# US 2019/0375816 A1 · High avidity antigen recognizing constructs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0375816 A1 - Document ID: US20190375816A1 - Status: Published application - Kind: A1 - Application number: 16/507,803 - Filed: 2019-07-10 - Published: 2019-12-12 - Earliest claimed: 2013-01-29 - Assignees: Max-DelbrüCk-Centrum FüR Molekulare Medizin (Mdc) Berlin-Buch - Applicants: Max-DelbrüCk-Centrum FüR Molekulare Medizin (Mdc) Berlin-Buch - Inventors: Thomas Blankenstein; Matthias Obenaus; Catarina Leitão - Web page: https://patentgrep.com/patent/US20190375816A1 ## CPC - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - A61P 35/00: Antineoplastic agents - C07K 14/70503: {Immunoglobulin superfamily} - C07K 16/2803: {against the immunoglobulin superfamily} - C07K 16/30: from tumour cells - G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites} - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C12N 15/62: DNA sequences coding for fusion proteins - G01N 2333/705: Assays involving receptors, cell surface antigens or cell surface determinants - 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 - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells—such as CD4 or CD8 positive T cells—which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new means for immune therapy, specifically adoptive T cell therapy, for treating cancer. ## Claims ### Claim 1 An antigen recognizing construct comprising a complementary determining region 3 (CDR3) having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NOs:1 to 6. ### Claim 2 (depends on 1) The antigen recognizing construct according to claim 1, wherein said construct binds specifically to the MAGE-A1 antigen. ### Claim 3 (depends on 1) The antigen recognizing construct according to claim 1, wherein the antigen recognizing construct is an antibody, or derivative or fragment thereof, or a T cell receptor (TCR), or derivative or fragment thereof. ### Claim 4 (depends on 1) The antigen recognizing construct according to claim 1, which is a TCR, the TCR comprising at least one alpha and/or beta TCR chain, a. wherein said TCR chain is encoded by at least one nucleic acid, the nucleic acid comprising a nucleotide sequence selected from (i) the TCR chain encoding equences in SEQ ID NO:13 to 21, or (ii) a sequence having at least 80% identity to a TCR encoding sequence in SEQ ID NO:13 to 21, or (iii) a sequence that due to the degeneracy of the genetic code encodes for an identical TCR as any one of the TCR encoding sequences in SEQ ID NO:13 to 21, but has a different sequence; or b. wherein said TCR chain comprises an amino acid sequence according to any one of the TCR chains shown in SEQ ID NOs:22-39, or an amino acid sequence having at least 80% identity to an amino acid sequence shown in SEQ ID NO:22 to 39. ### Claim 5 (depends on 1) The antigen recognizing construct according to claim 1, wherein said antigen recognizing construct induces an immune response. ### Claim 6 (depends on 3) A T cell receptor (TCR) according to claim 3, or derivative or fragment thereof, with a. an alpha chain comprising the CDR sequences shown in SEQ ID NO: 40, 41, and 1; and a beta chain comprising the CDR sequences shown in SEQ ID NO: 46, 47, and 4; or b. an alpha chain comprising the CDR sequences shown in SEQ ID NO: 42, 43, and 2; and a beta chain comprising the CDR sequences shown in SEQ ID NO: 48, 49, and 5; or c. an alpha chain comprising the CDR sequences shown in SEQ ID NO: 44, 45, and 3; and a beta chain comprising the CDR sequences shown in SEQ ID NO: 50, 51, and 6. ### Claim 7 (depends on 1) A nucleic acid encoding an antigen recognizing construct according to claim 1. ### Claim 8 (depends on 7) A vector comprising a nucleic acid according to claim 7. ### Claim 9 (depends on 1) A host cell comprising an antigen recognizing construct according to claim 1, or a nucleic acid encoding an antigen recognizing construct according to claim 1. ### Claim 10 (depends on 9) The host cell according to claim 9, which is a lymphocyte. ### Claim 11 (depends on 1) A method for the diagnosis, prevention and/or treatment of a proliferative disease wherein said method comprises the use of an antigen recognizing construct according to claim 1 or a nucleic acid encoding an antigen recognizing construct according to claim 1. ### Claim 12 (depends on 11) The method according to claim 11, wherein the method comprises adoptive T cell therapy. ### Claim 13 (depends on 1) A method for the manufacturing of a MAGE-A1 specific antigen recognizing construct (ARC) expressing cell line, comprising: a. providing a suitable host cell, b. providing a genetic construct encoding for an ARC, wherein said ARC comprises a CDR3 having an amino acid sequence with at least 90% sequence identity to an amino acid sequence selected from SEQ ID Nos. 1 to 6, or wherein said ARC is an ARC according to claim 1, c. introducing into said suitable host cell said genetic construct, d. expressing said genetic construct by said suitable host cell. ### Claim 14 (depends on 13) The method according claim 13, further comprising purification of the ARC from the cell and, optionally, reconstitution of the translated ARC-fragments in a T-cell. ### Claim 15 (depends on 2) The antigen recognizing construct, according to claim 2, wherein said construct specifically binds to the human MAGE-A1278-286 epitope. ### Claim 16 (depends on 5) The antigen recognizing construct, according to claim 5, wherein the immune response is characterized by an increase in interferon (IFN) γ levels. ### Claim 17 (depends on 10) The host cell, according to claim 10, which is a CD4 positive or CD8 positive T lymphocyte. ### Claim 18 (depends on 11) The method, according to claim 11, used to treat a tumor disease. ### Claim 19 (depends on 18) The method, according to claim 18, wherein the disease is characterized by differential expression of the MAGE-A1 antigen.