Described are stable topical formulations useful in the treatment of viral wart infection, demodex infection and bacterial infection of the skin, and genitalia and the method of treating viral wart infection, demodex infection and bacterial infection of the skin, and genitalia with said compositions.

The present invention relates to antibodies and antigen-binding fragments thereof that bind to PD-1, and to methods of using such antibodies and antigen-binding fragments. For example, the present invention provides humanized anti-PD-1 antibodies and methods of use thereof.

The present invention relates to nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and derivatives thereof as an immunostimulating agent/adjuvant and to compositions containing same, optionally comprising an additional adjuvant. The present invention furthermore relates to a pharmaceutical composition or to a vaccine, each containing nucleic acids of formula (I) above and/or derivatives thereof as an immunostimulating agent, and optionally at least one additional pharmaceutically active component, e.g. an antigenic agent. The present invention relates likewise to the use of the pharmaceutical composition or of the vaccine for the treatment of cancer diseases, infectious diseases, allergies and autoimmune diseases etc. Likewise, the present invention includes the use of nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.

The present invention relates to compounds of: ##STR00001##
or a pharmaceutically acceptable salt thereof, wherein A is C.sub.5 alkyl, C.sub.6 alkyl, C.sub.5 alkenyl, C.sub.6 alkenyl, C(O)—(CH.sub.2).sub.n—CH.sub.3 or CH(OH)—(CH.sub.2).sub.n—CH.sub.3 wherein n is 3 or 4; R.sub.1 is H, F or OH; R.sub.2 is C.sub.5 alkyl, C.sub.6 alkyl, C.sub.5 alkenyl, C.sub.6 alkenyl, C(O)—(CH.sub.2).sub.n—CH.sub.3 or CH(OH)—(CH.sub.2).sub.n—CH.sub.3 wherein n is 3 or 4; R.sub.3 is H, F, OH or CH.sub.2Ph; R.sub.4 is H, F or OH; Q is 1) (CH.sub.2).sub.mC(O)OH wherein m is 1 or 2, 2) CH(CH.sub.3)C(O)OH, 3) C(CH.sub.3).sub.2C(O)OH, 4) CH(F)—C(O)OH, 5) CF.sub.2—C(O)OH, or 6) C(O)—C(O)OH;
and compositions comprising the same and the method using the same for the prevention or treatment of various fibrotic diseases and conditions in subjects, including pulmonary fibrosis, liver fibrosis, skin fibrosis, renal fibrosis, pancreas fibrosis, systemic sclerosis, cardiac fibrosis or macular degeneration.

The present disclosure relates to crystalline solid forms of a stimulator of soluble guanylate cyclase (sGC), Compound I: ##STR00001##
Also provided herein are methods for the preparation of these solid forms. The invention also relates to pharmaceutical formulations and dosage forms comprising these solid forms and their uses thereof, alone or in combination with one or more additional agents, for treating and/or preventing various diseases or disorders; these diseases or disorders are ones that may benefit from sGC stimulation or from an increase in the concentration of nitric oxide (NO) and/or cyclic guanosine monophosphate (cGMP).

A vaccine delivery method is presented that includes a composition including as one component a slurry matrix that is a liquid at room temperature and a gel at physiological pH, physiological salt concentrations and/or physiological temperatures and as a second component one or more antigens. Also included are methods of inducing an immune response in a subject and vaccinating a subject by administering such compositions.

Provided herein are compounds that inhibit the phosphorylation of MAPK and thus are useful in compositions and methods for treating cancer and inflammatory disease.

A compound represented by general formula (I) wherein all the symbols are as defined in the specification has a selective S1P5 receptor agonist activity due to having a linker from a phenyl group to a cyclic substituent in a dihydronaphthalene skeleton; i.e., due to having a short linker of one atom or less as L in general formula (I), and can therefore serve as an agent for treating S1P5-mediated disease, e. g., neurodegenerative disease such as schizophrenia. ##STR00001##

Provided is a conjugate formed between one or more linear polysaccharide chains and a peptide selected from one or more of the peptide components (a), (b), (c) or (d) as defined below: (a) a peptide component of formula (I), A-Q-B I wherein Q represents a structural fragment of formula (II), wherein: the squiggly lines and m have meanings given in the description and A and B have meanings given in the description, but may represent a peptide component of the amino acid sequence: [W-Lys-X1-Ser-U-X2-Y] n-W-Lys-X1-Ser-U-X2-Y--- (SEQ ID No: 3), wherein the dashed line, n, W, X1, U, X2 and Y have meanings given in the description; (b) a peptide component of the amino acid sequence: [Ala-Lys-X1-Ser-U-X2-Y] p-Ala-Lys-X1-Ser-U-X1-Y-G (SEQ ID No: 4) wherein p, G, X1, U, X2 and Y have meanings given in the description; (c) a peptide component of the amino acid sequence: W-Lys-X1-Ser-U-X2-Y-G (SEQ ID No: 5), wherein W, X1, U, X2, Y and G have meanings given in the description; or (d) a peptide component of the amino acid sequence: K-W1-Lys-X1-Ser-U1-X2-Y1-I-J (SEQ ID No: 6), wherein K, W1, U1, Y1, I, J, X1 and X2 have meanings as well as regioisomers, stereoisomers, and pharmaceutically- or cosmetically-acceptable salts of said conjugates, which conjugates are particularly useful in the treatment of conditions characterised by inflammation, including wounds, burns, and disorders of the mucosa, such as anorectal diseases, inflammatory bowel diseases, gynaecological diseases and dental diseases. Preferred linear polysaccharides include hyaluronic acid.

##STR00001##

Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses and innate immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens, a combination of adjuvants, and optionally may encode one or more soluble and secreted checkpoint inhibitor molecules. The adjuvants include latent membrane protein 1 (LMP1) from Epstein Barr virus and a fusion protein including LMP1 with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.