2205 results about "Moiety" patented technology

The present disclosure relates to compositions and methods for reversible fixation of biological samples using fixation reagents that form bis-carbamate crosslinks between amine-bearing moieties in biomolecules.

Provided herein are methods, compositions, and kits to spatially detect a polypeptide-nucleic acid complex or a protein-nucleic acid complex in a biological sample. For example, such methods can include contacting binding agents with a biological sample, wherein a binding agent specifically binds a polypeptide of a polypeptide-nucleic acid complex; aligning the biological sample with a substrate comprising a plurality of capture moieties, wherein the binding agent interacts with a capture moiety; releasing the nucleic acid of the binding agent-polypeptide-nucleic acid complex; hybridizing the released nucleic acid to a capture domain of a capture probe on an array; and using determined sequences of a spatial barcode in the capture probe and the released nucleic acid to determine the location of the released nucleic acid in the biological sample, thereby determining the location of the polypeptide-nucleic acid complex in the biological sample.

Ionizable cationic lipids, methods for synthesizing the same, intermediates useful in synthesis of the ionizable cationic lipids, and methods of synthesizing the intermediates are disclosed. The ionizable cationic lipids are useful as a component of lipid nanoparticles (LNP), which in turn can be used for delivering nucleic acids into cells in vivo or ex vivo. LNP compositions are also disclosed, including LNP comprising a functionalized lipid to enable conjugation of a binding moiety, and targeted LNP (tLNP), that is a LNP in which a binding moiety has been conjugated to the functionalized lipid and can serve as a targeting moiety to direct the tLNP to a desired tissue or cell type.

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

An antigen-binding molecule that binds to a target antigen, comprising (i) a target antigen-binding moiety, and (ii) at least one linker-payload moiety, wherein the antigen-binding molecule comprises (a) DNA damage response (DDR) inhibitor moiety, and (b) a DNA topoisomerase I (TOP1) inhibitor moiety.

Fusion proteins are provided that consist of essential elements such as one or more proteins / polypeptides capable of transporting into the endoplasmic reticulum (ER) and fragments or variants of interleukin 18 (IL-18) or IL-18. The proteins / polypeptides capable of transporting into the ER include, but are not limited to, immune globular proteins (e.g., Fc regions, VHH antibodies, and scFv), and globular proteins (e.g., serum albumin). In some embodiments, the IL-18 may be a pro-IL-18 similar to a natural precursor cytokine, wherein IL-18 is fused to the C-terminus of a propeptide or a propeptide variant thereof. In some embodiments, the fusion protein may further comprise a cleavable peptide linker.

An antigen-binding molecule that binds to HER2, comprising (i) a HER2-binding moiety, and (ii) at least one linker-payload moiety, wherein the antigen-binding molecule comprises (a) DNA damage response (DDR) inhibitor moiety, and (b) a DNA topoisomerase I (TOP1) inhibitor moiety.

The present disclosure relates to compositions and methods for reversible fixation of biological samples using fixation reagents that form bis-carbamate crosslinks between amine-bearing moieties in biomolecules.

A compound of Formula I,is provided. In Formula I, moiety A is a monocyclic ring or a polycyclic fused ring system; each of X1 to X2 and Z1 to Z3 is independently C or N; Y1 is C, N, O, S, Se, P, or As; K is a direct bond or a linker; each of A1 and A2 is C, Si, N, P, or As; each of L1, L2, and L3 is absent, a direct bond, or a linker; at least one of L1 to L4 is present; when L3 is present, X11 is C, whereas if L3 is absent, X11 is C or N; M is Pt or Pd; each R1, R2, RA, RB, RC, RD, Rα, and Rβ is hydrogen or a General Substituent defined herein and R* is a General Substituent defined herein. Formulations, OLEDs, and consumer products containing the compound are also provided.

A multifunctional organosilicon compound is provided which has the general formula XSi([OSiR2]p-0-SiR2Y)a(R1)3-a— ln the formula, X is selected from H and ethylenically un saturated moieties; each Y independently comprises a functional moiety selected from alkoxysilyl moieties, acryloxy moieties, and epoxide moieties; each R is an independently selected hydrocarbyl group; each R1 is an independently selected hydrocarbyl group; subscript a is 1, 2, or 3; and each subscript b is independently 0, 1, or 2. A method of preparing the multifunctional organosilicon compound is also provided. The method comprises reacting (A) an organosilanol compound and (B) a silane compound having at least two hydrolysable groups. A functionalized siloxane compound prepared from the multifunctional organosilicon compound, a method of preparing the functionalized siloxane compound, and an adhesive comprising the functionalized siloxane compound are also provided.

The invention provides heterobifunctional compounds comprising an effector protein binding moiety selected from mTor, PLK1, CDKI, CDK2, CDK9, BRD4, AURKA, AURKB, MEK, Src, c-KIT, KIF11, HSP90, tubulin, proteasome, topoisomerase or HD AC which is linked to a moiety that binds to a target protein selected from KRAS, HER2 or EGFR. Pharmaceutical compositions and their use in treating disease, such as cancer, are also disclosed.

The present disclosure relates in some aspects to methods, systems, and kits for sequencing a template nucleic acid molecule, where the methods comprise: (i) contacting a priming strand bound to the template nucleic acid molecule with a first plurality of nucleotide molecules and a polymerase coupled to a heterologous polynucleotide-binding moiety to form a complex comprising a 3′ terminus of the priming strand, the template nucleic acid molecule, the polymerase, and a nucleotide molecule of the first plurality of nucleotide molecules, wherein the polynucleotide-binding moiety enhances stability of the complex, and wherein the priming strand comprises a reversibly-terminated nucleotide at its 3′ end such that the nucleotide molecule of the transient complex is not incorporated; and (ii) detecting a presence of the nucleotide molecule in the complex to identify a complementary nucleotide in the template nucleic acid molecule.

A method of preparing an acrylate-functional branched organosilicon compound (“compound”) is provided, and comprises reacting (A) a branched organosilicon compound and (B) an acrylate compound in the presence of (C) a catalyst, wherein component (A) has the general formula X—Si(R1)3, where X comprises a halogen-functional moiety and each R1 is selected from R and —OSi(R4)3, with the proviso that at least one R1 is —OSi(R4)3; each R4 is selected from R, —OSi(R5)3, and —[OSiR2]mOSiR3; each R5 is selected from R, —OSi(R6)3, and —[OSiR2]mOSiR3; each R6 is selected from R and —[OSiR2]mOSiR3; each R is an independently selected hydrocarbyl group; and 0≤m≤100; with the proviso that at least one of R4, R5 and R6 is —[OSiR2]mOSiR3. The compound prepared by the method, a copolymer comprising the reaction product of the compound and a second compound, a method of forming the copolymer, and a composition comprising the copolymer are each also provided.

The invention relates to a ligand-effector moiety provided with at least one saponin and antibody-effector moiety provided with at least one saponin. An aspect of the invention is a composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention. The invention also relates to an antibody-drug conjugate comprising covalently linked saponin and to an antibody-oligonucleotide conjugate comprising covalently linked saponin. An aspect of the invention relates to a pharmaceutical composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin, for use as a medicament. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention for use in the treatment or prophylaxis of a cancer.

The present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.

Linkers for linking a therapeutic agent to other moieties, such as an Fc region of an antibody. A linker having two or more maleimide functional groups, which may be subjected to a nucleophilic conjugate addition reaction. A method for increasing the duration of action of a therapeutic agent by linking a novel linker to the Fc region of an antibody. Antibody drug conjugates having a longer duration of action than the drug alone.

The present disclose provides a method for classifying a sample derived from a subject. The method may comprise obtaining a sample comprising nucleic acid molecules from the subject. The method can comprise assaying the nucleic acid molecules to generate a data set comprising methylation states of one or more genomic regions. The one or more genomic regions can comprise differentially methylation regions (DMRs). The method can comprise processing at least a portion of the data set to generate an output indicative of cancer in the subject. The portion of the data set can pertain to a set of DMRs specific to the subject.

The present invention relates to a multi-aziridine compound having: a) at least 2 of the following structural units (A): (A) whereby R1 is H; R2 and R4 are independently chosen from H, a linear group containing from 1 to 8 carbon atoms and optionally containing one or more heteroatoms, a branched or cyclic group containing from 3 to 8 carbon atoms and optionally containing one or more heteroatoms, phenyl, benzyl, or pyridinyl; R3 is chosen from a linear group containing from 1 to 8 carbon atoms and optionally containing one or more heteroatoms, a branched or cyclic group containing from 3 to 8 carbon atoms and optionally containing one or more heteroatoms, phenyl, benzyl, or pyridinyl; or R2 and R3 (in case R2 is different than H) may be part of the same cyclic group containing from 3 to 8 carbon atoms; R′ and R″ are independently H or an aliphatic hydrocarbon group containing from 1 to 12 carbon atoms; and b) a molecular weight from 600 to 20000 Daltons, wherein the molecular weight is determined using MALDI-TOF mass spectrometry according to the description.

Provided herein are binding molecules comprising a human neonatal Fc receptor (FcRn) binding molecule and a moiety that does not specifically bind to a human antigen. Polynucleotides, vectors, host cells, and methods of production are also provided herein. Methods of treating an antibody-mediated disorder with an FcRn binding molecule or an FcRn / antigen-binding molecule are further provided.

A system and method for modeling one or more characteristics of a molecule using a quantum device implemented on quantum hardware is disclosed. Through control, via modulation, of coupling strengths between qubits on the quantum device and a comparison to an experimentally-measured nuclear magnetic resonance spectrum, J-coupling values may be deduced. These J-coupling values may then be used to recover the molecular structure of the given molecule. The control of coupling strengths may take place through an iterative process until convergence to the one or more characteristics is reached. In some embodiments, such a process may be implemented as part of a quantum computing service. In such cases, the quantum hardware may be local to the quantum computing service, or may be outsourced to a quantum hardware provider.

A fusion protein comprising at least one first polypeptide moiety and at least one second polypeptide moiety, wherein the first polypeptide moiety is a single-chain polypeptide capable of binding a target entity, and the second polypeptide moiety is a stabilizing polypeptide and comprises a single-chain α-helix-containing domain, wherein the second polypeptide moiety does not have binding affinity for said target entity. The presence of the second polypeptide moiety can improve at least one property of the fusion protein as compared to the property of the first polypeptide moiety alone, wherein said improved property is selected from the group consisting of: alkaline stability, recombinant protein expression and coupling to a support.

Provided is a compound for double targeting of a fibroblast activation protein and an integrin subtype, comprising: (i) a chelating ligand moiety (CL); (ii) a first targeting moiety (BT); and (iii) a second targeting moiety (CY), wherein (i), (ii), and (iii) are fixed, combined, or connected by means of any L; BT is a fibroblast activation protein (FAP)-specific binding ligand structure; CY is an integrin subunit αvβ3 or αvβ6-specific binding ligand structure; L is selected from one or a combination of L1, L2, L3, L4, L5, L6, and L7; L1, L2, L3, L4, L5, L6, and L7 are each independently a key, a monovalent joint, a divalent joint, or a trivalent joint. Also provided are a preparation method for the compound and use thereof.

Disclosed are microcapsule compositions having a microcapsule that contains a microcapsule core and a microcapsule shell encapsulating the microcapsule core. The microcapsule has a particle size of 1 micron to 100 microns in diameter. The microcapsule core contains an active material. The microcapsule shell is formed of at least three moieties, in which a first moiety is derived from a polygalactomannan, a second moiety is derived from a polyisocyanate, and a third moiety is derived from a multi-functional aldehyde or a tannic acid.

Provided herein are methods, compositions, and kits for detecting analytes of interest from biological samples using tagmentation. The method comprises: (a) hybridising a nucleic acid analyte to a capture probe on an array, wherein the capture probe comprises: (i) a spatial barcode and (ii) a capture domain; (b) extending the capture probe using the nucleic acid analyte as a template, thereby generating a barcoded nucleic acid molecule on the array, wherein the barcoded nucleic acid molecule comprises a complement of the sequence of the nucleic acid analyte; and (c) tagmenting the barcoded nucleic acid molecule or a derivative thereof using a transposome comprising a transposase to insert a transposon end sequence into the barcoded nucleic acid molecule or the derivative thereof, thereby generating a barcoded nucleic acid fragment, wherein the barcoded nucleic acid fragment comprises: (i) the barcode, (ii) the transposon end sequence, and (iii) at least a portion of a sequence of the nucleic acid analyte or a complement thereof.

In some aspects, the present disclosure provides systems for forming hydrogels that comprise (i) a reactive multi-arm polymer that comprises three or more polymer arms linked to a core region, each arm comprising a polyether segment and a reactive moiety comprising a cyclic imide carboxy-C1-C5-alkyl ester end group or each arm comprising a polyether segment and a reactive moiety comprising a C2-C6-isocyanoalkyl end group and (ii) a polyamino compound comprising at least two amino (-NH2) groups, wherein the reactive multi-arm polymer and the polyamino compound react to form a crosslinked hydrogel that does not contain ester groups and has long-term stability in vivo. In some aspects, the present disclosure provides methods of treatment using such systems and hydrolysis-resistant crosslinked hydrogels formed from such systems.

A compound of Formula Ir(LA)x(LB)y(LC)z is provided where x and y are independently 1 or 2; z is 0 or 1; and x+y+z=3; first ligand LA includes a structure of Formula I,ligand LB includes a structure of Formula II:and ligand LC is a bidentate ligand. In the compounds, moiety B is a polycyclic fused ring system comprising at least four rings; each of moiety C and moiety D is a monocyclic ring or a polycyclic fused ring system; each of X1 to X4 and Z1 to Z6 is C or N; L0 is a direct bond or a linking group; YA is a linking group; each substituent is hydrogen or a General Substituent defined herein; and any two substituents may be joined or fused to form a ring. Formulations, OLEDs, and consumer products containing the compound are also provided.

Functionalized and crosslinked material, which may optionally be employed as a sorbent, as well as methods of making such materials and systems of using such materials are provided. The processes, methods, systems and materials herein can be used for the separation of carbon dioxide from fluid streams. In one aspect, a method of forming functionalized crosslinked particles comprises introducing at least a portion of a surface of each porous particle in at least a subset of a plurality of porous particles to a crosslinking agent and a first reagent comprising at least one adsorbing moiety. Examples of adsorbing moiety include silane-functionalized amines, amino-functionalized silanes (aminosilane), and polyamines. In some aspects the method further comprises introducing the porous particles to a second reagent comprising at least one interaction moiety such as a silane-functionalized amine, amino-functionalized silane (aminosilane), or polyamine. Examples of crosslinking agent include dialdehyde, diisocyanates, dihaloalkane, diepoxide and dianhydrides.

The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

The present disclosure relates to targeting moieties such as peptides that can bind to B7-H3. The disclosure also provides targeting constructs, which may include a targeting moiety attached, via an optional linker, to a chelating agent for association of a cargo. Methods of making the constructs and formulations thereof are also provided. Methods of using the constructs and / or formulations thereof to treat subjects, for example, to treat or prevent cancer, are also described.

Disclosed are drug conjugates comprising a targeting moiety conjugated to a drug molecule, wherein the targeting moiety binds to a cell adhesion moiety and / or receptor expressed on a Schwann cell to mediate targeted delivery of the drug conjugate to the Schwann cell, and wherein the drug molecule modifies expression or activity of a disease-associated molecule, and / or confers a cytotoxic effect, in the Schwann cell. Further disclosed herein are methods of targeted delivery of a drug to the Schwann cells.