223 results about "CD47" patented technology

This disclosure provides novel bispecific antibodies that specifically bind to CD47 and Programmed Death-Ligand 1 (PD-L1). The disclosure further relates to methods of making the bispecific antibodies and nucleic acids encoding the antibodies. The disclosure further relates to therapeutic methods for use of the bispecific antibodies in the treatment of a condition associated with malignant cells expressing CD47 and / or PD-L1.

Provided by the present invention are a bispecific T-cell engager, recombinant oncolytic virus thereof, and use thereof. The present invention provides an αCD47 and αCD3 bispecific T-cell engager. The present invention also provides an isolated nucleic acid molecule that encodes said bispecific T-cell engager. The present invention also provides an expression framework of said bispecific T-cell engager BiTE. The present invention also provides a recombinant oncolytic virus, and said oncolytic virus is operably inserted with or contains the expression framework of said bispecific T-cell engager BiTE. In the present invention, the bispecific T-cell engager is combined with the oncolytic virus, and in comparison with pure gene therapy or virotherapy, the oncolytic virus significantly enhances the inhibition capability on malignant tumors.

The invention relates to a method or application of combination of an anti-TROP2 antibody drug conjugate and an anti-PD-L1 / CD47 bispecific antibody or antigen binding fragment in tumor treatment.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell.

The present disclosure generally relates to binding agents capable of targeting tumor cells and / or immune cells and their use to treat cancer. The binding agents of the present disclosure comprise one or more antigen-binding domains of a single-domain antibody capable of binding to cluster of differentiation 36 (CD36), programmed cell death protein 1 (PD-1), and / or cluster of differentiation 47 (CD47). The binding agents of the present disclosure may be monospecific or multispecific and may be in monomeric or multimeric form.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell, a virus-infected cell, or a fibrotic cell.

Methods are provided for targeting cells for depletion, including without limitation tumor cells such as solid tumor cells, in a regimen comprising contacting the tumor and immune effector cells with an effective dose of an anti-MSDC agent that reduces the abundance, immunosuppressive activity, or tumor recruitment of CXCR2+ granulocytic-myeloid derived suppressor cells, for example, an inhibitor of CXCR2; in combination with an effective dose of an inhibitor of CD47 / SIRPα signaling.

The present invention provides methods of treating ischemic and traumatic central nervous system injury by administering an antagonist of the interaction between CD47 and SIRPa. Also provided are method of increasing efferocytosis after a traumatic or ischemic CNS injury by administering an antagonist of the interaction between CD47 and SIRPa.

Disclosed herein are monospecific and multispecific single chain antibodies having specificity for one or more of CD47, PD-L1, HSA, CD33, LAG3, and CD16.

The present disclosure generally relates to binding agents that are capable of targeting tumor cells and immune cells. The binding agents of the present disclosure are multispecific and comprise antigen binding domains that are capable of binding to Dopamine Receptor D2 (DR2), to Programmed Cell Death Protein 1 (PD-1) and / or to Cluster of Differentiation 47 (CD47). The multispecific binding agents of the present disclosure may be used to treat subjects in need thereof.

Provided is an antibody capable of specifically binding to CD38, or an antigen-binding portion thereof. Also provided is a recombinant fusion protein, comprising: i) a CD38 antibody or an antigen-binding portion thereof; and ii) a CD47 binding peptide, wherein the CD47 binding peptide is linked to an N-terminus of a heavy chain or light chain of the CD38 antibody or the antigen-binding portion thereof, and the CD47 binding peptide is an extracellular Ig-like domain of a signal regulatory protein (SIRP).

The present application provides a monoclonal antibody targeting human carcinoembryonic antigen CEACAM5 / 6, and a bispecific antibody capable of simultaneously targeting human carcinoembryonic antigen CEACAM5 / 6 and human CD47, a preparation method and applications. Specifically, it relates to an anti-human CD47 antibody and antigen-binding fragments thereof capable of simultaneously (1) specifically binding to human CD47 protein and blocking its binding to SIRPalpha, thereby thus blocking the inhibitory effect of CD47 on SIRPalpha-expressing macrophages; (2) specifically binding to human carcinoembryonic protein CEACAM5 / 6. The present application also relates to a preparation method and uses of the bispecific antibody.

Provided is an antibody capable of specifically binding to CD38, or an antigen-binding portion thereof. Also provided is a recombinant fusion protein, comprising: i) a CD38 antibody or an antigen-binding portion thereof; and ii) a CD47 binding peptide, wherein the CD47 binding peptide is linked to an N-terminus of a heavy chain or light chain of the CD38 antibody or the antigen-binding portion thereof, and the CD47 binding peptide is an extracellular Ig-like domain of a signal regulatory protein (SIRP).

Antibodies are provided which comprise at least one Fab portion that binds CD47 and at least one Fab portion that binds the tumor associated antigen (TAA) CD20; wherein the Fab portion that binds CD47 exhibits low affinity for CD47; and, wherein the Fab portion that binds CD20 exhibits high affinity for CD20; and, wherein the antibody selectively binds CD47 and blocks CD47 interaction with SIRPα in tumor cells while exhibiting no substantial binding to CD47 in normal cells.

The invention discloses an antigen binding polypeptide combined with CD47 or an antigen binding part and application thereof. Specifically, the invention provides an antigen binding polypeptide binding CD47 and an antigen binding part thereof, nucleic acid encoding the antigen binding polypeptide and the antigen binding part, a carrier containing the nucleic acid, a cell containing the carrier, a pharmaceutical composition containing the antigen binding polypeptide and the antigen binding part, and application of the antigen binding polypeptide and the antigen binding part in reducing tumors or inhibiting growth of tumor cells, treating cancers, promoting phagocytosis of macrophages and the like.

The present disclosure relates to antibodies and antibody derivatives that bind to CD47 (also known as IAP, MER6 and OA3) and methods of using the same. In certain embodiments, an anti-CD47 antibody or antibody derivative disclosed herein exhibits reduced binding to a red blood cell.

The invention discloses a coupling molecule with an effect of promoting macrophages to selectively swallow extracellular goods as well as a preparation method and application of the coupling molecule, and belongs to the technical field of biological medicines. The coupling molecule disclosed by the invention is a double-targeting polypeptide and consists of a macrophage targeting peptide fragment, a linker and a target cell targeting peptide fragment, wherein the target cell targeting peptide fragment comprises peptide fragments targeting tumor cells and apoptotic cells. One end of the dual-targeting polypeptide is connected with macrophages, the other end of the dual-targeting polypeptide is connected with tumor cells / apoptotic cells, and the interaction between the macrophages and the tumor cells / apoptotic cells is improved in a molecular glue mode. Aiming at tumor cells, the dual-targeting polypeptide can enhance the phagocytosis and killing effects of macrophages on the tumor cells under the action of a CD47 antibody, so that the anti-tumor effect is achieved; aiming at apoptotic cells, the dual-targeting polypeptide can promote the interplant effect of macrophages, so that the anti-inflammatory effect is achieved. Therefore, the dual-targeting polypeptide disclosed by the invention has relatively good drug development potential.

Disclosed herein are monospecific and multispecific single-chain antibodies specific for one or more of CD47, PD-L1, HSA, CD33, LAG3, and CD16.

Non-human animals, and methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of an endogenous cluster of differentiation (CD) gene, in particular a humanization of a CD47 gene. Said non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous CD47 gene so that said non-human animals express a CD47 polypeptide that includes a human portion and a non-human portion (e.g., a murine portion).

The present invention relates to a method for intracellular delivery of a target substance by CD47-mediated endocytosis and, more specifically, to an improved method for intracellular delivery of a target substance by CD47-mediated endocytosis initiated / induced by interaction between a ligand for CD47 and CD47 expressed on a target cell.

To provide an immune checkpoint inhibitor targeting immune checkpoint proteins PD-L1 and CD47.SOLUTION: Provided is a bispecific single domain antibody that bispecifically binds to PD-L1 and CD47, comprising a first VHH domain or an antigen-binding fragment thereof that specifically binds to PD-L1 and a second VHH domain or an antigen-binding fragment thereof that specifically binds to CD47, where the first VHH domain or the antigen-binding fragment thereof includes CDR1, CDR2, and CDR3 each having a specific amino acid sequence, and the second VHH domain or the antigen-binding fragment thereof includes CDR1, CDR2, and CDR3 each having a specific amino acid sequence.SELECTED DRAWING: Figure 10

Provided is a use of a recombinant fusion protein in the preparation of a drug for treating an autoimmune disease that can benefit from the reduction or elimination of CD20+B cells (for example, CD20+ B cell depletion therapy). The recombinant fusion protein comprises i) a CD47-binding peptide, and ii) an anti-CD20 antibody or an antigen-binding portion thereof, wherein the CD47-binding peptide comprises a first extracellular Ig-like domain (SIRPαD1) of signal regulatory protein α (SIRPα), and the anti-CD20 antibody or the antigen-binding portion thereof comprises a heavy chain variable region, a heavy chain constant region, a light chain variable region, and a light chain constant region. The heavy chain variable region comprises VH-CDR1, VH-CDR2, and VH-CDR3, and the light chain variable region comprises VL-CDR1, VL-CDR2, and VL-CDR3, wherein the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 respectively comprise amino acid sequences as shown in GYTFTSYN (SEQ ID NO: 1), IYPGNGDT (SEQ ID NO: 2), ARSTYYGGDWYFNV (SEQ ID NO: 3), SSVSY (SEQ ID NO: 4), ATS, and QQWTSNPPT (SEQ ID NO: 5). The heavy chain constant region has the binding capacity for an FcR or a complement system protein. The CD47-binding peptide is linked to the N-terminus of the heavy chain variable region or light chain variable region of the anti-CD20 antibody or the antigen-binding portion thereof.

An mRNA composition for treating cancer is provided. The mRNA composition for treating cancer includes an mRNA encoding a CD47-targeted chimeric antigen receptor (CAR) and an mRNA encoding interleukin-12 (IL-12).

The present invention discloses a dual-target chimeric antigen receptor, CAR-T cells and applications thereof that co-express CD47 and IL-15, belonging to the field of genetic engineering technology. The dual-target chimeric antigen receptor includes a single-chain antibody scFv-EGFRvⅢ, a single-chain antibody scFv-VEGF, CD47, and IL-15; the artificial nucleotide sequence of the single-chain antibody scFv-EGFRvⅢ is shown in SEQ ID NO.6; the artificial nucleotide sequence of the single-chain antibody scFv-VEGF is shown in SEQ ID NO.9. The present invention can enhance the anti-tumor effect of CAR-T cells in glioblastoma by sequence optimization of the targets EGFRvⅢ and VEGF, and can locally exert the immunosuppressive function of the CD47-SIRPα signaling pathway by integrating the immune checkpoint molecules CD47 and interleukin-15.

Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-α v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-α v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-α polypeptide, an extracellular domain of a mouse SIRP-α polypeptide, an extracellular domain of a human SIRP-β polypeptide, and / or an extracellular domain of a human SIRP-γ polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-α polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-α polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

The present present disclosure relates to a CD47-SIRPα blocking agent of formula (I) stereoisomers thereof, and pharmaceutically acceptable salts, solvates, amides and esters of the compound of formula (I) and stereoisomer thereof for use in a method of treating or delaying progression of a disease or a disorder mediated by CD47-SIRPα pathway in a human subject suffering from said disease, such as cancer.

The present disclosure relates to a CD47-SIRPα blocking agent of formula (I) stereoisomers thereof, and pharmaceutically acceptable salts, solvates, amides and esters of the compound of formula (I) and stereoisomer thereof and Azacitidine for use in combination with Azacitidine in a method of treating or delaying progression of a disease or a disorder mediated by CD47-SIRPα pathway in a human subject suffering from said disease, such as hematological cancer.

Disclosed is a SIRPα-targeting antibody or an antigen-binding fragment thereof, comprising a light chain variable region and / or a heavy chain variable region. The antibody or the antigen-binding fragment thereof binds to human SIRPα-V1 and human SIRPα-V2, but weakly or does not bind to human SIRPβ and SIRPγ, does not bind to human T cells, and has the function of blocking the binding of SIRPα to CD47. Further disclosed are a bispecific antibody comprising same, a method for preparing the antibody or the antigen-binding fragment thereof and an application thereof. The unique properties of the disclosed antibody or the antigen-binding fragment thereof enable same to be more suitable for the development of drugs for an antibody or antigen-binding fragment against a human SIRPα target. As a candidate drug, same can be administered alone or in combination, providing a new or even better choice for the combined immunotherapy of tumors.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell, a virus-infected cell, or a fibrotic cell.