38 results about "Hinge region" patented technology

Provided is a chimeric antigen receptor targeting GCC, comprising: an scFv that specifically recognizes GCC, a CD8 hinge region or a CD28 hinge region, a CD8 transmembrane region or a CD28 transmembrane region, a CD28 co-stimulatory signal domain or a 4-1BB co-stimulatory signal domain, and a CD3ζ signal domain; the scFv that specifically recognizes GCC comprises a heavy chain variable region VH and a light chain variable region VL, the VH comprising an HC CDR1 having the amino acid sequence shown in SEQ ID NO: 1, an HC CDR2 having the amino acid sequence shown in SEQ ID NO: 2, and an HC CDR3 having the amino acid sequence shown in SEQ ID NO: 3, and the VL comprising an LC CDR1 having the amino acid sequence shown in SEQ ID NO: 4, an LC CDR2 having the amino acid sequence shown in SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence shown in SEQ ID NO: 6.

Provided are the antibodies including an amino acid sequence of X1X2X3X4X5CPPX6 or X11X12THX15CPPC in the hinge region, and the antibody-drug conjugates prepared using this antibody. The antibodies help to improve the homogeneity of the antibody-drug conjugates.

The present invention relates to a chimeric protein comprising at least one human amyloid P component and at least one fragment of an Fc region of a human antibody, the human amyloid P component and the fragment of an Fc region with which it is associated being bound to each other by means of a hinge region.

This specification provides a bispecific agonist antibody having a modified hinge region, and a method for using the same.

The present inventors succeeded in improving the antibody constant region to have increased stability under acid conditions, reduced heterogeneity originated from disulfide bonds in the hinge region, reduced heterogeneity originated from the H chain C terminus, and increased stability at high concentrations as well as in discovering novel constant region sequences having reduced Fcγ receptor-binding, while minimizing the generation of novel T-cell epitope peptides. As a result, the present inventors successfully discovered antibody constant regions with improved physicochemical properties (stability and homogeneity), immunogenicity, safety, and pharmacokinetics.

The present invention relates to a class of lipase mutations based on hinge region and tunnel engineering and their applications. Based on computer-aided design, the invention analyzes the amino acids in the hinge region of the lipase lid through molecular dynamics simulation and uses CAVER 3.0 software to analyze the amino acids in the amine channel. Using single-point mutagenesis, iterative, and combinatorial mutagenesis techniques, the obtained mutants contain one or more mutations at amino acids 37, 206, 207, 211, 212, and 213 of the amino acid sequence. The amino acid sequence of the lipase is shown in SEQ ID NO: 1. The mutants of the present invention can be used to catalyze the synthesis of corresponding aromatic amides from ortho-substituted anilines and have broad application prospects.

The invention is based on an immunomodulatory molecule, comprising an engineered protein binding domain, a linker and / or a hinge-region, and a domain for the activation and / or stimulation of an immune effector cell. The invention also pertains to an isolated nucleic acid comprising a sequence encoding for an immunomodulatory molecule according to this invention. Further provided is a method of obtaining a chimeric antigen receptor (CAR) expressing immune effector cell product, such as a CAR-T cell product, and / or a HLA-independent T cell receptor (HIT) expressing immune effector cell product, such as a HIT-T cell product, and / or a bispecific molecule expressing immune effector cell product, such as a bispecific T cell engager (BiTE) expressing immune effector cell product, comprising an immunomodulatory molecule, and / or a bispecific molecule, such as a BiTE, comprising an engineered protein binding domain. The invention also pertains to a product thereby obtainable, and to a pharmaceutical composition comprising the immunomodulatory molecule, the isolated nucleic acid, or the product obtainable by a method according to the present invention. Also provided is an immunomodulatory molecule, an isolated nucleic acid, a product, or a pharmaceutical composition according to this invention, for use in a method of diagnosis, prevention and / or treatment of a disease, or for preventing an organ transplant rejection, in a patient in need thereof.

This disclosure provides polypeptides comprising an antibody Fc region having a deletion of one or more cysteine residues in the hinge region and substitution with a sulfhydryl-containing residue of one or more CH3-inteface amino acids. Also, provided are Fc-fusion proteins and antibodies containing said polypeptides, nucleic acids and vectors encoding said polypeptides, along with host cells and methods for making said polypeptides.

Presented herein is a recombinant OPCML-Fc fusion protein molecule and methods of its use in cancer treatment where the Fc portion of the fusion protein molecule is only the CH2CH3 portion and lacks the hinge region containing the disulfide bridges preventing dimerization of the Fc portion and optimizing dimerization of the OPCML the D1 domain.

The present inventors succeeded in improving the antibody constant region to have increased stability under acid conditions, reduced heterogeneity originated from disulfide bonds in the hinge region, reduced heterogeneity originated from the H chain C terminus, and increased stability at high concentrations as well as in discovering novel constant region sequences having reduced Fcγ receptor-binding, while minimizing the generation of novel T-cell epitope peptides. As a result, the present inventors successfully discovered antibody constant regions with improved physicochemical properties (stability and homogeneity), immunogenicity, safety, and pharmacokinetics.

The invention relates to a chimeric antigen receptor targeting MUC18. The chimeric antigen receptor comprises an antibody fragment capable of specifically recognizing MUC18, an IgG4 hinge region, a CD8 transmembrane region or a CD28 transmembrane region, a CD28 costimulatory signal domain or a 4-1BB costimulatory signal domain and a CD3 zeta signal domain, the antibody fragment comprises a heavy chain variable region VH and a light chain variable region VL, the VH comprises an HC CDR1 of an amino acid sequence as shown in SEQ ID NO: 7, an HC CDR2 of an amino acid sequence as shown in SEQ ID NO: 8 and an HC CDR3 of an amino acid sequence as shown in SEQ ID NO: 9, and the VL comprises an LC CDR1 of an amino acid sequence as shown in SEQ ID NO: 10, an LC CDR2 of an RAS amino acid sequence and an LC CDR3 of an amino acid sequence as shown in SEQ ID NO: 11.

Some embodiments include a computer-assisted method of biomedical treatment design. For example, a computer system can select a compound model associated with a candidate compound that is structured to bind to a biological target to modulate the biological target into achieving a therapeutic effect. The computer system can then identify a structural feature in the compound model as a hinge region that connects domains in the candidate compound. The computer system then determines a mutation process to introduce a mutation at the hinge region such that the mutation activates the candidate compound. The computer system then generates an updated compound model based on the mutation added to the candidate compound to present in a treatment design interface.

The invention provides antibody heavy chain constant regions with a hinge region modified to reduce binding to Fcγ receptors. The modification occurs within positions 233-236 by replacement of natural residues by glycine(s) and / or deletion(s). Such modifications can reduce binding of an antibody bearing such a constant region to Fcγ receptors to background levels. The constant regions can be incorporated into any format of antibody or Fc fusion protein. Such antibodies or fusion proteins can be used in methods of treatment, particularly those in which the mechanisms of action of the antibody or Fc fusion protein is not primarily or at all dependent on effector functions, as is the case when an antibody inhibits a receptor-ligand interaction or agonizes a receptor.

Provided herein are recombinant OPCML-Fc fusion protein molecules and methods of use thereof in the treatment of cancer wherein the Fc portion of the fusion protein molecule is only the CH2CH3 portion and lacks a hinge region comprising a disulfide bridge, which prevents dimerization of the Fc portion and optimizes dimerization of the D1 domain of OPCML.

The invention relates to a chimeric antigen receptor targeting GCC. The chimeric antigen receptor comprises scFv capable of specifically recognizing GCC, a CD8 hinge region or a CD28 hinge region, a CD8 transmembrane region or a CD28 transmembrane region, a CD28 costimulatory signal domain or a 4-1BB costimulatory signal domain and a CD3 zeta signal domain, the scFv for specifically recognizing the GCC comprises a heavy chain variable region VH and a light chain variable region VL, the VH comprises an HC CDR1 of an amino acid sequence as shown in SEQ ID NO: 1, an HC CDR2 of an amino acid sequence as shown in SEQ ID NO: 2 and an HC CDR3 of an amino acid sequence as shown in SEQ ID NO: 3, and the VL comprises an LC CDR1 of an amino acid sequence as shown in SEQ ID NO: 4, an LC CDR2 of SEQ ID NO: 5 and an LC CDR3 of an amino acid sequence as shown in SEQ ID NO: 6.

The invention relates to a novel antibody capable of binding specifically to the human c-Met receptor and / or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region.The invention also relates to a composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.

The invention provides an immune effector cell targeting CD19 and CD20 and application of the immune effector cell. Comprising scFv targeting CD19 and CD20, a hinge region, a transmembrane region and an intracellular signal structural domain. The invention also provides a polynucleotide targeting CD19 and CD20, a corresponding expression vector, a CAR-T cell and an application of the CAR-T cell.

The present invention relates to a trispecific antibody that specifically binds to CD19, CD3, and CD28, which comprises a fragment derived from the IgD hinge region as a linker. The present invention further relates to the use of the trispecific antibody for treating tumors, such as hematological malignancies.

The present invention relates to a trispecific antibody specifically binding to CD19, CD3, and CD28, which trispecific antibody contains a fragment derived from an IgD hinge region as a linker. The present invention also relates to the use of the trispecific antibody for treating tumors such as malignant hematological tumors.

The clinical potential of multispecific antibodies like bispecific and trispecific antibodies shows great promise for targeting complex diseases. However, the generation of those molecules presents great challenges as in many cases it is desired to specifically drive the specific pairing of multiple polypeptide chains that are present in solutions. In the case of the heavy chains, there are two main regions that form a dimer interface. One of them is the CH3 region, which has been widely exploited by inserting either charge-pair mutations (CPMs) to steer the dimer interface or inserting large bulky residues into cavities (Knob in Hole) to physically favor and disfavor the dimer formation. However, each of these strategies may not be applied to every molecule and therefore there is the need for more tools. Here, we describe the engineering of the Hinge region with a small number of mutations that are capable to alone successfully drive the heavy chain dimerization.

In one embodiment, it was found that a preparation containing an antigen-binding molecule can be produced more efficiently and with high reproducibility by carrying out the following steps in chromatography, the antigen-binding molecule has at least one disulfide bond formed between amino acid residues in a region other than the hinge region; contacting a mixture containing the antigen-binding molecule and a misdisulfide-bonded form and / or a non-disulfide-bonded form of the antigen-binding molecule with a solution containing a reducing agent, the antigen binding molecule has at least one disulfide bond formed between amino acid residues in a region other than the hinge region; and subsequently, removing the reducing agent.

The invention provides antibody heavy chain constant regions with a hinge region modified to reduce binding to Fcγ receptors. The modification occurs within positions 233-236 by replacement of natural residues by glycine(s) and / or deletion(s). Such modifications can reduce binding of an antibody bearing such a constant region to Fcγ receptors to background levels. The constant regions can be incorporated into any format of antibody or Fc fusion protein. Such antibodies or fusion proteins can be used in methods of treatment, particularly those in which the mechanisms of action of the antibody or Fc fusion protein is not primarily or at all dependent on effector functions, as is the case when an antibody inhibits a receptor-ligand interaction or agonizes a receptor.

The present disclosure relates to stabilization of Fc-containing polypeptides. The present disclosure provides polypeptides comprising an antibody Fc region that lacks one or more cysteine residues in the hinge region, and one or more CH3 interface amino acids are substituted with thiol group-containing residues. Furthermore, Fc fusion proteins and antibodies containing the polypeptides, nucleic acids and vectors encoding the polypeptides, and host cells and methods for making the polypeptides are provided.

This invention discloses a MITA hinge region mutant polypeptide and its application in autoimmune diseases, relating to the field of protein and peptide drug technology. This invention provides a MITA hinge region mutant polypeptide with the amino acid sequence shown in SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, or SEQ ID NO.4, or polypeptides with appropriate lengths extended from both ends of these four polypeptides. This invention uses MITA, which is most commonly found in SAVI, as an example. N153S / + Using a mouse model as the research subject, it was found that SIP could almost completely eliminate the autoimmune phenotype in mice. The survival time of the treated model mice was significantly prolonged, the rate of weight loss was slowed, and the expression levels of inflammatory factors in the liver and brain of the model mice were significantly reduced. Therefore, SIP has potential application value in the treatment of SAVI and can be widely used in the preparation of drugs to treat SAVI autoimmune diseases caused by MITA gain-of-function mutations.

To provide improved chimeric co-stimulatory receptors (CCRs), fusion proteins, genetically modified immune effector cells, and use of these compositions to treat disease.SOLUTION: The present disclosure generally relates, in part, to improved CCR polypeptides, fusion proteins, and methods of using the same. Particularly, the invention provides fusion polypeptides comprising a CAR and a modified CCR polypeptide and their use in treating, preventing, or ameliorating at least one symptom of cancer. More particularly, the CCR comprises a modified hinge region, wherein the CAR / CCR fusion polypeptide displays reduced antigen-independent signaling, e.g., signaling in the absence of a CAR antigen.SELECTED DRAWING: None

Provided herein are antibodies, recombinant proteins, and methods of use thereof including, for example, immunoglobulin G (IgG) antibodies and recombinant proteins including a Fab region and an Fc region connected through a hinge region, where the hinge region is resistant to cleavage by a protease. Also, provided herein, inter alia, are immunoglobulin G (IgG) antibodies and recombinant proteins including a Fab region and an Fc region connected through a hinge region, and where the Fc region has higher affinity for a ligand compared to a wildtype Fc.

The invention discloses an MITA hinge region mutant polypeptide and application thereof in autoimmune diseases, and relates to the technical field of protein polypeptide drugs. The invention provides an MITA hinge region mutant polypeptide, the amino acid sequence of which is as shown in SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3 or SEQ ID NO.4, or a polypeptide formed by extending two ends of the four polypeptides by a proper length. The most common MITAN153S / + mouse model in SAVI is taken as a research object, and it is found that SIP can almost completely eliminate the autoimmune phenotype of the mouse, the lifetime of the treated model mouse is remarkably prolonged, the weight loss speed is slowed down, and the expression level of inflammatory factors in the liver and brain of the model mouse is remarkably reduced. Therefore, the SIP has potential application value for treating the SAVI, and can be widely applied to preparation of drugs for treating SAVI autoimmune diseases caused by MITA function acquired mutation.

The present invention relates to a trispecific antibody specifically binding to CD19, CD3, and CD28, which trispecific antibody contains a fragment derived from an IgD hinge region as a linker. The present invention also relates to the use of the trispecific antibody for treating tumors such as malignant hematological tumors.

The present application relates to an MUC18-targeting chimeric antigen receptor, which comprises an antibody fragment that specifically recognizes MUC18, an IgG4 hinge region, a CD8 transmembrane region or a CD28 transmembrane region, a CD28 costimulatory signaling domain or a 4-1BB costimulatory signaling domain, and a CD3ζ signaling domain. The antibody fragment contains a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH contains HC CDR1 having an amino acid sequence as shown in SEQ ID NO: 7, HC CDR2 having an amino acid sequence as shown in SEQ ID NO: 8, and HC CDR3 having an amino acid sequence as shown in SEQ ID NO: 9; and the VL contains LC CDR1 having an amino acid sequence as shown in SEQ ID NO: 10, LC CDR2 having an RAS amino acid sequence, and LC CDR3 having an amino acid sequence as shown in SEQ ID NO: 11.