The present invention relates to compounds of the formula (I) and in particular medicaments comprising at least one compound of the formula (I) for use in the treatment and/or prophylaxis of physiological and/or pathophysiological states in the triggering of which cathepsin D is involved, in particular for use in the treatment and/or prophylaxis of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia.

Provided is a method for making the compound of Formula 1. Various compounds utilized in that method are also provided, as are methods of making those compounds. Also provided is a compound having the formula XO—CO—(CH.sub.2).sub.nNH.sub.2, where n is an integer greater than 2. A method of making that compound is additionally provided. Further provided is a method of making a prodrug of a bioactive compound.

An antibody-drug conjugate having a structure represented by formula (I)

##STR00001##

wherein m is 1, 2, 3, or 4 and Ab is an anti-glypican-3 antibody having heavy and light chain CDRs as disclosed herein.

The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a proline derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.). The Michael adducts can bear a single substituent or dual substituents adjacent to the carbonyl. The Michael adducts can be efficiently converted to cyclically constrained protected γ-amino acid residues, which are essential for systematic conformational studies of γ-peptide foldamers. New methods are also provided to prepare other γ-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as α/γ-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.

Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology use.

Cyclooctene conjugates of therapeutic or diagnostic agents have improved aqueous solubility and can release the agents upon contact with a tetrazine-containing biomaterial. The cyclooctene conjugates provide site-selective delivery of agents at the location of the tetrazine-containing biomaterial in a subject. The compositions and methods have applications in the treatment of various diseases or conditions including cancer, tumor growths, and bacterial infections.

Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

This invention relates to prostate-specific membrane antigen (PSMA) antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are αPSMA antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the αPSMA antibodies of the invention are conjugated to one or more toxins. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, dolastatin analogs, and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology uses.

Provided is a method for modifying a chimeric antigen receptor-modified T cell (CAR-T cell). The method comprises expressing an SCFV-CDS TM-4-1BB-CD3ζ molecule in a T cell. The CAR-T cell prepared using the method can specifically recognize and bind to a tumor cell with elevated expression of a ROBO1 protein, and can be used to prevent and treat a corresponding tumor-related disease.

Provided is a method for producing an antibody-drug conjugate intermediate by addition of acid. An acid additive is used to convert the monomethyl auristatin derivative into a salt thereof to participate in the reaction. The addition of the acid additive can significantly improve the yield of the final product. In addition, the low price of the acid additive greatly reduces the production cost of the final ADC product. Moreover, the method of the present invention adopts a one-step preparation process, in addition to a higher yield of the final product, not only reducing the cost of the consumables, labor, equipment, site, raw materials and the like in the production, but also greatly reducing the production of the waste liquid, and thus reducing production costs and improving production efficiency, and making the method suitable for industrial large-scale production.