425 results about "HIV Positivity" patented technology

The invention discloses an anti-PD-L1 antibody coupling drug and a preparation method thereof, belongs to the field of biological medicines, and is used for preparing anti-cancer drugs. The antibody coupling medicine is formed by coupling an anti-PD-L1 antibody and a payload through a linker, a light chain variable region sequence of the antibody is a sequence recorded by SEQ ID NO: 1, a heavy chain variable region sequence of the antibody is a sequence recorded by SEQ ID NO: 2, the payload is an avixatecan derivative Dxd, and the ratio (DAR) of the payload to the antibody is 6-8. The antibody-conjugated drug has a better killing effect on PD-L1 positive tumor cells of human and dogs, and has fewer dimers and higher thermal stability at a high DAR value (DAR6-8), and an accelerated stability test shows that the antibody-conjugated drug has good structural stability and binding activity.

The invention belongs to the technical field of immunology and in vitro diagnosis, and relates to a monoclonal antibody aiming at bovine nodular skin disease virus (LSDV) L1R protein. According to the invention, the LSDV recombinant L1R protein with deletion of a transmembrane region (182-204aa) is obtained through expression; after a mouse is immunized by the protein, a monoclonal antibody 8D5 which is good in reactivity and specificity and aims at the LSDV L1R protein is screened out; heavy chain and light chain variable region sequences for coding the monoclonal antibody 8D5 are obtained; the monoclonal antibody 8D5 can be subjected to specific reaction with LSDV L1R protein, the recombinant protein L1R can be specifically recognized by bovine LSDV positive serum, meanwhile, the monoclonal antibody 8D5 can be used for establishing an LSDV ELISA antibody detection method, and a foundation is laid for LSDV diagnostic technology and vaccine research and development.

The invention belongs to the technical field of biological detection, and particularly relates to a monoclonal antibody 1D3 for detecting a porcine epidemic diarrhea virus antibody and application of the monoclonal antibody 1D3. The CDR sequences of the heavy chain variable region are respectively shown as SEQ ID NO.1-3, and the CDR sequences of the light chain variable region are respectively shown as SEQ ID NO.4-6. The antibody can specifically recognize PEDV / S1 protein, binding of the antibody can be competitively blocked by a PEDV specific neutralizing antibody in serum, and the antibody is suitable for establishing a blocking ELISA method. A detection tool based on the antibody has high specificity and sensitivity, and the blocking rate to PEDV positive serum is higher than 50%. The invention can be used for preparing a detection kit or evaluating the immune effect of a vaccine, and provides an efficient and accurate technical means for PEDV infection diagnosis and immune monitoring.

The invention discloses preparation of a human CD56 immune phage display antibody library, which comprises the following steps: S1, animal immunization: expressing recombinant hCD56 protein in escherichia coli, then immunizing a Balb / c mouse, and detecting immune titer; s2, splenocyte preparation: extracting RNA (Ribonucleic Acid) of immune mouse spleen cells, and performing reverse transcription to obtain cDNA (Complementary Deoxyribonucleic Acid); s3, preparation of an initial bacteriophage display library: amplifying a heavy chain variable region and a light chain variable region by using a PCR technology, and then assembling to form scFv; constructing scFv phagocytids, electrically transforming the scFv phagocytids into TG1 competent cells, and constructing a bacterial library; s4, constructing a phage single-chain library of the hCD56: infecting the bacterial library by using a helper phage M13K07, and constructing a phage single-chain antibody library; and S5, elutriation and screening of a phage library: specifically enriching a phage single-chain antibody library, screening positive clones from the phage single-chain antibody library, and determining a sequence. According to the invention, the human hCD56 antibody scFv sequence fragment can be screened out, and the research and development period is shortened.

The invention relates to an anti-RSV polypeptide membrane fusion inhibitor as well as a preparation method and application thereof. The invention discloses a compound, a pharmaceutical salt or a derivative thereof, a pharmaceutical composition and a preparation product containing the compound, and application of the compound and the pharmaceutical salt or the derivative in preparation of medicines for preventing and / or treating diseases caused by RSV or other paramyxoviridae viruses. The polypeptide disclosed by the invention shows the anti-RSV activity and safety which are obviously superior to those of positive control polypeptide. Molecular interaction experiments show that the polypeptide acts on the NHR region of the RSV F protein, and the fusion of the RSV virus and a target cell is prevented by forming an inactive six-helix structure with NHR, or by destroying the RSV NHR structure and inhibiting the process of forming a six-helix bundle by NHR and CHR in the F protein in the key step of RSV infection.

This invention belongs to the field of biodetection technology, specifically relating to a monoclonal antibody 1D3 for detecting porcine epidemic diarrhea virus (PEDV) and its applications. Its heavy chain variable region CDR sequences are SEQ ID NO. 1-3, and its light chain variable region CDR sequences are SEQ ID NO. 4-6. This antibody specifically recognizes the PEDV / S1 protein, and its binding can be competitively blocked by PEDV-specific neutralizing antibodies in serum, making it suitable for establishing a blocking ELISA method. Detection tools based on this antibody exhibit high specificity and sensitivity, with blocking rates exceeding 50% against PEDV-positive serum. This invention can be used to prepare detection kits or evaluate vaccine immunization efficacy, providing an efficient and accurate technical means for PEDV infection diagnosis and immune monitoring.

The invention relates to the technical field of antibodies, in particular to an antibody or an antigen binding fragment specifically binding to avian leukosis virus p27 protein and application of the antibody or the antigen binding fragment. The antibody or the antigen binding fragment contains a heavy chain variable region and a light chain variable region, the amino acid sequence of the heavy chain variable region is shown as SEQ.ID NO.1 or SEQ.ID NO.5, and the amino acid sequence of the light chain variable region is shown as SEQ.ID NO.3 or SEQ.ID NO.7. The antibody or the antigen binding fragment is positive in reaction with the avian leukosis virus, so that the antibody or the antigen binding fragment has good reaction characteristics with the avian leukosis virus.

The invention discloses an anti-CLDN6 nano antibody and related application thereof, and relates to the field of antibodies. The invention provides an anti-CLDN6 nano antibody, which comprises HCDR1, HCDR2 and HCDR3 in a heavy chain variable region of which the amino acid sequence is as shown in SEQ ID NO: 4, the nano antibody has excellent antigen binding activity, high specificity and good affinity, has relatively strong killing activity on cells with high expression of CLDN6, and can be used for preparing anti-CLDN6 drugs. The requirements of CLDN6 positive tumor immunotherapy on efficient, specific and high-penetrability antibody molecules are met, and a new strategy and means are provided for tumor therapy.

The invention provides bovine ephemeral fever virus positive serum as well as a preparation method and application thereof. The preparation method comprises the following steps: culturing bovine ephemeral fever virus by using MDBK suspension cells, inactivating by using beta-propiolactone, concentrating by using a 500kd hollow fiber column to obtain an antigen solution, and emulsifying the antigen solution and 61VG adjuvant according to a mass ratio of 1: 1.5 to prepare the vaccine; carrying out primary immunization and secondary immunization on the receptor, collecting blood of which the serum neutralizing antibody titer is greater than 1: 4096 14-21 days after the secondary immunization, and separating to obtain positive serum. The positive serum can be used for specific test, identification test and the like of the bovine ephemeral fever virus, can also be used for preparing related reagents, kits and standard substances, and provides efficient and normative technical support for prevention and control of bovine ephemeral fever.

The invention relates to a porcine reproductive and respiratory syndrome virus (PRRSV) dimer nucleocapsid (N) protein (PRRSV N-dimer) and application thereof. The PRRSV N-dimer is formed by connecting N protein amino acid sequences in series through (GGGGS) 3linker. According to the invention, a GGGGS 3linker nucleotide sequence is connected in series with a PRRSV NADC30-like strain N protein gene sequence to construct a prokaryotic expression vector, and a recombinant PRRSV N-dimer is expressed in escherichia coli. Through SDS-PAGE (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis) and Western-blot detection, the recombinant PRRSV N-dimer obtains soluble expression and can be subjected to a specific reaction with PRRSV positive serum; through detection by a freeze thawing method and an ELISA (Enzyme-Linked Immunosorbent Assay) method, compared with a PRRSV monomer N protein (PRRSV N-monomer), the PRRSV N-dimer protein can be stably preserved, and the immunoreactivity is better. A PRRSV antibody indirect enzyme-linked immunosorbent assay (iELISA) detection method is established on the basis of a PRRSV N-dimer, and can be applied to diagnosis and monitoring of PRRSV infection.

Provided herein are novel Glypican 3 (GPC3) antibodies or antigen binding fragments and GPC3 / CD3 bispecific antibodies. The present application also provides chimeric antigen receptors comprising the antibodies or antigen-binding fragments, related CAR-T cells, and preparation methods and uses of the same. The present application further provides pharmaceutical compositions comprising GPC3 antibodies or antigen binding fragments, related GPC3 / CD3 bispecific antibodies, related GPC3 CAR or CAR-T cells, and methods of treating cancer in a subject in need thereof by administering the Glypican 3 (GPC3) antibodies or antigen binding fragments, the bispecific antibodies, the chimeric antigen receptors, the CAR-T cells, or the pharmaceutical compositions. The cancers treated in accordance with the application include Glypican-3-positive cancers.

Provided herein are compositions, methods, and uses involving anti-Mucin-16 (MUC16) agents that immunospecifically bind an epitope of Mucin-16 (MUC16). Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer and diseases associated with positive MUC16 expression.

The present disclosure relates to an anti-Claudin 18.2 antibody and an application thereof. Specifically, the present invention relates to an anti-Claudin 18.2 antibody; a mouse-derived antibody, chimeric antibody, humanized antibody and antigen-binding fragment thereof which contain a CDR of the anti-Claudin 18.2 antibody, and a use thereof as a medicine. In particular, the present disclosure relates to a use of the anti-Claudin 18.2 antibody in the preparation of a drug for treating Claudin 18.2 positive diseases or disorders.

An anti-BDCA-2 antibody, a preparation method therefor, and a use thereof, relating to the field of antibodies. The preparation method for the anti-BDCA-2 antibody comprises: carrying out ELISA detection and screening on a hybridoma cell culture supernatant and an antigen protein to obtain a positive clone, and subcloning the positive clone to obtain the anti-BDCA-2 antibody. The anti-BDCA-2 antibody comprises a heavy chain and a light chain, wherein a variable region of the heavy chain and a variable region of the light chain are selected from amino acid sequences as shown in SEQ ID NOs: 1-22. The anti-BDCA-2 antibody and related drugs can be used for inhibiting the production of IFN-α by pDCs and preventing the over-activation of the pDCs. The anti-BDCA-2 antibody can effectively inhibit the activation of pDC cells and the production of IFN-α, and has great potential in resisting virus infection and preventing certain autoimmune diseases.

The disclosure provides compositions and methods for the preparation, manufacture and use of an adeno-associated virus (AAV) particle for the vectorized delivery of an antibody molecule that binds to HER2.

The invention provides a nucleic acid probe, a primer group, a kit, a detection method and application, and relates to the technical field of biology. The nucleotide sequence of the nucleic acid probe is as shown in SEQ ID NO. 1; wherein the 3'end of the nucleic acid probe is modified with MGB, and locked nucleic acid is modified at a base position corresponding to the difference between the swine fever wild strain and the swine fever vaccine strain in the nucleotide sequence. According to the nucleic acid probe, a specific sequence is utilized to precisely target a swine fever wild strain, and locked nucleic acid modification is introduced at a differential site, so that the recognition capability on single-base mismatch is remarkably enhanced, non-specific binding to a vaccine strain is thoroughly blocked, and false positive interference is eliminated; and 3 '-terminal MGB modification is matched to improve the binding stability and sensitivity, so that the efficient and accurate identification of the swine fever wild strain under the immune background is ensured.

The invention provides a preparation method and application of a genetically modified non-human mammal for producing a humanized antibody. The preparation method comprises the following steps: (1) destroying an endogenous heavy chain immune globulin locus of a non-human mammal; and (2) introducing a human IGHV gene, a human IGHD gene, a human IGHJ gene, and an endogenous IgHG gene, an endogenous IgHE gene, an endogenous IgHA gene and an endogenous LCR region of the non-human mammal into the non-human mammal obtained in the step (1). The non-human mammal prepared by the preparation method disclosed by the invention can efficiently generate a humanized complete antibody or a single-chain antibody or a nano antibody after being immunized by an antigen, and has relatively high immune titer, and moreover, the preparation method disclosed by the invention can be used for obtaining a positive animal with relatively high efficiency, so that the non-human mammal can be used for preparing the non-human mammal. Therefore, humanized mice with different antibody diversity can be easily prepared, and the nanometer antibody sequence diversity can be realized by using various strains of mice.

The invention relates to the technical field of biological medicines, in particular to a CKAP4-targeted tumor antigen peptide, a vaccine and application of the CKAP4-targeted tumor antigen peptide. The invention provides a high-immunogenicity tumor antigen peptide RLTELTKSI targeting human and mouse homologous CKAP4 protein, and the tumor antigen peptide and a vaccine thereof can realize efficient killing of CKAP4 positive tumor cells and remarkable inhibition of CT26 subcutaneous tumor by activating specific CD8 + T cell immune response. The traditional single-target limitation is broken through, the co-expression characteristic of CKAP4 in tumor cells and immunosuppressive cells (TAM / TAN) is utilized, a double-target and double-channel mechanism is initiated, and the immunosuppressive state of cold tumors is effectively reversed by inducing T cells to synchronously kill tumor cells and remodel an immune microenvironment. According to the technology, CKAP4 is expanded from an antibody target to a T cell vaccine target, lasting specific CTL response can be stimulated, the off-target risk of antibody treatment is avoided, a universal treatment scheme can be provided for solid tumors, and the clinical transformation potential and the treatment broad spectrum are remarkably improved.

The invention relates to the technical field of biological medicine, and particularly discloses a monoclonal neutralizing antibody for resisting respiratory syncytial virus and application of the monoclonal neutralizing antibody. The antibody provided by the invention can identify non-denatured RSV (L) protein through ELISA (enzyme-linked immunosorbent assay), but cannot identify denatured RSV (D) protein, and is a kappa IgG2b type antibody. The molecular marker is 0.0001 mu g / ml-1 mu g / ml, can positively recognize the RSV Pre-F protein, and has a gradient effect. The antibody can be used as a neutralizing active antibody in an ELISA double-antibody sandwich method, can be used for detecting the in-vitro potency of the RSV PreF protein, and plays an important role in evaluating the vaccine activity in the vaccine research and development process.

The invention belongs to the technical field of antibody preparation, and particularly relates to an anti-human transcription factor PU.1 monoclonal antibody and application thereof. The amino acid sequences of CDR1-3 on a light chain variable region of the monoclonal antibody are respectively shown as SEQ ID NO.3-5, and the amino acid sequences of CDR1-3 on a heavy chain variable region of the monoclonal antibody are respectively shown as SEQ ID NO.8-10. The antibody provided by the invention can specifically and sensitively recognize the human transcription factor PU.1 expressed in human cells / tissues, has good affinity to the PU.1 and excellent anti-interference capability, and has no cross reaction to other species of homologous proteins, so that the accuracy and reliability of immunodetection of the human PU.1 can be improved, the coincidence degree of a detection result and an actual situation is improved, and the human transcription factor PU.1 can be effectively identified. False positive or false negative results are effectively avoided, and an effective antibody tool and a detection means are provided for high-specificity, high-accuracy and high-sensitivity detection of the PU.1 protein.

The invention discloses a preparation method and application of a cat main allergen FEL-1 nano antibody FEL-1-Nb, and relates to the technical field of antibody preparation, and the preparation method comprises the following steps: preparing an immunogen; animal immunization and library construction; constructing and panning a phage display library; screening and identifying positive clone; and expression and purification of the nano antibody: cloning the positively cloned VHH gene to an expression vector such as a pET series, transforming an expression strain such as escherichia coli BL21 (DE3), carrying out IPTG induced expression, and purifying through an inclusion body purification method to obtain a high-purity nano antibody protein. The nano antibody FEL-1-Nb provided by the invention can be specifically bound with a cat main allergen FEL-1 protein, the unique amino acid sequence of the nano antibody FEL-1-Nb is shown as SEQIDNO: 1, high-affinity binding with the FEL-1 protein is ensured, the positive clone binding rate is high through phage display panning and ELISA verification, the phage recovery rate after the third round of panning is increased by more than 1000 times compared with the first round of panning, and the positive clone binding rate is higher than that of the first round of panning. Therefore, the nano antibody has excellent targeted recognition capability.

The invention provides an anti-BDCA-2 antibody as well as a preparation method and application thereof, and belongs to the field of antibodies. The invention provides a preparation method of an anti-BDCA-2 antibody, which comprises the following steps: carrying out ELISA detection screening on a hybridoma cell culture supernatant and an antigen protein to obtain a positive clone, and carrying out subcloning on the positive clone to obtain the anti-BDCA-2 antibody. The anti-BDCA-2 antibody comprises a heavy chain and a light chain, and a variable region of the heavy chain and a variable region of the light chain are selected from amino acid sequences as shown in SEQ ID NO: 1-22. The anti-BDCA-2 antibody and related drugs provided by the invention can be used for inhibiting generation of IFN-alpha by pDC and preventing excessive activation of pDC. The anti-BDCA-2 antibody produced by the invention can effectively inhibit the activation of pDC cells and the generation of IFN-alpha, and has great potential in resisting virus infection and preventing some autoimmune diseases.

The invention belongs to the field of biological immunity, and discloses a linear B cell epitope of African swine fever virus NP419L protein and application. The epitope sequence shows good immunoreactivity through ASFV positive pig serum recognition verification. The African swine fever positive serum can be identified by using the B cell epitope identified by the invention to carry out ELISA (Enzyme-Linked Immunosorbent Assay) experiment, and the sensitivity of the African swine fever positive serum is superior to that of NP419L protein full length and other truncated fragments. The epitope identified by the invention has high conservative property in reference ASFV strains in a plurality of popular regions in China, and has wide universality and adaptability. The kit can be widely applied to etiological diagnosis, serological diagnosis, immunological detection and disease prevention and treatment of African swine fever viruses, and can be applied to preparation of African swine fever vaccines, pathogenesis research and the like.

The application discloses a kind of 2-substituted benzylhydrazine-4-indole pyrimidine-5-carbonitrile derivatives and preparation method and application thereof.The derivative has general formula (I) structure: wherein R is hydroxyl or C1-C4 alkoxy, n=1~3.Preferred compound is 2-hydroxy, 4-hydroxy-3-methoxy, 2,3-dihydroxy or 2,4-dihydroxy substituted benzylhydrazine derivative.The application also provides key intermediate 2-hydrazine-4-(1H-indole-3-carbonyl) pyrimidine-5-carbonitrile and preparation method thereof.In vitro antitumor activity shows that the derivative has excellent inhibitory activity on human gastric cancer cell MGC-803, and the inhibition rate is up to 96.3% at 10 μmol / L, which is better than positive control doxorubicin.In vivo combination test shows synergistic effect with 5-fluorouracil or anti-PD-1 antibody.The compound of the application has mild synthesis route, high yield, various preparation forms, good safety, and can be applied in the preparation of anti-gastric cancer drugs.

The invention relates to a primer-probe set, comprising a forward primer having the nucleotide sequence of SEQ ID NO:1 and a reverse primer having the nucleotide sequence of SEQ ID NO:2, and a peptide nucleic acid (PNA) probe having the sequence of HEX-OO-(SEQ ID NO:3)-Lysine-BHQ1, which are used for differentiating the Peste des Petits Ruminants (PPR) virus vaccine and field strains and for preventing false positive results arising from the PPR vaccine, as well as to their operating temperatures. Said primer-probe set can differentiate between the vaccine strain containing the nucleotide sequence of SEQ ID NO:4 and the field strain containing the nucleotide sequence of SEQ ID NO:5. Thus, by means of said primer-probe set, false positive results arising from the PPR vaccine are prevented, and accordingly, unnecessary quarantine measures are also avoided.

CD24-positive malignant and benign tumors are treated by administration of a naturally occurring or modified oncolytic Zika virus. Diseases associated with abnormal T cell activation or T cell-mediated autoimmunity, wherein CD24 expression is increased, are also expected to be treated by administration of a naturally occurring or modified oncolytic Zika virus. Also contemplated are compounds and methods for treating and / or preventing Zika virus infection in a subject.

The application belongs to the technical field of biology and particularly relates to an ELISA kit for detecting chicken astrovirus type II antibodies and a preparation method. The Cell-ELISA experiment is carried out by using LMH cells infected with chicken astrovirus type II to detect the chicken astrovirus type II antibodies. The method has no cross reactivity with positive serum of Newcastle disease virus, avian influenza virus, chicken infectious anemia virus, avian leukosis virus, Marek's virus and chicken infectious bursal virus, which indicates that the method has good specificity. The Cell-ELISA method is used to detect the chicken serum sample to be detected by using whole virus infection, and is assembled into a kit for measuring chicken astrovirus antibodies in serum. The kit can be used for serological diagnosis of chicken astrovirus type II infection, monitoring of the level of antibodies, epidemiological investigation and the like, and provides a novel and effective detection means for prevention and treatment of chicken astrovirus type II.

This invention provides a kit for detecting anti-peroxidase-1-IgG antibodies, comprising the antigen protein peroxiredoxin-1 (peroxidase-1), a solid-phase carrier, labeled antibody, antigen dilution buffer, sample dilution buffer, antibody dilution buffer, substrate chromogenic agent, washing buffer, standards, positive control, and negative control. This kit utilizes an indirect reaction principle combined with magnetic microparticle chemiluminescence immunoassay to detect anti-peroxidase-1-IgG antibodies in the serum of the test sample. This invention is the first to identify autoantibodies against the target antigen peroxidase-1 in the serum of patients with autoimmune nephrotic syndrome. The provided kit provides a basis for domestic and international research on the molecular mechanisms and clinical diagnosis and treatment of autoimmune nephrotic syndrome related to peroxidase-1 and peroxidase-1-IgG autoantibodies.

The invention relates to the technical field of molecular generation, and discloses a reverse design method using a molecular spectrum as a medium to be applied to virus protein drug molecules, which comprises the following steps: firstly, constructing a data set containing a molecular SMILES identifier and a corresponding molecular spectrum, and carrying out drug-likeness and false positive preliminary screening on compounds by adopting Lipinski five rules and a PAINS mode; then training a conditional diffusion model, and generating a target molecular spectrum by taking specific drug properties as conditions; the spectrum is mapped into a molecular SMILES structure through a Transform decoder, so that accurate conversion from the spectrum to the molecule is realized; finally, through conformation optimization and stability verification, candidate drug molecules meeting specific treatment requirements are output. The method effectively avoids the invalid structure problem caused by cross-dimension generation, significantly improves the synthesizability and patent medicine potential of generated molecules, and is suitable for efficient molecular design of antiviral drugs, inhibitors and the like.

The invention belongs to the technical field of antibody preparation, and particularly relates to an anti-terminal deoxynucleotidyl transferase (TdT) antibody and application thereof. The amino acid sequences of CDR1-3 on a light chain variable region of the antibody are respectively shown as SEQ ID NO.3-5, and the amino acid sequences of CDR1-3 on a heavy chain variable region of the antibody are respectively shown as SEQ ID NO.8-10. The antibody disclosed by the invention can specifically recognize TdT protein naturally expressed in cells and tissues, has the advantages of high specificity, high affinity, high sensitivity and the like when being used for immunoblotting, immunohistochemistry and other immunodetection systems, is beneficial to reducing false positive and false negative rates in pathological diagnosis, improves the accuracy of immunodiagnosis, and has a good application prospect. The method has wide application potential in the field of immunological detection of living biological samples. In addition, the antibody disclosed by the invention has cross-species reaction characteristics on homologous TdT proteins of human, mice and rats, so that the application scene of the antibody is greatly expanded.