Piperazine heteroaryl derivative, preparation method therefor and use of same in medicine

The present invention relates to a piperazine heteroaryl derivative, a preparation method therefor and the use of same in medicine. In particular, the present invention relates to the piperazine heteroaryl derivative as shown in the general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and the use of same as a capsid protein inhibitor, in particular in the prevention and/or treatment of diseases such as hepatitis B, influenza, herpes, AIDS, etc. The definitions of each group in the general formula (I) are the same as those defined in the description.

Oxa spiro derivative, preparation method therefor, and applications thereof in medicines

The present invention relates to an oxa spiro derivative, a preparation method therefor, and applications thereof in medicines. Particularly, the present invention relates to an oxa spiro derivative represented by formula (I), a preparation method therefor, and a pharmaceutical composition comprising the derivative, applications thereof as an MOR receptor agonist, and applications in the preparation of drugs for treating and/or preventing pains and pains-related diseases. Substituent groups in the formula (I) are same as definitions in the specifications.

Azabicyclo-substituted triazole derivative, preparation method thereof, and application of same in medicine

The present invention relates to an azabicyclo-substituted triazole derivative, a preparation method thereof, and an application of the same in medicine. In particular, the present invention relates to a novel azabicyclo-substituted triazole derivative represented by general formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative, a use thereof as a therapeutic agent, especially as an oxytocin antagonist, and a use of the same in preparing a drug for treating or preventing a disease or disorder known or shown to have beneficial effect thereon with oxytocin being suppressed. The definition of each substituent in the general formula (I) is the same as the definition in the specification.

ANTI-PD-1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND PHARMACEUTICAL USE THEREOF

Provided are an anti-PD-1 antibody, an antigen-binding fragment thereof, and a pharmaceutical use thereof. Specifically, provided are a humanized anti-PD-1 antibody containing a specific CDR region and an antigen-binding fragment thereof, a pharmaceutical composition containing the anti-PD-1 antibody and the antigen-binding fragment thereof, and a use thereof as medicament. In particular, provided is a use of the humanized anti-PD-1 antibody in the preparation of the medicament for treating PD-1 associated diseases or disorders.

PHARMACEUTICAL COMPOSITION OF KOR RECEPTOR AGONIST

Disclosed in the present invention is a pharmaceutical composition of a KOR receptor agonist, which comprises 4-amino-N-[N2-[N-[N-[N-((R)-2-phenyl propyl)glycyl]-D-phenylalanyl]-D-leucyl]-D-lysyl]piperidine-4-carboxylic acid or available salts thereof, and an acetate buffer solution.

6-OXO-1,6-DIHYDROPYRIDAZINE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

A 6-oxo-1,6-dihydropyridazine derivative, a preparation method therefor and medical use thereof, in particular, a 6-oxo-1,6-dihydropyridazine derivative represented by general formula (I), a preparation method therefor, and a pharmaceutical composition containing the derivative, and use thereof as a NaV inhibitor and use thereof in the preparation of a drug for the treatment and/or prevention of pain and pain-related diseases. Each substituent in general formula (I) is the same as defined in the description.

HETEROARYL[4,3-C]PYRIMIDINE-5-AMINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND MEDICAL USES THEREOF

A heteroaryl[4,3-c]pyrimidin-5-amine derivative, a preparation method therefor, and medical uses thereof. Specifically, a heteroarylo[4,3-c]pyrimidin-5-amine derivative represented by a general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and uses thereof as therapeutic agents, in particular, a use as a A2a receptor antagonist and A use in preparation of a medicament for treatment of conditions or symptoms that are ameliorated by inhibiting the A2a receptor; various substituent groups in the general formula (I) have the identical meanings as those in the specification.

PCSK9 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND MEDICINAL APPLICATION THEREOF

The present invention provides a PCSK9 antibody, an antigen-binding fragment thereof, and a medicinal application thereof. Provided in the invention is a chimeric antibody and a humanized antibody, both comprising a CDR of the PCSK9 antibody, and a pharmaceutical composition comprising the PCSK9 antibody and an antigen-binding fragment thereof, and an application of the PCSK9 antibody as a lipid-lowering agent. The invention specifically relates to an application of a humanized PCSK9 antibody for preparing a pharmaceutical drug to treat a PCSK9-induced disease or symptom.

질소 함유 헤테로사이클릭 화합물, 이의 제조 방법 및 의학에서 이의 응용

A nitrogen-containing heterocyclic compound, a preparation method therefor, and an application thereof in medicines. Specifically, the present disclosure relates to a nitrogen-containing heterocyclic compound as represented by general formula (IM), a preparation method therefor, a pharmaceutical composition comprising the compound, a use of the pharmaceutical composition serving as a therapeutic agent, in particular as a PARP1 inhibitor, and a use of the pharmaceutical composition in the preparation of a drug for treating and/or preventing cancer.

Pd-1 antibody, antigen-binding fragments and pharmaceutical use thereof

PCSK9 antibody, antigen-binding fragment thereof, and medical application thereof

The present invention provides a PCSK9 antibody, an antigen-binding fragment thereof, and a medicinal application thereof. Provided in the invention is a chimeric antibody and a humanized antibody, both comprising a CDR of the PCSK9 antibody, and a pharmaceutical composition comprising the PCSK9 antibody and an antigen-binding fragment thereof, and an application of the PCSK9 antibody as a lipid-lowering agent. The invention specifically relates to an application of a humanized PCSK9 antibody for preparing a pharmaceutical drug to treat a PCSK9-induced disease or symptom.

IL-15 HETERODIMERIC PROTEIN AND USES THEREOF

Provided is an IL-15 heterodimeric protein, such as an IL-15/IL-15Rα heterodimeric protein. The IL-15 heterodimeric protein contains protein (I) and protein (II). Protein (I) is recombinantly produced by combining IL-15 or a variant thereof with a first Fc variant, and protein (II) is a second Fc variant, or recombinantly produced by combining IL-15Rα or a variant thereof with a second Fc variant. The first Fc variant and the second Fc variant are preferably linked via a “Knob-into-Hole” mode. Also provided are methods of using the IL-15 heterodimeric proteins to modulate an immune response. The provided IL-15 heterodimeric proteins have significant anti-tumor activity, better biological activity and prolonged in vivo half-life compared to the IL-15 molecule alone. 1. An IL-15 heterodimeric protein , comprising:protein (I) and protein (II);wherein protein (I) is recombinantly produced by combining IL-15 or a variant thereof with a first Fc variant;protein (II) is a second Fc variant, or is recombinantly produced by combining IL-15Rα or a variant thereof with a second Fc variant; andprotein (I) and protein (II) form a stable heterodimeric protein by an interaction between the first Fc variant and the second Fc variant.2. The IL-15 heterodimeric protein according to claim 1 , wherein the sequence of IL-15 comprises SEQ ID NO: 1.3. The IL-15 heterodimeric protein according to claim 1 , wherein protein (II) is a second Fc variant.4. The IL-15 heterodimeric protein according to claim 1 , wherein protein (II) is recombinantly produced by combining IL-15Rα or a variant thereof with a second Fc variant.5. The IL-15 heterodimeric protein according to claim 1 , wherein the IL-15Rα variant is an extracellular domain portion of IL-15Rα or a functional fragment thereof.6. The IL-15 heterodimeric protein according to claim 1 , wherein the sequence of the IL-15Rα variant is selected from the group consisting of SEQ ID NOs: 2-7.7. The IL-15 heterodimeric protein according to claim ...

Indole-formamide derivative, preparation method therefor and use thereof in medicine

Disclosed are an indole-formamide derivative, a preparation method therefor and the use thereof in medicine. In particular, disclosed are an indole-formamide derivative as shown in general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and the use thereof as an ROR agonist and the use thereof for preventing and/or treating a tumour or cancer.

Phenyl propanamide derivative, and manufacturing method and pharmaceutical application thereof

The present invention provides a phenyl propanamide derivative as represented by formula (I), a manufacturing method of the derivative, application of the derivative as a κ-opioid receptor (KOR) agonist, and application of the derivative for manufacturing a pharmaceutical product for treating and/or preventing pain or a pain-related disease.

Oxa spiro derivative, preparation method therefor, and applications thereof in medicines

The present invention relates to an oxa spiro derivative, a preparation method therefor, and applications thereof in medicines. Particularly, the present invention relates to an oxa spiro derivative represented by formula (I), a preparation method therefor, and a pharmaceutical composition comprising the derivative, applications thereof as an MOR receptor agonist, and applications in the preparation of drugs for treating and/or preventing pains and pains-related diseases. Substituent groups in the formula (I) are same as definitions in the specifications.

BISPECIFIC ANTIBODY SPECIFICALLY BOUND TO VEGF AND ANG2

The present disclosure provides a bispecific antibody specifically bound to VEGF and ANG2, comprising an anti-VEGF antibody or an antigen-binding fragment thereof that specifically binds to VEGF, and an anti-ANG2 single-domain antibody that specifically binds to ANG2, wherein the anti-ANG2 single domain antibody is directly or indirectly connected to the anti-VEGF antibody or an antigen-binding fragment thereof. The present disclosure further provides an anti-ANG2 single domain antibody and an antigen-binding fragment thereof, as well as a preparation and application of said antibody.

BENZIMIDAZOLE DERIVATIVES AS MODULATORS OF RETINOID-RELATED ORPHAN RECEPTOR GAMMA (ROR.GAMMA.) AND PHARMACEUTICAL USES THEREOF

The present invention relates to benzimidazole derivatives of formula (I) as inhibitors of retinoid-related orphan receptor gamma (ROR?) protein, pharmaceutical compositions containing the compounds, preparation methods thereof, and the use of the compounds as therapeutic agents for the treatment of ROR?-mediated diseases or disorders.

Fused tricyclic heterocycle compounds and therapeutic uses thereof

This application discloses a new class of fused tricyclic heterocycles of formula (I), preparation methods thereof, pharmaceutical compositions comprising these compounds, and pharmaceutically acceptable salts, solvates, or prodrugs thereof, and their uses for the treatment of diseases in which modulation of STING is beneficial, for example, cancers, pre-cancerous disorders, and viral infections.

PD-1 antibody, antigen-binding fragment thereof, and medical application thereof

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and medical use thereof, and further provides a chimeric antibody and humanized antibodies comprising a complementarity-determining region (CDR) of the antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and use of the antibody in preparing medicines for treating diseases or disorders.

Benzimidazole Derivatives as Modulators of Retinoid-Related Orphan Receptor Gamma (RORy) and Pharmaceutical Uses Thereof

The present invention relates to benzimidazole derivatives of formula (I) as inhibitors of retinoid-related orphan receptor gamma (RORγ) protein, pharmaceutical compositions containing the compounds, preparation methods thereof, and the use of the compounds as therapeutic agents for the treatment of RORγ-mediated diseases or disorders. 3. The compound of claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is selected from the group consisting of phenyl claim 1 , Ccycloalkyl claim 1 , and or 6 member heteroaryl claim 1 , preferably piperidinyl claim 1 , phenyl claim 1 , thienyl claim 1 , furyl claim 1 , or pyridinyl.8. The compound of claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Rat each occurrence is independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , alkoxy claim 1 , haloalkoxy claim 1 , cyano claim 1 , amino claim 1 , —OR claim 1 , and —NRR; and{'sub': 8', '11', '12, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R, Rand Rare as defined in .'}9. The compound of claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , and alkyl.11. The compound of claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof ...

STABLE ANTI-PD-1 ANTIBODY PHARMACEUTICAL PREPARATION AND APPLICATION THEREOF IN MEDICINE

A stable anti-PD-1 antibody pharmaceutical preparation and an application thereof in a medicine. The anti-PD-1 antibody pharmaceutical preparation comprises an anti-PD-1 antibody, a buffer, and can further comprise at least one type of stabilizer, and optionally can further comprise a surfactant. The anti-PD-1 antibody pharmaceutical preparation of the present invention can effectively suppress antibody aggregation and deamidation, thereby preventing degradation of an antibody product, resulting in a stable injectable pharmaceutical preparation. 1. (canceled)2. (canceled)3. The pharmaceutical formulation according to claim 22 , wherein the composition comprises an anti-PD-1 antibody comprising a heavy chain having the amino acid sequence of SEQ ID NO: 7 and a light chain having the amino acid sequence of SEQ ID NO: 8.4. The pharmaceutical formulation according to claim 3 , wherein the concentration of the anti-PD-1 antibody is in the range of 1 mg/ml to 60 mg/ml.5. The pharmaceutical formulation according to claim 22 , wherein the buffer is the acetate buffer.6. The pharmaceutical formulation according to claim 5 , wherein the concentration of the buffer is 1-50 mM.7. The pharmaceutical formulation according to claim 22 , wherein the pH of the formulation ranges from 4.5 to 6.0.8. (canceled)9. (canceled)10. The pharmaceutical formulation according to claim 22 , wherein the at least one stabilizer comprises a disaccharide selected from the group consisting of sucrose claim 22 , lactose claim 22 , trehalose claim 22 , and maltose.11. The pharmaceutical formulation according to claim 10 , wherein the disaccharide is at a concentration from 30 mg/ml to 120 mg/ml.12. The pharmaceutical formulation according to claim 22 , wherein the surfactant is the polyoxyethylene sorbitan fatty acid ester selected from the group consisting of polysorbate 20 claim 22 , 40 claim 22 , 60 and 80.13. The pharmaceutical formulation according to claim 12 , wherein the surfactant is at a ...

Pyrazolo-heteroaryl derivative, preparation method and medical use thereof

Disclosed are a pyrazolo-heteroaryl derivative, a preparation method and medical use thereof. In particular, the present invention relates to a new pyrazolo-heteroaryl derivative as shown in the general formula (I), a preparation method thereof and a pharmaceutical composition containing the derivative and the use thereof as a therapeutic agent, in particular as a TLR7 agonist, wherein each substituent in the general formula (I) is defined in the description.

Heteroaryl[4,3-c]pyrimidine-5-amine derivative, preparation method therefor, and medical uses thereof

A heteroaryl[4,3-c]pyrimidin-5-amine derivative, a preparation method therefor, and medical uses thereof. Specifically, a heteroarylo[4,3-c]pyrimidin-5-amine derivative represented by a general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and uses thereof as therapeutic agents, in particular, a use as a A ...

Interleukin 15 protein complex and use thereof

Provided in the application is a interleukin 15 (IL-15) protein complex. The IL-15 protein complex consists of a soluble fusion proteins (I) and (II), wherein the fusion protein (I) is a IL-15 polypeptide or a functionality fragment thereof, and the fusion protein (II) is a IL-15Rα polypeptide or a functionality fragment thereof. There are one or more amino acid sites on the fusion proteins (I) or (II) were mutated to Cys, which were paired with the corresponding Cys mutated from the amino acid sites on the fusion proteins (II) or(I) to form disulfide bonds. The IL-15 protein complex can be used for tumour therapy.

PYRAZOLO[1,5-A][1,3,5]TRIAZINE-2-AMINE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

Disclosed are a pyrazolo[1,5-a][1,3,5]triazine-2-amine derivative as shown in general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative and the use of same as a therapeutic agent, in particular the use thereof as an A2a receptor antagonist and the use thereof in the preparation of drugs for treating conditions or diseases improved by the inhibition of A2a receptors.

PYRAZOLO-HETEROARYL DERIVATIVE, PREPARATION METHOD AND MEDICAL USE THEREOF

Disclosed are a pyrazolo-heteroaryl derivative, a preparation method and medical use thereof. In particular, the present invention relates to a new pyrazolo-heteroaryl derivative as shown in the general formula (I), a preparation method thereof and a pharmaceutical composition containing the derivative and the use thereof as a therapeutic agent, in particular as a TLR7 agonist, wherein each substituent in the general formula (I) is defined in the description.

LIGAND-DRUG CONJUGATE OF EXATECAN ANALOGUE, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF

The present invention relates to a ligand-drug conjugate of an exatecan analogue, a preparation method therefor and an application thereof. Specifically, the present invention provides a ligand-drug conjugate having a structure shown in formula (-D), a preparation method therefor, a pharmaceutical composition containing same, and use thereof in preparation of drugs for treating cancers by means of receptor regulation. The definition of each substituent in formula (-D) is the same as that in the description.

METHOD FOR KNOCKING OUT TARGET GENE IN T CELL IN VITRO AND crRNA USED IN THE METHOD

Provided is a method for knocking out target genes in T cells in vitro based on the CRISPR-Cas9 system. Also provided are crRNAs that target the TRAC, B2M and PD1 genes, and a kit comprising sgRNA formed by linking the crRNA and tracrRNA corresponding to a Cas9 protein, the Cas9 protein, an oligo deoxyribonucleic acid (N-oligo) or a milt DNA fragment. The kit is used to knock out the TCR, B2M and/or PD1 genes in T cells. Also provided are T cells with gene knockout, obtained according to a method of the present invention and uses thereof. 1. A method for knocking out one or more target gene(s) in T cells in vitro , comprising:1) contacting sgRNAs targeting one or more target gene(s) in the T cells with a Cas9 protein, respectively, to form a protein-RNA complex comprising each of the sgRNAs and the Cas9;2) mixing the protein-RNA complex with an oligo deoxyribonucleic acid or a milt DNA fragment to obtain a mixture; and3) transforming the mixture into T cells,wherein the sgRNAs direct the Cas9 protein to the corresponding target sequences of the target gene and to hybridize with the target sequence, thereby the target gene is cleaved, and the cleavage efficiency of the target gene is greater than 75%.2. The method according to claim 1 , wherein the target gene is one or more genes selected from the group consisting of TRAC claim 1 , TRBC claim 1 , B2M and PD1 genes claim 1 , and each of the sgRNAs targets a coding sequence of the target gene or a regulatory sequence for the expression of the target gene.3. The method according to claim 1 , wherein each of the sgRNAs consists of claim 1 , from 5′ to 3′ claim 1 , a crRNA targeting the target gene and having 17-20 nucleotides (nt) in length claim 1 , linked to a tracrRNA corresponding to the Cas9 protein.4. The method according to claim 1 , wherein the oligo deoxyribonucleic acid is a double-stranded DNA with a length of 100-250 base pairs (bp) or a single-stranded DNA with a length of 100-250 nt.5. The method according ...

Method for preparing antibody-drug conjugate

A method for preparing an antibody-drug conjugate (ADC). In particular, the method mainly utilizes a combination of antibody biomolecules and an ion exchange carrier through electrostatic interaction to realize solid phase preparation of an ADC drug. Elution conditions are optimized, to control a drug-to-antibody coupling ratio (DAR) and separate a polymer-coupled drug, reduce the amount of a drug used in a coupling reaction, and enhance the targeted therapeutic effect of an ADC drug. The preparation method features fewer steps, simple operation, and programmable control, facilitating industrial scale-up production, and also realizing zero retention of reducing agents and organic solvents in the preparation process, significantly improving drug safety and reducing production costs.

Anti-CD73 antibody, antigen-binding fragment thereof and application thereof

Provided are an anti-CD73 antibody, an antigen-binding fragment thereof and an application thereof. Specifically, provided are a murine, chimeric or humanized anti-CD73 antibody comprising a specific CDR region and an antigen-binding fragment thereof. Also provided are a pharmaceutical composition comprising the anti-CD73 antibody or the antigen-binding fragment thereof and the use thereof as a diagnostic agent and a therapeutic agent for CD73-related diseases.

PD-1 antibody, antigen-binding fragment thereof, and medical application thereof

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and a medical application thereof, and further provides a chimeric antibody comprising a complementarity-determining region (CDR) of the antibody, a humanized antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and a purpose of the antibody in preparing medicine for treating diseases or symptoms.

Stable anti-PD-1 antibody pharmaceutical preparation and application thereof in medicine

A stable anti-PD-1 antibody pharmaceutical preparation and an application thereof in a medicine. The anti-PD-1 antibody pharmaceutical preparation comprises an anti-PD-1 antibody, a buffer, and can further comprise at least one type of stabilizer, and optionally can further comprise a surfactant. The anti-PD-1 antibody pharmaceutical preparation of the present invention can effectively suppress antibody aggregation and deamidation, thereby preventing degradation of an antibody product, obtaining a stable injected pharmaceutical preparation.

PD-L1 antibody, antigen fragment binding thereof and pharmaceutical use thereof

Provided in the present invention are a PD-L1 antibody, a fragment antigen binding thereof, and a use of the antibody or fragment antigen binding in the preparation of drugs for treating PD-L1-mediated diseases or conditions.

PYRROLOHETEROCYCLIC DERIVATIVE, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF IN MEDICINE

The present application provides a pyrroloheterocyclic derivative, a preparation method therefor, and an application thereof in medicine. Specifically, the present application provides a novel pyrroloheterocyclic derivative as represented by formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and an application of the derivative as a therapeutic agent, particularly as an ERK inhibitor, wherein substituents in the formula have the same definitions as those in the description.

METHOD FOR PREPARING ANTIBODY-DRUG CONJUGATE

A method for preparing an antibody-drug conjugate (ADC). In particular, the method mainly utilizes a combination of antibody biomolecules and an ion exchange carrier through electrostatic interaction to realize solid phase preparation of an ADC drug. Elution conditions are optimized, to control a drug-to-antibody coupling ratio (DAR) and separate a polymer-coupled drug, reduce the amount of a drug used in a coupling reaction, and enhance the targeted therapeutic effect of an ADC drug. The preparation method features fewer steps, simple operation, and programmable control, facilitating industrial scale-up production, and also realizing zero retention of reducing agents and organic solvents in the preparation process, significantly improving drug safety and reducing production costs.

B7-H3 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND MEDICAL USE THEREOF

The invention provides a B7-H3 antibody, an antigen-binding fragment thereof and a medical use thereof. Further, the present invention discloses a pharmaceutical composition comprising the B7-H3 antibody or antigen-binding fragment thereof, and the use thereof as a medicament. In particular, the invention discloses a use of a human B7-H3 human antibody or antigen-binding fragment thereof for the manufacture of a medicament for the treatment of a B7-H3-associated disease or condition.

INDOLE-FORMAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR AND USE THEREOF IN MEDICINE

Disclosed are an indole-formamide derivative, a preparation method therefor and the use thereof in medicine. In particular, disclosed are an indole-formamide derivative as shown in general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and the use thereof as an ROR agonist and the use thereof for preventing and/or treating a tumour or cancer.

3,4-BIPYRIDYL PYRAZOLE DERIVATIVE, AND PREPARATION METHOD THEREFOR AND MEDICAL APPLICATION THEREOF

The present invention relates to a 3,4-bipyridyl pyrazole derivative, and a preparation method therefor and a medical application thereof. Specifically, the present invention relates to a new 3,4-bipyridyl pyrazole derivative as shown in formula (I), a preparation method for the derivative, a pharmaceutical composition containing the derivative, a use of the derivative as a therapeutic agent, in particular as a TGF-ß inhibitor, and a use of the derivative in the preparation of a drug which treats, prevents or reduces cancer mediated by TGF-ß overexpression. The substituents in formula (I) have the same definitions as in the description.

PYRAZOLO[1,5-A][1,3,5]TRIAZINE-2-AMINE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

Disclosed are a pyrazolo[1,5-a][1,3,5]triazine-2-amine derivative as shown in general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative and the use of same as a therapeutic agent, in particular the use thereof as an Areceptor antagonist and the use thereof in the preparation of drugs for treating conditions or diseases improved by the inhibition of Areceptors. 2. The compound of formula (I) according to , or a tautomer , mesomer , racemate , enantiomer or diastereomer thereof , or a mixture thereof , or a pharmaceutically acceptable salt thereof , wherein Ris selected from the group consisting of hydrogen , halogen , alkyl , alkoxy , haloalkyl , haloalkoxy , hydroxyl , hydroxyalkyl , cyano , amino , nitro , cycloalkyl , heterocyclyl , heterocyclylalkyl , heterocyclyloxy , —OS(O)R , aryl and heteroaryl , wherein the alkyl , alkoxy , cycloalkyl , heterocyclyl , heterocyclylalkyl , heterocyclyloxy , aryl and heteroaryl are each optionally substituted by one or more substituents independently selected from the group consisting of halogen , alkyl , alkoxy , haloalkyl , hydroxyl , hydroxyalkyl , cyano , amino , nitro , cycloalkyl , heterocyclyl , heterocyclyloxy , aryl , heteroaryl and —OS(O)R; Ris as defined in .4. The compound of formula (I) according to claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer or a diastereomer thereof claim 1 , or a mixture thereof claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein ring A and ring B are identical or different and are each independently selected from the group consisting of aryl and heteroaryl claim 1 , preferably selected from the group consisting of phenyl claim 1 , pyridyl claim 1 , furyl and thienyl.6. The compound of formula (I) according to claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer or diastereomer thereof claim 1 , or a mixture thereof claim 1 , or a pharmaceutically acceptable ...

Anti-Claudin 18.2 antibody and application thereof

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.

Pyrroloheterocyclic derivative, preparation method therefor, and application thereof in medicine

The present application provides a pyrroloheterocyclic derivative, a preparation method therefor, and an application thereof in medicine. Specifically, the present application provides a novel pyrroloheterocyclic derivative as represented by formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and an application of the derivative as a therapeutic agent, particularly as an ERK inhibitor, wherein substituents in the formula have the same definitions as those in the description.

CONDENSED RING GROUP AZACYCLOBUTYL TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR AND USE THEREOF IN MEDICINE

The present invention relates to a condensed ring group azacyclobutyl triazole derivative, a preparation method therefor and use thereof in medicine. In particular, the present invention relates to a novel condensed ring group azacyclobutyl triazole derivative as represented by general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, use thereof as a therapeutic agent, in particular as an oxytocin antagonist, and use thereof in the preparation of a medicament used for treating or preventing a disease or a condition that is known or can exhibit a beneficial effect of inhibiting oxytocin. The definition for each substituent in general formula (I) is the same as that in the description.

ANTI-CD38 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND PHARMACEUTICAL USE

The present application provides an anti-CD38 antibody, an antigen-binding fragment thereof, and pharmaceutical use. Specifically, the present application provides a murine-derived antibody, a chimeric antibody, or a humanized antibody comprising a CDR region of the anti-CD38 antibody, a pharmaceutical composition comprising the anti-CD38 antibody or the antigen-binding fragment thereof, and an application thereof as a drug. In particular, the present application provides an application of a humanized anti-CD38 antibody in preparing a drug for treating a CD38 positive disease or disorder.

ANTI-CD73 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND APPLICATION THEREOF

Provided are an anti-CD73 antibody, an antigen-binding fragment thereof and an application thereof. Specifically, provided are a murine, chimeric or humanized anti-CD73 antibody comprising a specific CDR region and an antigen-binding fragment thereof. Also provided are a pharmaceutical composition comprising the anti-CD73 antibody or the antigen-binding fragment thereof and the use thereof as a diagnostic agent and a therapeutic agent for CD73-related diseases.

AZABICYCLO-SUBSTITUTED TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREOF, AND APPLICATION OF SAME IN MEDICINE

The present invention relates to an azabicyclo-substituted triazole derivative, a preparation method thereof, and an application of the same in medicine. In particular, the present invention relates to a novel azabicyclo-substituted triazole derivative represented by general formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative, a use thereof as a therapeutic agent, especially as an oxytocin antagonist, and a use of the same in preparing a drug for treating or preventing a disease or disorder known or shown to have beneficial effect thereon with oxytocin being suppressed. The definition of each substituent in the general formula (I) is the same as the definition in the specification.

PIPERAZINE HETEROARYL DERIVATIVE, PREPARATION METHOD THEREFOR AND USE OF SAME IN MEDICINE

The present invention relates to a piperazine heteroaryl derivative, a preparation method therefor and the use of same in medicine. In particular, the present invention relates to the piperazine heteroaryl derivative as shown in the general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and the use of same as a capsid protein inhibitor, in particular in the prevention and/or treatment of diseases such as hepatitis B, influenza, herpes, AIDS, etc. The definitions of each group in the general formula (I) are the same as those defined in the description.

ANTI-SCLEROSTIN ANTIBODY, ANTIGEN BINDING FRAGMENT AND MEDICAL USE THEREOF

Provided is a humanized antibody and chimeric antibody specifically binding human sclerostin. The antibodies can be used for treating human bone metabolism related diseases such as osteoporosis (OP).

ANTI-C-MET ANTIBODY AND ANTI-C-MET ANTIBODY-CYTOTOXIC DRUG CONJUGATE AND PHARMACEUTICAL USE THEREOF

Provided are an anti-c-Met antibody or antigen binding fragment, and an anti-c-Met antibody-cytotoxic drug conjugate, wherein the antibody or antigen binding fragment is a chimeric antibody or a humanized antibody. Also provided are a pharmaceutical composition containing a humanized anti-c-Met antibody or antigen binding fragment, antibody-cytotoxic drug conjugate, or a pharmaceutically acceptable salt or solvent compound thereof, applied in the treatment of cancer.

IL-6R antibody and antigen binding fragment thereof and medical use

Provided in the present invention are an IL-6R antibody and antigen binding fragment thereof. The IL-6R antibody is an alpaca-derived antibody, chimeric antibody and humanized antibody. Also provided in the present invention is the use of the antibody in the preparation of a drug for treating IL-6-related diseases.

DEUTERIUM ATOM-SUBSTITUTED INDOLE FORMAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR, AND MEDICAL APPLICATIONS THEREOF

A deuterium atom-substituted indole formamide derivative, a preparation method therefor, and medical applications thereof. Specifically, the present invention relates to a deuterium atom-substituted indole formamide derivative represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and uses of the derivative serving as an ROR agonist and uses of the derivative in preventing and/or treating tumors or cancers, definitions of substituent groups in general formula (I) being same as definitions in the specification.

ANTI-CLAUDIN 18.2 ANTIBODY AND APPLICATION THEREOF

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.

PD-1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND MEDICAL USE THEREOF

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and a medical application thereof, and further provides a chimeric antibody comprising a complementarity-determining region (CDR) of the antibody, a humanized antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and a purpose of the antibody in preparing medicine for treating diseases or symptoms.

Pcsk9 antibody, antigen-binding fragments and pharmaceutical use thereof

Pharmaceutical composition containing antibody against IL-5 and use thereof

Disclosed in the present application are a pharmaceutical composition containing an antibody against IL-5 and use thereof. In particular, disclosed in the present application is a pharmaceutical composition, which contains an IL-5 antibody or an antigen binding fragment thereof in a buffer solution. In addition, the pharmaceutical composition further contains a saccharide and a nonionic surfactant.

Indole macrocyclic derivative, preparation method therefor and application thereof in medicine

The present invention relates to an indole macrocyclic derivative, a preparation method therefor and an application thereof in medicine. Specifically, the present invention relates to an indole macrocyclic derivative represented by general formula (IM), a preparation method therefor, a pharmaceutical composition containing the derivative, and a use thereof as a therapeutic agent, especially as an MCL-1 inhibitor. Each substituent of general formula (IM) is the same as those defined in the description.

Azabicyclo-substituted triazole derivative, preparation method thereof, and application of same in medicine

The present invention relates to an azabicyclo-substituted triazole derivative, a preparation method thereof, and an application of the same in medicine. In particular, the present invention relates to a novel azabicyclo-substituted triazole derivative represented by general formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative, a use thereof as a therapeutic agent, especially as an oxytocin antagonist, and a use of the same in preparing a drug for treating or preventing a disease or disorder known or shown to have beneficial effect thereon with oxytocin being suppressed. The definition of each substituent in the general formula (I) is the same as the definition in the specification.

Bispecific antibody specifically bound to VEGF and ANG2

The present disclosure provides a bispecific antibody specifically bound to VEGF and ANG2, comprising an anti-VEGF antibody or an antigen-binding fragment thereof that specifically binds to VEGF, and an anti-ANG2 single-domain antibody that specifically binds to ANG2, wherein the anti-ANG2 single domain antibody is directly or indirectly connected to the anti-VEGF antibody or an antigen-binding fragment thereof. The present disclosure further provides an anti-ANG2 single domain antibody and an antigen-binding fragment thereof, as well as a preparation and application of said antibody.

Oxopicolinamide derivative, preparation method therefor and pharmaceutical use thereof

The present invention relates to an oxopicolinamide derivative, a preparation method therefor and the pharmaceutical use thereof. In particular, the present invention relates to the oxopicolinamide derivative as shown in the general formula (AI), a preparation method therefor and a pharmaceutical composition comprising the derivative, and to the use thereof as a therapeutic agent, in particular as an inhibitor of blood coagulation factor XIa (Factor XIa, FXIa for short) and the use thereof in the preparation of a drug for treating diseases such as thromboembolism, wherein the definition of each substituent in the general formula (AI) is the same as defined in the description.

Heteroaryl[4,3-c]pyrimidine-5-amine derivative, preparation method therefor, and medical uses thereof

A heteroaryl[4,3-c]pyrimidin-5-amine derivative, a preparation method therefor, and medical uses thereof. Specifically, a heteroarylo[4,3-c]pyrimidin-5-amine derivative represented by a general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and uses thereof as therapeutic agents, in particular, a use as a A ...

IL-6R ANTIBODY AND ANTIGEN-BINDING FRAGMENT THEREOF AND MEDICAL USE

Provided in the present invention are an IL-6R antibody and antigen binding fragment thereof. The IL-6R antibody is an alpaca-derived antibody, chimeric antibody and humanized antibody. Also provided in the present invention is the use of the antibody in the preparation of a drug for treating IL-6-related diseases.

BISPECIFIC PROTEIN

Provided are a human GCGR antibody, a GLP-1 peptide and a mutant thereof, as well as a bispecific protein formed by fusion of the GCGR antibody and the GLP-1 peptide and a preparation method therefor, which may be used for weight loss and diabetes treatment.

ANTI-ABETA ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND APPLICATION THEREOF

Murine, chimeric or humanized anti-Abeta antibody having a specific CDR region, an antigen-binding fragment thereof, a pharmaceutical composition thereof, and usage thereof. Use of a humanized anti-Abeta antibody for the preparation of drugs for the treatment of a disease or disorder (such as Alzheimer's disease) caused by amyloid beta protein.

OXOPICOLINAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR AND PHARMACEUTICAL USE THEREOF

The present invention relates to an oxopicolinamide derivative, a preparation method therefor and the pharmaceutical use thereof. In particular, the present invention relates to the oxopicolinamide derivative as shown in the general formula (AI), a preparation method therefor and a pharmaceutical composition comprising the derivative, and to the use thereof as a therapeutic agent, in particular as an inhibitor of blood coagulation factor XIa (Factor XIa, FXIa for short) and the use thereof in the preparation of a drug for treating diseases such as thromboembolism, wherein the definition of each substituent in the general formula (AI) is the same as defined in the description.

IL-15 HETERODIMERIC PROTEIN AND USES THEREOF

Disclosed are an IL-15 heterogeneous dimer protein and uses thereof. The IL-15 heterogeneous dimer protein comprises protein (I) and protein (II). The protein (I) is formed by means of reconstruction between IL-15 or a modification thereof and a first Fc modification; the protein (II) a second Fc modification, or is formed by means of reconstruction between IL-15Ra or a modification thereof and the second Fc modification; and the first Fc modification and the second Fc modification are connected in a manner of Knob-into-Hole. The IL-15 heterogeneous dimer protein has obvious tumor suppression activity, and has better bioactivity and an extended in-vivo half-life period compared with a single IL-15 molecule.

Oxopicolinamide derivative, preparation method therefor and pharmaceutical use thereof

The present invention relates to an oxopicolinamide derivative, a preparation method therefor and the pharmaceutical use thereof. In particular, the present invention relates to an oxopicolinamide derivative as shown in the general formula (AI), a preparation method therefor and a pharmaceutical composition comprising the derivative, and to the use thereof as a therapeutic agent, in particular as an inhibitor of blood coagulation factor XIa (Factor XIa, FXIa for short) and the use thereof in the preparation of a drug for treating diseases such as thromboembolism, wherein the definition of each substituent in the general formula (AI) is the same as defined in the description.

Oxopicolinamide derivative, preparation method therefor and pharmaceutical use thereof

The present invention relates to an oxopicolinamide derivative, a preparation method therefor and the pharmaceutical use thereof. In particular, the present invention relates to the oxopicolinamide derivative as shown in the general formula (AI), a preparation method therefor and a pharmaceutical composition comprising the derivative, and to the use thereof as a therapeutic agent, in particular as an inhibitor of blood coagulation factor XIa (Factor XIa, FXIa for short) and the use thereof in the preparation of a drug for treating diseases such as thromboembolism, wherein the definition of each substituent in the general formula (AI) is the same as defined in the description.

Benzimidazole derivatives as modulators of retinoid-related orphan receptor gamma (RORy) and pharmaceutical uses thereof

The present invention relates to benzimidazole derivatives of formula (I) as inhibitors of retinoid-related orphan receptor gamma (RORγ) protein, pharmaceutical compositions containing the compounds, preparation methods thereof, and the use of the compounds as therapeutic agents for the treatment of RORγ-mediated diseases or disorders.

Pyridopyrimidine derivative, preparation method therefor and medical use thereof

Disclosed are a pyridopyrimidine derivative as shown in general formula (I), a preparation method therefor and a pharmaceutical composition containing the derivative, and the use thereof as a therapeutic agent, particularly as a TLR8 agonist, wherein each substituent of general formula (I) is the same as those defined in the description.

Anti-CD38 antibody, antigen-binding fragment thereof, and pharmaceutical use

The present application provides an anti-CD38 antibody, an antigen-binding fragment thereof, and pharmaceutical use. Specifically, the present application provides a murine-derived antibody, a chimeric antibody, or a humanized antibody comprising a CDR region of the anti-CD38 antibody, a pharmaceutical composition comprising the anti-CD38 antibody or the antigen-binding fragment thereof, and an application thereof as a drug. In particular, the present application provides an application of a humanized anti-CD38 antibody in preparing a drug for treating a CD38 positive disease or disorder.

6-oxo-1,6-dihydropyridazine prodrug derivative, preparation method therefor, and application thereof in medicine

Specifically, the present invention relates to the 6-oxo-1,6-dihydropyridazine prodrug derivative shown in general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, a use thereof as a NaV inhibitor, and a use thereof in the preparation of a drug for the treatment and/or prevention of pain and pain-related diseases.

CD3 ANTIBODY AND PHARMACEUTICAL USE THEREOF

The present disclosure relates to a CD3 antibody and a pharmaceutical use thereof. Specifically, the present disclosure relates to forming a multi-specificity antibody by using a CD3 antibody and binding molecules of another target. The multi-specificity antibody may simultaneously bind to CD3 and another tumor-associated antigen, and bind and activate CD3-positive T cells while binding tumor-associated antigen-expressing cells, thereby promoting T cells specifically killing tumor cells that express tumor-associated antigens. In addition, the present disclosure also provides a preparation and application of a multi-specificity antibody.

BIFUNCTIONAL FUSION PROTEIN AND PHARMACEUTICAL USE THEREOF

Provided are a bifunctional fusion protein and pharmaceutical use thereof. Specifically, provided are a bifunctional fusion protein comprising an SIRP? peptide variant and an anti-human PD-L1 antibody, an SIRP? peptide variant, and pharmaceutical use thereof. The bifunctional fusion protein can specifically bind PD-L1 and CD47 to block the binding of PD-L1 or CD47 to a receptor or ligand thereof. In addition, also provided are preparation and application of the bifunctional fusion protein, and treatment of cancers and immune-related diseases.

PD-L1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND MEDICAL APPLICATION THEREOF

Provided in the present invention are a PD-L1 antibody, a fragment antigen binding thereof, and a use of the antibody or fragment antigen binding in the preparation of drugs for treating PD-L1-mediated diseases or conditions.

INTERLEUKIN 15 PROTEIN COMPLEX AND USE THEREOF

Provided in the application is a interleukin 15 (IL-15) protein complex. The IL-15 protein complex consists of a soluble fusion proteins (I) and (II), wherein the fusion protein (I) is a IL-15 polypeptide or a functionality fragment thereof, and the fusion protein (II) is a IL-15Ra polypeptide or a functionality fragment thereof. There are one or more amino acid sites on the fusion proteins (I) or (II) were mutated to Cys, which were paired with the corresponding Cys mutated from the amino acid sites on the fusion proteins (II) or(I) to form disulfide bonds. The IL-15 protein complex can be used for tumour therapy.

Anticuerpo pdi-1, fragmento unificador antígeno de la misma y aplicación médica de la misma

Sost antibody, antigen-binding fragments and pharmaceutical use thereof

PD-L1 antibody, antigen-binding fragment thereof and medical application thereof

The present invention relates to a PD-L1 antibody, antigen-binding fragments, and medical application thereof. Further, the present invention relates to chimeric antibodies and humanized antibodies comprising the CDR regions of the present PD-L1 antibody, as well as a pharmaceutical composition comprising the present PD-L1 antibody and the antigen-binding fragments thereof, and their use as anti-cancer drugs. In particular, the present invention relates to a humanized PD-L1 antibody and its use in preparation of a medicament for the treatment of PD-L1 mediated disease or disorder.

Stable anti-PD-1 antibody pharmaceutical preparation and application thereof in medicine

A stable anti-PD-1 antibody pharmaceutical preparation and an application thereof in a medicine. The anti-PD-1 antibody pharmaceutical preparation comprises an anti-PD-1 antibody, a buffer, and can further comprise at least one type of stabilizer, and optionally can further comprise a surfactant. The anti-PD-1 antibody pharmaceutical preparation of the present invention can effectively suppress antibody aggregation and deamidation, thereby preventing degradation of an antibody product, resulting in a stable injectable pharmaceutical preparation.

IL-6R ANTIBODY AND ANTIGEN BINDING FRAGMENT THEREOF AND MEDICAL USE

Provided in the present invention are an IL-6R antibody and antigen-binding fragment thereof. The IL-6R antibody is an alpaca-derived antibody, chimeric antibody and humanized antibody. Also provided in the present invention is the use of the antibody in the preparation of a drug for treating IL-6-related diseases. 120-. (canceled)21. An anti- human IL-6R monoclonal antibody or antigen-binding fragment thereof comprising CDR1 , CDR2 and CDR3 , whereinthe sequence of CDR1 is a sequence as set forth in SEQ ID NO: 15 or a variant sequence having 3, 2 or 1 amino acid differences from the sequence as set forth in SEQ ID NO: 15;the sequence of CDR2 is a sequence as set forth in SEQ ID NO: 16 or a variant sequence having 3, 2 or 1 amino acid differences from the sequence as set forth in SEQ ID NO: 16; andthe sequence of CDR3 is a sequence as set forth in SEQ ID NO: 17 or a variant sequence having 3, 2 or 1 amino acid differences from the sequence as set forth in SEQ ID NO: 17.22. The anti-human IL-6R monoclonal antibody or antigen-binding fragment thereof according to claim 21 , whereinthe CDR1 sequence is as set forth in SEQ ID NO: 15;the CDR2 sequence is as set forth in SEQ ID NO: 16; andthe CDR3 sequence is as set forth in SEQ ID NO: 17.23. The anti- human IL-6R monoclonal antibody or antigen-binding fragment thereof according to claim 21 , wherein the monoclonal antibody is selected from the group consisting of an alpaca-derived antibody claim 21 , a chimeric antibody claim 21 , and a humanized antibody.24. The anti- human IL-6R monoclonal antibody or antigen-binding fragment thereof according to claim 23 , wherein the monoclonal antibody comprises a VHH as set forth in SEQ ID NO: 14 or the humanized antibody comprises a variant of the VHH as set forth in SEQ ID NO: 14.25. The anti-human IL-6R monoclonal antibody or antigen-binding fragment thereof according to claim 24 , wherein:the variant of VHH has 1 to 15 humanized amino acid mutation(s) in a FR region of the VHH ...

Interleukin 15 protein complex and use thereof

Provided in the application is a interleukin 15 (IL-15) protein complex. The IL-15 protein complex consists of a soluble fusion proteins (I) and (II), wherein the fusion protein (I) is a IL-15 polypeptide or a functionality fragment thereof, and the fusion protein (II) is a IL-15Rα polypeptide or a functionality fragment thereof. There are one or more amino acid sites on the fusion proteins (I) or (II) were mutated to Cys, which were paired with the corresponding Cys mutated from the amino acid sites on the fusion proteins (II) or(I) to form disulfide bonds. The IL-15 protein complex can be used for tumour therapy.

Ligand-drug conjugate of exatecan analogue, preparation method therefor and application thereof

The present invention relates to a ligand-drug conjugate of an exatecan analogue, a preparation method therefor and an application thereof. Specifically, the present invention provides a ligand-drug conjugate having a structure shown in formula (-D), a preparation method therefor, a pharmaceutical composition containing same, and use thereof in preparation of drugs for treating cancers by means of receptor regulation. The definition of each substituent in formula (-D) is the same as that in the description.

IL-5 antibody, antigen binding fragment thereof, and medical application therefor

Provided are an IL-5 antibody, an antigen binding fragment thereof, and a medical application therefor. The present invention comprises a mouse-derived antibody containing an IL-5 antibody CDR region, a chimeric antibody, a humanized antibody, and a pharmaceutical composition comprising said IL-5 antibody and said antigen binding fragment thereof, as well as the use of the pharmaceutical composition as a drug.

PYRIDOPYRIMIDINE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

Disclosed are a pyridopyrimidine derivative as shown in general formula (I), a preparation method therefor and a pharmaceutical composition containing the derivative, and the use thereof as a therapeutic agent, particularly as a TLR8 agonist, wherein each substituent of general formula (I) is the same as those defined in the description.

INDOLE MACROCYCLIC DERIVATIVE, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF IN MEDICINE

The present invention relates to an indole macrocyclic derivative, a preparation method therefor and an application thereof in medicine. Specifically, the present invention relates to an indole macrocyclic derivative represented by general formula (IM), a preparation method therefor, a pharmaceutical composition containing the derivative, and a use thereof as a therapeutic agent, especially as an MCL-1 inhibitor. Each substituent of general formula (IM) is the same as those defined in the description.

6-OXO-1,6-DIHYDROPYRIDAZINE PRODRUG DERIVATIVE, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF IN MEDICINE

Specifically, the present invention relates to the 6-oxo-1,6-dihydropyridazine prodrug derivative shown in general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, a use thereof as a NaV inhibitor, and a use thereof in the preparation of a drug for the treatment and/or prevention of pain and pain-related diseases.

LAG-3 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND PHARMACEUTICAL APPLICATION THEREOF

Provided are a LAG-3 antibody, an antigen-binding fragment thereof, and a pharmaceutical application thereof. Further, provided are a chimeric antibody comprising a CDR of the LAG-3 antibody, a humanized antibody, a pharmaceutical composition comprising the LAG-3 antibody and the antigen-binding fragment thereof, and an application of the pharmaceutical composition as an antineoplastic drug. Particularly, provided is an application of a humanized LAG-3 antibody in preparation of drugs for treatment of diseases involving immune cells.

METHOD FOR KNOCKING OUT TARGET GENE IN T CELL IN VITRO AND CRRNA USED IN THE METHOD

Provided is a method for knocking out target genes in T cells in vitro based on the CRISPR-Cas9 system. Also provided are crRNA targeting target genes TRAC, B2M and PD1, and a kit comprising sgRNA formed by linking the crRNA and tracrRNA corresponding to a Cas9 protein, the Cas9 protein, an oligodeoxyribonucleic acid (N-oligo) or a milt DNA fragment. The kit is used to knock out the TCR, B2M and/or PD1 genes in T cells. Also provided are T cells with gene knock out obtained according to the method of the present invention and the use thereof.

OXA SPIRO DERIVATIVE, PREPARATION METHOD THEREFOR, AND APPLICATIONS THEREOF IN MEDICINES

The present invention relates to an oxa spiro derivative, a preparation method therefor, and applications thereof in medicines. Particularly, the present invention relates to an oxa spiro derivative represented by formula (I), a preparation method therefor, and a pharmaceutical composition comprising the derivative, applications thereof as an MOR receptor agonist, and applications in the preparation of drugs for treating and/or preventing pains and pains-related diseases. Substituent groups in the formula (I) are same as definitions in the specifications.

Anti-connective tissue growth factor antibody and application thereof

Provided are an anti-CTGF antibody comprising light chain and heavy chain variable regions and use thereof as a medicament, the antibody can be used for preparing a medicament for treating CTGF-related diseases or disorders.

Oxa spiro derivative, preparation method therefor, and applications thereof in medicines

The present invention relates to an oxa spiro derivative, a preparation method therefor, and applications thereof in medicines. Particularly, the present invention relates to an oxa spiro derivative represented by formula (I), a preparation method therefor, and a pharmaceutical composition comprising the derivative, applications thereof as an MOR receptor agonist, and applications in the preparation of drugs for treating and/or preventing pains and pains-related diseases. Substituent groups in the formula (I) are same as definitions in the specification.

PHENYL PROPANAMIDE DERIVATIVE, AND MANUFACTURING METHOD AND PHARMACEUTICAL APPLICATION THEREOF

The present invention provides a phenylpropanamide derivative as represented by formula (I), a manufacturing method of the derivative, application of the derivative as a κ-opioid receptor (KOR) agonist, and application of the derivative for manufacturing a pharmaceutical product for treating and/or preventing pain or a pain-related disease.

Anti-c-Met antibody and anti-c-Met antibody-cytotoxic drug conjugate and pharmaceutical use thereof

Provided are an anti-c-Met antibody or antigen binding fragment, and an anti-c-Met antibody-cytotoxic drug conjugate, wherein the antibody or antigen binding fragment is a chimeric antibody or a humanized antibody. Also provided are a pharmaceutical composition containing a humanized anti-c-Met antibody or antigen binding fragment, antibody-cytotoxic drug conjugate, or a pharmaceutically acceptable salt or solvent compound thereof, applied in the treatment of cancer.

Condensed ring group azacyclobutyl triazole derivative, preparation method therefor and use thereof in medicine

The present invention relates to a condensed ring group azacyclobutyl triazole derivative, a preparation method therefor and use thereof in medicine. In particular, the present invention relates to a novel condensed ring group azacyclobutyl triazole derivative as represented by general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, use thereof as a therapeutic agent, in particular as an oxytocin antagonist, and use thereof in the preparation of a medicament used for treating or preventing a disease or a condition that is known or can exhibit a beneficial effect of inhibiting oxytocin. The definition for each substituent in general formula (I) is the same as that in the description.

Phenyl propanamide derivative, and manufacturing method and pharmaceutical application thereof

The present invention provides a phenyl propanamide derivative as represented by formula (I), a manufacturing method of the derivative, application of the derivative as a κ-opioid receptor (KOR) agonist, and application of the derivative for manufacturing a pharmaceutical product for treating and/or preventing pain or a pain-related disease.

IL-5 ANTIBODY, ANTIGEN BINDING FRAGMENT THEREOF, AND MEDICAL APPLICATION THEREFOR

Provided are an IL-5 antibody, an antigen binding fragment thereof, and a medical application therefor. The present invention comprises a mouse-derived antibody containing an IL-5 antibody CDR region, a chimeric antibody, a humanized antibody, and a pharmaceutical composition comprising said IL-5 antibody and said antigen binding fragment thereof, as well as the use of the pharmaceutical composition as a drug.

ANTI-B7H3 ANTIBODY-EXATECAN ANALOG CONJUGATE AND MEDICINAL USE THEREOF

Disclosed by the present invention are an anti-B7H3 antibody-exatecan analog conjugate, a preparation method therefor and an anti-tumor medicinal use thereof.

PHARMACEUTICAL COMPOSITION CONTAINING ANTIBODY AGAINST IL-5 AND USE THEREOF

Disclosed in the present application are a pharmaceutical composition containing an antibody against IL-5 and use thereof. In particular, disclosed in the present application is a pharmaceutical composition, which contains an IL-5 antibody or an antigen binding fragment thereof in a buffer solution. In addition, the pharmaceutical composition further contains a saccharide and a nonionic surfactant.

THIENOHETEROCYCLIC DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

Provided are a thienoheterocyclic derivative, a preparation method therefor and the medical use thereof. In particular, provided are a thienoheterocyclic derivative represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, the use of same as a therapeutic agent, particularly as an ERK inhibitor, and the use of same in the preparation of a drug for treating or preventing cancers, inflammation or other proliferative diseases, wherein each substituent of general formula (I) is the same as defined in the description.

BENZOPIPERIDINE DERIVATIVE, PREPARATION METHOD THEREOF AND MEDICAL USE THEREOF

The present invention relates to a benzopiperidine derivative, a preparation method thereof and a medical use thereof. In particular, the present invention relates to a benzopiperidine derivative as shown by general formula (I), a preparation method thereof and a pharmaceutical composition containing the derivative, as well as a use thereof as an estrogen receptor modulator in the prevention and/or treatment of estrogen receptor-mediated or dependent diseases or conditions. Preferably, the disease is breast cancer. The substituents in general formula (I) are the same as those defined in the description.

THROMBIN ANTIBODY, ANTIGEN-BINDING FRAGMENT AND PHARMACEUTICAL USE THEREOF

Provided are a thrombin antibody, an antigen-binding fragment and a pharmaceutical use thereof. Further provided are a chimeric antibody and a humanized antibody comprising a thrombin antibody CDR region, and a pharmaceutical composition comprising the thrombin antibody and the antigen-binding fragment thereof, as well as the use thereof as an anticoagulant drug. In particular, provided is a use of the humanized thrombin antibody in preparing a drug for treating a thrombin-mediated disease or condition.

JAK INHIBITION BLOCKS RNA INTERFERENCE ASSOCIATED TOXICITIES

The instant invention provides a method for treating patients by administering a JAK inhibitor. The instant invention provides a method for treating patients by administering a JAK inhibitor wherein the JAK inhibitor is a JAK2 inhibitor. The instant invention provides a method for treating patients by administering a JAK inhibitor wherein the JAK inhibitor is selected from selected from Jak2-IA, AG490, Pyridone 6, WP1066, LS104, TG101209, TG101348, CP690,550, CP352,664, INCB18424, WHI-P154, CMP6, SB1518, XL019, CEP-701, INCB20, AUH-6-96 and AZ960. 1. A method for treating a patient , wherein the patient will be or is currently being treated with a lipid-based nucleic acid therapeutic , by administering a JAK inhibitor.2. The method of wherein the JAK inhibitor is a JAK2 inhibitor.3. The method of wherein the JAK inhibitor is selected from Jak2-IA claim 1 , AG490 claim 1 , Pyridone 6 claim 1 , WP1066 claim 1 , LS104 claim 1 , TG101209 claim 1 , TG101348 claim 1 , CP690 claim 1 ,550 claim 1 , CP352 claim 1 ,664 claim 1 , INCB18424 claim 1 , WHI-P154 claim 1 , CMP6 claim 1 , SB1518 claim 1 , XL019 claim 1 , CEP-701 claim 1 , INCB20 claim 1 , AUH-6-96 and AZ960.4. The method of wherein the patient is pre-treated with a JAK inhibitor.5. The method of wherein the patient is co-treated with a JAK inhibitor. Synthetic small interfering RNA (siRNA) duplexes hold a great promise to become a new therapeutic entity as they are able to silence gene expression specifically in a sequence-dependent manner by triggering RNA interference (RNAi), an evolutionarily conserved cellular process for repressing gene expression. Given the fact that naked siRNAs, even with optimized sequences and chemical modifications, lack drug-like pharmacokinetic properties, tissue bioavailability and the ability of entering cells, a major hurdle for harnessing siRNA for broad therapeutic use is the effective and safe delivery of siRNA to the diseased tissues and cells via systemic administration. Many ...

STABLE ANTI-PD-1 ANTIBODY PHARMACEUTICAL PREPARATION AND APPLICATION THEREOF IN MEDICINE

A stable anti-PD-1 antibody pharmaceutical preparation and an application thereof in a medicine. The anti-PD-1 antibody pharmaceutical preparation comprises an anti-PD-1 antibody, a buffer, and can further comprise at least one type of stabilizer, and optionally can further con a surfactant. The anti-PD-1 antibody pharmaceutical preparation of the present invention can effectively suppress antibody aggregation and deamidation, thereby preventing degradation of an antibody product, obtaining a stable injected pharmaceutical preparation. 1. An anti-PD-1 antibody comprising a heavy chain having the amino acid sequence of SEQ ID NO: 7 and alight chain having the amino acid sequence of SEQ ID NO: 8.2. A pharmaceutical composition comprising the anti-PD-1 antibody of .3. The pharmaceutical composition of claim 2 , being an injectable pharmaceutical formulation further comprising water for injection.4. A lyophilized powder prepared from the pharmaceutical formulation of .5. A method of blocking the binding of PD-1 to PD-L1 in a subject in need thereof claim 2 , comprising administering to the subject the pharmaceutical composition of .6. The method of claim 5 , wherein the subject is in need of a treatment of a cancer selected from the group consisting of breast cancer claim 5 , lung cancer claim 5 , stomach cancer claim 5 , intestinal cancer claim 5 , kidney cancer claim 5 , and melanoma.7. The method of claim 5 , wherein the pharmaceutical composition is an injectable pharmaceutical formulation further comprising water for injection.8. A method of blocking the binding of PD-1 to PD-L1 in a subject in need thereof claim 5 , comprising administering to the subject a stable pharmaceutical formulation comprising:(i) an anti-PD-1 antibody comprising a heavy chain having the amino acid sequence of SEQ ID NO: 7 and a light chain having the amino acid sequence of SEQ ID NO: 8;(ii) a buffer selected from the group consisting of an acetate buffer, a citrate buffer, a succinate ...

PCSK9 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND MEDICAL APPLICATION THEREOF

The present invention provides a PCSK9 antibody, an antigen-binding fragment thereof, and a medicinal application thereof. Provided in the invention is a chimeric antibody and a humanized antibody, both comprising a CDR of the PCSK9 antibody, and a pharmaceutical composition comprising the PCSK9 antibody and an antigen-binding fragment thereof, and an application of the PCSK9 antibody as a lipid-lowering agent. The invention specifically relates to an application of a humanized PCSK9 antibody for preparing a pharmaceutical drug to treat a PCSK9-induced disease or symptom. 13.-. (canceled)4. A PCSK9 antibody or the antigen-binding fragment thereof , wherein the antibody comprises a HCDR1 , a HCDR2 , and a HCDR3 as shown in SEQ ID NO: 12 , SEQ ID NO: 13 and SEQ ID NO: 14 , respectively , or comprises a HCDR1 , a HCDR2 and a HCDR3 having at least 95% identity to SEQ ID NO: 12 , SEQ ID NO: 13 and SEQ ID NO: 14 , respectively; anda LCDR1, a LCDR2, and a LCDR3 as shown in SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17, respectively, or comprises a LCDR1, a LCDR2, and a LCDR3 having at least 95% identity to these sequences SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17, respectively.5. The PCSK9 antibody or the antigen-binding fragment thereof according to claim 4 , wherein the PCSK9 antibody or antigen-binding fragment thereof is a murine antibody or fragment thereof.6. The PCSK9 antibody or the antigen-binding fragment thereof according to claim 4 , wherein the PCSK9 antibody light chain variable region further comprises light chain FR regions derived from a murine κ chain or a variant thereof claim 4 , or light chain FR regions derived from a murine λ chain or a variant thereof; wherein the PCSK9 antibody heavy chain variable region further comprises heavy chain FR regions derived from a murine IgG1 or a variant thereof claim 4 , or heavy chain FR regions derived from a murine IgG2 or a variant thereof claim 4 , or heavy chain FR regions derived from a murine IgG3 or a ...

CONDENSED RING GROUP AZACYCLOBUTYL TRIAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR AND USE THEREOF IN MEDICINE

A condensed ring group azacyclobutyl triazole derivative, a preparation method therefor and use thereof in medicine are provided. In particular, a condensed ring group azacyclobutyl triazole derivative as represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, use thereof as a therapeutic agent, in particular as an oxytocin antagonist, and for treating or preventing a disease or a condition that is known or can exhibit a beneficial effect of inhibiting oxytocin are provided. The definition for each substituent in general formula (I) is the same as that in the description. 5. The compound according to claim 1 , wherein ring A is pyridyl or benzodioxole.7. The compound according to claim 1 , wherein Ris alkyl claim 1 , wherein the alkyl is optionally substituted by one or more substituents selected from the group consisting of alkoxy claim 1 , halogen claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , hydroxy claim 1 , NHS(O)Rand NHC(O)OR; Ris alkyl; and s is 0 claim 1 , 1 or 2.8. The compound according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl and haloalkyl.9. The compound according to claim 1 , wherein Ris alkoxy.10. The compound according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , cyano claim 1 , oxo and —C(O)OR; and Ris alkyl.11. The compound according to claim 1 , wherein n is 1 or 2; and m is 0 or 1.16. A pharmaceutical composition comprising the compound according to claim 1 , and one or more pharmaceutically acceptable carriers claim 1 , diluents or excipients.1719.-. (canceled)20. A method of antagonizing oxytocin in a subject in need thereof claim 16 , the method comprising administering to the subject the pharmaceutical composition ...

INDOLE MACROCYCLIC DERIVATIVE, PREPARATION METHOD THEREOF AND APPLICATION THEREOF IN MEDICINE

The present invention relates to an indole macrocyclic derivative, a preparation method therefor and an application thereof in medicine. Specifically, the present invention relates to an indole macrocyclic derivative represented by general formula (IM), a preparation method therefor, a pharmaceutical composition containing the derivative, and a use thereof as a therapeutic agent, especially as an MCL-1 inhibitor. Each substituent of general formula (IM) is the same as those defined in the description. 2. (canceled)3. (canceled)68.-. (canceled)10. (canceled)11. (canceled)1316.-. (canceled)19. (canceled)21. (canceled)25. (canceled)28. (canceled)30. A pharmaceutical composition comprising the compound of formula (IM) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , and one or more pharmaceutically acceptable carrier(s) claim 1 , diluent(s) or excipient(s).31. A method for inhibiting MCL-1 claim 1 , the method comprising a step of administering to a patient in need thereof a therapeutically effective dose of the compound of formula (IM) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to .32. A method for preventing or treating MCL-1-mediated diseases claim 1 , the method comprising a step of administering to a patient in need thereof a preventively or therapeutically effective dose of the compound of formula (IM) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to .33. A method for treating tumors claim 1 , autoimmune diseases or immune system diseases claim 1 , the method comprising a step of ...

METHOD FOR PREPARING ANTIBODY-DRUG CONJUGATE

A method for preparing an antibody-drug conjugate (ADC). In particular, the method mainly utilizes a combination of antibody biomolecules and an ion exchange carrier through electrostatic interaction to realize solid phase preparation of an ADC drug. Elution conditions are optimized, to control a drug-to-antibody coupling ratio (DAR) and separate a polymer-coupled drug, reduce the amount of a drug used in a coupling reaction, and enhance the targeted therapeutic effect of an ADC drug. The preparation method features fewer steps, simple operation, and programmable control, facilitating industrial scale-up production, and also realizing zero retention of reducing agents and organic solvents in the preparation process, significantly improving drug safety and reducing production costs. 1. A method for preparing an antigen-binding protein-drug conjugate , wherein the method comprises the following steps:1) immobilizing an antigen-binding protein on an ion exchange carrier to form an immobilized antigen-binding protein;2) contacting the immobilized antigen-binding protein with a drug to form an antigen-binding protein-drug conjugate;3) eluting the antigen-binding protein-drug conjugate from the ion exchange carrier.2. The method of claim 1 , wherein said ion exchange carrier is selected from the group consisting of ion exchange resins claim 1 , ion exchange membranes claim 1 , ion exchange fibers claim 1 , preferably ion exchange resins.3. The method of or claim 1 , wherein the ion exchange carrier is a cation exchange carrier claim 1 , and the cation exchange carrier preferably contains a strongly acidic reaction ligand claim 1 , and the strongly acidic reaction ligand is preferably a sulfonate.4. The method of any one of to claim 1 , wherein the immobilized antigen-binding protein in step 2) is coupled to a drug claim 1 , and the coupling reaction is that the antigen-binding protein and the drug are linked through an interaction between a nucleophilic group and an ...

B7-H3 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND MEDICAL USE THEREOF

A B7-H3 antibody, an antigen-binding fragment thereof and a medical use thereof are provided. Furthermore, a pharmaceutical composition containing the B7-H3 antibody or antigen-binding fragment thereof, and the use thereof as a medicament are provided. In particular, a use of a human B7-H3 antibody or antigen-binding fragment thereof for the manufacture of a medicament for the treatment of a B7-H3-associated disease or condition are described. 1. A monoclonal anti-B7-H3 antibody or antigen-binding fragment thereof , which binds to human B7-H3 , comprising:(i)an antibody heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NOs: 10, 11 and 12, respectively; andan antibody light chain variable region comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NOs: 13, 14 and 15, respectively; or(ii)an antibody heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NOs: 16, 17 and 18, respectively; andan antibody light chain variable region comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NOs: 19, 20 and 21, respectively.2. The monoclonal anti-B7-H3 antibody or antigen-binding fragment thereof according to claim 1 , wherein the monoclonal antibody is a recombinant antibody.3. The monoclonal anti-B7-H3 antibody or antigen-binding fragment thereof according to claim 2 , wherein the monoclonal antibody is a human recombinant antibody or antigen-binding fragment thereof.4. The monoclonal anti-B7-H3 antibody or antigen-binding fragment thereof according to claim 3 , wherein the framework (FR) sequences of the light chain and heavy chain variable regions of the human recombinant antibody are derived from a human germline light chain and heavy chain claim 3 , respectively claim 3 , or mutant sequences thereof.5. The monoclonal anti-B7-H3 antibody or antigen-binding fragment thereof according to claim 4 , wherein the human ...

HETEROARYL[4,3-C]PYRIMIDINE-5-AMINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND MEDICAL USES THEREOF

A heteroaryl[4,3-c]pyrimidin-5-amine derivative, a preparation method therefor, and medical uses thereof are provided. Specifically, a heteroaryl[4,3-c]pyrimidin-5-amine derivative of formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and uses thereof as therapeutic agents are provided. In particular, the provided compounds can be used as Ata receptor antagonists and for treatment of conditions or symptoms that are ameliorated by inhibiting the Ata receptor. The various substituent groups in the formula (I) have the meanings as described in the specification. 2. The compound of according to claim 1 , wherein Ris selected from the group consisting of cyano claim 1 , cycloalkyl claim 1 , heterocyclyl claim 1 , aryl and heteroaryl claim 1 , wherein the cycloalkyl claim 1 , heterocyclyl claim 1 , aryl and heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , alkoxy claim 1 , oxo claim 1 , cycloalkyl claim 1 , heterocyclyl and R; Ris heterocyclylalkyl claim 1 , wherein the heterocyclyl of the heterocyclylalkyl is optionally substituted by one or more alkyl.5. The compound according to claim 3 , wherein ring B is selected from the group consisting of phenyl claim 3 , pyridyl claim 3 , pyrazolyl claim 3 , pyridin-2-one claim 3 , imidazolyl claim 3 , pyrrolyl claim 3 , furyl claim 3 , thienyl claim 3 , piperidinyl claim 3 , tetrahydropyridyl claim 3 , isoquinolyl claim 3 , quinolyl claim 3 , quinoxalinyl claim 3 , indolyl claim 3 , indazolyl claim 3 , benzofuranyl and benzothienyl.7. The compound according to claim 1 , wherein ring A is aryl or heteroaryl.8. The compound according to claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halogen and alkyl.9. The compound according to claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halogen and alkyl.14 ...

TRICYCLIC COMPOUNDS AS STING AGONISTS, AND PREPARATION METHODS AND MEDICINAL USES THEREOF

Compounds of formula (I) useful as agonists of stimulator of interferon genes (STING), the preparation method therefor, pharmaceutical compositions comprising the compounds, and the pharmaceutical uses for the treatment of STING-mediated diseases or disorders are disclosed. 3. The compound of , or a tautomer , cis- or trans-isomer , mesomer , racemate , enantiomer , diastereomer , or mixture thereof , or a pharmaceutically acceptable salt , solvate , or prodrug thereof , wherein G , G , Gand Gare identical or different , and each is independently CR; wherein Rat each occurrence is independently as defined in .4. The compound according to claim 1 , or a tautomer claim 1 , cis- or trans-isomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Rand Rare identical or different claim 1 , and each is independently aryl or heteroaryl; wherein the aryl or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen claim 1 , alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , amino claim 1 , nitro claim 1 , cyano claim 1 , hydroxy claim 1 , hydroxyalkyl claim 1 , cycloalkyl claim 1 , heterocyclyl claim 1 , aryl claim 1 , and heteroaryl.5. The compound according to claim 1 , or a tautomer claim 1 , cis- or trans-isomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Rand Rare each hydrogen.7. The compound according to claim 1 , or a tautomer claim 1 , cis- or trans-isomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or ...

6-OXO-1,6-DIHYDROPYRIDAZINE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

A 6-oxo-1,6-dihydropyridazine derivative, a preparation method therefor and medical use thereof, in particular, a 6-oxo-1,6-dihydropyridazine derivative represented by general formula (I), a preparation method therefor, and a pharmaceutical composition containing the derivative, and use thereof as a Nav inhibitor and use thereof in the preparation of a drug for the treatment and/or prevention of pain and pain-related diseases. Each substituent in general formula (I) is the same as defined in the description. 3. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein M is selected from the group consisting of O atom claim 1 , CHand S atom.6. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of hydrogen atom claim 1 , halogen claim 1 , alkyl claim 1 , alkoxy claim 1 , haloalkyl and haloalkoxy.7. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of hydrogen atom claim 1 , halogen claim 1 , alkyl claim 1 , deuterated alkyl claim 1 , alkoxy claim 1 , deuterated alkoxy claim 1 , hydroxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , cycloalkyl and cycloalkyloxy.8. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim ...

FIVE-MEMBERED HETEROARYL RING BRIDGED RING DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

The present invention relates to a five-membered heteroaryl ring bridged ring derivative, a preparation method therefor and the medical use thereof. In particular, the present invention relates to a new five-membered heteroaryl ring bridged ring derivative as shown in formula (I), a preparation method therefor and a pharmaceutical composition comprising the derivative, and the use thereof as a therapeutic agent, in particular as a TGF-β inhibitor, and the use in the preparation of a drug for treating, preventing or reducing cancers mediated by the over-expression of TGF-β, wherein the definition of each substituent in the general formula (I) is the same as defined in the description. 4: The compound of formula (I) according to claim 1 , wherein Ris alkyl or halogen claim 1 , preferably methyl claim 1 , ethyl claim 1 , chlorine claim 1 , bromine or fluorine.15: A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of the compound of formula (I) claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt thereof according to claim 1 , and one or more pharmaceutically acceptable carriers claim 1 , diluents or excipients.16: (canceled)17: A method for treating claim 1 , preventing or reducing tumor cell metastasis claim 1 , comprising administering to a patient in need thereof a therapeutically effective amount of the compound of formula (I) claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt thereof according to .18: (canceled)19: A method for treating claim 1 , preventing or reducing cancer mediated by TGF-β overexpression claim 1 , comprising administering to a patient in need thereof a therapeutically effective amount of the compound of formula (I) claim 1 , or a tautomer ...

INTERLEUKIN 15 PROTEIN COMPLEX AND USE THEREOF

An interleukin 15 (IL-15) protein complex is provided. The IL-15 protein complex includes soluble fusion proteins (I) and (II), wherein the fusion protein (I) is an IL-15 polypeptide or a functional fragment thereof, and the soluble fusion protein (II) is an IL-15Rα polypeptide or a functional fragment thereof. The soluble fusion protein (I) has at least one amino acid residue mutated to a cysteine (Cys) residue, which pairs with a corresponding mutated Cys residue on the soluble fusion protein (II), or vice versa, to form one or more disulfide bonds. The IL-15 protein complex can be used for tumor therapy. 1. An IL-15 protein complex comprising a soluble fusion protein (I) and a soluble fusion protein (II) , wherein:the soluble fusion protein (I) is an IL-15 polypeptide or a functional fragment thereof; and the soluble fusion protein (II) is an IL-15Rα polypeptide or a functional fragment thereof;wherein at least one of the soluble fusion protein (I) and the soluble fusion protein (II) comprises at least one Cys residue introduced by substitution of at least one amino acid residue of the at least one of the soluble fusion protein (I) and soluble fusion protein (II), and a disulfide bond is formed by pairing of corresponding Cys residues of the soluble fusion protein (II) and the soluble fusion protein (I).2. The IL-15 protein complex according to claim 1 , wherein at least one of the soluble fusion protein (I) and soluble fusion protein (II) is covalently linked to an Fc fragment or a mutant thereof.3. The IL-15 protein complex according to claim 1 , wherein the soluble fusion protein (I) comprises an amino acid Cys mutation at residue L45 claim 1 , Q48 claim 1 , V49 claim 1 , L52 claim 1 , E53 claim 1 , C88 or E89 of the IL-15 polypeptide or a functional fragment thereof.4. The IL-15 protein complex according to claim 1 , wherein the sequence of the soluble fusion protein (I) comprises SEQ ID NO: 2.5. The IL-15 protein complex according to claim 1 , wherein the ...

Anti-pd-1 antibody, antigen-binding fragment thereof and pharmaceutical use thereof

Provided are an anti-PD-1 antibody, an antigen-binding fragment thereof, and a pharmaceutical use thereof. Specifically, provided are a humanized anti-PD-1 antibody containing a specific CDR region and an antigen-binding fragment thereof, a pharmaceutical composition containing the anti-PD-1 antibody and the antigen-binding fragment thereof, and a used thereof as medicament. In particular, provided is a use of the humanized anti-PD-1 antibody in the preparation of the medicament for treating PD-1 associated diseases or disorders.

PHARMACEUTICAL COMPOSITION CONTAINING ANTIBODY AGAINST IL-5 AND USE THEREOF

Disclosed in the present application are a pharmaceutical composition containing an antibody against IL-5 and use thereof. In particular, disclosed in the present application is a pharmaceutical composition, which contains an IL-5 antibody or an antigen binding fragment thereof in a buffer solution. In addition, the pharmaceutical composition further contains a saccharide and a nonionic surfactant. 1. A pharmaceutical composition , comprising an anti-IL-5 antibody or an antigen-binding fragment thereof , a buffer and a surfactant , wherein the buffer is any one selected from the group consisting of acetic acid-sodium acetate , succinic acid-sodium succinate , histidine-hydrochloride and citric acid-sodium citrate buffer , preferably acetic acid-sodium acetate or succinic acid-sodium succinate buffer; wherein , the anti-IL-5 antibody or the antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region selected from the group consisting of i) to vi):i) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in amino acid sequence SEQ ID NOs: 16, 17 and 18, respectively, anda light chain variable region comprising LCDR1, LCDR2 and LCDR3 as shown in amino acid sequence SEQ ID NOs: 19, 20 and 21, respectively;ii) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in amino acid sequence SEQ ID NOs: 22, 23 and 24, respectively, anda light chain variable region comprising LCDR1, LCDR2 and LCDR3 as shown in amino acid sequence SEQ ID NOs: 25, 26 and 27, respectively;iii) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in amino acid sequence SEQ ID NOs: 28, 29 and 30, respectively, anda light chain variable region comprising LCDR1, LCDR2 and LCDR3 as shown in amino acid sequence SEQ ID NOs: 31, 32 and 33, respectively;iv) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in amino acid sequence SEQ ID NOs: 34, 35 and 36, respectively, anda light ...

ANTI-SCLEROSTIN ANTIBODY, ANTIGEN BINDING FRAGMENT AND MEDICAL USE THEREOF

Provided is a humanized antibody and chimeric antibody that specifically binds human sclerostin. The antibodies can be used for treating human bone metabolism related diseases such as osteoporosis (OP). 1. An antibody or antigen-binding fragment thereof that specifically binds to human sclerostin , comprising:a heavy chain variable region HCDR sequence comprising amino acid sequences of SEQ ID NO: 7, SEQ ID NO: 8 or SEQ ID NO: 9, or a mutant sequence thereof, or an amino acid sequence having at least 95% sequence identity thereto; anda light chain variable region LCDR sequence comprising amino acid sequences of SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12, or a mutant sequence thereof, or an amino acid sequence having at least 95% sequence identity thereto.24.-. (canceled)5. The antibody or antigen-binding fragment thereof that specifically binds to human sclerostin according to claim 1 , wherein the mutant sequence of the CDR region has 1 to 3 amino acid mutations that optimize antibody activity.6. The antibody or antigen-binding fragment thereof that specifically binds to human sclerostin according to claim 1 , wherein the antibody or the antigen-binding fragment thereof is a murine antibody or fragment thereof.7. The antibody or antigen-binding fragment thereof that specifically binds to human sclerostin according to claim 6 , wherein the heavy chain variable region sequence of the murine antibody comprises SEQ ID NO: 5 claim 6 , or a sequence having at least 95% identity to SEQ ID NO: 5.8. The antibody or antigen-binding fragment thereof that specifically binds to human sclerostin according to claim 6 , wherein the light chain variable region sequence of the murine antibody comprises SEQ ID NO: 6 claim 6 , or a sequence having at least 95% identity to SEQ ID NO: 6.9. (canceled)10. The antibody or antigen-binding fragment thereof that specifically binds to human sclerostin according to claim 1 , wherein the antibody or the antigen-binding fragment thereof is a ...

B7-H3 Antibody, Antigen-Binding Fragment Thereof And Medical Use Thereof

A B7-H3 antibody, an antigen-binding fragment thereof and a medical use thereof are provided. Furthermore, a pharmaceutical composition containing the B7-H3 antibody or antigen-binding fragment thereof, and the use thereof as a medicament are provided. In particular, a use of a human B7-H3 antibody or antigen-binding fragment thereof for the manufacture of a medicament for the treatment of a B7-H3-associated disease or condition are described. 1. A method for treating a disease related to a B7-H3 positive cell , wherein the method comprises administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a monoclonal anti-B7-H3 antibody or antigen-binding fragment thereof comprising:(i) an antibody heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NOs: 10, 11 and 12, respectively; and an antibody light chain variable region comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NOs: 13, 14 and 15, respectively; or(ii) an antibody heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NOs: 16, 17 and 18, respectively; and an antibody light chain variable region comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NOs: 19, 20 and 21, respectively.2. The method according to claim 1 , wherein the monoclonal antibody is a recombinant antibody.3. The method according to claim 1 , wherein the monoclonal antibody is a human recombinant antibody or antigen-binding fragment thereof4. The method according to claim 3 , wherein the human recombinant antibody or antigen-binding fragment thereof comprises a human germline light chain framework (FR) sequence or a modified human germline light chain FR sequence claim 3 , and a human germline heavy chain FR sequence or a modified human germline heavy chain FR sequence.5. The method according to claim 4 , wherein the human ...

Anti-c-met antibody and anti-c-met antibody-cytotoxic drug conjugate and pharmaceutical use thereof

Provided are an anti-c-Met antibody or an antigen binding fragment thereof, and an anti-c-Met antibody-cytotoxic drug conjugate, wherein the antibody or antigen binding fragment thereof is a chimeric antibody or a humanized antibody. Also provided are pharmaceutical compositions containing the humanized anti-c-Met antibody or antigen binding fragment thereof, the antibody-cytotoxic drug conjugate, or pharmaceutically acceptable salts or solvents thereof, that are used in the treatment of cancer.

INDAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL APPLICATION THEREOF

An indazole derivative, a preparation method therefor, and a pharmaceutical application thereof. In particular, the present invention relates to an indazole derivative represented by general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and a use of the derivative as an estrogen receptor modulator in the prevention and/or treatment of an estrogen receptor mediated or dependent disease or condition, the disease being particularly preferably breast cancer. The definition of each substituent in the general formula (I) is the same as that in the description. 2. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring A is selected from the group consisting of C-Ccycloalkyl and 3 to 6 membered heterocyclyl; the heterocyclyl contains one to three heteroatoms selected from the group consisting of N claim 1 , O and S.3. (canceled)6. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein G is an N atom.7. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris selected from the group consisting of halogen and hydrogen atom.8. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris a haloalkyl.9. The compound of formula (I) or the tautomer claim ...

ANTI-CD38 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND PHARMACEUTICAL USE

The present application provides an anti-CD38 antibody, an antigen-binding fragment thereof, and pharmaceutical use. Specifically, the present application provides a murine-derived antibody, a chimeric antibody or a humanized antibody comprising a CDR region of the anti-CD38 antibdoy, a pharmaceutical composition comprising the anti-CD38 antibody or the antigen-binding fragment thereof, and an application thereof as a drug. In particular, the present application provides an application of a humanized anti-CD38 antibody in preparing a drug for treating a CD38 positive disease or disorder. 1. An anti-CD38 antibody or an antigen-binding fragment thereof , wherein the anti-CD38 antibody or the antigen-binding fragment specifically binds to human CD38 , the antibody or the antigen-binding fragment thereof comprising:(i)a heavy chain HCDR1, the amino acid sequence thereof is as shown in SEQ ID No: 15 or has 3, 2 or 1 amino acid(s) difference(s) when compared with SEQ ID No: 15,a heavy chain HCDR2, the amino acid sequence thereof is as shown in SEQ ID No: 16 or has 3, 2 or 1 amino acid(s) difference(s) when compared with SEQ ID No: 16,a heavy chain HCDR3, the amino acid sequence thereof is as shown in SEQ ID No: 17 or has 3, 2 or 1 amino acid(s) difference(s) when compared with SEQ ID No: 17,a light chain LCDR1, the amino acid sequence thereof is as shown in SEQ ID No: 18 or has 3, 2 or 1 amino acid(s) difference(s) when compared with SEQ ID No: 18,a light chain LCDR2, the amino acid sequence thereof is as shown in SEQ ID No: 19 or has 3, 2 or 1 amino acid(s) difference(s) when compared with SEQ ID No: 19, anda light chain LCDR3, the amino acid sequence thereof is as shown in SEQ ID No: 20 or has 3, 2 or 1 amino acid(s) difference(s) when compared with SEQ ID No: 20; or(ii)a heavy chain HCDR1, the amino acid sequence thereof is as shown in SEQ ID No: 9 or has 3, 2 or 1 amino acid(s) difference(s) when compared with SEQ ID No: 9,a heavy chain HCDR2, the amino acid sequence ...

Indole-formamide derivative, preparation method therefor and use thereof in medicine

A solid dispersion, a method for preparing same, and a solid preparation comprising the solid dispersion. The solid dispersion contains (R)-4-amino-1-(1-(but-2-ynylacyl)pyrrolidin-3-yl)-3-(4-(2,6-difluorophenoxy)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-d]pyridazine-7-one or a pharmaceutically acceptable salt thereof, and a carrier material. The carrier material is selected from hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate.

HETEROARYL-PYRAZOLE DERIVATIVE, AND PREPARATION METHOD THEREFOR AND MEDICAL APPLICATION THEREOF

A heteroaryl-pyrazole derivative, and a preparation method therefor and a medical application thereof are described. Specifically, a new heteroaryl-pyrazole derivative as shown in formula (I), a preparation method for the derivative, a pharmaceutical composition containing the derivative, and a use of the derivative as a therapeutic agent, in particular as a TLR7 agonist, are described. The substituents in formula (I) have the same definitions as in the description. 3. The compound according to claim 1 , wherein the ring A is phenyl or pyridyl.5. The compound according to claim 1 , wherein Lis —O—.6. The compound according to claim 1 , wherein Ris alkyl.7. The compound according to claim 1 , wherein Lis alkylene.13. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of the compound according to claim 1 , and one or more pharmaceutically acceptable carriers claim 1 , diluents or excipients.1419.-. (canceled)20. A method of agonizing TLR7 in a subject in need thereof claim 13 , the method comprising contacting the pharmaceutical composition according to with the TLR7.21. A method of treating an infection caused by viruses in a patient in need thereof claim 13 , the method comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition according to .22. The method according to claim 21 , wherein the virus is selected from the group consisting of dengue virus claim 21 , yellow fever virus claim 21 , West Nile virus claim 21 , Japanese encephalitis virus claim 21 , tick-borne encephalitis virus claim 21 , Kunjin virus claim 21 , Murray Valley encephalitis virus claim 21 , St. Louis encephalitis virus claim 21 , Omsk hemorrhagic fever virus claim 21 , bovine viral diarrhea virus claim 21 , Zika virus claim 21 , HIV claim 21 , HBV claim 21 , HCV claim 21 , HPV claim 21 , RSV claim 21 , SARS and influenza virus.23. A method of treating or preventing a cancer in a patient in need thereof claim 13 ...

PIPERAZINE HETEROARYL DERIVATIVE, PREPARATION METHOD THEREFOR AND USE OF SAME IN MEDICINE

The present invention relates to a piperazine heteroaryl derivative, a preparation method therefor and the use of same in medicine. In particular, the present invention relates to the piperazine heteroaryl derivative as shown in the general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and the use of same as a capsid protein inhibitor, in particular in the prevention and/or treatment of diseases such as hepatitis B, influenza, herpes, AIDS, etc. The definitions of each group in the general formula (I) are the same as those defined in the description. 119-. (canceled)23. The compound according to claim 20 , wherein ring A is phenyl or pyridyl.25. The compound according to claim 20 , wherein Ris selected from the group consisting of alkyl claim 20 , haloalkyl claim 20 , cycloalkyl claim 20 , heterocyclyl and aryl claim 20 , wherein the alkyl claim 20 , cycloalkyl claim 20 , heterocyclyl and aryl are optionally further substituted by one or more substituents selected from the group consisting of halogen claim 20 , alkyl claim 20 , alkoxy and hydroxy.27. The compound according to claim 20 , wherein Ris hydrogen or alkyl.28. The compound according to claim 20 , wherein Ris selected from the group consisting of hydrogen claim 20 , halogen claim 20 , alkyl claim 20 , haloalkyl and cyano.36. A pharmaceutical composition claim 20 , comprising a therapeutically effective amount of the compound according to claim 20 , and a pharmaceutically acceptable carrier claim 20 , diluent claim 20 , or excipient.37. (canceled)38. A method of treating a viral infection in a subject in need thereof claim 36 , the method comprising administering the pharmaceutical composition according to to the subject.39. The method of claim 38 , wherein the viral infection is selected from the group consisting of: hepatitis B claim 38 , influenza claim 38 , herpes and AIDS. The present invention belongs to the field of medicine, and relates to a ...

FUSION PROTEIN CONTAINING TGF-ß RECEPTOR AND MEDICINAL USES THEREOF

The present invention provides a fusion protein containing TGF-β receptor and pharmaceutical use thereof. Further, the present invention provides a bifunctional fusion protein comprising the PD-L1 antibody targeting portion and the TGF-βRII extracellular domain, and a pharmaceutical composition comprising the fusion protein containing TGF-β receptor, and the use thereof in the preparation of anti-cancer drug. 1. A fusion protein , comprising a targeting moiety and a TGF-β receptor moiety , wherein the TGF-β receptor moiety is an N-terminal truncated form of the extracellular domain of TGF-βRII having a deletion of 26 or fewer contiguous amino acids at the N-terminus of the extracellular domain of TGF-βRII.2. The fusion protein according to claim 1 , wherein the N-terminal truncated form of the extracellular domain of TGF-βRII comprises a deletion of 14-21 contiguous amino acids at the N-terminus of the extracellular domain of TGF-βRII.3. The fusion protein according to claim 2 , wherein the extracellular domain of TGF-βRII has the amino acid sequence of SEQ ID NO: 13.4. The fusion protein according to claim 1 , wherein the targeting moiety is a cell-specific targeting moiety.5. The fusion protein according to claim 4 , wherein the cell-specific targeting moiety is a cancer cell-specific targeting moiety selected from the group consisting of an antibody or antigen-binding fragment thereof claim 4 , a growth factor claim 4 , a hormone claim 4 , a peptide claim 4 , a receptor and a cytokine.6. The fusion protein according to claim 5 , wherein the antibody or antigen-binding fragment thereof is selected from the group consisting of a full length antibody claim 5 , a chimeric antibody claim 5 , Fab′ claim 5 , Fab claim 5 , F(ab′) claim 5 , a single domain antibody claim 5 , Fv claim 5 , scFv claim 5 , a small antibody claim 5 , a bi-specific antibody claim 5 , and a tri-specific antibody or mixture thereof.7. The fusion protein according to claim 6 , wherein the antibody ...

PHARMACEUTICAL COMPOSITION OF KOR RECEPTOR AGONIST

Disclosed in the present invention is a pharmaceutical composition of a KOR receptor agonist, which comprises 4-amino-N—[N2-[N—[N—[N-((R)-2-phenyl propyl)glycyl]-D-phenylalanyl]-D-leucyl]-D-lysyl]piperidine-4-carboxylic acid or available salts thereof, and an acetate buffer solution. 1. A pharmaceutical composition , comprising the active ingredient 4-amino-N—[N2-[N—[N—[N-((R)-2-phenylpropyl)glycyl]-D-phenylalanyl]-D-leucyl]-D-lysyl]piperidine-4-carboxylic acid or a pharmaceutical acceptable salt thereof and a buffer solution , which is preferably an acetate buffer solution , and more preferably an acetic acid-sodium acetate buffer solution.2. The pharmaceutical composition according to claim 1 , wherein the pH of the pharmaceutical composition is about 2.0 to 6.0 claim 1 , and preferably about 3.0 to 5.0.3. The pharmaceutical composition according to claim 1 , wherein the concentration of the buffer solution is about 1 to 150 mM claim 1 , preferably about 10 to 80 mM claim 1 , and most preferably about 20 mM.4. The pharmaceutical composition according to claim 1 , wherein the concentration of the active ingredient or a pharmaceutically acceptable salt thereof is about 0.1 to 1.0 mg/ml.5. The pharmaceutical composition according to claim 1 , wherein the osmotic pressure of the pharmaceutical composition is about 280 to 320 mOsmol/kg.6. The pharmaceutical composition according to claim 1 , further comprising a saccharide claim 1 , which is preferably mannitol.7. The pharmaceutical composition according to claim 6 , wherein the concentration of the saccharide is about 2 to 100 mg/ml claim 6 , preferably about 10 to 80 mg/ml claim 6 , and most preferably about 45 mg/ml.8. The pharmaceutical composition according to claim 1 , comprising:(a) 0.1 to 1.0 mg/ml of the active ingredient 4-amino-N—[N2-[N—[N—[N-((R)-2-phenylpropyl)glycyl]-D-phenylalanyl]-D-leucyl]-D-lysyl]piperidine-4-carboxylic acid or a pharmaceutical acceptable salt thereof,(b) 1 to 150 mM of an acetic acid ...

OXOPICOLINAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR AND PHARMACEUTICAL USE THEREOF

The present invention relates to an oxopicolinamide derivative, a preparation method therefor and the pharmaceutical use thereof. In particular, the present invention relates to an oxopicolinamide derivative as shown in the general formula (AI), a preparation method therefor and a pharmaceutical composition comprising the derivative, and to the use thereof as a therapeutic agent, in particular as an inhibitor of blood coagulation factor XIa (Factor XIa, FXIa for short) and the use thereof in the preparation of a drug for treating diseases such as thromboembolism, wherein the definition of each substituent in the general formula (AI) is the same as defined in the description. 6. The compound according to claim 1 , wherein each Ris identical or different claim 1 , and each is independently selected from the group consisting of alkyl claim 1 , alkoxy claim 1 , oxo claim 1 , halogen claim 1 , haloalkyl claim 1 , cyano claim 1 , hydroxy claim 1 , —C(O)OR claim 1 , —NHC(O)OR claim 1 , —C(O)NRR claim 1 , —CHNHC(O)OR claim 1 , —CHNRR claim 1 , —C(O)OCH(R)Rand —S(O)R; Ris selected from the group consisting of hydrogen claim 1 , alkyl claim 1 , hydroxy and amino; Rand Rare identical or different claim 1 , and each is independently selected from the group consisting of hydrogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , cycloalkyl claim 1 , heterocyclyl claim 1 , —C(O)ORand —OC(O)OR claim 1 , wherein the cycloalkyl and heterocyclyl are each optionally substituted by one or more groups selected from the group consisting of deuterium claim 1 , halogen claim 1 , alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , oxo claim 1 , amino claim 1 , nitro claim 1 , cyano claim 1 , hydroxy and hydroxyalkyl; and Ris alkyl.7. The compound according to claim 1 , wherein Ris —C(O)R; Ris selected from the group consisting of alkyl claim 1 , cycloalkyl and haloalkyl claim 1 , wherein the alkyl and cycloalkyl are each optionally substituted by one or more groups selected from the group ...

1,2,4-TRIAZINE-3-AMINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND USE THEREOF IN MEDICINE

A 1,2,4-triazine-3-amine derivative, a preparation therefor, and use thereof in medicine are provided. Specifically, a 1,2,4-triazine-3-amine derivative as represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and use thereof as a therapeutic agent, in particular as an Aor Areceptor antagonist, and use thereof in the preparation of a medicament for treating a condition or disorder that is ameliorated by means of inhibition of the Aor Areceptor are provided. Each substituent in general formula (I) is defined in the description. 6. A pharmaceutical composition claim 1 , comprising the compound according to claim 1 , and one or more pharmaceutically acceptable carriers claim 1 , diluents or excipients.7. A pharmaceutical composition claim 3 , comprising the compound according to claim 3 , and one or more pharmaceutically acceptable carriers claim 3 , diluents or excipients.8. A method for treating a disease or condition in a subject claim 1 , the method comprising administering to the subject the compound according to claim 1 , wherein the disease or condition is selected from the group consisting of cancer claim 1 , depression claim 1 , Parkinson's disease claim 1 , Huntington's disease claim 1 , Alzheimer's disease claim 1 , abnormal movement disorder claim 1 , sleep disorder claim 1 , wherein the cancer is selected from the group consisting of melanoma claim 1 , brain tumor claim 1 , esophageal cancer claim 1 , stomach cancer claim 1 , liver cancer claim 1 , pancreatic cancer claim 1 , colorectal cancer claim 1 , lung cancer claim 1 , kidney cancer claim 1 , breast cancer claim 1 , ovarian cancer claim 1 , prostate cancer claim 1 , skin cancer claim 1 , neuroblastoma claim 1 , sarcoma claim 1 , osteochondroma claim 1 , osteoma claim 1 , osteosarcoma claim 1 , seminoma claim 1 , testicular tumor claim 1 , uterine cancer claim 1 , head and neck cancer claim 1 , multiple myeloma claim 1 , malignant ...

OXOPICOLINAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR AND PHARMACEUTICAL USE THEREOF

The present invention relates to an oxopicolinamide derivative, a preparationmethod therefor and the pharmaceutical use thereof. In particular, the present invention relates to an oxopicolinamide derivative as shown in the general formula (AI), a preparation method therefor and a pharmaceutical composition comprising the derivative, and to the use thereof as a therapeutic agent, in particular as an inhibitor of blood coagulation factor XIa (Factor XIa, FXIa for short) and the use thereof in the preparation of a drug for treating diseases such as thromboembolism, wherein the definition of each substituent in the general formula (AI) is the same as defined in the description. 125-. (canceled)30. A method for preventing and/or treating a factor XIa mediated disease claim 28 , comprising administering to a patient in need thereof an effective amount of the pharmaceutical composition according to .31. A method for preventing and/or treating a cardiovascular and cerebrovascular disease claim 28 , comprising administering to a patient in need thereof an effective amount of the pharmaceutical composition according to .32. A method for preventing and/or treating a factor XIa mediated disease claim 29 , comprising administering to a patient in need thereof an effective amount of the pharmaceutical composition according to .33. A method for preventing and/or treating a cardiovascular and cerebrovascular disease claim 29 , comprising administering to a patient in need thereof an effective amount of the pharmaceutical composition according to . This application is a Section 371 of International Application No. PCT/CN2017/099579, filed Aug. 30, 2017, which was published in the Chinese language on Mar. 8, 2018, under International Publication No. WO 2018/041122 A1, which claims priority under 35 U.S.C. § 119(b) to Chinese Application Nos. 201610789384.9, filed Aug. 31, 2016 and 201710014133.8, filed Jan. 9, 2017, the disclosures of which are incorporated herein by reference in ...

CD73 INHIBITORS AND THERAPEUTIC USES THEREOF

This application discloses CD73 inhibitors represented by the general formula (I) and analogs thereof, pharmaceutical compositions containing these compounds, methods of preparing them, and use of these compounds as therapeutic agents for the treatment of diseases or conditions associated with CD73 activity, such as various cancers. 4. The compound according to , or a tautomer , or a pharmaceutically acceptable salt , solvate , or prodrug thereof , wherein Q is selected from the group consisting of —CH—O—C(R)(R)— , —CH—NH—C(R)(R)— , —CH—S—C(R)(R)— , —CHS(O)—C(R)(R)— , -phenyl-O—C(R)(R)— , —CH-phenyl-O—C(R)(R)— , and —CH-heterocyclyl-; and wherein Rand Rare as defined in .5. The compound according to claim 1 , or a tautomer claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Rand Rare each hydrogen; and Rand Rare each independently selected from the group consisting of hydroxy claim 1 , hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , and hydroxyalkyl.8. The compound according to claim 1 , or a tautomer claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Rand Rare each independently selected from the group consisting of hydrogen claim 1 , alkyl claim 1 , and —C(RR)—O—C(O)OR.9. The compound according to claim 1 , or a tautomer claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , and haloalkoxy.10. The compound according to claim 1 , or a tautomer claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , alkoxy claim 1 , haloalkyl claim 1 , and ...

LAG-3 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND PHARMACEUTICAL APPLICATION THEREOF

Provided are a LAG-3 antibody, an antigen-binding fragment thereof, and a pharmaceutical application thereof. Further, provided are a chimeric antibody comprising a CDR of the LAG-3 antibody, a humanized antibody, a pharmaceutical composition comprising the LAG-3 antibody and the antigen-binding fragment thereof, and an application of the pharmaceutical composition as an antineoplastic drug. Particularly, provided is an application of a humanized LAG-3 antibody in preparation of drugs for treatment of diseases involving immune cells. 1. A LAG-3 antibody or the antigen-binding fragment thereof , comprising any one or more CDR region sequences selected from the following (i) or (ii) , or the amino acid sequences with at least 85% identity to the follows:(i) HCDR regions as shown in SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11; and LCDR regions as shown in SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17; or(ii) HCDR regions as shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14; and LCDR regions as shown in SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20.2. The LAG-3 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody heavy chain variable region comprises HCDR1 claim 1 , HCDR2 and HCDR3 as shown in SEQ ID NO:9 claim 1 , SEQ ID NO:10 and SEQ ID NO: 11 claim 1 , respectively claim 1 , or the amino acid sequences with at least 85% identity to these sequences; or the antibody heavy chain variable region comprises HCDR1 claim 1 , HCDR2 and HCDR3 as shown in SEQ ID NO: 12 claim 1 ,SEQ ID NO: 13 and SEQ ID NO: 14 claim 1 , respectively claim 1 , or the amino acid sequences with at least 85% identity to these sequences.3. The LAG-3 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody light chain variable region comprises LCDR1 claim 1 , LCDR2 and LCDR3 as shown in SEQ ID NO: 15 claim 1 , SEQ ID NO: 16 and SEQ ID NO:17, respectively, or the amino acid sequences with at least 85% identity to these ...

TIGIT ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND MEDICAL USE THEREOF

A TIGIT antibody, an antigen-binding fragment thereof, and a medical use thereof. The present invention relates to a murine antibody, a chimeric antibody, and a humanized antibody comprising a CDR region of the TIGIT antibody, and a pharmaceutical composition comprising the TIGIT antibody and the antigen-binding fragment thereof, and a use thereof as a medicament. In particular, the present invention also relates to a use of a humanized TIGIT antibody for preparing a medicament for the treatment of TIGIT-associated diseases or conditions. 1. A monoclonal antibody or antigen-binding fragment thereof specifically binding to human TIGIT , comprising a heavy chain variable region and a light chain variable region , wherein:i) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as set forth in amino acid sequences of SEQ ID NOs: 15, 16 and 17, or HCDR variants having 3, 2, or 1 amino acid difference(s) from HCDR1, HCDR2 and HCDR3 as set forth in SEQ ID NOs: 15, 16 and 17, respectively; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as set forth in amino acid sequences of SEQ ID NOs: 18, 19 and 20, or LCDR variants having 3, 2, or 1 amino acid difference(s) from LCDR1, LCDR2 and LCDR3 as set forth in SEQ ID NOs: 18, 19 and 20, respectively; orii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as set forth in amino acid sequences of SEQ ID NOs: 21, 22 and 23, or HCDR variants having 3, 2, or 1 amino acid difference(s) from HCDR1, HCDR2 and HCDR3 as set forth in SEQ ID NOs: 21, 22 and 23, respectively; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as set forth in amino acid sequences of SEQ ID NOs: 24, 25 and 26, or LCDR variants having 3, 2, or 1 amino acid difference(s) from LCDR1, LCDR2 and LCDR3 as set forth in SEQ ID NOs: 24, 25 and 26, respectively; oriii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as set forth in amino acid sequences of SEQ ID NOs: 27, 28 and 29, or HCDR ...

ANTI-B7H3 ANTIBODY-EXATECAN ANALOG CONJUGATE AND MEDICINAL USE THEREOF

Disclosed by the present invention are an anti-B7H3 antibody-exatecan analog conjugate, a preparation method therefor and an anti-tumor medicinal use thereof. 2. The ligand-drug conjugate of formula (Pc-L-Y-Dr) or the pharmaceutically acceptable salt or solvate thereof according to claim 1 , wherein the anti-B7H3 antibody or the antigen-binding fragment thereof comprises:the heavy chains HCDR1, HCDR2 and HCDR3 represented by the amino acid sequences of SEQ ID NO: 8, 9 and 10 respectively, or HCDR variants having 3, 2 or 1 amino acid difference(s) from HCDR1, HCDR2 and HCDR3 represented by SEQ ID NO: 8, 9 and 10 respectively; andthe light chains LCDR1, LCDR2 and LCDR3 represented by the amino acid sequences of SEQ ID NO: 11, 12 and 13 respectively, or LCDR variants having 3, 2 or 1 amino acid difference(s) from LCDR1, LCDR2 and LCDR3 represented by SEQ ID NO: 11, 12 and 13 respectively.3. (canceled)4. The ligand-drug conjugate of formula (Pc-L-Y-Dr) or the pharmaceutically acceptable salt or solvate thereof according to claim 1 , wherein the anti-B7H3 antibody or the antigen-binding fragment thereof comprises a heavy chain variable region and/or a light chain variable region:wherein the amino acid sequence of the heavy chain variable region is represented by SEQ ID NO: 6 or has at least 95% sequence identity with SEQ ID NO: 6, the amino acid sequence of the light chain variable region is represented by SEQ ID NO: 7 or has at least 95% sequence identity with SEQ ID NO: 7.5. (canceled)6. The ligand-drug conjugate of formula (Pc-L-Y-Dr) or the pharmaceutically acceptable salt or solvate thereof according to claim 1 , wherein Pc is a full-length antibody claim 1 , wherein the full-length antibody is selected from the group consisting of:the h1702 antibody consisting of the heavy chain sequence represented by SEQ ID NO: 14 and the light chain sequence represented by SEQ ID NO: 15, andthe h1702DS antibody consisting of the heavy chain sequence represented by SEQ ID NO: 14 ...

LIGAND-DRUG CONJUGATE OF EXATECAN ANALOGUE, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF

The present invention relates to a ligand-drug conjugate of an exatecan analogue, a preparation method therefor and an application thereof. Specifically, the present invention provides a ligand-drug conjugate having a structure shown in formula (-D), a preparation method therefor, a pharmaceutical composition containing same, and use thereof in preparation of drugs for treating cancers by means of receptor regulation. The definition of each substituent in formula (-D) is the same as that in the description. 47.-. (canceled)8. The ligand-drug conjugate or the pharmaceutically acceptable salt or solvate thereof according to claim 3 , wherein n is 2 to 8 claim 3 , which can be an integer or a decimal.9. The ligand-drug conjugate or the pharmaceutically acceptable salt or solvate thereof according to claim 3 , wherein the linker unit -L- is -L-L-L-L- claim 3 ,{'sup': 1', '3, 'sub': 2', '1-8', '1-8', '1-8, 'Lis selected from the group consisting of -(succinimide-3-yl-N)—W—C(O)—, —CH—C(O)—NR—W—C(O)— and —C(O)—W—C(O)—, wherein W is selected from the group consisting of Calkyl, Calkyl-cycloalkyl and linear heteroalkyl comprising 1 to 8 atom(s), the heteroalkyl comprises 1 to 3 heteroatom(s) selected from the group consisting of N, O and S, wherein the Calkyl, cycloalkyl and linear heteroalkyl are each independently optionally further substituted by one or more substituent(s) selected from the group consisting of halogen, hydroxy, cyano, amino, alkyl, chloroalkyl, deuterated alkyl, alkoxy and cycloalkyl;'}{'sup': 2', '4', '1', '4', '1', '1', '1, 'sub': 2', '2', '2', '2', '2', '2', '2', '2, 'Lis selected from the group consisting of —NR(CHCHO)pCHCHC(O)—, —NR(CHCHO)pCHC(O)—, —S(CH)pC(O)— and a chemical bond, wherein pis an integer from 1 to 20;'}{'sup': '3', 'Lis a peptide residue composed of 2 to 7 amino acids, wherein the amino acids are optionally further substituted by one or more substituent(s) selected from the group consisting of halogen, hydroxy, cyano, amino, alkyl, ...

IL-5 ANTIBODY, ANTIGEN BINDING FRAGMENT THEREOF, AND MEDICAL APPLICATION THEREFOR

Provided are an IL-5 antibody, an antigen binding fragment thereof, and a medical application therefor. The present invention comprises a mouse-derived antibody containing an IL-5 antibody CDR region, a chimeric antibody, a humanized antibody, and a pharmaceutical composition comprising said IL-5 antibody and said antigen binding fragment thereof, as well as the use of the pharmaceutical composition as a drug. 1. A monoclonal antibody or antigen-binding fragment thereof specifically binding to human IL-5 , wherein the monoclonal antibody comprises a heavy chain variable region and a light chain variable region , wherein ,(i) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 region as set forth in amino acid sequences of SEQ ID NOs: 16-18, or HCDR variants having 3, 2, or 1 amino acid difference(s) from HCDR1, HCDR2 and HCDR3 region as set forth in SEQ ID NOs: 16-18, respectively; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 region as set forth in amino acid sequences of SEQ ID NOs: 19-21, or LCDR variants having 3, 2, or 1 amino acid difference(s) from LCDR1, LCDR2 and LCDR3 region as set forth in SEQ ID NOs: 19-21, respectively; or(ii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 region as set forth in amino acid sequences of SEQ ID NOs: 22-24, or HCDR variants having 3, 2, or 1 amino acid difference(s) from HCDR1, HCDR2 and HCDR3 region as set forth in SEQ ID NOs: 22-24, respectively; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 region as set forth in amino acid sequences of SEQ ID NOs: 25-27, or LCDR variants having 3, 2, or 1 amino acid difference(s) from LCDR1, LCDR2 and LCDR3 region as set forth in SEQ ID NOs: 25-27, respectively; or(iii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 region as set forth in amino acid sequences of SEQ ID NOs: 28-30, or HCDR variants having 3, 2, or 1 amino acid difference(s) from HCDR1, HCDR2 and HCDR3 region as set forth in ...

3,4-BIPYRIDYL PYRAZOLE DERIVATIVE, AND PREPARATION METHOD THEREFOR AND MEDICAL APPLICATION THEREOF

The present invention relates to a 3,4-bipyridyl pyrazole derivative, and a preparation method therefor and a medical application thereof. Specifically, the present invention relates to a new 3,4-bipyridyl pyrazole derivative as shown in formula (I), a preparation method for the derivative, a pharmaceutical composition containing the derivative, a use of the derivative as a therapeutic agent, in particular as a TGF-β inhibitor, and a use of the derivative in the preparation of a drug which treats, prevents or reduces cancer mediated by TGF-β overexpression. The substituents in formula (I) have the same definitions as in the description. 3. The compound of formula (I) according to or , wherein Ris selected from the group consisting of cyano , —C(O)Rand —S(O)R , Ris hydroxy or alkyl , preferably , Ris cyano or methanesulfonyl , and s is 1.4. The compound of formula (I) according to any one of to , wherein Ris alkyl.9. A pharmaceutical composition , comprising a therapeutically effective amount of the compound of formula (I) , or a tautomer , mesomer , racemate , enantiomer , diastereomer thereof , or mixture thereof , or a pharmaceutically acceptable salt thereof according to any one of to , and one or more pharmaceutically acceptable carriers , diluents or excipients.10. The compound , or a tautomer , mesomer , racemate , enantiomer , diastereomer thereof , or mixture thereof , or a pharmaceutically acceptable salt thereof according to any one of to , or the pharmaceutical composition according to , for use as a medicament.11. The compound , or a tautomer , mesomer , racemate , enantiomer , diastereomer thereof , or mixture thereof , or a pharmaceutically acceptable salt thereof according to any one of to , or the pharmaceutical composition according to , for use as a TGF-β receptor kinase inhibitor.12. Use of the compound , or a tautomer , mesomer , racemate , enantiomer , diastereomer thereof , or mixture thereof , or a pharmaceutically acceptable salt thereof ...

PCSK9 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND MEDICAL USES THEREOF

The present invention provides a PCSK9 antibody, an antigen-binding fragment thereof, and medical uses thereof. 1. A PCSK9 antibody specifically binding to PCSK9 or an antigen-binding fragment thereof , comprising:{'sup': 1', '1, 'i) a HCDR1 having the sequence of GYXIH (SEQ ID NO: 43), wherein Xis T, D or E;'}{'sup': 2', '3', '4', '2', '3', '4, 'ii) a HCDR2 having the sequence of XIXPSXTYTKFNQKFKD (SEQ ID NO: 44), wherein Xis Y or E; Xis N, L, I or V; and Xis S, G or A;'}{'sup': 5', '6', '7', '8', '5', '6', '7', '8, 'iii) a HCDR3 having the sequence of AREXIXXNYWFFDX(SEQ ID NO: 45), wherein Xis R or N; Xis Y or F; Xis S or F; and Xis V or R;'}{'sub': 1', '2', '3', '1', '2', '3, 'iv) a LCDR1 having the sequence of KASQNVYXXVX(SEQ ID NO: 46), wherein Xis T or W; Xis A or E; and Xis A, D or V;'}{'sub': 4', '5', '6', '4', '5', '6, 'v) a LCDR2 having the sequence of XXXNRYT (SEQ ID NO: 47), wherein Xis S, E or Q; Xis A or M; and Xis S or V; and'}{'sub': 7', '8', '9', '10', '7', '8', '9', '10, 'vi) a LCDR3 having the sequence of QQXSXXPXT (SEQ ID NO: 48), wherein Xis Y, F or L; Xis S or W; Xis Y, F, Q or S; and Xis Y, D or E.'}24.-. (canceled)5. The PCSK9 antibody specifically binding to PCSK9 or the antigen-binding fragment thereof according to claim 1 , wherein the HCDR1 has the amino acid sequence of SEQ ID NO:14 claim 1 , SEQ ID NO:20 claim 1 , or SEQ ID NO:21 claim 1 , or an amino acid sequence having at least 95% identity to the above sequences;the HCDR2 has the amino acid sequence of SEQ ID NO: 15, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27, or an amino acid sequence having at least 95% identity to the above sequences; andthe HCDR3 has the amino acid sequence of SEQ ID NO:16, SEQ ID NO:28, SEQ ID NO:29, or SEQ ID NO:30, or an amino acid sequence having at least 95% identity to the above sequences.6. The PCSK9 antibody specifically binding to PCSK9 or the antigen-binding fragment thereof according to claim 1 , ...

Deuterium Atom-Substituted Indole Formamide Derivative, Preparation Method Therefor, and Medical Applications Thereof

A deuterium atom-substituted indole formamide derivative, a preparation method therefor, and medical applications thereof. Specifically, the present invention relates to a deuterium atom-substituted indole formamide derivative represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and uses of the derivative serving as an ROR agonist and uses of the derivative in preventing and/or treating tumors or cancers, definitions of substituent groups in general formula (I) being same as definitions in the specification. 2. The compound according to claim 1 , wherein ring A is selected from the group consisting of a phenyl claim 1 , pyridyl claim 1 , imidazolyl claim 1 , pyrazolyl claim 1 , piperidinyl and morpholinyl; and ring B is a phenyl or pyridyl.4. The compound according to claim 1 , wherein Ris a H atom or D atom; Ris selected from the group consisting of a H atom claim 1 , D atom and alkyl claim 1 , wherein the alkyl is optionally substituted by one or more substituents selected from the group consisting of a D atom claim 1 , hydroxy claim 1 , halogen claim 1 , amino and —OR.5. The compound according to claim 1 , wherein Ris selected from the group consisting of an alkyl claim 1 , haloalkyl claim 1 , cycloalkyl and heterocyclyl claim 1 , wherein the alkyl is optionally substituted by one or more substituents selected from the group consisting of a D atom claim 1 , halogen claim 1 , hydroxy claim 1 , amino claim 1 , cyano claim 1 , nitro claim 1 , alkoxy claim 1 , haloalkoxy and hydroxyalkyl.6. The compound according to claim 1 , wherein Rand Rare identical or different and are each independently selected from the group consisting of a H atom and D atom.9. The compound according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of a H atom claim 1 , D atom claim 1 , halogen and alkyl.10. The compound according to claim 1 , wherein Ris an ...

OXA SPIRO DERIVATIVE, PREPARATION METHOD THEREFOR, AND APPLICATIONS THEREOF IN MEDICINES

The present invention relates to an oxa spiro derivative, a preparation method therefor, and applications thereof in medicines. Particularly, the present invention relates to an oxa spiro derivative represented by formula (I), a preparation method therefor, and a pharmaceutical composition comprising the derivative, applications thereof as an MOR receptor agonist, and applications in the preparation of drugs for treating and/or preventing pains and pains-related diseases. Substituent groups in the formula (I) are same as definitions in the specification. 2. The compound according to claim 1 , wherein ring A is selected from the group consisting of 5 to 6 membered heterocyclyl and 5 to 6 membered cycloalkyl.3. The compound according to claim 1 , wherein R is pyridyl.5. The compound according to claim 1 , wherein Ris hydrogen or halogen.6. The compound according to claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , alkyl claim 1 , oxo claim 1 , alkoxy claim 1 , hydroxy claim 1 , halogen and —OR claim 1 , wherein the alkyl and alkoxy are each optionally substituted by one or more groups selected from the group consisting of deuterium claim 1 , alkyl claim 1 , halogen claim 1 , hydroxy claim 1 , amino claim 1 , alkoxycarbonyl claim 1 , nitro claim 1 , cyano claim 1 , alkoxy claim 1 , hydroxyalkyl claim 1 , cycloalkyl claim 1 , heterocyclyl claim 1 , aryl and heteroaryl; and Ris selected from the group consisting of hydrogen claim 1 , alkyl and cycloalkyl claim 1 , wherein the alkyl is optionally substituted by halogen or cycloalkyl.10. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1 , and one or more pharmaceutically acceptable carriers claim 1 , diluents or excipients.1116.-. (canceled)17. The compound according to claim 6 , wherein Ris alkyl claim 6 , wherein the alkyl is optionally substituted by alkoxy claim 6 , cycloalkyl or haloalkyl; and Ris hydrogen claim 6 , alkyl claim ...

PD-1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND MEDICAL APPLICATION THEREOF

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and medical use thereof, and further provides a chimeric antibody and humanized antibodies comprising a complementarity-determining region (CDR) of the antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and use of the antibody in preparing medicines for treating diseases or disorders. 1. An anti-PD1 antibody or an antigen-binding fragment thereof , comprising a light chain variable region and a heavy chain variable region , wherein the heavy chain variable region is identical to the heavy chain variable region of an antibody heavy chain having the amino acid sequence of SEQ ID NO: 11 , or a variant thereof containing 1 to 10 amino acid mutation(s) in the heavy chain framework region.2. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises the variant having a G44R amino acid mutation in the heavy chain framework region claim 1 , wherein the position of the amino acid mutation is according to Kabat numbering.3. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region is identical to the light chain variable region of an antibody light chain having the amino acid sequence of in SEQ ID NO: 12 or a variant thereof claim 1 , wherein the variant contains 1 to 10 amino acid mutation(s) in the light chain framework region.4. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 3 , wherein the light chain variable region comprises the variant having an A43S amino acid mutation in the light chain framework region claim 3 , wherein the position of the amino acid mutation is according to Kabat numbering.5. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 3 , wherein the light chain variable region comprises amino acid ...

BENZOPIPERIDINE DERIVATIVE, PREPARATION METHOD THEREOF AND MEDICAL USE THEREOF

The present invention relates to a benzopiperidine derivative, a preparation method thereof and a medical use thereof. In particular, the present invention relates to a benzopiperidine derivative as shown by general formula (I), a preparation method thereof and a pharmaceutical composition containing the derivative, as well as a use thereof as an estrogen receptor modulator in the prevention and/or treatment of estrogen receptor-mediated or dependent diseases or conditions. Preferably, the disease is breast cancer. The substituents in the general formula (I) are the same as those defined in the description. 2. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring A is heteroaryl.4. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring B is aryl.7. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris hydrogen or halogen.8. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , alkoxy and cycloalkyl claim 1 , wherein the alkyl is optionally substituted by one or more groups selected from the group consisting of halogen claim 1 , alkoxy and cycloalkyl.9. The compound of formula (I) or the tautomer ...

THROMBIN ANTIBODY, ANTIGEN-BINDING FRAGMENT AND PHARMACEUTICAL USE THEREOF

Provided are a thrombin antibody, an antigen-binding fragment and a pharmaceutical use thereof. Further provided are a chimeric antibody and a humanized antibody comprising a thrombin antibody CDR region, and a pharmaceutical composition comprising the thrombin antibody and the antigen-binding fragment thereof, as well as the use thereof as an anticoagulant drug. In particular, provided is a use of the humanized thrombin antibody in preparing a drug for treating a thrombin-mediated disease or condition. 1. (canceled)2. A thrombin antibody or the antigen-binding fragment thereof comprising a HCDR1 , a HCDR2 , and a HCDR3 as shown in SEQ ID NO:7 , SEQ ID NO:8 , and SEQ ID NO: 21 , respectively; and a LCDR1 , a LCDR2 , and a LCDR3 as shown in SEQ ID NO: 10 , SEQ ID NO: 11 , and SEQ ID NO: 12 , respectively , {'br': None, 'sub': 1', '2', '3, 'DHYXG XSYVFDX\u2003\u2003(I);'}, 'wherein the sequence of SEQ ID NO: 21 is represented by formula (I){'sub': 1', '2', '3, 'wherein Xis selected from the group consisting of H, I, L and M; Xis selected from N and A; Xis selected from the group consisting of Y, S, L and T.'}4. (canceled)5. The thrombin antibody or the antigen-binding fragment thereof according to claim 2 , wherein the thrombin antibody or the antigen-binding fragment thereof is a murine antibody or the functional fragment thereof.6. The thrombin antibody or the antigen-binding fragment thereof according to claim 2 , wherein the thrombin antibody or the antigen-binding fragment thereof further comprises a light chain FR region derived from murine κ chain or a variant thereof claim 2 , or further comprises a light chain FR region derived from murine λ chain or a variant thereof; and/or wherein the thrombin antibody or the antigen-binding fragment thereof further comprises a heavy chain FR region derived from murine IgG1 or a variant thereof claim 2 , further comprises a heavy chain FR region derived from murine IgG2 or a variant thereof claim 2 , or further comprises a ...

PD-L1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND MEDICAL APPLICATION THEREOF

The present invention relates to a PD-L1 antibody, antigen-binding fragments, and medical application thereof. Further, the present invention relates to chimeric antibodies and humanized antibodies comprising the CDR regions of the present PD-L1 antibody, as well as a pharmaceutical composition comprising the present PD-L1 antibody and the antigen-binding fragments thereof, and their use as anti-cancer drugs. In particular, the present invention relates to a humanized PD-L1 antibody and its use in preparation of a medicament for the treatment of PD-L1 mediated disease or disorder. 1. A PD-L1 antibody or antigen-binding fragment thereof , comprising at least one of: a heavy chain variable region comprising:{'sub': '1', 'a heavy chain CDR1 (HCDR1) of NDYWX(SEQ ID NO: 10) or SYWMH (SEQ ID NO: 16), or a mutant sequence thereof;'}{'sub': 4', '5, 'a heavy chain CDR2 (HCDR2) of YISYTGSTYYNPSLKS (SEQ ID NO: 11) or RIXPNSG XTSYNEKFKN (SEQ ID NO: 17), or a mutant sequence thereof; and'}a heavy chain CDR3 (HCDR3) of SGGWLAPFDY (SEQ ID NO: 12) or GGSSYDYFDY (SEQ ID NO: 18), or a mutant sequence thereof; anda light chain variable region comprising:{'sub': 2', '3, 'a light chain CDR1 (LCDR1) of KSSQSLFYXSNQKXSLA(SEQ ID NO: 13) or RASESVSIHGTHLMH (SEQ ID NO: 19), or a mutant sequence thereof;'}a light chain CDR2 (LCDR2) of GASTRES (SEQ ID NO: 14) or AASNLES (SEQ ID NO: 20), or a mutant sequence thereof; anda light chain CDR3 (LCDR3) of QQYYGYPYT (SEQ ID NO: 15) or QQSFEDPLT (SEQ ID NO: 21) ,or a mutant sequence thereof;{'sub': 1', '2', '3', '4', '5, 'wherein Xis N or T, Xis R or H, Xis N or H, Xis H or G, and Xis G or F.'}2. The PD-L1 antibody or antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises the HCDR1 claim 1 , HCDR2 and HCDR3 of SEQ ID NO: 10 claim 1 , SEQ ID NO: 11 and SEQ ID NO: 12 claim 1 , respectively; or SEQ ID NO: 16 claim 1 , SEQ ID NO: 17 and SEQ ID NO: 18 claim 1 , respectively; or a mutant sequence thereof.3. ...

PD-L1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND PHARMACEUTICAL USE THEREOF

A novel PD-L1 antibody, an antigen-binding fragment thereof, and a pharmaceutical use thereof. A humanized antibody comprising a CDR of the PD-L1 antibody, a pharmaceutical composition comprising the PD-L1 antibody and the antigen-binding fragment thereof and a use of the PD-L1 antibody as a drug. A use of a humanized PD-L1 antibody in preparing a drug for treating diseases or disorders associated with PD-L1. 1. A monoclonal antibody or an antigen-binding fragment thereof , wherein the monoclonal antibody or the antigen-binding fragment thereof binds to human PD-L1 and comprises a heavy chain variable region and a light chain variable region , wherein:{'sub': 1', '2', '3, '(I) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having amino acid sequences of SEQ ID NOs: 10, 12 and 13, respectively; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively; wherein Xis F or M, Xis R or V and Xis N or H in the HCDR2 of SEQ ID NO: 12; or'}{'sub': 1', '2', '3, '(ii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively; wherein Xis F or M, Xis R or V and Xis N or H in the HCDR2 of SEQ ID NO: 12; or'}(iii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having amino acid sequences of SEQ ID NOs: 20, 21 and 22, respectively; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NOs: 23, 24 and 25, respectively: wherein HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3 are not simultaneously SEQ ID NOs: 30, 38, 22, 23, 40 and 25, respectively,{'sub': 4', '5', '6', '7', '8', '9', '10', '11', '12', '13', '14', '15', '16', '17, 'Wherein Xis S or D, Xis Y or K, Xis H or M, Xis T, S, H or G, Xis S, N or ...

CD96 Antibody, Antigen-Binding Fragment and Pharmaceutical use Thereof

Provided are a CD96 antibody, an antigen-binding fragment and a pharmaceutical use thereof. Further provided are a murine antibody, a chimeric antibody and a humanized antibody comprising the CDR region of the CD96 antibody, and a pharmaceutical composition comprising the CD96 antibody and the antigen-binding fragment thereof, and the use of same as a drug. In particular, provided is a use of a humanized CD96 antibody in the preparation of a drug for treating CD96-related diseases or conditions. 1. A monoclonal antibody or an antigen-binding fragment thereof that specifically binds to human CD96 , wherein the monoclonal antibody comprises a heavy chain variable region and a light chain variable region , wherein:(i) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having the amino acid sequences of SEQ ID NO: 16, 17 and 18, respectively, or variants thereof having 1, 2 or 3 amino acid mutations in the respective amino acid sequences; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having the amino acid sequences of SEQ ID NO: 19, 20 and 21, respectively, or variants thereof having 1, 2 or 3 amino acid mutations in the respective amino acid sequences; or(ii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 are shown in having the amino acid sequences of SEQ ID NO: 22, 23 and 24, respectively, or variants thereof having 1, 2 or 3 amino acid mutations in the respective amino acid sequences; and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having the amino acid sequences of SEQ ID NO: 25, 26 and 27, respectively, or variants thereof having 1, 2 or 3 amino acid mutations in the respective amino acid sequences; or(iii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having the amino acid sequences of SEQ ID NO: 28, 29 and 30, respectively, or variants thereof having 1, 2 or 3 amino acid mutations in the respective amino acid sequences; and the light chain variable region comprises ...

1,2,4-TRIAZINE-3-AMINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND USE THEREOF IN MEDICINE

A 1,2,4-triazine-3-amine derivative, a preparation therefor, and use thereof in medicine are provided. Specifically, a 1,2,4-triazine-3-amine derivative as represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and use thereof as a therapeutic agent, in particular as an Aor Areceptor antagonist, and use thereof in the preparation of a medicament for treating a condition or disorder that is ameliorated by means of inhibition of the Aor Areceptor are provided. Each substituent in general formula (I) is defined in the description. 4. The compound according to claim 1 , wherein ring A is selected from the group consisting of phenyl claim 1 , pyridyl claim 1 , thienyl and furanyl.6. The compound according to claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , alkoxy claim 1 , cyano claim 1 , cycloalkyl claim 1 , haloalkyl claim 1 , heterocyclyl and —C(O)NRR; and Rand Rare as defined in .7. The compound according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , deuterated alkyl claim 1 , alkoxy claim 1 , cyano claim 1 , cycloalkyl and heterocyclyl claim 1 , wherein the alkyl and alkoxy are each independently optionally substituted by one or more substituents selected from the group consisting of halogen claim 1 , deuterium claim 1 , hydroxy claim 1 , cyano claim 1 , amino claim 1 , nitro claim 1 , cycloalkyl and heterocyclyl.8. The compound according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of hydrogen claim 1 , alkyl and halogen.12. A pharmaceutical composition claim 1 , comprising the compound according to claim 1 , and one or more pharmaceutically acceptable carriers claim 1 , diluents or excipients.1318.-. (canceled)19. A method ...

PD-1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND MEDICAL APPLICATION THEREOF

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and medical use thereof, and further provides a chimeric antibody and humanized antibodies comprising a complementarity-determining region (CDR) of the antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and use of the antibody in preparing medicines for treating diseases or disorders. 1. APD-1 antibody or an antigen-binding fragment thereof , comprising:a light chain variable region comprising at least one LCDR selected from those sequences as shown in: SEQ ID NO: 6, SEQ ID NO: 7 or SEQ ID NO: 8; anda heavy chain variable region comprising at least one HCDR region selected from those sequences as shown in: SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5.2. The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR1 as shown in SEQ ID NO: 6.3. The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR2 as shown in SEQ ID NO: 7.4. The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR3 as shown in SEQ ID NO: 8.53. The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a HCDR1 as shown in SEQ ID NO: .64. The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a HCDR2 as shown in SEQ ID NO: .75. The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a HCDR3 as shown in SEQ ID NO: .8. The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR1 claim 1 , a LCDR2 and a LCDR3 as shown in ...

Tim-3 antibody, antigen binding fragment thereof, and medicinal uses thereof

A TIM-3 antibody, an antigen-binding fragment thereof, and medical uses thereof are described. More specifically, the present invention provides a rat-derived antibody containing a CDR region of the TIM-3 antibody, a chimeric antibody or a human-derived antibody thereof, and a pharmaceutical composition containing the TIM-3 antibody and the antigen-binding fragment thereof, as well as uses thereof serving as a drug. In particular, the present invention provides uses of a human-derived TIM-3 antibody in the preparation of drugs for treating TIM-3 -related conditions.

PD-L1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND MEDICAL APPLICATION THEREOF

The present invention relates to a PD-L1 antibody, antigen-binding fragments, and medical application thereof. Further, the present invention relates to chimeric antibodies and humanized antibodies comprising the CDR regions of the present PD-L1 antibody, as well as a pharmaceutical composition comprising the present PD-L1 antibody and the antigen-binding fragments thereof, and their use as anti-cancer drugs. In particular, the present invention relates to a humanized PD-L1 antibody and its use in preparation of a medicament for the treatment of PD-L1 mediated disease or disorder. 2. The method according to claim 1 , wherein the disease or disorder is cancer.3. The method according to claim 2 , wherein the cancer is a PD-L1-expressing cancer selected from the group consisting of breast cancer claim 2 , lung cancer claim 2 , stomach cancer claim 2 , intestinal cancer claim 2 , renal cancer claim 2 , melanoma claim 2 , non-small cell lung cancer and bladder cancer; and most preferably is selected from the group consisting of non-small cell lung cancer claim 2 , melanoma claim 2 , bladder cancer and renal cancer.4. The method according to claim 1 , wherein the heavy chain variable region comprises the HCDR1 claim 1 , HCDR2 and HCDR3 of SEQ ID NO: 10 claim 1 , SEQ ID NO: 11 and SEQ ID NO: 12 claim 1 , respectively; or SEQ ID NO: 16 claim 1 , SEQ ID NO: 17 and SEQ ID NO: 18 claim 1 , respectively.5. The method according to claim 1 , wherein the light chain variable region comprises the LCDR1 claim 1 , LCDR2 and LCDR3 of SEQ ID NO: 13 claim 1 , SEQ ID NO: 14 claim 1 , and SEQ ID NO: 15 claim 1 , respectively; or SEQ ID NO: 19 claim 1 , SEQ ID NO: 20 and SEQ ID NO: 21 claim 1 , respectively.6. The method according to claim 1 , wherein the antibody light chain variable region further comprises a light chain framework (FR) region derived from murine κ chain claim 1 , or murine λ-chain; and the antibody heavy chain variable region further comprises a heavy chain FR region ...

Anti-connective tissue growth factor antibody and application thereof

Provided are an anti-CTGF antibody comprising variable regions of a light chain and a heavy chain and a use thereof as a drug. The antibody may be used to prepare drugs for treating CTGF-related diseases or conditions.

Anti-c-Met antibody and anti-c-Met antibody-cytotoxic drug conjugate and pharmaceutical use thereof

Provided are an anti-c-Met antibody or an antigen binding fragment thereof, and an anti-c-Met antibody-cytotoxic drug conjugate, wherein the antibody or antigen binding fragment thereof is a chimeric antibody or a humanized antibody. Also provided are pharmaceutical compositions containing the humanized anti-c-Met antibody or antigen binding fragment thereof, the antibody-cytotoxic drug conjugate, or pharmaceutically acceptable salts or solvents thereof, that are used in the treatment of cancer.

Il-15 heterogeneous dimer protein and uses thereof.

Se describe una proteína dimérica heterogénea IL-15 y los usos de la misma. El proteína dimérica heterogénea IL-15 comprende una proteína (I) y una proteína (II). La proteína (I) se forma por medio de una reconstrucción entre la IL-15 o una modificación de la misma y una primera modificación Fc; la proteína (II), una segunda modificación Fc, o se forma por medio de la reconstrucción entre el IL-l5Ra o una modificación del mismo y la segunda modificación Fc; y la primera modificación Fc y la segunda modificación Fc están conectadas de un manera de botón en ojal. La proteína dimérica heterogénea IL-15 tiene actividad supresora de tumores evidente y tiene mejor bioactividad y en un periodo extendido de vida media in vivo, en comparación con una molécula de la IL-15.

Tigit antibody, antigen-binding fragment thereof, and medical use thereof

A TIGIT antibody, an antigen-binding fragment thereof, and a medical use thereof. The present invention relates to a murine antibody, a chimeric antibody, and a humanized antibody comprising a CDR region of the TIGIT antibody, and a pharmaceutical composition comprising the TIGIT antibody and the antigen-binding fragment thereof, and a use thereof as a medicament. In particular, the present invention also relates to a use of a humanized TIGIT antibody for preparing a medicament for the treatment of TIGIT-associated diseases or conditions.

Cd96 antibody, antigen-binding fragment and pharmaceutical use thereof

Provided are a CD96 antibody, an antigen-binding fragment and a pharmaceutical use thereof. Further provided are a murine antibody, a chimeric antibody and a humanized antibody comprising the CDR region of the CD96 antibody, and a pharmaceutical composition comprising the CD96 antibody and the antigen-binding fragment thereof, and the use of same as a drug. In particular, provided is a use of a humanized CD96 antibody in the preparation of a drug for treating CD96-related diseases or conditions.

BIFUNCTIONAL FUSION PROTEIN AND PHARMACEUTICAL USE THEREOF

Provided are a bifunctional fusion protein and pharmaceutical use thereof. Specifically, provided are a bifunctional fusion protein comprising an SIRPγ peptide variant and an anti-human PD-L1 antibody, an SIRPγ peptide variant, and pharmaceutical use thereof. The bifunctional fusion protein can specifically bind PD-L1 and CD47 to block the binding of PD-L1 or CD47 to a receptor or ligand thereof. In addition, also provided are preparation and application of the bifunctional fusion protein, and treatment of cancers and immune-related diseases.

Pcsk9 antibody, antigen-binding fragment thereof, and medicinal application thereof

il-6r antibody and antigen binding fragment thereof and medical use

Na presente invenção, são fornecidos, um anticorpo IL-6R e fragmento de ligação de antígeno do mesmo. O anticorpo IL-6R é um anticorpo derivado de alpaca, anticorpo quimérico e anticorpo humanizado. Também é fornecido, na presente invenção, o uso do anticorpo na preparação de um fármaco para o tratamento de doenças relacionadas à IL-6. In the present invention, an IL-6R antibody and antigen binding fragment thereof are provided. The IL-6R antibody is an antibody derived from alpaca, chimeric antibody and humanized antibody. Also provided in the present invention is the use of the antibody in the preparation of a drug for the treatment of diseases related to IL-6.

Anti-cd73 antibody, antigen-binding fragment thereof and application thereof

Provided are an anti-CD73 antibody, an antigen-binding fragment thereof, and an application thereof. Specifically, provided are a murine, chimeric or humanized anti-CD73 antibody comprising a specific CDR region and an antigen-binding fragment thereof. Also provided are a pharmaceutical composition comprising the anti-CD73 antibody or the antigen-binding fragment thereof and the use thereof as a diagnostic agent and a therapeutic agent for CD73-related diseases.

Heteroaryl-pyrazole derivative, and preparation method therefor and medical application thereof

A heteroaryl-pyrazole derivative, and a preparation method therefor and a medical application thereof are described. Specifically, a new heteroaryl-pyrazole derivative as shown in formula (I), a preparation method for the derivative, a pharmaceutical composition containing the derivative, and a use of the derivative as a therapeutic agent, in particular as a TLR7 agonist, are described. The substituents in formula (I) have the same definitions as in the description.

Anti-trop-2 antidody-exatecan analog conjugate and medical use thereof

Provided in the present invention are an anti-TROP-2 antibody-exatecan analog conjugate and the medical use thereof. Specifically, provided in the present invention is an anti-TROP-2 antibody-exatecan analog conjugate represented by the general formula (Pc-L-Y-D), wherein Pc is an anti-TROP-2 antibody or an antigen-binding fragment thereof.

Pyridine-pyrimidine derivative, preparation method therefor and pharmaceutical use thereof

A pyridine-pyrimidine derivative, a preparation method therefor and a pharmaceutical use thereof. In particular, the present disclosure relates to a pyridine-pyrimidine derivative as shown in general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and a use thereof as a therapeutic agent, especially a use thereof as an SOS1 inhibitor and a use thereof in preparation of drugs for treating diseases, conditions or disorders improved by inhibiting SOS1.

Anti-CD70 antibody and application thereof

The present disclosure relates to an anti-CD70 antibody and an application thereof. Specifically, the present disclosure relates to an anti-CD70 antibody, which comprises a light chain variable region and a heavy chain variable region of the antibody, and a use thereof as a drug.

Pd-1 antibody, antigen-binding fragment thereof, and medical use thereof

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and a medical application thereof, and further provides a chimeric antibody comprising a complementarity-determining region (CDR) of the antibody, a humanized antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and a purpose of the antibody in preparing medicine for treating diseases or symptoms.

Anti-connective tissue growth factor antibody and application thereof

Provided are an anti-CTGF antibody comprising variable regions of a light chain and a heavy chain and a use thereof as a drug. The antibody may be used to prepare drugs for treating CTGF-related diseases or conditions.

Anti-sclerostin antibody, antigen binding fragment and medical use thereof

Provided is a humanized antibody and chimeric antibody specifically binding human sclerostin. The antibodies can be used for treating human bone metabolism related diseases such as osteoporosis (OP).

Interleukin 15 protein complex and use thereof

Provided in the application is a interleukin 15 (IL-15) protein complex. The IL-15 protein complex consists of a soluble fusion proteins (I) and (II), wherein the fusion protein (I) is a IL-15 polypeptide or a functionality fragment thereof, and the fusion protein (II) is a IL-15Ra polypeptide or a functionality fragment thereof. There are one or more amino acid sites on the fusion proteins (I) or (II) were mutated to Cys, which were paired with the corresponding Cys mutated from the amino acid sites on the fusion proteins (II) or(I) to form disulfide bonds. The IL-15 protein complex can be used for tumour therapy.

Pd-1 antibody, antigen-binding fragment thereof, and medical application thereof

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and medical use thereof, and further provides a chimeric antibody and humanized antibodies comprising a complementarity-determining region (CDR) of the antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and use of the antibody in preparing medicines for treating diseases or disorders.

Pd-1 antibody, antigen-binding fragment thereof, and medical application thereof

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and a medical application thereof, and further provides a chimeric antibody comprising a complementarity-determining region (CDR) of the antibody, a humanized antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and a purpose of the antibody in preparing medicine for treating diseases or symptoms.

SULFONYLBENZAMIDE DERIVATIVE AND ITS COJUGATE, METHOD OF PREPARATION AND ITS USE

DERIVADO DE SULFONILBENZAMIDA E SEU COJUGADO, MÉTODO DE PREPARAÇÃO DO MESMO E SEU USO. A presente invenção se refere a um derivado de sulfonilbenzamida e seu conjugado, um método de preparação do mesmo e seu uso. Em particular, é fornecido um derivado de sulfonilbenzamida que possui uma estrutura como representada pela fórmula (D), seu conjugado, um método de preparação do mesmo, uma composição farmacêutica que contenha o mesmo e seu uso na preparação de um fármaco para o tratamento de cânceres por meio da regulação de receptor. Cada substituinte na fórmula geral (D) é como definido na descrição. SULFONYLBENZAMIDE DERIVATIVE AND ITS COJUGATE, METHOD OF PREPARATION AND ITS USE. The present invention relates to a sulfonylbenzamide derivative and its conjugate, a method of preparing the same and its use. In particular, a sulfonylbenzamide derivative having a structure as represented by formula (D), its conjugate, a method of preparing the same, a pharmaceutical composition containing the same and its use in the preparation of a drug for the treatment of cancers through receptor regulation. Each substituent in the general formula (D) is as defined in the description.

pd-1 antibody, antigen binding fragment thereof and medical use thereof

a presente invenção fornece um anticorpo pd-1 humano, um fragmento de ligação ao antígeno do mesmo e uso médico dos mesmos e fornece ainda um anticorpo quimérico e anticorpos humanizados compreendendo uma região determinante de complementaridade (cdr) do anticorpo, uma composição farmacêutica compreendendo o anticorpo pd-1 humano e o fragmento de ligação ao antígeno do mesmo e uso do anticorpo no preparo de medicamentos para o tratamento de doenças ou distúrbios. The present invention provides a human pd-1 antibody, antigen-binding fragment thereof and medical use thereof and further provides a chimeric antibody and humanized antibodies comprising an antibody complementarity determining region (cdr), a pharmaceutical composition comprising the human pd-1 antibody and antigen binding fragment thereof and use of the antibody in the preparation of medicaments for the treatment of diseases or disorders.

Il-15 heterogeneous dimer protein and uses thereof

The present invention relates to an IL-15 heterodimeric protein and uses thereof and further relates to an IL-15/IL-15Rα heterodimeric protein. The IL-15 heterodimeric protein comprises protein (I) and protein (II), wherein said protein (I) is reassembled and formed by IL-15 or its variant with a first Fc variant; wherein said protein (II) is the second Fc variant, or reassembled and formed by IL-15Rα or its variant with a second Fc variant. The first Fc variant and the second Fc variant are linked via "Knob-into-Hole" mode. The IL-15 heterodimeric protein of the present invention has significant anti-tumor activity, better biological activity and prolonged in vivo half-life compared to IL-15 molecule alone.

Substituted fused bicyclic derivative, preparation method therefor, and application thereof in medicines

The present application relates to a substituted fused bicyclic derivative, a preparation method therefor, and an application thereof in medicines. Specifically, the present application relates to a novel substituted fused bicyclic derivative as represented by formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, an application thereof as a therapeutic agent, in particular, as an ERK inhibitor, and an application thereof in preparation of medicines for treatment and/or prevention of cancer, inflammation, or other proliferative diseases, wherein the definitions of the substituents in formula (I) are the same as those in the description.

Pyrazolo-heteroaryl derivative, preparation method and medical use thereof

Disclosed are a pyrazolo-heteroaryl derivative, a preparation method and medical use thereof. In particular, the present invention relates to a new pyrazolo-heteroaryl derivative as shown in the general formula (I), a preparation method thereof and a pharmaceutical composition containing the derivative and the use thereof as a therapeutic agent, in particular as a TLR7 agonist, wherein each substituent in the general formula (I) is defined in the description.

PD-L1 antibody, antigen-binding fragment thereof, and pharmaceutical use thereof

A novel PD-L1 antibody, an antigen-binding fragment thereof, and a pharmaceutical use thereof. A humanized antibody comprising a CDR of the PD-L1 antibody, a pharmaceutical composition comprising the PD-L1 antibody and the antigen-binding fragment thereof, and a use of the PD-L1 antibody as a drug. A use of a humanized PD-L1 antibody in preparing a drug for treating diseases or disorders associated with PD-L1.

CD73 inhibitors and therapeutic uses thereof

This application discloses CD73 inhibitors represented by the general formula (I) and analogs thereof, pharmaceutical compositions containing these compounds, methods of preparing them, and use of these compounds as therapeutic agents for the treatment of diseases or conditions associated with CD73 activity, such as various cancers.

Benzopiperidine derivative, preparation method thereof and medical use thereof

Fused bicyclic derivative, preparation method therefor, and pharmaceutical use thereof

A fused bicyclic derivative shown in general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and a use thereof as a therapeutic agent, particularly the use thereof as an AKT1/2/3(AKT pan) inhibitor and the use in the preparation of a medication for treating and/or preventing tumors. Each group in general formula (I) is as defined in the description.

Cd3 antibody and pharmaceutical use thereof

The present disclosure relates to a CD3 antibody and a pharmaceutical use thereof. Specifically, the present disclosure relates to forming a multi-specificity antibody by using CD3 antibody and binding molecules of another target. The multi-specificity antibody may simultaneously bind to CD3 and another tumor-associated antigen, and bind and activate CD3-positive T cells while binding tumor-associated antigen-expressing cells, thereby promoting T cells specifically killing tumor cells that express tumor-associated antigens. In addition, the present disclosure also provides a preparation and application of a multi-specific antibody.

Lag-3 antibody, antigen-binding fragment thereof, and pharmaceutical application thereof

Phenyl propanamide derivative, and manufacturing method and pharmaceutical application thereof.

La presente invención proporciona un derivado de fenilpropanamida como es representado por la fórmula (I), un método de fabricación del derivado, la aplicación del derivado como agonista del receptor de K-opioide (KOR) y la aplicación del derivado para fabricar un producto farmacéutico para el tratamiento y/o la prevención del dolor o una enfermedad relacionada con el dolor. (ver Fórmula).

Pd-1 antibody, antigen-binding fragment thereof, and medical application thereof