174 results about "Fc domain" patented technology

This invention provides a tetrahedral antibody comprising a first, second, third, and fourth domain, wherein the first and second domains are Fab or Fc domains; wherein each of the first and second domains comprise a first polypeptide chain comprising a first N-terminus of the domain, and a second polypeptide chain comprising a second N-terminus of the domain; wherein the first N-terminus of the first domain and the first N-terminus of the second domain are joined to each other by a non-peptidyl linkage, which can be a covalent linkage or a non-covalent linkage between first and second dimerizing polypeptides attached to the first N-termini of the first and second domains, respectively; and wherein the third and fourth domains are attached at their respective C-termini to the second N-termini of the first and second domains, respectively, or the N-termini of the first and second dimerizing polypeptides.

The present application relates to antigen binding molecules comprising a pair of biparatomotic target binding domains, a pair of cytokine receptor binding domains and an Fc domain wherein the target binding domains concurrently bind to a target antigen and the cytokine receptor binding domains bind to a subunit of a cytokine receptor complex. Biparatopic assembly of the cytokine receptor binding domain in the presence of the target antigen allows for selective activation of cytokine receptors and efficient mimicking of cytokine activity in a targeted manner.

The present disclosure relates to compositions and methods for treating viral infections. Compositions and methods for treating viral infections include conjugates comprising a viral neuraminidase inhibitor (e.g., zanamivir, peramivir, or an analog thereof) linked to an Fc monomer, an Fc domain, and an Fc binding peptide, albumin, or an albumin binding peptide. In particular, the conjugates are useful in the treatment of viral infections (e.g., influenza virus infections).

The disclosure provides conjugates including an Fc domain monomer or Fc domain covalently linked to a moiety that binds to or inhibits CD73. The disclosure also provides pharmaceutical compositions including such conjugates and uses of such conjugates in the treatment of cancer.

The present disclosure relates to binding proteins comprising: a first transferrin receptor 1 binding moiety M1 comprising an immunoglobulin heavy chain variable region (VH) and an immunoglobulin light chain variable region (VL) and having the ability to selectively bind to an epitope located in the hTfR1 protease-like domain; and a second portion M2, the M2 comprising an antibody Fc domain. In the binding protein, M1 and M2 are linked to each other by at least one peptide linker between M1 and M2.

The present invention relates to modulators of TNF signalling for use in treating and / or preventing acute pain. In particular, a modulator of TNF signalling may be a tumour necrosis factor receptor 2 (TNFR2) agonist comprising (i) a TNFR2 binding domain comprising three TNF homology domains (THD) that specifically bind to TNFR2; and (ii) an Fc domain. The present invention further relates to combinations of a TNFR2 agonist and an inhibitor of tumour necrosis factor receptor 1 (TNFR1) signalling.

The present invention provides novel recombinant IL-33 proteins and methods of use thereof. In some embodiments the recombinant IL-33 proteins are Fc fusion proteins comprising an IL-33 domain and an Fc domain.

The present disclosure relates to VEGF antagonists. VEGF antagonists disclosed herein comprise a VEGF binding domain and a multimerization domain. Certain VEGF antagonists disclosed herein comprise five or more dimers, each dimer comprising two polypeptides, each polypeptide comprising a VEGF binding domain and a multimerization domain comprising an IgG Fc domain and, optionally, an IgM tailpiece. The disclosure further provides pharmaceutical compositions comprising the VEGF antagonists and methods of use of the VEGF antagonists in therapy, e.g., for treating angiogenic eye disorders. Also disclosed are nucleic acids encoding the VEGF antagonists, recombinant cells that express the VEGF antagonists, and methods of producing the VEGF antagonists.

The disclosure provides Fc polypeptides wherein the Fc domain comprises at least one amino acid substitution that reduces binding affinity to an Fc receptor and / or effector function comprising one or more, two or more, three or more, four or more, or all five amino acid substitutions selected from L234A, L235A, G237A, K322A, and P329G, wherein the residues are numbered according to the EU index, preferably wherein the Fc polypeptide is an antibody. In some embodiments, the antibody is an anti-GIP antibody. In some embodiments, the antibody further comprises the three M252Y, S254T and T256E substitutions or the two M428L and N434S substitutions, which extend the half-life of the antibody.

This invention provides low-viscosity antigen-binding proteins and methods for producing them. [Solution] The present invention relates to a method for reducing the viscosity of an antigen-binding protein by modifying the sequence in the framework region and / or Fc domain, which has been shown to be associated with high viscosity. The present invention provides antigen-binding proteins, particularly antibodies, that have been mutated to reduce viscosity. Preferred antigen-binding proteins according to the present invention include antibodies, as shown in Figure 1B, having one or more, preferably all, of the following: VH1|1-18 germline subfamily substitution; VH3|3-33 germline subfamily substitution; VK3|L16 germline subfamily substitution; VK3|L6 germline subfamily substitution; or Fc substitution.

An aqueous solution composition having a pH in the range of 4.0 to 8.5, comprising: an antibody construct comprising an Fc domain; optionally, one or more buffering agents which are a substance having at least one ionizable group, have a pKa in the range of 3.0 to 9.5, and have a pKa within 2 pH units of the pH of the composition; optionally, one or more neutral amino acids; and an uncharged tension regulator; wherein the total concentration of the buffer in the composition is 0-5 mM; and wherein the composition has a total ionic strength of less than 20 mM, excluding the contribution of engineered protein constructs.

The preparation of a library of bispecific binders expressed in eukaryotic cells described herein is a method for producing a cloned library of eukaryotic cells containing DNA encoding a diverse library of bispecific binders, the present invention relates to bispecific conjugates, in particular bispecific conjugates comprising a first binding domain coupled to a first Fc domain and a second binding domain coupled to a second Fc domain.

This disclosure provides one or more oligomannose-type N-glycans and glycosylated Fc domain variants containing Fc domain mutations. The disclosure also provides nucleic acids encoding Fc domain variants and host cells for constructing Fc domain variants. Methods for increasing the yield of Fc domain variants and methods for treating diseases using Fc domain variants are also provided.

The present invention relates to compositions and methods of GDNF fusion polypeptides, wherein the GDNF fusion polypeptides include an Fc domain, an albumin-binding peptide, a fibronectin domain, or a human serum albumin, joined to a GDNF variant either directly or by the way of a linker. The GDNF fusion polypeptides may used to treat metabolic diseases, such as obesity and Type-1 and Type-2 diabetes, and neurological diseases, such as Amyotrophic lateral sclerosis (ALS) and Parkinson's disease.

The present invention relates to antibodies that bind to IgE and their use in the treatment of autoimmune diseases, particularly Bullous Pemphigoid (BP) and Chronic Spontaneous Urticaria (CSU). The anti-IgE antibodies comprise a variant Fc domain that binds to the Fc receptor FcRn with increased affinity relative to a wild-type Fc domain. The anti-IgE antibodies may comprise a variant Fc domain comprising the amino acids Y, T, E, K, F and Y at EU positions 252, 254, 256, 433, 434 and 436, respectively, wherein the variant Fc domain binds to human FcRn with increased affinity relative to a wild-type human IgG Fc domain.

Antibody-based binding agents derived from human and camelid immunoglobulins are described, as well as strains of yeast engineered to secrete the binding agents, and methods of treating and preventing Clostridium difficile infections using the engineered strains of yeast. These binding agents recognize and bind with specificity to Clostridium difficile toxin A and / or toxin B and in some cases exhibit toxin neutralizing activity. The binding agents include camelid VHH peptide monomers, linked groups of VHH peptide monomers, VHH peptide monomers joined to antibody Fc domains, and VHH peptide monomers joined to IgG antibodies.

The present invention relates to a fusion protein, immunogenic composition, recombinant vaccine, and molecular architecture design and application, etc., for the prevention of Streptococcus Pneumoniae infection. The present invention starts from the protein molecular tertiary structures of ply and PhtD, and via creatively screening, the C-terminal domain of ply protein and the N-terminal domain of phtD protein are finally selected to construct a fusion protein, and the elements such as Fc domain and STABILON are further added. The fusion protein molecule of the present invention can weaken tissue lesions caused by Streptococcus Pneumoniae infection, has good immunogenicity, has an effective preventive and immunoprotective effect, and efficiently prevents Streptococcus Pneumoniae infection. The immunogenic composition, fusion protein, and recombinant vaccine for preventing Streptococcus Pneumoniae infection of the present invention have broad application prospects.

The present invention relates to the combined use of Fc [gamma] RIIb (CD32B) and CD20 specific antibodies, and specifically provides a method of treating a patient having a target cell expressing Fc [gamma] RIIb, the method comprising administering in combination (i) an antibody molecule that specifically binds to a surface antigen of the target cell, the antibody molecule having an Fc domain capable of binding Fc [gamma] RIIb; and (ii) an agent that inhibits or reduces binding between the Fc domain of the antibody molecule and Fc [gamma] RIIb, characterized in that the patient is selected on the basis of an increase in Fc [gamma] RIIb expression level of its target cell.

The present invention provides a pharmaceutical composition for use in a method of treating pulmonary arterial hypertension (PAH). [Solution] A pharmaceutical composition for use in a method for treating pulmonary arterial hypertension (PAH) in a patient in need, comprising an ActRIIA fusion protein, wherein the ActRIIA fusion protein is (i) ActRIIA polypeptide containing a specific amino acid sequence, (ii) Fc domains containing an amino acid sequence that is at least 95% identical to a specific amino acid sequence, (iii) comprising a linker domain located between the ActRIIA polypeptide and the Fc domain, Herein, the ActRIIA fusion protein is administered in a first dose of 0.3 mg / kg and a second dose of 0.7 mg / kg, wherein the second dose is administered after confirming that the patient has an acceptable hemoglobin level and / or platelet count, in a pharmaceutical composition.

There remains a need for effective therapeutic agents for the treatment of TGFβ superfamily-associated disorders. [Solution] Polypeptides comprising an activin receptor type IIB (ActRIIB) ectodomain (ECD) variant are provided. In some embodiments, the polypeptides of the present disclosure comprise an ActRIIB-ECD variant fused to an Fc domain portion. The present disclosure also provides pharmaceutical compositions and methods using the polypeptides to treat diseases and conditions associated with TGF-β superfamily ligand signaling, such as metabolic disorders, diabetes, obesity, cardiometabolic disease, pulmonary hypertension, fibrosis, muscle weakness and atrophy, bone damage, and / or low red blood cell levels (e.g., anemia).

The present invention provides, among other things, a masked cytokine comprising an interleukin 2 (IL-2) polypeptide, a VHH masking moiety, an anti-PD1 targeting moiety, and an engineered Fc domain comprising a tumor-associated protease cleavage site. In such masked cytokine, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavage site in the Fc domain, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

The present disclosure provides inter alia, molecules comprising an autoantibody-binding domain and at least one modified Fc domain. The present disclosure also provides methods and compositions that allow for selective depletion and / or neutralization of pathogenic autoantibodies.

The present invention relates to antibodies that bind to IgE and their use in the treatment of autoimmune diseases, particularly Bullous Pemphigoid (BP) and Chronic Spontaneous Urticaria (CSU). The anti-IgE antibodies comprise a variant Fc domain that binds to the Fc receptor FcRn with increased affinity relative to a wild-type Fc domain. The anti-IgE antibodies may comprise a variant Fc domain comprising the amino acids Y, T, E, K, F and Y at EU positions 252, 254, 256, 433, 434 and 436, respectively, wherein the variant Fc domain binds to human FcRn with increased affinity relative to a wild-type human IgG Fc domain.

The invention provides a method of treating a patient having target cells that express FcγRIIb, the method comprising administering (i) an antibody molecule that specifically binds a surface antigen of the target cell, which antibody molecule has an Fc domain capable of binding FcγRIIb; in combination with (ii) an agent that prevents or reduces binding between the Fc domain of the antibody molecule and FcγRIIb; characterized in that the patient is selected on the basis that their target cells express an elevated level of FcγRIIb.

Provided are transferrin receptor binding VHH domains as well as delivery complexes and methods for targeting cells of interest for delivery of an active cargo such as an oligomeric agent. In particular, the delivery complex may comprise modified Fc domain and a transferrin receptor binding VHH domain.

Described herein are methods to affect binding by a multivalent binding molecule to a FZD receptor and a Wnt co-receptor on a cell wherein binding by the multivalent binding molecule to both FZD receptor and co-receptor on the cell activates a Wnt signaling pathway. Also described herein are multivalent binding molecules comprising a FZD receptor binding domain and a Wnt co-receptor biding domain on either end of an Fc domain that activate a Wnt signaling pathway and methods for their use.

The present invention relates to a Fab-arm (Fab-arm) exchange prevention Fc variant, the effector function of which is reduced due to elimination of binding force with Fc [gamma] Rs and C1q, and the human antibody Fc domain variant of the present invention is a novel variant different from the conventional Fab-arm exchange prevention variant, which can overcome the Fab arm exchange phenomenon, which is the disadvantage of IgG4, and which does not bind to all human Fc [gamma] Rs and C1q, and which can be used as a novel human antibody Fc domain variant having a reduced effector function due to elimination of binding force with Fc [gamma] Rs and C1q. The compound does not bind to mouse and monkey Fc [gamma] Rs, has excellent blood half-life and thermal stability, and thus can be used for preventing immune cell / normal cell death (toxicity) caused by a therapeutic antibody or an antibody Fc region of an Fc-fusion protein drug.

The present disclosure relates to VEGF antagonists. VEGF antagonists disclosed herein comprise a VEGF binding domain and a multimerization domain. Certain VEGF antagonists disclosed herein comprise five or more dimers, each dimer comprising two polypeptides, each polypeptide comprising a VEGF binding domain and a multimerization domain comprising an IgG Fc domain and, optionally, an IgM tailpiece. The disclosure further provides pharmaceutical compositions comprising the VEGF antagonists and methods of use of the VEGF antagonists in therapy, e.g., for treating angiogenic eye disorders. Also disclosed are nucleic acids encoding the VEGF antagonists, recombinant cells that express the VEGF antagonists, and methods of producing the VEGF antagonists.

The present disclosure provides a method of treating an autoimmune disease or inflammatory disease in an individual comprising administering to the individual a combination therapy. The combination therapy comprises a CD-2 binding molecule comprising a CD2-binding domain linked to an Fc domain and a composition comprising modified regulatory T (Treg) cells. The CD-2 binding molecule is administered first to precondition the individual for administration of the composition comprising the modified Treg cells.

The present disclosure relates to a cleavable vector and a cytokine prodrug linked to the cleavable vector, wherein the cleavable vector is an engineered Fc domain comprising at least one tumor-associated protease cleavage site. Upon cleavage at the cleavage site of the vector Fc domain, the cytokine is released from the masking moiety. The platform provides enzymatically induced prodrug activation. The present disclosure also provides pharmaceutical compositions comprising the cleavable vector-linked cytokine prodrugs, for use as medicaments and methods of treating diseases and administering.