70 results about "Blocking antibody" patented technology

The embodiment of the invention is to conformationally constrain neutralizing B cell epitopes of CoV-2, CoV-n B cell epitopes of the open reading frame proteins, including the membrane S protein, constrained by protein scaffolds, including camelid VHH nanobody in order to elicit neutralizing and blocking antibodies against viral infection. B cell epitopes are molecularly evolved by ribosome display to preempt emerging viral B cell epitopes. Moreover, CTL epitopes are designed from the open reading frame protein for eliciting cell mediated viral protection. Furthermore, mRNA vaccines are prepared for eliciting protective immunity and prevent cytokine storms.

The present invention relates to antibodies, and fragments thereof, that bind and inhibit CD73. The invention also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g., cancer.

Provided are a fully human TSH receptor (TSHR) blocking monoclonal antibody for treating hyperthyroidism, and a preparation method therefor and a use thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and memory single B cells specifically recognizing a TSHR in the peripheral blood of patients having high titers of TSHR blocking antibody (TSH-stimulating blocking antibody, TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells for antibody property screening and validation, to obtain a blocking monoclonal antibody specifically targeting human TSHR. The fully human TSHR blocking monoclonal antibody can specifically bind to the TSHR, has good inhibitory activity in vitro and in vivo experiments, and has broad application prospects in the development of treatment of Graves' diseases.

The invention discloses a group of blocking monoclonal antibodies of an SH1 homologous cluster fully human thyrotropin receptor (TSHR) (a TSH receptor, TSHR) as well as a preparation method and application of the blocking monoclonal antibodies of the SH1 homologous cluster fully human thyrotropin receptor (TSHR). The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH receptor blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the synthesis and secretion of thyroid hormone are inhibited; expression and fibrosis of effector cell orbital fibroblasts TSHR for inhibiting thyroid-related eye diseases are remarkably relieved, and wide application prospects are achieved in treatment of Graves' diseases and diseases such as thyroid eye diseases caused by hyperthyroidism.

The invention discloses a group of blocking monoclonal antibodies of a CHK36 homologous cluster fully human TSH receptor (TSHR) as well as a preparation method and application of the blocking monoclonal antibodies. The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH-blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells, so as to obtain the TSHR-TBAb-TSHR-TBAb. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the synthesis and secretion of thyroid hormone are inhibited; according to the present invention, with the application of the compound, the expression and the fibrosis of the effector cell orbit fibroblast TSHR inhibiting the thyroid-related eye disease can be significantly reduced, and the wide application prospect is provided in the treatment of Graves' disease (Graves' disease, GD) and diseases caused by hyperthyroidism, such as thyroid eye disease (thyroid eye disease, TED), and the like.

Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality worldwide. Acute exacerbation of COPD (AE-COPD) in patients are mostly due to respiratory infection and are associated with an inexorable decline in lung function, enhanced oedema as well as airway and systemic inflammation. Previous results show that treatment with anti-IL-20Rb blocking antibodies increased the bacterial clearance in control mice infected by S. pneumoniae and protected CS-exposed mice from bacterial infection, by decreasing the bacterial burden and the inflammatory infiltrate. Therefore there is an interest for generating monoclonal antibodies specific for IL-20Rb with a neutralizing activity for their use in the treatment of AE-COPD. The present invention fulfills this need by providing antibodies having specificity for IL-20Rb.

The invention relates to the technical field of biological medicines, and discloses a blocking antibody targeting CXCL6 and an application of the blocking antibody in preparation of antitumor drugs. The antibody or antigen-binding fragment thereof is capable of binding specifically to human CXCL6 protein with high affinity (e.g., Kd < = 1 nM). According to the invention, the specificity and high affinity of the antibody are verified by Western Blot, immunofluorescence, immunohistochemistry and surface plasmon resonance (SPR) technologies. Functional experiments show that the antibody can effectively block CXCL6-induced neutrophil chemotaxis, including in Transwell, a three-dimensional gel model and a zebra fish living body model. Besides, in a mouse MC38 colon cancer model, the antibody shows remarkable anti-tumor activity and can inhibit tumor growth driven by CXCL6. The invention also provides a pharmaceutical composition containing the antibody, and application of the antibody in preparation of drugs for preventing or treating diseases (such as inflammatory diseases, autoimmune diseases and cancers) related to abnormal expression or activity of CXCL6.

The invention belongs to the technical field of immunohistochemical detection, and discloses a modified composite sealing buffer solution as well as a preparation method and detection application thereof. The modified composite blocking buffer solution comprises a basic buffer system, a composite blocking agent, a nonionic detergent, an endogenous interferent blocking agent and an antibody stabilizer, wherein the basic buffer system provides a stable pH environment and ionic strength; the composite sealing agent firstly occupies a shielding site, and the background is lowered; the nonionic detergent destroys hydrophobic interaction, effectively elute and loosen adsorbed molecules, and promote dissolution of components with relatively strong hydrophobicity; the endogenous interferent blocker can be combined with a receptor firstly, so that non-specific combination of an antibody and the receptor is blocked, and the problem of specific background is solved; the antibody stabilizer can protect the activity of the detection reagent and maintain the stability, and the obtained modified composite sealing buffer solution and the kit thereof have the advantages of multiple cooperative sealing mechanisms, prospective blocking of endogenous interference, improvement of the stability, compatibility and high efficiency of the antibody and the like.

The present invention relates to the treatment of locally advanced and metastatic muscle-invasive bladder cancers (MIBC). The present invention provides compositions to be used in immunotherapy of MIBC, especially in combination with an anti-PD-1 / PD-L1 / PD-L2 antibody-based therapy. The present invention also provides biomarkers of response to anti-PD-1 / PD-L1 / PD-L2 immune checkpoint blocking antibodies (ICBs), alone or together with anti-CTLA4 antibodies and / or chemotherapy, for best guiding their neoadjuvant use and avoid unefficient administration of potentially toxic drugs to patients with localized bladder cancers.

The present invention relates to an activatable transmembrane construct and an activatable degrader comprising the same, the activatable transmembrane construct comprising a cell penetrating portion, a cleavable portion and a shielding portion wherein the cell penetrating portion is selected from: a transmembrane peptide, an oligosaccharide peptide and any combination thereof, and / or the shielding portion is selected from a shielding peptide. The activatable transmembrane construct is connected with a target molecule binding part to form an activatable degradant. After the cleavable part is subjected to enzyme digestion, the cell penetrating part shielded by the shielding part is activated, so that the target molecule binding part connected with the cell penetrating part can be mediated to enter the cell to be degraded. After being connected with the activatable transmembrane construct, either a blocking antibody or a non-blocking antibody can achieve the effects of activating T cells and killing tumor cells, and the activatable transmembrane construct has additional benefits.

Provided are a set of fully human TSH receptor (TSHR)-blocking monoclonal antibodies targeting a CHK36 homolog cluster, a preparation method therefor, and an application thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and single memory B cells that specifically recognize TSHR in peripheral blood of a patient with a high titer of TSH-blocking antibodies (TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells to perform screening and validation of antibody properties to obtain a blocking monoclonal antibody that specifically targets human TSHR. The fully human TSH receptor-blocking monoclonal antibodies specifically bind to a TSHR, and effectively block signal transduction after a TSH binds to a receptor, inhibit the synthetic secretion of thyroid hormones, and significantly reduce and inhibit TSHR expression and fibrosis in orbital fibroblasts of effector cells associated with thyroid-related ocular diseases. The fully human TSH receptor-blocking monoclonal antibodies have broad application prospects in the treatment of Graves' disease (GD) and other diseases caused by hyperthyroidism, such as thyroid eye disease (TED).

Methods of improving PD-1 based immunotherapy in a subject suffering from a solid cancer, comprising decreasing bone morphogenetic protein 1 (BMP1) levels or function in T cells or in a tumor microenvironment (TME) or extracellular matrix (ECM) of the solid cancer are provided. Methods of treating a solid cancer comprising administering a PD-1 based immunotherapy and decreasing BMP1 levels or function in T cells or a TME or ECM of the solid cancer are also provided. Antibody drug conjugates comprising an anti-PDl blocking antibody and a BMP1 inhibiting small molecule or antibody or antigen binding fragment thereof small molecule inhibitor and pharmaceutical compositions for use in the methods of the invention are also provided.

The invention discloses a microsatellite stable colorectal cancer combination therapy based on a PCSK9 inhibitor, and belongs to the technical field of cancer treatment. The medicine for treating the microsatellite stable colorectal cancer comprises a PCSK9 inhibitor and a composition, and the composition comprises a PD-1 antibody and / or 5-fluorouracil. The invention provides a combination therapy of a PCSK9 blocking antibody combined with chemotherapy and immunotherapy. The combination therapy comprises a combination of a PCSK9 inhibitor, a PD-1 antibody and 5-FU for treatment of microsatellite stable colorectal cancer. The combination therapy can significantly enhance the sensitivity of the microsatellite stable colorectal cancer to 5-FU chemotherapy.

The application discloses a pancreatic cancer immunotherapy drug composition for jointly targeting CD96 and PD-1, relates to the technical field of biological medicine, and comprises an anti-human CD96 blocking antibody and an anti-human PD-1 blocking antibody. By jointly blocking the double immune checkpoints of CD96 and PD-1, the pancreatic cancer immunotherapy drug composition presents a significant synergistic effect compared with single antibody treatment, can effectively enhance the killing activity of T cells on pancreatic cancer cells, reverses the immune suppression microenvironment of pancreatic cancer, and restores the anti-tumor immune response of the body. The in-vivo experimental results show that the drug composition can significantly inhibit the growth of transplanted tumors, reduce the tumor volume and the tumor weight, and the tumor inhibition effect is obviously better than that of a single drug group. The preparation has stable properties and simple administration, and provides a safe and effective new immunotherapy scheme with a conversion application prospect for clinically refractory pancreatic cancer.

The invention relates to a polyclonal antibody capable of specifically recognizing human and mouse FBXO45 proteins. The immunogen of the antibody is the 127th-143rd amino acid sequence (as shown in SEQ ID NO: 1) of the FBXO45 protein. The invention also provides an application of the FBXO45 protein polyclonal antibody. The antibody disclosed by the invention has high affinity and high specificity, can stably recognize human and mouse FBXO45 protein, and can be used for Western blot detection; the method is high in purity, low in background signal and suitable for scientific research and clinical development; a key tool is provided for researching the functional mechanism of the FBXO45 in lung cancer, COPD and other diseases; the polypeptide has the potential of developing diagnostic kits, functional blocking antibodies and drugs, and has good social and economic benefits.

This disclosure provides methods for treating Hodgkin lymphoma in a subject comprising nivolumab, a PD-1 blocking antibody, which inhibits immune-tumor attack in patients with relapsed or refractory Hodgkin lymphoma.

Most of therapeutic failures in chemotherapy during cancer invasion and metastasis are attributed to drug resistance. The inventors aimed to investigate the potential of targeting the secreted protein, eAGR2 as a novel adjuvant strategy to enhance the effectiveness of chemotherapy and overcoming chemoresistance in cancer therapy. Remarkably, extracellular AGR2 (eAGR2) demonstrated the ability to enhance resistance to both (doxorubicin and tamoxifen) treatments. Furthermore, even in the case of drug-resistant cancer cells that exhibited inherent resistance to chemotherapy, supplementation with an AGR2-blocking antibody restored sensitivity to tamoxifen in vitro. Thus, the inventor shed light on previously unknown chemotherapy resistance in resistant breast cancer cells, which can be effectively overcome by blocking eAGR2. Consequently, the inhibition of eAGR2 emerges as a promising adjunctive approach for concurrent administration alongside existing first- and second-line cancer therapies. This not only has the potential to bolster the efficacy of chemotherapy but also to prevent tumour chemoresistance.

The invention relates to the technical field of biological detection, in particular to an infectious bovine rhinotracheitis virus gB monoclonal antibody with a blocking effect and application of the infectious bovine rhinotracheitis virus gB monoclonal antibody. The amino acid sequence of the variable region of the heavy chain of the infectious bovine rhinotracheitis virus gB monoclonal antibody is as shown in SEQ ID No.2. The amino acid sequence of the light chain variable region is as shown in SEQ ID No.4. The amino acid sequence of the heavy chain variable region is formed by coding a nucleotide sequence of the heavy chain variable region, and is as shown in SEQ ID No. 1; the amino acid sequence of the light chain variable region is formed by coding a nucleotide sequence of the light chain variable region, and is shown as SEQ ID No.3. The infectious bovine rhinotracheitis virus gB monoclonal antibody can specifically recognize the infectious bovine rhinotracheitis virus gB protein, and the infectious bovine rhinotracheitis virus neutralizing antibody in bovine serum can effectively block the reaction between the monoclonal antibody and the infectious bovine rhinotracheitis virus gB protein. The monoclonal antibody can be used for establishing an infectious bovine rhinotracheitis virus gB protein blocking ELISA antibody detection method. The invention relates to an infectious bovine rihinotracheitis virus gB monoclonal antibody and application thereof, which provide material support and technical support for development of detection and diagnosis technologies of infectious bovine rihinotracheitis in China and are beneficial to further promotion of purification of infectious bovine rihinotracheitis in China and improvement of culture benefits.

The present application relates to an activin receptor II antibody and a use. The activin receptor II antibody comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3. A mutation relative to CDRs of a parental antibody includes one or more selected from the following: a heavy chain CDR2 V54A mutation, a heavy chain CDR2 G56L mutation, a heavy chain CDR2 T58K mutation, a heavy chain CDR3 G99S mutation, a heavy chain CDR3 G99T mutation, a light chain CDR1 G24H mutation, a light chain CDR1 D28W mutation, a light chain CDR1 Y32F mutation, a light chain CDR2 P57E mutation, a light chain CDR3 S97A mutation, and a light chain CDR3 Y99N mutation. A balanced activin receptor II dual-blocking antibody that exhibits higher affinity for ActRIIA while not significantly reducing affinity for ActRIIB is obtained by screening.

Provided herein are compositions, methods, and kits for treating inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis, in a mammal in need thereof. The methods include administering to a subject with IBD a combination therapy comprising a therapeutically effective amount of a chemokine receptor 9 (CCR9) inhibitor compound and a therapeutically effective amount of an anti-IL-23 antibody. Kits comprising the CCR9 inhibitor compound and the anti-IL-23 antibody are also provided herein.

A method for phase separation-based modification of a chimeric antigen receptor, and the use thereof. It has been discovered that the intracellular domain of CD28 can undergo phase separation with the intracellular domains of Lck and PD-1 and regulate T cell activation, and upon researching the molecular mechanisms of CD28 / Lck and CD28 / PD-1 phase separation, it has been discovered that two mutations of the intracellular domain of CD28 inhibits phase separation thereof with PD-1 and do not affect phase separation thereof with Lck. Incorporating the intracellular domain of CD28 having the two mutations in CAR-T design facilitates CAR-T resistance to PD-1 inhibition, and the therapeutic efficacy may be further improved by joint use with PD-1 blocking antibodies.

The invention discloses a preparation method and application of a Taq DNA polymerase monoclonal antibody based on structural domain analysis, which are specifically different from a traditional method using full-length Taq polymerase as an immunogen (the method generally cannot generate a functional blocking antibody due to a hidden epitope which is difficult to approach). According to the invention, by adopting a structure-oriented and domain-specific strategy, the exposure of epitopes related to active sites is remarkably enhanced, and a novel antigen Taq-P protein is developed. Based on the antigen, a high-specificity inhibitory monoclonal antibody is prepared, and the antibody is expected to become a core component of a high-performance hot start PCR reagent. According to the invention, a novel and generalizable mode is established for the development of a core diagnostic reagent, a key raw material is provided for gene detection and molecular diagnosis, and a valuable methodological framework is contributed to the development of propulsor engineering and biotechnology reagents.

To provide a novel treatment method for treating organ fibrosis in a subject.SOLUTION: A method for treating organ fibrosis in a subject comprises administering to a subject a therapeutically effective amount of one or more antibodies or antigen binding fragments thereof that bind to and block soluble ephrin-B2 ectodomain.SELECTED DRAWING: None

The present disclosure provides antigen binding proteins that specifically bind PD-1. The present disclosure further provides mouse anti-mouse PD-1 blocking antibodies, engineered cells, and methods of making and using the antigen binding proteins, anti-PD-1 antibodies, and cells of the disclosure. Aspects of the disclosure further relate to a polypeptide comprising any one of the complementary determining regions of the present disclosure.

The present application relates to an anti-PD-1 and OX-40 bifunctional antibody and a preparation method and application thereof. The bifunctional antibody comprises an antibody domain targeting PD-1 and an antibody domain targeting OX-40. The present application designs a novel anti-PD-1 / OX-40 bifunctional antibody, constructs a specific structure bifunctional antibody by using a PD-1 activating antibody and an OX-40 blocking antibody, and the whole synergizes, has high affinity to PD-1, can activate PD-1 activity and its signal pathway, has high affinity to OX40, can block OX40 / OX40L interaction and its signal transduction, inhibits T cell proliferation, inhibits CD25 or PD-1 positive CD4 + T cell production can be applied to the development of related drugs for treating inflammatory or autoimmune diseases.

The invention discloses a group of blocking monoclonal antibodies of an SH23 homologous cluster fully human thyrotropin receptor (TSHR) (a TSH receptor, TSHR), a preparation method of the blocking monoclonal antibodies, and an application of the blocking monoclonal antibodies of the SH23 homologous cluster fully human thyrotropin receptor (TSHR), the SH23 homologous cluster fully human thyrotropin receptor (TSHR) and the preparation method of the blocking monoclonal antibodies. The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH-blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells, so as to obtain the TSHR-TBAb-TSHR-TBAb. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the compound disclosed by the invention has good inhibitory activity in vitro and in vivo experiments, and has a wide application prospect in the aspect of treating Graves' diseases (Graves' disease, GD) and diseases caused by hyperthyroidism, such as thyroid eye diseases (thyroid eye disease, TED) and the like.

The invention relates to the technical field of antibodies, and particularly provides an antibody specifically bound with African swine fever virus p34 protein or an antigen binding fragment thereof and application thereof. The antibody or the antigen binding fragment thereof comprises a heavy chain variable region as shown in SEQ ID NO.1 and a light chain variable region as shown in SEQ ID NO.3, and the antibody or the antigen binding fragment thereof can recognize ASFV p34 protein with high specificity. The invention also provides a nucleic acid molecule for coding the antibody or the antigen binding fragment thereof, an expression vector, a recombinant cell and other biological materials. The antibody or the antigen binding fragment thereof can be used for preparing an African swine fever virus detection product, particularly a blocking ELISA antibody detection kit, and the kit has the advantages of high sensitivity, strong specificity, simplicity and convenience in operation and the like, and is suitable for serological monitoring and diagnosis of ASFV. The invention provides an effective detection tool for prevention and control of African swine fever.

An antibody, preferably a blocking antibody, and most preferably a monoclonal antibody (mAb), specific for human endothelial cell protein C receptor (EPCR) such as mAbs JRK 1494 or JRK 1535 is used to reduce or attenuate joint swelling, macrophage infiltration, iron deposition and / or blood vessel formation and to treat arthropathy in a hemophilic subject.

Blocking antibodies against αMβ2 (CBP-α-αMβ2), αM (CBP-α-αM), α3 (CBP-α-α3), and anti-TGFβ as well as inhibitors of Talin2 reverse fibrosis in a mouse fibrosis model. Accordingly, aspects of the disclosure relate to inhibitors of Talin2 and inhibitors of the integrins αMβ2, αM, and α3. Aspects relate to a method for treating and / or reversing fibrosis in a subject comprising administering a composition comprising an inhibitor of Talin2 or a composition comprising a nucleic acid of the disclosure. Further aspects relate to a method for treating and / or reversing fibrosis in a subject comprising administering a composition comprising an antibody conjugate of the disclosure or a composition comprising an inhibitor or blocking agent of integrin α3, αM, αMβ2, or combinations thereof to the subject. Methods also include treating kidney fibrosis in a subject comprising administering a composition comprising an anti-TGFβ antibody operatively linked to an ECM-affinity peptide. The methods may be for reducing or decreasing the amount of existing fibrosis. The methods differ from traditional methods for treating fibrosis, since the current methods do not delay or inhibit the progression of fibrosis, but instead have shown to reverse, reduce, and / or decrease existing fibrosis. Accordingly, methods of the disclosure may be used in a manner that provides treatment to existing fibrosis rather than a prophylactic to prevent more fibrosis.

The invention discloses a coupling protein as well as a preparation method and application thereof. According to the preparation method disclosed by the invention, in-vitro self-coupling of the rotavirus VP8 protein and the norovirus VP1 protein is realized by utilizing a Spatier-Spytag system, the prepared coupled protein can induce a neutralizing antibody with higher titer aiming at the rotavirus, and the immunogenicity of the norovirus VP1 protein is not influenced; the immunized animal / human body can generate a high-titer specific IgG binding antibody, a serum blocking antibody and a neutralizing antibody aiming at the two viruses. The coupling protein has a wide application prospect in vaccines for resisting infant diarrhea viruses (norovirus and rotavirus).