# US 10,865,243 B2 · Chimeric antigen receptor and its use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,865,243 B2 - Document ID: US10865243B2 - Status: Granted - Kind: B2 - Application number: 15/325,638 - Filed: 2015-07-16 - Published: 2017-05-25 - Granted: 2020-12-15 - Earliest claimed: 2014-07-16 - Applicants: Hinrich Abken; Andreas Hombach - Inventors: Hinrich Abken; Andreas Hombach - Web page: https://patentgrep.com/patent/US10865243B2 ## CPC - C07K 16/2803: {against the immunoglobulin superfamily} - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - C07K 14/70521: {CD28, CD152} - C07K 14/70535: {Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)} - C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95} - C07K 16/3007: {Carcino-embryonic Antigens} - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/622: Single chain antibody (scFv) - C07K 2319/00: Fusion polypeptide - C07K 2319/02: containing a signal sequence - C07K 2319/03: containing a transmembrane segment - 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) - 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 In a first aspect, the present invention relates to a recombinant polypeptide containing a domain comprising at least two antibody units whereby the first antibody unit is an anti-CD30 single chain antibody unit while the second antibody unit is a antibody unit being specific for an antigen present on the surface of a predetermined target cell. In particular, the present invention relates to a recombinant polypeptide containing at least the following domains starting from the N-terminus to the C-terminus: a first domain containing an anti-CD30 single chain antibody unit, in particular, HRS3 scFv of SEQ ID No. 2 or homologs thereof having at least 70% identity with SEQ ID No. 2 binding specifically to CD30, and an antibody unit said antibody unit being specific for an antigen present on the surface of a predetermined target cell, in particular, being specific for a tumor-associated antigen; optionally a spacer domain; a trans-membrane domain; and a cytoplasmatic signalling domain. In a further aspect, the present invention relates to a nucleic acid molecule encoding the polypeptide according to the present invention, as well as vectors and cells containing the same. Moreover, lymphocytes are provided, in particular T-cells like CD8+ or a CD4+ T-cell expressing on its surface chimeric antigen receptors containing an anti-CD30 single chain antibody unit and an antibody unit whereby said antibody unit being specific for an antigen present on the surface of a predetermined target cell. Immune cells modified with the polypeptide show improved functions, in particular in the treatment of cancer, in particular CD30− cancer. That is, the cells are for use in adapted cell therapy for treating cancer in a subject in need thereof. ## Claims ### Claim 1 A nucleic acid molecule comprising a nucleic acid sequence encoding a recombinant polypeptide containing at least the following domains starting from the N-terminus to the C-terminus: a first domain containing i) an anti-CD30 single chain antibody unit and ii) an antibody unit specific for an antigen present on a surface of a predetermined target cell, wherein the target cell is CD30 negative; optionally a spacer domain; a trans-membrane domain; and a cytoplasmatic signalling domain, wherein the anti-CD30 single chain antibody unit in the first domain is HRS3 scFv of SEQ ID NO. 2 or homologs thereof having at least 95% identity with SEQ ID NO. 2 binding specifically to CD30. ### Claim 2 (depends on 1) The nucleic acid molecule according to claim 1, wherein said recombinant polypeptide further comprises a leader sequence being located N-terminally to the first domain containing the anti-CD30 single chain antibody unit and the antibody unit specific for the antigen present on the surface of the predetermined target cell being CD30 negative. ### Claim 3 (depends on 1) The nucleic acid molecule according to claim 1, wherein the anti-CD30 single chain antibody unit is the HRS3 scFv peptide of the SEQ ID No. 2. ### Claim 4 (depends on 1) The nucleic acid molecule according to claim 1, wherein the spacer domain is present and is an IgG1 CH2 CH3 domain of SEQ ID No. 6 or homologs thereof having at least 95% identity therewith. ### Claim 5 (depends on 1) The nucleic acid molecule according to claim 1, wherein the trans-membrane domain is obtained from CD28. ### Claim 6 (depends on 1) The nucleic acid molecule according to claim 1, wherein the intracellular domain contains a CD3zeta or a Fc-epsilon receptor I-gamma signalling chain or a costimulatory unit. ### Claim 7 (depends on 1) The nucleic acid molecule according to claim 1, wherein the intracellular domain is a CD28 signalling domain. ### Claim 8 (depends on 1) The nucleic acid molecule according to claim 1, wherein the antibody unit specific for the antigen present on the surface of the predetermined target cell being CD30 negative binds to a tumor-associated antigen selected from the group consisting of carcinoembryonic antigen (CEA), CA19-9, CA72-4 (TAG-72), PSCA, Muc-1, HMW-MAA p97 melanotransferrin, fetal actelycholin receptor, ErbB2 (Her2/neu), multi-drug-resistance protein (MDR), CD19, CD20, and TOSO. ### Claim 9 (depends on 1) The nucleic acid molecule according to claim 1, wherein the antibody unit specific for the predetermined target cell being CD30 negative binds to one or more viral antigens. ### Claim 10 (depends on 1) A vector comprising the nucleic acid sequence according to claim 1. ### Claim 11 (depends on 1) A cell, cell line or host cell containing a nucleic acid molecule according to claim 1 wherein the nucleic acid molecule is isolated, combined with other nucleic acids, or part of a vector. ### Claim 12 (depends on 11) The cell, cell line or host cell according to claim 11 wherein the cell or host cell is a modified peripheral blood cell. ### Claim 13 (depends on 4) The nucleic acid molecule of claim 4, wherein the spacer domain is a mutated IgG1 CH2 CH3 domain according to SEQ ID No. 6. ### Claim 14 (depends on 6) The nucleic acid molecule of claim 6, wherein the intracellular domain is the CD3zeta signalling unit of SEQ ID No. 10 or a homolog thereof having at least 95% homology. ### Claim 15 (depends on 6) The nucleic acid molecule of claim 6, wherein the intracellular domain is the IgE Fc epsilon receptor-I gamma-signalling unit of SEQ ID No. 12 or a homolog thereof having at least 95% homology. ### Claim 16 (depends on 1) The nucleic acid molecule of claim 1, wherein said predetermined target cell is a tumor-associated antigen. ### Claim 17 (depends on 1) The nucleic acid molecule of claim 1 having SEQ ID No. 13. ### Claim 18 (depends on 10) The vector of claim 10, wherein the vector is a viral vector. ### Claim 19 (depends on 12) The cell, cell line or host cell of claim 12, wherein the modified peripheral blood cell is a CD8+ T-cell or a CD4+ T-cell. ### Claim 20 (depends on 9) The nucleic acid molecule of claim 9, wherein the one or more viral antigens are selected from the group consisting of heptatis virus B-associated antigen S or L, and cytomegalovirus-associated antigen. ### Claim 21 (depends on 7) The nucleic acid molecule of claim 7, wherein the CD28 signalling domain lacks the LCK binding motif.