12750results about "Hybrid peptides" patented technology

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes (e.g., wherein each complex is of the exemplary formula shown below) comprising a phosphorodiamidate morpholino oligomer (e.g., useful for targeting DMD) covalently linked to an antibody (e.g., anti-TfR1 antibody). In some embodiments, the complexes are formulated with histidine (e.g., L-histidine) and sucrose at a specified pH (e.g., about 5.0 to 7.0). Also provided are uses of these formulations for treating a subject having a mutated DMD allele associated with Duchenne Muscular Dystrophy.

The invention provides a polypeptide or a derivative and a pharmaceutically acceptable salt thereof. The amino acid sequence of the polypeptide is as shown in SEQ ID NO: 1. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof disclosed by the invention can be combined with GLP-1R and GCGR, and is used for effectively activating the GLP-1R and the GCGR. Therefore, the polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be used for detecting GLP-1R and / or GCGR, and can also be used for treating or preventing GLP-1R and / or GCGR related diseases (such as metabolic disorder related diseases, such as obesity, diabetes, fatty liver diseases, non-alcoholic fatty liver diseases and the like).

The invention relates to the field of biotechnology and medicine, and more particularly to a polypeptide having the amino acid sequence SEQ ID NO: 1 and being capable of inhibiting RAS-GTPase activity, to the use of said polypeptide to produce a drug for treating stomach cancer or rectal cancer in a dose of 0.81-3.00 mg / kg, as well as to a drug based on said polypeptide for the treatment of stomach cancer or rectal cancer, and to a method for treating stomach cancer or rectal cancer by intraperitoneally administering said drug to a subject in an amount of 150 ml twice at an interval of 7 days.

The invention provides an anti-human serum albumin nano antibody and application thereof, and belongs to the technical field of antibodies. The invention provides an anti-human serum albumin nano antibody HSA-32 with relatively high affinity, and the anti-human serum albumin nano antibody HSA-32 is subjected to humanized transformation, so that three obtained humanized anti-human serum albumin nano antibodies can be used for reducing the immunogenicity of the HSA-32 and improving the immunogenicity of the HSA-32; and high specificity and high affinity of combination with the human serum albumin and stability and solubility of the antibody are maintained. The anti-human serum albumin nano antibody can be used for separation, purification and detection of human serum albumin and separation and purification of polypeptide, protein or antibody drugs fused with the anti-human serum albumin nano antibody. Meanwhile, the anti-human serum albumin nano-antibody can effectively prolong the half-life period of polypeptide, protein and antibody drugs fused with the anti-human serum albumin nano-antibody, and can be used for developing long-acting polypeptide, protein or antibody drugs.

To provide methods for treating a subject having or at risk of developing a neurocognitive disorder, such as frontotemporal lobar degeneration or neuronal ceroid lipofuscinosis.SOLUTION: Provided is a method comprising administering, to a subject diagnosed as having a neurocognitive disorder (NCD), a composition comprising a population of cells comprising a transgene encoding a progranulin (PGRN) or a granulin (GRN).SELECTED DRAWING: Figure 1A

A recombinant humanized collagen and a preparation method therefor. The recombinant humanized type III collagen can be efficiently and stably expressed in three expression systems of yeast, Escherichia coli, and CHO cells, and has the biological activity superior to that of a commercially available collagen product. The recombinant humanized type III collagen has structural characteristics and functional activity similar to those of a natural collagen, and thus has wide application prospects in biomedical materials, tissue engineering products, cosmetics, foods, health care products or drugs, medical instruments, medical cosmetology and the like.

The present invention discloses a human serum albumin-targeting nanobody and its application. A variety of human serum albumin-targeting nanobodies that can be used to construct long-acting fusion protein drugs and their immune screening methods are disclosed. The antibody is composed only of the heavy chain variable region and can be fused and expressed with therapeutic proteins or polypeptide drugs such as interleukin, interferon, and tumor necrosis factor in an Escherichia coli expression system. The fusion protein has the activity of specifically binding to human serum albumin, has a relatively high affinity, can effectively extend the drug half-life, and does not affect the biological activity of the recombinant protein drug at the same time.

The invention discloses a bovine serum albumin combined nano antibody and a preparation method and application thereof, the amino acid sequence of the bovine serum albumin combined nano antibody Nb1 is shown as SEQ.ID No.1, the nano antibody Nb not only has high affinity to bovine serum albumin, but also has good binding activity to both human serum albumin and mouse serum albumin, and the nano antibody Nb has high affinity to human serum albumin and mouse serum albumin. And the antibody has a relatively good broad-spectrum application range, and can be widely applied to the aspects of drug half-life period enhancement, tumor targeted therapy and imaging, immunodetection or diagnosis, recombinant albumin purification or enrichment and the like.

Aspects of the disclosure relate to methods of reducing fatigue in a subject having myotonic dystrophy type 1 (DM1). Aspects of the disclosure relate to methods of treating one or more symptoms assessable by the MDHI (e.g., a GI symptom, myotonia, upper extremity function impairment, fatigue, mobility impairment, impairment in the ability to perform activities, pain, vision impairment, communication impairment, sleep impairment, emotional issues, cognitive impairment, social satisfaction impairment, social performance impairment, breathing impairment, swallowing impairment, and / or hearing impairment) in a subject having myotonic dystrophy type 1 (DM1). In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., a DMPK- targeting oligonucleotide) covalently linked to an antibody (e.g., anti-TfRl antibody).

The invention belongs to the technical field of immunology, and particularly relates to a targeted IL-6 biological nano antibody and application thereof. The invention discloses a nano antibody for targeting IL-6, which comprises a heavy chain variable region containing CDR1, CDR2 and CDR3, and has the functions of identifying and combining IL-6. The invention also discloses a composition containing the nano antibody or the IL-6 binding molecule, and an application of the composition containing the nano antibody and the IL-6 binding molecule in preparation of drugs for treating IL-6 related diseases. The nano antibody, the BCMA binding molecule and the composition can recognize and bind IL-6, and have a potential effect of treating IL-6 related diseases.

The invention discloses a recombinant humanized XVII type collagen as well as an expression vector and a genetically engineered bacterium thereof. Four functional fragments with high activity are obtained through screening, one of the fragments is optimized and then combined according to a certain sequence to obtain recombinant humanized XVII type collagen JYC1703, or one of the fragments is optimized and then combined according to a certain sequence, and GPP sequences are fused at an amino terminal and a carboxyl terminal respectively to obtain recombinant humanized XVII type collagen JYC1701 and JYC1702, and the recombinant humanized XVII type collagen JYC1701 and JYC1702 are combined according to a certain sequence to obtain the recombinant humanized XVII type collagen JYC1701 and JYC1702. After codon optimization, amplifying and cloning into an expression vector, transforming into pichia pastoris competent cells after enzyme digestion linearization, and screening high-copy recombinants through G418 resistance gradient, so as to obtain pichia pastoris genetically engineered bacteria for expressing recombinant humanized XVII type collagen. The recombinant humanized XVII type collagen JYC1701, JYC1702 and JYC1703 disclosed by the invention show excellent functions of promoting cell adhesion, cell proliferation and cell migration, and are suitable for preparing products such as skin care products or medical instruments and the like.

The invention discloses a polypeptide and application thereof in preparation of a medicine for preventing and / or treating cancers. The amino acid sequence of the polypeptide is shown as SEQ ID No. 1 or SEQ ID No. 2. The cancer is at least one of breast cancer, colorectal cancer, leukemia, esophageal cancer, pancreatic cancer, brain glioma, kidney cancer, skin cancer, osteosarcoma, ovarian cancer and prostate cancer. The invention designs and synthesizes the polypeptide of a targeted staphylococcus tumor protein compound SND1-MTDH containing a nuclease structural domain 1 (SND1 and a heteromucin (MTDH), finds that the polypeptide has excellent inhibitory activity on various different types of human cancer cells for the first time, and provides an optional scheme for broad-spectrum anti-cancer drugs. The polypeptide applied in the invention is simple in synthesis process and low in production cost.

The invention provides a fusion protein and application thereof in preparation of Brazilian sweet. The fusion protein comprises a tag protein and a Brazilian sweet protein which are connected by a linker; wherein the linker comprises an amino acid sequence as shown in SEQ ID NO: 1, and the amino acid sequence as shown in SEQ ID NO: 1 is directly connected with the Brazilian sweet protein. The invention also provides a preparation method of the Brazilian sweet protein. The preparation method comprises the following steps: treating the fusion protein by using TEV protease and obtaining the Brazilian sweet protein. Large-scale expression of the fusion protein and the brazitame protein is realized by utilizing an escherichia coli expression system, and the obtained brazitame protein can be correctly folded and has high sweetness.

The invention belongs to the field of biological medicines, and particularly relates to a varicella-zoster virus gE fusion protein as well as a preparation method and application thereof. The varicella-zoster virus gE fusion protein comprises an amino acid sequence as shown in SEQ ID NO: 1 and at least one of the following fragments: a signal peptide, a Foldon sequence, a Ferritin sequence and a His tag sequence, the signal peptide can improve the protein expression quantity, the Foldon sequence can improve the stability of the protein, the particle size of an antigen can be increased, the immunogenicity of the antigen can be improved, and the fusion protein can be used for preparing a medicine for treating the varicella-zoster virus gE fusion protein. The Ferritin sequence can enhance immune response, a vaccine prepared from the gE fusion protein has excellent immunogenicity, and compared with a commercially available vaccine Shingrix, higher humoral immunity and cellular immunity levels can be induced.

The present invention belongs to the field of biopharmaceutical technology, and specifically relates to a method for preparing GLP-1 or its analogs. The present invention provides a leader peptide, and a fusion protein comprising the leader peptide. The leader peptide or fusion protein is used to prepare a semaglutide precursor polypeptide, and the results show that the yield of the prokaryotic expression fusion protein can reach 26g / L, and the purity of the precursor polypeptide obtained after enzyme cleavage is higher than 95%. The precursor polypeptide is further side-chain modified and connected with a dipeptide to efficiently prepare semaglutide.

The invention relates to a fusion protein based on Cas12i3 and application of the fusion protein in mediating gene editing, the fusion protein is formed by fusing NLSSV 40, Cas12i3, NLS, IEE and XTEN, the amino acid sequence of the NLSSV 40 is shown as SEQ ID No. 3, the amino acid sequence of the Cas12i3 is shown as SEQ ID No. 5, the amino acid sequence of the NLS is shown as SEQ ID No. 7, the amino acid sequence of the IEE is shown as SEQ ID No. 9, and the amino acid sequence of the XTEN is shown as SEQ ID No. 11.

The invention discloses a fusion protein and application thereof in preparation of a semeglutide precursor polypeptide, N (N is greater than or equal to 1) semeglutide fragments GLP-1 (11-37) are connected through KR, and then the semeglutide fragments GLP-1 (11-37), enterokinase enzyme cutting sites and fusion protein tags are subjected to fusion tandem expression in sequence, so that the semeglutide precursor polypeptide is obtained. The obtained fusion protein is a fusion protein tag-restriction enzyme cutting site-N-linked semeglutide fragment GLP-1 (11-37), and the fusion protein tag is an albumin affinity peptide (SEQ ID NO.1). The fusion protein is subjected to competent heterologous expression in escherichia coli BL21 (DE3), an engineering strain is constructed, and then fermentation expression is performed by using a shake flask, so that the thallus fermentation density is greatly improved, the expression of a target protein in an inclusion body is promoted, the yield of the target protein is improved, and the method has a good industrial application prospect. The fusion protein can be further successfully recognized by commercial enterokinase, KEX2 enzyme and carboxypeptidase B and cut to release the precursor polypeptide of the semeglutide.

The invention discloses a bovine I-type alpha interferon-ferritin fusion protein, a mutant thereof, a preparation method and an application of the bovine I-type alpha interferon-ferritin fusion protein. The bovine I-type alpha interferon is fused with a ferritin subunit, and interferon molecules are highly repeatedly and orderly displayed on the surface of a ferritin nanocage by utilizing the self-assembly characteristic of ferritin, so that the expression level, the structural stability and the antiviral activity of the interferon are remarkably improved. The fusion protein is further subjected to single-site or multi-site rational design mutation, and a mutant with significantly improved antiviral activity and stability is obtained. According to the invention, a silkworm or insect cell eukaryotic expression system is adopted to express the fusion protein or the mutant thereof, and the expression system is safe to operate, simple and convenient in procedure, low in cost and extremely beneficial to large-scale industrial production; the prepared fusion protein or mutant nanoparticles have application prospects in preparation of drugs or reagents for preventing or treating bovine viral diseases.

The invention provides a monoclonal antibody of a p-Tau217 protein and an application of the monoclonal antibody. In particular, the present invention provides an antibody or an antigen binding fragment thereof targeting a p-Tau217 protein. The antibody provided by the invention can specifically recognize and bind the p-Tau217 protein, does not recognize p-Tau181 and non-phosphorylated Tau protein, and can be used for preparing a detection preparation or a kit for diagnosing diseases related to the p-Tau217 protein, such as Alzheimer's disease.

The invention belongs to the field of interferon gene engineering, and discloses a long-acting cat omega2 interferon recombinant protein FeIFN-omega2-Fc and application, and the FeIFN-omega2-Fc provided by the invention has the characteristics of high activity, obvious antiviral effect and long half-life period. The applicant carries out effective fusion and mutation on the basis of omega2 interferon, and finally obtains the recombinant protein FeIFN-omega2-Fc. The protein obviously activates downstream signal factors of interferon, has the effect of resisting various cat viruses, shows good safety and curative effect when cat herpes treatment experiments are carried out on cats, and compared with FeIFN-omega2, the half-life period of recombinant interferon is obviously prolonged. The FeIFN-omega2-Fc has a good antiviral effect, can effectively prevent and treat cat viral diseases, has a wide application prospect, and particularly has a relatively good popularization potential in clinical treatment.

The invention belongs to the technical field of biological medicines, and particularly discloses an epidermal growth factor-linker polypeptide-collagen, and the linker polypeptide has an amino acid sequence as shown in SEQ ID No.1. The linker polypeptide capable of connecting the EGF and the collagen is designed and synthesized, the N end of the linker polypeptide simulates an EGF receptor structure and can be combined with the EGF, and the linker polypeptide is connected with the EGF through non-covalent Van der Waals force, so that the structure of the EGF cannot be damaged; the C terminal of the linker polypeptide is rich in lysine residues, and can be covalently crosslinked to collagen through glutamine transaminase to form EGF-linker polypeptide-collagen. The protein solution taking EGF-linker polypeptide-collagen as active ingredients is low in cytotoxicity and high in biological safety, and meanwhile, the action time of the epidermal growth factor can be remarkably prolonged. In addition, a stable repairing microenvironment can be formed on the surface of the endometrium, and the endometrium injury repairing effect is remarkably improved.

The invention relates to the technical field of a preparation method of a type A recombinant botulinum toxin, in particular to a type A botulinum toxin obtained by adopting a gene recombination technology, and the amino acid sequence of the type A botulinum toxin is consistent with the sequence of the type A botulinum toxin prepared by extracting and purifying a wild strain Clostridium botulinum. According to the technical scheme, the single-chain protein of the botulinum toxin A sequentially comprises a botulinum toxin A light chain or a modified botulinum toxin A light chain, a connecting region and a botulinum toxin A heavy chain. According to the scheme, the high-quality recombinant botulinum toxin A is obtained after the single-chain protein is subjected to fermentation, crude purification, enzyme digestion and fine purification. According to the technical scheme, the problems of complex process, long period, high safety risk and the like in the existing process for preparing the botulinum toxin A from the wild bacterial strain clostridium botulinum can be solved, and meanwhile, the problem that the amino acid sequence consistent with that of the botulinum toxin A prepared from the wild bacterial strain clostridium botulinum cannot be obtained through the existing gene recombination technology is solved.

The invention discloses a fatty acid modified coronavirus antigen and application thereof, and belongs to the field of biological medicine. The fatty acid modified coronavirus antigen contains fatty acid modified N-terminal cysteine (Cys) and a coronavirus antigen, and can contain a connecting structural domain; the coronavirus antigen is a coronavirus spike protein (S protein) receptor binding domain (RBD). The fatty acid modified coronavirus S protein RBD can be self-polymerized into nanoparticles, and compared with the RBD which is not subjected to fatty acid modification, the antigen can induce faster and higher humoral immunity through injection immunity, can induce mucosal immunity and humoral immunity through respiratory tract atomization immunity, and is a candidate mucosal vaccine with potential medical value.

The invention belongs to the technical field of biology, and provides a nanometer antibody targeting Nectin-4, and a nucleic acid molecule and an expression vector for coding the nanometer antibody targeting Nectin-4. The invention also provides a chimeric antigen receptor which comprises an extracellular antigen binding domain, a transmembrane domain and an intracellular domain, and the extracellular antigen binding domain is a Nectin-4 nano antibody; the invention also provides a chimeric antigen receptor CAR which contains the nano antibody as scFv and co-expresses CXCR1, a CAR-T cell constructed by the chimeric antigen receptor CAR, and an enhanced CAR-T cell obtained by modifying the CAR-T cell with microbial short-chain fatty acid, so as to improve the infiltration and anti-tumor activity of the CAR-T cell targeting Nectin-4.

The invention provides an anti-CDH17 antigen binding fragment, an antibody and application thereof. CDR1 of a heavy chain variable region of the antigen binding fragment comprises amino acid sequences as shown in SEQ ID NO.1-3, CDR2 of the heavy chain variable region of the antigen binding fragment comprises amino acid sequences as shown in SEQ ID NO.4-6, and CDR3 of the heavy chain variable region of the antigen binding fragment comprises amino acid sequences as shown in SEQ ID NO.7-9; cDR1 of a light chain variable region of the antigen binding fragment comprises amino acid sequences as shown in SEQ ID NO.10 to 12, CDR2 of the light chain variable region of the antigen binding fragment comprises amino acid sequences as shown in SEQ ID NO.13 to 15, and CDR3 of the light chain variable region of the antigen binding fragment comprises amino acid sequences as shown in SEQ ID NO.16 to 18. The antigen binding fragment and the anti-CDH17 antibody provided by the invention have high specificity, and a chimeric antigen receptor and a CAR-T cell prepared from the antibody have obvious cytotoxicity on cells stably expressing CDH17 protein.

The invention relates to the technical field of recombinant protein expression, in particular to recombinant human-derived III-type collagen as well as a preparation method and application thereof. The invention provides a recombinant human source III type collagen. The amino acid sequence of the recombinant human source III type collagen is shown as SEQ ID NO. 1. The recombinant human-derived III-type collagen prepared by the invention can be better applied to a human body, better exerts biological functions of the collagen, avoids repulsive interaction, is high in safety, can effectively promote cell proliferation and oxidation resistance, and is high in expression yield, stable in batches and good in quality; the recombinant human III type collagen prepared by the invention has the potential of being applied to preparation and production of biological medicines and cosmetics.

The present disclosure provides lipid nanoparticle compositions comprising a nucleic acid encoding a therapeutic polypeptide. The disclosure also provides novel IL-15 polypeptides, fusion proteins comprising the IL-15 polypeptides, and nucleic acids encoding the IL-15 polypeptides and the fusion proteins.

The invention discloses a nanometer antibody targeting FAP, a CAR-T cell and application of the nanometer antibody and the CAR-T cell. The invention provides nano-antibodies VHH1 and VHH2 capable of simultaneously recognizing human or mouse FAP. The nano-antibodies VHH1 and VHH2 are used as antigen binding regions to be constructed in a human or mouse CAR structure, and human or mouse FAP-CAR-T cells with a killing function can be prepared. Results of the mouse FAP-CAR-T cell or the human FAP-CAR-T cell provided by the invention show that the FAP-CAR-T cell has a good treatment effect on removal of FAP positive cells, and is a novel FAP-CAR-T cell which is expected to be applied to clinical solid tumor CAR-T therapy.

The invention relates to the technical field of biology, in particular to a swine transmissible gastroenteritis virus epitope vaccine and a preparation method and application thereof, the amino acid sequence of FliCS.T-TGEV-S fusion protein is shown as SEQ ID NO.3, and the nucleotide sequence of the FliCS.T-TGEV-S fusion protein is shown as SEQ ID NO.4. The fusion protein FliCS.T-TGEV-S prepared by the invention is used as an epitope vaccine based on dominant antigen epitopes of TGEV, and combines advanced means such as immunodominant epitopes, a fusion protein technology and genetic engineering, so that the specificity and the protection effect of the vaccine are enhanced. The vaccine not only can induce high-level antibody response and effectively inhibit TGEV infection, but also has relatively high safety and stability. Compared with a traditional vaccine, the vaccine has remarkable advantages in the aspects of production cost, immune efficacy, protection durability and the like, and a feasible TGE prevention and control scheme is provided for the pig industry.