CA2469714A1 - Multifunctional monoclonal antibodies directed to peptidoglycan of gram-positive bacteria - Google Patents
Multifunctional monoclonal antibodies directed to peptidoglycan of gram-positive bacteria Download PDFInfo
- Publication number
- CA2469714A1 CA2469714A1 CA002469714A CA2469714A CA2469714A1 CA 2469714 A1 CA2469714 A1 CA 2469714A1 CA 002469714 A CA002469714 A CA 002469714A CA 2469714 A CA2469714 A CA 2469714A CA 2469714 A1 CA2469714 A1 CA 2469714A1
- Authority
- CA
- Canada
- Prior art keywords
- mab
- medicament
- patient
- gram
- positive bacteria
- 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.)
- Abandoned
Links
- 241000192125 Firmicutes Species 0.000 title claims abstract 10
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 title claims abstract 7
- 108010013639 Peptidoglycan Proteins 0.000 title claims abstract 7
- 230000001681 protective effect Effects 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims 17
- 238000000034 method Methods 0.000 claims 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 210000004408 hybridoma Anatomy 0.000 claims 2
- 229920001184 polypeptide Polymers 0.000 claims 2
- 229960005486 vaccine Drugs 0.000 claims 2
- 241000194107 Bacillus megaterium Species 0.000 claims 1
- 244000063299 Bacillus subtilis Species 0.000 claims 1
- 235000014469 Bacillus subtilis Nutrition 0.000 claims 1
- 238000002965 ELISA Methods 0.000 claims 1
- 241000194032 Enterococcus faecalis Species 0.000 claims 1
- 206010061598 Immunodeficiency Diseases 0.000 claims 1
- 241000186779 Listeria monocytogenes Species 0.000 claims 1
- 241000191967 Staphylococcus aureus Species 0.000 claims 1
- 241000191963 Staphylococcus epidermidis Species 0.000 claims 1
- 241000194019 Streptococcus mutans Species 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000000941 anti-staphylcoccal effect Effects 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 229940032049 enterococcus faecalis Drugs 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 238000007914 intraventricular administration Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 230000009871 nonspecific binding Effects 0.000 claims 1
- 230000000625 opsonophagocytic effect Effects 0.000 claims 1
- 230000002028 premature Effects 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 241000894006 Bacteria Species 0.000 abstract 2
- 206010057249 Phagocytosis Diseases 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 230000008782 phagocytosis Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
- C07K16/1271—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Micrococcaceae (F), e.g. Staphylococcus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
- C07K16/1275—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Streptococcus (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
- C07K16/1278—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Bacillus (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
- C07K16/1296—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Listeria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Abstract
The present invention encompasses protective monoclonal antibodies that bind to peptidoglycan of Gram-positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro and block nasal colonization by Gram-positive bacteria in vivo. The invention also provides human, humanized and chimeric antibodies. The invention also sets forth the heavy chain and light chain variable regions of an antibody within the invention.
Claims (22)
1. A medicament comprising, a therapeutically effective amount of at least one MAb that binds to peptidoglycan (PepG) of Gram-positive bacteria; wherein said MAb provides therapeutically beneficial outcome upon administration to a patient.
2. The medicament of claim 1, wherein administration reduces the number of Gram-positive bacteria in a patient.
3. The medicament of claim 1, wherein at least one MAb binds PepG
of Gram-positive bacteria at a level at least two-fold greater than background in an ELISA.
of Gram-positive bacteria at a level at least two-fold greater than background in an ELISA.
4. The medicament of claim 1, wherein at least one MAb enhances opsonophagocytic of Gram-positive bacteria by at least 50%.
5. The medicament of claim 1, further comprising a pharmaceutically acceptable carrier.
6. The medicament of claim 1, further comprising further comprises at least one anti-staphylococcal drug.
7. The medicament of claim 1, further comprising at least one MAb that binds to lipoteichoic acid (LTA) of Gram-positive bacteria.
8. The medicament of claim 1, wherein at least one MAb blocks colonization by Gram-positive bacteria upon instillation into the nares of a patient.
9. The medicament of claim 1 wherein at least one MAb specifically binds PepG of a Gram-positive bacteria selected from Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Bacillus subtilis, Bacillus megaterium, Enterococcus faecalis, and Listeria monocytogenes.
10. The medicament of claim 1, wherein at least one MAb is selected from MAb-11-232.3, MAb-11-248.2, MAb-11-569.3, MAb-11-232.3 IE9, MAb-99-110FC12 IE4, A130, and M130.
11. The medicament of claim 1, wherein at least one MAb comprises a variable region comprising a polypeptide having the amino acid sequences selected from SEQ ID Nos.: 1 and 3.
12. The medicament of claim 1, wherein at least one MAb comprises a variable region comprising a polypeptide having at least 80% identity with the amino acid sequences selected from SEQ ID Nos.: 1 and 3.
13. The medicament of claim 1, wherein at least one MAb is selected from chimeric, humanized, and human MAbs.
l4.The medicament of claim 1, wherein at least one MAb comprises a modified Fc portion, wherein said modification reduces nonspecific binding of the MAb via the Fc portion.
15. The medicament of claim 1, wherein at least one MAb is selected from a Fab, Fab', F(ab')2, Fv, SFv, and scFv.
16. A method for treating a patient comprising, administering a therapeutically effective amount the medicament of any of claims 1-15 to a patient.
l7.The method of claim 16, wherein the patient is selected from a hospitalized an infant, a premature infant, a burn victim, an elderly patient, an immunocompromised patient, an immununosuppressed patient, a patient undergoing an invasive procedure, and a health care worker.
18. The method of claim 1, wherein the protective monoclonal antibody is administered by a route selected from intravenous, intraperitoneal, intracorporeal injection, intra-articular, intraventricular, intrathecal, intramuscular, subcutaneous, intranasal, intravaginal, and oral.
19. The hybridoma cell line deposited at the ATCC under accession no.
PTA-2492.
PTA-2492.
20. The hybridoma cell line deposited at the ATCC under accession no.
PTA-3659.
PTA-3659.
21.A vaccine comprising at least one purified PepG, peptides, fragments and epitopes therof, in a pharmaceutically acceptable carrier.
22.A method for treating a patient comprising, administering a therapeutically effective amount of the vaccine of claim 21.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34180601P | 2001-12-21 | 2001-12-21 | |
| US34344401P | 2001-12-21 | 2001-12-21 | |
| US60/341,806 | 2001-12-21 | ||
| US60/343,444 | 2001-12-21 | ||
| PCT/US2002/041032 WO2003059259A2 (en) | 2001-12-21 | 2002-12-23 | Multifunctional monoclonal antibodies directed to peptidoglycan of gram-positive bacteria |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2469714A1 true CA2469714A1 (en) | 2003-07-24 |
Family
ID=26992674
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002469714A Abandoned CA2469714A1 (en) | 2001-12-21 | 2002-12-23 | Multifunctional monoclonal antibodies directed to peptidoglycan of gram-positive bacteria |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1470237A4 (en) |
| JP (2) | JP2005524624A (en) |
| AU (2) | AU2002364740A1 (en) |
| CA (1) | CA2469714A1 (en) |
| WO (1) | WO2003059259A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749652A (en) * | 2017-03-14 | 2017-05-31 | 天津喜诺生物医药有限公司 | A kind of polyclonal antibody of aureus peptide glycan |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101508390B1 (en) | 2006-06-06 | 2015-04-08 | 크루셀 홀란드 비.브이. | Human binding molecules having killing activity against staphylococci and uses thereof |
| MX2008014978A (en) | 2006-06-06 | 2008-12-09 | Crucell Holland Bv | Human binding molecules having killing activity against enterococci and staphylococcus aureus and uses thereof. |
| NZ594945A (en) * | 2006-06-06 | 2013-03-28 | Crucell Holland Bv | Human binding molecules having killing activity against enterococci and staphylococcus aureus and uses thereof |
| JP2008255084A (en) * | 2007-04-04 | 2008-10-23 | Isako Hashimoto | Anti-pollinosis agent or foodstuff |
| AU2009246510B2 (en) * | 2008-05-12 | 2014-02-13 | Strox Biopharmaceuticals, Llc | Staphylococcus aureus-specific antibody preparations |
| WO2010085590A1 (en) * | 2009-01-23 | 2010-07-29 | Biosynexus Incorporated | Opsonic and protective antibodies specific for lipoteichoic acid gram positive bacteria |
| JP2015522692A (en) | 2012-07-16 | 2015-08-06 | ファイザー・インク | Sugar and its use |
| WO2014142117A1 (en) * | 2013-03-12 | 2014-09-18 | 全薬工業株式会社 | Anti-staphylococcus antibody, method for manufacturing same, and usage of same |
| EP3872166A4 (en) * | 2018-10-25 | 2022-09-14 | Nissui Pharmaceutical Co., Ltd. | Cell collection method |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4596769A (en) * | 1984-03-05 | 1986-06-24 | Temple University | Monoclonal antibodies to peptidoglycan and methods of preparing same |
| US6610293B1 (en) * | 1997-06-16 | 2003-08-26 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine | Opsonic and protective monoclonal and chimeric antibodies specific for lipoteichoic acid of gram positive bacteria |
| US6936258B1 (en) * | 1999-03-19 | 2005-08-30 | Nabi Biopharmaceuticals | Staphylococcus antigen and vaccine |
| GB2356402B (en) * | 2000-07-22 | 2001-10-31 | Michael G Morgan | Use of radio-labelled antibody to bacterial compounds in the diagnosis of focal infection in humans |
-
2002
- 2002-12-23 EP EP02806494A patent/EP1470237A4/en not_active Withdrawn
- 2002-12-23 AU AU2002364740A patent/AU2002364740A1/en not_active Abandoned
- 2002-12-23 CA CA002469714A patent/CA2469714A1/en not_active Abandoned
- 2002-12-23 JP JP2003559424A patent/JP2005524624A/en active Pending
- 2002-12-23 WO PCT/US2002/041032 patent/WO2003059259A2/en active Application Filing
-
2009
- 2009-08-17 AU AU2009210372A patent/AU2009210372B2/en not_active Ceased
- 2009-08-24 JP JP2009193403A patent/JP2010013454A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749652A (en) * | 2017-03-14 | 2017-05-31 | 天津喜诺生物医药有限公司 | A kind of polyclonal antibody of aureus peptide glycan |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003059259A2 (en) | 2003-07-24 |
| JP2005524624A (en) | 2005-08-18 |
| AU2002364740A1 (en) | 2003-07-30 |
| JP2010013454A (en) | 2010-01-21 |
| EP1470237A4 (en) | 2006-02-01 |
| AU2009210372B2 (en) | 2012-07-26 |
| WO2003059259A3 (en) | 2004-06-17 |
| AU2009210372A1 (en) | 2009-09-10 |
| EP1470237A2 (en) | 2004-10-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20140325 |