# US 11,111,286 B2 · T cell receptors and immune therapy using the same against PRAME positive cancers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,111,286 B2 - Document ID: US11111286B2 - Status: Granted - Kind: B2 - Application number: 16/731,139 - Filed: 2019-12-31 - Published: 2020-04-23 - Granted: 2021-09-07 - Earliest claimed: 2017-03-23 - Assignees: Immatics Biotechnologies GmbH - Applicants: Immatics Biotechnologies GmbH - Inventors: Leonie Alten; Dominik Maurer; Sebastian Bunk; Claudia Wagner; Mathias Ferber - Web page: https://patentgrep.com/patent/US11111286B2 ## CPC - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00) - A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells - A61K 40/32: T-cell receptors [TCR] - A61K 40/427: {PRAME} - C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE} - C07K 16/3053: {Skin, nerves, brain} - C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]} - C12N 5/10: Cells modified by introduction of foreign genetic material - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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) - 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 antigen recognizing constructs against tumor associated antigens (TAA), in particular against Preferentially Expressed Antigen of Melanoma (PRAME). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and TAA binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of TAA expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention. ## Claims ### Claim 1 A method of treating a patient who has a PRAME positive cancer, wherein the PRAME positive cancer is capable of presenting a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in the context of HLA-A*02 on the cell surface, comprising administering to the patient a population of transformed CD8+T cells expressing at least one vector encoding a T cell receptor (TCR), wherein the TCR comprises an α variable domain comprising CDR1α, CDR2α, and CDR3α of SEQ ID NO: 130, wherein the sequence of the α variable domain is at least 95% identical to SEQ ID NO:130, and a β variable domain comprising CDR1β, CDR2β, and CDR3β of SEQ ID NO: 136, wherein the sequence of the β variable domain is at least 95% identical to SEQ ID NO:136, wherein the TCR is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02, and wherein the cancer is selected from acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal, or anorectum, cancer of the eye, cancer of the intrahepatic bile duct, cancer of the joints, cancer of the neck, gallbladder, or pleura, cancer of the nose, nasal cavity, or middle ear, cancer of the oral cavity, cancer of the vagina, cancer of the vulva, chronic lymphocytic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, glioma, Hodgkin lymphoma, hypopharynx cancer, kidney cancer, larynx cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, nasopharynx cancer, non-Hodgkin lymphoma, cancer of the oropharynx, ovarian cancer, cancer of the penis, pancreatic cancer, peritoneum, omentum, and mesentery cancer, pharynx cancer, prostate cancer, rectal cancer, renal cancer, skin cancer, small intestine cancer, soft tissue cancer, stomach cancer, testicular cancer, thyroid cancer, cancer of the uterus, ureter cancer, and urinary bladder cancer. ### Claim 2 (depends on 1) The method of claim 1, wherein the population of transformed cells are produced by a method comprising isolating a CD8+T cell from a subject, transforming the cell with at least one vector encoding the TCR to produce a transformed cell, and expanding the transformed cell to produce the population of transformed cells. ### Claim 3 (depends on 2) The method of claim 2, wherein the subject is the patient. ### Claim 4 (depends on 2) The method of claim 2, wherein the subject is a healthy donor. ### Claim 5 (depends on 1) The method of claim 1, wherein the population of transformed cells are administered in the form of a pharmaceutical composition. ### Claim 6 (depends on 5) The method of claim 5, wherein the pharmaceutical composition comprises a chemotherapeutic agent selected from the group consisting of asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, and vincristine. ### Claim 7 (depends on 1) The method of claim 1, wherein the CDR1α consists of the amino acid sequence of SEQ ID NO: 127, the CDR2α comprises the amino acid sequence of SEQ ID NO: 128, the CDR3α comprises the amino acid sequence of SEQ ID NO: 129, the CDR1β consists of the amino acid sequences of SEQ ID NO: 133, the CDR2β comprises the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprises the amino acid sequence of SEQ ID NO: 135. ### Claim 8 (depends on 1) The method of claim 1, wherein the CDR1α comprises the amino acid sequence of SEQ ID NO: 127, the CDR2α consists of the amino acid sequence of SEQ ID NO: 128, the CDR3α comprises the amino acid sequence of SEQ ID NO: 129, the CDR1β comprises the amino acid sequences of SEQ ID NO: 133, the CDR2β consists of the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprises the amino acid sequence of SEQ ID NO: 135. ### Claim 9 (depends on 1) The method of claim 1, wherein the CDR1α comprises the amino acid sequence of SEQ ID NO: 127, the CDR2α comprises the amino acid sequence of SEQ ID NO: 128, the CDR3α consists of the amino acid sequence of SEQ ID NO: 129, the CDR1β comprises the amino acid sequences of SEQ ID NO: 133, the CDR2β comprises the amino acid sequence of SEQ ID NO: 134, and the CDR3β consists of the amino acid sequence of SEQ ID NO: 135. ### Claim 10 (depends on 1) The method of claim 1, wherein the CDR1α consists of the amino acid sequence of SEQ ID NO: 127, the CDR2α consists of the amino acid sequence of SEQ ID NO: 128, the CDR3α comprises the amino acid sequence of SEQ ID NO: 129, the CDR1β consists of the amino acid sequences of SEQ ID NO: 133, the CDR2β consists of the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprises the amino acid sequence of SEQ ID NO: 135. ### Claim 11 (depends on 1) The method of claim 1, wherein the CDR1α consists of the amino acid sequence of SEQ ID NO: 127, the CDR2α comprises the amino acid sequence of SEQ ID NO: 128, the CDR3α consists of the amino acid sequence of SEQ ID NO: 129, the CDR1β consists of the amino acid sequences of SEQ ID NO: 133, the CDR2β comprises the amino acid sequence of SEQ ID NO: 134, and the CDR3β consists of the amino acid sequence of SEQ ID NO: 135. ### Claim 12 (depends on 1) The method of claim 1, wherein the CDR1α comprises the amino acid sequence of SEQ ID NO: 127, the CDR2α consists of the amino acid sequence of SEQ ID NO: 128, the CDR3α consists of the amino acid sequence of SEQ ID NO: 129, the CDR1β comprises the amino acid sequences of SEQ ID NO: 133, the CDR2β consists of the amino acid sequence of SEQ ID NO: 134, and the CDR3β consists of the amino acid sequence of SEQ ID NO: 135. ### Claim 13 (depends on 1) The method of claim 1, wherein the CDR1α consists of the amino acid sequence of SEQ ID NO: 127, the CDR2α consists of the amino acid sequence of SEQ ID NO: 128, the CDR3α consists of the amino acid sequence of SEQ ID NO: 129, the CDR1β consists of the amino acid sequences of SEQ ID NO: 133, the CDR2β consists of the amino acid sequence of SEQ ID NO: 134, and the CDR3β consists of the amino acid sequence of SEQ ID NO: 135. ### Claim 14 (depends on 1) The method of claim 1, wherein the cancer is melanoma. ### Claim 15 (depends on 1) The method of claim 1, wherein the cancer is bone cancer. ### Claim 16 (depends on 1) The method of claim 1, wherein the cancer is breast cancer. ### Claim 17 (depends on 1) The method of claim 1, wherein the cancer is lung cancer. ### Claim 18 (depends on 1) The method of claim 1, wherein the cancer is urinary bladder cancer. ### Claim 19 (depends on 1) The method of claim 1, wherein the TCR comprises an α chain comprising the amino acid sequence SEQ ID NO: 132 and a β chain comprising the amino acid sequence of SEQ ID NO: 138. ### Claim 20 (depends on 1) The method of claim 1, wherein the α variable domain comprises SEQ ID NO: 130 and the β, variable domain comprises SEQ ID NO: 136.