An IC spatial array for a captured ligand assay is described. Materials to prepare and methods to produce the IC spatial array are also provided. The IC spatial array includes a matrix substrate including capture probes anchored to the matrix substrate such that the capture probes have a barcode unique to the capture probe's spatial location within the matrix substrate and the capture probe has a free end for capturing analytes from a sample.
A nanoparticle for delivering an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor to a subject and methods for treating inflamed tissue in a subject using the nanoparticle.
Foldable intraocular lens (IOL) having a total dioptric power and comprising an optic portion (12) having main anterior and posterior optical surfaces, and incorporating an internal optical feature (13) positioned between the main anterior and posterior optical surfaces are described. The optic portion has a diameter of greater than 6.0 mm and a maximum central cross-sectional area of less than 2 mm2 along the diameter, and the internal optical feature positively contributes to the total dioptric power of the intraocular lens. A method of forming the IOL may include: providing a foldable IOL having an optic portion comprising an optical, polymeric lens material and having an anterior surface and posterior surface and an optical axis intersecting the surfaces; and forming at least one laser-modified layer disposed between the anterior surface and the posterior surface with light pulses from a laser by scanning the light pulses along regions of the optical, polymeric material to cause changes in the refractive index of the polymeric lens material; wherein the laser-modified layer forms the internal optical feature that positively contributes to the total dioptric power of the IOL. A method of inserting the IOL into an eye may include folding the IOL, making an incision of less than 3.0 mm length, and inserting the folded IOL through the incision.
Methods are disclosed for delivering a composition comprising an adeno-associated virus (AAV) to one or more kidney cell types in a subject with or without immunity against AAV, including locally delivering to the kidney of the subject an adeno-associated virus (AAV) comprising a genome and an AAV capsid protein via renal pelvic injection, wherein the renal pelvic injection comprises direct renal pelvic injection or retrograde transureteral renal pelvic injection. Methods are also disclosed for treating a kidney disorder in a subject with or without immunity against AAV, comprising locally delivering to the kidney of the subject via renal pelvic injection, including direct renal pelvic injection and retrograde transureteral renal pelvic injection, an adeno-associated virus (AAV) comprising a genome and an AAV capsid protein, wherein the genome encodes a therapeutic agent that treats the kidney disorder in the subject. The AAV can be AAVKP1, AAVKP2, AAVKP3, AAVDJ, AAV2G9, AAV2.7m8, AAV3, AAVLK03, or AAVShH10.
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
C08L 67/04 - Polyesters derived from hydroxy carboxylic acids, e.g. lactones
Disclosed are halo substituted derivative compounds of sobetirome with improved pharmacological characteristics relative to sobetirome, pharmaceutical compositions that include those compounds and methods of treating diseases such as neurodegenerative disorders using those pharmaceutical compositions.
C07C 43/315 - Compounds having groups containing oxygen atoms singly bound to carbon atoms not being acetal carbon atoms
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07C 39/07 - Alkylated phenols containing only methyl groups as alkyl groups, e.g. cresols, xylenols
C07C 59/115 - Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups containing halogen
C07C 65/34 - Compounds having carboxyl groups bound to carbon atoms of six-membered aromatic rings and containing any of the groups OH, O-metal, —CHO, keto, ether, groups, groups, or groups containing keto groups polycyclic
C07C 235/20 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
C07F 7/08 - Compounds having one or more C—Si linkages
7.
SYSTEMS AND METHODS FOR PHASE-STABILIZED COMPLEX DECORRELATION ANGIOGRAPHY
Disclosed are methods and systems for phase-stabilized complex decorrelation (PSCD) optical coherence tomography (OCT) angiography (OCTA). In embodiments, a PSCD OCT A method includes performing phase stabilization on a complex-valued OCT data set to generate a phase-stabilized OCT dataset. The method further includes performing a complex decorrelation on the phase-stabilized OCT dataset to generate an OCTA dataset. One or more OCTA images may be generated based on the OCTA dataset. Other embodiments may be described and claimed.
A61B 3/10 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions
A61B 3/12 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
8.
INHIBITION OF CONTACT PATHWAY ACTIVATION FOR THE TREATMENT OF NEUROINFLAMMATION
The United States Government as represented by the Department of Veterans Affairs (USA)
Inventor
Mccarty, Owen
Tucker, Erik
Verbout, Norah
Offner, Halina
Kohs, Tia
Abstract
Methods of treating neuroinflammation in a subject by administering to the subject an agent that inhibits activation of coagulation factor XI (FXI), inhibits the activity of activated FXI (FXIa), or reduces expression of FXI are described. The agent that inhibits activation of FXI can be a monoclonal antibody specific for FXI, such as a monoclonal antibody having the complementarity determining region (CDR) sequences of anti-FXI antibody 14E11. Small molecule inhibitors and antisense compounds directed to FXI or FXIa are also contemplated as agents that inhibit activity of FXIa or reduce expression of FXI. The neuroinflammation in the subject can be associated with any one of a number of different diseases or disorders, such as an autoimmune disease of the central nervous system (CNS) or a neurodegenerative disease.
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Provided are substituted 8-methylquinazolin-4(3H)-one compounds useful as PARP inhibitors for the treatment of cancer and asthma, as well as pharmaceutical compositions comprising them and methods for their synthesis.
C07D 239/90 - Oxygen atoms with acyclic radicals attached in position 2 or 3
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
in vivoin vivo are provided. Systems and methods described herein include cells genetically modified to achieve at least two of: expression of a recombinant receptor, modulated expression of a trafficking signal, or modulated expression of a retention signal. The genetic constructs can be used to facilitate localized action of cellular therapies.
The present disclosure relates generally to dis-arming immune cell product sensitivity to androgens. Provided herein are methods, systems, and compositions for disarming androgen receptor (AR) activity in immune cells, for instance in the context of CAR-T cell therapy, allogenic T cell therapy, DC vaccines, macrophage therapy, myeloid/macrophage antigen receptor therapy, NK cell therapy, and so forth. Different methods for reducing AR function are described.
THE UNITED STATES GOVERNMENT AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (USA)
YEDA RESEARCH AND DEVELOPMENT CO. LTD. (Israel)
Inventor
Vandenbark, Arthur, A.
Kulkarni, Rajan
Meza-Romero, Roberto
Pellegrino, Bianca
Shachar, Idit
Abstract
Methods of treating a subject with cancer with a recombinant polypeptide including an antigenic peptide covalently linked to a DRα1 domain or portion thereof comprising a glutamine residue at a position corresponding to amino acid 45 of SEQ ID NO: 1 or SEQ ID NO: 2 are provided. In some examples, the subject is resistant to immune checkpoint blockade treatment and/or has a tumor that does not express a BRAF mutation.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present disclosure provides recombinant adenovirus-associated viral vectors for the delivery of CCR5 binding agents with increased effector function and circulation half-life that are useful for treating and preventing HIV and methods of use thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
The present disclosure provides CCR5 binding agents with increased effector function and circulation half-life that are useful for preventing or treating HIV.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
Disclosed herein are therapeutic constructs including a delivery particle, at least one anti-cancer agent (e.g., a mitotic kinase inhibitor), and at least one immune checkpoint inhibitor. Also disclosed are therapeutic constructs including a mitotic kinase inhibitor, an immune checkpoint inhibitor, and a chemical linker. These therapeutic constructs cause cancer death by both therapeutic and immune effects and promote targeted delivery of more therapeutics to the surviving cancer cells in a positive feed-back loop. They enhance therapeutic index of free drugs and can be used intratumorally or systemically. This strategy can treat broad cancer types and is particular useful for cancer without obvious receptors for cancer-targeted delivery of otherwise toxic therapeutics.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Disclosed are adeno-associated viral vectors and plasmids encoding the same. Also disclosed are methods of using adeno-associated viral vectors to deliver a protein of interest to the subject. The disclosed vectors have phenotypes including but not limited to increased retention in the blood of a subject, avoidance of the liver, and transduction of the brain and other tissues.
Provided herein are libraries of nerve-specific fluorescent contrast agents of substituted 8-methyl-phenoxazine compounds of Formula (I) with excitation and emission profile comparable to US FDA approved methylene blue (MB) and indocyanine green (ICG), respectively, allowing for real-time intraoperative imaging using clinical-grade surgical systems. Also provided 700 nm lead candidates with substantially improved water-solubility, fully negating the need for formulation development with the added advantage of improved safety profiles for patient use in the clinic as well as decreased overall cost of clinical translation.
Provided herein are libraries of nerve-specific fluorescent contrast agents of substituted 8-methyl-phenoxazine compounds of Formula (I) with excitation and emission profile comparable to US FDA approved methylene blue (MB) and indocyanine green (ICG), respectively, allowing for real-time intraoperative imaging using clinical-grade surgical systems. Also provided 700 nm lead candidates with substantially improved water-solubility, fully negating the need for formulation development with the added advantage of improved safety profiles for patient use in the clinic as well as decreased overall cost of clinical translation.
Methods are disclosed for delivering a composition comprising an adeno-associated virus (AAV) to one or more kidney cell types in a subject, comprising locally delivering to the kidney of the subject an adeno-associated virus (AAV) comprising a genome and an AAVKP1, AAVKP2, AAVKP3, AAVDJ, AAV2G9, or AAV2.7m8 capsid protein. Methods are also disclosed for treating a kidney disorder in a subject, comprising locally delivering to the kidney of the subject an adeno-associated virus (AAV) comprising a genome and an AAVKP1, AAVKP2, AAVKP3, AAVDJ, AAV2G9, or AAV2.7m8 capsid protein, wherein the genome encodes a therapeutic agent that treats the kidney disorder in the subject.
The present disclosure is concerned with substituted phenyl ethynyl pyrimidine compounds that are capable of inhibiting a viral infection and methods of treating alphavirus viral infections such as, for example, chikungunya, Eastern equine encephalitis (EEEV), Western equine encephalitis (WEEV), and Venezuelan equine encephalitis using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
C07D 239/26 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 513/12 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups , or in which the condensed system contains three hetero rings
C07F 9/6512 - Six-membered rings having the nitrogen atoms in positions 1 and 3
21.
SINGLE-DOMAIN ANTIBODIES THAT BIND THE CONSTANT REGION OF IMMUNOGLOBULINS
Single-domain antibodies that bind the constant (Fc) region of an immunoglobulin antibody are described. In embodiments, the single-domain antibodies covalently bind the Fc region of IgG. The single-domain antibodies can include a crosslinker for covalent attachment to a primary antibody and can be conjugated to a detectable label for use in techniques such as oligo barcoding, mass spectrometry, various imaging/omics platforms, liquid biopsy, and therapeutics.
Disclosed herein are peptides useful for targeting the retina, and may be useful for targeting specific cells in the retina. The peptides may have a Formula I or V:
Disclosed herein are peptides useful for targeting the retina, and may be useful for targeting specific cells in the retina. The peptides may have a Formula I or V:
R1—X1—X2—(X3)n—X4—X5—X6—X7—R2 Formula I
Disclosed herein are peptides useful for targeting the retina, and may be useful for targeting specific cells in the retina. The peptides may have a Formula I or V:
R1—X1—X2—(X3)n—X4—X5—X6—X7—R2 Formula I
R1-Asn-Val-Ser-Ala-Tyr-Pro-Thr-R2 Formula V.
Disclosed herein are peptides useful for targeting the retina, and may be useful for targeting specific cells in the retina. The peptides may have a Formula I or V:
R1—X1—X2—(X3)n—X4—X5—X6—X7—R2 Formula I
R1-Asn-Val-Ser-Ala-Tyr-Pro-Thr-R2 Formula V.
Also disclosed are conjugates and compositions comprising the peptides. The compositions may comprise a desired agent to be delivered to the retina, such as a therapeutic agent and/or an imaging agent. Methods for administering the peptide, conjugates, and/or composition to a subject also are disclosed.
The present invention concerns the use of a COX2 inhibitor selected from the group of indomethacin, meloxicam, tenoxicam, lornoxicam, diclofenac, tolfenamic acid, etoricoxib, parecoxib, and rofecoxib, and an immune checkpoint inhibitor, such as those selected from the group of atezolizumab, avelumab, durvalumab, envafolimab, cosibelimab, socazolimab, MEDI4736, STI-3031, and LY3300054, in the treatment of solid tumors.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present disclosure is concerned with substituted phenyl ethynyl pyrimidine compounds that are capable of inhibiting a viral infection and methods of treating alphavirus viral infections such as, for example, chikungunya, Eastern equine encephalitis (EEEV), Western equine encephalitis (WEEV). and Venezuelan equine encephalitis using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
C07D 239/26 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
25.
PROTEIN / POLYPEPTIDE SEQUENCING BY EXPANSION (PROSE)
Described herein are methods and systems useful to analyze proteins/polypeptides, including sequentially sequencing individual polypeptides, as well as compounds useful in carrying out such methods. Such compounds include those depicted in Formulas (I)-(XX). In embodiments, the methods involve expanding the distance between each amino acid of a polypeptide chain by transferring individual amino acids, in order, from a donor polypeptide to a polymer (e.g., a nucleic acid backbone) to form a hybrid polymer (a PROSE construct), then sequencing the individual amino acids along the PROSE construct. Such sequencing may involve nanopore-type sequencing, SMRT-sequencing, and the like.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
G01N 31/00 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroupsApparatus specially adapted for such methods
26.
METHODS FOR SELECTING MELANOMA PATIENTS FOR THERAPY AND METHODS OF REDUCING OR PREVENTING MELANOMA METASTASIS
The present disclosure provides the use of inhibitor(s) of an activity of HMG-CoA reductase (HMGCR) (a statin) to reduce and/or prevent future metastasis and prolong survival inpatients diagnosed with melanoma, for instance determined to be at high-risk of melanoma progression, such as melanoma metastasis. Also disclosed are methods for treating patients with a statin. Optionally, described methods involve measurement of a gene expression profile signature in the primary melanoma.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
A61K 31/366 - Lactones having six-membered rings, e.g. delta-lactones
A61K 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
A61K 31/455 - Nicotinic acid, i.e. niacinDerivatives thereof, e.g. esters, amides
Various embodiments herein provide methods to obtain corneoscleral surface profiles from optical coherence tomography (OCT) data and/or another three-dimensional (3D) volumetric scan of the eye. The OCT data may be obtained using radial scans. The limbal junction may be estimated from the radial profiles of the central moments of OCT axial scans. The external topographic limbus may be located using curve fitting of a scleral topography map and/or corneal topography map. Elevation profiles and topographic maps of the anterior eye, referenced to the best-fit topographic limbal circle and its associated plane and central axis, are constructed. The reference coordinate allows the generation of maps and radial profiles for surface elevation, axial radius, and tangential radius. Using ellipsoidal fitting, the corneal height, corneal principal meridians and associated radii of curvature, and scleral principal meridians and associated radii of curvature, are calculated.
The present disclosure relates to methods and systems involved with spatial encoding/decoding of features. Provided orthogonal cleavage-ligation sequencing (OCLS) systems encode two or more orthogonal recognition sites for restriction enzymes, such as Type IIS enzymes, for decoding of visual barcodes. Decoding employs specific orthogonal ligation of differentially-labeled probes, which enables visual distinguishing of the barcodes at each feature. This process can be repeated over cycles and in parallel.
C12Q 1/6837 - Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C40B 20/04 - Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
The present invention concerns phthalazinone-based compounds of that inhibit the PARP-1 protein, the compounds having Formula (I):
The present invention concerns phthalazinone-based compounds of that inhibit the PARP-1 protein, the compounds having Formula (I):
The use of sobetirome or a prodrug or derivative thereof, including Sob-AM2, for treating a disease, disorder, or condition associated with or suspected of being associated with dysmyelination, such as Pitt-Hopkins Syndrome, is disclosed.
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/4453 - Non-condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
A61K 31/46 - 8-Azabicyclo [3.2.1] octaneDerivatives thereof, e.g. atropine, cocaine
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Describe herein are nucleic acid oligonucleotides (oligos) including Hairpin Tag nucleic acid molecules and DNA/RNA Hybrid Hairpin Tag nucleic acid molecules, and capture oligo (CO) nucleic acid molecules and DNA/RNA chimeric CO nucleic acid molecules; spatially encoding capture arrays; use of the oligos in coding and decoding features; and use of the oligos and/or arrays and other provided comments, including in methods and workflows for spatial encoding and quantification of targets, such as biomarkers in biological samples.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
C40B 70/00 - Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or barcodes
B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
32.
METHODS FOR DIAGNOSIS AND TREATMENT OF INFERTILITY
In one aspect, the present invention relates to a method of identifying an infertile or a hypofertile subject, wherein the method comprises comparing the sperm TFAM level from the spermatozoa of the subject with that of a reference TFAM level, wherein the lower level TFAM from the spermatozoa of the subject relative to the reference indicates that the subject is infertile or hypofertile.
A61K 35/52 - SpermProstateSeminal fluidLeydig cells of testes
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61P 15/08 - Drugs for genital or sexual disordersContraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
G01N 27/623 - Ion mobility spectrometry combined with mass spectrometry
Peptide sequencing methods are described, in which the non-attached termini of surface end-immobilized peptides are functionalized with a universal docking strand (DS) DNA oligonucleotide. A library of signal molecules (such as fluorophores), each of which is conjugated to an imaging strand (IS) oligo complementary to the DS oligo, is used for characterizing each sequential terminal amino acid of the peptide. Computer assisted analysis is used to identify each amino acid, based on differences in the measured signal that are caused by proximity of the signal molecule(s) to each terminal amino acid.
The Board of Trustees of the Leland Stanford Junior University (USA)
Inventor
Malhotra, Sanjay
Pandrala, Mallesh
Tailor, Dhanir
Bruyneel, Arne A.N.
Mercola, Mark
Hnatiuk Hnatiuk, Anna P.
Abstract
Provided herein are compounds, pharmaceutical formulations, and methods for treatment of cancer, particularly including chronic myeloid leukemias, and neurodegenerative disorders in a subject.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
C07D 233/90 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
35.
4-AMINOQUINOLINES FOR TREATMENT OF MULTIDRUG RESISTANT MALARIA
United States Government as represented by the Department of Veterans Affairs (USA)
Oregon Health & Science University (USA)
Inventor
Handford, Mason J.
Riscoe, Michael
Abstract
The present invention concerns substituted N-(4-(piperidin-4-yl)phenyl)quinolin-4-amine and N-(4-(piperazin-1-yl)phenyl)quinolin-4-amine compounds having the general Formula (I), below, and useful in the treatment of malaria, including Multidrug Resistant Malaria. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
The present invention concerns substituted N-(4-(piperidin-4-yl)phenyl)quinolin-4-amine and N-(4-(piperazin-1-yl)phenyl)quinolin-4-amine compounds having the general Formula (I), below, and useful in the treatment of malaria, including Multidrug Resistant Malaria. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
The United States Government as Represented by the Department of Veterans Affairs (USA)
Inventor
Riscoe, Michael K.
Nilsen, Aaron
Jin, Haihong
Pou, Sovitj
Winter, Rolf W.
Dodean, Rozalia Ana
Liebman, Katherine M.
Abstract
Described herein are new synthetic routes for production of Endochin-Like Quinolone (ELQ) compounds. Synthetic routes to 3-substituted 4(1H)-quinolones are presented that are amenable to industrial scale preparation. One herein presented approach is relatively short, does not require palladium, and involves no chromatographic separation. A second herein presented approach is similarly relatively short, does not require palladium, involves no chromatographic separation, and also avoids high vacuum distillation. Additionally, both approaches require no protecting group chemistry because the insoluble 4(1H)-quinolone is not formed until the final reaction step.
The present disclosure relates to molecular barcodes comprising a set of one or more identimers. Methods of using the molecular barcodes, such as to classify a material, are disclosed. Methods of making the molecular barcodes and systems for using the molecular barcodes are disclosed herein.
Board of Regents, The University of Texas System (USA)
Inventor
Moukha-Chafiq, Omar
Pathak, Ashish Kumar
Karyakarte, Shuklendu D.
Bratton, Larry D.
Augelli-Szafran, Corinne E.
Diamond, Michael
Shi, Pei Yong
Hirsch, Alec Jay
Smith, Jessica Lee
Streblow, Daniel
Haese, Nicole
Ying, Baoling
Abstract
The present disclosure is concerned with 6-aza-nucleoside prodrugs that are capable of inhibiting a viral infection and methods of treating viral infections such as, for example, human immunodeficiency virus (HIV), human papillomavirus (HPV), chicken pox, infectious mononucleosis, mumps, measles, rubella, shingles, ebola, viral gastroenteritis, viral hepatitis, viral meningitis, human metapneumovirus, human parainfluenza virus type 1, parainfluenza virus type 2, parainfluenza virus type 3, respiratory syncytial virus, viral pneumonia, yellow fever virus, tick-borne encephalitis virus, Chikungunya virus (CHIKV), Venezuelan equine encephalitis (VEEV), Eastern equine encephalitis (EEEV), Western equine encephalitis (WEEV), dengue (DENV), influenza, West Nile virus (WNV), zika (ZIKV), Middle East Respiratory Syndromes (MERS), Severe Acute Respiratory Syndrome (SARS), and coronavirus disease 2019 (COVID-19), using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
The present disclosure relates to pyridazin-3(2H)-one and pyridin-2(1H)-one core compounds, related compounds, and their use in treating a disease or condition responsive to inhibition of at least one PARP protein. The compounds and methods may be used in treating a disease or condition responsive to inhibition of PARP7 and optionally one or more additional PARP proteins.
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
Stents useable for treating venous stenosis are disclosed. In embodiments, a stent is configured to be auxetic, expanding axially as it is expanded radially, to prevent the imposition of tension on portions of a blood vessel adjacent to the stented portion of the blood vessel, and thereby prevent a narrowing of the adjacent portions and improving luminal gain. The stent may include one or more cross members that are deformable axially, to allow the axial length of the stent to be adjusted while maintaining a constant diameter, and further to allow the stent to be curved to conform to vessel curvature.
A61F 2/915 - Stents in a form characterised by wire-like elementsStents in a form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheets or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
42.
IMMUNOGENIC CONSTRUCTS, COMPOSITIONS, AND METHODS FOR INDUCING IMMUNE RESPONSE
Disclosed are immunogenic constructs including: a nanoparticle; a cationic polymer electrostatically bound to an exterior surface of the nanoparticle and a stabilizer bound to the cationic polymer or the exterior surface of the nanoparticle; and an antigen or antigen producing agent. Optionally, the constructs may include adjuvant and/or one or more functional oligonucleotide(s) (e.g., siRNA or pDNA). Also disclosed are methods of using the provided immunogenic constructs for co-delivering an adjuvant, antigen, and optionally siRNA to a cell, inducing immune response in a subject, and treating or preventing an infectious disease in a subject.
A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
11222 is a ring moiety selected from the group of imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, phenyl, and pyridinyl, each optionally substituted; for use as inhibitors against native BCR-ABL kinase protein and clinically important BCR-ABL mutations such as T315I, F317L, E255K and Y253F for the treatment of diseases that include chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML).
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
The present technology relates to compounds of any one of Formula I, II, IIa, III, IV, and/or V as described herein and their tautomers and/or pharmaceutically acceptable salts, compositions, and methods of uses thereof.
C07C 235/42 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
A61P 25/00 - Drugs for disorders of the nervous system
C07C 235/38 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
C07C 235/56 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
C07D 203/04 - Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
C07D 211/14 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
C07D 231/14 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
C07D 261/18 - Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
C07D 295/135 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
C07D 295/185 - Radicals derived from carboxylic acids from aliphatic carboxylic acids
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
45.
SIGNAL ATTENUATION-COMPENSATED AND PROJECTION RESOLVED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY (SACPR-OCTA)
Disclosed are methods and systems for signal attenuation-compensated projection-resolved (sacPR) optical coherence tomography angiography (OCTA). The sacPR OCTA may be free of segmentation and vascular contrast enhancement. In some embodiments, projection artifacts may be suppressed with signal compensation including flow and large vessel shadow compensation for projection removal and wavelet-based compensation for noise suppression.
Provided herein are novel compounds of Formula (I):
Provided herein are novel compounds of Formula (I):
Provided herein are novel compounds of Formula (I):
wherein R1 is selected from the group of C1-C20 alkyl, —CH2—CH2—CH2—NH—C(=O)—C=C, and —CH2—CH2—CH2—N(CH3)—C (=O)—C=C; along with compositions comprising them and uses, including as dental adhesive compositions.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61K 31/4741 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
The Board of Trustees of the Leland Stanford Junior University (USA)
Inventor
Malhotra, Sanjay V.
Tailor, Dhanir
Dheeraj, Arpit
Abstract
Provided herein are novel azopodophyllotoxin analog compounds, pharmaceutical compositions comprising them, and their use as inhibitors of Y box protein 1 (YB1 or YBX1) in treatments for conditions including gynecological, breast, bladder, kidney, head and neck, neuronal, and prostate cancers, lymphomas, and leukemias. Methods of their use in sensitizing resistant cancers to treatment with anticancer agents and radiation are also provided.
A61K 31/4355 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
Embodiments include a delivery device for an auxetic device. The delivery device is comprised of an outer constraining device and a longitudinal controlling device disposed concentrically within the outer constraining device and offset to form a chamber for receiving the auxetic device. A mechanism coupled to the outer constraining device and the longitudinal controlling device allows the chamber size to adjust longitudinally as the auxetic device is deployed. Other embodiments may be described and/or claimed.
A61F 2/966 - Instruments specially adapted for placement or removal of stents or stent-grafts having an outer sleeve with relative longitudinal movement between outer sleeve and prosthesis, e.g. using a push rod
A61F 2/95 - Instruments specially adapted for placement or removal of stents or stent-grafts
The present invention concerns a novel enantiomer of 9-(3-fluorophenyl)-5-(2- hydroxyethyl)-6,9-dihydro-[l,3]dioxolo[4,5-g]furo[3,4-b]quinolin-8(5H)-one (SU056), as well as pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising it, and its uses in medical treatments, particularly including cancer treatments.
A61K 31/4741 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
Methods and systems are provided for trans-cervical delivery of agents for various purposes, including contraception and tubal patency evaluation. The trans-cervical delivery system comprises at least one port; a tubular shaft coupled to the port, the tubular shaft including at least one hollow channel traversing an interior length of the tubular shaft; and an agent delivery end coupled to the tubular shaft, the agent delivery end including at least one flexible catheter and a plug. The trans-cervical delivery system of the present disclosure integrates a pre-formed wire frame into the agent delivery end that enables self-positioning of the catheter and assists in gaining precise access to the cornual regions of a uterus by an operator. In one example, the trans-cervical delivery system may be utilized for selective delivery of a foam agent to fallopian tubes non-surgically.
A61F 6/22 - Vas deferens occludersFallopian occluders implantable in tubes
A61B 17/12 - Surgical instruments, devices or methods for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels or umbilical cord
A61B 17/42 - Gynaecological or obstetrical instruments or methods
A61M 25/04 - Holding devices, e.g. on the body in the body, e.g. expansible
Disclosed is a handheld laser probe for laser thermal conjunctivoplasty, the handheld laser comprising: a forceps; and a line focused laser light source coupled to the forceps, wherein the forceps are configured to grasp a conjunctival fold and hold the fold in a light beam of the line focused laser, and wherein the line focused laser beam is configured to uniformly heat the conjunctival fold held in the forceps. Disclosed are systems for laser thermal conjunctivoplasty including the handheld laser. Disclosed are methods of conjunctivoplasty using the handheld laser probe.
The present disclosure relates to a gastrointestinal delivery device of a chitosan dressing, where the delivery device is capable of stop bleeding, in particular in connection with TURP procedures. The delivery device may be used in all gastrointestinal bleeding applications and can be used with a biocompatible, foldable, thin profile, chitosan dressing. Various aspects of the device and its uses are provided herein.
The present disclosure relates to compositions, systems, and methods for treating cancer. In particular, the present disclosure relates to compositions, systems, and methods for characterizing and treating prostate cancer (e.g., castration-resistant prostate cancer).
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
58.
VOLUME-BASED LAYER-INDEPENDENT FRAMEWORK FOR DETECTION OF RETINAL PATHOLOGY
Disclosed herein is a method for detecting retinal pathologies in three dimensions using structural and angiographic OCT. The method in accordance with the present disclosure may operate by detecting deviations in reflectance and perfusion from a depth-normalized standard retina created by merging and averaging scans from healthy subjects. In one example, the deviations from the standard retina highlight key pathologic features, while depth-normalization obviates the need to segment retinal layers. Additionally, a composite pathology index is disclosed herein that measures average deviation from the standard retina. The present method is amenable to automation and may be implemented in an integrated system and/or provided in the form of software encoded on a computer-readable medium.
A library of mutant adeno-associated virus (AAV) 9 capsid proteins and compositions thereof are described. The mutant AAV9 capsid proteins can be selected to target expression in the liver, lungs, skeletal muscle, pancreas, kidney, brain, heart, intestine, spleen, and/or testis; detarget the liver; improve vector yield; and/or prolong the half-life. Methods of using the mutant AAV9 capsids for expression of a transgene in a subject are also provided.
THE UNITED STATES GOVERNMENT AS REPRESENTED BY THE DEPT OF VETERANS AFFAIRS (USA)
Inventor
Riscoe, Michael, K.
Nilsen, Aaron
Doggett, J., Stone
Alday, Holland
Abstract
Provided herein are Endochin-Like Quinolone (ELQ) compounds of Formula (I): or a pharmaceutically acceptable salt thereof, along with pharmaceutical compositions comprising them and methods for their use in treating or preventing parasitic diseases, including malaria, toxoplasmosis, and babesiosis.
C07D 215/22 - Oxygen atoms attached in position 2 or 4
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
Provided is an ex vivo system allowing for assessment of tumor and other cell responses to pluralities of agents or agent combinations using a microdose delivery microdevice implanted into an ex vivo tissue sample. The microdevice permits localized intra-tissue sample agent delivery and provides the ability to predict the drug efficacy within days after application. Systems for maintaining tissue samples ex vivo over hours to weeks are provided, which can be used to house tissue samples during exposure of the tissue to microdoses of agents applied using the delivery microdevices. Also provided are biomarkers (galectin and/or neuropilin) useful in evaluating the efficacy of agents.
The United States Govenment Department of Veterans Affairs (USA)
Inventor
Neuwelt, Edward A.
Abstract
Described herein is a method for eliminating or reducing ototoxicity in patients receiving a platinum based chemotherapeutic. In particular, are methods of reducing ototoxicity in a pediatric patient. The methods described herein include administering an effective amount of sodium thiosulfate to a patient in need thereof to reduce ototoxicity.
Methods and systems for identifying levels of an ophthalmic disease are described. An example method includes generating, by a convolutional neural network (CNN) and using a 3D image of a retina, a vector. The method further includes generating, by a first model and using the vector, a first likelihood that the retina exhibits a first level of an disease and generating, by a second model and using the vector, a second likelihood that the retina exhibits a second level of the disease. The method further includes determining whether the retina exhibits an absence of the ophthalmic disease, the first level of the disease, or the second level of the disease based on the first likelihood and the second likelihood. Further, an indication of whether the retina exhibits the absence of the ophthalmic disease, the first level of the ophthalmic disease, or the second level of the ophthalmic disease is output.
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
A61B 3/10 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions
A61B 3/12 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
64.
SMALL MOLECULES PROMOTING SYMPATHETIC NERVE REGENERATION
The present invention concerns novel compounds, pharmaceutical compositions, and methods for promoting nerve regeneration, particularly including sympathetic nerve regeneration in the heart following a myocardial infarction and damage to the central nervous system, such as after a cerebrovascular accident, through inhibitory extracellular matrix that includes chondroitin sulfate roteoglycans (CSPG).
C07C 233/55 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton
C07C 229/56 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho- position
C07C 205/59 - Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
65.
STABILIZED HYDROPHOBIC NANOPARTICLES FOR ULTRASOUND IMAGING
Disclosed are nanoparticle-based ultrasound contrast agents that comprise a sub-100 nanometer nanoparticle core, a hydrophobic layer, and a stabilization layer, and methods of producing such ultrasound contrast agents. The stabilization layer comprises molecules that are spaced apart on the stabilization layer to provide bubble nucleation sites that initiate cavitation of the bubbles in response to acoustic intensity delivered by ultrasound equipment.
The present disclosure relates to a gastrointestinal delivery device of a dressing, where the delivery device is capable of fitting through a narrow channel before expanding and applying the dressing. The gastrointestinal delivery device may be used in all gastrointestinal bleeding applications and can be used with a biocompatible, foldable, thin profile, chitosan dressing. Various aspects of the device and its uses are provided herein.
Disclosed are clinical decompensation monitoring platforms and methods. An example platform includes a wearable device to acquire photoplethysmography (PPG) waveform data representing a person's heart rate variability (HRV). Also disclosed are methods for collecting and verifying the HRV data, scoring and selecting optimal segments of HRV data for further processing that entails detecting clinically significant changes in a high frequency (HF) component, and passively monitoring clinical decompensation for providing patient feedback with individualized coping mechanisms.
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
A61B 5/11 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb
Compounds are described having albumin binding groups, where said compounds can be complexed with therapeutic and/or diagnostic agents and further can include targeting functionality. When introduced into the circulatory system the compounds and complexes bind serum albumin, and thereby exhibit useful properties including enhanced circulatory half-life, improved uptake by target tissues, and improved target/nontarget ratios. These properties make the compounds and complexes useful in therapeutic and diagnostic methods.
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
Disclosed is a meal detection and meal size estimation machine learning technology. In some embodiments, the techniques entail applying to a trained multioutput neural network model a set of input features, the set of input features representing glucoregulatory management data, insulin on board, and time of day, the trained multioutput neural network model representing multiple fully connected layers and an output layer formed from first and second branches, the first branch providing a meal detection output and the second branch providing a carbohydrate estimation output; receiving from the meal detection output a meal detection indication; and receiving from the carbohydrate estimation output a meal size estimation.
A61M 5/168 - Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value
G16H 20/17 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
A61F 2/00 - Filters implantable into blood vesselsProstheses, i.e. artificial substitutes or replacements for parts of the bodyAppliances for connecting them with the bodyDevices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
70.
COMPOSITIONS AND METHODS FOR MODULATING ANTIGEN BINDING ACTIVITY
The present disclosure describes compositions, kits and methods for immunoglobulin blocking constructs that may be crosslinked to immunoglobulins to form blocked immunoglobulin complexes useful for selectively modulating the native binding activity of immunoglobulins and enhancing their utility as research tools and therapeutic treatments. Further, wherein a blocking construct for modulating binding activity of an antigen binding domain is disclosed.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
Disclosed herein are embodiments of a nanoparticle suitable for use in providing hyperthermia treatment. The nanoparticle may be a cobalt-doped iron oxide nanoparticle. Also disclosed are compositions comprising the nanoparticle. The composition may further comprise a polymer and/or a targeting moiety. Further disclosed and methods for making the nanoparticle and the composition, and embodiments of a method for using the nanoparticle or a composition thereof. The nanoparticle may be useful for treating cancer, and/or endometriosis.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
72.
Therapeutic constructs for co-delivery of mitotic kinase inhibitor and immune checkpoint inhibitor
Disclosed herein are therapeutic constructs including a delivery particle, at least one mitotic kinase inhibitor, and at least one immune checkpoint inhibitor. Also disclosed are therapeutic constructs including a mitotic kinase inhibitor, an immune checkpoint inhibitor, and a chemical linker. These therapeutic constructs cause cancer death by both therapeutic and immune effects and promote targeted delivery of more therapeutics to the surviving cancer cells in a positive feed-back loop. They enhance therapeutic index of free drugs and can be used intratumorally or systemically. This strategy can treat broad cancer types and is particular useful for cancer without obvious receptors for cancer-targeted delivery of otherwise toxic therapeutics.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 9/00 - Medicinal preparations characterised by special physical form
B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
73.
DENTIN MATRIX PROTEIN MATERIALS AND ASSOCIATED METHODS
The present disclosure describes compositions, kits and methods for promoting regeneration of dental tissue, particular dental pulp tissue. In some embodiments, a composition for promoting regeneration of dental tissue includes a dentin extracellular matrix material (dECM). In some embodiments, the dECM comprises dentin matrix proteins having an origin selected from human, ovine, porcine, and bovine.
Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the sequencing library includes whole genome nucleic acids from the plurality of single cells. In one embodiment, the method includes generating nucleosome-depleted nuclei by chemical treatment while maintaining integrity of the nuclei. Also provided herein are compositions, such as compositions that include chemically treated nucleosome-depleted isolated nuclei.
The present invention concerns small molecule inhibitors or modulators of Enolase 1 (ENO1) and/or Enolase 3 (ENO3) that are useful in the treatment of cancers such as triple negative breast cancer, pancreatic cancer, and leukemias, including those in hyperglycemic and hyperinsulinemic subjects.
Methods and systems for generating biomarker activation maps (BAMs) are described. An example method includes identifying a medical image depicting at least a portion of a subject; generating a BAM by inputting the medical image into a trained, U-shaped neural network (NN); and outputting the BAM overlaying the medical image, the BAM indicating at least one biomarker depicted in the medical image that is indicative of a disease.
A61B 3/10 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
77.
DIAGNOSTIC CLASSIFICATION OF CORNEAL DISEASES BASED ON ARTIFICIAL INTELLIGENCE
Disclosed are artificial intelligence (AI) based systems and methods for characterizing corneal shape abnormalities. The methods and systems of the present disclosure utilize AI models comprising neural networks for disease classification based on maps of corneal shape, thickness, and reflectance. These methods may be used to differentiate corneas having keratoconus from other conditions which may cause distortion of corneal shape, such as warpage of the cornea. The present system is amenable to automation and may be implemented in an integrated system or provided in the form of software encoded on a computer-readable medium.
A61B 3/107 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for determining the shape or measuring the curvature of the cornea
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
The present disclosure relates to phthalazinone compounds and related compounds and their use in treating a disease or condition responsive to inhibition of PARP7.
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
The present invention provides novel Zwitterionic cell-permeant and water-soluble rhodamine dye compounds, pharmaceutical composition comprising them, and methods for their use in quantitative imaging applications, particularly substituted 5,5-dimethyl-10-phenyl-3,5-dihydrodibenzo[b,e]siline and 9- phenyl-3H-xanthene compounds of Formula (I).
Diagnostic methods for identifying cancer bearing subjects appropriate for treatment with CPX-351 include genetic and ex vivo testing of cells from a candidate subject. Combination treatment with CPX-351 and FLT-3 inhibitors improve CPX-351 uptake and toxicity.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
84.
Method for Reducing Ototoxicity in Pediatric Patients Receiving Plantinum-Based Chemotherapy
The United States Government as represented by The Department of Veterans Affairs (USA)
Inventor
Neuwelt, Edward A.
Abstract
Described herein is a method for eliminating or reducing ototoxicity in patients receiving a platinum based chemotherapeutic. In particular, are methods of reducing ototoxicity in a pediatric patient. The methods described herein include administering an effective amount of sodium thiosulfate to a patient in need thereof to reduce ototoxicity.
Techniques are provided for operating a high-intensity ultrasound ablation catheter with improved positioning relative to a target tissue. The catheter position and orientation can be manipulated by an operator based on real-time signal processing and display of the tissue surface reflected wave. By maximizing the amplitude and minimizing the time delay of the tissue-reflected wave, the transducer and tissue surface are aligned to be parallel. The catheter can then be operated in a therapy mode to form a lesion, where the lesion is predicted to form in a direction perpendicular to the tissue surface in contact with the catheter.
Surgical clips and surgical applicators used in performing rapid tissue closure in either minimally invasive surgeries or traditional open procedures are provided. In one example approach, a surgical clip comprises opposing sides extending from a top portion and terminating at tips positioned below the top portion. The resting position of the clip is its closed position. Edges of the top portion and the opposing sides form opposing faces perpendicular to the opposing sides. The opposing faces are angled inwardly towards each other at a region of the faces adjacent to the top portion. Grooves are formed in each of the opposing sides. The grooves are configured to engage inwardly turned tracks of a clip applicator such that, when a force is applied to the clip, the opposing sides bend outwardly away from each other to place the clip in an intermediate open position.
A61B 17/122 - Clamps or clips, e.g. for the umbilical cord
A61B 17/128 - Surgical instruments, devices or methods for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels or umbilical cord for applying or removing clamps or clips
88.
Methods, Systems, and Apparatuses for Quantitative Analysis of Heterogeneous Biomarker Distribution
Methods, systems, and apparatuses for detecting and describing heterogeneity in a cell sample are disclosed herein. A plurality of fields of view (FOV) are generated for one or more areas of interest (AOI) within an image of the cell sample are generated. Hyperspectral or multispectral data from each FOV is organized into an image stack containing one or more z-layers, with each z-layer containing intensity data for a single marker at each pixel in the FOV. A cluster analysis is applied to the image stacks, wherein the clustering algorithm groups pixels having a similar ratio of detectable marker intensity across layers of the z-axis, thereby generating a plurality of clusters having similar expression patterns.
Described herein are systems and methods for sorting particles in fluids. Systems may comprise a microfluidic chamber, at least one array of electrodes arranged on the substrate, and a controller. The microfluidic chamber is configured to allow fluid to flow therethrough. The microfluidic chamber includes a substrate. The at least one array of electrodes is arranged on the substrate. The at least one array of electrodes is configured to apply dielectrophoretic (DEP) forces to the fluid flowing through the microfluidic chamber. A respective electrode of the at least one array of electrodes is configured to have a V-shape. The controller is configured to control the at least one array of electrodes.
Acute myeloid leukemia (AML) is a cancer of neoplastic myeloid-lineage cells. Conventional therapeutic approaches have had limited success with recently approved drug regimens offering transient improvements. Integration of genomic data, transcriptomic data, ex vivo drug sensitivity data, and clinical annotations for a large cohort of AML patient samples show that drug sensitivity is governed broadly by AML cell differentiation state. Platelet endothelial aggregation receptor 1 (PEAR1) was identified as a biomarker that can predict clinical outcome in AML patients < 45 years old. Methods of diagnosis, prognosis, and treatment are described.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61P 35/02 - Antineoplastic agents specific for leukemia
91.
CELL-FREE RNA BIOMARKERS FOR THE DETECTION OF CANCER OR PREDISPOSITION TO CANCER
Methods of detecting or treating cancer or predisposition to cancer are provided, the methods including analyzing a level of one or more cell-free RNA (cfRNA) biomarkers selected from AIDA, CAI, CENPE, CPOX, ELL2, EPB42, HBG1, HBG2, NEK2, NUSAP1, APOE, C3, CP, DHCR24, EGA, FGB, EGG, HRG, IFITM3, ATP IB 1, FPR3, SMC4, TXNDC16, ASPM, WRN, ZRANB2-AS2, BMX, CDC42BPA, KNL1, CACNA1A, ABCB7, HIST1H2BF, PSIP1, TMEM150C, ZC3H6, C9orfl6, CPQ, DYNC1I2, ECM1, and HIST1H2AH, or any combination thereof, in the biological sample; and performing a differential expression analysis comparing the level of each of the one or more cfRNA biomarkers to a corresponding control value (CV); in which differential expression shown by the differential expression analysis between the one or more cfRNA biomarkers and corresponding CVs indicates cancer or a predisposition for cancer in the subject.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
92.
CANCER THERAPEUTIC COMPOSITIONS AND METHODS TARGETING DNASE1L3
Methods for treating a subject with cancer, including administering to the subject an effective amount of an inhibitor of DNAse1L3 and an effective amount of radiation therapy are provided. In some examples, the methods involve enhancing or inducing response of tumor-associated immune cells in the subject, including administering to the subject an effective amount of radiation therapy, and administering to the subject an effective amount of an inhibitor of DNAse1L3, thereby enhancing or inducing the response of tumor-associated immune cells in the subject. In some examples, the tumor-associated immune cells comprise dendritic cells or macrophages.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
93.
METHODS AND SYSTEMS FOR INCREASING CAPTURE POTENTIAL OF A SPATIAL ARRAY
An IC spatial array for a captured ligand assay is described. Materials to prepare and methods to produce the IC spatial array are also provided. The IC spatial array includes a matrix substrate including capture probes anchored to the matrix substrate such that the capture probes have a barcode unique to the capture probe's spatial location within the matrix substrate and the capture probe has a free end for capturing analytes from a sample.
A transducer fixation apparatus is configured to position and secure to a skin surface of a patient a transducer to allow repeated or continuous monitoring of blood flow in a subsurface vessel. The transducer fixation apparatus includes a housing having a plurality of flexible attachment wings that attach and conform in shape to the skin surface using an adhesive material present on each of the wing undersides. In some embodiments the wings may be biased upward away from the skin surface to facilitate positioning of the fixation apparatus prior to skin attachment. Alternative embodiments include a detachable retainer clip to hold the wings away from the mounting surface during placement as well as an optional positioning wand to aid with placement. Other embodiments may include a separate flexible attachment wing configured to hold a gel pad for acoustic coupling to the skin surface, the separate flexible attachment wing intended to be joined to the housing of the transducer fixation apparatus prior to skin surface attachment.
A gas-driven, pressure-regulated ventilator (10, 210) provides support for spontaneous breathing and non-breathing patients. The ventilator provides short pressure cycled and constant flow ventilatory support that allows the patient to receive consistent and reliable ventilatory breaths. The ventilator is designed to allow a clinician to adjust Peak Inspiratory Pressure (PIP) and Positive End Expiratory Pressure (PEEP) values and the duration of inhalation and exhalation flows in a breath cycle to accommodate patient-specific ventilation needs.
Provided herein are novel compounds, compositions, that can used as clickable, photo-affinity labeling (PAL) probes methods for use in screening NAD+ binding proteins.
C07H 19/207 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine-adenine dinucleotide or nicotinamide-adenine dinucleotide
G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes
G01N 33/533 - Production of labelled immunochemicals with fluorescent label
C12Q 1/32 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving oxidoreductase involving dehydrogenase
A guide structure (10) is configured for placement on a patient's skin and holding a medical probe (61) for adjustable positioning over the patient's skin during vascular line placement. A preferred guide structure includes a U-shaped base (12) having two arms (14, 16) separated by an open space (18). A carriage (50) for a medical probe holder (60) is movable along carriage guide surfaces (40, 42) of the arms of the base and thereby forms a movable bridge spanning the open space. The medical probe holder carrying a medical probe is movable in a direction transverse to the arms of the base to set the medical probe to a desired distance into the open space. A carriage translation actuator (62) operatively associated with the carriage enables movement of the carriage and thereby adjusts the position of the medical probe over the surface of the patient's skin.
Disclosed herein are peptides useful for targeting the retina, and may be useful for targeting specific cells in the retina. The peptides may have a Formula I: R1123n45677-R2or a formula V: R1-Asn-Val-Ser-Ala-Tyr-Pro-Thr-R2. Also disclosed are conjugates and compositions comprising the peptides. The compositions may comprise a desired agent to be delivered to the retina, such as a therapeutic agent and/or an imaging agent. Methods for administering the peptide, conjugates, and/or composition to a subject also are disclosed.
A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
99.
METHODS FOR USING TRANSCRIPTION-DEPENDENT DIRECTED EVOLUTION OF AAV CAPSIDS
Disclosed are methods for performing transcription-dependent directed evolution (TRADE) and novel AAV capsids selected using such methods. This disclosure also provides novel AAV capsid mutants. TRADE technology was used to identify novel AAV vectors that mediate neuronal transduction in the brain following intravenous administration. Application of TRADE in vivo resulted in the identification of new AAV capsids that can transduce neurons more efficiently and more specifically than AAV9 in the brain following administration of the new AAV capsids. The disclosed methods may be used to identify AAV capsids that target various cell populations.
Foldable intraocular lens (IOL) having a total dioptric power and comprising an optic portion (12) having main anterior and posterior optical surfaces, and incorporating an internal optical feature (13) positioned between the main anterior and posterior optical surfaces are described. The optic portion has a diameter of greater than 6.0 mm and a maximum central cross-sectional area of less than 2 mm2 along the diameter, and the internal optical feature positively contributes to the total dioptric power of the intraocular lens. A method of forming the IOL may include: providing a foldable IOL having an optic portion comprising an optical, polymeric lens material and having an anterior surface and posterior surface and an optical axis intersecting the surfaces; and forming at least one laser-modified layer disposed between the anterior surface and the posterior surface with light pulses from a laser by scanning the light pulses along regions of the optical, polymeric material to cause changes in the refractive index of the polymeric lens material; wherein the laser- modified layer forms the internal optical feature that positively contributes to the total dioptric power of the IOL. A method of inserting the IOL into an eye may include folding the IOL, making an incision of less than 3.0 mm length, and inserting the folded IOL through the incision.
