29 results about "Ankyrin Repeat Protein" patented technology

The present invention relates to recombinant binding proteins comprising an ankyrin repeat domain with binding specificity for soluble mesothelin or membrane-bound mesothelin. In addition, the invention relates to nucleic acids encoding such recombinant binding proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer in a mammal, including a human.

The present disclosure relates to multispecific proteins comprising designed ankyrin repeat domains with binding specificity for different targets, such as, e.g. CD40 and FAP. In addition, the present disclosure relates to nucleic acids encoding such multispecific proteins, pharmaceutical compositions comprising such multispecific proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer, in a mammal, including a human.

The present invention relates to MSLN-specific binding constructs comprising a designed ankyrin repeat domain with binding specificity for MSLN and a chelator capable of bonding to a radionuclide, as well as to such MSLN-specific binding constructs comprising a half-life extending moiety with binding specificity for serum albumin. The invention further relates to methods of producing such radio-labelled MSLN-specific binding constructs, pharmaceutical compositions comprising such constructs, and the use of such constructs or pharmaceutical compositions in methods for treating, imaging or diagnosing diseases, such as cancer.

The invention relates to combination and combination therapies, particularly for the treatment of a myeloid malignancy, such as acute myeloid leukemia (AML) or a myelodysplastic syndrome (MDS). The combination therapies include (i) a recombinant binding protein comprising (a) an ankyrin repeat domain specifically binding CD3 and (b) at least one, at least two, or at least three further ankyrin repeat domains, wherein each of the at least one, at least two, or at least three further ankyrin repeat domains specifically binds one tumor-associated antigen, suitably one selected from the group consisting of CD123, CD33 and CD70, and (ii) a Bcl-2 inhibitor, e.g., venetoclax, or a pharmaceutically acceptable salt thereof and / or (iii) a hypomethylating agent, e.g., azacitidine or decitabine.

Provided are therapies comprising immune effector cells, such as T cells, engineered to express an antigen receptor, such as a T cell receptor or a chimeric antigen receptor.SOLUTION: It is demonstrated that antigen receptor-engineered immune effector cells can be generated in vitro / ex vivo as well as in vitro by delivering a nucleic acid encoding an antigen receptor for genetic modification to a cell using a particle comprising the nucleic acid and a targeting molecule for targeting the immune effector cell, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are provided that are high affinity binders for CD8 binding to CD8 receptors on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8 targeting DARPins (CD8 - DARPins) can deliver genes exclusively and specifically to human CD8 + T cells in vitro and in vivo.SELECTED DRAWING: None

The present invention relates to recombinant binding proteins comprising a designed ankyrin repeat domain with binding specificity for DLL3. In addition, the invention relates to nucleic acids encoding such binding proteins, pharmaceutical compositions comprising such binding proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods of treating diseases, such as cancer, in a mammal, including a human.

In an embodiment, the present disclosure pertains to a method of treating or preventing C. difficile infections. In some embodiments, the method includes administering an anti-toxin to a subject in need thereof. In some embodiments, the anti-toxin includes a designed ankyrin repeat protein (DARPin). In an additional embodiments, the present disclosure pertains to a composition including an anti-toxin for treating or preventing C. difficile infections. In some embodiments, the anti-toxin includes a DARPin. In some embodiments, the anti-toxin is a monomeric or dimeric DARPin for the neutralization of Clostridium difficile toxin B (TcdB).

The present invention relates to recombinant binding proteins comprising a designed ankyrin repeat domain with binding specificity for DLL3. In addition, the invention relates to nucleic acids encoding such binding proteins, pharmaceutical compositions comprising such binding proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods of treating diseases, such as cancer, in a mammal, including a human.

The present invention relates to recombinant binding proteins comprising a first designed ankyrin repeat domain which has a first binding specificity for a first target and a second binding specificity for a second target, wherein the binding of said first domain to said first and second targets is mutually exclusive, and wherein the first target is CD117 and the second target is a CD47-specific binding agent. The invention also provides further recombinant proteins comprising said first dual-specific repeat domain and additional therapeutic agents such as binding agents. Further disclosed are nucleic acids encoding such recombinant proteins, pharmaceutical compositions comprising such recombinant proteins or nucleic acids and the use of such recombinant proteins, nucleic acids or pharmaceutical compositions in methods for treating diseases, such as cancer in a mammal, including a human. Designed ankyrin repeat domains with binding specificity for a CD47-specific ankyrin repeat domain are also disclosed.

The present disclosure provides compositions comprising a designed ankyrin repeat protein (DARPin) for use in treating Shiga toxin (Stx)-producing Escherichia coli (STEC) and related diseases, including hemolytic uremic syndrome (HUS). The high thermostability and high microbial expression yield make DARPin an attractive alternative to antibody therapeutics. The present disclosure provides monomer proteins, dimer proteins, and trimer proteins, as well as pharmaceutical compositions and methods utilizing the same.

Disclosed herein are nanoparticle conjugates (e.g., anti-angiogenic and / or immunomodulatory nanoparticle conjugates, e.g., high-affinity Designed Ankyrin Repeat Protein (DARPin)-based binders targeting one or more cancer and / or immune receptors). The nanoparticle conjugates are useful for therapeutics and / or diagnostics and have a diameter (e.g., average diameter) no greater than 20 nanometers (e.g., as measured by dynamic light scattering (DLS) in aqueous solution, e.g., saline solution).

The present invention relates to multispecific binding proteins comprising binding domains with dual-binding specificity for at least one disease-associated antigen, suitably tumor-associated antigen and an immune cell surface antigen. Said binding domains with dual-binding specificity bind to the two targets in a mutually exclusive way, thereby functioning as a molecular switch, such as, e.g., a switch to control activation or deactivation of a therapeutic agent. Said binding proteins are formatted as T cell engagers to optionally comprise a binding domain with co-stimulatory activity, such as CD2. Said binding domains are preferably ankyrin repeat domains, e.g. designed ankyrin repeat domains (DARPins). The invention further relates to nucleic acids, pharmaceutical compositions, recombinant expression vectors and host cells, and the use of such proteins, nucleic acids or pharmaceutical compositions in methods for treating diseases, such as cancer.

The present invention relates to DLL3-specific binding constructs comprising a designed ankyrin repeat domain with binding specificity for DLL3, a connector, and a chelator capable of bonding to a radionuclide, such as Pb-212, as well as to such DLL3-specific binding constructs comprising a half-life extending moiety with binding specificity for serum albumin. The invention further relates to methods of producing such radio-labelled DLL3-specific binding constructs, pharmaceutical compositions comprising such constructs, and the use of such constructs or pharmaceutical compositions in methods for treating, imaging or diagnosing diseases, such as cancer.

The present invention relates to recombinant binding proteins comprising an ankyrin repeat domain, wherein the ankyrin repeat domain has binding specificity for CD16a. In addition, the invention relates to nucleic acids encoding such recombinant binding proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer in a mammal, including a human.

Disclosed are a recombinant binding protein targeting TSLP and the use thereof. The recombinant binding protein comprises at least one ankyrin repeat domain that specifically binds to TSLP, wherein the ankyrin repeat domain comprises three tandem binding domains, and each binding domain comprises four binding active regions. The recombinant binding protein of the present invention has excellent binding activity to TSLP, and effectively blocks the interaction between TSLP and a receptor thereof, thereby effectively controlling TSLP-related diseases.

The present disclosure relates to designed ankyrin repeat domains with binding specificity for serum albumin and, in particular, to such designed ankyrin repeat domains with improved stability. The disclosure further relates to recombinant binding proteins comprising such designed ankyrin repeat domain(s), nucleic acids encoding such designed ankyrin repeat domains or proteins, pharmaceutical compositions comprising such proteins and the use of such proteins or pharmaceutical compositions in the treatment of diseases.

Disclosed are bispecific molecules, referred to herein as ubiquibodies, that are able to ubiquitinate target cell surface receptors on a target cell. The ubiquibodies can be engineered from fusion polypeptides comprising 1) variable domains of antibodies that specifically bind a target cell surface receptor and 2) variable domains of antibodies that specifically bind a transmembrane E3 ubiquitin ligase (TMUL). Either or both components of the ubiquibodies can also be engineered from non-antibody scaffolds including but not limited to nanobodies, monobodies, cyclic peptides, small molecules, and designed ankyrin repeat proteins (Darpins).

Described herein are proteins comprising an ankyrin repeat domain having an N-terminal capping module with improved properties, as well as corresponding protein libraries, pharmaceutical compositions and nucleic acids encoding such proteins. In other aspects, the disclosure relates to methods using such proteins, corresponding protein libraries or pharmaceutical compositions.

The present disclosure relates to compositions and methods for the treatment and / or prevention of SARS-COV-2 infections. In one embodiment the method comprises the delivery of a pharmaceutical composition comprising a SARS-COV-2 neutralizing synthetic protein, optionally wherein the protein is a trimeric protein composed of designed ankyrin repeat protein (DARPin) fused with a T4 foldon peptide that is administered non-invasively such as by nasal inhalation.

The present invention relates to recombinant binding proteins comprising a designed ankyrin repeat domain with binding specificity for CD117. In addition, the invention relates to nucleic acids encoding such binding proteins, pharmaceutical compositions comprising such binding proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods of treating medical conditions, such as cancer, and in methods of conditioning a mammal, including a human, for a stem cell transplant, such as a hematopoietic stem cell transplant.

The invention provides a specific envelope protein as well as a lentiviral vector and application thereof. The specific envelope protein comprises F protein Nipah-F of a Nipah virus, an antibody and G protein modified protein derived from the Nipah virus. The envelope protein derived from the Nipah virus is modified, so that the envelope protein retains the membrane melting capability and obtains the specific targeting capability of cells. The method is characterized in that targeting proteins with a ligand recognition function, such as a single-chain antibody scFv, an ankyrin repeat protein DARPin and the like, are fused with a G protein modified protein derived from the Nipah virus, and are connected with a Nipah-F protein. The specific envelope protein is used for packaging lentivirus, retrovirus vectors, viroid and other vectors, so that the vectors specifically recognize antigens on cell membranes, and cell targeting nucleic acid delivery is completed. According to the invention, T cells can be modified in vivo, and genetically modified T cells can be generated in vivo, so that procedures related to return CAR-T cell therapy are greatly reduced.

The present invention relates to an immunoreactive molecule that specifically recognises and binds to human Ankyrin Repeat Domain-Containing Protein 30A (NY-BR-1) and, in particular, to an immunoreactive molecule, which shows no cross-reactivity to other human Ankyrin repeat domain containing proteins. The invention further relates to the use of such immunoreactive molecules in the treatment of cancer as well as in companion diagnostics methods.

The invention is based on designed ankyrin repeat proteins (DARPins) specifically binding to a DNA binding domain of human p53. The DARPins of the invention are capable of forming a binding interface with the DNA binding domain of p53, and upon binding facilitate p53 protein stability. The DARPins of the invention are for use in the treatment of p53 related diseases such as cancer. Further, the invention pertains to nucleic acid constructs encoding the DARPin of the invention, methods for their production and cells comprising the DARPins or nucleic acid constructs of the invention.

The present invention relates to recombinant binding proteins comprising an ankyrin repeat domain, wherein the ankyrin repeat domain has binding specificity for CD2. Furthermore, the invention relates to nucleic acids encoding such recombinant binding proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating diseases, such as cancer, in mammals, including humans.

The present invention relates to DLL3-specific binding constructs comprising a designed ankyrin repeat domain with binding specificity for DLL3, a connector, and a chelator capable of bonding to a radionuclide, such as Pb-212, as well as to such DLL3-specific binding constructs comprising a half-life extending moiety with binding specificity for serum albumin. The invention further relates to methods of producing such radio-labelled DLL3-specific binding constructs, pharmaceutical compositions comprising such constructs, and the use of such constructs or pharmaceutical compositions in methods for treating, imaging or diagnosing diseases, such as cancer.

The present invention relates to designed ankyrin repeat domains with binding specificity for serum albumin, and in particular to such designed ankyrin repeat domains with improved stability. The invention further relates to recombinant binding proteins comprising such designed ankyrin repeat domains, nucleic acids encoding such designed ankyrin repeat domains or proteins, pharmaceutical compositions comprising such proteins, and the use of such proteins or pharmaceutical compositions in the treatment of diseases.

The present invention relates to designed ankyrin repeat domains with altered surface residues, as well as to proteins comprising such a designed ankyrin repeat domain, nucleic acids encoding such domains or proteins, methods of preparing such proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such proteins, nucleic acids or pharmaceutical compositions in the treatment of diseases.

Disclosed herein are nanoparticle conjugates (e.g., anti-angiogenic and / or immunomodulatory nanoparticle conjugates, e.g., high-affinity Designed Ankyrin Repeat Protein (DARPin)-based binders targeting one or more cancer and / or immune receptors). The nanoparticle conjugates are useful for therapeutics and / or diagnostics and have a diameter (e.g., average diameter) no greater than 20 nanometers (e.g., as measured by dynamic light scattering (DLS) in aqueous solution, e.g., saline solution).

The present invention relates to an agent that inhibits the expression or activity of the G Protein-Coupled Receptor 182 (GPR182) protein for use in the treatment or prevention of a pathological condition selected from myocardial infarction, myocardial ischemia, myocardial necrosis, cardiac hypertrophy, cardiac fibrosis, limb ischemia, ischemia-related tissue degeneration, stroke and a cancer, wherein (a) the agent that inhibits the expression of the GPR182 protein is selected from an siRNA, miRNA, shRNA, a ribozyme and an antisense nucleic acid molecule; and / or (b) the agent that inhibits the activity of the GPR182 protein specifically binds to the GPR182 protein and inhibits binding of one or more endogenous ligands to the GPR182 protein, and wherein the agent is selected from an antibody, an Fc fusion polypeptide, an adnectin, an affibody, an affilin, an anticalin, an atrimer, an avimer, an evibody, a Kunitz-type domain, a designed ankyrin repeat protein (DARPin), a fynomer, a peptide or peptidomimetic, an aptamer, and a small molecule; or any combination and / or hetero-or homo-oligomeric, covalent or non-covalent complex thereof.