The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
2.
T-Cell Modulatory Multimeric Polypeptides and Methods of Use Thereof
The present disclosure provides T-cell modulatory antigen-presenting polypeptides, including single-chain antigen-presenting polypeptides and multimeric antigen-presenting polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding T-cell modulatory antigen-presenting polypeptides of the present disclosure, as well as cells genetically modified with the nucleic acids. A T-cell modulatory antigen-presenting polypeptide of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides methods of modulating activity of a T cell.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
3.
Interleukin-2 Polypeptides, Fusion Polypeptides, and Methods of Use Thereof
IL-2 variant polypeptides and compositions comprising one or more IL-2 variant polypeptides, e.g., fusion polypeptides, having reduced affinity to IL-2Rα and IL-2Rβ are disclosed, as well as method for their use, e.g., in treatments involving cancer vaccines, TCR-T cell therapy and CAR-T cell therapy. Such polypeptides do not systemically activate multiple immune cell subsets, as native IL-2 delivered in high doses would, but rather predominantly activate only T cells whose T cell receptors (TCRs) are engaged with a peptide-MHC complex (pMHC) presented by an antigen presenting cell, which can thus provide a useful therapeutic index for pharmaceutical compositions comprising such polypeptides.
The present disclosure provides Transforming Growth Factor Beta (TGF-β) polypeptide constructs and complexes that find use in, for example, therapeutic treatment of diseases including autoimmune diseases. Also described are nucleic acids that encode the constructs and complexes and methods of preparing the constructs and complexes in cell-based expression systems.
The present disclosure provides Multimeric Antigen-Presenting Polypeptides (MAPPs) for the presentation of epitopes in the context of a class II MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding the MAPPs. MAPPs are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including metabolic disorders, cancers, autoimmune diseases, allergies, T1D, and/or celiac disease.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
6.
PROTEINS FOR MODULATING CELL THERAPY PRODUCTS AND METHODS OF USE THEREOF
This disclosure provides modulatory polypeptides (“CT-MP”) that bind to and modulate cell therapy products such as CAR-T cells that comprise antigen binding polypeptides, e.g., CARs or other polypeptides that bind cancer-associated antigens. This disclosure further provides methods of increasing the number and/or activity of such cell therapy products, as well as methods of treating cancer.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
This disclosure provides a method of treating an HPV16-associated cancer in an individual, the method comprising administering to the individual a T-cell modulatory protein (TMP) and an PD-(L)1 CPI that targets PD-1 or PD-L1, i.e., a "PD-(L)1 CPI", where (A) the individual previously was determined to have progressive disease based on RECIST 1.1 criteria following (i) monotherapy with a PD-(L)1 CPI, or (ii) combination therapy comprising treatment with a PD-(L)1 CPI and a therapeutic agent other than the TMP, or (B) where the individual has a PD-L1 Combined Positive Score (PD-L1 CPS) of 0 or more than 0 but less than 1.
The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07K 14/79 - Transferrins, e.g. lactoferrins, ovotransferrins
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/62 - DNA sequences coding for fusion proteins
The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07K 14/79 - Transferrins, e.g. lactoferrins, ovotransferrins
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/62 - DNA sequences coding for fusion proteins
10.
T-CELL MODULATORY POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor. A TMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
The present disclosure provides a single-chain T-cell modulatory polypeptide (TMP) that includes an NKG2 peptide, an HLA-E heavy chain polypeptide, a beta-2 microglobulin polypeptide, and an immunoglobulin Fc polypeptide. The TMP can also include an immunomodulatory polypeptide and/or a cancer-targeting polypeptide. The TMPs are useful in methods of modulating an immune response, which methods are also provided.
C12N 15/62 - DNA sequences coding for fusion proteins
C12N 15/79 - Vectors or expression systems specially adapted for eukaryotic hosts
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present disclosure provides a T-cell modulatory multimeric polypeptide (TMMP) comprising at least one heterodimer, where the heterodimer comprises first and second polypeptide chains and where the heterodimer includes an NKG2 peptide, an HLA-E heavy chain polypeptide, a beta-2 microglobulin polypeptide, and an immunoglobulin Fc polypeptide. The heterodimer can also include an immunomodulatory polypeptide and/or a cancer-targeting polypeptide. The TMMPs are useful in methods of modulating an immune response, which methods are also provided.
C12N 15/62 - DNA sequences coding for fusion proteins
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide, an epitope-presenting peptide, and class I MHC polypeptides. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
15.
MULTIMERIC T-CELL MODULATORY POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulation multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present disclosure provides T cell modulatory polypeptide-epitope conjugates (T-Cell-MP-epitope conjugates) comprising a chemical conjugation site at which a coronavirus peptide epitope is covalently attached and at least one immunomodulatory polypeptide sequence. The T-Cell-MP-epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T-cells specific to the coronavirus peptide epitope in an epitope selective/specific manner, and accordingly, for treating individuals with a coronavirus infection including long COVID. Alternatively, when the T-Cell-MP-epitope conjugate is redirected to a neoplastic cell by a targeting sequence, the redirected T-Cell-MP-epitope conjugate may be used to treat neoplasms including various cancers.
A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
The present disclosure provides T cell modulatory polypeptide-epitope conjugates (T-Cell-MP-epitope conjugates) comprising a chemical conjugation site at which an NY-ESO (e.g., NY-ESO-1 or NY-ESO-2) or a MAGE (e.g., MAGEA4) peptide epitope is covalently attached and at least one immunomodulatory polypeptide sequence that may be variant selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The T-Cell-MP-epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T-cells specific to the NY-ESO or MAGE peptide epitope in an epitope selective/specific manner, and accordingly, for treating individuals with, for example, cancers expressing the covalently attached epitope. The disclosure also provides T-Cell-MP-epitope conjugates with targeting sequences that can server to, among other things, localize the T-Cell-MP-epitope conjugates to a specific tissue or cell type.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
18.
Modified Cytotoxic T Cells and Methods of Use Thereof
The present disclosure provides modified cytotoxic T cells (mCTLs), where the mCTLs comprise: a) one or more nucleic acids comprising nucleotide sequences encoding a T-cell receptor (TCR) specific for MHC class I polypeptides that present a human papilloma virus (HPV) E7 peptide comprising the amino acid sequence YMLDLQPETT (SEQ ID NO:1) or YMLDLQPET (SEQ ID NO:2); and b) one or more nucleic acids comprising nucleotide sequences encoding a chimeric antigen receptor (CAR), where the CAR comprises an antigen-binding domain specific for a cancer-associated antigen. The present disclosure provides methods of producing the mCTLs. The present disclosure provides methods of treating cancer, comprising administering the mCTLs to an individual in need thereof.
The present disclosure provides immune cell binding polypeptides (ICBPs) that include a binding moiety that can bind to ILT2 and/or ILT4 polypeptides, at least one immunoinhibitory polypeptide, and a scaffold polypeptide. The ICBPs are useful for inducing immunological tolerance. The present disclosure provides methods of inducing immunological tolerance.
The present disclosure provides a single-chain T-cell engaging polypeptide (TEP) comprising a peptide epitope, class I major histocompatibility complex polypeptides, one or more immunomodulatory polypeptides, an immunoglobulin Fc polypeptide or a non-immunoglobulin scaffold polypeptide, and a tumor-targeting polypeptide. The present disclosure provides methods of treating cancer, comprising administering the TEP to an individual in need thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
21.
T-CELL MODULATORY POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides a peptide-major histocompatibility complex (pMHC) polypeptide comprising a peptide epitope and class I MHC polypeptides. The present disclosure provides fusion molecules comprising a pMHC polypeptide and a heterologous fusion partner. The present disclosure provides single-chain T-cell modulatory polypeptides that comprise a pMHC polypeptide, one or more immunomodulatory polypeptide, and an immunoglobulin (Ig) Fc or a non-Ig scaffold. A TMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The present disclosure provides a peptide-major histocompatibility complex (pMHC) polypeptide comprising a KRAS peptide and class I MHC polypeptides. The present disclosure provides fusion molecules comprising a pMHC polypeptide and a heterologous fusion partner. The present disclosure provides single-chain T-cell modulatory polypeptides that comprise a pMHC polypeptide, one or more immunomodulatory polypeptide, and an immunoglobulin (Ig) Fc or a non-Ig scaffold. A TMP is useful for modulating the activity of a T cell, for modulating an immune response in an individual, and/or for treating an individual who has a KRAS-associated cancer.
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The present disclosure provides T-cell modulatory multimeric polypeptides (“T-Cell-MMPs”) comprising an immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”) and a location for covalently attaching a molecule that can serve as an epitope, such as an epitope peptide. Once the epitope molecule is attached the resulting T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for IL-2R, to the T-cells in an epitope selective/specific manner, and accordingly, for modulating an immune response in an individual.
A61K 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
24.
MULTIMERIC T-CELL MODULATORY POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting alpha-feto protein peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
The present disclosure provides T-cell modulatory multimeric polypeptides (T.M.MPs) that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor-1 (WT-1) peptide. A TMMP is useful for modulating the activity of a T cell. and for modulating an immune response in an individual, e.g., for the treatment of a cancer associated with WT-1.
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting a human papillomavirus (HPV) peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
C07K 16/08 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
27.
T-CELL MODULATORY MULTIMERIC POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) that comprise (i) an optional immunomodulatory polypeptide such as a variant IL-2 polypeptide, (ii) class I HLA major histocompatibility complex (MHC) polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), (iii) a peptide that presents an epitope to a T-cell receptor, which together with the class I MHC polypeptides forms a peptide-MHC complex (pMHC), (iv) a tumor-targeting polypeptide, and (v) an optional Ig Fc polypeptide or other scaffold. Such TMMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual, and for “redirecting” a patient's repertoire of antiviral T cells to attack and kill cancer cells.
C07K 14/74 - Major histocompatibility complex [MHC]
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
28.
MHC CLASS II T-CELL MODULATORY MULTIMERIC POLYPEPTIDES FOR TREATING TYPE 1 DIABETES MELLITUS (T1D) AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.
The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) for the presentation of T1D epitopes in the context of a Class II MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding those MAPPs. MAPPs of the present disclosure are useful for selectively modulating activity of T cells having T cell receptors that recognize the T1D epitopes presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
31.
Antigen-Presenting Polypeptides with Chemical Conjugation Sites and Methods of Use Thereof
The present disclosure provides antigen presenting polypeptide comprising a TGF-β MOD that is reversibly masked and acts as a TGF-β receptor agonist. The antigen presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, Type 1 Diabetes (T1D) associated epitope containing polypeptides. The antigen-presenting polypeptides and their T1D-associated epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment of T1D.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present disclosure provides antigen presenting polypeptide comprising a TGF-β MOD that is reversibly masked and acts as a TGF-β receptor agonist. The antigen presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, epitope containing polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding antigen-presenting polypeptides comprising one or more chemical conjugation sites, as well as cells genetically modified with the nucleic acids. The antigen-presenting poly peptides and their epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment of diseases and disorders including autoimmune diseases, allergies, GVHD, HGVD, and metabolic disorder.
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 39/00 - Medicinal preparations containing antigens or antibodies
35.
Antigen Presenting Polypeptide Complexes Bearing TGF-Beta and Methods of Use Thereof
The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) that comprise a TID-associated peptide epitope and a reversibly masked TGF-β peptide capable of acting as an agonist of cellular TGF-β receptors. The MAPPs are capable of presenting the TID-associated peptide epitope in the context of a Class II MHC receptor to T cells. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding those MAPPs. MAPPs of the present disclosure are useful for selectively modulating activity of a T cells having T cell receptors that recognize the TID epitopes presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have TID.
The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) that comprise a peptide epitope and a reversibly masked TGF-β peptide capable of acting as an agonist of cellular TGF-β receptors. The MAPPs are capable of presenting the peptide epitope in the context of a Class II MHC receptor to T cells. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding the MAPPs. The MAPPs are useful for selectively modulating activity of a T cells having T cell receptors that recognize the epitope presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including autoimmune diseases, graft vs. host disease, host vs. graft disease, and/or allergies.
The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07K 14/79 - Transferrins, e.g. lactoferrins, ovotransferrins
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/62 - DNA sequences coding for fusion proteins
38.
T-cell modulatory multimeric polypeptides and methods of use thereof
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present disclosure provides T-cell modulatory polypeptides (TMPs) comprising an AI peptide epitope, MHC class II polypeptides, one or more immunomodulatory polypeptides, a TGF-β polypeptide, and a masking polypeptide. A TMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have an autoimmune disease.
The present disclosure provides T-cell modulatory polypeptides (TMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, one or more immunomodulatory polypeptides, a TGF-β polypeptide, and a masking polypeptide. A TMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.
IL-2 variant polypeptides and compositions comprising one or more IL-2 variant polypeptides, e.g., fusion polypeptides, having reduced affinity to IL-2Rα and IL-2Rβ are disclosed, as well as method for their use, e.g., in treatments involving cancer vaccines, TCR-T cell therapy and CAR-T cell therapy. Such polypeptides do not systemically activate multiple immune cell subsets, as native IL-2 delivered in high doses would, but rather predominantly activate only T cells whose T cell receptors (TCRs) are engaged with a peptide-MHC complex (pMHC) presented by an antigen presenting cell, which can thus provide a useful therapeutic index for pharmaceutical compositions comprising such polypeptides.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present disclosure provides T cell modulatory polypeptides (T-Cell-MPs) comprising a chemical conjugation site at which a KRAS epitope has been conjugated and at least one immunomodulatory polypeptide sequence that may be selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The T-Cell-epitope conjugates are useful for modulating (e.g., increasing proliferation or cytotoxic activity) the activity of T cells specific to the conjugate epitope, and accordingly for use as therapeutics. The T-Cell-epitope conjugates find use in treating a variety of cancers associated with KRAS.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 39/00 - Medicinal preparations containing antigens or antibodies
43.
T-cell modulatory multimeric polypeptides and methods of use thereof
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), and a peptide that presents an epitope to a T-cell receptor. A TMP of the present disclosure is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise a MOD, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor. A TMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Biopharmaceutical preparations for treating cancer, autoimmune diseases and infectious diseases; immunotherapeutic preparations for treating cancer, autoimmune diseases and infectious diseases
48.
ANTIGEN-PRESENTING POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides antigen-presenting polypeptides, including single-chain antigen-presenting polypeptides and multimeric antigen-presenting polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding antigen-presenting polypeptides of the present disclosure, as well as cells genetically modified with the nucleic acids. An antigen-presenting polypeptide of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides methods of modulating activity of a T cell.
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), a peptide that presents an epitope to a T-cell receptor, and a tumor-targeting polypeptide. A TMMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
Disclosed are MHC Class II constructs (CIICs) comprising DQ and DR gene products that can present peptide epitopes associated with cancers, allergies, autoimmune diseases (e.g., T1D and celiac disease), GVHD, HGVD, and infections to T cell receptors. The CIICs may also comprise sequences of immunomodulatory molecules (MODs) such as IL-2 or PD-L1 that can modulate receptors on the surface of T cells. CIICs are expressible at levels up to about 350 mg/l in culture, and are substantially stable to multiple freeze thaw cycles and to thermal denaturation at 42 °C fThe stability of CIICs and their ability to present peptide epitopes and MODs to T cells and their renders them useful as therapeutics for in vitro and in vivo methods of treating various cancers, allergies, autoimmune diseases (e.g., T1D and celiac disease), GVHD, HGVD, and infections.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
The present disclosure provides Transforming Growth Factor Beta (TGF-β) polypeptide constructs and complexes that find use in, for example, therapeutic treatment of diseases including autoimmune diseases and metabolic diseases and disorders. Also described are nucleic acids that encode the constructs and complexes and methods of preparing the constructs and complexes in cell-based expression systems.
The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) for the presentation of KRAS antigens in the context of a class I MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids. MAPPs of the present disclosure are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 14/74 - Major histocompatibility complex [MHC]
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07K 14/74 - Major histocompatibility complex [MHC]
C07K 14/79 - Transferrins, e.g. lactoferrins, ovotransferrins
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/62 - DNA sequences coding for fusion proteins
57.
MHC class II T-cell modulatory multimeric polypeptides for treating type 1 diabetes mellitus (T1D) and methods of use thereof
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and PD-L1 polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.
The present disclosure provides modified cytotoxic T cells (mCTLs), where the mCTLs comprise: a) one or more nucleic acids comprising nucleotide sequences encoding a T-cell receptor (TCR) specific for MHC class I polypeptides that present a human papilloma virus (HPV) E7 peptide comprising the amino acid sequence YMLDLQPETT (SEQ ID NO:1) or YMLDLQPET (SEQ ID NO:2); and b) one or more nucleic acids comprising nucleotide sequences encoding a chimeric antigen receptor (CAR), where the CAR comprises an antigen-binding domain specific for a cancer-associated antigen. The present disclosure provides methods of producing the mCTLs. The present disclosure provides methods of treating cancer, comprising administering the mCTLs to an individual in need thereof.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present disclosure provides T cell modulatory polypeptides (TMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), and a Betacoronavirus (e.g., a SARS-CoV-2) peptide that presents an epitope to a T-cell receptor. A TMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/74 - Major histocompatibility complex [MHC]
C12N 15/62 - DNA sequences coding for fusion proteins
61.
T-CELL ENGAGING POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides a single-chain T-cell engaging polypeptide (TEP) comprising a peptide epitope, class I major histocompatibility complex polypeptides, one or more immunomodulatory polypeptides, an immunoglobulin Fc polypeptide or a non-immunoglobulin scaffold polypeptide, and a tumor-targeting polypeptide. The present disclosure provides methods of treating cancer, comprising administering the TEP to an individual in need thereof.
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising an autoimmune dis-ease-associated-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have an autoimmune disease.
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.
The present disclosure provides immune cell binding polypeptides (ICBPs) that include a binding moiety that can bind to ILT2 and/or ILT4 polypeptides, at least one immunoinhibitory polypeptide, and a scaffold polypeptide. The ICBPs are useful for inducing immunological tolerance. The present disclosure provides methods of inducing immunological tolerance.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
65.
T-CELL MODULATORY MULTIMERIC POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory multimeric polypeptides comprising two different immunomodulatory polypeptides, at least one of which is a variant immunomodulatory polypeptide. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
The present disclosure provides T cell modulatory polypeptides (T-Cell-MPs) comprising a chemical conjugation site and at least one immunomodulatory polypeptide sequence that may be selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The unconjugated T-Cell-MPs may be conjugated to a molecule displaying an epitope to form a T-Cell-MP-epitope conjugate. The T-Cell-epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T cells specific to the conjugate epitope, and accordingly for use as therapeutics.
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
The present disclosure provides T cell modulatory polypeptide-epitope conjugates (T-Cell-MP-epitope conjugates) comprising a chemical conjugation site at which an NY-ESO (e.g., NY-ESO-1 or NY-ESO-2) or a MAGE (e.g., MAGEA4) peptide epitope is covalently attached and at least one immunomodulatory polypeptide sequence that may be variant selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The T-Cell-MP-epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T-cells specific to the NY-ESO or MAGE peptide epitope in an epitope selective/specific manner, and accordingly, for treating individuals with, for example, cancers expressing the covalently attached epitope. The disclosure also provides T-Cell-MP-epitope conjugates with targeting sequences that can server to, among other things, localize the T-Cell-MP-epitope conjugates to a specific tissue or cell type.
A61K 39/385 - Haptens or antigens, bound to carriers
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present disclosure provides T cell modulatory polypeptide-epitope conjugates (T-Cell-MP-epitope conjugates) comprising a chemical conjugation site at which a coronavirus peptide epitope is covalently attached and at least one immunomodulatory polypeptide sequence. The T-Cell-MP-epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T-cells specific to the coronavirus peptide epitope in an epitope selective/specific manner, and accordingly, for treating individuals with a coronavirus infection including long COVID. Alternatively, when the T-Cell-MP-epitope conjugate is redirected to a neoplastic cell by a targeting sequence, the redirected T-Cell-MP-epitope conjugate may be used to treat neoplasms including various cancers.
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present disclosure provides Multimeric Antigen-Presenting Polypeptides (MAPPs) for the presentation of epitopes in the context of a class II MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding the MAPPs. MAPPs are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers, autoimmune diseases and/or allergies.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/74 - Major histocompatibility complex [MHC]
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
73.
Antigen Presenting Polypeptide Complexes and Methods of Use Thereof
The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) for the presentation of antigens in the context of a class I MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids. MAPPs of the present disclosure are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers, autoimmune diseases and/or allergies.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) that comprise comprise (i) an optional immunomodulatory polypeptide such as a variant IL-2 polypeptide, (ii) class I HLA major histocompatibility complex (MHC) polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), (iii) a peptide that presents an epitope to a T-cell receptor, which together with the class I MHC polypeptides forms a peptide-MHC complex (pMHC), (iv) a tumor-targeting polypeptide, and (v) an optional Ig Fc polypeptide or other scaffold. Such TMMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual, and for "redirecting" a patient's repertoire of antiviral T cells to attack and kill cancer cells.
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor-1 (WT-1) peptide. A TMMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual, e.g., for the treatment of a cancer associated with WT-1.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
76.
MULTIMERIC T-CELL MODULATORY POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory multi-merit polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 39/00 - Medicinal preparations containing antigens or antibodies
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Biopharmaceutical preparations for treating cancer, autoimmune diseases and infectious diseases; immunotherapeutic preparations for treating cancer, autoimmune diseases and infectious diseases
78.
T-CELL MODULATORY MULTIMERIC POLYPEPTIDES WITH CONJUGATION SITES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMPs) conjugated to a coronavirus epitope and comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). By presenting the coronavirus epitope and MOD to a T-cell, the T-Cell-MMP-coronavirus epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T-cells specific to the coronavirus peptide in an epitope selective/specific manner, and accordingly, for treating individuals with a coronavirus infection.
The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
80.
Antigen-Presenting Polypeptides with Chemical Conjugation Sites and Methods of Use Thereof
The present disclosure provides antigen-presenting polypeptides, including single-chain antigen-presenting polypeptides and multimeric antigen-presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, epitope containing polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding antigen-presenting polypeptides comprising one or more chemical conjugation sites, as well as cells genetically modified with the nucleic acids. The single-chain and multimeric antigen-presenting polypeptides and their epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment.
The present disclosure provides a chimeric molecule comprising: a) a T-cell modulatory multimeric polypeptide (TMMP); and b) a nucleic acid component, where the nucleic acid component comprises a nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising an antibody that binds a cancer-associated antigen. The TMMP binds to and activates a target T cell; the nucleic acid component is taken up by the target T cell such that the target T cell expresses the CAR on its surface. The present disclosure provides methods of making the chimeric molecule. The present disclosure provides treatment methods comprising administering the chimeric molecule.
The present disclosure provides in vitro modified cytotoxic T cells (CTLs) that comprise: a) a T-cell receptor (TCR) specific for a preselected antigen in a human; and b) a nucleic acid(s) encoding a chimeric antigen receptor (CAR) specific for a cancer-associated antigen. The present disclosure provides methods of producing the modified CTLs. The present disclosure provides of treating cancer, comprising administering the modified CTLs to an individual in need thereof.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/62 - DNA sequences coding for fusion proteins
83.
MULTIMERIC T-CELL MODULATORY POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide, an epitope-presenting peptide, and class I MHC polypeptides. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 39/00 - Medicinal preparations containing antigens or antibodies
84.
ANTIGEN PRESENTING POLYPEPTIDE COMPLEXES AND METHODS OF USE THEREOF
The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) for the presentation of T1D epitopes in the context of a Class II MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding those MAPPs. MAPPs of the present disclosure are useful for selectively modulating activity of T cells having T cell receptors that recognize the T1D epitopes presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.
The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
The present disclosure provides T-cell modulatory polypeptides (TMPs) comprising an AI peptide epitope, MHC class II polypeptides, one or more immunomodulatory polypeptides, a TGF-β polypeptide, and a masking polypeptide. A TMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have an autoimmune disease.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61P 37/00 - Drugs for immunological or allergic disorders
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
in vitroin vivoin vivo as a method of treatment of diseases and disorders including autoimmune diseases, allergies, GVHD, HGVD, and metabolic disorder.
The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) that comprise a peptide epitope and a reversibly masked TGF-β peptide capable of acting as an agonist of cellular TGF-β receptors. The MAPPs are capable of presenting the peptide epitope in the context of a Class II MHC receptor to T cells. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding the MAPPs. The MAPPs are useful for selectively modulating activity of a T cells having T cell receptors that recognize the epitope presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including autoimmune diseases, graft vs. host disease, host vs. graft disease, and/or allergies.
The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) that comprise a TID-associated peptide epitope and a reversibly masked TGF-β peptide capable of acting as an agonist of cellular TGF-β receptors. The MAPPs are capable of presenting the TID-associated peptide epitope in the context of a Class II MHC receptor to T cells. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding those MAPPs. MAPPs of the present disclosure are useful for selectively modulating activity of a T cells having T cell receptors that recognize the TID epitopes presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have TID.
The present disclosure provides T-cell modulatory polypeptides (TMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, one or more immunomodulatory polypeptides, a TGF-β polypeptide, and a masking polypeptide. A TMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), and a peptide that presents an epitope to a T-cell receptor. A TMP of the present disclosure is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
A61K 38/02 - Peptides of undefined number of amino acidsDerivatives thereof
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/385 - Haptens or antigens, bound to carriers
A61K 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
95.
T-CELL MODULATORY POLYPEPTIDES AND METHODS OF USE THEREOF
The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise a MOD, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor. A TMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
A61K 38/02 - Peptides of undefined number of amino acidsDerivatives thereof
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/385 - Haptens or antigens, bound to carriers
A61K 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
96.
T-cell modulatory multimeric polypeptides and methods of use thereof
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), a peptide that presents an epitope to a T-cell receptor, and a tumor-targeting polypeptide. A TMMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
The present disclosure provides Transforming Growth Factor Beta (TGF-β) polypeptide constructs and complexes that find use in, for example, therapeutic treatment of diseases including autoimmune diseases and metabolic diseases and disorders. Also described are nucleic acids that encode the constructs and complexes and methods of preparing the constructs and complexes in cell-based expression systems.
The present disclosure provides T cell modulatory polypeptides (T-Cell-MPs) comprising a chemical conjugation site at which a KRAS epitope has been conjugated and at least one immunomodulatory polypeptide sequence that may be selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The T-Cell-epitope conjugates are useful for modulating (e.g., increasing proliferation or cytotoxic activity) the activity of T cells specific to the conjugate epitope, and accordingly for use as therapeutics. The T-Cell-epitope conjugates find use in treating a variety of cancers associated with KRAS.
