Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.

The invention provides novel personalized therapies, kits, transmittable forms of information and methods for use in treating subjects having TMPRSS2:ERG positive prostate cancer, which we show is amenable to therapeutic treatment with a PRMT5 inhibitor. Kits, methods of screening for candidate PRMT5 inhibitors, and associated methods of treatment are also provided.

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

The present invention provides a cell-penetrating-peptide multi-arm-PEG medicine conjugate having a general formula I, II, III, IV or V. As compared with linear-chain-type PEG-cell-penetrating-peptide conjugates, the multi-arm PEG has multiple end groups, and has introduction sites for multiple functional groups, which can connect to multiple different active groups. In addition, the cell-penetrating-peptide multi-arm-PEG medicine conjugate to enable the medicine to enter the pathogenetic cells in a targeting manner, to achieve precise treatment. The present invention further provides use of a cell-penetrating-peptide multi-arm-PEG medicine conjugate having targeting ability in preparation of a targeting medicine, especially use of a cell-penetrating-peptide multi-arm-PEG medicine conjugate having targeting ability in the treatment of eye age-related macular degeneration, asthma and pulmonary fibrosis.

Provided herein are trioxacarcin-antibody drug conjugates of Formula (A): and pharmaceutically acceptable salts thereof, comprising at least one instance of the group -L.sup.1-(A-L.sup.2)a-B attached thereto, wherein a is an integer between 1 and 10, inclusive, L.sup.1 is absent or is a linking group, A is a moiety formed from the reaction of two complimentary groups (X and Y), L.sup.2 is absent or is another linking group, and B is an antibody or antibody fragment. Also provided are methods of preparing these antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the trioxacarcin-antibody drug conjugates, novel trioxacarcins without an antibody conjugated thereto, pharmaceutical compositions thereof, and methods of their use and treatment. ##STR00001##

The disclosure provides compositions and methods relating to the treatment of pain, such as pain from rheumatoid arthritis. By creating conjugates of antibodies that target C5aR and siRNA's that target C5 expression, a dual mode therapeutic that targets two different aspects of C5's inflammatory signaling.

Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKKα/β and IκBα, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC.sub.50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

Aspects of the disclosure relate to methods of purifying complexes comprising a protein (e.g., antibody) covalently linked to an oligonucleotide. In some embodiments, complexes comprising a protein covalently linked to an oligonucleotide are purified and isolated from unlinked oligonucleotide using an mixed-mode resin that comprises positively-charged metal sites and negatively charged ionic sites, e.g., hydroxyapatite resin. In some embodiments, complexes comprising a protein covalently linked to an oligonucleotide are purified from a mixture comprising the complexes, unlinked protein, and unlinked oligonucleotide using a purification step involving hydrophobic interaction chromatography resin followed by a purification step involving mixed-mode resin.

The present description relates to a method for binding to a target molecule having an aldehyde compound derived from N-(2-aminoethyl)pyrrole, which compound also has a moiety of interest, to compounds (conjugates) obtained by this method, having both the target molecule and the moiety of interest and to novel substances derived from N-(2-aminoethyl)pyrrole. In one embodiment, the compound has the formula of Formula II ##STR00001##
wherein R1, R2 and R3 independently are H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein R4, R5, R6, R7 and R8 independently are H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or -LM, wherein L is absent or is a linker and M is a moiety of interest selected from a nucleotide, an oligonucleotide, a peptide, a label, a cytotoxic agent, a partner of a binding pair and a functional group, wherein two of R4, R5, R6, R7, and R8 optionally are linked to form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted heterocycloalkyl, and T is a target molecule selected from the group consisting of a solid phase, a polypeptide, a protein, a carbohydrate, a nucleotide and a nucleic acid, with the proviso that at least one of R4, R5, R6, R7 or R8 is -LM.

Provided herein are therapeutic agents having specificity for having inhibitory activity against cancer cells that overexpress human epidermal growth factor receptor (HER) genes, including therapeutic agents comprising one or more HER-targeting peptides, pharmaceutical compositions comprising such therapeutic agents, and methods of using such compositions to treat or prevent a cancer or other disease condition associated with HER overexpression.