CA2264484A1 - Human plasma hyaluronidase - Google Patents
Human plasma hyaluronidaseInfo
- Publication number
- CA2264484A1 CA2264484A1 CA002264484A CA2264484A CA2264484A1 CA 2264484 A1 CA2264484 A1 CA 2264484A1 CA 002264484 A CA002264484 A CA 002264484A CA 2264484 A CA2264484 A CA 2264484A CA 2264484 A1 CA2264484 A1 CA 2264484A1
- Authority
- CA
- Canada
- Prior art keywords
- hphase
- antibody
- sample
- human plasma
- aahase
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01035—Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2474—Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01036—Hyaluronoglucuronidase (3.2.1.36)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA).
Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression.
The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.
Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression.
The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.
Claims (17)
1. An antibody characterized by its ability to bind to native human plasma hyaluronidase (hpHAse).
2. An antibody that specifically binds to native human plasma hyaluronidase (hpHAse) produced by the process comprising the steps of:
(a) incubating a candidate antibody with a sample comprising native hpHAse, said incubating being for a time sufficient for formation of antibody-hpHAse complexes;
(b) contacting the sample with an insoluble support having anti-antibody and detectably-labeled hyaluronic acid bound thereto for a time sufficient for formation of anti-antibody-candidate antibody-hpHAse complexes; and (c) exposing the sample in contact with the support to an acidic pH of about
(a) incubating a candidate antibody with a sample comprising native hpHAse, said incubating being for a time sufficient for formation of antibody-hpHAse complexes;
(b) contacting the sample with an insoluble support having anti-antibody and detectably-labeled hyaluronic acid bound thereto for a time sufficient for formation of anti-antibody-candidate antibody-hpHAse complexes; and (c) exposing the sample in contact with the support to an acidic pH of about
3.4 to 3.7, thereby allowing hpHAse in the antibody-hpHAse complex to degrade the detectably labeled hyaluronic acid;
wherein samples associated with hyaluronic acid degradation comprise an anti-hpHAse antibody.
3. A hybridoma cell line 17E9 having ATCC accession number ATCC
HB-12213.
wherein samples associated with hyaluronic acid degradation comprise an anti-hpHAse antibody.
3. A hybridoma cell line 17E9 having ATCC accession number ATCC
HB-12213.
4. A hybridoma cell line 4D5 having ATCC accession number ATCC
HB-12214.
HB-12214.
5. A method for screening candidate antibodies for binding to a native acid active hyaluronidase (aaHAse), the method comprising the steps of:
(a) incubating a candidate antibody with a sample consisting native aaHAse, said incubating being for a time sufficient for formation of antibody-aaHAse complexes;
(b) contacting the sample with an insoluble support having anti-antibody and detectably-labeled hyaluronic acid bound thereto for a time sufficient for formation of anti-antibody-candidate antibody-hpHAse complexes; and (c) exposing the sample in contact with the support to an acidic pH of about 3.4 to 3.7, thereby allowing hpHAse in the antibody-aaHAse complex to degrade the detectably labeled hyaluronic acid;
wherein samples associated with hyaluronic acid degradation comprise an anti-aaHAse antibody.
(a) incubating a candidate antibody with a sample consisting native aaHAse, said incubating being for a time sufficient for formation of antibody-aaHAse complexes;
(b) contacting the sample with an insoluble support having anti-antibody and detectably-labeled hyaluronic acid bound thereto for a time sufficient for formation of anti-antibody-candidate antibody-hpHAse complexes; and (c) exposing the sample in contact with the support to an acidic pH of about 3.4 to 3.7, thereby allowing hpHAse in the antibody-aaHAse complex to degrade the detectably labeled hyaluronic acid;
wherein samples associated with hyaluronic acid degradation comprise an anti-aaHAse antibody.
6. A method of purifying human plasma hyaluronidase (hpHAse) from a sample, the method comprising;
contacting a sample comprising hpHAse with an anti-hpHAse antibody, said contacting being for a time sufficient for formation of anti-hpHAse antibody-hpHAse complexes;
isolating hpHAse from the complexes.
contacting a sample comprising hpHAse with an anti-hpHAse antibody, said contacting being for a time sufficient for formation of anti-hpHAse antibody-hpHAse complexes;
isolating hpHAse from the complexes.
7. A device for immunopurification of native human plasma hyaluronidase (hpHAse) comprising:
an insoluble support; and an anti-hpHAse antibody characterized by an ability to bind hpHAse with a binding affinity of 10 7 1/mole or more.
an insoluble support; and an anti-hpHAse antibody characterized by an ability to bind hpHAse with a binding affinity of 10 7 1/mole or more.
8. An assay device for detection of hyaluronidase activity comprising:
an insoluble support;
biotinylated hyaluronic acid (bHA) covalently bound to the support, where the biotinylated hyaluronic acid being the product of a one-step reaction of hyaluronic acid, 1-ethyl-dimethylaminopropyl carbodiamide (EDC) and biotin hydrazide.
an insoluble support;
biotinylated hyaluronic acid (bHA) covalently bound to the support, where the biotinylated hyaluronic acid being the product of a one-step reaction of hyaluronic acid, 1-ethyl-dimethylaminopropyl carbodiamide (EDC) and biotin hydrazide.
9. A method for identifying a patient having or susceptible to a condition associated with a LuCa-1 defect, the method comprising the steps of:
contacting a sample from the patient with an anti-hpHAse antibody, the sample being selected from the group consisting of tissue, blood, plasma, serum,and urine, said contacting being for a time sufficient for formation of anti-hpHAse antibody-hpHAse complexes;
detecting the amount of hpHAse present in the sample; and comparing the amount of hpHAse detected in the sample with an amount of hpHAse in a control sample containing a known amount of hpHAse correlated with a normal level of hpHAse;
wherein detection of an amount of hpHAse in the patient sample that is less than the amount of hpHAse in the control sample is indicative of a LuCa-1 defectin the patient.
contacting a sample from the patient with an anti-hpHAse antibody, the sample being selected from the group consisting of tissue, blood, plasma, serum,and urine, said contacting being for a time sufficient for formation of anti-hpHAse antibody-hpHAse complexes;
detecting the amount of hpHAse present in the sample; and comparing the amount of hpHAse detected in the sample with an amount of hpHAse in a control sample containing a known amount of hpHAse correlated with a normal level of hpHAse;
wherein detection of an amount of hpHAse in the patient sample that is less than the amount of hpHAse in the control sample is indicative of a LuCa-1 defectin the patient.
10. Substantially purified human plasma hyaluronidase characterized by a fatty acid moiety that is resistant to cleavage by phospholipase C, phospholipase D, and N-glycosidase-F.
11. A method of purifying a native acid active hyaluronidase (aaHAse) from a sample, the method comprising the steps of:
(a) dissolving a sample suspected of containing an aaHAse in a solution at a temperature substantially less than room temperature, the solution comprising a non-ionic detergent;
(b) raising the temperature of the solution to a temperature substantially greater than room temperature, said raising resulting in the formation of a detergent-rich phase comprising aaHAse and a detergent-poor phase; and (c) isolating aaHAse from the detergent-rich phase.
(a) dissolving a sample suspected of containing an aaHAse in a solution at a temperature substantially less than room temperature, the solution comprising a non-ionic detergent;
(b) raising the temperature of the solution to a temperature substantially greater than room temperature, said raising resulting in the formation of a detergent-rich phase comprising aaHAse and a detergent-poor phase; and (c) isolating aaHAse from the detergent-rich phase.
12. An expression system for production of recombinant hpHAse, the system comprising a transformed cell containing a nucleic acid construct comprising hpHAse-encoding nucleic acid operably linked to a eukaryotic promoter.
13. A formulation for administration of human plasma hyaluronidase (hpHAse) to a patient having a condition associated with a LuCa-1 gene defect comprising:
a) a therapeutically effective amount of a substantially pure human plasma hyaluronidase polypeptide; and b) a pharmaceutically acceptable carrier.
a) a therapeutically effective amount of a substantially pure human plasma hyaluronidase polypeptide; and b) a pharmaceutically acceptable carrier.
14. The use of human plasma hyaluronidase for the treatment or prevention of cancer associated with a LuCa-1 defect.
15. The use of a construct comprising a nucleotide sequence encoding a human plasma hyaluronidase polypeptide and a eukaryotic promoting sequence operably linked thereto for the treatment or prevention of cancer associated with a defective LuCa-1 gene.
16. An isolated recombinant human plasma hyaluronidase polypeptide.
17. A method of making a recombinant human plasma hyaluronidase polypeptide, the method comprising the steps of:
introducing into a host cell a nucleotide sequence encoding a human plasma hyaluronidase polypeptide;
culturing the host cell so as to allow for expression of the polypeptide from the introduced sequence; and isolating human plasma hyaluronidase polypeptide.
introducing into a host cell a nucleotide sequence encoding a human plasma hyaluronidase polypeptide;
culturing the host cell so as to allow for expression of the polypeptide from the introduced sequence; and isolating human plasma hyaluronidase polypeptide.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/733,360 | 1996-10-17 | ||
| US08/733,360 US6103525A (en) | 1996-10-17 | 1996-10-17 | Hybridoma cell lines producing monoclonal antibodies that bind to human plasma hyaluronidase |
| US08/916,935 | 1997-08-21 | ||
| US08/916,935 US6193963B1 (en) | 1996-10-17 | 1997-08-21 | Method of treating tumor-bearing patients with human plasma hyaluronidase |
| PCT/US1997/018089 WO1998016655A1 (en) | 1996-10-17 | 1997-10-07 | Human plasma hyaluronidase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2264484A1 true CA2264484A1 (en) | 1998-04-23 |
| CA2264484C CA2264484C (en) | 2012-02-07 |
Family
ID=27112566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2264484A Expired - Fee Related CA2264484C (en) | 1996-10-17 | 1997-10-07 | Human plasma hyaluronidase |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US6193963B1 (en) |
| EP (1) | EP0961833B1 (en) |
| JP (1) | JP4503708B2 (en) |
| AT (1) | ATE464391T1 (en) |
| AU (1) | AU730705B2 (en) |
| CA (1) | CA2264484C (en) |
| HK (1) | HK1021648A1 (en) |
| WO (1) | WO1998016655A1 (en) |
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| WO1996003497A1 (en) | 1994-07-22 | 1996-02-08 | Seikagaku Corporation | Novel hyaluronidase |
| JP3657644B2 (en) * | 1995-03-30 | 2005-06-08 | 森永乳業株式会社 | Monoclonal antibodies and hybridomas |
| US5747027A (en) * | 1995-04-07 | 1998-05-05 | The Regents Of The University Of California | BH55 hyaluronidase |
-
1997
- 1997-08-21 US US08/916,935 patent/US6193963B1/en not_active Expired - Lifetime
- 1997-10-07 WO PCT/US1997/018089 patent/WO1998016655A1/en active Application Filing
- 1997-10-07 JP JP51783498A patent/JP4503708B2/en not_active Expired - Fee Related
- 1997-10-07 AT AT97910003T patent/ATE464391T1/en not_active IP Right Cessation
- 1997-10-07 AU AU47482/97A patent/AU730705B2/en not_active Ceased
- 1997-10-07 CA CA2264484A patent/CA2264484C/en not_active Expired - Fee Related
- 1997-10-07 EP EP97910003A patent/EP0961833B1/en not_active Expired - Lifetime
-
2000
- 2000-01-28 HK HK00100518.3A patent/HK1021648A1/en not_active IP Right Cessation
-
2001
- 2001-02-27 US US09/795,914 patent/US7148201B2/en not_active Expired - Fee Related
-
2003
- 2003-07-18 US US10/622,283 patent/US7105330B2/en not_active Expired - Fee Related
-
2006
- 2006-10-03 US US11/538,246 patent/US7781397B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP4503708B2 (en) | 2010-07-14 |
| US20030170243A1 (en) | 2003-09-11 |
| US6193963B1 (en) | 2001-02-27 |
| US20070134228A1 (en) | 2007-06-14 |
| AU4748297A (en) | 1998-05-11 |
| EP0961833B1 (en) | 2010-04-14 |
| WO1998016655A1 (en) | 1998-04-23 |
| AU730705B2 (en) | 2001-03-15 |
| HK1021648A1 (en) | 2000-06-23 |
| US7148201B2 (en) | 2006-12-12 |
| US7781397B2 (en) | 2010-08-24 |
| ATE464391T1 (en) | 2010-04-15 |
| US20040096921A1 (en) | 2004-05-20 |
| US7105330B2 (en) | 2006-09-12 |
| EP0961833A1 (en) | 1999-12-08 |
| EP0961833A4 (en) | 2002-10-16 |
| JP2001508646A (en) | 2001-07-03 |
| CA2264484C (en) | 2012-02-07 |
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