Abstract

The present disclosure relates to use of Carboxypeptidase E (CPE) for treating or preventing onset or progression of a neurodegenerative disease.

IPC Classes  ?

• A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• 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

Abstract

The invention relates to treatments for fibrosis by administering a neutrophil elastase inhibitor, such as alvelestat. In particular, the invention relates to treatments for fibrosis in combination with another disease, such as organ rejection, for example bronchiolitis obliterans syndrome optionally associated with graft-versus-host- disease.

IPC Classes  ?

• A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection

Abstract

Methods for producing synthetic single-domain monoclonal antibody libraries using humanized llama nanobody framework sequences, libraries obtainable by the method, as well as antibodies selected from the libraries are described. In particular, synthetic single-domain monoclonal antibodies that specifically bind to the spike protein of SARS-CoV-2 and neutralize SARS-CoV-2 infection are described. Use of the disclosed antibodies for the detection, prophylaxis and treatment of SARS-CoV-2 infection is described.

IPC Classes  ?

• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses

Abstract

Various embodiments for systems and methods for automatically detecting ellipsoid zone loss in SD-OCT imaging are disclosed herein.

IPC Classes  ?

• G06T 7/00 - Image analysis

Abstract

Mixed lineage kinase (MLK) inhibitors are disclosed. The compounds inhibit kinase activity. The compounds may be used to treat diseases or conditions characterized at least in part by overexpression of one or more MLKs. The compounds have a structure according to formula I, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof.

IPC Classes  ?

• A61K 31/4427 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
• A61K 31/437 - 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 nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61P 35/00 - Antineoplastic agents
• 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 401/14 - 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 three or more hetero rings
• C07D 487/08 - Bridged systems

Abstract

Methods are disclosed for inhibiting a HIV infection in a subject. These methods include administering to the subject an effective amount of a recombinant gp120 protein comprising a deletion of HIV-1 Envelope residues 137-152 according to the HXBc2 numbering system, or a nucleic acid molecule encoding the recombinant gp120 protein, wherein the recombinant gp120 protein elicits an immune response to HIV-1. The methods also include administering to the subject an effective amount of a SAMT-247 microbicide.

IPC Classes  ?

• A61K 39/12 - Viral antigens
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 39/21 - Retroviridae, e.g. equine infectious anemia virus
• A61P 31/18 - Antivirals for RNA viruses for HIV
• C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses

Abstract

Small molecule compounds that selectively bind to non-canonical G-quadruplex (G4) structures, such as G4s in DNA found in various types of genes described herein, along with methods of using the compounds to reduce or inhibit protein (e.g., N-Myc protein) expression in cells, such as cancer cells. The compounds have a structure according to formulas described herein, or a stereoisomer, tautomer, or pharmaceutically effective salt or ester thereof.

IPC Classes  ?

• C07D 413/04 - 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 directly linked by a ring-member-to-ring- member bond
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Abstract

Single-domain shark variable new antigen receptor (VNAR) monoclonal antibodies that specifically bind programmed death-ligand 1 (PD-L1) are described. The PD-L1-specific VNAR antibodies are capable of binding PD-L1-expressing tumor cells from human, mouse and canine origin. Immune cells expressing chimeric antigen receptors (CARs) developed using the VNAR antibodies can be used to kill PD-L1-positive tumor cells, for example in animal models of liver cancer and breast cancer.

IPC Classes  ?

• 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 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61P 35/00 - Antineoplastic agents
• C12N 5/22 - Human cells
• C12N 15/13 - Immunoglobulins
• G01N 33/577 - Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies

Abstract

A scaffold containing two layers is provided for attaching retinal pigment epithelial (RPE) cells, photoreceptor progenitor (PRP) cells, or both. The scaffold includes a first layer containing poly(lactic-co-glycolic acid) (PLGA), and a second layer containing polycaprolactone (PCL) loops. Scaffolds containing mature RPE cells and PRP cells can be implanted into the eye of a subject to treat a retinal degenerative disease, retinal dysfunction, retinal degradation, retinal damage, or loss of retinal pigment epithelium.

IPC Classes  ?

• A61L 27/18 - Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• A61L 27/38 - Animal cells
• A61L 27/48 - Composite materials, i.e. layered or containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
• A61L 27/56 - Porous or cellular materials

Abstract

Methods are disclosed for producing macular, central or peripheral human retinal pigment epithelial (RPE) cells. These methods include: a) culturing stem cells, such as induced pluripotent stem cells (iPSCs), in a retinal induction medium to initiate differentiation of the cells into RPE progenitor cells; b) culturing the RPE progenitor cells in a retinal differentiation medium to further differentiate the RPE progenitor cells into committed RPE cells; c) culturing the committed RPE cells in a retinal medium to form immature RPE cells; and d) culturing the immature RPE cells in a RPE maturation medium including a retinoic acid receptor (RAR) antagonist and/or a canonical Wnt inhibitor, thereby producing macular, central or peripheral human RPE cells.

IPC Classes  ?

• C12N 5/079 - Neural cells
• A61K 35/30 - Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue

Abstract

This disclosure relates generally to lentiviral vectors useful for the treatment of a disease or condition, for example, Wiskott-Aldrich Syndrome (WAS) or Sickle Cell Disease (SCD).

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• C12N 15/86 - Viral vectors

Abstract

Recombinant chimeric bovine/human parainfluenza virus 3 (rB/HPIV3) vectors expressing a recombinant Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) protein as well as methods of their use and manufacture, are provided. The rB/HPIV3 vector comprises a genome comprising a heterologous gene encoding the recombinant SARS-CoV-2 S protein. Nucleic acid molecules comprising the sequence of the genome or antigenome of the disclosed rB/HPIV3 vectors are also provided. The disclosed rB/HPIV3 vectors can be used, for example, to induce an immune response to SARS-CoV-2 and HPIV3 in a subject.

IPC Classes  ?

• A61K 39/155 - Paramyxoviridae, e.g. parainfluenza virus
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus

Abstract

Methods are disclosed herein for modulating osteoclast fusion. In some embodiments, these methods include administering an effective amount of a Lupus autoantigen (La) protein, or an agent that modulates La protein expression or activity, to a subject in need thereof, thereby modulating osteoclast fusion in the subject. In some embodiments, the method increases osteoclast fusion and bone resorption. In other embodiments, the method decreases osteoclast fusion and bone resorption.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
• A61P 19/10 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
• A61P 35/04 - Antineoplastic agents specific for metastasis

Abstract

The present disclosure relates to a vaccine comprising an amphiphile having the formula S-[B]-[U]-H and at least one peptide antigen conjugate having the formula selected from [S]-[E1]-A-[E2]-[U]-H and H-[U]-[E1]-A-[E2]-[S], wherein the amphiphile and/or the at least one peptide antigen conjugate comprises a dendron amplifier. The vaccine is useful in treating or preventing a cancer, an autoimmune disease, an allergy, an infectious disease, a cardiovascular disease, or a neurodegenerative disease.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61K 39/35 - Allergens
• A61P 35/00 - Antineoplastic agents
• A61P 37/08 - Antiallergic agents

Abstract

Disclosed are isolated or purified T cell receptors (TCRs), wherein the TCRs have antigenic specificity for a CD22 amino acid sequence presented by a human leukocyte antigen (HLA) Class I molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants

Abstract

Single-domain antibodies against SARS-CoV-2 are provided. The single-domain antibodies have been shown to have neutralizing activity against SARS-CoV-2 and can be used as a diagnostic and/or therapeutic in patients with coronavirus infection, such as COVID-19; and in diseases and disorders related to, or resulting from, coronavirus infection.

IPC Classes  ?

• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses

Abstract

Disclosed are monoclonal antibodies, antigen binding fragments, and bi-specific antibodies that specifically bind a coronavirus spike protein, such as SARS-CoV-2. Also disclosed is the use of these antibodies for inhibiting a coronavirus infection, such as a SARS-CoV-2 infection. In addition, disclosed are methods for detecting a coronavirus, such as SARS-CoV-2, in a biological sample, using the disclosed antibodies.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 31/14 - Antivirals for RNA viruses
• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses

Abstract

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to scaffold molecules having anti-hRPN13 activity, proteolysis targeting chimeras (PROTACs) incorporating the same, methods of making same, pharmaceutical compositions comprising same, and methods of treating cancers involving aberrant hRpn13 activity and/or the presence of hRpn13-Pru/hRpn13Pru or variants thereof using the same.

IPC Classes  ?

• C07C 255/44 - Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms at least one of the singly-bound nitrogen atoms being acylated

Abstract

Provided herein are methods of treating a subject with cancer using a therapeutically effective amount of one or more one or more tumor-specific antibody-IR700 molecules. The methods can further include administering to the subject a therapeutically effective amount of(a) one or more CTLA4 antibody-IR700 molecules, one or more PD-L1 antibody-IR700 molecules, or combinations thereof, (b) one or more reducing agents, (c) one or more immunoactivators, or combinations of a, b, and c, for example, either simultaneously or substantially simultaneously with the tumor-specific antibody-IR700 molecules, or sequentially (for example, within about 0 to 24 hours). The method also includes irradiating the subject or cancer cells in the subject (for example, a tumor or cancer cells in the blood) at a wavelength of 660 to 740 nm at a dose of at least 1 J/cm2. The use of one or more reducing agents can reduce edema resulting from treatment.

IPC Classes  ?

• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention is related to the development of novel compounds and methods for the treatment and/or prevention of malaria. The compounds prevent the formation by the malaria parasite of the piasmodium surface anion channel (PSAC) on the surface of the host cell. The compounds and methods described herein are effective against infection by a wide variety of Plasmodia strains known as the causative agent of malaria.

IPC Classes  ?

• C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 33/06 - Antimalarials
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 417/14 - 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 three or more hetero rings

Abstract

A replication-competent adenovirus type 4 (Ad4) modified to express the SARS-CoV-2 spike protein is described. The genome of the recombinant Ad4 is modified to have a deletion of at least a portion of the adenovirus E3 region to accommodate insertion of the spike protein coding sequence. Administration of the recombinant Ad4 to the upper respiratory tract elicits mucosal immunity, which is important for protection against SARS-CoV-2 infection and for preventing transmission of the virus.

IPC Classes  ?

• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus

Abstract

Disclosed are compounds for treating or preventing a disease or disorder responsive to antagonism of a P2Y14R receptor agonist in a mammal in need thereof, for example, compounds of formulas (I) and (II), wherein R1-R8, X, Y, Z, X', Y', Z', and A are as defined herein, that are useful in treating an inflammatory such as asthma, cystic fibrosis, and sterile inflammation of the kidney.

IPC Classes  ?

• C07D 211/18 - 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 substituted hydrocarbon radicals attached to ring carbon atoms
• A61K 31/4192 - 1,2,3-Triazoles
• A61K 31/44 - Non-condensed pyridines; Hydrogenated derivatives thereof
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 209/02 - Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
• C07D 211/34 - 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 substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• C07D 211/70 - 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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07D 223/04 - Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07D 249/06 - 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
• C07D 255/02 - Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups not condensed with other rings
• C07D 261/08 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two 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 403/10 - 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

Abstract

In an embodiment, the invention provides an isolated population of exosomes comprising interleukin-27 (IL-27) or interleukin-35 (IL-35). In an embodiment, the invention also provides a method of preparing a population of exosomes comprising interleukin-27 (IL-27), the method comprising: (a) isolating CD19+ B2 cells or B1a cells; (b) activating the isolated cells with a LPS or a BCR agonist to provide activated cells; and (c) isolating exosomes secreted from the activated cells. In an embodiment, the invention also provides a method of preparing a population of exosomes comprising interleukin-35 (IL-35), the method comprising: (a) isolating CD138+ plasma cells; (b) activating the isolated cells with a LPS or a BCR agonist to provide activated cells; and (c) isolating exosomes secreted from the activated cells. Additional embodiments of the invention are as described.

IPC Classes  ?

• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C12N 5/0781 - B cells; Progenitors thereof
• A61K 38/20 - Interleukins
• A61P 37/02 - Immunomodulators

Abstract

Some embodiments of the disclosure include inventive compounds (e.g., compounds of Formula (I)) and compositions (e.g., pharmaceutical compositions) which inhibit IRAK and/or FLT3 and which can be used for treating, for example, certain diseases. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as hematopoietic cancers, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), etc.), Additional embodiments provide disease treatment using combinations of the inventive IRAK and/or FLT3 inhibiting compounds with other therapies, such as cancer therapies.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• A61P 35/00 - Antineoplastic agents
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or

Abstract

The disclosure provides a method of treating or preventing a bacterial infection in a subject comprising administering a therapeutically effective amount of a combination of a bacterial type IIA topoisomerase inhibitor, or a pharmaceutically acceptable salt thereof and a compound Formula I, or a pharmaceutically acceptable salt thereof, to the subject, where the compound of Formula I is (Formula (I)) where the variables, e.g. Y1, Y2, and R1-R4, are described herein. The bacterial type IIA topoisomerase inhibitor can be a quinolone antibiotic such as ciprofloxacin.

IPC Classes  ?

• A61K 31/4375 - 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 six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
• A61P 31/04 - Antibacterial agents

Abstract

Antisense oligonucleotides (ASOs) are provided which are capable of modulating splicing by preventing inclusion of an UNC13A cryptic exon into an UNC13A mature mRNA. Such ASOs may be used as a medicament, for example, to treat neurodegenerative disorders, particularly those associated with TDP-43 pathology.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• 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

Abstract

Disclosed is a class of knotted cyclic peptides. Related pharmaceutical compositions and methods of using the peptides and methods of synthesizing the peptides are also disclosed.

IPC Classes  ?

• C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61K 38/00 - Medicinal preparations containing peptides
• C12N 9/90 - Isomerases (5.)

Abstract

The invention is directed to methods of treating or preventing a Rhabdoviridae virus infection in a mammal comprising administering griffithsin, or a fragment or mutant thereof, to the mammal.

IPC Classes  ?

• A61K 38/00 - Medicinal preparations containing peptides
• A61K 38/16 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• A61P 31/12 - Antivirals
• A61P 31/18 - Antivirals for RNA viruses for HIV
• C07K 14/405 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from algae

Abstract

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 13 with aspartic acid. The TCRs may recognize G13D RAS presented by an HLA-DQ heterodimer. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 35/12 - Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells

Abstract

Provided is a method of treating cancer, particularly cancers associated with an overexpression of polo-like kinase (Plk1), comprising administering a compound of formula (I) or a pharmaceutically acceptable salt thereof in which ring A, X1, X2, X3, X4, X5, R2, R3, R4, n, bond a, and bond b are described herein. Exemplary compounds of formula (I) and pharmaceutically acceptable salts thereof, especially those that selectively inhibit the polo box domain of Plk1, also are provided.

IPC Classes  ?

• A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

The present disclosure provides a method of treating an autosomal dominant hypocalcemia type 1 (ADH1) with a therapeutically effective amount of a compound of formula (I), in particular CLTX-305, wherein the therapeutically effective amount of the compound increases a blood calcium concentration (cCa) to a range of about 7.5 mg/dL to about 10.5 mg/dL, such as about 8.5 mg/dL to about 10.5 mg/dL. Also provided herein is a dosing finding method for treating an autosomal dominant hypocalcemia type 1 (ADH1) with a therapeutically effective amount of a compound of formula (I) or CLTX-305 according to one or more dosing regimens.

IPC Classes  ?

• A61K 31/195 - Carboxylic acids, e.g. valproic acid having an amino group
• A61P 3/14 - Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis

Abstract

Disclosed are methods of obtaining a cell population enriched for T cells with a phenotype, the method comprising: (a) obtaining a bulk population of T cells from a tumor sample of a patient; (b) specifically selecting T cells with a phenotype comprising markers CD3+, CD39-, and CD69- from the bulk population; and (c) separating the cells selected in (b) from cells which lack the phenotype to obtain a cell population enriched for T cells with the phenotype. Related methods of treating or preventing cancer, methods of selecting a therapy for a cancer patient, and methods for predicting the clinical response to immunotherapy in a cancer patient are also disclosed. Isolated or purified cell population obtained according to the methods and related pharmaceutical compositions are also disclosed.

IPC Classes  ?

• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing

Abstract

Leucine zipper-bearing kinase (LZK) targeted degraders are disclosed. The compounds have a general formula Q-L-Z where Q is an LZK binding moiety, L is a linker, and Z is an E3-ligase binding moiety. The compounds inhibit LZK activity and/or degrade LZK. The compounds may be used to treat diseases or conditions characterized at least in part by LZK overexpression.

IPC Classes  ?

• C07D 401/14 - 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 three or more hetero rings
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
• A61P 35/00 - Antineoplastic agents

Abstract

Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53R273C or human p53Y220C. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C07K 14/725 - T-cell receptors

Abstract

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with aspartic acid. The TCRs may recognize G12D RAS presented by an HLA-DR heterodimer. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors

Abstract

The present disclosure provides embodiments of devices that are useful in the structural remodeling of various parts of the cardiovascular system, most notably the heart. Certain of the disclosed devices relate to RAMIN procedures ("remodeling and ablation using myocardial interstitial navigation"). RAMIN procedures, as described herein, represent a new family of non-surgical catheter-based procedures in order to accomplish ablation, drug delivery, re-shaping, pacing, and related structural heart interventional procedures, as desired.

IPC Classes  ?

• A61F 2/06 - Blood vessels
• A61M 25/10 - Balloon catheters

Abstract

Method embodiments are disclosed for treating retinal degeneration in a subject in need thereof. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of compound, and/or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, or tautomer thereof, selected from 3-(dibutylamino)-1-(1,3-dichloro-6-(trifluoromethyl)phenanthren-9-yl)propan-1-ol hydrochloride or a compound having a structure according to a formula selected from Formula I, II, or III, as described herein. In some non-limiting examples, the subject has retinitis pigmentosa, LCA, Stargardt's macular dystrophy, cone-rod dystrophy, choroideremia or age-related macular degeneration.

IPC Classes  ?

• A61K 31/473 - Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
• A61K 31/475 - Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
• A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• A61P 27/02 - Ophthalmic agents

Abstract

The present invention is directed to a polymer platform comprising poly(L-lysine succinylated) which specifically targets scavenger receptor A1. This platform may be used to conjugate different types of drugs to the polymer for treatment of specific diseases or conditions in a patient. The resulting conjugates display moderate stability or controlled drug release, and allows for delivery and release of drugs and other therapeutic moieties to tissues/cells that express scavenger receptor A1 in a controlled manner.

IPC Classes  ?

• A61K 31/365 - Lactones
• 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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• A61P 33/00 - Antiparasitic agents
• A61P 35/00 - Antineoplastic agents

Abstract

Reported herein are novel recombinant respiratory syncytial viruses (RSV) having an attenuated phenotype. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Also provided are polynucleotide sequences capable of encoding the described viruses, as well as methods for producing and using the viruses.

IPC Classes  ?

• A61K 39/12 - Viral antigens

Abstract

Provided is a polynucleotide encoding a respiratory syncytial virus (RSV) variant having an attenuated phenotype comprising a modified RSV genome or antigenome that encodes a mutant RSV protein P that differs from a parental RSV protein P at one or more amino acid residues. In some embodiments, the polynucleotide is recombinant. The invention also relates to methods of vaccinating an animal with the RSV variant or a pharmaceutical composition containing the RSV variant or inducing an immune response by administering the RSV variant to an animal, and further relates to methods of producing an RSV variant vaccine. In some embodiments, the animal is a human.

IPC Classes  ?

• C07K 14/135 - Respiratory syncytial virus

Abstract

Chimeric antigen receptors including (a) an antigen binding domain; (b) a transmembrane domain; and (c) an intracellular domain comprising a first intracellular signaling domain from CD28 homolog (CD28H) and a second intracellular signaling domain are provided. In some examples, the second intracellular domain is from 2B4, TCR?, FceR1?, or DAP12. Chimeric antigen receptors including (a) an antigen binding domain; (b) a transmembrane domain; and (c) an intracellular domain comprising a first intracellular signaling domain from CD28H, a second intracellular signaling domain from 2B4, and a third intracellular signaling domain are also provided. In some examples, the third intracellular domain is from TCR?, FceR1?, or DAP12. Nucleic acid molecules encoding the CARs and expression vectors including the nucleic acids are also provided. Isolated cells (such as T cells or natural killer cells) expressing the CARs and methods of treating a subject with cancer with the isolated cells are provided.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants

Abstract

A lyophilized product of cyclic-di-AMP requires special production equipment and is thus not suitable for large-scale production. Crystals of cyclic-di-AMP free acid are unstable under severe conditions at 105°C. Then, the present invention addresses the problem of providing a cyclic-di-AMP (Formula I) crystal that can be easily acquired in a large amount and is very stable under the severe conditions at 105°C. Crystals of c-di-AMP sodium salt according to the present invention are extremely stable even under the severe conditions at 105°C. Further, the crystals of c-di-AMP sodium salt according to the present invention can be prepared in a large amount by a simple process including adjusting a c-diAMP aqueous solution at pH 5.2-12.0 and then adding an organic solvent thereto.

IPC Classes  ?

• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C12N 5/078 - Cells from blood or from the immune system
• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
• 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 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• 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 diseases; Gene therapy
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
• G01N 33/569 - Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses

Abstract

Provided are methods of preparing an enriched population of T cells having antigenic specificity for a target antigen. The method may comprise isolating T cells from a blood sample of a patient; selecting the isolated T cells which have a gene expression profile; and separating the selected T cells from the unselected cells. The separated selected T cells provide an enriched population of T cells having antigenic specificity for the target antigen. Methods of isolating a TCR, preparing a population of cells that express a TCR, isolated TCRs, isolated populations of cells, pharmaceutical compositions, and methods of treating or preventing a condition in a mammal are also provided.

IPC Classes  ?

• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C12N 5/078 - Cells from blood or from the immune system
• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
• 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 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 diseases; Gene therapy
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA

Abstract

Antibodies that bind SARS-CoV Spike protein, SARS-CoV-2 Spike protein, and methods of using same for treating or preventing conditions associated with SARS or COVID-19 and for detecting SARS-CoV or SARS-CoV-2.

IPC Classes  ?

• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
• A61P 31/14 - Antivirals for RNA viruses

Abstract

Antibodies that bind SARS-CoV spike protein, SARS-CoV-2 spike protein, and methods of using same for treating or preventing conditions associated with SARS or COVID-19 and for detecting SARS-CoV or SARS-CoV-2.

IPC Classes  ?

• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
• A61P 31/14 - Antivirals for RNA viruses

Abstract

Ex vivo analysis can be performed by mounting a portion of live tissue resected from a patient on a sample platform. Using the sample platform, the resected tissue portion can be positioned within a perfusion chamber. Perfusate is flowed through the perfusion chamber and into contact with the resected tissue portion such that diffusion of oxygen occurs between the perfusate and the resected tissue portion. During the flowing, the resected tissue portion maintains a competent immune system. Drugs can be added to the perfusate flow to ascertain the effect on the tissue. The sample platform is designed to be removable from the perfusion chamber for analysis of the tissue by imaging or other investigation techniques, for experimental treatment, or for any other purpose. After removal, the sample platform can be returned to the perfusion chamber for continued viability of the tissue.

IPC Classes  ?

• A01N 1/02 - Preservation of living parts
• C12M 1/00 - Apparatus for enzymology or microbiology
• C12M 1/02 - Apparatus for enzymology or microbiology with heat exchange means
• C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means
• C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus

Abstract

The disclosure provides non-naturally occurring mutant neuraminidase (NA) polypeptides that improve expression and/or modifies the open/closed tetramerie conformational state of the NA polypeptide, and uses thereof.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/145 - Orthomyxoviridae, e.g. influenza virus

Abstract

A method of target enrichment or depletion from a sample with an analyte is described. A probe has one of a left-handed PNA pair and a targeting moiety, in which the left-handed PNA pair are a complementary pair of PNAs that are chiral and have a cyclic backbone modification that induces a left-handed helical structure. A capture surface has the other of the left-handed PNA pair; and the left-handed PNA pair bind to hybridize the probe to the capture surface, which may be a magnetic bead.

IPC Classes  ?

• C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• C12Q 1/6813 - Hybridisation assays
• C12Q 1/6832 - Enhancement of hybridisation reaction
• C07K 19/00 - Hybrid peptides

Abstract

Disclosed herein are systems and methods for predicting risk of late age-related macular degeneration (AMD). The method may include receiving one or more color fundus photograph (CFP) images from both eyes of a patient, classifying each CFP image, and predicting the risk of late AMD by estimating a time to late AMD. Classifying each CFP image may include extract one or more deep features for macular drusen and pigmentary abnormalities in each CFP image, grading the drusen and pigmentary abnormalities and/or detecting the presence of RPD in each CFP image. Predicting the risk of late AMD may include estimating a time to late AMD using a Cox proportional hazard model using the presence of RPD, the one or more deep features, and/or the graded drusen and pigmentary abnormalities.

IPC Classes  ?

• 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
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

Methods for generating multipotent radial glia-like cells and astrocyte-like cells from human pluripotent stem cells are provided along with the related compositions.

IPC Classes  ?

• C12N 5/079 - Neural cells

Abstract

Described herein is a method of treating pain by administering to a subject in need of treatment for pain a pharmaceutical composition including a therapeutically effective amount of margaric acid. Also described are pharmaceutical compositions such as topical and transdermal compositions including margaric acid and a pharmaceutically acceptable excipient. Further described is a composition for the treatment of pain including margaric acid, eicosapentaenoic acid, and a pharmaceutically acceptable excipient.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/20 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid
• A61K 31/202 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid having three or more double bonds, e.g. linolenic acid
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with aspartic acid presented by a human leukocyte antigen (HLA) Class I molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors

Abstract

Disclosed are isolated or purified T cell receptors (TCRs), wherein the TCRs have antigenic specificity for a mutated RAS amino acid sequence presented by a human leukocyte antigen (HLA) Class I molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors

Abstract

SARS-CoV-2 S ectodomain trimers stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the SARS-CoV-2 S ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to SARS-CoV-2 S in a subject, for example, an immune response that inhibits SARS-CoV-2 infection in the subject.

IPC Classes  ?

• C07K 14/165 - Coronaviridae, e.g. avian infectious bronchitis virus
• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61K 39/12 - Viral antigens
• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
• A61K 39/385 - Haptens or antigens, bound to carriers
• A61P 31/14 - Antivirals for RNA viruses
• C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
• C12N 15/50 - Coronaviridae, e.g. infectious bronchitis virus, transmissible gastroenteritis virus
• C12N 15/86 - Viral vectors

Abstract

The invention provides human immunogenic epitopes of HEMO and HHLA2 human endogenous retroviruses (HERVs), which can be used as a peptide, polypeptide (protein), and/or in a vaccine or other composition for the prevention or therapy of cancer. The invention further provides a nucleic acid encoding the peptide or polypeptide (protein), a vector comprising the nucleic acid, a cell comprising the peptide, polypeptide (protein), nucleic acid, or vector, and compositions thereof.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 7/00 - Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof

Abstract

Methods are disclosed for treating a cone rod homeobox transcription factor (CRX) autosomal dominant retinopathy in a subject. These methods include administering to the subject an effective amount of a nucleic acid molecule comprising a retinal specific promoter operably linked to a nucleic acid molecule encoding a CRX protein. Compositions are disclosed that include an effective amount of a nucleic acid molecule comprising a retinal specific promoter operably linked to a nucleic acid molecule encoding CRX, for use in treating a CRX autosomal dominant retinopathy in a subject. A retinal specific promoter is disclosed that includes the nucleotide sequence of SEQ ID NO: 1.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• A61P 27/02 - Ophthalmic agents
• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 15/12 - Genes encoding animal proteins
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• C12N 15/864 - Parvoviral vectors

Abstract

Described is the preparation of novel fentanyl haptens of Formula (1) through (6) and their use in the preparation of effective fentanyl vaccines.

IPC Classes  ?

• C07D 211/06 - 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
• A61K 31/4468 - Non-condensed piperidines, e.g. piperocaine having a nitrogen atom directly attached in position 4, e.g. clebopride, fentanyl
• A61P 25/36 - Opioid-abuse
• C07D 211/58 - Nitrogen atoms attached in position 4

Abstract

Disclosed are anti-C3d antibodies or fragments thereof. Also disclosed are methods of killing cancer cells, methods of preparing anti-C3d antibodies, and pharmaceutical compositions.

IPC Classes  ?

• 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 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• A61K 51/10 - Antibodies or immunoglobulins; Fragments thereof
• A61P 35/00 - Antineoplastic agents
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C12N 15/13 - Immunoglobulins
• C12P 21/08 - Monoclonal antibodies

Abstract

An improved antibody-drug conjugate (ADC) targeting CD276-positive tumors is described. The ADC includes a CD276-specific IgG1 antibody having a heavy chain modified to prevent interaction of its Fc domain with endogenous Fc receptors and to introduce a cysteine for site-specific conjugation of the drug. The CD276-specific ADC is capable of potently eradicating CD276-positive tumors in several animal models.

IPC Classes  ?

• 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 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61P 35/00 - Antineoplastic agents

Abstract

Embodiments of immunogens comprising a recombinant Mumps (MuV) F ectodomain trimer stabilized in a prefusion conformation or a recombinant Measles (MeV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also provided are embodiments of immunogens comprising chimeric proteins comprising the recombinant MuV or MeV F ectodomain trimer and one or more MuV HN or MeV H ectodomains. Also disclosed are nucleic acids encoding the immunogens and methods of their production. Methods for inducing an immune response in a subject by administering a disclosed immunogen to the subject are also provided. In some embodiments, the immune response treats or inhibits MuV and/or MeV infection in a subject.

IPC Classes  ?

• C07K 14/12 - Mumps virus; Measles virus
• A61K 39/165 - Mumps or measles virus
• A61P 31/14 - Antivirals for RNA viruses
• A61P 37/04 - Immunostimulants
• C12N 15/45 - Paramyxoviridae, e.g. measles virus, mumps virus, Newcastle disease virus, canine distemper virus, rinderpest virus, respiratory syncytial viruses

Abstract

The invention provides methods and compositions involving the compounds N'-(3,5-dimethylbenzoyl)picolinohydrazide; N'-(pyrid in-2- yl)picolinohydrazide or pharmaceutically acceptable salts thereof for inhibiting the function of histone demethylases in vivo and in vitro, as well as methods for treating cancer comprising the administration of such compositions.

IPC Classes  ?

• A61K 31/4402 - Non-condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
• A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61P 35/00 - Antineoplastic agents
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

Disclosed herein, inter alia, are compounds and methods for inhibiting Taspasel and the treatment of cancer.

IPC Classes  ?

• C07D 295/04 - 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
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

Single-domain monoclonal antibodies that specifically bind B7H3 (also known as CD276) are described. The single-domain antibodies include camel VHH and rabbit VH domain nanobodies selected from phage display libraries. Chimeric antigen receptors (CARs) and other antibody conjugates targeted to B7H3 are also described. The single-domain antibodies and conjugates thereof can be used for the diagnosis and treatment of B7H3 expressing solid tumors.

IPC Classes  ?

• 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 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
• C07K 16/46 - Hybrid immunoglobulins
• C07K 17/00 - Carrier-bound or immobilised peptides; Preparation thereof
• C07K 19/00 - Hybrid peptides
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/13 - Immunoglobulins
• C12N 15/62 - DNA sequences coding for fusion proteins
• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer

Abstract

The invention relates to treatments for organ rejection, in particular to treatments for lung transplant associated bronchiolitis obliterans syndrome by administering a neutrophil elastase inhibitor, such as alvelestat. The invention also relates to treatments for graft versus host disease.

IPC Classes  ?

• A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection

Abstract

Ephrin type receptor tyrosine kinase inhibitors, also known as Eph tyrosine kinase receptor inhibitors, for treating cancer, an inflammatory disease, an autoimmune disease, or a degenerative disease characterized at least in part by the abnormal activity or expression of the Eph receptor tyrosine kinase. The inhibitors are particularly useful for treating colorectal cancer.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• 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
• A61P 35/00 - Antineoplastic agents
• C07D 251/22 - Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms
• C07D 401/04 - 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 directly linked by a ring-member-to-ring- member bond
• C07D 401/14 - 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 three or more hetero rings
• 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
• 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 471/04 - Ortho-condensed systems

Abstract

Disclosed herein are methods of diagnosing or prognosing aggressive prostate cancer in a subject and methods of treating a subject with aggressive prostate cancer. For example, the methods can include measuring increased expression of aggressive prostate cancer-related molecules (such as FOLH1, SPARC, TGFB1, CAMKK2, NCOA2, EGFR, or PSA) and optionally administering a therapeutically effective amount of aggressive prostate cancer therapy.

IPC Classes  ?

• C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving enzymes not classifiable in groups
• C12Q 1/34 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
• G01N 33/483 - Physical analysis of biological material

Abstract

The present disclosure provides methods for determining the amount of FXN or FXN fusion protein in a sample, e.g, a tissue sample, by using mass spectrometry.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Abstract

Disclosed is the use of a nucleotide reverse transcriptase inhibitor, a nucleotide reverse transcriptase inhibitor, and an integrase inhibitor prior to an exposure to a potential human immunodeficiency virus (HIV) infection, to protect the subject from the HIV infection. In some embodiments, a prophylactically effective amount of emtricitabine (FTC), a prophylactically effective amount of tenofovir or a tenofovir prodrug, such as tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), a prophylactically effective amount of the integrase inhibitor elvitegravir (EVG), and optionally cobicistat (COBI) are used to inhibit or prevent an HIV infection, wherein these agents are administered only prior to the exposure. In specific non-limiting examples, only one dose of the anti-retroviral viral agents is administered to a subject prior to the exposure.

IPC Classes  ?

• A61K 31/47 - Quinolines; Isoquinolines
• A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/52 - Purines, e.g. adenine
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 31/18 - Antivirals for RNA viruses for HIV

Abstract

Disclosed are monoclonal antibodies and antigen binding fragments that specifically bind epidermal growth factor receptor (EGFR) variant (v) III, conjugates thereof, and chimeric antigen receptors. Nucleic acid molecules encoding the heavy and light chain domains of the antibodies, and the chimeric antigen receptors (CARs), are also disclosed, as are host cells expressing the nucleic acid molecules. In addition, disclosed is the use of these monoclonal antibodies, antigen binding fragments, conjugates, and T cells expressing the CARs, such as for the treatment of a tumor expressing EGFRvIII. Also disclosed are methods for detecting a tumor that expresses EGFRvIII.

IPC Classes  ?

• 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 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61P 35/00 - Antineoplastic agents
• C07K 14/21 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Pseudomonadaceae (F)
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 16/46 - Hybrid immunoglobulins
• C07K 19/00 - Hybrid peptides
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/13 - Immunoglobulins
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53R175H or human p53Y220C. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/12 - Genes encoding animal proteins
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer

Abstract

The invention is directed to an isolated population of mammal cells comprising about 75 % or higher B-1a regulatory cells expressing the cell surface inhibitory receptors lymphocyte-activation gene 3 (LAG-3), programmed cell death protein 1 (PD-1), and C-X-C chemokine receptor type 4 (CXCR4), and secreting interleukin-27 (IL-27). The invention is also directed to methods of preparing and using the cell population to suppress the immune system and/or to treat or prevent diseases.

IPC Classes  ?

• C12N 5/0781 - B cells; Progenitors thereof
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 38/20 - Interleukins
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 27/02 - Ophthalmic agents
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• C07K 14/54 - Interleukins (IL)
• C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
• C12Q 1/04 - Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor

Abstract

The present disclosure generally relates to, inter alia, antibodies and chimeric antigen receptors (CARs) that bind a Glypican 2 (GPC2) antigen. The disclosure also provides compositions and methods useful for producing such antibodies and CARs, as well as methods for the diagnosis, prevention, and/or treatment of health conditions associated with the GPC2 antigen expression.

IPC Classes  ?

• 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 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61P 35/00 - Antineoplastic agents
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• C07K 19/00 - Hybrid peptides
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/13 - Immunoglobulins
• C12N 15/62 - DNA sequences coding for fusion proteins
• G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer

Abstract

Provided herein are methods and systems for high-resolution, cerebrospinal fluid-suppressed T2*-weighted magnetic resonance imaging of cortical lesions.

IPC Classes  ?

• G01R 33/56 - Image enhancement or correction, e.g. subtraction or averaging techniques
• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography

Abstract

Using the Cross-Over-Dual-Variable Domain (CODv) format, the present disclosure relates to compositions comprising trispecific and/ or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation, and wherein a second pair of polypeptides possess a single variable domain. Also provided herein are methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins for the treatment and/or prevention of HIV/AIDS.

IPC Classes  ?

• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
• A61P 31/18 - Antivirals for RNA viruses for 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
• C07K 16/46 - Hybrid immunoglobulins

Abstract

Disclosed herein are novel compounds including dopamine D3 receptor agonists, compositions thereof, methods of use thereof, and processes of synthesizing the same. Further disclosed are D3R selective agonist compounds, specifically bitopic ligands comprising chirality.

IPC Classes  ?

• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

Monoclonal antibodies that specifically bind glypican-1 (GPC1) are described. Chimeric antigen receptor (CAR) T cells, immunotoxins and other antibody conjugates based on the GPC1-specific antibodies are also described. The disclosed CAR T cells, immunotoxins, GPC1-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of GPC1-positive pancreatic cancer and other cancers.

IPC Classes  ?

• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans

Abstract

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with arginine. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors
• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61P 35/00 - Antineoplastic agents
• C07K 14/82 - Translation products from oncogenes
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

Camel single-domain monoclonal antibodies that specifically bind human and mouse mesothelin are described. Chimeric antigen receptor (CAR) T cells and antibody conjugates based on the mesothelin-specific antibodies are also described. The disclosed CAR T cells, mesothelin-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of mesothelin-positive cancers.

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells

Abstract

Tissue replacement implants are disclosed that include polarized retinal pigment epithelial cells on a poly(lactic-co-glycolic acid) (PLGA) scaffold, wherein the PLGA scaffold is 20-30 microns in thickness, has a DL-lactide/glycotide ratio of about 1:1, an average pore size of less than about 1 micron, and a fiber diameter of about 150 to about 650 nm. Also disclosed are methods of treating a subject with a retinal degenerative disease, retinal or retinal pigment epithelium dysfunction, retinal degradation, retinal damage, or loss of retinal pigment epithelium. These methods include locally administering to the eye of the subject the tissue replacement implant. In further embodiments, methods are disclosed for producing the tissue replacement implant.

IPC Classes  ?

• A61L 27/38 - Animal cells
• A61L 27/54 - Biologically active materials, e.g. therapeutic substances
• A61L 27/58 - Materials at least partially resorbable by the body

Abstract

Methods of decreasing cell viability of cancer cells, increasing apoptosis of cancer cells, and treating cancer in a mammal with cancer are provided. The methods include administering (i) a polypeptide comprising an amino acid sequence with at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1, (ii) a nucleic acid molecule comprising a nucleic acid sequence encoding the polypeptide, (iii) a vector comprising the nucleic acid molecule, (iv) a recombinant cell comprising any one of (i)-(iii), and/or (v) a composition comprising any one of (i)-(iv).

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated RAS amino acid sequence presented by a HLA-A3 molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors

Abstract

Embodiments of recombinant HIV-1 gp120 proteins that contain a V1 deletion are disclosed. Also provided are gp140, gp145, and gp160 proteins containing the V1 deletion, as well as HIV-1 Env ectodomain trimers containing protomers containing the V1 deletion. Nucleic acid molecules encoding these proteins are also provided. In several embodiments, the disclosed recombinant HIV-1 proteins and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA

Abstract

Halogenated analogs of 5-aza-2'-deoxycytidine, such as halogenated analogs of 5-aza-4'-thio-2'-deoxycytidine (5-aza-T-dCyd) are described. Pharmaceutical compositions including a halogenated analog and methods of using the halogenated analogs to inhibit neoplasia are described. In some examples, the halogenated analogs have a structure according to formula Ia, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof:

IPC Classes  ?

• C07H 19/12 - Triazine radicals
• A61K 31/706 - 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

Abstract

The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to a cell comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)) and a dominant negative Fas polypeptide. In certain embodiments, the cells are antigen-directed and exhibit enhanced cell persistence, and enhanced anti-target treatment efficacy.

IPC Classes  ?

• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 14/725 - T-cell receptors
• 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

Abstract

An embodiment of the invention provides nucleic acids comprising a nucleotide sequence encoding chimeric antigen receptor (CAR) amino acid constructs. Polypeptides, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CAR constructs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61P 35/02 - Antineoplastic agents specific for leukemia
• C07K 19/00 - Hybrid peptides

Abstract

Disclosed herein are novel methods of treating pain in a patient in need thereof by providing to the patient a selective dopamine D3 receptor antagonist/partial agonist which when used with an opioid analgesic, can mitigate the development of opioid dependence, by preventing the need for dose escalation while either maintaining the opioid analgesic effect or providing analgesia with a lower dose of the opioid. In addition, the D3 antagonists/partial agonists described herein may be used to augment the effectiveness of current Medication Assisted Treatment regimens (e.g. methadone or buprenorphine) for the treatment of opioid use disorders.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
• A61P 25/36 - Opioid-abuse

Abstract

The present disclosure is directed to methods for preventing or treating helminth (e.g., filarial) diseases in animals. The methods are accomplished by administering to the animal a therapeutically effective amount of an inhibitor of UDP-glucoronosyl transferase (UGT) or immunoglobulin I- set domain containing protein (Igl-DCP, also known as BMA-Lad-2). The inhibitors include those known to inhibit glucuronyltransferase enzyme activity as well as cell adhesion molecule inhibitors and antibodies specific for Igl-DCP and/or UGT.

IPC Classes  ?

• A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• A01N 43/54 - 1,3-Diazines; Hydrogenated 1,3-diazines
• A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• A61P 33/10 - Anthelmintics

Abstract

Cyanine fluorophores including a nine-carbon polymethine bridge are disclosed. The cyanine fluorophores have absorbance and/or emission maxima in the near-infrared (NIR) and short-wave infrared (SWIR) wavelength ranges. Methods of making and using the cyanine fluorophores are also disclosed. The compounds are useful in fluorescence imaging, more particularly in cancer treatment. The compounds have generic formula (I):

IPC Classes  ?

• C09B 23/01 - Methine or polymethine dyes, e.g. cyanine dyes characterised by the methine chain
• A61K 31/404 - Indoles, e.g. pindolol
• C07D 417/08 - 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 carbon chain containing alicyclic rings
• G01N 33/483 - Physical analysis of biological material

Abstract

Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

IPC Classes  ?

• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/725 - T-cell receptors
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells

Abstract

Methods and technologies for the treatment of methylmalonic acidemia.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
• C12N 9/90 - Isomerases (5.)
• C12N 15/09 - Recombinant DNA-technology
• C12N 15/61 - Isomerases (5)
• C12N 15/864 - Parvoviral vectors

Abstract

Pharmaceutical compositions are disclosed that includes a therapeutically effective amount of a purified viable Gram negative bacteria and a pharmaceutically acceptable carrier. The pharmaceutical compositions are formulated for topical administration. Methods of treating atopic dermatitis using these pharmaceutical compositions are also disclosed.

IPC Classes  ?

• A61K 35/74 - Bacteria
• A61K 35/741 - Probiotics
• A61K 39/02 - Bacterial antigens
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
• A61P 17/00 - Drugs for dermatological disorders
• A61P 17/04 - Antipruritics

Abstract

: Disclosed are monoclonal antibodies that specifically bind emtricitabine (FTC). Methods are also disclosed for using these antibodies to detect FTC in samples. In some embodiments, these methods are of use for determining if a subject is complying with a therapeutic or prophylactic protocol. In other embodiments, methods are disclosed for determining the dose of FTC to administer to a subject.

IPC Classes  ?

• C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
• G01N 33/577 - Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies

Abstract

Embodiments of vesicles comprising embedded cytotoxic agents are disclosed, as well as methods of making and using the vesicles. Pharmaceutical compositions including the vesicles also are disclosed. The vesicles include a binary lipid bilayer surrounding a cavity, wherein the vesicle binary lipid bilayer includes (i) a non-bilayer forming lipid (or combination of non-bilayer forming lipids) and a PEGylated lipid; and (i) a cytotoxic agent embedded within the vesicle wall.

IPC Classes  ?

• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
• A61K 9/127 - Liposomes
• A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
• A61P 35/00 - Antineoplastic agents

Abstract

An affinity matured anti-CD22 human monoclonal antibody exhibiting significantly higher affinity (less than 50 pM) compared to the parental antibody (affinity of about 2 nM) is described. The anti-CD22 variant antibody or a fragment thereof, such as a single-chain variable fragment (scFv), can be used as the antigen-binding portion of chimeric antigen receptors (CARs), antibody-drug conjugates (ADCs), immunotoxins or multi-specific antibodies for the treatment of B-cell malignancies.

IPC Classes  ?

• 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 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• A61P 35/02 - Antineoplastic agents specific for leukemia
• C07K 14/725 - T-cell receptors

Abstract

The present invention concerns novel pharmaceutically active triterpene amine derivatives, pharmaceutical compositions containing the same, their use as medicaments, and the use of the compounds for the manufacture of specific medicaments. The present invention also concerns a method of treatment involving administration of the triterpene amine compounds. Specifically, the compounds are derivatives of betulinic acid having substitutions at one or more of the C-3, C-28 and C-19 positions as further described herein. The novel compounds are useful as antiretroviral agents. In particular, the novel compounds are useful for the treatment of Human Immunodeficiency Virus-1 (HIV-1).

IPC Classes  ?

• C07J 63/00 - Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
• A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• A61K 31/58 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
• A61P 31/18 - Antivirals for RNA viruses for HIV
• C07J 43/00 - Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta[a]hydrophenanthrene skeleton
• C07J 53/00 - Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by condensation with carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms

Abstract

A process for the preparation of (2R,6R)-hydroxynorketamine is provided. The process requires no chromatography purification and affords the (2R,6R)-hydroxynorketamine in eight steps with a 26% overall yield and greater than 97% purity.

IPC Classes  ?

• C07C 221/00 - Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• C07C 225/20 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton

Abstract

Disclosed are pharmaceutical formulations comprising a compound of formula (I): in which R1, R2, R3, and R4 are as described herein, or a pharmaceutically acceptable salt thereof. Also provided are methods for treating pancreatic adenocarcinoma comprising administration of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and methods of detecting the change in expression levels of one or both of FoxA1 and FoxO6 in a pancreatic adenocarcinoma tumor sample from a mammal, wherein the mammal has been administered a compound of formula (I), or a pharmaceutically acceptable salt thereof.

IPC Classes  ?

• A61K 9/107 - Emulsions
• 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 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 47/10 - Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• A61K 47/12 - Carboxylic acids; Salts or anhydrides thereof
• A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
• A61P 35/00 - Antineoplastic agents
• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer

Abstract

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated EGFR amino acid sequence with a E746-A750 deletion. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C07K 14/725 - T-cell receptors

Abstract

Provided are methods of producing an isolated population of T cells, the method comprising culturing isolated T cells in vitro in the presence of hydroxycitric acid, and/or a salt thereof, wherein the salt is potassium hydroxycitrate or sodium hydroxycitrate. Also provided are related isolated populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer in a mammal.

IPC Classes  ?

• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
• A61K 31/191 - Acyclic acids having two or more hydroxy groups, e.g. gluconic acid

Abstract

Disclosed are live, chimeric non-human Mononegavirales vectors that allow a cell to express at least one protein from at least one human pathogen. In addition, compositions comprising the vectors, methods and kits for eliciting an immune response in a host, and methods of making the vectors are disclosed, in accordance with embodiments of the invention.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 39/12 - Viral antigens
• A61P 31/14 - Antivirals for RNA viruses