CA2192678A1 - Mn gene and protein - Google Patents

Mn gene and protein

Info

Publication number
CA2192678A1
CA2192678A1 CA002192678A CA2192678A CA2192678A1 CA 2192678 A1 CA2192678 A1 CA 2192678A1 CA 002192678 A CA002192678 A CA 002192678A CA 2192678 A CA2192678 A CA 2192678A CA 2192678 A1 CA2192678 A1 CA 2192678A1
Authority
CA
Canada
Prior art keywords
seq
nucleic acid
protein
exclusive
polypeptide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002192678A
Other languages
French (fr)
Other versions
CA2192678C (en
Inventor
Jan Zavada
Silvia Pastorekova
Jaromir Pastorek
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute of Virology (Slovak Academy of Science)
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US08/260,190 external-priority patent/US6774117B1/en
Priority claimed from US08/487,077 external-priority patent/US6069242A/en
Priority claimed from US08/481,658 external-priority patent/US5955075A/en
Priority claimed from US08/486,756 external-priority patent/US5981711A/en
Priority claimed from US08/485,863 external-priority patent/US6093548A/en
Priority claimed from US08/485,049 external-priority patent/US6204370B1/en
Priority claimed from US08/485,862 external-priority patent/US5989838A/en
Application filed by Individual filed Critical Individual
Publication of CA2192678A1 publication Critical patent/CA2192678A1/en
Publication of CA2192678C publication Critical patent/CA2192678C/en
Application granted granted Critical
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/82Translation products from oncogenes
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069Reproductive system, e.g. ovaria, uterus, testes, prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Cell Biology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Oncology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

A complete genomic sequence including a full-length cDNA sequence for the MN
gene, a putative oncogene, is disclosed, as well as proteins/polypeptides encoded thereby Recombinant nucleic acid molecules for expressing MN proteins/polypeptides and recombinant proteins are also provided. Expression of the MN gene is disclosed as being associated with tumorigenicity, and the invention concerns methods and compositions for detecting and/or quantitating MN antigen and/or MN-specific antibodies in vertebrate samples that are diagnostic/prognostic for neoplastic and preneoplastic disease. Test kits embodying the immunoassays of this invention are provided, MN-specific antibodies are disclosed that can be used diagnostically/prognostically, therapeutically, for imaging, and/or for affinity purification of MN proteins/polypeptides. Also provided are nucleic acid probes for the MN
gene as well as test kits comprising said probes The invention also concerns vaccines comprising MN proteins/polypeptides which are effective to immunize a vertebrate against neoplastic diseases associated with the expression of MN proteins. The invention still further concerns antisense nucleic acid sequences that can be used to inhibit MN gene expression, and polymerase chain reaction (PCR) assays to detect genetic rearrangements in MN genes.

Claims (28)

1. An isolated nucleic acid containing at least twenty-seven nucleotides wherein the nucleotide sequence for said nucleic acid is selected from the group consisting of:
(a) SEQ. ID. NOS.: 1, 5, 27, 28, 30-33, and 38, and nucleotide sequences complementary to SEQ. ID. NOS.: 1, 5, 27, 28, 30-33 and 38.
(b) nucleotide sequences that hybridize under stringent hybridization conditions to: SEQ. ID. NO.: 5 exclusive of the nucleotide sequence from 3660 to 3951 and exclusive of the exon sequences represented by SEQ. ID. NOS.: 29-38, or to the complement of SEQ. ID.
NO.: 5 exclusive of said nucleotide sequence from 3660 to 3951 and exclusive of said exon sequences repesented by SEQ. ID. NOS.: 29-38: and (c) nucleotide sequences that differ from the nucleotide sequences of (a) and (b) in codon sequence due to the degeneracy of the genetic code.
2. An isolated nucleic acid according to Claim 1 wherein said nucleotide sequence is selected from the group consisting of:
(a) SEQ. ID. NO.: 5 and its complement;
(b) nucleotide sequences that hybridize under stringent conditions to SEQ. ID. NO.: 5 exclusive of the nucleotide sequence from 3660 to 3951 and exclusive of the exon sequences represented by SEQ. ID.
NOS.: 29-38 or to the complement of SEQ. ID. NO.: 5 exclusive of said nucleotide sequence from 3660 to 3951 and exclusive of said exon sequences represented by SEQ. ID. NOS.: 29-38;
(c) nucleotide sequences that differ from the nucleotide sequences of (a) or (b) in codon sequence due to the degeneracy of the genetic code.
3. An isolated nucleic acid containing at least sixteen nucleotides wherein the nucleotide sequence therefor is selected from the group consisting of:

(a) the MN nucleotide sequences contained in plasmids A4a, XE1 and XE3 which were deposited at the American Type Culture Collection (ATCC) in Rockville, Maryland in the United State of America under the respective ATCC Nos. 97199, 97200, and 97198;
(b) nucleotide sequences that hybridize under stringent conditions to the MN nucleotide sequences of (a) with the proviso that excluded from said MN nucleotide sequences of (a) are the nucleotide sequence from 3660 to 3951 of SEQ. ID. NO.: 5 and MN exon sequences represented by SEQ. ID. NOS.: 29-38; and (c) nucleotide sequences that differ from the nucleotide sequences of (a) or (b) in codon sequence due to the degeneracy of the genetic code.
4. An isolated nucleic acid according to Claim 3 which functions as a polymerase chain reaction primer for MN nucleic acid sequences, and which is from 16 to about 50 nucleotides in length.
5. An isolated nucleic acid, containing at least fifty nucleotides, encoding an MN protein or polypeptide that is specifically bound either by monoclonal antibodies designated M75 secreted by the hybridoma VU-M75 deposited at the American Type Culture Collection (ATCC) in Rockville, Maryland in the United States of America under ATCC
No. HB 11128, or by monoclonal antibodies designated MN12 secreted by the hybridoma MN 12.2.2 deposited at the ATCC under ATCC No. 11647, or by both of said monoclonal antibodies.
6. An isolated nucleic acid which is operatively linked to an expression control sequence within a vector wherein said nucleic acid is selected from the group consisting of:
(a) SEQ. ID. NO.: 1 and its complement;
(b) nucleic acids that hybridize under stringent hybridization conditions to SEQ. ID. NO.: 1 exclusive of the nucleotide sequence from 124 to 1522, or to the complement of SEQ. ID. NO.: 1 exclusive of said nucleotide sequence from 124 to 1522;and (c) nucleic acids that differ from the nucleic acid sequences of (a) and (b) due to the degeneracy of the genetic code.
7. A unicellular host, which is either prokaryotic or eukaryotic, that is transformed or transfected with the isolated nucleic acid operatively linked to an expression control sequence in a vector according to Claim 6.
8. A method of recombinantly producing an MN protein, MN fusion protein or MN polypeptide comprising the steps of:
(a) transforming a unicellular host with the isolated nucleic acid operatively linked to an expression control sequence in a vector according to Claim 6;
(b) culturing said unicellular host so that said MN protein or polypeptide is expressed; and (c) extracting and isolating said MN protein or polypeptide.
9. A recombinant nucleic acid encoding a fusion protein, that consists essentially of an MN protein or polypeptide and a non-MN protein or polypeptide, wherein the nucleotide sequence for the portion of the nucleic acid encoding the MN protein or polypeptide is selected from the group consisting of:
(a) SEQ. ID. NO.: 1;
(b) nucleotide sequences that hybridize under stringent conditions to SEQ. ID. NO.: 1 exclusive of the nucleotide sequence from 124 to 1522 or to the complement of SEQ. ID. NO.: 1 exclusive of said nucleotide sequence from 124 to 1522; and (c) degenerate variants of SEQ. ID. NO.: 1 and of the nucleotide sequences of (b);
wherein the nucleic acid encoding said MN protein or polypeptide contains at least twenty-nine nucleotides.
10. A method of detecting mutations in an isolated MN gene and/or fragment(s) thereof comprising the steps of:
amplifying one or more fragment(s) of said gene by the polymerase chain reaction (PCR); and determining whether said one or more fragments contain any mutations.
11. An MN protein, MN fusion protein or MN polypeptide, wherein said MN protein, MN polypeptide or the MN protein portion of said MN fusion protein is encoded by a nucleic acid of at least twenty-nine nucleotides which is selected from the group consisting of:
(a) SEQ. ID. NO.: 1;
(b) nucleotide sequences that hybridize under stringent hybridization conditions to SEQ. ID. NO.: 1 exclusive of the nucleotide sequence from 124 to 1522 or to the complement of SEQ. ID. NO.: 1 exclusive of said nucleotide sequence from 124 to 1522; and (c) nucleotide sequences that differ from SEQ. ID. NO.: 1 or from the sequences of (b) in codon sequence due to the degeneracy of the genetic code.
12. An MN protein, MN fusion protein, or MN polypeptide wherein said MN protein or polypeptide has, and wherein said MN fusion protein contains, an amino acid sequence selected from the group consisting of SEQ. ID. NOS.: 2, 6, 10, 11, 13-16, 50, 51 and 53.
13. A vaccine comprising an immunogenic amount of one or more MN proteins, MN fusion proteins, and/or MN polypeptides according to Claims 11 or 12 dispersed in a physiologically acceptable, nontoxic vehicle, which amount is effective to immunize a vertebrate against a neoplastic disease associated with expression of MN antigen.
14. An antibody which specifically binds to an MN protein, an MN fusion protein and/or an MN polypeptide according to Claims 11 or 12, with the proviso that said antibody is not a monoclonal antibody designated M75 produced by a hybridoma designated VU-M75 that was deposited at the American Type Culture Collection (ATCC) in Rockville, Maryland in the United States of America under ATCC No. HB 11128.
15. A monoclonal antibody according to Claim 14 which is designated MN12 and is secreted by the hybridoma MN 12.2.2 which was deposited at the American Type Culture Collection (ATCC) in Rockville, Maryland in the United States of American under ATCC No. HB 11647.
16. An antibody according to Claim 14 which specifically binds to an MN antigen epitope selected from the group of epitopes represented by the following amino acid sequences SEQ. ID. NOS. 10-16.
17. An antibody according to Claim 14 which is linked to an imaging agent, to a chemotherapeutic agent or to a toxic agent.
18. A method of imaging pre-neoplastic or neoplastic disease in a patient comprising:
(a) injecting said patient with antibody linked to an imaging agent according to Claim 17; and (b) detecting the binding of said antibody.
19. A hybridoma designated MN 12.2.2 which produces the monoclonal antibody MN12, and which was deposited at the American Type Culture Collection (ATCC) in Rockville Maryland in the United States of America under ATCC Accession No. HB 11647.
20. A method of delivering a chemotherapeutic agent or toxic agent to a cancer cell which comprises contacting said cell with an antibody linked to a chemotherapeutic agent or to a toxic agent according to Claim 17.
21. A method of treating neoplastic disease in a patient comprising administering to said patient a therapeutically effective amount of a composition comprising antibodies which specifically bind to an MN
protein, an MN fusion protein and/or an MN polypeptide according to Claims 11 or 12.
22. A method of detecting and/or quantitating in a vertebrate sample MN antigen comprising the steps of:
(a) contacting said sample with one or more antibodies according to Claims 14, 15 or 16; and (b) detecting and/or quantitating binding of said antibody in said sample.
23. A method according to Claim 22 wherein said vertebrate sample is a human tissue specimen, such as, a cell smear, a histological section from a biopsied tissue or organ, or an imprint preparation.
24. A method according to Claim 23 wherein said tissue specimen is ovarian, endometrial, or cervical.
25. A method of detecting and/or quantitating MN-specific antibodies in a vertebrate sample comprising the steps of:
(a) contacting and incubating the vertebrate sample with an MN protein, an MN fusion protein and/or an MN polypeptide according to Claims 11 or 12; and (b) detecting and/or quantitating binding of said MN protein, MN fusion protein and/or MN polypeptide to antibody in said sample.
26. A method of treating neoplastic disease and/or pre-neoplastic disease comprising inhibiting the expression of MN genes by administering one or more antisense nucleic acid sequences that hybridize under stringent conditions to mRNA transcribed from MN genes.
27. Vectors containing an MN nucleic acid sequence wherein said MN nucleic acid sequence is selected from the group consisting of:
(a) SEQ. ID. NO.:5 and its complement;
(b) nucleic acids that hybridize to SEQ. ID. NO.:5 exclusive of the nucleotide sequence from 3660 to 3951 and exclusive of the exon sequences of SEQ. ID. NOS.: 29-38, or to the complement of SEQ. ID.
NO.: 5 exclusive of said nucleotide sequence from 3660 to 3951 and exclusive of said exons of SEQ. ID. NOS.: 29-38; and (c) nucleic acids that differ from the nucleic acids of (a) or (b) due to the degeneracy of the genetic code;
wherein said nucleic acid is at least twenty-nine nucleotides in length.
28. Vectors containing an MN nucleic acid sequence according to Claim 27 selected from the group consisting of the plasmids A4a, XE1 and XE3 which are deposited at the American Type Culture Collection (ATCC) in Rockville, Maryland in the United States of America under the respective ATCC accession numbers 97199, 97200 and 97198.
CA2192678A 1994-06-15 1995-06-15 Mn gene and protein Expired - Lifetime CA2192678C (en)

Applications Claiming Priority (17)

Application Number Priority Date Filing Date Title
US08/260,190 1994-06-15
US08/260,190 US6774117B1 (en) 1992-03-11 1994-06-15 MN gene and protein
US44750495A 1995-06-07 1995-06-07
US08/447,504 1995-06-07
US08/485,862 1995-06-07
US08/481,658 US5955075A (en) 1992-03-11 1995-06-07 Method of inhibiting tumor growth using antibodies to MN protein
US08/486,756 US5981711A (en) 1992-03-11 1995-06-07 MN-specific antibodies and hybridomas
US08/485,863 US6093548A (en) 1992-03-11 1995-06-07 Detection and quantitation of MN-specific antibodies.
US08/485,049 US6204370B1 (en) 1992-03-11 1995-06-07 MN gene and protein
US08/487,077 1995-06-07
US08/485,049 1995-06-07
US08/487,077 US6069242A (en) 1992-03-11 1995-06-07 MN gene and protein
US08/485,863 1995-06-07
US08/485,862 US5989838A (en) 1992-03-11 1995-06-07 Immunological methods of detecting MN proteins and MN polypeptides
US08/481,658 1995-06-07
US08/486,756 1995-06-07
PCT/US1995/007628 WO1995034650A2 (en) 1994-06-15 1995-06-15 Mn gene and protein

Publications (2)

Publication Number Publication Date
CA2192678A1 true CA2192678A1 (en) 1995-12-21
CA2192678C CA2192678C (en) 2010-12-14

Family

ID=27575294

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2192678A Expired - Lifetime CA2192678C (en) 1994-06-15 1995-06-15 Mn gene and protein

Country Status (3)

Country Link
AU (1) AU2861695A (en)
CA (1) CA2192678C (en)
WO (1) WO1995034650A2 (en)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5387676A (en) * 1992-03-11 1995-02-07 Ciba Corning Diagnostics Corp. MN gene and protein
US6297051B1 (en) 1997-01-24 2001-10-02 Institute Of Virology, Slovak Academy Of Sciences MN gene and protein
US6297041B1 (en) 1992-03-11 2001-10-02 Institute Of Virology, Slovak Academy Of Sciences MN gene and protein
JP3910798B2 (en) * 1998-10-23 2007-04-25 インスティトゥート オブ ヴァイロロジー MN gene and protein
US7713704B1 (en) 1998-10-23 2010-05-11 Institute Of Virology Of The Slovak Academy Of Science MN gene and protein
US20080146780A1 (en) 1999-10-22 2008-06-19 Jan Zavada MN Gene and Protein
US6902890B1 (en) 1999-11-04 2005-06-07 Diadexus, Inc. Method of diagnosing monitoring, staging, imaging and treating cancer
US7572891B2 (en) 2000-02-14 2009-08-11 The Regents Of The University Of California Kidney-specific tumor vaccine directed against kidney tumor antigen G-250
AR036833A1 (en) * 2001-10-18 2004-10-06 Bayer Corp HUMAN ANTIBODIES THAT JOIN MN AND HAVE NEUTRALIZING ACTIVITY OF CELLULAR ADHESION.
US7910549B2 (en) 2001-12-13 2011-03-22 Institute Of Virology Of The Slovak Academy Of Sciences MN gene and protein
SI3031910T1 (en) 2002-02-21 2018-05-31 Institute Of Virology Slovak Academy Of Sciences Mn/ca ix-specific monoclonal antibodies generated from mn/ca ix-deficient mice and methods of use
HUE026218T2 (en) * 2002-02-21 2016-05-30 Inst Virology MN/CA IX-specific monoclonal antibodies generated from MN/CA IX-deficient mice and methods of use
US8936914B2 (en) * 2002-04-16 2015-01-20 The Regents Of The University Of California Methods of renal cell carcinoma prognosis and treatment selection with carbonic anhydrase IX
WO2004048544A2 (en) 2002-11-26 2004-06-10 Bayer Healthcare Ca ix-specific inhibitors
JP4426621B2 (en) 2004-05-04 2010-03-03 バイエル ヘルスケア エルエルシー Prognosis of MN / CA IX / CA9 and kidney cancer
EP2076611A4 (en) 2006-10-12 2010-08-25 Inst Virology Mn/ca9 splice variants
US7820159B2 (en) 2006-10-31 2010-10-26 Instiute of Virology of the Slovak Academy of Sciences MN/CA IX and EGFR pathway inhibition
CA2673560C (en) 2006-12-22 2017-08-22 The Regents Of The University Of California New fusion molecule based on novel taa variant
US8097423B2 (en) 2007-07-30 2012-01-17 Institute Of Virology MN/CA IX and breast cancer therapy
WO2014128258A1 (en) 2013-02-22 2014-08-28 Wilex Ag Caix stratification based cancer treatment

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5387676A (en) * 1992-03-11 1995-02-07 Ciba Corning Diagnostics Corp. MN gene and protein

Also Published As

Publication number Publication date
AU2861695A (en) 1996-01-05
CA2192678C (en) 2010-12-14
MX9606402A (en) 1998-10-31
WO1995034650A3 (en) 1996-02-15
WO1995034650A2 (en) 1995-12-21

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Effective date: 20150615