. In the initial growth stage, animal cells having nucleic acid encoding the polypeptide are cultured at a starting osmolality of about 280-330 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. This is followed by a production phase, where the cultured animal cells of the growth phase are inoculated at a cell seed density of at least 1.0.times.10.sup.6 cells/mL and the cells are cultured at a starting osmolarity of about 400-600 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. Preferably, the glutamine concentration in the cell culture medium is simultaneously controlled in order to curtail production of lactic acid and ammonia which result from unnecessarily high glutamine concentrations.

Abstract: Novel 2 polypeptides with binding affinity for the p185.sup.HER2 receptor, designated heregulin 2-.alpha. and heregulin 2-.beta., have been identified and purified from human tissue. The cDNA encoding the novel heregulin 2-.alpha. has been isolated from human tissue and sequenced. Provided herein is nucleic acid sequence of the heregulin 2-.alpha. useful in the production of heregulin 2-.alpha. by recombinant means. Further provided an amino acid sequence of heregulin 2-.alpha. and heregulin 2-.beta.. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.

Abstract: A method for enhancing the survival and/or proliferation of Schwann cells (especially human Schwann cells) in cell culture is disclosed which involves culturing the cells in serum free culture medium comprising gas6 and other mitogenic agents, such as heregulin and forskolin. The culturing step is generally preceded by a pre-incubation period wherein nerve tissue comprising the Schwann cells is cultured under appropriate conditions and for a period of time such that demyelination occurs. The isolated Schwann cells can be used as cellular prostheses to treat patients with nervous system injuries. The invention also provides a cell culture medium for culturing Schwann cells.

Abstract: A novel polypeptide with binding affinity for the p185.sup.HER2 receptor, designated heregulin-.alpha., has been identified and purified from cultured human cells. DNA sequences encoding additional heregulin polypeptides, designated heregulin-.alpha., heregulin-.beta.1, heregulin-.beta.2, heregulin-.beta.2-like, and heregulin-.beta.3, have been isolated, sequenced and expressed. Provided herein are nucleic acid sequences encoding the amino acid sequences of heregulins useful in the production of heregulins by recombinant means. Further provided are the amino acid sequences of heregulins and purification methods therefor. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.

Abstract: Methods are provided for the preparation in recombinant host cells of biologically active soluble variants of discretely encoded, heteromultimer polypeptide receptors. Such variants are synthesized by the secretion from recombinant transformants of transmembrane-modified heteromultimer receptors. Preferred receptors are extracellular matrix, cell surface, or plasma protein-binding receptors such as GPIIb-IIIa.

Abstract: Novel 2 polypeptides with binding affinity for the p185.sup.HER2 receptor, designated heregulin 2-.alpha. and heregulin 2-.beta., have been identified and purified from human tissue. The cDNA encoding the novel heregulin 2-.alpha. has been isolated from human tissue and sequenced. Provided herein is nucleic acid sequence of the heregulin 2-.alpha. useful in the production of heregulin 2-.alpha. by recombinant means. Further provided an amino acid sequence of heregulin 2-.alpha. and heregulin 2-.beta.. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.

Abstract: A novel bronchial or bronchiolar epithelial cell from normal neonatal mammalian lung has been isolated, established and maintained for multiple passages in the absence of serum, without undergoing crisis or senescence. By careful manipulation of the nutritional/hormonal microenvironment we have been able to select, from a heterogeneous population, a single epithelial cell type which can maintain highly differentiated features in vitro. This cell type has characteristics of bronchiolar epithelial cells. A clonal line, RL-65, has been selected and observed for more than 3 years in continuous culture. It has been characterized by ultrastructural, morphological and biochemical criteria.

Abstract: The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. "Protuberances" are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine).

Abstract: Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.

Abstract: The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. "Protuberances" are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine).