Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
  • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
  • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
  • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
  • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
  • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
  • C07K7/04—Linear peptides containing only normal peptide links
  • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K39/00—Medicinal preparations containing antigens or antibodies
  • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K2317/00—Immunoglobulins specific features
  • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
  • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K2317/00—Immunoglobulins specific features
  • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
  • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
  • C07K2317/622—Single chain antibody (scFv)
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K2319/00—Fusion polypeptide
  • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
  • C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K2319/00—Fusion polypeptide
  • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
  • C07K2319/10—Fusion polypeptide containing a localisation/targetting motif containing a tag for extracellular membrane crossing, e.g. TAT or VP22
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K2319/00—Fusion polypeptide
  • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K2319/00—Fusion polypeptide
  • C07K2319/50—Fusion polypeptide containing protease site
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
  • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
  • C12N2710/00011—Details
  • C12N2710/16011—Herpesviridae
  • C12N2710/16411—Rhadinovirus, e.g. human herpesvirus 8
  • C12N2710/16422—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
  • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
  • C12N2710/00011—Details
  • C12N2710/16011—Herpesviridae
  • C12N2710/16411—Rhadinovirus, e.g. human herpesvirus 8
  • C12N2710/16433—Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory

Definitions

• a lymphoproliferative, inflammatory, or immune disorder such as an autoimmune disease especially one mediated by inappropriately activated B or T cells.
• the method includes the step of administering to the subject an effective amount of a nucleic acid (such as an expression cassette or vector) encoding the peptide of the present invention including the fusion protein as described above and herein or an effective amount of the pharmaceutical composition described above and herein.
• the cancer is a primary effusion lymphoma (PEL).
• FIGS. 1A-1I Viral protein sequence based cancer drug.
• FIG. 1A Discovery of hijacking transcription machinery in KSHV reactivating cells (Chen et al., J. Virol 2017). Nascent RNA-FISH along with IF A shows accumulation of cellular RNA polymerase II at the site of viral gene transcription.
• FIG. 1B Reporter assay. KSHV ORF50 overexpression inhibits MYC activation.
• FIG. 1C Chromatin immunoprecipitation with Mass Spectrometry. Proteins inducibly interact with both ORF50 and RNA polII are shown.
• Non-limiting examples of amino acid substitutions Key protein elements were conserved in other gamma-herpesviral homologs. Our current peptide is shown in the middle and proposed substitutions of amino acids are marked in red. In vitro and in vivo experiments are repeated with new peptides and also improvement made with the changes in stability (PK/PD) and tumor killing effects (PEL xenograft model) are examined.
• PK/PD changes in stability
• PEL xenograft model tumor killing effects
• FIG. 3 Effect on CD 19+ B cell response upon sCD40L stimulation.
• vector and “expression vector” refer to a nucleic acid construct, generated recombinantly or synthetically, with a series of specified nucleic acid elements that permit transcription of a particular nucleic acid sequence (e.g., encoding an antigen and/or fusion protein of the invention) in a host cell or engineered cell.
• a vector includes a polynucleotide to be transcribed, operably linked to a promoter.
• the term “therapeutically effective amount” or “sufficient amount” refers to the amount of a system, recombinant polynucleotide, or composition described herein that is sufficient to effect beneficial or desired results.
• the therapeutically effective amount may vary depending upon one or more of: the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the immune status of the subject, the manner of administration and the like, which can readily be determined by one of ordinary skill in the art.
• the specific amount may vary depending on one or more of: the particular agent chosen, the target cell type, the location of the target cell in the subject, the dosing regimen to be followed, whether it is administered in combination with other compounds, timing of administration, and the physical delivery system in which it is carried.
• an effective amount is determined by such considerations as may be known in the art.
• the amount must be effective to achieve the desired therapeutic effect in a subject suffering from a disease such as an infectious disease or cancer.
• the desired therapeutic effect may include, for example, amelioration of undesired symptoms associated with the disease, prevention of the manifestation of such symptoms before they occur, slowing down the progression of symptoms associated with the disease, slowing down or limiting any irreversible damage caused by the disease, lessening the severity of or curing the disease, or improving the survival rate or providing more rapid recovery from the disease.
• the amount may also be effective to prevent the development of the disease.
• a “heterologous polypeptide” or “heterologous polynucleotide” to SEQ ID NO: 1 or its encoding sequence is one derived from an origin different from the protein of which SEQ ID NO: 1 is a naturally-occurring fragment.
• the fusion of SEQ ID NO: 1 (or its coding sequence) with a heterologous polypeptide (or polynucleotide sequence) does not result in a longer polypeptide or polynucleotide sequence that can be found in nature as an intact protein (or its coding sequence) or a segment thereof.
• Another example includes targeting IgE-producing B cells in the skin or systemically in allergic diseases such as atopic dermatitis.
• suppressor cells such as Foxp3 + T regulatory cells or myeloid derived suppressor cells in tumors can be concomitantly targeted to increase the overall anti-tumor efficacy.
• the peptide and the antibody are separated by a linker, e.g., a linker with a protease (for example, matrix metalloprotease) cleavage site so as to liberate the peptide in the vicinity of the target cell.
• a linker e.g., a linker with a protease (for example, matrix metalloprotease) cleavage site so as to liberate the peptide in the vicinity of the target cell.
• an antibody or antibody fragment can be chemically linked to the peptide.
• any molecule that binds specifically to a MYC-dependent cancer cell or to a target lymphoid cell such as B or T cell
• ligands to receptors on the surface of MYC- dependent cancer cells can be used.
• the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is an antigen-binding fragment, such as a F(ab’)2, Fab’, Fab, scFv, and the like.
• the term "antibody or antigen-binding fragment" can also encompass multi-specific and hybrid antibodies, with dual or multiple antigen or epitope specificities. In particular embodiments, the antibody is a single chain antibody.
• N- ⁇ -protected amino acids having protected side chains are added stepwise to a growing polypeptide chain linked by its C-terminal and to a solid support, i.e., polystyrene beads.
• the peptides are synthesized by linking an amino group of an N- ⁇ - deprotected amino acid to an ⁇ -carboxy group of an N- ⁇ -protected amino acid that has been activated by reacting it with a reagent such as dicyclohexylcarbodiimide. The attachment of a free amino group to the activated carboxyl leads to peptide bond formation.
• the most commonly used N- ⁇ -protecting groups include Boc, which is acid labile, and Fmoc, which is base labile.
• the expression cassette should also contain a transcription termination region downstream of the structural gene to provide for efficient termination.
• the termination region may be obtained from the same gene as the promoter sequence or may be obtained from different genes.
• the dosage forms typically include a conventional pharmaceutical carrier or excipient and may additionally include other medicinal agents, carriers, adjuvants, diluents, tissue permeation enhancers, solubilizers, and the like.
• Appropriate excipients can be tailored to the particular dosage form and route of administration by methods well known in the art (see, e.g., REMINGTON’S PHARMACEUTICAL SCIENCES, supra).
• Example 9 Inhibition of inflammatory cytokine production in vivo

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• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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• Micro-Organisms Or Cultivation Processes Thereof (AREA)
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• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

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• 2021
  • 2021-10-21 KR KR1020237015229A patent/KR20230092938A/ko active Pending
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