Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Hormone or other secreted growth regulatory factor,...
Patent
1994-06-27
2000-07-25
Eisenschenk, Frank C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Hormone or other secreted growth regulatory factor,...
4241841, 4241451, 424 851, A61K 3900, A61K 39395, A61K 4505
Patent
active
060934050
DESCRIPTION:
BRIEF SUMMARY
Nucleic Acid Research, Vol 11, No. 3, February 1993, Arlington, Virginia, pages 555-573 describes native molecules of murine interferon .alpha. 1 and .alpha. 2. GB-A-2 157 697 describes native molecultes of bovine interferon .alpha.. WO-A-8 805 783 desribes peptides homologous to a fragment of the retroviral molecule of murine virus MLV p15E, these peptides being endowed with suppressive properties, also the use of these peptides as immunizing agents against a retroviral infection or on the contrary to induce an immunosuppression.
The present invention relates to immunogenic compounds with in particular an anti-cytokine effect, a preparation process, pharmaceutical compositions and kits containing them.
The present invention has two subjects: (vaccination). They are: characteristic of the cytokine, which are capable of inducing an immune response in vivo in contrast with native cytokine, the activation processes of T-cells, pharmaceutical compositions containing them. vaccination and aiming to repair homeostatic disorders caused by over-production of a cytokine. This new vaccination strategy could be used on its own or, in the case of a microbial infection, combined with a conventional vaccination (active immunization directed against the infectious agent).
Cytokines are proteins which modulate cell activity or proliferation, whose production is generally local and transitory and which act in a paracrine or autocrine manner. In what follows, the term "cytokine" incorporates families of endogenic molecules of various denominations: lymphokines, monokines, interleukins, interferons, colonization factors and growth factors, neuro peptides.
The known cytokines are in particular interferon-.alpha. (IFN-.alpha.), interferon-.beta. (IFN-.beta.), gamma-interferon (gamma-IFN), interleukin-1 (IL-1) in .alpha. and .beta. forms, interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF) in .alpha. and .beta. forms, transforming growth factors (TGF-.beta.), in .beta.1, .beta.2, .beta.3, .beta.1.2 forms, and colony-stimulating factors (CSF) such as the granulocyte macrophage-stimulating factor (GM-CSF), the granulocyte colony-stimulating factor (G-CSF) and the macrophage-stimulating factor (M-CSF) and the epithelial growth factor (EGF), somatostatin, endorphins, the various "releasing factors" or "inhibitory factors" such as TRF.
Certain pathological states due to an infection, such as AIDS or herpes, can stem from homeostatic disorders induced by an over-production of cytokine(s) such as IFN-.alpha. or TNF.
Other pathological conditions (malignant tumor, allergy, auto-immune illness) can also be the consequence of homeo-static disorders.
In order to treat some of these pathological conditions, the use of anti-cytokine-neutralizing monoclonal antibodies (MAbs) was proposed for therapeutic purposes. Some of them have already been successfully experimented with. Such MAbs are intended to neutralize hyperproduction of a cytokine.
It is now proposed to substitute this passive therapy of serotherapy type with an active therapy of vaccinal type which consists of the administration of an inactivated immunogenic cytokine, or of one of its inactivated analogues. In fact it is a question of inducing an immune response of the organism against the native cytokine which is produced in excess. This active therapy, just like the administration of MAbs, would bring about a "buffer" effect, but it would certainly be in a more refined and more suitable manner. In addition, this new therapy avoids the necessity of humanizing the MAbs of animal origin (murine) which is a long and delicate stage in the development of MAbs for therapeutical purposes.
On the other hand, IFN-.alpha., -.beta. as well as TGF-.beta. are in particular known as growth inhibitors of the immunity cells (cytostasis).
The immune system is presented with two functional aspects: non-specific immunity and specific immunity, also called memorized immunity. Non-specific im
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Bizzini Bernard
Zagury Daniel
Zagury Jean-Fran.cedilla.ois
Eisenschenk Frank C.
NEOVACS
Parkin Jeffrey S.
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