CA2598510A1 - Q3 sparc deletion mutant and uses thereof - Google Patents

Q3 sparc deletion mutant and uses thereof Download PDF

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Publication number
CA2598510A1
CA2598510A1 CA002598510A CA2598510A CA2598510A1 CA 2598510 A1 CA2598510 A1 CA 2598510A1 CA 002598510 A CA002598510 A CA 002598510A CA 2598510 A CA2598510 A CA 2598510A CA 2598510 A1 CA2598510 A1 CA 2598510A1
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Canada
Prior art keywords
antibody
polypeptide
composition
therapeutic agent
disease
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Granted
Application number
CA002598510A
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French (fr)
Other versions
CA2598510C (en
Inventor
Vuong Trieu
Neil P. Desai
Patrick Soon-Shiong
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Abraxis Bioscience LLC
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Individual
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Publication of CA2598510A1 publication Critical patent/CA2598510A1/en
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Publication of CA2598510C publication Critical patent/CA2598510C/en
Expired - Fee Related legal-status Critical Current
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/191—Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4747—Apoptosis related proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/82—Translation products from oncogenes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Abstract

The invention provides for SPARC polypeptides with a mutation corresponding to a deletion of the third glutamine in the mature form of the human SPARC
protein, nucleic acids encoding such polypeptides, antibodies against such polypeptides, and methods of the use of such polypeptides, nucleic acids, and antibodies.

Claims (64)

1. An isolated SPARC polypeptide comprising an amino acid sequence wherein the glutamine corresponding to amino acid 20 in SEQ ID NO: 1 is deleted.
2. The SPARC polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2.
3. An isolated nucleic acid molecule encoding the SPARC polypeptide of claim 1.
4. The nucleic acid molecule of claim 3, wherein the nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 3.
5. A vector comprising the nucleic acid sequence of claim 3.
6. The vector of claim 5 further comprising a promoter controlling the expression of the SPARC polypeptide encoding nucleic acid sequences.
7. A cell comprising the nucleic acid molecule of claim 3.
8. The cell of claim 7, wherein the cell is a prokaryotic cell.
9. The cell of claim 7, wherein the cell is a eukaryotic cell.
10. A method of making the polypeptide of claim 1 comprising:

a. transforming cells with a nucleic acid encoding the polypeptide of claim 1, b. inducing the expression of the polypeptide by the transformed cells, and c. purifying the polypeptide.
11. A composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.
12. A method of treating a disease in a mammal comprising administering the polypeptide of claim 1 to the mammal.
13. The method of claim 12, wherein the disease is a cell proliferative disease.
14. A method of sensitizing a disease in a mammal comprising administering the polypeptide of claim 1 to the mammal.
15. The method of claim 14, further comprising administering one or more therapeutic agents..
16. The method of claim 14, wherein the disease is a cancer.
17. The composition of claim 11, wherein the polypeptide is coupled to a therapeutic agent.
18. The composition of claim 17, wherein the therapeutic agent is a radionuclide, drug, polypeptide or toxin.
19. The composition of claim 11, wherein the polypeptide is coupled to a polyethylene glycol.
20. A composition comprising an antibody or fragment thereof with recognition for the polypeptide of claim 1 and a pharmaceutically acceptable carrier.
21. The composition of claim 20, wherein a therapeutic agent is coupled to the antibody or fragment thereof.
22. The composition of claim 20, wherein said antibody or fragments thereof are humanized and include monovalent Fab', divalent Fab2, scfv, diabody, or a chimera.
23. The composition of claim 20, wherein said therapeutic agent is a drug, radionuclide, polypeptide or toxin.
24. The composition of claim 20, wherein the antibody is polyclonal and is manufactured in non-human animals.
25. The composition of claim 20, wherein the antibody is humanized.
26. The composition of claim 20, wherein the antibody is monoclonal is manufactured by fusion of a single line producing anti-SPARC antibody with a myeloma line.
27. The composition of claim 20, wherein the antibody is made in vitro either through peptide synthesizer or by conversion of display phage into antibody or mutagenesis/synthesis of variable regions of the heavy and light chain genes for antibody.
28. The composition of claim 20, wherein the antibody is either monovalent or multivalent, wherein the antibody is further either monospecific or bispecific.
29. The composition of claim 20, wherein the therapeutic agent is cytotoxic paclitaxel, doxorubicin, or camptothecin.
30. The composition of claim 20, wherein the therapeutic agent is a kinase inhibitor.
31. The composition of claim 20, wherein the therapeutic agent is a biological molecule.
32. The composition of claim 20, wherein the therapeutic agent is a radionuclide.
33. The composition of claim 20, wherein the therapeutic agent is the antibody itself and wherein the antibody mediates complement activation, cell mediated cytotoxicity against the tumor or combinations thereof.
34. The composition of claim 20, wherein the route of administration is intravenous, intraperitoneal, intratumoral, or inhalational.
35. A method for delivering a therapeutic agent to a tumor in a mammal comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a therapeutic agent and a pharmaceutically acceptable carrier, the therapeutic agent comprising a chemotherapeutic agent or radioactive agent coupled to an antibody recognizing the polypeptide of claim 1.
36. The method of claim 35, wherein the antibody is polyclonal and is manufactured in non-human animals.
37. The method of claim 35, wherein the antibody is humanized.
38. The method of claim 35, wherein the antibody is monoclonal is manufactured by fusion of a single line producing anti-SPARC antibody with a myeloma line.
39. The method of claim 35, wherein the antibody is made in vitro either through peptide synthesizer or by conversion of display phage into antibody or mutagenesis/synthesis of variable regions of the heavy and light chain genes for antibody.
40. The method of claim 35, wherein the antibody is either monovalent or multivalent, wherein the antibody is further either monospecific or bispecific.
41. The method of claim 35, wherein the therapeutic agent is paclitaxel, doxorubicin or camptothecin.
42. The method of claim 35, wherein the therapeutic agent is a kinase inhibitor.
43. The method of claim 35, wherein the therapeutic agent is a biological molecules.
44. The method of claim 35, wherein the therapeutic agent is a radionuclide.
45. The method of claim 35, wherein the therapeutic agent is the antibody itself and wherein the antibody mediates complement activation, cell mediated cytotoxicity against the tumor or combinations thereof.
46. The method of claim 35, wherein the tumor is located in the bladder, liver, ovary, kidney, gut, brain, or breast.
47. The method of claim 35, wherein the mammal is a human.
48. The method of claim 35, wherein the route of administration is intravenous, intraperitoneal, intratumoral, or inhalational.
49. A method for delivering a diagnostic agent to a tumor in a mammal comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a diagnostic agent coupled to an antibody recognizing the protein of claim 1 and a pharmaceutically acceptable carrier.
50. The method of claim 49, wherein said diagnostic agent includes radioactive agents, MRI contrast agent, contrast agent, ultrasound contrast agent and PET
contrast agent.
51. The composition of claim 20, wherein the antibody also binds wild type SPARC polypeptides.
52. A method of classifying a disease comprising detecting a SPARC polypeptide with a deletion of the glutamine at corresponding to amino acid position 20 in SEQ ID NO: 1.
53. The method of claim 52, wherein the disease involves neoangiogenesis.
54. The method of claim 52, wherein the disease is a proliferative disease.
55. The method of claim 54, wherein the proliferative disease is a cancer.
56. The method of claim 52, wherein the mutant SPARC polypeptide detected comprises the amino acid sequence of SEQ ID NO: 2.
57. A method of classifying a disease comprising detecting a nucleic acid encoding a SPARC polypeptide with a deletion of the glutamine at the position corresponding to amino acid position 20 of SEQ ID NO: 1.
58. The method of claim 57, wherein the disease involves neoangiogenesis.
59. The method of claim-57, wherein the disease is a proliferative disease.
60. The method of claim 59, wherein the proliferative disease is a cancer.
61. The method of claim 57, wherein the nucleic acid is DNA or RNA.
62. The method of claim 57, wherein the mutant SPARC nucleic acid detected comprises the nucleic sequence of SEQ ID NO: 3.
63. The method of claim 57, wherein the nucleic acid encoding a SPARC
polypeptide is detected using a method comprising a polymerase chain reaction.
64. The method of claim 63, wherein the polymerase chain reaction uses one or more forward primers selected from primers comprising the sequences of SEQ ID
NOS: 7-9 and a reverse primer comprising the sequence of SEQ ID NO: 10.
CA2598510A 2005-02-18 2006-02-17 Q3 sparc deletion mutant and uses thereof Expired - Fee Related CA2598510C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US65426105P 2005-02-18 2005-02-18
US60/654,261 2005-02-18
PCT/US2006/005615 WO2006112930A2 (en) 2005-02-18 2006-02-17 Q3 sparc deletion mutant and uses thereof

Publications (2)

Publication Number Publication Date
CA2598510A1 true CA2598510A1 (en) 2006-10-26
CA2598510C CA2598510C (en) 2011-12-20

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Family Applications (1)

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Country Status (7)

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US (3) US7332568B2 (en)
EP (1) EP1869077A2 (en)
JP (1) JP2008535475A (en)
CN (1) CN101160321A (en)
AU (1) AU2006237613A1 (en)
CA (1) CA2598510C (en)
WO (1) WO2006112930A2 (en)

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Also Published As

Publication number Publication date
US7332568B2 (en) 2008-02-19
JP2008535475A (en) 2008-09-04
EP1869077A2 (en) 2007-12-26
US20080182258A1 (en) 2008-07-31
CN101160321A (en) 2008-04-09
US20060199248A1 (en) 2006-09-07
WO2006112930A2 (en) 2006-10-26
CA2598510C (en) 2011-12-20
US20110009337A1 (en) 2011-01-13
AU2006237613A1 (en) 2006-10-26
WO2006112930A3 (en) 2007-04-05

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