EP1061959A2 - Radioimmunpharmakon zur behandlung der hiv-1-infektion - Google Patents
Radioimmunpharmakon zur behandlung der hiv-1-infektionInfo
- Publication number
- EP1061959A2 EP1061959A2 EP99919038A EP99919038A EP1061959A2 EP 1061959 A2 EP1061959 A2 EP 1061959A2 EP 99919038 A EP99919038 A EP 99919038A EP 99919038 A EP99919038 A EP 99919038A EP 1061959 A2 EP1061959 A2 EP 1061959A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- hiv
- radioimmunoconjugate
- radioimmuno
- cells
- infected
- 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.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1027—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants
- A61K51/1039—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants against T-cell receptors
Definitions
- Radioimmune drug for the treatment of HIV-1 infection is Radioimmune drug for the treatment of HIV-1 infection.
- HIV infection leads to a progressive immune deficiency due to loss of the CD4 + T helper cells infected with HIV. If the number of these cells falls below a threshold value of 350 / ⁇ l or if the viral load in the blood exceeds 30,000 RNA copies / ⁇ l, antiretroviral therapy is preferred today with an orally administered combination of three medications consisting of two inhibitors of reverse transcriptase (RTI) and a protease inhibitor (PI). This replicates and slows down the replication of the HI viruses.
- RTI reverse transcriptase
- PI protease inhibitor
- HTV-replicating host cells cannot be eliminated with these agents. HIV infection persists as a life-threatening infection. A cure for HIV infection is still not possible.
- HIV and HIV-infected cells can be labeled with antibodies, but these do not trigger the desired immune response, which leads to the elimination of the infected cells, because the latter is already compromised by the HIV infection.
- the body's own cytotoxic immune response, which is disturbed by HIV infection, must therefore be replaced by a targeted, artificially induced death of all HIV-infected cells, if possible.
- Radionuclides as radioiodine therapy from the treatment of benign and malignant thyroid diseases has been known in Germany for over 50 years as the most important method of nuclear medicine therapy and has proven to be low in side effects. To date, late complications, particularly malignant induction, have not been demonstrated (Moser 1996).
- MIBG I-labeled meta-iodo-benzyl-guanidine
- J adioimmunotherapies including 131 J-labeled anti-CEA IgG for colorectal cancer (Blumenthal et al. 1992, Blumenthal 1994), and 131 J-labeled anti-CD20 and anti CD22 antibodies in B cell lymphoma (Kaminski et al 1993, Press et al. 1993, Press et al. 1995, Press et al. 1995).
- AZ WO 94/04191 AI describes a treatment method for the complete elimination of all cells carrying CD4 receptors, i.e. healthy and HIV-infected cells. Two options are mentioned for this, on the one hand the
- Radioimmune drugs should be taken after antiretroviral therapy has been used to reduce the viral load, and the possible problems of bone marrow and thyroid damage may be covered by stem cell transplantation and or thyroid medication. This is intended to overcome the disadvantages of the pharmaceuticals and treatment methods described in the abovementioned printed publications and to solve a global health problem which has so far been expanding unhindered.
- the compound is a human gp41 specific monoclonal antibody with the isotope 131 I into consideration.
- the retroviral transmembrane glycoprotein gp41 is firmly integrated into the viral and cellular lipid membrane and, unlike the surface protein gpl20, cannot dissociate by shedding from the virus or from the HIV-infected cell.
- a suitable component of a radioimmunoconjugate and well characterized would be, for example, the human monoclonal antibody 2F5, which binds to a highly conserved epitope which is therefore widespread in the different HTV-1 isolates (Muster et al. 1993).
- the short half-life of the radionuclides J, P, Y and Sr requires preparation close to the center or rapid transport of the radioimmuno-conjugate
- the prerequisite for the therapy of HIV patients with short-lived radionuclides is therefore the establishment of specialized interdisciplinary centers, in which, in addition to professional therapy for HIV-infected people (including standard antiretroviral therapy), timely application of the radioimmuno-conjugate is also guaranteed under radiation protection law aspects.
- a prerequisite for successful therapy is the reduction of the viral load by pretreating the patient with the modern standard triple therapy, as is generally known. This allows a higher dose of the radioimmune drug to be applied to the HIV-infected cells in order to eliminate them. Otherwise the preparation would be trapped by free virus particles and the cytotoxic effect would be reduced.
- thyroid diagnostics and thyroid blockade must also be carried out according to the known scheme.
- the radioimmunoconjugate should be administered intravenously. This generally requires hospitalization over several days in order to shield the patient from the environment until the radiation has decayed.
- the preparation can be administered peripherally or centrally as a bolus, short infusion or continuous therapy over several days with a dose of probably 50 - 300 mCi.
- the dose is given once or in the form of cycles at intervals of several weeks.
- the radioimmunoconjugate binds specifically with the help of the monoclonal antibody to an epitope of a retroviral transmembrane or surface glycoprotein (gp41 or gpl20) integrated in the cell wall of the HIV-1 replicating cell. So this at this Cell-fixed radionuclide emits ⁇ -radiation into the surrounding area. In particular, the cell infected with HIV-1 infected with numerous radioimmuno-conjugates is damaged.
- gp41 or gpl20 retroviral transmembrane or surface glycoprotein
- the radiation energy of an ⁇ or ⁇ emitter such as m J has a range of up to 40 cell diameters. Malignant transformations of healthy cells as a result of radiation damage are extremely rare and can hardly be recorded statistically. If a healthy cell is damaged, it also loses its ability to divide in most cases and reproductive or programmed cell death (apoptosis) occurs. The radiation of surrounding healthy cells also plays a subordinate role in the radioimmunotherapy of HIV-infected T lymphocytes, since these are predominantly in the circulation and healthy cells therefore only experience radiation exposure for a short time.
- a third major advantage is that internalization of our radioimmuno-conjugates, in contrast to the antibody-toxin conjugates of WO 91/10742 AI, is not necessary and that radionuclides do not bind unspecifically to healthy cells like toxins.
- the aim of radioimmunotherapy for HIV infection with the radioimmunoconjugates described in this patent application is the targeted, complete elimination of HTV-1 replicating cells and thus the healing of HIV-infected persons or at least a significant delay in the course of the disease, an improvement in quality of life and a reduction healthcare costs.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1998109785 DE19809785C2 (de) | 1998-03-08 | 1998-03-08 | Radioimmunpharmakon zur Behandlung der HIV-1-Infektion |
DE19809785 | 1998-03-08 | ||
PCT/DE1999/000598 WO1999045969A2 (de) | 1998-03-08 | 1999-03-05 | Radioimmunpharmakon zur behandlung der hiv-1-infektion |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1061959A2 true EP1061959A2 (de) | 2000-12-27 |
Family
ID=7860044
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99919038A Withdrawn EP1061959A2 (de) | 1998-03-08 | 1999-03-05 | Radioimmunpharmakon zur behandlung der hiv-1-infektion |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1061959A2 (ja) |
JP (1) | JP2002506051A (ja) |
AU (1) | AU3698199A (ja) |
DE (1) | DE19809785C2 (ja) |
WO (1) | WO1999045969A2 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU4497199A (en) * | 1998-04-15 | 1999-11-08 | Ingrid-Corina Bergter | Cd4 radio-immunological pharmaceuticals for the treatment of hiv infections |
DE59907027D1 (de) * | 1998-06-29 | 2003-10-23 | Wolfgang Bergter | Antivirale und antiretrovirale radioimmunpharmaka auf der basis von alpha- und beta-strahlern |
CN1238499C (zh) * | 2002-07-29 | 2006-01-25 | 清华大学 | 艾滋病病毒0型株的一种抗体及其生产细胞系与应用 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK169582B1 (da) * | 1986-06-23 | 1994-12-12 | Squibb Bristol Myers Co | Humant monoklonalt antistof, der er i stand til at reagere med en epitop på LAV/HTLV-III kappeglycoproteinet gp41, cellelinier, som producerer sådant antistof, farmaceutisk præparat indeholdende antistoffet samt fremgangsmåde til bestemmelse af nærværelsen af LAV/HTLV-III i en biologisk prøve og fremgangsmåde til separering af specifikke antigendeterminanter af LAV/HTLV-III under anvendelse af ant |
CA1339857C (en) * | 1987-05-29 | 1998-05-05 | Cecily Rou-Yun Sun | Monoclonal antibodies to gp120 which neutraleze hiv-1 |
CA2028121A1 (en) * | 1989-02-28 | 1990-08-29 | Susan Zolla-Pazner | Human monoclonal antibodies to human immunodeficiency virus |
CA1339415C (en) * | 1989-08-24 | 1997-09-02 | Milton David Goldenberg | Detection and treatment of infections with immunoconjugates |
EP0511300A4 (en) * | 1990-01-16 | 1993-05-26 | Replgien Corporation | Monoclonal antibody specific for non-immunodominant epitope of hiv proteins |
GB9217124D0 (en) * | 1992-08-13 | 1992-09-23 | Antisoma Ltd | Medical treatment |
CA2145757A1 (en) * | 1992-09-30 | 1994-04-14 | Dennis R. Burton | Human neutralizing monoclonal antibodies to human immunodeficiency virus |
WO1995010777A1 (en) * | 1993-10-15 | 1995-04-20 | Rakowicz Szulczynska Ewa M | Detection and treatment of breast and gynecological cancer |
-
1998
- 1998-03-08 DE DE1998109785 patent/DE19809785C2/de not_active Expired - Fee Related
-
1999
- 1999-03-05 JP JP2000535382A patent/JP2002506051A/ja active Pending
- 1999-03-05 WO PCT/DE1999/000598 patent/WO1999045969A2/de not_active Application Discontinuation
- 1999-03-05 EP EP99919038A patent/EP1061959A2/de not_active Withdrawn
- 1999-03-05 AU AU36981/99A patent/AU3698199A/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO9945969A3 * |
Also Published As
Publication number | Publication date |
---|---|
WO1999045969A3 (de) | 2000-02-17 |
DE19809785A1 (de) | 1999-09-09 |
JP2002506051A (ja) | 2002-02-26 |
DE19809785C2 (de) | 2000-02-10 |
WO1999045969A2 (de) | 1999-09-16 |
AU3698199A (en) | 1999-09-27 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20001006 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): CH DE ES FR GB IT LI |
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17Q | First examination report despatched |
Effective date: 20040616 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20041027 |