# US 5,352,447 A · Immunotoxins for treatment of intracranial lesions and as adjunct to chemotherapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,352,447 A - Document ID: US5352447A - Status: Granted - Kind: A - Application number: 07/925,417 - Filed: 1992-08-10 - Granted: 1994-10-04 - Earliest claimed: 1987-10-05 - Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services - Inventors: Virginia Johnson; Richard J. Youle - Web page: https://patentgrep.com/patent/US5352447A ## CPC - C07K 14/34: from Corynebacterium (G) - A61K 47/644: {Transferrin, e.g. a lactoferrin or ovotransferrin} - A61K 47/6829: {Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A} - A61K 47/6857: {the tumour determinant being from lung cancer cell} - A61K 47/6865: {the tumour determinant being from skin, nerves or brain cancer cell} - 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) - Y10S 424/832: involving bacterial toxin that has modified amino acid sequence - 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) - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract A potent and specific immunotoxin is prepared by coupling a binding-site inactivated diphtheria toxin (CRM 107) to a new binding moiety consisting of transferrin or a monoclonal antibody against the human transferrin receptor. These immunotoxins are tumor specific and lack the nonspecific toxicity produced by the binding activity of the native toxin. The immunotoxin is useful in treating primary brain tumors, metastatic tumors to the brain, CSF-borne tumors, leptomeningeal leukemia and leptomeningeal carcinomatosis. ## Claims ### Claim 1 A method of treating central nervous system tumors or prophylaxing against metastatic lesions to the central nervous system comprising administering a tumor-inhibiting amount of a conjugate comprising a diphtheria toxin, wherein said diphtheria toxin lacks an active cell binding activity, attached to a moiety which binds to transferrin receptors, wherein said moiety which binds to transferrin receptors is selected from the group consisting of an anti-transferrin receptor antibody and transferrin, and wherein the mode of administration is intracranial or intrathecal. ### Claim 2 (depends on 1) A method of treating central nervous system tumors according to claim 1, wherein said mutant diphtheria toxin is selected from the group consisting of CRM102, CRM103 and CRM107. ### Claim 3 (depends on 2) A method of treating central nervous system tumors according to claim 2, wherein said mutant diphtheria toxin is CRM103. ### Claim 4 (depends on 2) A method of treating central nervous system tumors according to claim 2, wherein said mutant diphtheria toxin is CRM107. ### Claim 5 (depends on 1) The method of claim 1, wherein the conjugate is administered intrathecally. ### Claim 6 (depends on 1) The method of claim 1, wherein the conjugate is administered intraventricularly. ### Claim 7 (depends on 1) The method of claim 1, wherein the conjugate is administered into the cavity left by a surgical resection of the tumor. ### Claim 8 (depends on 1) The method of claim 1, wherein the central nervous system tumor treated or the metastatic lesion to the central nervous system prophylaxed against are secondary tumors arising from a primary breast malignancy. ### Claim 9 (depends on 1) The method of claim 1, wherein the central nervous system tumor treated or the metastatic lesion to the central nervous system prophylaxed against are secondary tumors arising from a primary lung malignancy. ### Claim 10 (depends on 1) The method of claim 1, wherein the central nervous system tumor treated or the metastatic lesion to the central nervous system prophylaxed against are secondary tumors arising from a primary prostate malignancy.