59 results about "Human sequence" patented technology

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

Disclosed herein are methods for humanizing antibodies based on selecting variable region framework sequences from human antibody genes by comparing canonical CDR structure types for CDR sequences of the variable region of a non-human antibody to canonical CDR structure types for corresponding CDRs from a library of human antibody sequences, preferably germline antibody gene segments. Human antibody variable regions having similar canonical CDR structure types to the non-human CDRs form a subset of member human antibody sequences from which to select human framework sequences. The subset members may be further ranked by amino acid similarity between the human and the non-human CDR sequences. Top ranking human sequences are selected to provide the framework sequences for constructing a chimeric antibody that functionally replaces human CDR sequences with the non-human CDR counterparts using the selected subset member human frameworks, thereby providing a humanized antibody of high affinity and low immunogenicity without need for comparing framework sequences between the non-human and human antibodies. Chimeric antibodies made according to the method are also disclosed.

The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

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.

The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Methods useful for human adapting non-human monoclonal antibodies are disclosed. The methods select candidate human antibody framework sequences from a database of human germline genes or human sequences with somatic mutations.

The invention relates to transgenic non-human animals capable of producing high affinity human sequence antibodies. The invention is also directed to human sequence antibodies specific for human antigens, such as, human CD4. The invention also is directed to methods for producing human sequence antibodies.

The present invention relates to anti-PD1 and anti-CD19 bispecific antibody and applications thereof, wherein the anti-PD1 and anti-CD19 bispecific antibody, or a variant, or a functional fragment thereof comprises: a domain capable of specifically recognizing and binding an immune cell surface antigen PD-1, wherein the domain comprises the heavy chain variable region (anti-PD-1 VH) of an anti-PD-1 specific antibody; and a domain capable of specifically recognizing and binding CD19, wherein the domain comprises the heavy chain variable region (anti-CD19 VH) of an anti-CD19 specific antibody. According to the present invention, the bispecific antibody has the whole human sequence, such that the occurrence of HAMA in clinical treatment application is effectively avoided, the occurrence of drug resistance can be effectively reduced, and the utilization efficiency and the treatment effect of the medicine can be improved; and the anti-PD-1 and anti-CD19 bispecific antibody can well mediate T cells to efficiently and specifically kill B-lymphocyte derived tumor cells compared to the existing anti-PD-1 specific antibody and the existing anti-CD19 specific antibody.

The present invention encompasses monoclonal antibodies that bind to lipoteichoic acid (LTA) of Gram positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro. The invention also provides antibodies having human sequences (chimeric, humanized and human antibodies). The invention also sets forth the variable regions of three antibodies within the invention and presents the striking homology between them.

The invention discloses a method for humanizing an antibody. In the invention, through comparing a standard CDR (Complementarity-Determining Region) structure type of a CDR sequence in a variable region of an inhuman antibody with a standard CDR structure type of a corresponding CDR in a human antibody sequence library, a frame sequence of the variable region is selected from human antibody genes, preferably the gene segments of an embryonic system antibody. The variable region of the human antibody which has the standard CDR structure type similar to an inhuman CDR forms a subgroup of a member antibody sequence and a human frame sequence can be selected from the subgroup. The subgroup members can be further rated through the amino acid similarity between the human and inhuman CDR sequences. The ahead human sequence in the rating is selected to provide the frame sequence and construct a chimeric antibody by utilizing the selected the subgroup member human frame. The chimeric antibody replaces the human CDR sequence by the counterpart functionality of the inhuman CDR, therefore, the humanized antibody which has high affinity and low immunogenicity is provided without comparing the frame sequences between the inhuman antibody and the human antibody. The invention also discloses the chimeric antibody prepared according to the method of the invention.

The present invention concerns a process by which a misfold in an Fc fusion molecule can be prevented or corrected. In one embodiment, the process comprises (a) preparing a pharmacologically active compound comprising an Fc domain; (b) treating the fusion molecule with a copper (II) halide; and (c) isolating the treated fusion molecule. The pharmacologically active compound can be an antibody or a fusion molecule comprising a pharmacologically active domain and an Fc domain. The preferred copper (II) halide is CuCl₂. The preferred concentration thereof is at least about 10 mM for fusion molecules prepared in E. coli; at least about 30 mM for fusion molecules prepared in CHO cells. The process can be employed with any number of pharmacologically active domains. Preferred pharmacologically active domains include OPG proteins, leptin proteins, soluble portions of TNF receptors (e.g., wherein the fusion molecule is etanercept), IL-1ra proteins, and TPO-mimetic peptides. The Fc domain preferably has a human sequence, with an Fc sequence derived from IgG1 most preferred. An exemplary Fc sequence is shown in FIG. 5 hereinafter.

The invention provides specific binding members (e.g., antibodies or antigen-binding fragments thereof) which bind to RANKL originating from multiple species. An epitope recognized by the specific binding members can be selected from surface exposed loop domains that bind to and activate its cognate receptor, RANK (Receptor Activator of NFkB), on the surface of osteoclast precursors and other cell types. The invention provides peptides for generating such anti-RANKL antibodies, including murine sequences, other non-human sequences and cross-reactive peptides. The specific binding members are useful in the diagnosis and treatment of lytic bone diseases, including osteoporosis, rheumatoid arthritis, bone metastasis and hypercalcemia of malignancy, glucocorticoid-induced bone loss, a periodontal disease or condition, a cancer and Juvenile Paget's Disease. The binding members can also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or antigen-binding fragments thereof.

A hybridoma cell line producing high levels of human sequence antibody. Also described is a hybridoma cell line producing human sequence antibodies that is adapted for growth in serum-free media or animal-derived-components-free media. A hybridoma cell line producing anti-CTLA4 antibodies is most preferred.

The invention discloses a partition method on human motion 3D data. First, use manifold analysis method ISOMAP to map the original human sequence motion data to the low dimensional manifold space; secondly, utilize a heuristic method to detect rough partition points of different types of movement in the motion data sequence, then long sequence of human motion data are partitioned to several segments; last, for every two segments concatenated in time in the low dimensional manifold space use K-average clustering algorithm to compute the accurate partition point.

Current humanization approaches for immunoglobulins focus mostly on modifying the framework regions into human sequences. Herein is provided a method for humanizing antibody complementarity-determining regions (CDRs) through functional humanization to reduce the potential immunogenicity of non-human CDR-containing antibodies. CDRs with high sequence homology to the parent CDR are identified from a database of human CDR sequences. One or more human CDRs that are highly homologous to the parent CDR sequence can be used to replace the corresponding CDRs of murine immunoglobulins (or their humanized, or re-engineered versions). Human CDRs that improve or have minimal effects on the antigen binding affinity and specificity are adopted.

Provided herein, inter alia, are non-human animals comprising nucleic acid sequences encoding a C3 protein that comprises a human sequence as well as transgenic non-human animals comprising a C3 gene that is human in whole or in part as well as methods for using the same to screen for candidate therapeutic molecules to treat complement-related nephropathies. Also provided herein are methods for improving kidney function in an individual diagnosed with or thought to have a complement-related nephropathy.

The present invention provides a bi-functional fusion protein simultaneously targeting the complement and the vascular endothelial growth factor (VEGF). The bi-functional fusion proteins contain two or more domains of human proteins and are of all human sequences, and thus are expected to be non-immunogenic, and potentially can be used therapeutically in human targeting complement and VEGF related diseases.