An improved method of deprotection in solid phase peptide synthesis is disclosed. In particular the deprotecting composition is added in high concentration and small volume to the mixture of the coupling solution, the growing peptide chain, and any excess activated acid from the preceding coupling cycle, and without any draining step between the coupling step of the previous cycle and the addition of the deprotection composition for the successive cycle. Thereafter, the ambient pressure in the vessel is reduced with a vacuum pull to remove the deprotecting composition without any draining step and without otherwise adversely affecting the remaining materials in the vessel or causing problems in subsequent steps in the SPPS cycle.

Cell-targeted cytotoxic agents, including sortase serine protease constructs, are provided. Such compounds can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant sortase serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity.

Cell-targeted cytotoxic agents, including sortase serine protease constructs, are provided. Such compounds can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant sortase serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity.

Disclosed is a method for producing hybrid or non-hybrid recombinant glycoprotein hormones, for example the recombinant equine chorionic gonadotropin (r-eCG), the hybrid recombinant chorionic gonadotropin, the recombinant thyroid-stimulating hormone (r-TSH), the recombinant luteinising hormone (r-LH), the luteinising hormone and the recombinant follicle-stimulating hormone (r-FSH). In addition, the present invention relates to the recombinant glycoprotein hormones comprising the equine α and β subunits, inter alia, the α subunit of mammals and equine β subunit, where the two subunits are fused in a simple chain, and chain-modifying agents, which hormones are easier to purify, more homogeneous, easier to produce on an industrial scale without using animals, in comparison with the wild glycoprotein hormone The hormones are useful for inducing animal reproduction, ovulation induction, superovulation induction, follicle growth, oestrus induction, anoestrus reversal, puberty induction in animals, both with and without commercial interest.

The present invention, pertains in general to the field of stabilization of FSH formulations, in particular liquid FSH formulations. The stabilization is achieved by the addition of salts comprising pharmaceutically acceptable alkali metal cations, in preferred embodiments by the addition of pharmaceutically acceptable salts, i.e. sodium salts or potassium salts.

A nucleic acid sequence is provided that encodes a chimeric protein comprising a ligand that comprises a naturally occurring or modified follicle stimulating hormone sequence, e.g., an FSHβ sequence, or fragment thereof, which ligand binds to human follicle stimulating hormone (FSH) receptor, linked to either (a) a nucleic acid sequence that encodes an extracellular hinge domain, a transmembrane domain, a co-stimulatory signaling region, and a signaling endodomain; or (b) a nucleic acid sequence that encodes a ligand that binds to NKG2D. The vector containing the nucleic acid sequence, the chimeric proteins so encoded, and modified T cells expressing the chimeric protein, as well as method of using these compositions for the treatment of FSHR-expressing cancers or tumor cells are also provided.

A nucleic acid sequence is provided that encodes a chimeric protein comprising a ligand that comprises a naturally occurring or modified follicle stimulating hormone sequence, e.g., an FSHβ sequence, or fragment thereof, which ligand binds to human follicle stimulating hormone (FSH) receptor, linked to either (a) a nucleic acid sequence that encodes an extracellular hinge domain, a transmembrane domain, a co-stimulatory signaling region, and a signaling endodomain; or (b) a nucleic acid sequence that encodes a ligand that binds to NKG2D. The vector containing the nucleic acid sequence, the chimeric proteins so encoded, and modified T cells expressing the chimeric protein, as well as method of using these compositions for the treatment of FSHR-expressing cancers or tumor cells are also provided.

This invention is directed to the use of a chorionic gonadotrophin carboxy terminal peptide (CTP) or fragments thereof for modifying a polypeptide or a fragment thereof in order to increase the hydrodynamic volume of the polypeptide or fragment thereof.

The present invention relates to the field of medicinal synthesis, and discloses a method for synthesizing degarelix. The method of the present invention as a whole divides the synthesis of degarelix into two parts from amino acids at positions 5 and 6, employs proper protective groups in part of the protected amino acids therein, and finally uses in association with a specific acidolysis agent to complete the whole synthesis process. In the present invention, a proper synthesizing scheme is selected, and adaptive protective group and acidolysis agent are selected, so that the overall synthesis process is optimized, the purity of degarelix is significantly improved with a higer total yield, and the production of the toxic hydantoin degradation product is avoided.

The present invention relates to the field of medicinal synthesis, and discloses a method for synthesizing degarelix. The method of the present invention as a whole divides the synthesis of degarelix into two parts from amino acids at positions 5 and 6, employs proper protective groups in part of the protected amino acids therein, and finally uses in association with a specific acidolysis agent to complete the whole synthesis process. In the present invention, a proper synthesizing scheme is selected, and adaptive protective group and acidolysis agent are selected, so that the overall synthesis process is optimized, the purity of degarelix is significantly improved with a higer total yield, and the production of the toxic hydantoin degradation product is avoided.