2151results about How to "Low immunogenicity" patented technology

The present invention relates to novel methods for generating variant proteins with increased host string content, and proteins that are engineered using these methods.

Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and / or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.

The invention provides an aqueous formulation comprising water and a protein, and methods of making the same. The aqueous formulation of the invention may be a high protein formulation and / or may have low levels of conductivity resulting from the low levels of ionic excipients. Also included in the invention are formulations comprising water and proteins having low osmolality.

The invention relates to polypeptide conjugates comprising a polypeptide exhibiting G-CSF activity and having an amino acid sequence that differs from the amino acid sequence of human G-CSF in at least one specified introduced and / or removed amino acid residue comprising an attachment group for a non-polypeptide moiety, and having at least one non-polypeptide moiety attached to an attachment group of the polypeptide. The attachment group may e.g. be a lysine, cysteine, aspartic acid or glutamic acid residue or a glycosylation site, and the non-polypeptide moiety may e.g. be a polymer such as polyethylene glycol or an oligosaccharide. The conjugate, which has a reduced in vitro bioactivity compared to hG-CSF, has one or more improved properties such as increased biological half-life and increased stimulation of neutrophils.

PEG and related polymer derivatives having weak, hydrolytically unstable linkages near the reactive end of the polymer are provided for conjugation to drugs, including proteins, enzymes, small molecules, and others. These derivatives provide a sufficient circulation period for a drug-PEG conjugate, followed by hydrolytic breakdown of the conjugate and release of the bound molecule. In some cases, drugs that demonstrate reduced activity when permanently coupled to PEG maintain a therapeutically suitable activity when coupled to a degradable PEG in accordance with the invention. The PEG derivatives of the invention can be used to impart improved water solubility, increased size, a slower rate of kidney clearance, and reduced immunogenicity to a conjugate formed by attachment thereto. Controlled hydrolytic release of the bound molecule into an aqueous environment can then enhance the drug's delivery profile by providing a delivery system which employs such polymers and utilizes the teachings provided herein.

This invention relates to humanized antibodies and antibody preparations produced from transgenic non-human animals. The non-human animals are genetically engineered to contain one or more humanized immunoglobulin loci which are capable of undergoing gene rearrangement and gene conversion in the transgenic non-human animals to produce diversified humanized immunoglobulins. The present invention further relates to novel sequences, recombination vectors and transgenic vectors useful for making these transgenic animals. The humanized antibodies of the present invention have minimal immunogenicity to humans and are appropriate for use in the therapeutic treatment of human subjects.

The present inventors succeeded in discovering specific amino acid mutations in the variable region, framework region, and constant region of TOCILIZUMAB, and this enables to reduce immunogenicity risk and the heterogeneity originated from disulfide bonds in the hinge region, as well as to improve antigen binding activity, pharmacokinetics, stability under acidic conditions, and stability in high concentration preparations.

The present invention relates to a process for preparing a cross-linked polysaccharide gel comprising contacting a polysaccharide with a cross-linking agent and a masking agent to form a cross-linked polysaccharide gel having resistance to degradation under physiological conditions.

This invention relates to Factor VIII muteins that are covalently bound, at one or more predefined sites that are not an N-terminal amine, to one or more biocompatible polymers such as polyethylene glycol. The mutein conjugates retain FVIII procoagulant activity, are capable of correcting human factor VIII deficiencies and have improved pharmacokinetic properties.

The present invention provides a method for inducing a cancer specific immune response against MUC1 using an immunogenic glycopeptide. Other aspects of the invention are a pharmaceutical composition comprising the immunogenic glycopeptide and a cancer vaccine comprising the immunogenic glycopeptide. Another aspect is an antibody generated using the immunogenic glycopeptide and the use of said antibody in therapy and diagnosis.

The invention provides an aqueous formulation comprising water and a protein, and methods of making the same. The aqueous formulation of the invention may be a high protein formulation and / or may have low levels of conductity resulting from the low levels of ionic excipients. Also included in the invention are formulations comprising water and proteins having low osmolality.

The present invention is directed to phenylalanine ammonia-lyase (PAL) produced by prokaryotes, wherein such prokaryotic PAL wherein the PAL variant has a greater phenylalanine-converting activity and / or a reduced immunogenicity as compared to a wild-type PAL. The invention thus provides compositions of bacterial PAL and biologically active fragments, mutants, variants and analogs thereof, as well as methods for the production, purification, and use of such compositions for therapeutic and industrial purposes.

A method of cutting tissue material of biology origin employs a plotted water-jet or RF cutting system. The cutting system is computer controlled and includes a water-jet or RF cutting means combined with a motion system. The cutting energy is selected so that communication of thermal energy into the segment beyond the edge is minimized to avoid damaging the segment adjacent the edge.

The invention discloses biologically related substances modified by a multifunctional H-type polyethylene glycol derivative. The derivative comprises a linear main axis LPEG and four PEG branched chains, and n1, n2, n3 and n4 are polymerization degrees of the branched chains, respectively; U1 and U2 are trivalent branching groups connecting the main axis LPEG with two PEG branched chains; F1 and F2 contain functional groups or their protected forms R01, and the number of R01 is one or more than one. Any linking group in the molecule or linking groups formed with adjacent heteroatom groups are stable or degradable; any PEG chain segment in the molecule independently shows polydispersity or monodispersity. One H-type molecule can modify multiple types of or multiple biologically related substances; the modified product has a flexible branching structure, a high drug loading capacity, optimized pharmacokinetics and tissue distribution, and can also carry two biologically related substances with different functions, so as to generate fluorescence property or targeting function.

The invention discloses a multifunctional H-type polyethylene glycol derivative and a preparation method thereof. The structure is as shown in formula (1) in the description, wherein a linear main axis LPEG and four PEG branched chains are included, and n1, n2, n3 and n4 are polymerization degrees of the branched chains, respectively; U1 and U2 are trivalent branching groups connecting the main axis LPEG with two PEG branched chains; F1 and F2 contain functional groups or their protected forms R01, and contain or do not contain branching groups G, and correspondingly, the number of R01 is one or more than one; F1 is the same as or different from F2; any linking group in the molecule or linking groups formed with adjacent heteroatom groups are stable or degradable; any PEG chain segment in the molecule independently shows polydispersity or monodispersity. The functionalized polyethylene glycol is diverse in branching structure and branching arm length, is adjustable and easily-controllable in various parameters and performance indexes, and is wide in application.

Methods are described for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The disclosure also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies with a modified isoelectric point. The disclosure further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.