WO1998014577B1 - Nucleotide and protein sequence of mammastatin and methods of use - Google Patents
Nucleotide and protein sequence of mammastatin and methods of useInfo
- Publication number
- WO1998014577B1 WO1998014577B1 PCT/US1997/018026 US9718026W WO9814577B1 WO 1998014577 B1 WO1998014577 B1 WO 1998014577B1 US 9718026 W US9718026 W US 9718026W WO 9814577 B1 WO9814577 B1 WO 9814577B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- mammastatin
- kda
- composition
- dna sequence
- nucleic acid
- Prior art date
Links
- 108010016172 mammastatin Proteins 0.000 title claims abstract 30
- 208000020600 Mammastatin Diseases 0.000 title claims abstract 29
- 238000000034 method Methods 0.000 title claims 4
- 108090000623 proteins and genes Chemical group 0.000 title claims 2
- 102000004169 proteins and genes Human genes 0.000 title claims 2
- 239000002773 nucleotide Substances 0.000 title 1
- 125000003729 nucleotide group Chemical group 0.000 title 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract 11
- 210000004216 mammary stem cell Anatomy 0.000 claims abstract 8
- 150000007523 nucleic acids Chemical group 0.000 claims abstract 6
- 230000012010 growth Effects 0.000 claims abstract 4
- 206010006187 Breast cancer Diseases 0.000 claims abstract 3
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract 3
- 210000004027 cell Anatomy 0.000 claims abstract 2
- 230000010261 cell growth Effects 0.000 claims abstract 2
- 206010061289 metastatic neoplasm Diseases 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims 8
- 230000002401 inhibitory effect Effects 0.000 claims 4
- 201000009030 Carcinoma Diseases 0.000 claims 3
- 238000009472 formulation Methods 0.000 claims 3
- 239000000523 sample Substances 0.000 claims 3
- 108091026890 Coding region Proteins 0.000 claims 2
- 238000009007 Diagnostic Kit Methods 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 238000012423 maintenance Methods 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000012544 monitoring process Methods 0.000 claims 2
- 239000013610 patient sample Substances 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 239000012472 biological sample Substances 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 210000001124 body fluid Anatomy 0.000 claims 1
- 239000010839 body fluid Substances 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000013612 plasmid Substances 0.000 claims 1
- 239000003966 growth inhibitor Substances 0.000 abstract 1
- 230000001394 metastastic effect Effects 0.000 abstract 1
Abstract
A nucleic acid sequence encoding Mammastatin, a specific mammary cell growth inhibitor. Mammastatin is encoded by a single nucleic acid sequence and has an approximate molecular weight of 44 kDa in its inactive, non-phosphorylated form. Normal mammary cells express functional phosphorylated forms having approximate molecular weights of 53 kDa and 49 kDa. Metastatic mammary cells either do not express Mammastatin at all, or do not express the 53 kDa or 49 kDa, phosphorylated forms. Mammary cancer cells are inhibited in their growth by the administration of phosphorylated Mammastatin.
Claims
1. A substantially purified and isolated nucleic acid composition comprising the coding sequence of the human nucleic acid sequence insert of pMammB, ATCC No.
97451.
2. A substantially purified and isolated protein comprising the amino acid sequence encoded by the DNA Sequence of claim 1.
3. A recombinant protein produced from the nucleic acid sequence of claim 1.
4. A plasmid or vector comprising the coding sequence of nucleic acid sequence of claim 1.
5. A diagnostic kit for the determination of Mammastatin comprising the composition of claim 1.
6. A diagnostic kit for the determination of Mammastatin comprising anti- Mammastatin antibodies and Mammastatin standards.
7. A pharmaceutical composition comprising the composition of claim 2 or claim 3.
8. A method for the diagnosis or monitoring of mammary cell carcinoma comprising: analyzing a patient' s blood or tissue for the presence of Mammastatin protein; and correlating the absence or reduction of Mammastatin as compared with a normal control with mammary cell carcinoma.
9. The method of claim 1 , wherein said analyzing is determining the presence or absence of 53 kDa, 49 kDa, and 44 kDa Mammastatin in the patient sample, and wherein said correlating is correlating the absence or reduction of 53 kDa or 49 kDa Mammastatin as compared with a normal control with the presence of mammary cell carcinoma.
10. A method of monitoring the level of functional Mammastatin in a human subject comprising the steps of: analyzing a biological sample of body fluid or tissue of the subject for the presence of three molecular weight forms of Mammastatin having the approximate sizes 53 kDa, 49 kDa and 44 kDa; and correlating a reduced amount of 53 kDa or 49 kDa or 44 kDa Mammastatin relative to a normal or prior patient sample control with a reduced amount of functional Mammastatin.
11. The use of a mammary cell growth inhibiting amount of mammastatin in the manufacture of a medicament for the treatment of breast cancer.
12. The use of mammastatin of claim 11 characterized by the mammastatin encoded by the composition of claim 1.
13. The use of mammastatin of claim 11 characterized by the mammastatin of claims 2 , 3 or 7.
14. The use of mammastatin of claim 11 characterized by a high dose formulation for treatment of initial metastatic disease.
15. he use of mammastatin of claim 11 characterized by a maintenance dose formulation for maintaining therapeutically effective levels of mammastatin invivo.
16. The use of mammastatin of claim 15 characterized by a maintenance dose formulation for continuously maintaining therapeutically effective levels of mammastatin without inducing feedback inhibition.
17. The use of claim 16 characterized by a dose of mammastatin, sufficient to maintain therapeutically effective levels for continuous treatment for 28 days followed by 3 days without treatment.
18. The use of a growth inhibiting amount of mammastatin in the manufacture of a medicament for inhibiting the growth of human mammary cells.
19. The use of claim 18 characterized by inhibiting the growth of human mammary cancer cells.
20. The use of claim 18 characterized by the composition of claims 2, 3 or 7.
21. The use of claim 18 characterized by the mammastatin encoded by the sequence of claim 1.
22. A probe that hybridizes to or is complementary to a DNA sequence of claim 1.
23. A probe of claim 22 that hybridizes to a DNA sequence coding for a peptide with Seq. ID No. 3.
24. A probe of claim 22 that hybridizes to a DNA sequence coding for a peptide with Seq. ID No.4.
25. A primer that hybridizes to the DNA sequence of claim 1.
26. A primer of claim 25 that has a DNA Sequence of Seq. ID No. 6 or Seq. ID No.8.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP97945531A EP0929675A2 (en) | 1996-10-03 | 1997-10-03 | Nucleotide and protein sequence of mammastatin and methods of use |
| CA2267095A CA2267095C (en) | 1996-10-03 | 1997-10-03 | Nucleotide and protein sequence of mammastatin and methods of use |
| BR9713248-9A BR9713248A (en) | 1996-10-03 | 1997-10-03 | Sequence of nucleotides and mamstatin proteins and processes of use |
| IL12924197A IL129241A0 (en) | 1996-10-03 | 1997-10-03 | Nucleotide and protein sequence of mammastatin and methods of use |
| JP51695598A JP4452331B2 (en) | 1996-10-03 | 1997-10-03 | Mammastatin nucleotide and protein sequences and uses thereof |
| AU46709/97A AU733380B2 (en) | 1996-10-03 | 1997-10-03 | Nucleotide and protein sequence of mammastatin and methods of use |
| EA199900256A EA199900256A1 (en) | 1996-10-03 | 1997-10-03 | NUCLEOTIDE AND PROTEIN SEQUENCE OF MAMMASTATINE AND METHODS OF APPLICATION |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2731596P | 1996-10-03 | 1996-10-03 | |
| US60/027,315 | 1996-10-03 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| WO1998014577A2 WO1998014577A2 (en) | 1998-04-09 |
| WO1998014577A3 WO1998014577A3 (en) | 1998-04-09 |
| WO1998014577B1 true WO1998014577B1 (en) | 1998-07-30 |
| WO1998014577A9 WO1998014577A9 (en) | 1998-08-27 |
Family
ID=21836977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/018026 WO1998014577A2 (en) | 1996-10-03 | 1997-10-03 | Nucleotide and protein sequence of mammastatin and methods of use |
Country Status (8)
| Country | Link |
|---|---|
| US (6) | US6451765B1 (en) |
| EP (2) | EP0929675A2 (en) |
| JP (2) | JP4452331B2 (en) |
| AU (1) | AU733380B2 (en) |
| BR (1) | BR9713248A (en) |
| CA (1) | CA2267095C (en) |
| EA (1) | EA199900256A1 (en) |
| WO (1) | WO1998014577A2 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6500937B1 (en) | 1996-10-03 | 2002-12-31 | University Of Michigan | Nucleotide sequence encoding a mammary cell growth inhibitor |
| CA2267095C (en) * | 1996-10-03 | 2010-08-10 | Biotherapies, Inc. | Nucleotide and protein sequence of mammastatin and methods of use |
| AU783373B2 (en) * | 1999-06-18 | 2005-10-20 | Biotherapies, Inc. | Epithelial cell growth inhibitors |
| US6939714B2 (en) | 1999-06-18 | 2005-09-06 | Biotherapies, Inc. | Epithelial cell growth inhibitors |
| WO2001000832A1 (en) | 1999-06-28 | 2001-01-04 | Genentech, Inc. | Methods for making apo-2 ligand using divalent metal ions |
| US20030212263A1 (en) * | 2000-06-19 | 2003-11-13 | The University Of Michigan | Mammastatin sequence variant C |
| WO2001098496A1 (en) * | 2000-06-19 | 2001-12-27 | The University Of Michigan | Mammastatin sequence variant c |
| CA3112837A1 (en) * | 2018-10-19 | 2020-04-23 | Translate Bio, Inc. | Pumpless encapsulation of messenger rna |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4379839A (en) | 1977-05-23 | 1983-04-12 | The Trustees Of Columbia University In The City Of New York | Method for detecting cancer |
| US4753894A (en) | 1984-02-08 | 1988-06-28 | Cetus Corporation | Monoclonal anti-human breast cancer antibodies |
| EP0414807A4 (en) * | 1988-05-20 | 1991-07-03 | The Regents Of The University Of Michigan | Human mammary cell growth inhibitor and methods of production and use |
| JPH05506351A (en) * | 1988-05-20 | 1993-09-22 | ザ リージェンツ オブ ザ ユニバーシティー オブ ミシガン | Antibodies to human breast cell growth inhibitors and methods of production and use thereof |
| US6500937B1 (en) * | 1996-10-03 | 2002-12-31 | University Of Michigan | Nucleotide sequence encoding a mammary cell growth inhibitor |
| CA2267095C (en) * | 1996-10-03 | 2010-08-10 | Biotherapies, Inc. | Nucleotide and protein sequence of mammastatin and methods of use |
-
1997
- 1997-10-03 CA CA2267095A patent/CA2267095C/en not_active Expired - Fee Related
- 1997-10-03 EA EA199900256A patent/EA199900256A1/en unknown
- 1997-10-03 WO PCT/US1997/018026 patent/WO1998014577A2/en active Application Filing
- 1997-10-03 EP EP97945531A patent/EP0929675A2/en not_active Ceased
- 1997-10-03 AU AU46709/97A patent/AU733380B2/en not_active Ceased
- 1997-10-03 EP EP07019672A patent/EP1935899A1/en not_active Withdrawn
- 1997-10-03 BR BR9713248-9A patent/BR9713248A/en not_active Application Discontinuation
- 1997-10-03 JP JP51695598A patent/JP4452331B2/en not_active Expired - Fee Related
-
1999
- 1999-04-02 US US09/285,379 patent/US6451765B1/en not_active Expired - Fee Related
- 1999-08-06 US US09/369,912 patent/US6492504B2/en not_active Expired - Fee Related
-
2002
- 2002-07-09 US US10/193,524 patent/US7323173B2/en not_active Expired - Fee Related
- 2002-07-09 US US10/192,915 patent/US7332287B2/en not_active Expired - Fee Related
-
2008
- 2008-02-07 US US12/027,799 patent/US20090011434A1/en not_active Abandoned
-
2009
- 2009-08-14 JP JP2009188028A patent/JP2010031013A/en active Pending
-
2010
- 2010-09-22 US US12/888,214 patent/US20110039279A1/en not_active Abandoned
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