# US 7,407,751 B2 · Methods for the detection and prognosis of breast tumors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,407,751 B2 - Document ID: US7407751B2 - Status: Granted - Kind: B2 - Application number: 10/679,951 - Filed: 2003-10-06 - Published: 2004-10-07 - Granted: 2008-08-05 - Earliest claimed: 2001-04-06 - Assignees: Wilex AG - Inventors: Thomas Luther; Viktor Magdolen; Manfred Schmitt; Matthias Kotzsch - Web page: https://patentgrep.com/patent/US7407751B2 ## CPC - C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 35/00: Antineoplastic agents - C07K 16/30: from tumour cells - C07K 16/3015: {Breast} - C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate} - A61K 2039/505: {comprising antibodies} - 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: 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 - 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 This invention relates to the production of specific antibodies for the detection of human tumor associated urokinase-type plasminogen activator receptor (uPAR) deletion variants in biological samples as well as to their diagnostic and therapeutic application. ## Claims ### Claim 1 A method for the detection of a breast tumors associated with the generation of at least one uPAR deletion variant comprising the steps of: (a) obtaining a cDNA containing sample from a breast tumor to be investigated, and (b) analyzing the cDNA of said sample to determine whether alternative splicing of uPAR has occurred and at least one uPAR deletion variant has been generated, wherein the at least one uPAR deletion variant is del4+5, wherein the tumor sample is obtained from a human patient, and wherein the presence of the at least one uPAR deletion variant in said tumor indicates the presence of a tumor associated with the generation of at least one uPAR deletion variant. ### Claim 2 (depends on 1) The method according to claim 1, wherein the step of analyzing the cDNA of said sample comprises: amplifying the cDNA to obtain a quantified control amplification product comprising the nucleic acid coding for wild type uPAR and a quantified amplification product comprising the nucleic acid coding for the at least one uPAR deletion variant, and determining the ratio of wild type uPAR:uPAR deletion variant by comparing the quantified amplification products. ### Claim 3 (depends on 2) The method according to claim 2, wherein the amplification of the cDNA is done by real-time RT-PCR amplification. ### Claim 4 (depends on 2) The method according to claim 2, wherein the ratio of wild type uPAR:uPAR deletion variant is greater than 0.043. ### Claim 5 (depends on 1) The method according to claim 1, wherein the cDNA is amplified with a first set of primers complementary to sequences contained in regions bridging the deleted sequences in uPAR deletion variants to obtain the amplification product comprising the nucleic acid coding for the at least one uPAR deletion variant, and wherein the cDNA is amplified with a second set of primers complementary to sequences contained in the wild type uPAR to obtain the control amplification product comprising the nucleic acid coding for wild type uPAR. ### Claim 6 (depends on 1) The method according to claim 1, wherein the method provides a prognosis for the tumor associated with the generation of at least one uPAR deletion variant. ### Claim 7 (depends on 6) The method according to claim 6, wherein the prognosis comprises characterization of the tumor, said characterization comprising indicating whether the tumor is more invasive, is more likely to have metastasis, is more likely to have a shorter disease free survival period or is more likely to have a higher rate of recurrence than a tumor not associated with the generation of uPAR deletion variants. ### Claim 8 A method of providing a prognosis for a breast tumor-bearing patient comprising the steps of: (a) obtaining a cDNA containing sample from a breast tumor of said patient, (b) analyzing the cDNA of said sample to determine whether alternative splicing of uPAR has occurred and at least one uPAR deletion variant has been generated, wherein the at least one uPAR deletion variant is del4+5, and (c) correlating the presence of the at least one uPAR deletion variant in the tumor of the patient with a prognosis of the patient. ### Claim 9 (depends on 8) The method according to claim 8, wherein the step of analyzing the cDNA of said sample comprises: amplifying the cDNA to obtain a quantified control amplification product comprising the nucleic acid coding for wild type uPAR and a quantified amplification product comprising the nucleic acid coding for the at least one uPAR deletion variant, and determining the ratio of wild type uPAR:uPAR deletion variant by comparing the quantified amplification products. ### Claim 10 (depends on 9) The method according to claim 9, wherein the amplification of the cDNA is done by real-time RT-PCR amplification. ### Claim 11 (depends on 8) The method according to claim 8, wherein the cDNA is amplified with a first set of primers complementary to sequences contained in regions bridging the deleted sequences in uPAR deletion variants to obtain the amplification product comprising the nucleic acid coding for the at least one uPAR deletion variant, and wherein the cDNA is amplified with a second set of primers complementary to sequences contained in the wild type uPAR to obtain the control amplification product comprising the nucleic acid coding for wild type uPAR.