121 results about "Human Epidermal Growth Factor Receptor 2" patented technology

The present invention relates to a method for prognosing cancer in a subject with triple negative (TN) breast cancer, whose tumors lack expression of the estrogen receptor (ER), the progesterone receptor (PR) and normal (not amplified) levels of the human epidermal growth factor receptor 2 (HER2). Methods and biomarkers are disclosed that are useful for predicting the overall survival (OS) potential of cancer in a subject with triple negative breast cancer or for predicting metastatic disease in a subject with triple negative breast cancer. For example, the method comprises detecting in a sample from a subject one or more biomarkers selected from the group consisting of ANK3, CD24, EIF1, KLF6, KRAS, KRT1, MAP2K4, SDC4, SLC2A3, STK3, TFAP2C, and WRN. An increase or decrease in one or more biomarkers as compared to a standard is prognostic of OS of TN breast cancer. Likewise, in another example, the method comprises detecting in a sample from a subject one or more biomarkers selected from the group consisting of ANG, DICER1, EIF1, and MSH6. An increase or decrease in one or more biomarkers as compared to a standard is prognostic of metastasis of TN breast cancer.

Bispecific antibodies which comprise antigen-binding regions binding to two different epitopes of human epidermal growth factor receptor 2 (HER2), and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods of preparing and using the antibodies are also disclosed.

A method for determining an expression of human epidermal growth factor receptor 2 (HER2) of a subject. The method includes providing a sample from the subject; measuring one of (i) amounts of two or more proteins in the sample, each protein having a molecular weight substantially equal to 4740, 8404, 8419, 8435, 8450, 8455, 8465, 8570, 8607 or 8626 atomic mass units, and (ii) amounts of at least one of human cystein-rich intestinal protein 1 (CRIP1), one or more variants of the human cystein-rich intestinal protein 1 (CRIP1 variants), and proteolytic digestion products thereof in the sample; and comparing the amounts of the proteins to control amounts, which control amounts are determinative of the expression of the human epidermal growth factor receptor 2.

The invention belongs to the field of biotechnology, and discloses a FISH (fluorescence in situ hybridization) probe, a kit and a detection method for detecting Her2 (human epidermal growth factor receptor 2) gene free from repetitive sequence. The Her2 gene is used as a template to perform polymerase chain reaction on non-repetitive sequence in the Her2 gene, the amplification product is DNA (deoxyribonucleic acid) fragments with 350-800 different base pairs, the repetitive sequence in the Her2 gene is eliminated so as to form the product free from repetitive sequence; after the product is in fluorescence labeling, the Her2 gene free from repetitive FISH is obtained for the Her2 gene FISH detection. The Her2 gene FISH probe obtained by the invention can eliminate the repetitive sequence, the non-specific background signal of the Her2 gene FISH probe can be obviously reduced, and the specificity of the FISH probe is improved.

Isolated monoclonal antibodies which bind to human epidermal growth factor receptor 2 (HER2), and related anti-body-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies are also disclosed.

Described herein are isolated bi-specific antigen binding constructs, e.g., antibodies. The bi-specific antigen binding constructs include two antigen binding polypeptide constructs, e.g., a Fab and an scFv. The first antigen-binding polypeptide construct monovalently and specifically binds to extracellular domain 4 (ECD4) of HER2 (human epidermal growth factor receptor 2); the second antigen-binding polypeptide construct monovalently and specifically binds to an extracellular domain (ECD) of HER3 (human epidermal growth factor receptor 3). One antigen binding polypeptide construct is a Fab format and the other antigen binding polypeptide construct is an scFv format. The bi-specific antigen binding constructs includes an Fc having two Fc polypeptides each having a CH3 domain for dimerization. Each Fc polypeptide is linked to the C-terminus of one of the antigen binding polypeptide constructs with or without a linker.

Bispecific antibodies which comprise antigen-binding regions binding to two different epitopes of human epidermal growth factor receptor 2 (HER2), and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods of preparing and using the antibodies are also disclosed.

The invention relates to a polypeptide for specifically targeting a human epidermal growth factor receptor 2 (HER2) protein. The polypeptide is shown in the following general formula 1 of X1X2X3X4X5X6X7RX8YWX9X10X11X12X13X14X15X16X17RX18X19X20X21YX22. The invention also relates to a nucleotide sequence for coding the polypeptide, an expression vector for expressing the polypeptide and a host cell. The invention also relates to the polypeptide and its bivalent or multivalent, a pharmaceutical composition prepared from the polypeptide or its bivalent or multivalent as a targeting polypeptide, a preparation for killing cancer cells and a developing agent, and a use of the polypeptide and its bivalent or multivalent. The polypeptide has HER2 positive cell targeting effects and strong selectivity. The polypeptide can be prepared by a chemical synthesis method and has the advantages of high purity, small molecular weight, strong singularity, no immunogenicity, safety and reliability.

Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

The invention discloses a fluorescence in situ hybridization probe and kit for detecting HER-2 (human epidermal growth factor receptor-2) gene amplification and relates to an FISH (fluorescence in situ hybridization) kit. The fluorescence in situ hybridization kit for detecting HER-2 gene amplification comprises an LSP HER-2 / CSP 17 probe and DAPI redyeing liquid; and the probe is marked by adopting a random primer method and is a fluorescence in situ hybridization double-color probe, an HER-2 gene is indicated by a red signal, and the internal control CSP17 is indicated by a green signal. An FFPE tissue slice is used as a detection sample, the FISH method is adopted for detecting the HER-2 gene amplification state, and the probe and the kit can be used for diagnosis of molecular markers for invasive breast cancer and stomach cancer and assisting in clinical medication selection.

The invention discloses a detection primer combination and a kit for HER2 (human epidermal growth factor receptor 2) gene amplification. The detection primer combination comprises an HER2 primer combination and a GAPDH reference primer combination; each combination comprises upstream and downstream amplification primers of a target gene of the combination and a Taqman fluorescent probe. The kit comprises the detection primer combination, a positive quality control and a negative quality control. By using the detection primer combination and the kit, whether the HER2 gene in patients with breast carcinoma is amplified or not can be detected quickly and simply; compared with the FISH (fluorescent in situ hybridization) method, a method using the detection primer combination and the kit is high in detection sensitivity, low time consumption, generally 1.5 to 2 hours for acquiring reaction results, low in cost, low in false positive ratio, and suitable for large-scale clinical development; thus, quick, effective and accurate detection is achieved for HER2 gene amplification, and timely disease treatment and treatment effect monitoring are guaranteed.

The invention provides a preparation method of a breast cancer-specific epitope polypeptide-loaded dendritic cell vaccine, and the method comprises the following steps: loading dendritic cells with identified human leukocyte antigen A201 positive epitope polypeptide of human epidermal growth factor receptor 2, breast cancer drug resistance protein and IQ motif and Sec7 structural domain 1 protein which specifically express in breast cancer (namely polypeptide comprising the amino acid sequence shown in any of SEQ ID No.1-6) to prepare into the dendritic cell vaccine which can induce strong breast cancer-targeting cytotoxic T lymphocyte response. The invention also provides a kit comprising the breast cancer-specific epitope polypeptide-loaded dendritic cell vaccine.

Isolated monoclonal antibodies which bind to human epidermal growth factor receptor 2 (HER2), and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies are also disclosed.

Isolated monoclonal antibodies which bind to human epidermal growth factor receptor 2 (HER2), and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies are also disclosed.

The present invention relates to a method for prognosing cancer in a subject with triple negative (TN) breast cancer, whose tumors lack expression of the estrogen receptor (ER), the progesterone receptor (PR) and normal (not amplified) levels of the human epidermal growth factor receptor 2 (HER2). Methods and biomarkers are disclosed that are useful for predicting the overall survival (OS) potential of cancer in a subject with triple negative breast cancer or for predicting metastatic disease in a subject with triple negative breast cancer. For example, the method comprises detecting in a sample from a subject one or more biomarkers selected from the group consisting of ANK3, CD24, EIF1, KLF6, KRAS, KRT1, MAP2K4, SDC4, SLC2A3, STK3, TFAP2C, and WRN. An increase or decrease in one or more biomarkers as compared to a standard is prognostic of OS of TN breast cancer. Likewise, in another example, the method comprises detecting in a sample from a subject one or more biomarkers selected from the group consisting of ANG, DICER1, EIF1, and MSH6. An increase or decrease in one or more biomarkers as compared to a standard is prognostic of metastasis of TN breast cancer.

The invention relates to polypeptide capable of specifically targeting HER2 (human epidermal growth factor receptor 2) protein and an application of the polypeptide. The polypeptide is shown by the following general formula: X1X2X3X4X5LX6X7X8NPX9X10X11X12X13. The invention also relates to a nucleotide sequence for coding the polypeptide, and an expression vector for expressing the polypeptide, and host cells; and the invention also relates to the polypeptide, a bivalent or a multivalent formed by the polypeptide, and a pharmaceutical composition which is formed by the polypeptide serving as a targeting polypeptide, a preparation capable of killing cancer cells, and an imaging preparation, as well as applications of the polypeptide, the bivalent or the multivalent, and the pharmaceutical composition. The polypeptide provided by the invention can achieve a targeting effect on positive tumor cells of HER2, is strong in selectivity, can be prepared by adopting a chemical synthesis method, is high in purity, small in molecular weight and strong in specificity, and is free of immunogenicity, safe and reliable.

The invention relates to a method of typing a sample from a breast cancer patient. More specifically, the invention relates to a method for classification of breast cancer according to the presence or absence of Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal growth factor Receptor 2 (ERBB2; HER2). More specifically, the invention provides methods and means to classify breast cancer as ER positive, triple negative (ER−, PR− and HER2−) and HER2+.

The invention discloses a nucleotide sequence and a kit for detecting a human epidermal growth factor receptor-2 (HER-2), which belong to the technical field of molecular diagnosis. A primer and a probe for detecting the HER-2 provided by the invention can be used for specifically amplifying and detecting amplification of an HER-2 gene. The invention also discloses the detection kit for detectingthe HER-2 gene based on a microdroplet type PCR (Polymerase Chain Reaction) system, so that the amplification of the HER-2 gene can be quickly, sensitively and accurately detected. The nucleotide sequence and the kit provided by the invention have the advantages of simplicity and convenience in operation, high specificity, high sensibility, low cost, high throughput and the like, can be used for quickly detecting clinic HER-2 gene amplification, and provide references for diagnosis and treatment of the clinic human epidermal growth factor receptor-2.

The present invention relates to the treatment of breast cancer which is estrogen receptor positive (ER+) and / or human epidermal growth factor receptor 2 positive (HER2) and / or progesterone receptor positive (PR) and / or facilitates chromatin transcription positive (FACT+) with a curaxin, including curaxin 137. The present invention also pertains to a method of identifying a subject who has a breast cancer tumor and is likely to respond to treatment with a curaxin.

The invention provides a cell prepared product containing CD8+T cells. The invention also provides a method for preparing the cell prepared product containing the modified CD8+T cells, as well as application of the cell prepared product in treating HER2 positive tumors.

Isolated monoclonal antibodies which bind to human epidermal growth factor receptor 2 (HER2), and related anti-body-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies are also disclosed.

The invention discloses a growth medium for cultivating stem cells. The growth medium contains a basal culture medium and an additive, wherein the additive contains an antibody for resisting a human vascular endothelial growth factor, an antibody for resisting a human epidermal growth factor receptor 1, an antibody for resisting a human epidermal growth factor receptor 2 and vernine-5-sodium triphosphate. The invention also provides use of the growth medium in cultivation of umbilical cord mesenchymal stem cells, and also discloses a method for cultivating the umbilical cord mesenchymal stem cells. According to the method, the umbilical cord mesenchymal stem cells are inoculated and cultivated in the growth medium. Through the technical scheme, the in vitro amplification capability of the umbilical cord mesenchymal stem cells can be greatly improved.

The invention relates to a HER2 (Human Epidermal Growth Factor Receptor 2) protein nucleotide aptamer, a complex, a composition and applications thereof, and in particular relates to an HER2 (Human Epidermalgrowth Factor Receptor-2) protein specificity combined nucleotide aptamer which has the sequence shown in SEQ ID NO:5. The invention further relates to the complex formed by combining the HER2 protein specificity combined nucleotide aptamer with a chemotherapeutic medicine or wrapping the HER2 protein specificity combined nucleotide aptamer and the chemotherapeutic medicine in a nanoparticle together, the composition comprising the complex, and anti-tumor application as well as an tumor targeted imaging application of the nucleotide aptamer, the complex and the composition.

The invention discloses a kit for amplifying a Her2 (Human epidermal growth factor receptor-2) gene in human peripheral blood circulating tumor DNA (Deoxyribonucleic Acid). By adopting component setting of the kit and a result reading scheme, a detection process is simple and convenient and the operability is strong. A detection result is reliable and has good specificity; meanwhile, a real-time fluorescence PCR (Polymerase Chain Reaction) technology is used for detecting an amplification level of the Her2 gene in a breast cancer tissue specimen through calculating a deltaCt value; the kit can be used for a plurality of research fields including breast cancer auxiliary diagnosis carried out through detection of ctDNA of the blood, clinical application, prognosis and the like.

The invention discloses a method for detecting the concentration of human epidermal growth factor receptor-2 (HER-2). The method comprises the following steps: grinding, cleaning and drying gold electrodes; inserting the gold electrodes into a polypeptide solution for carrying out self-assembly, and then closing the gold electrodes with mercapto hexanol; respectively dripping HER-2 with different concentrations onto the surfaces of the gold electrodes for carrying out reactions, and then enabling the gold electrodes to react with an aptamer; dripping molybdate onto the surfaces of the gold electrodes for carrying out reactions to obtain a plurality of to-be-detected gold electrodes; respectively measuring the gold electrodes by using a square wave voltammetry to obtain a plurality of square wave voltammetric curves, and making a standard curve according to peak currents in all the curves and the corresponding concentrations of the HER-2; dripping the HER-2 to be detected onto the surface of the gold electrode assembled with polypeptide for carrying out a reaction, then enabling the gold electrode to react with the aptamer, dripping molybdate onto the surface of the gold electrode, measuring by using the square wave voltammetry to obtain a square wave voltammetric curve, and contrasting the peak current with the standard curve to obtain the concentration of the HER-2. The detection method is convenient and fast, good in selectivity, high in sensitivity and wide in detection range.

The invention provides specific HER2 (human epidermal growth factor receptor 2) protein targeted polypeptide. The polypeptide is a mutant obtained with pertuzumab 46-65th amino acid as a template, can be specifically combined with HER2 high-expression positive breast cancer cells, and has the higher affinity than pertuzumab. The invention further provides a derivative of the polypeptide. The derivative is a bivalent or polyvalent formed from the polypeptide. The polypeptide has the character of targeting HER2 positive cancer cells, and is high in selectivity. The polypeptide can be prepared through a chemical synthesis method, is high in purity, small in molecular weight, strong in specificity, free of immunogenicity, safe and reliable, and can be used for cancer targeted therapy or cancer targeted molecular imaging and diagnosis.

The invention provides a bispecific antibody capable of resisting human epidermal growth factor receptor 2 (HER2) and human insulin-like growth factor-IR (IGF-IR), and a preparation method and applications thereof. The bispecific antibody comprises a first antigen binding domain used for specific binding of HER2, and a second antigen binding domain used for specific binding of IGF-IR; the first antigen binding domain and the second antigen binding domain both comprise an antibody heavy chain variable structural domain (VH) and an antibody light chain variable structural domain (VL); the first antigen binding domain is an antibody variable structural domain capable of realizing specific binding with HER2; and the second antigen binding domain is an antibody variable structural domain capable of realizing specific binding with IGF-IR. The preparation method comprises following steps: synthesis of cDNA sequences used for coding the bispecific antibody; the cDNA sequences are inserted into a carrier for construction of an expression vector; expression of the expression vector is realized in host cells, and the bispecific antibody obtained by expression is separated and purified. The bispecific antibody can be used for preparing medicines used for treating human cancer, especially human breast cancer.

The invention relates to an inhibitor containing fused ring derivative as well as a preparation method and application thereof. Particularly, the invention relates to a compound as shown in a generalformula (I), a preparation method thereof, a pharmaceutical composition containing the compound, and application of the compound as a kinase inhibitor, particularly as a receptor tyrosine kinase inhibitor (TKI), more particularly as an EGFR (epidermal growth factor receptor) or HER2 (human epidermal growth factor receptor 2) inhibitor to treatment of cancer, inflammation, chronic liver diseases, diabetes, cardiovascular diseases, AIDS and other related diseases. Each substituent in the general formula (I) is the same as the definition in the specification.

A non-aqueous single pot synthesis of [18F]SFB is set forth. The [18F]SFB produced with this method is then used, for example, to label a peptide or an engineered antibody fragment (diabody) targeting human epidermal growth factor receptor 2 (HER2) as representative examples of labeled compounds for use as an injectable composition to locate abnormal tissue, specifically tumors within an animal or human using a PET scan.

The invention discloses a Mefatinib composition, a related compound, and a preparation method and application of the Mefatinib composition. The Mefatinib composition comprises Mefatinib disclosed in aformula (I) and compound, wherein the normalized percentage content of the compound is 1.0% or lower, and the compound is disclosed by a formula (II) which is not zero. The Mefatinib composition canbe used for treating or preventing various adaptation diseases related to EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal growth factor Receptor-2) kinase functions, and a toxic reaction occurrence rate is low. The compound disclosed by the formula (II) can be used as the standard substance of relevant substances in the Mefatinib, and is used for the quality control of Mefatinibraw material drugs or preparations. The formula (I) and the formula (II) are shown in the description.