# US 10,934,356 B2 · Checkpoint blockade and microsatellite instability > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,934,356 B2 - Document ID: US10934356B2 - Status: Granted - Kind: B2 - Application number: 16/144,549 - Filed: 2018-09-27 - Published: 2019-01-24 - Granted: 2021-03-02 - Earliest claimed: 2014-11-13 - Assignees: The Johns Hopkins University - Applicants: The Johns Hopkins University - Inventors: Luis Diaz; Bert Vogelstein; Kenneth W. Kinzler; Nickolas Papadopoulos; Dung Le; Drew M. Pardoll; Suzanne L. Topalian - Web page: https://patentgrep.com/patent/US10934356B2 ## CPC - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - C07K 16/2803: {against the immunoglobulin superfamily} - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 13/08: of the prostate - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 35/00: Antineoplastic agents - C07K 16/2818: {against CD28 or CD152} - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - C07K 16/30: from tumour cells - C07K 16/40: against enzymes - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C12Y 113/11052: Indoleamine 2,3-dioxygenase (1.13.11.52), i.e. indoleamine 2,3-dioxygenase 1 - A61K 2039/505: {comprising antibodies} - A61K 2039/55: {characterised by the host/recipient, e.g. newborn with maternal antibodies} - C07K 2317/00: Immunoglobulins specific features - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/156: Polymorphic or mutational markers - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - C12Y: ENZYMES - 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 Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce. ## Claims ### Claim 1 A method for treating cancer in a patient in need thereof, comprising: determining that the patient has a tumor that exhibits a high microsatellite instability (MSI-high) or a mismatch repair (MMR) deficiency status; administering an effective amount of pembrolizumab to the patient; determining that the patient exhibits an outcome that is improved as compared to a corresponding outcome that would be observed in a reference patient that has been administered pembrolizumab, wherein the reference patient has a tumor that does not exhibit a MSI-high or a MMR deficiency status; and wherein the patient has received a prior cancer therapy drug. ### Claim 2 (depends on 1) The method of claim 1, wherein the step of determining that the patient has a tumor that exhibits a high microsatellite instability (MSI-high) status includes detecting in a tumor sample obtained from the patient a microsatellite marker in a DNA sequence. ### Claim 3 (depends on 2) The method of claim 2, wherein the microsatellite marker is BAT-25, BAT-26, MONO-27, NR-21 or NR-24. ### Claim 4 (depends on 1) The method of claim 1, wherein the step of determining that the patient has a tumor that exhibits a MMR deficiency status includes detecting in a tumor sample obtained from the patient a mismatch repair marker in a DNA sequence. ### Claim 5 (depends on 1) The method of claim 1, wherein the MMR deficiency status of the tumor is detected by immunohistochemistry. ### Claim 6 (depends on 1) The method of claim 1, wherein the cancer in the patient has progressed after the patient received the prior cancer therapy drug. ### Claim 7 (depends on 1) The method of claim 1, wherein the outcome that is improved is an improved objective response rate (ORR), an improved progression-free survival (PFS), or an improved overall survival. ### Claim 8 (depends on 7) The method of claim 7, wherein the outcome is assessed in the patient within approximately 20 weeks after administering pembrolizumab. ### Claim 9 (depends on 1) The method of claim 1, wherein the cancer is a metastatic cancer. ### Claim 10 (depends on 1) The method of claim 1, wherein the cancer is a metastatic colorectal cancer. ### Claim 11 A method for treating cancer in a patient in need thereof, the method comprising: detecting a high microsatellite instability (MSI-high) or a mismatch repair (MMR) deficiency status in a tumor sample from the patient; wherein the tumor sample exhibits an instability of one or more microsatellite markers or a deficiency of one or more mismatch repair markers; administering an effective amount of pembrolizumab to the patient; determining that the patient exhibits an outcome that is improved as compared to a corresponding outcome that would be observed in a reference patient that has been administered pembrolizumab, wherein reference patient has a tumor that does not exhibit an instability of the one or more microsatellite markers or a deficiency of the one or more mismatch repair markers; and wherein the patient has received a prior cancer therapy drug. ### Claim 12 (depends on 11) The method of claim 11, wherein the microsatellite marker is BAT-25, BAT-26, MONO-27, NR-21, or NR-24. ### Claim 13 (depends on 11) The method of claim 11, wherein the cancer is a metastatic cancer. ### Claim 14 (depends on 11) The method of claim 11, wherein the cancer is a metastatic colorectal cancer. ### Claim 15 (depends on 14) The method of claim 14, wherein the metastatic colorectal cancer in the patient has progressed after the patient received the prior cancer therapy drug. ### Claim 16 (depends on 11) The method of claim 11, wherein the outcome that is improved is an improved objective response rate (ORR), an improved progression-free survival (PFS), or an improved overall survival. ### Claim 17 (depends on 16) The method of claim 16, wherein the outcome is assessed in the patient at 20 weeks after administering pembrolizumab. ### Claim 18 (depends on 11) The method of claim 11, wherein pembrolizumab is administered by intravenous infusion. ### Claim 19 A method for treating cancer in a patient in need thereof comprising: selecting a patient who has an unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair (MMR) deficient solid tumor, the tumor having progressed following a cancer therapy; administering an effective amount of pembrolizumab to the patient; and determining that the patient exhibits an outcome that is improved as compared to a corresponding outcome that would be observed in a reference patient that has been administered pembrolizumab, wherein the reference patient has a tumor that does not exhibit a MSI-high or a MMR deficiency status. ### Claim 20 (depends on 19) The method of claim 19, wherein the solid tumor exhibits instability in a microsatellite marker. ### Claim 21 (depends on 20) The method of claim 20, wherein the microsatellite marker is BAT-25, BAT-26, MONO-27, NR-21 or NR-24. ### Claim 22 (depends on 19) The method of claim 19, wherein the outcome that is improved is an improved objective response rate (ORR), an improved progression-free survival (PFS), or an improved overall survival. ### Claim 23 A method for treating cancer in a population of cancer patients in need thereof, comprising: administering an effective amount of pembrolizumab to patients in the population of cancer patients, which patients have a tumor that exhibits a high microsatellite instability (MSI-high) or a mismatch repair (MMR) deficiency status, said tumor having progressed following a prior treatment; and observing an objective response rate of about 12% to 96% in the population of cancer patients after administration of pembrolizumab. ### Claim 24 (depends on 23) The method of claim 23, wherein the tumor exhibits instability of a microsatellite marker. ### Claim 25 (depends on 24) The method of claim 24, wherein the microsatellite marker is BAT-25, BAT-26, MONO-27, NR-21 or NR-24. ### Claim 26 (depends on 23) The method of claim 23, wherein the cancer is a metastatic cancer. ### Claim 27 (depends on 23) The method of claim 23, wherein the objective response rate is assessed in the population of cancer patients at 20 weeks after administering pembrolizumab. ### Claim 28 (depends on 23) The method of claim 23, wherein the cancer is not colorectal cancer.