# US 5,344,760 A · Method of cancer detection > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,344,760 A - Document ID: US5344760A - Status: Granted - Kind: A - Application number: 07/889,718 - Filed: 1992-05-27 - Granted: 1994-09-06 - Earliest claimed: 1991-06-03 - Assignees: Ciba Corning Diagnostics Corp. - Inventors: Jeanne P. Harvey; Victoria A. Crebbin; Roger P. Walker; Victor Liu; Susan L. Hammond; Patricia A. McDonald - Web page: https://patentgrep.com/patent/US5344760A ## CPC - G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels} - C07K 14/71: for growth factors; for growth regulators - Y10S 436/822: Identified hapten - 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) - 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) - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract Diagnostic/prognostic methods are provided for detecting and/or quantitating in the body fluids, preferably serum, of mammals carrying a malignant tumor burden, elevated levels of a portion of the epidermal growth factor receptor (EGFr) which comprises substantially the EGFr ectodomain having a molecular weight in the range of from about 90 kilodaltons (kd) to about 115 kd, preferably from about 95 kd to about 105 kd, and more preferably about 100 kd. Substantially pure compositions comprising said EGFr ectodoman protein and/or fragments thereof are disclosed as well as test kits for performing the disclosed assays. ## Claims ### Claim 1 A diagnostic/prognostic method for sguamous cell carcinoma or urinary tract cancer comprising detecting and/or guantitating in a mammalian urine or bladder wash sample a portion of the epidermal growth factor (EGFr) which comprises substantially the EGFr ectodomain and which has a molecular weight in the range of from about 90 kilodaltons (kd) to about 115 kd, wherein an elevated concentration of said portion above the concentration for healthy mammals or for those with benign disease indicates the presence of squamous cell carcinoma or uninary tract cancer. ### Claim 2 (depends on 1) A diagnostic/prognostic method according to claim 1 wherein said molecular weight range is from about 95 kd to about 105 kd. ### Claim 3 (depends on 1) A diagnostic/prognostic method according to claim 1 where said molecular weight range is about 100 kd. ### Claim 4 (depends on 1) A diagnostic/prognostic method according to claim 1 wherein one end of the amino acid sequence for said EGFr portion is substantially identical in sequence to that reported for the N-terminus of the EGFr. ### Claim 5 (depends on 1) A diagnostic/prognostic method according to claim 1 wherein the N-terminal twenty amino acids of said EGFr portion are substantially identical to the N-terminal twenty amino acids of the EGFr. ### Claim 6 (depends on 1) A diagnostic/prognostic method for urinary tract cancer according to claim 1 wherein the mammalian sample is a bladder wash. ### Claim 7 (depends on 1) A diagnostic/prognostic method according to claim 1 wherein an immunoassay and/or Western blot is used. ### Claim 8 (depends on 1) A diagnostic/prognostic method according claim 1 wherein a lectin binding and/or ligand binding assay is used. ### Claim 9 (depends on 1) A diagnostic/prognostic method according to claim 1 wherein the squamous cell carcinoma is of the lungs, cervix, or head and neck. ### Claim 10 (depends on 1) A diagnostic/prognostic method according to claim 1 wherein the sguamous cell carcinoma or urinary tract cancer is selected from the group consisting of urinary tract cancer selected from the group consisting of bladder and kidney cancers; sguamous cell carcinomas of the head and neck; and lung cancer. ### Claim 11 (depends on 1) A diagnostic/prognostic method according to claim 1 wherein said urine or bladder wash sample is human. ### Claim 12 (depends on 1) A diagnostic/prognostic method according to claim 1 which comprises the use of an ELISA assay or equivalent assay which can be unamplified or amplified using avidin/biotin technology. ### Claim 13 (depends on 1) The diagnostic/prognostic method according to claim 1 which comprises contacting a composition containing antibodies reactive with said EGFr portion with said mammalian urine or bladder wash sample and determining whether said antibodies bind to a protein in said sample. ### Claim 14 (depends on 13) A diagnostic/prognostic method according to claim 13 wherein a competitive immunoassay format is used, and wherein said composition further comprises labeled proteins and/or polypeptides from the EGFr ectodomain. ### Claim 15 (depends on 13) A diagnostic/prognostic method according to claim 13 wherein a competitive immunoassay format is used, and wherein said composition further comprises labeled anti-idiotype antibodies to antibodies reactive with epitopes on the EGFr ectodomain. ### Claim 16 (depends on 1) A diagnostic/prognostic method for squamous cell carcinoma according to claim 1 wherein the mammalian sample is urine. ### Claim 17 (depends on 16) A diagnostic/prognostic method according to claim 16 wherein the urine sample is human. ### Claim 18 (depends on 1) A diagnostic/prognostic method according to claim 1 wherein the urinary tract cancer is bladder cancer or kidney cancer. ### Claim 19 (depends on 18) A diagnostic/prognostic method according to claim 18 wherein the urinary tract cancer is bladder cancer. ### Claim 20 (depends on 1) A diagnostic/prognostic method according to claim 1 which comprises the use of a bridge immunoassay format which is a sandwich assay wherein an immunocomplex is formed in a liquid reaction between said EGFr portion and antibodies reactive therewith, wherein one of said antibodies is conjugated to a hapten and one of which is enzymatically labeled, and wherein a biotinylated bridge antibody raised against said hapten is then added to the reaction mixture and links said immunocomplex to a solid phase that has been coated with avidin or streptavidin. ### Claim 21 (depends on 20) A diagnostic/prognostic method according to claim 20 wherein the antibodies are monoclonal, the hapten is fluorescein isothiocyanate (FITC) and the enzymatic label is horseradish peroxidase. ### Claim 22 A diagnostic/prognostic method for detecting squamous cell carcinoma or urinary tract cancer in a patient which comprises: a. contacting a urine sample or bladder wash sample from said patient with a composition of antibodies having specificity for one or more epitopes within the EGFr ectodomain; and b. determining the amount of protein bound by the antibodies, wherein an elevated level of binding above the binding level for healthy humans or for those with benign disease indicates the presence of squamous cell carcinoma or urinary tract cancer. ### Claim 23 (depends on 22) A diagnostic/prognostic method according to claim 22 wherein the antibodies have specificity for one or more epitopes within the N-terminal 600 amino acids of the EGFr ectodomain. ### Claim 24 (depends on 22) A method according to claim 22 wherein the patient's sample is urine.