# US 2019/0169309 A1 · Removal of cancer cells by circulating virus-specific cytotoxic t-cells using cancer cell targeted mhc class 1 compromising multi-function proteins > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0169309 A1 - Document ID: US20190169309A1 - Status: Published application - Kind: A1 - Application number: 16/049,201 - Filed: 2018-07-30 - Published: 2019-06-06 - Earliest claimed: 2012-11-30 - Assignees: Roche Glycart AG - Applicants: Roche Glycart AG - Inventors: Christian Klein; Hendrik Knoetgen; Martina Schmittnaegel; Pablo Umana - Web page: https://patentgrep.com/patent/US20190169309A1 ## CPC - C07K 16/3053: {Skin, nerves, brain} - A61P 31/12: Antivirals - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 14/70539: {MHC-molecules, e.g. HLA-molecules} - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 16/30: from tumour cells - C07K 16/46: Hybrid immunoglobulins (hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00) - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - A61K 2039/505: {comprising antibodies} - A61K 2039/572: {cytotoxic response} - C07K 2317/35: Valency - C07K 2317/41: Glycosylation, sialylation, or fucosylation - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/622: Single chain antibody (scFv) - C07K 2319/00: Fusion polypeptide - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies - C07K 2319/74: containing a fusion for binding to a cell surface receptor - C12N 2710/16133: Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Herein is reported a multi-function protein, characterized in that it comprises exactly one antigen presenting domain, exactly one antibody Fc-region, and at least one antigen binding site, wherein the antigen presenting domain comprises in N- to C-terminal direction either (i) a β2-microglobulin, and (ii) the extracellular domains α1, α2, and α3 of a class I MHC molecule with a relative frequency of less than 1%, or (i) a T-cell response eliciting peptide, (ii) a β2-microglobulin, and (iii) the extracellular domains α1, α2, and α3 of a class I MHC molecule with a relative frequency of 1% or more, wherein the antigen binding site binds to a cancer cell surface antigen. ## Claims ### Claim 1 A multi-function protein, characterized in that it comprises exactly one antigen presenting domain, exactly one antibody Fc-region, and at least one antigen binding site, wherein the antigen presenting domain comprises in N- to C-terminal direction either (i) a T-cell response eliciting peptide, (ii) a β2-microglobulin, and (iii) the extracellular domains α1, α2, and α3 of a class I MHC molecule with a relative frequency of 1% or more, or (i) a T-cell response eliciting peptide, (ii) the extracellular domains α1, α2, and α3 of a class I MHC molecule with a relative frequency of 1% or more, and (iii) a β2-microglobulin, wherein the antigen binding site binds to a melanoma-associated chondroitin sulfate proteoglycan (MCSP). ### Claim 2 (depends on 1) The multi-function protein according to claim 1, characterized in that the antibody Fc-region comprises a first and second disulfide-linked Fc-region polypeptide, whereby the antigen binding site comprises the first Fc-region polypeptide. ### Claim 3 (depends on 1) The multi-function protein according to claim 1, characterized in that the antigen binding site comprises i) a pair of an antibody heavy chain and an antibody light chain, or ii) a scFv fusion polypeptide comprising in N- to C-terminal direction a scFv antibody fragment and an antibody Fc-region polypeptide, or iii) a scFab fusion polypeptide comprising in N- to C-terminal direction a scFab and an antibody Fc-region polypeptide. ### Claim 4 (depends on 1) The multi-function protein according to claim 1, characterized in that i) the antigen presenting domain is linked to the N-terminus of the heavy chain or to the N-terminus of the light chain of the antigen binding site, or ii) the antigen presenting domain is linked to the C-terminus of the heavy chain or to the C-terminus of the light chain of the antigen binding site, or iii) the antigen presenting domain is linked to the N- or C-terminus of the scFv fusion polypeptide, or iv) the antigen presenting domain is linked to the N- or C-terminus of the scFab fusion polypeptide, or iv) the antigen presenting domain is linked to the N- or C-terminus of the second Fc-region polypeptide. ### Claim 5 (canceled) ### Claim 6 (depends on 1) The multi-function protein according to claim 1, characterized in that the T-cell response eliciting peptide is a virus-derived peptide. ### Claim 7 (depends on 6) The multi-function protein according to claim 6, characterized in that the virus-derived peptide is a human cytomegalovirus-derived peptide. ### Claim 8 (depends on 1) The multi-function protein according to claim 1, characterized in that the virus-derived peptide has the amino acid sequence of SEQ ID NO: 01. ### Claim 9 (depends on 1) The multi-function protein according to claim 1, characterized in that the class I MHC molecule with a relative frequency of 1% or more is selected from the group comprising HLA-A*0201, HLA-A*1101, HLA-A*2402, HLA-A*340101, HLA-C*0304, HLA-C*0401, and HLA-C*0702. ### Claim 10 (depends on 1) The multi-function protein according to claim 1, characterized in that the class I MEC molecule with a relative frequency of less than 1% is selected from the group comprising HLA-B*4201, HLA-B*5901, HLA-B*6701, and HLA-B*7802. ### Claim 11 (depends on 1) The multi-function protein according to claim 1, characterized in that the antigen presenting domain comprises (i) a virus-derived peptide, (ii) β2-microglobulin, and (iii) the soluble HLA-A allele A*0201. ### Claim 12 (depends on 1) The multi-function protein according to claim 1, characterized in that the antigen presenting domain comprises in N- to C-terminal direction: (i) a virus-derived peptide that has an amino acid sequence selected from the group comprising SEQ ID NO: 01 to SEQ ID NO: 70, (ii) a first linker peptide that has an amino acid sequence selected from the group comprising SEQ ID NO: 77, 78, 79, 82, 83, and 84, (iii) a β2-microglobulin that has an amino acid sequence of SEQ ID NO: 71, (iv) a second linker peptide that has an amino acid sequence selected from the group comprising SEQ ID NO: 77, 78, 79, 82, 83, and 84, (v) the extracellular domains α1, α2, and α3 of a class I MHC molecule that has an amino acid sequence of SEQ ID NO: 72, and (vi) a third linker peptide that has an amino acid sequence selected from the group comprising SEQ ID NO: 73, 77, 78, 79, 82, 83, 84, and 136. ### Claim 13 (depends on 1) A pharmaceutical formulation comprising the multi-function protein according to claim 1 and optionally a pharmaceutically acceptable carrier. ### Claim 14 (canceled) ### Claim 15 (canceled) ### Claim 16 (canceled) ### Claim 17 (canceled) ### Claim 18 (depends on 13) A method of treating cancer comprising administering to a subject in need thereof the pharmaceutical formulation according to claim 13. ### Claim 19 (depends on 1) A method of attracting virus-specific cytotoxic T-cells to a target comprising administering to a subject in need thereof the multi-specific protein according to claim 1. ### Claim 20 (depends on 1) A method of removing cancer cells or virus infected cells comprising administering to a subject in need thereof the multi-specific protein according to claim 1.