50 results about "Ankyrin" patented technology

The present invention relates to recombinant binding proteins comprising an ankyrin repeat domain with binding specificity for soluble mesothelin or membrane-bound mesothelin. In addition, the invention relates to nucleic acids encoding such recombinant binding proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer in a mammal, including a human.

The invention belongs to the technical field of gene engineering, and particularly relates to application of a wheat gene to regulation and control of plant drought tolerance. The wheat gene provided by the invention is a TaANK-TPR44 gene, and the nucleotide sequence of the TaANK-TPR44 gene is as shown in SEQ ID NO. 1. In order to develop the specific functional characteristics of ankyrin genes from different plant sources, the TaANK-TPR44 gene is over-expressed and transformed into arabidopsis thaliana for functional verification, and the result shows that the drought tolerance of the arabidopsis thaliana with the over-expressed TaANK-TPR44 gene is remarkably improved compared with that of wild arabidopsis thaliana, and the drought tolerance of the arabidopsis thaliana with the over-expressed TaANK-TPR44 gene is remarkably improved compared with that of wild arabidopsis thaliana. Therefore, the TaANK-TPR44 gene plays a positive regulation role in the wheat drought tolerance process, a theoretical basis and gene resources are provided for wheat molecular breeding, and the TaANK-TPR44 gene has very important significance for obtaining drought-tolerant high-yield strains and improving the wheat drought tolerance in the future.

The present disclosure relates to multispecific proteins comprising designed ankyrin repeat domains with binding specificity for different targets, such as, e.g. CD40 and FAP. In addition, the present disclosure relates to nucleic acids encoding such multispecific proteins, pharmaceutical compositions comprising such multispecific proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer, in a mammal, including a human.

The present invention relates to MSLN-specific binding constructs comprising a designed ankyrin repeat domain with binding specificity for MSLN and a chelator capable of bonding to a radionuclide, as well as to such MSLN-specific binding constructs comprising a half-life extending moiety with binding specificity for serum albumin. The invention further relates to methods of producing such radio-labelled MSLN-specific binding constructs, pharmaceutical compositions comprising such constructs, and the use of such constructs or pharmaceutical compositions in methods for treating, imaging or diagnosing diseases, such as cancer.

The invention belongs to the technical field of biology, and particularly relates to ANK1 gene nonsense mutation and application. The invention firstly provides an ANK1 gene non-sense mutation c.2230 Cgt and an ANK1 gene non-sense mutation c.2230 Cgt. The invention relates to the field of genetic engineering, and in particular relates to nonsense mutation T (p.Q744X), the nonsense mutation significantly reduces the expression of ankyrin, and further causes phenotypic changes such as abnormal cell morphology and increased osmotic fragility after K562 erythroid differentiation, which indicates that the K562 is related to the pathological process of hereditary polycythemia spheroides (HS), and indicates that the mutation has pathogenicity; secondly, a treatment evaluation system taking drug-induced translation readthrough and adenine base editing as a core is constructed around the mutation, a new strategy and a technical platform are provided for precise molecular treatment of the ANK1 nonsense mutant HS, and important clinical transformation prospects and application values are achieved.

The present invention provides certain tetrazole derivatives that are inhibitors of transient receptor potential ankyrin 1 (TRPA1) and are thus useful in the treatment of diseases that can be treated by inhibition of TRPA1. Pharmaceutical compositions containing the compounds and methods of making the compounds are also provided.

The present disclosure provides an engineered population of natural killer cells wherein the NK cells express at least one polypeptide selected from the group consisting of human leukocyte antigen E, human leukocyte antigen F, and human leukocyte antigen G. The NK cell comprises a genetically modified disruption of one or more copies of an endogenous beta-2 microglobulin and a genetically modified disruption of one or more copies of a human leukocyte antigen class II-related gene, the human leukocyte antigen class II-related gene is selected from a protein containing regulatory factor X-related ankyrin, a regulatory factor 5, a regulatory factor X-related protein and a class II trans-activator. Also provided are a method of producing human pluripotent stem cell-derived engineered natural killer cells without feeder cells, and a method of treating a disease or condition in a subject by administering the NK cells to the subject.

The invention belongs to the technical field of genetic engineering, and discloses application of an anchoring protein INP-N in a PET degrading enzyme system displayed on the surface. According to the invention, after efficient anchoring protein INP-N is screened, FAST-PETase is mediated by the efficient anchoring protein INP-N to construct recombinant escherichia coli of which the surface displays PET degrading enzyme. Furthermore, hydrophobin HFBII is introduced into the surface display system, so that the relative enzyme activity of the PET degrading enzyme is improved by 1.1 times or more. Meanwhile, FAST-PETase and carboxylesterase Est30KL are synchronously expressed, so that the proportion of TPA in a degradation product can reach 95% or above. In addition, the PET degrading enzyme surface display system provided by the invention is excellent in cycle performance, more than 65% of activity can still be retained when PET is cyclically degraded for the third time, and the application cost can be greatly reduced. The method can be applied to the fields of degradation of PET products, preparation of PET degradation agents or BHET degradation agents and the like.

The invention relates to combination and combination therapies, particularly for the treatment of a myeloid malignancy, such as acute myeloid leukemia (AML) or a myelodysplastic syndrome (MDS). The combination therapies include (i) a recombinant binding protein comprising (a) an ankyrin repeat domain specifically binding CD3 and (b) at least one, at least two, or at least three further ankyrin repeat domains, wherein each of the at least one, at least two, or at least three further ankyrin repeat domains specifically binds one tumor-associated antigen, suitably one selected from the group consisting of CD123, CD33 and CD70, and (ii) a Bcl-2 inhibitor, e.g., venetoclax, or a pharmaceutically acceptable salt thereof and / or (iii) a hypomethylating agent, e.g., azacitidine or decitabine.

Provided are therapies comprising immune effector cells, such as T cells, engineered to express an antigen receptor, such as a T cell receptor or a chimeric antigen receptor.SOLUTION: It is demonstrated that antigen receptor-engineered immune effector cells can be generated in vitro / ex vivo as well as in vitro by delivering a nucleic acid encoding an antigen receptor for genetic modification to a cell using a particle comprising the nucleic acid and a targeting molecule for targeting the immune effector cell, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are provided that are high affinity binders for CD8 binding to CD8 receptors on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8 targeting DARPins (CD8 - DARPins) can deliver genes exclusively and specifically to human CD8 + T cells in vitro and in vivo.SELECTED DRAWING: None

In an embodiment, the present disclosure pertains to a method of treating or preventing C. difficile infections. In some embodiments, the method includes administering an anti-toxin to a subject in need thereof. In some embodiments, the anti-toxin includes a designed ankyrin repeat protein (DARPin). In an additional embodiments, the present disclosure pertains to a composition including an anti-toxin for treating or preventing C. difficile infections. In some embodiments, the anti-toxin includes a DARPin. In some embodiments, the anti-toxin is a monomeric or dimeric DARPin for the neutralization of Clostridium difficile toxin B (TcdB).

The present invention relates to recombinant binding proteins comprising a designed ankyrin repeat domain with binding specificity for DLL3. In addition, the invention relates to nucleic acids encoding such binding proteins, pharmaceutical compositions comprising such binding proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods of treating diseases, such as cancer, in a mammal, including a human.

The present invention provides certain tetrazole derivatives which are inhibitors of Transient Receptor Potential Ankyrin 1 (TRPA1) and are therefore useful in the treatment of diseases which can be treated by inhibition of TRPA1. Also provided are pharmaceutical compositions containing the compounds and methods of preparing the compounds.

Provided in the present invention are a heteroaromatic acetamide derivative and the preparation and the use thereof, wherein the heteroaromatic acetamide derivative is a heteroaromatic acetamide compound as shown in general formula (I), or a pharmaceutically acceptable salt and / or solvate thereof. According to the present invention, experiments have confirmed that the heteroaromatic acetamide derivative of the present invention can specifically bind to transient receptor potential ankyrin 1 (TRPA1) and inhibit or reduce the activity thereof, and can be used for treating diseases mediated by TRPA1. The present invention further provides a method for preparing the heteroaromatic acetamide derivative, and a drug and pharmaceutical composition containing the heteroaromatic acetamide derivative.

The present invention provides certain tetrazole derivatives that are inhibitors of transient receptor potential ankyrin 1 (TRPA1) and are therefore useful in treating diseases treatable by inhibiting TRPA1. The present invention also provides pharmaceutical compositions containing the same and methods for preparing the compounds.

The present invention relates to recombinant binding proteins comprising a first designed ankyrin repeat domain which has a first binding specificity for a first target and a second binding specificity for a second target, wherein the binding of said first domain to said first and second targets is mutually exclusive, and wherein the first target is CD117 and the second target is a CD47-specific binding agent. The invention also provides further recombinant proteins comprising said first dual-specific repeat domain and additional therapeutic agents such as binding agents. Further disclosed are nucleic acids encoding such recombinant proteins, pharmaceutical compositions comprising such recombinant proteins or nucleic acids and the use of such recombinant proteins, nucleic acids or pharmaceutical compositions in methods for treating diseases, such as cancer in a mammal, including a human. Designed ankyrin repeat domains with binding specificity for a CD47-specific ankyrin repeat domain are also disclosed.

The present invention relates to designed ankyrin repeat domains having a reduced isoelectric point (pI) and / or having a reduced number of basic amino acid residues. The invention also provides such repeat domains linked to a drug moiety, such as a radionuclide or cytotoxic agent. The invention also provides methods for producing such repeat domains, and the use of such repeat domains in therapeutic and / or diagnostic methods. Furthermore, the invention provides recombinant proteins comprising such repeat domains, nucleic acids encoding such repeat domains or recombinant proteins, pharmaceutical compositions comprising such repeat domains, recombinant protein nucleic acids, recombinant expression vectors and host cells, and the use of such proteins, nucleic acids or pharmaceutical compositions in methods for the treatment of diseases such as cancer.

This invention provides certain tetrazolium derivatives that are inhibitors of transient receptor potential ankylosing protein 1 (TRPA1), and are therefore useful for treating diseases that can be treated by inhibiting TRPA1. Pharmaceutical compositions containing these derivatives and methods for preparing said compounds are also provided.

The present disclosure provides compositions comprising a designed ankyrin repeat protein (DARPin) for use in treating Shiga toxin (Stx)-producing Escherichia coli (STEC) and related diseases, including hemolytic uremic syndrome (HUS). The high thermostability and high microbial expression yield make DARPin an attractive alternative to antibody therapeutics. The present disclosure provides monomer proteins, dimer proteins, and trimer proteins, as well as pharmaceutical compositions and methods utilizing the same.

Disclosed herein are nanoparticle conjugates (e.g., anti-angiogenic and / or immunomodulatory nanoparticle conjugates, e.g., high-affinity Designed Ankyrin Repeat Protein (DARPin)-based binders targeting one or more cancer and / or immune receptors). The nanoparticle conjugates are useful for therapeutics and / or diagnostics and have a diameter (e.g., average diameter) no greater than 20 nanometers (e.g., as measured by dynamic light scattering (DLS) in aqueous solution, e.g., saline solution).

This invention provides certain tetrazolium derivatives that are inhibitors of transient receptor potential ankylosing protein 1 (TRPA1), and are therefore suitable for treating diseases that can be treated by inhibiting TRPA1. Pharmaceutical compositions containing said compounds and methods for preparing said compounds are also provided.

In particular, the present invention provides a method for the preparation of a transitory receptor potential ankyrin 1 (transient receptor potential ankyrin 1), and a transitory receptor potential ankyrin 1 (transitory receptor potential ankyrin 1). The present invention relates to certain tetrazole derivatives of inhibitors of TRPA1, and thus are useful in the treatment of diseases that can be treated by inhibition of TRPA1. The invention also provides pharmaceutical compositions containing the same and methods of preparing the compounds.

The present invention relates to multispecific binding proteins comprising binding domains with dual-binding specificity for at least one disease-associated antigen, suitably tumor-associated antigen and an immune cell surface antigen. Said binding domains with dual-binding specificity bind to the two targets in a mutually exclusive way, thereby functioning as a molecular switch, such as, e.g., a switch to control activation or deactivation of a therapeutic agent. Said binding proteins are formatted as T cell engagers to optionally comprise a binding domain with co-stimulatory activity, such as CD2. Said binding domains are preferably ankyrin repeat domains, e.g. designed ankyrin repeat domains (DARPins). The invention further relates to nucleic acids, pharmaceutical compositions, recombinant expression vectors and host cells, and the use of such proteins, nucleic acids or pharmaceutical compositions in methods for treating diseases, such as cancer.

The present invention relates to recombinant binding proteins comprising an ankyrin repeat domain, wherein the ankyrin repeat domain has binding specificity for CD16a. In addition, the invention relates to nucleic acids encoding such recombinant binding proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer in a mammal, including a human.

In particular, the present invention provides a method for the preparation of a transitory receptor potential ankyrin 1 (transient receptor potential ankyrin 1), and a transitory receptor potential ankyrin 1 (transitory receptor potential ankyrin 1). The present invention relates to certain tetrazole derivatives of inhibitors of TRPA1, and thus are useful in the treatment of diseases that can be treated by inhibition of TRPA1. The invention also provides pharmaceutical compositions containing the same and methods of preparing the compounds.

The present disclosure provides methods of treating and preventing trigeminal nerve pain with modulators of oxidative stress (e.g., NRF2 transcription network activators and / or inhibitors of transient receptor potential ankyrin 1 (TRPA1)) and compositions thereof.

Disclosed are a recombinant binding protein targeting TSLP and the use thereof. The recombinant binding protein comprises at least one ankyrin repeat domain that specifically binds to TSLP, wherein the ankyrin repeat domain comprises three tandem binding domains, and each binding domain comprises four binding active regions. The recombinant binding protein of the present invention has excellent binding activity to TSLP, and effectively blocks the interaction between TSLP and a receptor thereof, thereby effectively controlling TSLP-related diseases.

This invention provides certain tetrazolium derivatives that are inhibitors of transient receptor potential ankylosing protein 1 (TRPA1), and are therefore useful for treating diseases that can be treated by inhibiting TRPA1. Pharmaceutical compositions containing these derivatives and methods for preparing said compounds are also provided.

According to the present invention, four types of anchor proteins, which conform to the inherent characteristics of CDV and can mediate the stable introduction of bioactive molecules, are explored as modified cell-derived vesicles (Cells-derived vesicles) that can be used as drug delivery carriers, thereby completing the present invention. It is confirmed that the anchor protein is used as a membrane protein specifically and abundantly existing in CDV, and the CDV containing the anchor protein can more stably load bioactive molecules. For example, the result of a comparative experiment using a fluorescent protein has been confirmed that the CDV into which the anchor protein is introduced has more efficiently loaded with the fluorescent protein than the CDV without the anchor protein. Moreover, it has been confirmed that when a cancer cell-targeting antibody is loaded in the modified CDV of the present invention, not only the cancer cell targeting ability is increased, but also the modified CDV is more effectively absorbed by cancer cells. That is, the CDV according to the present invention can stably load a plurality of bioactive molecules and deliver the bioactive molecules to a desired target as BioDrone modified by an anchor protein, and is expected to be used in drug delivery and treatment platforms for a plurality of drugs.

Described herein is a protein display selection method which uncouples a protein of interest (POI) library from the display selection system. Display of the POI can be achieved by forming a covalent bond between the POI and the anchor protein post expression either by enzymatic protein ligation (e.g. SpyLigase, SnoopLigase, sortase, butelase, peptiligase etc.) or by spontaneous covalent bond formation (e.g. SpyTag / SpyCatcher, SnoopTag / SnoopCatcher, etc.). The POI library is fused to a tethering sequence, for example SpyTag, at the C-terminus of the POI which then forms a covalent bond to a capture sequence found on an anchor protein, for example, the SpyCatcher-fused anchor protein, e.g., a SpyCatcher-geneIII protein (SpyCatcher-pIII) fusion, for the most common form of phage display. Nucleic acid constructs, host cell systems and methods of producing the protein display systems are also provided.