72 results about "Antibody Suppression" patented technology

The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1 / PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.

The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. In some embodiments, such anti-complement C1s antibodies inhibit proteolytic activity of C1s. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.

The present invention is directed to antagonistic antibodies and antigen binding fragments thereof having binding specificity for PACAP. These antibodies inhibit, block or neutralize at least one biological effect associated with PACAP, e.g., vasodilation. In exemplary embodiments these antibodies and antigen binding fragments thereof may comprise specific VH, VL, and CDR polypeptides described herein. In some embodiments these antibodies and antigen binding fragments thereof bind to and / or compete for binding to specific epitope(s) on human PACAP. The invention is further directed to using these antagonistic anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, mast cell degranulation, and / or neuronal activation, are therapeutically beneficial, e.g., headache and migraine indications.

The present invention relates to humanized antibodies that specifically bind to IL-1R3 or a fragment or derivative thereof or a polypeptide that contains at least a portion of said antibody that is sufficient to confer IL-1R3 binding specificity. Said antibodies inhibit IL-1R3 induced NFkB activity. They also inhibit IL-1alpha, IL-1beta, IL-33, and / or IL-36 stimulated NFkB activity.The invention further relates to use of said humanized antibody in the treatment of an IL-1R3 mediated disease such as cancer.The present invention also encompasses a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody according to the invention. The pharmaceutical composition can be used in treating a IL-1R3 mediated disease such as cancer.

The invention provides antibodies that specifically bind tau. The antibodies inhibit or delay tau-associated pathologies and associated symptomatic deterioration.

The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. In some embodiments, such anti-complement C1s antibodies inhibit proteolytic activity of C1s. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.

The present invention provides antibodies that bind to interleukin-33 (IL-33) and methods of using the same. The invention includes antibodies that inhibit or attenuate IL-33-mediated signaling. The antibodies of the invention may function to block the interaction between IL-33 and ST2. Alternatively, certain antibodies of the invention inhibit or attenuate IL-33-mediated signaling without blocking the IL-33 / ST2 interaction. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human IL-33 with high affinity. The antibodies of the invention are useful for the treatment of diseases and disorders associated with IL-33 signaling and / or IL-33 cellular expression, such as inflammatory diseases, or allergic diseases.

The present disclosure provides antibodies that specifically bind to human FAM19A5 and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human FAM19A5 and modulate FAM19A5 activity, e.g., inhibit, suppress, reduce, or reverse the onset of reactive gliosis and / or excessive proliferation of reactive astrocytes, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as central nervous system damage, a degenerative brain disorder, or a neuropathic pain, by administering an antibody that specifically binds to human FAM19A5.

To provide cross-species anti-latent TGF-β 1 antibodies which inhibit a protease mediated activation of latent TGF-β 1 without inhibiting integrin mediated activation of latent TGF-β 1.SOLUTION: To obtain the anti-latent TGF-β 1 antibodies of the present invention, anti-latent TGF-β 1 antibodies which inhibit a protease mediated activation of latent TGF-β 1 without inhibiting integrin mediated activation of latent TGF-β 1 are screened, and then humanized, and further optimized. The invention also provides combination therapies comprising an anti-latent TGF-β 1 antibody and one or more immune checkpoint inhibitors, preferably PD-1 axis binding antagonists.SELECTED DRAWING: None

Pharmaceutical compositions and therapeutic methods are provided comprising a single-domain antibody consisting of SEQ ID NO:1 and a pharmaceutically acceptable carrier. The antibody inhibits KRAS GTPase activity and inhibits phosphorylation of STAT3. In certain embodiments, inhibition of KRAS results in decreased phosphorylation of ERK1 / 2. The antibody reduces tumor cell surface PD-L1 expression and reduces VEGF production. The antibody crosses the blood-brain barrier following systemic administration and may exhibit sustained biological activity in vivo. Methods are provided for treating KRAS-mutant cancers, including pancreatic cancer and triple negative breast cancer, and for enhancing anti-tumor immunity through reduction of PD-L1 expression.

It is an object of the present invention to provide anti-latent TGF-beta 1 antibodies and methods of using such antibodies. The present invention provides an anti-latent TGF-[beta] 1 antibody which inhibits protease-mediated activation of latent TGF-[beta] 1 without inhibiting integrin-mediated activation of latent TGF-[beta] 1 or which partially inhibits activation of integrin-mediated latent TGF-[beta] 1, or the antibody inhibits protease-mediated latent TGF-beta 1 activation but has a small effect on inhibition of integrin-mediated latent TGF-beta 1 activation. The present invention also provides optimized anti-latent TGF-beta 1 antibodies wherein the pH dependent binding properties are improved. The anti-latent TGF-beta 1 antibody can be used to treat fibrosis or cancer. For example, the anti-latent TGF-beta1 antibodies may be used to treat renal fibrosis, hepatic fibrosis, and pulmonary fibrosis.

The present disclosure relates to humanized antibodies that specifically bind to IL-1R3 or a fragment or derivative thereof or a polypeptide that contains at least a portion of said antibody that is sufficient to confer IL-1R3 binding specificity. Said antibodies inhibit IL-1R3 induced NFkB activity. They also inhibit IL-1alpha, IL-1beta, IL-33, and / or IL-36 stimulated NFkB activity. The disclosure further relates to use of said humanized antibody in the treatment of an IL-1R3 mediated disease such as cancer. The disclosure finally encompasses a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody according to the invention. The pharmaceutical composition can be used in treating a IL-1R3 mediated disease such as cancer.

The present application relates to anti-complement Cls antibodies and uses thereof. The present disclosure provides antibodies that bind complement Cls protein; and nucleic acid molecules encoding such antibodies. The present disclosure also provides compositions comprising such antibodies, and methods of making and using such antibodies, nucleic acid molecules, and compositions. The present disclosure provides an isolated, humanized monoclonal antibody that inhibits cleavage of complement component G4, wherein the antibody does not inhibit cleavage of complement component C2. In some cases, the antibody inhibits a component of the classical complement pathway, in some cases the classical complement pathway component is Cls. In some cases, the antibody does not inhibit protease activity of Cls.

The invention discloses an ATP hydrolase antibody efficient screening method based on a fluorescent probe, the method comprises two detection schemes of a biochemical system and a cell system, in the biochemical system, the antibody inhibition rate is directly calculated by quantifying the residual amount of ENTPD2 protein after ATP hydrolysis; in a cell system, cells over-expressing ENTPD2 are used for verifying the inhibition function of the antibody on transmembrane enzyme. According to the biochemical system method, antibody purification is not needed, primary screening can be completed only through 5-15 microliters of B cell supernate, the screening accuracy is high (the cell system can be used as an antibody obtained through verification and screening), the result is consistent with the in-vivo drug effect result, the method is suitable for development of anti-ENTPD2 antibody drugs, and the research and development cost is remarkably reduced.

To provide an agent for reducing iron overload in patients having conditions such as beta-thalassaemia and myelodysplastic syndrome (MDS).SOLUTION: Antibodies to enzyme matriptase-2 (MTP-2) are presented. Inhibiting MTP-2 reduces uptake of dietary iron and reduces release of iron from cellular stores in the body. Inhibitors of MTP-2 (such as antibodies to a serine protease domain) can be used to treat iron overload, which is a feature of diseases such as beta-thalassaemia and which otherwise leads to toxic accumulation of iron. Combination of an MTP-2 inhibitor with an activin receptor ligand trap, or with erythropoeitin, provides additional therapeutic effects.SELECTED DRAWING: Figure 1

Recombinantly expressed variant antibodies that have enhanced affinity for TL1A and enhanced potency relative to the parent antibody from which they were derived are provided. The antibodies inhibit the interaction between TL1A and the death receptor 3 (DR3). The antibodies, or a composition thereof, may be used to treat one or more of asthma, COPD, pulmonary fibrosis, cystic fibrosis, inflammatory bowel disease, a gastrointestinal disease associated with cystic fibrosis, Crohn's disease, colitis, ulcerative colitis, irritable bowel syndrome, eosinophilic esophagitis, atopic dermatitis, eczema, scleroderma, arthritis, or rheumatoid arthritis.

The present invention relates to an antibody or antigen-binding fragment thereof that specifically binds to IGFBP3. The antibody inhibits or reduces the binding of IGFBP3 to the TMEM219 receptor. The present invention also relates to a method for producing the antibody, a pharmaceutical composition containing the antibody, and its use.

This invention provides novel human antibodies that bind to human galectin-9, and their therapeutic use in the treatment of cancer. [Solution] Provided are isolated anti-galectin-9 antibodies that bind to epitopes in the glycan recognition domain (CRD) of galectin-9 polypeptides, and methods for using anti-galectin-9 antibodies to inhibit galectin-9-mediated signaling pathways or to eliminate diseased cells expressing galectin-9. Such anti-galectin-9 antibodies may also be used to diagnose and / or treat galectin-9-related diseases, such as autoimmune diseases and solid tumors.

In one aspect, the invention provides an isolated antibody, or antigen-binding fragment thereof, comprising a bioactive peptide amino acid sequence, wherein the bioactive peptide amino acid sequence is an inhibitor of the complement system and is fused to at least one of: (i) the amino terminal region of at least one of: a light chain variable region and / or a heavy chain variable region; or (ii) the carboxy terminal region of at least one of: a light chain constant region and / or a heavy chain constant region, wherein the antibody inhibits complement activation.

Recent studies indicate that sIL7R is involved in the development of autoimmune diseases. The present invention provides methods and compositions for a novel antibody therapeutic against the soluble isoform of the interleukin 7 receptor (sIL7R), a potent driver of self-destructive immune responses that cause autoimmune diseases including multiple sclerosis, lupus nephritis, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, and many other autoimmune diseases. The present invention includes antibodies specific for sIL7R that inhibit SIL7R, a driver of autoimmunity, without inhibiting mIL7R, thereby reducing the severity of or preventing autoimmunity without activating immunosuppressive mechanisms.

To provide anti-KLK7 antibody, anti-KLK5 antibody, multispecific anti-KLK5 / KLK7 antibody and methods of use.SOLUTION: The disclosure provides an isolated antibody that binds to human kallikrein related peptidase 7 (KLK7), where the antibody inhibits human KLK7-mediated cleavage of a substrate of a certain amino acid sequence, and / or binds to human KLK7 with a KD of less than 10 pM, or less than 9 pM, or less than 8 pM, or less than 7 pM, or less than 6 pM, or less than 5 pM as measured by surface plasmon resonance, and the antibody binds to a specific epitope of KLK7.SELECTED DRAWING: Figure 19B

To provide antibodies for the improved treatment of iron-related diseases, in particular, iron-restricted disorders caused by excessive hepcidin, e.g., anemia of chronic disease (ACD), iron-refractory iron deficiency anemia (IRIDA) and anemia of chronic kidney disease (CKD).SOLUTION: The present invention provides an isolated antibody that specifically binds human Repulsive Guidance Molecule C (RGMc), where: a) the antibody is a full-length antibody or antigen-binding fragment thereof; b) the antibody does not bind human Repulsive Guidance Molecule A (RGMa) and human Repulsive Guidance Molecule B (RGMb); and c) the antibody inhibits or reduces RGMc interaction with BMP6,.SELECTED DRAWING: None

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.

Antibodies to the enzyme matriptase-2 (MTP-2) are presented. Inhibiting MTP-2 reduces uptake of dietary iron and reduces the release of iron from cellular stores in the body. Inhibitors of MTP-2 (such as antibodies to the serine protease domain) can be used to treat iron overload, which is a feature of diseases such as beta-thalassaemia and which otherwise leads to toxic accumulation of iron. Combination of an MTP-2 inhibitor with an activin receptor ligand trap, or with erythropoietin, provides additional therapeutic effects.

The invention discloses an application of combination of oncolytic virus, chemotherapeutic drug and anti-PD-1 monoclonal antibody in treatment of gastric cancer liver metastasis. Specifically, the invention provides an application of an active component combination, the active component combination comprises a recombinant human type 5 adenovirus, a chemotherapeutic drug and an optional anti-PD-1 monoclonal antibody, and the active component combination is used for preparing a pharmaceutical composition for synergistically treating gastric cancer liver metastasis. Clinical experiments prove that the active component composition disclosed by the invention can effectively and synergistically inhibit liver metastasis of gastric cancer.

The present invention relates to an antibody or antigen binding fragment thereof that binds specifically to IGFBP3 and does not displace the binding of IGF-I to IGFBP3. The antibody inhibits or reduces the binding of IGFBP3 to the TMEM219 receptor. The invention also relates to methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

The present invention provides antibodies against activated protein C (APC). Certain disclosed antibodies inhibit the anticoagulant activity of APC while maintaining its beneficial cytoprotective functions. The present invention also provides nucleic acids, vectors, and host cells for producing the antibodies disclosed herein, as well as methods of using the antibodies to treat medical conditions such as hemorrhage, sepsis, and inflammation.

Method of treating a nerve injury in a subject in need thereof, the method comprising: administering a therapeutically effective amount of a therapeutic agent to the subject, wherein the therapeutic agent is selected from the group consisting of metaxalone and a Formin-2 inhibitor, such as an antibody, an antibody fragment, an inhibitory nucleic acid molecule, or a small molecule, wherein the inhibitory nucleic acid molecule substantially silences Fmn2.

In ovarian carcinoma, Müllerian Inhibiting Substance (MIS) type II receptor (MISRII) and the MIS / MISRII signaling pathway are potential therapeutic targets. Conversely, the role of the three MIS type I receptors (MISRI; ALK2, ALK3 and ALK6) in this cancer needs to be clarified. Using four ovarian cancer cell lines and ovarian cancer cells isolated from patients' tumor ascites, the inventors found that ALK2 and ALK3 are the two main MISRIs involved in MIS signaling at low and high MIS concentrations, respectively. Moreover, high MIS concentrations were associated with apoptosis and decreased clonogenic survival, whereas low MIS concentrations improved cancer cell viability. Finally, the inventors showed that anti-MIS antibody B10 inhibited MIS pro-survival effect. These last results open the way to an innovative therapeutic approach to suppress MIS proliferative effect, instead of administering high doses of MIS to induce cancer cell apoptosis.

Monoclonal antibodies and antigen-binding fragments that specifically bind to coronavirus spike proteins, such as SARS-CoV-2, are disclosed. Use of these antibodies to inhibit coronavirus infection is also disclosed. Additionally, methods are disclosed for detecting coronaviruses in biological samples using the disclosed antibodies. A panel of human monoclonal antibodies (mAbs) that target multiple coronaviruses have been isolated. These mAbs inhibit coronavirus infection and can therefore be used as prophylactics to block coronavirus infection and as tools for the development of next-generation vaccines that provide more broad protection against coronaviruses.