34 results about "ErbB Receptors" patented technology

The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anri-ErbB receptor antibody-maytansinoid conjugates.

The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anri-ErbB receptor antibody-maytansinoid conjugates.

The invention provides a method for determining the activation status of receptor tyrosine kinase (RTK) pathways in either cell samples or patient samples by measuring receptor dimerization and relative amounts of protein-protein complexes or activated effector proteins that are characteristic of an RTK pathway. The invention also provides a method of using such status information to select patients responsive to pathway-specific drugs, and more particularly, to methods for measuring ErbB receptors and receptor complexes and using such information to select patients responsive to ErbB pathway-specific drugs. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in RTK activation. After binding, molecular tags are released and separated from the assay mixture for analysis.

The invention provides a method for determining the activation status of receptor tyrosine kinase (RTK) pathways in either cell samples or patient samples by measuring receptor dimerization and relative amounts of protein-protein complexes or activated effector proteins that are characteristic of an RTK pathway. The invention also provides a method of using such status information to select patients responsive to pathway-specific drugs, and more particularly, to methods for measuring ErbB receptors and receptor complexes and using such information to select patients responsive to ErbB pathway-specific drugs. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in RTK activation. After binding, molecular tags are released and separated from the assay mixture for analysis.

The invention provides a method of determining whether tumor cells or tissue is responsive to treatment with an ErbB pathway-specific drug. In accordance with the invention, measurements are made on such cells or tissues to determine values for total ErbB receptors of one or more types, ErbB receptor dimers of one or more types and their phosphorylation states, and / or one or more ErbB signaling pathway effector proteins and their phosphorylation states. These quantities, or a response index based on them, are positively or negatively correlated with cell or tissue responsiveness to treatment with an ErbB pathway-specific drug. In one aspect, such correlations are determined from a model of the mechanism of action of a ErbB pathway-specific drug on an ErbB pathway. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in ErbB pathway activation. After binding, molecular tags are released and separated from the assay mixture for analysis.

The invention relates to new peptide compounds capable of modulating cell proliferation, differentiation, survival and / or motility. The peptide compounds of the invention comprise short peptide fragments of the ErbB receptor and are capable of binding to ErbB and modulating activity of the receptor. The invention also relates to antibodies capable of binding to an epitope comprising a peptide sequence of the invention, pharmaceutical compositions comprising the peptide sequences and / or antibodies and uses thereof for treatment of conditions wherein modulating activity of ErbB is needed.

The present invention provides a method of screening NRG mutant for activating ErbB acceptor specifically. The method includes the following steps: establishing 3D model of complex of NRG, ErbB3, ErbB4, NRG / ErbB3 and NRG / ErbB4 in a homogeneous model establishing process; molecular kinetically simulating conformation and stability of NRG / ErbB3 and NRG / ErbB4; MM / PBSA process of calculating the binding free energy between NRG and ErbB3 or ErbB4; scanning and calculating process based on alanine theory to determine the NRG and acceptor affinity change during the mutation from NRG residue to alanine and determining NRG mutant for activating ErbB acceptor specifically. The present invention also provides the NRG mutant and its application and preparation process.

The invention concerns quinazoline derivatives of Formula (I) wherein each of Q<1>, Z, R<1> and Q<2> have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

The invention provides a method of detecting ErbB receptor mutations comprising the steps of providing a bio-fluid sample from a patient; extracting DNA from said sample; and screening said DNA for the presence of one or more mutations that alter tyrosine kinase activity in the receptor.

The invention relates to a set of isolated marker genes comprising at least one gene identified as having differential expression as between patients who are responders and non responders to an erbB receptor tyrosine kinase inhibitor; said gene set comprising one or more genes selected from at least the group consisting of the 51 genes listed herein including gene-specific oligonucleotides derived from said genes; and uses of such sets in diagnostic applications.

The invention provides a method for detecting ErbB receptor mutations comprising the steps of providing a bio-fluid sample from a patient; extracting DNA from said sample; and screening said DNA for the presence of one or more mutations that alter tyrosine kinase activity in the receptor.

The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anti-ErbB receptor antibody-maytansinoid conjugates.

The present invention relates to monitoring of ErbB receptor levels in methods and kits for determining the prognosis of cancer in a subject or improving the effectiveness of a cancer treatment. The invention also provides a method for predicting the recurrence of clinical signs of a cancer in a subject. In some embodiments, the invention provides methods for predicting the development of resistance to a chemotherapy regimen. In other embodiments, the invention provides methods for improving the effectiveness of a cancer treatment in a subject by monitoring levels of ErbB-2, ErbB-3 and / or ErbB-4. Preferably, the subject in the methods of the invention has been previously treated with a chemotherapy regimen for an ErbB-1 positive tumor.

The invention relates to the use of an antibody or a fragment thereof, specific against substance P, for the manufacture of a medicament for therapeutic treatment of a cancer expressing NK1 receptor and / or a ErbB receptor family member (i.e. the epidermal growth factor receptors family), by direct administration to a mammal, including a human. The administration of an antibody against substance P to a panel of breast cancer cell lines, inhibits HER2 activation and expression, causing a downregulation of different genes involved in cell cycle progression, like cyclin D1, cyclin E, cdk4 and cdk2. A decrease in proliferation and an arrest in G1 phase of cell cycle are observed. On the other hand, the antibody causes an induction of apoptosis.

The truncated ErbB2 receptor (p95ErbB2) is shown to differ from the full-length ErbB2 receptor in its association with other ErbB receptors. The truncated receptor preferentially associated with ErbB3, whereas full length ErbB2 heterodimerizes with either EGFR or ErbB3. Consistent with p95ErbB2 heterodimerization with ErbB3, it is shown that heregulin (an ErbB3 ligand) stimulates p95ErbB2 phosphorylation in breast cancer cell lines. Described herein are methods of identifying patients suitable for treatment with a p95ErbB2 inhibitor, and methods of treating such patients.

The invention provides application of an ErbB receptor stimulant to preparation of a medicament for treating epilepsy. The ErbB receptor stimulant has the advantages: the inhibiting effect of the ErbB4 stimulant NRG1 on epilepsy is disclosed, the organism of epilepsy is studied intensively, a research direction for studying a novel effective 'target' and a molecule of an epilepsy inhibiting medicament is provided, and a basis is laid for the screening of a novel medicament for treating brain diseases based on neuronal excitability changes.

The present invention provides a CAR-T cell self-expressing a PD-1 immunological checkpoint inhibitory antibody and targeting a chimeric antigen receptor of ErbB receptor family and a use thereof. TheT cell comprises a coding sequence expressing the chimeric antigen receptor targeting the ErbB receptor family and a coding sequence of the PD1 antibody; and / or expressing the chimeric antigen receptor targeting the ErbB receptor family and the PD1 antibody. The T cell has better proliferation and activation ability than those of a T cell singly targeting the chimeric antigen receptor of the ErbBreceptor family, can overcome inhibition of an immune microenvironment, promotes apoptosis of tumor cells, and exerts an anti-tumor immune response and a tumor cell killing function.

The invention relates to novel bispecific antibodies and their use in tumor therapy. The novel antibodies have the ability to bind to ErbB receptors, preferably ErbB1 receptors, which are overexpressed on many cancer tissues. Since the different specificities of the antigen-binding sites are directed to different epitopes within the binding domain of same or different ErbB receptors, these antibodies are more effective with respect to inhibition and down-regulation of the ErbB receptor and the corresponding signaling cascade.

The invention provides methods for treating pancreatic dysfunction, particularly diabetes, in mammals using ErbB receptor ligands, such as heregulin, betacellulin, and EGF. Methods of treating such conditions using anti-ErbB receptor agonist antibodies are further provided. The methods of the invention may be performed by direct administration of such therapeutically useful agents to mammals, or alternatively, by exposing certain pancreatic cell types to such agents in vitro and subsequently transplanting the treated cells to a mammal.

The invention provides an application of an ErbB receptor agonist in preparing medicines for treating ischemic cerebrovascular diseases By using neuronal injury models in vivo and in vitro as a research platform, the protection function of NRG1 to neuronal cell injuries and experimental cerebral ischemia are discovered, simultaneously the possible molecular mechanism of NRG1 is fully researched, and the cerebral protection effect by regulating and controlling NRG1-ErbB4 associated signal pathway after ischemic cerebral ischemia is fully argued, thus the study of NRG1 and associated ErbB4 agonist open up wide prospects for developing novel medicines for protecting cerebral neurocyte and controlling ischemic cerebrovascular diseases.

The present invention provides heregulin variants that are capable of binding an ErbB receptor. Included in the invention are variants of human heregulins, and, in particular, variants of human heregulin-β1 having enhanced affinity for the ErbB-3 and ErbB-4 receptors. These variants include at least one amino acid substitution and can include further modifications. The invention also provides nucleic acid molecules encoding heregulin variants and related vectors, host cells, pharmaceutical compositions, and methods.

The present invention relates to a new class of biomarkers in patient samples comprising dimers of ErbB cell surface membrane receptors. In one aspect, the invention includes a method of determining a disease state or a health condition, wherein such condition is correlated with one or more ErbB cell surface membrane receptors measured directly in a patient sample, particularly a fixed tissue sample. associated with the number of aggregates. In another aspect, the invention includes a method of determining the status of cancer in a sample from an individual, wherein a measure of the amount of one or more ErbB cell surface receptor dimers in the cells of the sample is correlated with the status, comprising Presence or absence of a precancerous state, presence or absence of a cancerous state, cancer prognosis, or responsiveness to therapy. Preferably, the methods of the invention are carried out by employing panels of binding compounds with releasable molecular tags specific for various components of one or more types of receptor dimers. After binding, the molecular tags are released and isolated from the assay mixture for analysis.

The invention relates to novel bispecific antibodies and their use in tumor therapy. The novel antibodies have the ability to bind to ErbB receptors, preferably ErbB1 receptors, which are overexpressed on many cancer tissues. Since the different specificities of the antigen-binding sites are directed to different epitopes within the binding domain of same or different ErbB receptors, these antibodies are more effective with respect to inhibition and down-regulation of the ErbB receptor and the corresponding signaling cascade.

The invention relates to new peptide compounds capable of modulating cell proliferation, differentiation, survival and / or motility. The peptide compounds of the invention comprise short peptide fragments of the ErbB receptor and are capable of binding to ErbB and modulating activity of the receptor. The invention also relates to antibodies capable of binding to an epitope comprising a peptide sequence of the invention, pharmaceutical compositions comprising the peptide sequences and / or antibodies and uses thereof for treatment of conditions wherein modulating activity of ErbB is needed.

The present invention relates to nucleic acid and amino acid sequences of previously unknown ErbB ligands that are splice variants of previously known ErbB ligands, to compositions comprising these sequences and uses thereof in the diagnosis, treatment, and prevention of diseases and disorders mediated by ErbB receptors. Specifically, the present invention relates to splice variants lacking the C-loop of an intact EGF domain.

The invention provides a chimeric antigen receptor T cell of self-expression CD40 activated antibody and targeted ErbB receptor family and application thereof. The T cell contains a coding sequence ofa chimeric antigen receptor for expressing the targeted ErbB receptor family and a coding sequence of a CD40 activated antibody; and / or a chimeric antigen receptor and CD40 activated antibody expressing the targeted ErbB receptor family. The T cell has better reproduction activation performance and tumor cell killing function than those of a chimeric antigen receptor T cell of single targeted ErbB receptor family.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of receptor tyrosine kinase antagonists / inhibitors, especially ErbB receptor antagonists, more preferably EGF receptor (Her 1) antagonists and anti-angiogenic agents, preferably integrin antagonists, optionally together with agents or therapy forms that have additive or synergistic efficacy when administered together with the combination of antagonists / inhibitors, such as chemotherapeutic agents and or radiation therapy. The therapy can result in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone.

The present invention relates to certain 4-substituted 1H-pyrrolo[2,3-b]pyridine compounds of the formula (I) and pharmaceutically acceptable salts thereof. These compounds is useful in the treatmentor prevention of a disease or medical condition mediated through certain mutated forms of ErbB receptor, especially of Exon20 Her2 and EGFR mutations.

The present invention pertains to the field of cancer therapy using anti-cancer antibodies. The medical use of anti-MUC1 antibodies in combination with inhibitors of the ErbB receptor family is provided which show synergistic anti-cancer efficacy.