The problem to be addressed by the present invention is to provide improved recombinant FcγRIIb and FcγRIIa that do not require refolding and exhibit high productivity and thermal stability, and to provide a method for producing the same. Said problem is solved by improved recombinant FcγRIIb comprising at least the amino acid residues of the extracellular domain of human FcγRIIb (No. 43 to No. 215 in UniProt No. P31994), wherein, in said amino acid residues, at least one amino acid substitution has occurred at a position corresponding to No. 82, 94, 98, 104, 105, or 139 in UniProt No. P31994. Said problem is also solved by improved recombinant FcγRIIa comprising at least the amino acid residues of the extracellular domain of human FcγRIIa (No. 34 to No. 206 in UniProt No. P12318-1), wherein, in said amino acid residues, at least one amino acid substitution has occurred at a position corresponding to No. 73, 85, 89, 95, 96, or 130 in UniProt No. P12318-1.

The present disclosure relates to a polypeptide containing an Fc domain in which a part of an amino acid sequence of a human antibody Fc domain is substituted with another amino acid sequence, or an aglycosylated antibody containing the same. The Fc domain of the present disclosure is optimized by substituting a part of an amino acid sequence of a wild-type Fc domain with another amino acid sequence. Therefore, it is useful in treatment of cancer due to superior selective binding ability to FcγRIIIa among Fc receptors, and can be prepared as a homogeneous aglycosylated antibody through bacterial culture.

The present invention provides novel blockers of the potassium channel Kv1.3, polynucleotides encoding them, and methods of making and using them.

Described herein are novel compositions comprising, for example, PDCL3 polypeptides having VEGFR-2 inhibitory activity, inhibitory PDCL3 antibodies and PDCL3-binding fragments thereof, or PDCL3 inhibitory nucleic acid molecules, and methods of their use in anti-angiogenesis and anti-tumor proliferation and invasiveness therapies, such as the treatment of cancer, as well as the treatment of those vascular diseases where pathological angiogenesis plays a role, such as in carotid artery disease, macular degeneration, and plaque neovascularization. Also described herein are novel compositions comprising engineered PDCL3 polypeptides having enhanced chaperone activity, recombinant cells comprising such engineered PDCL3 polypeptides having enhanced chaperone activity, and methods thereof for therapeutic protein production and in vitro protein synthesis.

A method for predicting cell membrane permeability of a cyclic peptide enables versatile design of a cyclic peptide with cell membrane permeability. The method includes a first step of acquiring a structure of the cyclic peptide; a second step of calculating a molecular shape factor r which is calculated by Expression (1) after a step of carrying out an ellipsoidal approximation for obtaining each of axis lengths a, b, and c in a case where an axis length in a longest axis direction of a main chain structure is denoted by a, and axis lengths in two other directions which are orthogonal to a and are orthogonal to each other are denoted by b and c in the structure acquired in the first step; and a third step of determining that the cyclic peptide having the molecular shape factor r in a range of 0.4 to 0.6 has cell membrane permeability.

[00001]$\begin{array}{cc}r=\frac{2\sqrt{b^2+c^2}}{\sqrt{a^2+b^2}+\sqrt{c^2+a^2}}& \left(1\right)\end{array}$

The present invention pertains to inter alia therapeutic delivery vesicles, for instance exosomes or microvesicles, comprising polypeptide constructs, methods for producing said therapeutic delivery vesicles, pharmaceutical compositions and medical uses thereof. The therapeutic polypeptide constructs comprised in the extracellular delivery vesicles enable sequestering target molecules of interest, to treat e.g. neuro-inflammatory diseases and cancer.

Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

The present application in one aspect provide Fc-containing polypeptide conjugates comprising an Fc-containing polypeptide conjugated to a conjugate moiety, wherein the Fc-containing polypeptide comprises an N-glycosylated Fc region comprising an acceptor glutamine residue flanked by an N-glycosylation site and wherein the conjugate moiety is conjugated to the Fc-containing polypeptide via the acceptor glutamine residue. Also provided are methods of making such Fc-containing polypeptide conjugates by using a wildtype or engineered transglutaminases. Further provided are engineered transglutaminases specifically designed for carrying out such reactions.

The present application in one aspect provide Fc-containing polypeptide conjugates comprising an Fc-containing polypeptide conjugated to a conjugate moiety, wherein the Fc-containing polypeptide comprises an N-glycosylated Fc region comprising an acceptor glutamine residue flanked by an N-glycosylation site and wherein the conjugate moiety is conjugated to the Fc-containing polypeptide via the acceptor glutamine residue. Also provided are methods of making such Fc-containing polypeptide conjugates by using a wildtype or engineered transglutaminases. Further provided are engineered transglutaminases specifically designed for carrying out such reactions.

The present invention discloses modified Staphylococcus aureus HIa proteins which show reduced tendency to aggregate, improving protein stability and yield. Said modified HIa proteins optionally also contain glycosylation site consensus sequences. The invention also discloses a conjugate comprising a modified HIa protein and an antigen (for example a Staphylococcus aureus saccharide antigen), wherein the antigen is linked to an amino acid residue of the modified HIa protein.