3162 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 optically detectable label (102, 500) is provided comprising a nucleic acid backbone (108, 504) comprising multiple attachment positions (306, 308, 506a, 506b, 506c, 506d) including at least a first attachment position and a second attachment position. The optically detectable label (102, 500) further comprises multiple labelling moieties (106a, 106b, 106c, 106d, 106e, 310, 312, 502a, 502b, 502c, 502d), including at least a first labelling moiety and a second labelling moiety, each labelling moiety (106a, 106b, 106c, 106d, 106e, 310, 312, 502a, 502b, 502c, 502d) attached to a different one of the attachment positions (306, 308, 506a, 506b, 506c, 506d) of the nucleic acid backbone (108, 504). The first labelling moiety and the second labelling moiety are configured to form an energy transfer donor and acceptor pair. Further, the nucleic acid backbone (108, 504) has at least a first spatial state (300, 500a) and a second spatial state (322, 500b), wherein in the first spatial state the attachment position to which the first labelling moiety and the attachment position to which the second labelling moiety are attached to, are in proximity in order to enable an energy transfer between the first labelling moiety and the second labelling moiety. Moreover, the nucleic acid backbone (108, 504) is in the first spatial state (300, 500a) when a first staple strand (302, 510, 512) is bound to the nucleic acid backbone (108, 504). In further aspects, a marker (100) comprising the optically detectable label (102, 500) is provided and a method for analysing a biological sample.

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 Ir(LA)x(LB)y(LC)z, where x and y are 1 or 2; z is 0 or 1; and x+y+z=3. In the compound, LA comprises Formula I,ligand LB comprises Formula II,and ligand LC is a bidentate ligand. In Formulas I and II, moiety A is a monocyclic ring or a polycyclic fused ring system; each of X1 to X14 is C or N; Y is a linking group; each R1-R2, R, R′, and RA-RE is hydrogen or a General Substituent defined herein; at least one of R1 and R2 is a tertiary alkyl group; and (1) at least one pair of RB or RC substituents are joined or fused to form a ring, or (2) at least one RC or RB comprises an electron-withdrawing group other than nitrile, or (3) X11 is N, R1 is a tertiary alkyl group. Formulations, OLEDs, and consumer products containing the compound are also provided.

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 present disclosure relates to compounds, compositions and methods for treating diseases or conditions mediated by aberrant histone deacetylase 8 (HDAC8) activity. In some embodiments, the disclosed compounds comprise an HDAC8 targeting ligand TL moiety covalently linked to a degradation determinant moiety that recruits E3 ubiquitin ligase to HDAC8. In some embodiments, the degradation determinant can bind to an E3 ligase, which is a von Hippel-Lindau (VHL) tumor suppressor, and the E3 ligase can bind to an E3 ligase, which is a Von Hippel-Lindau (VHL) tumor suppressor.

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 application relates to a composition comprising (a) at least one immune checkpoint inhibitor and (b) at least one conjugate, wherein said conjugate is comprising (i) a target binding moiety, (ii) at least one amatoxin, and (iii) optionally at least one linker connecting said target binding moiety with said at least one amatoxin. The present application further relates to said composition for use in treating a patient having a cancer, and to a pharmaceutical formulation comprising said composition and additional excipients, as well as to methods of producing and using said composition (FIG. 1).

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 invention the invention concerns bifunctional compounds of Formula (I) A-T-L1-AG, Formula (II) A-L1-Con(L2-AG)n or Formula (III) Ak´-Th-L3 ii-AGj' wherein A is a protein that binds to the hinge region of galactose deficient IgA1 antibodies or a protein that binds to autoantibodies of galactose deficient IgA antibodies and AG is an asiaglycoprotein receptor binding moiety (ASGPR binding moiety). L1, Con and L2 are part of a linker between A and AG. The A has the ability to bind to antibodies that are a cause of IgA nephropathy and the asiaglycoprotein receptor binding moiety binds to hepatic cells thereby initiating endocytosis and removal of the antibodies that are a cause of IgA nephropathy from the blood stream.

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.

It is an object of the present invention to provide drugs that bind specifically to FAPα, are effective in the treatment and diagnosis of tumors or cancers expressing FAPα, for example, in the treatment and diagnosis of solid cancers such as pancreatic cancer, sarcoma, esophageal cancer, lung cancer, breast cancer, prostate cancer, head and neck cancer, ovarian cancer, colon cancer, neuroendocrine tumor, thyroid cancer, uterine cancer, liver cancer and the like (particularly, pancreatic cancer), and have a lower risk of prolonged side effects. The present invention provides a conjugate comprising a radioactive moiety comprising an aryl group substituted with a radionuclide selected from 211At, 210At, 131I, 125I, 124I, 123I, 77Br and 76Br, and a bioactive moiety having an affinity for fibroblast activation protein α (FAPα).

There is provided a compound of Formula I, wherein: Qa represents Z or A-Q-B, and Q is a structural fragment of Formula II,wherein: the squiggly lines, R and m have meanings given in the description, and wherein A and B have meanings given in the description, but may represent a peptide component of Formula (IV),[(W)r-Lys-X1-T-U-X2-Y] n- (W)r-Lys-X1-T-U-X2-Y (IV) (SEQ ID No: 1) in which n, r, T, W, X1, U, X2 and Y have meanings given in the description, each L independently represents a lipid as defined in the description, and D represents one or more optional montelukast moieties, which compounds are useful in medicine, including as pharmaceutical excipients, adhesives and film-forming materials and / or are useful in the treatment of conditions characterised by inflammation, including wounds, burns, and disorders of the mucosa, such as anorectal diseases, inflammatory bowel diseases, gynecological diseases and dental diseases.

Multispecific molecules that include an anti-G6B antibody or binding fragment thereof, an anti-CD34 antibody or binding fragment thereof; and one, two or all of: an immune cell engager (e.g., selected from an NK cell engager, a T cell engager, a B cell engager, a dendritic cell engager, and a macrophage cell engager); a cytokine molecule; a modulator of a cytokine molecule; a stromal modifying moiety; or any combination thereof are disclosed. Additionally disclosed are nucleic acids encoding the same, and methods of treating conditions or diseases using the aforementioned molecules.

Photoswitchable photoinitiators comprising a photochromic molecule including one or more substituents at least one of which comprises a substituted or unsubstituted alpha-diketone moiety represented by general formula Ar1—C(═O)—C(═O)—Ar2, wherein Ar1 and Ar2 are the same or different and are independently a substituted or unsubstituted aryl group or a substituted or unsubstituted heteroaryl group. Preferably the photochromic molecule comprises a benzospiropyran molecule, a naphthopyran molecule, or a spironaphthoxazine molecule. Photohardenable compositions, hardenable resin compositions, and methods for forming an object, which photohardenable compositions, hardenable resin compositions, and methods include a photoswitchable photoinitiator described herein, are also disclosed.

The present disclosure relates to targeting moieties such as peptides that can bind to DLL3. 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.

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.

The invention provides an oxygen-carrying protein molecule and a preparation method and application thereof, and relates to the technical field of functional protein preparation, the oxygen-carrying protein molecule comprises at least one cysteine part and at least one histidine part, the cysteine part comprises acetyl or ethyl maleoyl, and the histidine part comprises histidine. The histidine moiety includes a benzimidazole derivative group. The benzimidazole derivative is adopted as an auxiliary molecule and participates in the modification process of the sulfydryl modified compound on the hemoglobin, the modification site selectivity is improved, the conformational change is reduced, and the modification degree is accurately controlled, so that the oxygen binding force P50 of the modified hemoglobin is effectively improved.