WO1994026293B1 - Immunologic enhancement with intermittent interleukin-2 therapy - Google Patents
Immunologic enhancement with intermittent interleukin-2 therapyInfo
- Publication number
- WO1994026293B1 WO1994026293B1 PCT/US1994/005397 US9405397W WO9426293B1 WO 1994026293 B1 WO1994026293 B1 WO 1994026293B1 US 9405397 W US9405397 W US 9405397W WO 9426293 B1 WO9426293 B1 WO 9426293B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- patient
- administrations
- period
- therapy
- amount
- Prior art date
Links
- 102000000588 Interleukin-2 Human genes 0.000 title claims abstract 21
- 108010002350 Interleukin-2 Proteins 0.000 title claims abstract 21
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract 11
- 230000001900 immune effect Effects 0.000 title claims 5
- 210000000987 Immune System Anatomy 0.000 claims abstract 6
- 201000010099 disease Diseases 0.000 claims abstract 6
- 210000001744 T-Lymphocytes Anatomy 0.000 claims abstract 5
- 230000001177 retroviral Effects 0.000 claims abstract 5
- 230000000798 anti-retroviral Effects 0.000 claims abstract 4
- 210000004698 Lymphocytes Anatomy 0.000 claims abstract 3
- 230000000694 effects Effects 0.000 claims abstract 3
- 238000011065 in-situ storage Methods 0.000 claims abstract 3
- 102000010789 Interleukin-2 Receptors Human genes 0.000 claims abstract 2
- 108010038453 Interleukin-2 Receptors Proteins 0.000 claims abstract 2
- HBOMLICNUCNMMY-XLPZGREQSA-N Zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims abstract 2
- 229960002555 Zidovudine Drugs 0.000 claims abstract 2
- 230000003213 activating Effects 0.000 claims abstract 2
- 230000035492 administration Effects 0.000 claims 23
- 239000000203 mixture Substances 0.000 claims 8
- 239000003795 chemical substances by application Substances 0.000 claims 5
- 201000009910 diseases by infectious agent Diseases 0.000 claims 3
- 239000000411 inducer Substances 0.000 claims 3
- 238000001802 infusion Methods 0.000 claims 3
- 230000000051 modifying Effects 0.000 claims 3
- 239000007929 subcutaneous injection Substances 0.000 claims 3
- 230000001419 dependent Effects 0.000 claims 2
- 230000001717 pathogenic Effects 0.000 claims 2
- 244000052769 pathogens Species 0.000 claims 2
- 230000001131 transforming Effects 0.000 claims 2
- 230000024932 T cell mediated immunity Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000036039 immunity Effects 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 238000010254 subcutaneous injection Methods 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
- 210000004027 cells Anatomy 0.000 abstract 2
- 230000026683 transduction Effects 0.000 abstract 2
- 238000010361 transduction Methods 0.000 abstract 2
- 102000006992 Interferon-alpha Human genes 0.000 abstract 1
- 108010047761 Interferon-alpha Proteins 0.000 abstract 1
- 238000001415 gene therapy Methods 0.000 abstract 1
- 230000002459 sustained Effects 0.000 abstract 1
Abstract
A method for activating a mammalian immune system entails a series of continuous IL-2 infusions that are effected intermittently over an extended period. For exemple, IL-2 can be administered continuously for a period that is on the order of 5 days in length, and successive infusions of this nature can be separated by a period of at least 4 weeks. Sustained beneficial effects, including elevated CD4 cell counts, restoration of lymphocyte function and an increase in the number of IL-2 receptors, are achieved with such intermittent IL-2 therapy, which can be combined with another therapy which targets a specific disease state, such as an anti-retroviral therapy comprising, for example, the administration of AZT, ddI or interferon alpha. In addition, IL-2 administration can be employed to facilitate in situ transduction of T cells in the context of gene therapy. By this approach the cells are first activated in vivo via the aforementioned IL-2 therapy, and transduction then is effected by delivering a genetically engineered retroviral vector directly to the patient.
Claims
1. The use of an amount of IL-2 in the preparation of an agent for use in a method for treating a disease state characterized by an immunological impairment, where
(A) said amount is sufficient to increase the level of helper/inducer T-cell function in a patient suffering such an impairment and
(B) said patient is administered said IL-2 in a series of administrations effected intermittently, each of said administrations being conducted over a period of time of from 1 day to 2 weeks, and successive administrations being separated by a period of at least 4 weeks.
2. A use as claimed in claim 1, wherein said amount is sufficient to increase CD4 T-cell function in said patient.
3. A use as claimed in claim 1, wherein said amount is sufficient to increase expression of IL-2 receptors in said patient.
4. A use as claimed in claim 1, wherein said administration is effected by continuous infusion.
5. A use as claimed in claim 1, wherein said administration is effected by subcutaneous injections.
6. A use as claimed in claim 1, wherein each of said administrations comprises a dosage of IL-2 of from 1.8 to 24 MU/day.
7. A use as claimed in claim 4, wherein said period of time of each of said administrations is on the order of five days.
8. A use as claimed in claim 1, wherein said disease state is characterized by an infection of said patient by a pathogen against which a cellular immune response is a relevant mechanism for specific immunity for said pathogen in said patient.
9. A use as claimed in claim 6, wherein said disease state comprises a secondary infection of said patient, and wherein said patient has a suppressed immune system.
10. A composition of matter comprising (i) a container suitable for holding a solution to be infused into a patient, (ii) a liquid preparation comprising an amount of IL-2 in a pharmaceutically acceptable carrier such that said preparation represents an IL-2 dosage of between about 1.8 to about 24 MU/day, and (iii) instructions on administering said preparation to a patient suffering from an immunological impairment or infectious disease in a series of administrations effected intermittently, such that each of said administrations is conducted over a period of time of from 1 day to 2 weeks, and such that successive administrations are separated by a period of at least 4 weeks.
11. A composition as claimed in claim 10, wherein said preparation is suitable for continuous infusion.
12. A composition as claimed in claim 10, wherein said preparation is suitable for subcutaneous injection.
13. A composition as claimed in claim 10, wherein said instructions further direct administering a therapy to said patient prior to or concomitantly with said adminsitration, said therapy targeting a specific disease state.
14. A composition as claimed in claim 13, wherein said therapy is an anti-retroviral therapy.
15. A composition as claimed in claim 14, wherein said anti-retroviral therapy comprises administering zidovudine to said patient.
16. A composition as claimed in claim 10, wherein said instructions further direct administering to said patient a retroviral vector to effect in situ transformation of lymphocytes.
17. A composition as claimed in claim 16, wherein said instructions further direct that said retroviral vector be administered on the 4th to 7th day of IL-2 administration.
18. The use of an amount of IL-2 in the preparation of an agent for use in a method for modulating the immune system of a patient in need thereof, where
(A) said amount is sufficient to increase the level of helper/inducer T-cell function in said patient,
(B) said patient is administered said IL-2 by a series of administrations effected intermittently, each of said administrations being conducted over a period of time of from 1 day to 2 weeks, and successive administrations being separated by a period of at least 4 weeks and
(C) said patient is administered a retroviral vector to effect in situ transformation of lymphocytes.
STATEMENT UNDER ARTICLE19
Attached are replacement pages 28-30 for the application. Original claim 13 has been canceled. Independent claim 1 has been amended to recite the use of an amount of IL-2 in the preparation of an agent for use in a method for treating a disease state characterized by an immunological impairment, where the patient is administered IL-2 in a series of administrations effected intermittently, wherein each of the administrations are conducted over a period of time of from 1 day to 2 weeks, and successive administrations are separated by a period of at least 4 weeks. Dependent claims 4 and 5 have been added to recite the embodiments wherein the administration is effected by continuous infusion and subcutaneous injections, respectively. Support for these amendments is found at page 8 of the as-filed specification.
The remaining dependent claims and independent claim 10 have been amended along similar lines, and claim 18 has been added to recite the use of an amount of IL-2 in the preparation of an agent for use in a method for modulating the immune system of patient in need thereof, as disclosed at pages 14-15 of the as-filed application. These amendments do not go beyond the disclosure of the application as filed. Claims 1-18 are clearly distinguished from the references cited in the International Search Report. The closest references appear to be EP 426 521 and EP 452 598, which are directed to the use of IL-2 in the treatment of cancer. These references teach the administration of IL-2 at a dose of 2-20 X 106 U/m2/day, with successive administrations separated by about 1 week. These references do not defeat the novelty or inventive step of the present invention, which is directed to the use of an amount of IL-2 in the preparation of an agent for use in a method of activating the immune system of a patient suffering from an immunological impairment.
In particular, these references do not teach or suggest that the IL-2 is administered in an amount sufficient to increase the level of helper/inducer T-cell function in the patient, or that successive administrations are separated by a period of at least 4 weeks, as recited in the instant claims. Moreover, these references do not disclose the prior or concomitant administration of an anti-retroviral therapy to a patient, as recited in claims 14 and 15, or the modulation of a patient's immune system by the administration of a retroviral vector, as recited in claims 16-18.
In view of the instant amendments and remarks, it is believed that the claims are patentable over the cited references.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52574694A JP4275193B2 (en) | 1993-05-19 | 1994-05-19 | Immunity enhancement by intermittent interleukin-2 therapy |
| EP94920673A EP0702560B1 (en) | 1993-05-19 | 1994-05-19 | Immunologic enhancement with intermittent interleukin-2 therapy |
| DK94920673T DK0702560T3 (en) | 1993-05-19 | 1994-05-19 | Immune boosting by intermittent interleukin-2 treatment |
| DE69428992T DE69428992T2 (en) | 1993-05-19 | 1994-05-19 | IMMUNOLOGICAL IMPROVEMENT WITH INTERMITTENT INTERLEUKIN-2 THERAPY |
| AT94920673T ATE208206T1 (en) | 1993-05-19 | 1994-05-19 | IMMUNOLOGICAL IMPROVEMENT WITH INTERMITTENT INTERLEUKIN-2 THERAPY |
| AU71377/94A AU691504B2 (en) | 1993-05-19 | 1994-05-19 | Immunologic enhancement with intermittent interleukin-2 therapy |
| US08/452,440 US5696079A (en) | 1993-05-19 | 1995-05-26 | Immunologic enhancement with intermittent interleukin-2 therapy |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/063,315 | 1993-05-19 | ||
| US08/063,315 US5419900A (en) | 1993-05-19 | 1993-05-19 | Immunologic enhancement with intermittent interleukin-2 therapy |
Related Parent Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US08/063,315 Continuation US5419900A (en) | 1993-05-19 | 1993-05-19 | Immunologic enhancement with intermittent interleukin-2 therapy |
| US08/063,315 Continuation-In-Part US5419900A (en) | 1993-05-19 | 1993-05-19 | Immunologic enhancement with intermittent interleukin-2 therapy |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US48707595A Continuation | 1993-05-19 | 1995-06-07 | |
| US48707595A Continuation-In-Part | 1993-05-19 | 1995-06-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1994026293A1 WO1994026293A1 (en) | 1994-11-24 |
| WO1994026293B1 true WO1994026293B1 (en) | 1995-01-26 |
Family
ID=22048393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1994/005397 WO1994026293A1 (en) | 1993-05-19 | 1994-05-19 | Immunologic enhancement with intermittent interleukin-2 therapy |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US5419900A (en) |
| EP (1) | EP0702560B1 (en) |
| JP (1) | JP4275193B2 (en) |
| AT (1) | ATE208206T1 (en) |
| AU (1) | AU691504B2 (en) |
| CA (1) | CA2163219A1 (en) |
| DE (1) | DE69428992T2 (en) |
| DK (1) | DK0702560T3 (en) |
| ES (1) | ES2167370T3 (en) |
| PT (1) | PT702560E (en) |
| WO (1) | WO1994026293A1 (en) |
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| US5419900A (en) | 1993-05-19 | 1995-05-30 | The United States Of America As Represented By The Department Of Of Health And Human Services | Immunologic enhancement with intermittent interleukin-2 therapy |
| US5696079A (en) * | 1993-05-19 | 1997-12-09 | The United States Of America As Represented By The Department Of Health And Human Services | Immunologic enhancement with intermittent interleukin-2 therapy |
| US5872154A (en) * | 1995-02-24 | 1999-02-16 | The Trustees Of The University Of Pennsylvania | Method of reducing an immune response to a recombinant adenovirus |
| WO1997014812A2 (en) * | 1995-10-16 | 1997-04-24 | Chiron Corporation | Method of screening for factors that modulate gene expression |
| KR100220645B1 (en) * | 1997-07-04 | 1999-09-15 | 구광시 | Process for producing benzene derivatives |
| CA2310805A1 (en) * | 1997-11-24 | 1999-06-03 | Johnson T. Wong | Methods for treatment of hiv or other infections using a t cell or viral activator and anti-retroviral combination therapy |
| JP4776075B2 (en) * | 1998-12-31 | 2011-09-21 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | Modified HIVENV polypeptide |
| US7935805B1 (en) * | 1998-12-31 | 2011-05-03 | Novartis Vaccines & Diagnostics, Inc | Polynucleotides encoding antigenic HIV Type C polypeptides, polypeptides and uses thereof |
| US6602705B1 (en) * | 1998-12-31 | 2003-08-05 | Chiron Corporation | Expression of HIV polypeptides and production of virus-like particles |
| AU2487300A (en) * | 1998-12-31 | 2000-07-31 | Chiron Corporation | Polynucleotides encoding antigenic hiv type c polypeptides, polypeptides and uses thereof |
| US6921530B1 (en) * | 1999-09-24 | 2005-07-26 | Cornell Research Foundation, Inc. | Low dose IL-2 for potentiation of immunity |
| FR2813793B1 (en) * | 2000-09-08 | 2003-01-24 | Aventis Pasteur | USE OF LIPOPEPTIDES FOR IMMUNOTHERAPY OF HIV + SUBJECTS |
| CA2421409A1 (en) * | 2000-09-08 | 2002-03-14 | Aventis Pasteur | Use of lipopeptides for immunotherapy of hiv-positive subjects |
| US6579521B2 (en) | 2000-10-20 | 2003-06-17 | Chiron Corporation | Methods of therapy for HIV infection |
| US20060159657A1 (en) * | 2001-06-14 | 2006-07-20 | Macromed, Incorporated | Formulations of lymphokines and method of use thereof for local or both local and systemic control of proliferative cell disorders |
| US20030003074A1 (en) * | 2001-06-14 | 2003-01-02 | Macromed, Inc. | Formulations of lymphokines and method of use thereof for local or both local and systemic control of proliferative cell disorders |
| EP2292772A1 (en) * | 2001-07-05 | 2011-03-09 | Novartis Vaccines and Diagnostics, Inc. | HIV vaccination with a DNA encoding a HIV polypeptide and a HIV polypeptide |
| US7211659B2 (en) * | 2001-07-05 | 2007-05-01 | Chiron Corporation | Polynucleotides encoding antigenic HIV type C polypeptides, polypeptides and uses thereof |
| CA2456470A1 (en) * | 2001-08-13 | 2003-02-27 | University Of Southern California | Interleukin-2 mutants with reduced toxicity |
| AU2002316578A1 (en) * | 2001-08-31 | 2003-03-18 | Chiron Corporation | Polynucleotides encoding antigenic hiv type b polypeptides, polypeptides and uses thereof |
| US20030170614A1 (en) * | 2001-08-31 | 2003-09-11 | Megede Jan Zur | Polynucleotides encoding antigenic HIV type B polypeptides, polypeptides and uses thereof |
| RU2201762C1 (en) * | 2001-10-09 | 2003-04-10 | Свадовский Александр Игоревич | Method for treating intracerebral tumor |
| US7939090B2 (en) | 2003-10-21 | 2011-05-10 | Cedars-Sinai Medical Center | System and method for the treatment of cancer, including cancers of the central nervous system |
| US20070098685A1 (en) * | 2005-01-19 | 2007-05-03 | Brand Stephen J | Methods and kits to treat chronic inflammatory immune diseases by administering a proteasome inhibitor and an interleukin 2 receptor agonist |
| EP2084267B1 (en) | 2006-09-26 | 2018-04-11 | Cedars-Sinai Medical Center | Cancer stem cell antigen vaccines and methods |
| US8871211B2 (en) | 2006-09-28 | 2014-10-28 | Cedars-Sinai Medical Center | Cancer vaccines and vaccination methods |
| PL2328923T3 (en) | 2008-09-02 | 2016-06-30 | Cedars Sinai Medical Center | Cd133 epitopes |
| DK2427485T3 (en) | 2009-05-07 | 2017-03-13 | Immunocellular Therapeutics Ltd | CD133 epitopes |
| US9273283B2 (en) | 2009-10-29 | 2016-03-01 | The Trustees Of Dartmouth College | Method of producing T cell receptor-deficient T cells expressing a chimeric receptor |
| US9181527B2 (en) | 2009-10-29 | 2015-11-10 | The Trustees Of Dartmouth College | T cell receptor-deficient T cell compositions |
| WO2013033626A2 (en) | 2011-08-31 | 2013-03-07 | Trustees Of Dartmouth College | Nkp30 receptor targeted therapeutics |
| US9790278B2 (en) | 2012-05-07 | 2017-10-17 | The Trustees Of Dartmouth College | Anti-B7-H6 antibody, fusion proteins, and methods of using the same |
| CA2898474A1 (en) | 2013-02-14 | 2014-08-21 | Immunocellular Therapeutics, Ltd. | Cancer vaccines and vaccination methods |
| EP3204119B1 (en) | 2014-10-09 | 2021-06-09 | Dana-Farber Cancer Institute, Inc. | Multiple-variable il-2 dose regimen for treating immune disorders |
| AU2018372167B2 (en) | 2017-11-21 | 2023-12-07 | The Board Of Trustees Of The Leland Stanford Junior University | Partial agonists of interleukin-2 |
| MX2022008771A (en) | 2020-01-14 | 2022-10-07 | Synthekine Inc | Biased il2 muteins methods and compositions. |
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| US4908433A (en) * | 1984-04-25 | 1990-03-13 | Sloan-Kettering Institute For Cancer Research | Uses of interleukin-2 |
| US4863730A (en) | 1986-03-21 | 1989-09-05 | Cenfold Holdings, S.A. | Immunotherapy for AIDS patients |
| US4868157A (en) | 1987-10-05 | 1989-09-19 | Merck & Co., Inc. | Dipeptidyl 2-amino-1,2-dideoxy-D-glucose derivatives as host resistance enhancers in AIDS-immunocompromised hosts and methods of use |
| US4866157A (en) * | 1987-11-10 | 1989-09-12 | Sugio Otani | Thermosetting aromatic resin composition |
| DE3818054C2 (en) * | 1988-05-27 | 1994-02-17 | Biotest Pharma Gmbh | Use of a combination of an antigen or a vaccine and human interleukin for the treatment of non-responsiveness to immunological defect states |
| FR2653020B1 (en) * | 1989-10-17 | 1993-03-26 | Roussel Uclaf | USE OF A POLYPEPTIDE HAVING THE ACTIVITY OF HUMAN INTERLEUKIN 2 FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF LEUKEMIA. |
| US5026687A (en) * | 1990-01-03 | 1991-06-25 | The United States Of America As Represented By The Department Of Health And Human Services | Treatment of human retroviral infections with 2',3'-dideoxyinosine alone and in combination with other antiviral compounds |
| CA2074720C (en) | 1990-01-26 | 2002-07-23 | Martin A. Cheever | Immune reactivity to expressed activated oncogenes for diagnosis and treatment of malignancy |
| FR2660863B1 (en) * | 1990-04-17 | 1994-01-21 | Roussel Uclaf | USE OF A POLYPEPTIDE HAVING THE ACTIVITY OF HUMAN INTERLEUKIN 2 FOR THE PREPARATION OF A PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF PRIMITIVE CANCERS OF THE POWDER. |
| US5419900A (en) | 1993-05-19 | 1995-05-30 | The United States Of America As Represented By The Department Of Of Health And Human Services | Immunologic enhancement with intermittent interleukin-2 therapy |
| US5696079A (en) | 1993-05-19 | 1997-12-09 | The United States Of America As Represented By The Department Of Health And Human Services | Immunologic enhancement with intermittent interleukin-2 therapy |
-
1993
- 1993-05-19 US US08/063,315 patent/US5419900A/en not_active Expired - Lifetime
-
1994
- 1994-05-19 CA CA002163219A patent/CA2163219A1/en not_active Withdrawn
- 1994-05-19 WO PCT/US1994/005397 patent/WO1994026293A1/en active IP Right Grant
- 1994-05-19 AU AU71377/94A patent/AU691504B2/en not_active Expired
- 1994-05-19 PT PT94920673T patent/PT702560E/en unknown
- 1994-05-19 DK DK94920673T patent/DK0702560T3/en active
- 1994-05-19 EP EP94920673A patent/EP0702560B1/en not_active Expired - Lifetime
- 1994-05-19 ES ES94920673T patent/ES2167370T3/en not_active Expired - Lifetime
- 1994-05-19 AT AT94920673T patent/ATE208206T1/en active
- 1994-05-19 JP JP52574694A patent/JP4275193B2/en not_active Expired - Lifetime
- 1994-05-19 DE DE69428992T patent/DE69428992T2/en not_active Expired - Lifetime
-
1997
- 1997-09-02 US US08/922,218 patent/US6190656B1/en not_active Expired - Lifetime
-
2000
- 2000-08-09 US US09/635,286 patent/US6548055B1/en not_active Expired - Lifetime
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