Abstract: The present disclosure relates to immunoglobulins and immunoglobulin conjugates with reduced oligomerization and efficient labeling and compositions, methods of generating such immunoglobulins and immunoglobulin conjugates and methods of using such immunoglobulin conjugates particularly in the treatment and prevention of disease.

Abstract: The present disclosure relates generally to multi-specific Fab fusion proteins (MSFP) which comprise an antibody Fab fragment with both N-termini fused to a fusion moiety (fusion moiety A or B). MSFP containing the Fab fragment exhibit significantly reduced binding ability of the Fab fragment to the Fab target. Binding of the Fab to its target is restored when the MSFP is clustered on a cell surface by binding of the fusion moieties to their target. The reduced binding of the Fab to its target, especially when presented on a cell surface in its native state, absent fusion moiety binding provides advantages such as: reduced side effects and allows desirable pharmacological effects of selectivity and specificity in a controlled manner.

Abstract: The invention relates to an expression construct for the expression of polypeptides in host cells using alternative splicing. The expression construct can be used for the expression of polypeptides such as antibodies, antibody fragments and bispecific antibodies by expressing the gene products required for protein expression at the ratio leading to the highest titres or the best product quality profile.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

Abstract: The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

Abstract: Provided is a humanized or chimeric antibody or fragment thereof capable of binding to interleukin-10 (IL-10), wherein said antibody or fragment thereof: (i) binds to the same region of IL-10 as the IL-10 receptor ?(IL-I10Ra) and is not capable of binding IL-10 when the IL-10 is bound to the IL- 10 receptor; and (ii) binds to IL-10 in homodimeric form by binding a discontinuous epitope comprising residues of both monomers. Further provided are related products and methods involving the use of the antibody or fragment thereof.

Abstract: The present invention is directed to fusion proteins having an IL-21 cytokine portion and an anti-CD20 antibody portion, and methods of using such fusion proteins. The invention also provides pharmaceutical compositions and kits utilizing the IL-21-anti-CD20 fusion proteins. In particular, the methods, kits and compositions of the invention are useful in the treatment of cancer and autoimmune diseases.

Abstract: The Invention relates to a chimeric protein comprising at least one clotting factor and at least a portion of an immunoglobulin constant region. The invention relates to a method of treating a hemostatic disorder comprising administering a therapeutically effective amount of a chimeric protein wherein the chimeric protein comprises at least one clotting factor and at least a portion of an immunoglobulin constant region.

Abstract: New chimeric molecules involving in their structure, a combination of the extracellular domain (EC) of the FasL protein and a domain enabling oligomerisation of this Fas Ligand (FasL) EC domain, such as the Ig-like (so-called Ig in the following pages) domain of the gp190 receptor for the Leukemia Inhibitory Factor (LIF), or involving in their structure variants of the domains. Also, compositions including the chimeric molecule defined herein and the use of these chimeric molecules especially to trigger cytotoxic activity toward cells sensitive to FasL.

Abstract: Provided are bispecific antibodies having a full-size antibody portion with two light chains and two heavy chains, wherein the two heavy chains each is fused to a single-chain variable fragment (scFv) portion. In certain embodiments, the full-size antibody has specificity to EGFR and the scFv has specificity to VEGF.

Abstract: Polypeptides are provided that are capable of significantly inhibiting andor neutralizing P aeruginosa. The polypeptides comprise two or more immunoglobulin single variable domains that are directed against the PcrV protein of P. aeruginosa, wherein the “first” immunoglobulin single variable domain and the “second” immunoglobulin single variable domain have different paratopes.

Abstract: The present invention relates to a binding molecule that specifically binds to two different epitopes of an antigen expressed on tumor cells, wherein the binding molecule comprises: (a) a first binding (poly)peptide that specifically binds to a first epitope of said antigen expressed on tumor cells, wherein said first binding (poly)peptide is a Fyn SH3-derived polypeptide; and (b) a second binding (poly)peptide that specifically binds to a second epitope of said antigen expressed on tumor cells. The present invention further relates to a nucleic acid molecule encoding the binding molecule of the invention, a vector comprising said nucleic acid molecule as well as a host cell or a non-human host transformed with said vector. The invention further relates to a method of producing a binding molecule of the invention as well as to pharmaceutical and diagnostic composition.

Abstract: The present invention relates to bispecific, tetravalent antigen binding proteins, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: The present invention relates to a binding molecule comprising at least three domains comprised in at least one polypeptide chain, wherein the first binding domain is a binding domain which is capable of binding to a cell surface molecule on a target cell, the second binding domain is a binding domain which is capable of binding to the T cell CD3 receptor complex, and the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

Abstract: The present invention relates to immunoglobulins that bind Fc?RIIb+ cells and coengage the antigen on the cell's surface and an Fc?RIIb on the cell's surface, methods for their generation, and methods for using the immunoglobulins.

Abstract: The present invention refers to monoclonal humanized antibodies, which bind to the extracellular domain of the AXL receptor tyrosine kinase and which at least partially inhibit AXL activity.

Abstract: The present invention relates to immunoglobulins that bind Fc?RIIb+ cells and coengage the antigen on the cell's surface and an Fc?RIIb on the cell's surface, methods for their generation, and methods for using the immunoglobulins.

Abstract: Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

Abstract: The present invention relates to bispecific, bivalent antibodies against human vascular endothelial growth factor (VEGF/VEGF-A) and against human angiopoietin-2 (ANG-2), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: The invention provides methods for isolating cells, particularly antibody-secreting cells that have a high likelihood of secreting antibodies specific for a desired antigen for the purpose of making monoclonal antibodies.

Abstract: The disclosure relates to penetration-enhanced targeted proteins and their uses for therapeutics delivery.

Abstract: The present invention relates to tri- or tetraspecific antibodies, their manufacture and use.

Abstract: The invention provides a chimeric antigen receptor (CAR) (a) an antigen binding domain of HN1 or SS, a transmembrane domain, and an intracellular T cell signaling domain, or (b) an antigen binding domain of SS1, a transmembrane domain, an intracellular T cell signaling domain, and a granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor 2 leader. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.

Abstract: A bispecific chimeric protein including a designed ankyrin repeat protein (DARPin), and an IgG antibody, an scFv-Fc antibody fragment, or a combination thereof, linked to the DARPin; a method for treating or preventing cancer using the same; and related methods and compositions.

Abstract: Disclosed herein are monoclonal antibodies specific for factor XI (fXI) that prevent activation of fXI by factor XIIa (fXIIa). The monoclonal antibodies are universal fXI antibodies, capable of binding all mammalian species tested. The anti-fXI monoclonal antibodies prolong clotting time in mammalian plasmas. Moreover, administration of the fXI monoclonal antibodies disclosed herein results in inhibition of thrombosis without altering hemostasis in animal models of thrombosis. Thus, provided herein are monoclonal antibodies specific for fXI that block activation of fXI by fXIIa, compositions and immunoconjugates comprising such antibodies and their methods of use.

Abstract: The present application discloses humanized 1H7 antibodies. The antibodies bind to human alpha synuclein and can be used for treatment and diagnosis of Lewy body disease.

Abstract: This disclosure relates to combination therapies comprising anti-Pseudomonas Psl and PcrV binding molecules and related compositions, for use in prevention and treatment of Pseudomonas infection.

Abstract: Provided herein are methods and compositions for treating a subject suffering from an enzyme deficiency in the central nervous system (CNS). The bifunctional fusion antibodies provided herein comprise an antibody to an endogenous blood brain barrier (BBB) receptor and an enzyme deficient in mucopolysaccharidosis III (MPS-III). The fusion antibodies provided herein comprise N-sulfoglucosamine sulfohydrolase (SGSH), alpha-N-acetylgulcosaminidase (NAGLU), heparin-alpha-glucosaminide N-acetyltransferase (HGSNAT), or N-acetylglucosamine-6-sulfatase (GNS). The methods of treating an enzyme deficiency in the CNS comprise systemic administration of a fusion antibody provided herein.

Abstract: The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster3 of BCMA, and the second binding domain is capable of binding to the Tcell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

Abstract: The present disclosure relates to a symmetric bispecific antibody of the class IgG4 comprising two heavy chains which each comprise a variable domain, CH1 domain and a hinge region, wherein in each heavy chain: the cysteine in the CH1 domain which forms an inter-chain disulphide bond with a cysteine in a light chain is substituted with another amino acid; and optionally one or more of the amino acids positioned in the upper hinge region is substituted with cysteine, wherein the constant region sequence of each heavy chain is similar or identical and the variable region in each heavy chain is different, formulations comprising the same, the use of each of the above in treatment and processes for preparing said antibodies and formulations.

Abstract: The present disclosure provides an asymmetric mixed antibody comprising two heavy chains or heavy chain fragments each comprising at least a variable region, a hinge region and a CH1 domain, wherein a first heavy chain or fragment thereof is a class IgG4 and has: a the inter-chain cysteine at position 127, numbered according to the Kabat numbering system, in the CH1 domain is substituted with another amino acid; and b optionally one or more of the amino acids positioned in the upper hinge region is substituted with cysteine, and wherein the second heavy chain or fragment thereof is characterised in that part or all of the chain has a different amino acid sequence to said first heavy chain in at least the region outside the variable region (for example the constant region), formulations comprising the same, therapeutic used of both of the above, and processes for preparing the antibodies and formulation.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: A method of preparing an antibody suitable for use in a canine is provided. Also provided are caninised antibodies which specifically bind to canine neuronal growth factor (NGF) and neutralise the ability of canine NGF to bind to the p75 or TrkA canine NGF receptor. The invention extends to nucleic acids encoding same and to methods of treating pain and arthritis in a canine using said antibodies and/or nucleic acids.

Abstract: Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Abstract: An object of the present invention is to provide a novel anti-human CCR7 antibody useful as a therapeutic agent for tissue fibrosis or cancer, and a pharmaceutical composition containing the anti-human CCR7 antibody, and the like. An anti-human CCR7 antibody specifically binding to an extracellular domain of human CCR7, having a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 7, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 47, SEQ ID NO: 57, SEQ ID NO: 67, or SEQ ID NO: 77 is provided. Also provided is an anti-human CCR7 antibody having heavy chain CDRs 1-3 and light chain CDRs 1-3 containing amino acid sequences represented by SEQ ID NOs: 5-10, 15-20, 25-30, 35-40, 45-50, 55-60, 65-70, or 75-80. Preferably, the antibody has an activity of interfering with a CCR7-dependent intracellular signal transduction mechanism caused by CCR7 ligand stimulation.

Abstract: The present invention relates to a bispecific (monoclonal) antibody molecule with a first binding domain binding an antigen on CD8+ T-cells that does not naturally occur in and/or on CD8+ T-cells and a second binding domain binding to a tumor specific antigen naturally occurring on the surface of a tumor cell. The bispecific (monoclonal) antibody molecules are particularly useful in combination with transduced CD8+ T-cells comprising an antigen which does not naturally occur in and/or on CD8+ T-cells and/or a T-cell receptor.

Abstract: The present invention relates to Fc variants having decreased affinity for Fc?RIIb, methods for their generation, Fc polypeptides comprising optimized Fc variants, and methods for using optimized Fc variants.

Abstract: The invention relates to factor D inhibitors, which bind to factor D and block the functional activity of factor D in complement activation. The inhibitors include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab?)2 and Fv, small molecules, including peptides, oligonucleotides, peptidomimetics and organic compounds. A monoclonal antibody which bound to factor D and blocked its ability to activate complement was generated and designated 166-32. The hybridoma producing this antibody was deposited at the American Type Culture Collection, 10801 University Blvd., Manassas, Va. 20110-2209, under Accession Number HB-12476.

Abstract: The invention relates to isolated, synthetic or recombinant antibodies and functional parts thereof specific for multiple influenza A virus subtypes. The invention further relates to the use of such antibodies for diagnosis of an influenza A virus infection and as a medicament and/or prophylactic agent for at least in part treating or alleviating symptoms of an influenza A virus infection.

Abstract: The present disclosure relates to antibodies directed to CD25 and uses of such antibodies, for example to suppress organ transplant rejection or to treat multiple sclerosis.

Abstract: Recombinant antibodies (including binding fragments thereof) that bind IgE are described, along with compositions and methods of using the same in the treatment of subjects in need thereof, including subjects afflicted with atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria, gastro-intestinal inflammation, or oral-pharyngeal inflammation. In some embodiments, the antibody is a single chain variable fragment (scFv) or a disulfide linked variable fragment (sdFv). In some embodiments, the subject is a dog, cat, or horse.

Abstract: Nucleic acids encoding various monocyte-derived proteins and related compositions, including purified proteins and specific antibodies are described. Methods of using such composition are also provided.

Abstract: A peptide is disclosed of the general structure: Z—W—Y, wherein Z and Y are independently a one to eight amino acid sequence wherein the amino acids are selected from glycine and alanine and W is a non-hydrolyzable pHis analogue. Such peptides can be used to produce sequence-independent anti-phosphohistidine antibodies. Also provided are antibodies that specifically bind to a peptide comprising a phosphohistidine (or a non-hydrolyzable pHis analogue) but fail to specifically bind to an identical peptide containing histidine instead of phosphohistidine.

Abstract: The present invention provides binding agents comprising peptides capable of binding myostatin and inhibiting its activity. In one embodiment the binding agent comprises at least one myostatin-binding peptide attached directly or indirectly to at least one vehicle such as a polymer or an Fc domain. The binding agents of the present invention produced increased lean muscle mass when administered to animals and decreased fat to muscle ratios. Therapeutic compositions containing the binding agents of the present invention are useful for treating muscle-wasting disorders and metabolic disorders including diabetes and obesity.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Abstract: The present disclosure provides isolated binding molecules that bind to human 4-1BB, nucleic acid molecules encoding an amino acid sequence of the binding molecules, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using the binding molecules or compositions.

Abstract: A method for producing a variant of a parent polypeptide including a Fc region, which variant exhibits reduced binding to the protein C1q and to at least one receptor Fcg? R as compared to the parent polypeptide.

Abstract: The present invention provides molecules, including IgGs, non-IgG immunoglobulins, proteins and non-protein agents, that have increased in vivo half-lives due to the presence of an IgG constant domain, or a portion thereof that binds the FcRn, having one or more amino acid modifications that increase the affinity of the constant domain or fragment for FcRn. Such proteins and molecules with increased half-lives have the advantage that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such molecules.

Abstract: A protein complex comprising a first polypeptide comprising a first antigen-binding region; a second polypeptide comprising a second antigen-binding region; and a linker connecting the first polypeptide and the second polypeptide, wherein the first antigen-binding region is a single stranded polypeptide comprising a first light chain antigen-binding region and a first heavy chain antigen-binding region, the second antigen-binding region is a single stranded polypeptide comprising a second light chain antigen-binding region and a second heavy chain antigen-binding region, and the linker connects the C-terminal of the first polypeptide and the N-terminal of the second polypeptide, and comprises a tag including a cleavable amino acid sequence at one terminal or both terminals of the linker; as well as a bispecific antibody derived from the protein complex, and related compositions and methods.