20 results about "Chimeric molecules" patented technology

Disclosed are substituted heterocyclic compounds and proteolysis-targeting chimeric molecules (PROTACs). The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC. The disclosed PROTACs are shown to induce degradation of c-MYC protein. The substituted heterocyclic compounds and proteolysis-targeting chimeric molecules (PROTACs) disclosed, herein may be utilized as therapeutics for treating cancer and cell proliferative disorders.

To provide tumor-associated antigens suitable for targeted antibody therapy against cancer.SOLUTION: Antigen binding molecules that specifically bind ALPPL2 and ALPP, but not ALPL and ALPI are provided. Also provided are chimeric molecules and pharmaceutical compositions comprising the antigen-binding molecules, methods of reducing the expression or activity of ALPPL2 in cancer cells, and methods of treating cancers in a subject.SELECTED DRAWING: None

A platform for therapy provides: a chimeric molecule comprising one or more auto-antigens linked by a linker to a fluorescent protein; a chimeric molecule comprising three or more components linked by linker, the components comprising two or more auto-antigens of an autoimmune disease and one or more ablative molecule and / or toxin or one or more fluorescent molecules; a chimeric molecule comprising two or more components linked by linker, the components comprising an antibody or an antigen binding fragment thereof to an autoimmune disease associated HLA class or HLA class II molecule and one or more ablative molecules and / or toxins or one or more fluorescent molecules; and a chimeric molecule comprising two or more components linked by linker, the components comprising an antibody or an antigen binding fragment thereof to a disease associated T-cell receptor and one or more fluorescent molecules or one or more ablative molecule and / or toxin

Described herein are methods and compositions relating to a chimeric molecule comprising: a degradation domain; and a targeting domain capable of specifically directing said degradation domain to a substrate, wherein said targeting domain is heterologous to said degradation domain.

This invention provides a polyfunctional chemical conjugation molecule that has been found to be useful as a modifier for target substrates. [Solution] A polyfunctional chemical conjugation molecule is provided, comprising a localization portion, a chemical linker portion, an activator portion, a first orientation adapter that interconnects the chemical linker portion to the activator portion at one end, and optionally a second orientation adapter that interconnects the chemical linker molecule to the localization portion at a different end. The molecule provides a use for post-translational modification of a polymer that is not a natural substrate of the activator portion. Diseases or disorders may be treated or prevented by this molecule.

The technology described herein is directed to improved chimeric molecules for, e.g, the treatment of cancer. As described herein, the inventors have developed novel chimeric aptamer-siRNA molecules (AsiCs) which demonstrate improved efficacy over existing AsiCs and which can successfully synergize in treating cancer. These AsiC's target cancer cell markers to direct therapeutic siRNA molecules specifically to cancer cells, increasing delivery efficacy and therapeutic effectiveness while reducing the potential for side effects.

Organic compounds for target identification, drug discovery, chemical library production, high-throughput screening, fluorophore conjugation, chemiluminescent compound conjugation, creation of proximity induced modulators (e.g., protein degraders) / chimeric molecules, or a combination thereof are described. The compounds can contain small molecule moieties for identification of their potential targets; an isocyanate, photoactivatable groups; chemical moieties for enrichment and detection of target-small molecule moiety interactions; proximity induced modulator element; fluorophores; chemiluminescent groups; or combinations thereof.

The invention relates to inverted chimera siRNA molecules and their use for the inhibition of expression of one or more target genes. The invention further relates to the inhibition of expression of c-Myc, or the dual inhibition of c-Myc and KRAS, using RNA interference, chemically-modified oligonucleotides, and / or chimeric siRNA multivalent combinations.

Disclosed herein is a botulinum neurotoxin (BoNT) polypeptide with a modified receptor binding domain (HC) having one or more amino acid mutations that modify the binding of the BoNT to the receptor. Specific mutations and combinations of mutations are also disclosed. Isolated modified HC, polypeptides comprising the modified HC, chimeric molecules, pharmaceutical compositions, and methods of making and using the same are also disclosed. Methods of identifying additional such modified receptor binding domains, are further disclosed.

Provided herein are methods for treating or preventing, or ameliorating at least one symptom of, a neurodegenerative disease associated with TDP-43 pathology, comprising administering to a subject an effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a conservative variant thereof, optionally linked to a protein destabilization domain sequence, or a nucleic acid molecule encoding said peptide. Also provided is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a conservative variant thereof, a chimeric molecule comprising said peptide linked to a protein destabilization domain sequence, and a polynucleotide encoding said peptide or chimeric molecule.

The invention relates to the technical field of biological medicine, in particular to a lysosome targeting chimeric molecule based on IGF2R-D11 structural domain targeting polypeptide and application of the lysosome targeting chimeric molecule. A novel polypeptide capable of being specifically combined with an insulin-like growth factor 2 receptor is obtained by screening through a phage display technology, the polypeptide is used as a key component and is fused with a targeting antibody through a genetic engineering method, and a bifunctional chimeric molecule capable of efficiently internalizing and mediating target protein targeting lysosome is constructed. A new technical platform is provided for the field of targeted protein degradation, and the method has important application value in the fields of tumor immunotherapy, autoimmune diseases and the like.

Methods of modulating an immune response for the treatment of cancer includes compositions which comprise chimeric molecules with an anti-CD47 binding domain and an immunomodulatory agent.

Provided herein are methods for treating or preventing, or ameliorating at least one symptom of, a neurodegenerative disease associated with TDP-43 pathology, comprising administering to a subject an effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a conservative variant thereof, optionally linked to a protein destabilization domain sequence, or a nucleic acid molecule encoding said peptide. Also provided is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a conservative variant thereof, a chimeric molecule comprising said peptide linked to a protein destabilization domain sequence, and a polynucleotide encoding said peptide or chimeric molecule.

The present invention relates to a 3,4-dihydrophthalazine-1(2H)-one compound represented by formula (I), pharmaceutically acceptable salts thereof, prodrugs, stable isotope derivatives, isomers, solvates, or polymorphs thereof, and pharmaceutical compositions comprising the above compound. Furthermore, the present invention also provides a method for preparing the compound represented by formula (I). The compound is used as a modulator of targeted ubiquitination, particularly for the treatment of diseases related to the CRBN protein. The compound is also used for the preparation of related proteolytic chimeric molecules (PROTACs) for CRL4 CRBN It can also be used as a ligand for E3 ubiquitin ligase. JPEG2026520709000104.jpg38149

The present disclosure provides a chimeric molecule comprising: a) a T-cell modulatory multimeric polypeptide (TMMP); and b) a nucleic acid component, where the nucleic acid component comprises a nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising an antibody that binds a cancer-associated antigen. The TMMP binds to and activates a target T cell; the nucleic acid component is taken up by the target T cell such that the target T cell expresses the CAR on its surface. The present disclosure provides methods of making the chimeric molecule. The present disclosure provides treatment methods comprising administering the chimeric molecule.

The invention is directed to methods of purifying a chimeric protein comprising subjecting the chimeric protein to a factor VIII-specific affinity chromatography, and subjecting the chimeric protein to an AEX chromatography; wherein the chimeric protein comprises a factor VIII protein or a fragment thereof. The chimeric protein purified by the present methods shows improved factor VIII activity.

Provided is a method for preparing a circular RNA or chimeric RNA by means of an RNA self-splicing ribozyme or self-splicing pair. By means of a self-splicing reaction, both ends of two independent linear RNA molecules are respectively linked to each other to form a circular RNA molecule; or one end of one linear RNA molecule is linked to one end of the other independent RNA molecule to form a chimeric RNA molecule. The chemical modification levels of the two linear RNA molecules may be independently regulated, and then the two linear RNA molecules are linked to form a circular RNA or a chimeric RNA molecule, thereby achieving chemical modification with controllable modification types and modification levels for specific regions of the circular RNA molecule or the chimeric RNA molecule. The site-specific controllable RNA modification method can significantly improve the likelihood of RNAs becoming therapeutics and reduce toxic and side effects, thereby promoting the development of RNA vaccines and drugs.

The present invention is directed to provide novel RNA molecules, chimeric NA molecules, double-stranded RNA molecules, and double-stranded chimeric NA molecules. Specifically, an embodiment of the present invention is an RNA molecule for RNA interference to target a mutant allele with a point mutation, in which (1) the molecule has a nucleotide sequence complementary to a nucleotide sequence of a coding region of the mutant allele; and (2) when counted from the base at the 5′-end in a nucleotide sequence complementary to a nucleotide sequence of the mutant allele, (2-1) a base at position 5 or 6 is mismatched to a base in the mutant allele; (2-2) a position 10 or 11 corresponds to the position of the point mutation; and (2-3) a group at the 2′-position of a pentose at positions 6-8 or positions 7 and 8 is modified with, e.g., OCH3. In this RNA molecule, one or more ribonucleotides may be replaced by, e.g., a deoxyribonucleotide. The molecule may form a double-stranded RNA with a complementary strand.

The present disclosure relates to electrophilic reactive linkers, which find utility labeling target substrates according to the formula L1-El, El-L1, or L1-El-L2, wherein El is an electrophilic reactive group and wherein L1 and L2 are linking molecules. Molecules according to the present invention find use, for example, in multifunctional chimeric molecules (e.g., bifunctional molecules), which make substrate modifications such as post-translational modifications to targets that are not the natural substrate; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.

Provided are chimeric molecules, compositions, and applications thereof that specifically bind to natriuretic peptide receptor C (NPR-C). The disclosed chimera comprises an NPR-C binding domain and a target-binding domain. Through NPR-C-mediated endocytosis, the chimera enables the intracellular degradation of the target by lysosomal enzymes. The chimeric molecules can rapidly, conveniently, and precisely degrade target proteins. Their modular design permits broad applicability to proteins such as secreted proteins and membrane-associated proteins. These chimeric molecules exhibit high bioavailability and low immunogenicity, thus being broadly applicable for the treatment of diseases including cancer, neurodegenerative diseases, psychiatric disease, central nervous system diseases, inflammatory diseases, autoimmune diseases, metabolic syndrome, tissue fibrotic disease, cardiovascular diseases, respiratory diseases, digestive diseases, renal diseases, hematologic diseases, infectious diseases, rare diseases and aging-related disease.