Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector
Reexamination Certificate
1999-05-25
2002-09-24
Scheiner, Laurie (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
C530S351000, C435S069100
Reexamination Certificate
active
06455045
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
Immunogenic compounds with in particular an anti-cytokine effect, preparation process, pharmaceutical compositions and kits containing them.
2. Description of the Related Art
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:
1) Compounds which are all prepared and used as active immunization agents (vaccination). They are:
compounds derived from a cytokine through loss of the biological activity characteristic of the cytokine, which are capable of inducing an immune response in vivo in contrast with native cytokine,
peptide sites of HIV-1 selected because of their possible interference with the activation processes of T-cells,
HIV virus particles depleted of their genomic RNA, as well as pharmaceutical compositions containing them.
2) A prophylactic or therapeutic treatment consisting of an anti-cytokine 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-&agr; (IFN-&agr;), interferon-&bgr; (IFN-&bgr;), gamma-interferon (gamma-IFN), interleukin-1 (IL-1) in &agr; and &bgr; 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 &agr; and B forms, transforming growth factor-&bgr; (TGF-&bgr;), in &bgr;1, &bgr;2, &bgr;3, &bgr;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-&agr; 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-&agr;, -&bgr; as well as TGF-&bgr; 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 immunity consists of a first line of defence, capable of stopping most of the pathogenic agents before a real infection is established. The mechanisms of specific immunity then come into action. They release a reaction directed specifically against the responsible germ, bringing about its destruction.
The phenomena of specific and non-specific immunity are the purpose of cells and molecules distributed throughout the organism. Non-specific immunity uses in particular phagocytic cells and killer or NK (natural killer) cells as well as soluble factors such as lysozyme, complement and a family of antiviral agents with a wide range of action, that is the interferons.
Subsequently, it was revealed that the interferons can be produced under physiological or physiopathological conditions which are not necessarily associated with viral infections. In fact a certain number of interferon synthesis inducers exist which are non-viral substances.
In addition to their anti-viral effect in the simple control of an infection, interferons possess an anti-proliferative (cytostatic) activity in vivo which gives them anti-tumor properties, and immunoregulatory properties of specific immune reactions. However, everyone agrees that this regulatory effect is extremely complex.
Acquired specific immunity is itself the phenomenon of a co-operation of macrophages, B lymphocytes (humor-mediated immunity) and T lymphocytes (cell-mediated immunity).
In a general and schematic manner, there exist two major types of specific immune response: humoral-type response which is characterized by the production of antibodies by the B lymphocytes and cell-mediated immune response which uses effector cells, that is essentially the T
8
lymphocytes (cytotoxic lymphocytes). These responses are initially activated by antigen-presenting cells and modulated by regulatory cells, that is the T
4
lymphocytes (auxiliary T lymphocytes) and the suppressor T lymphocytes.
In its three major lines, the specific immune response functions as follows:
Antigen-presenting cells (monocytes, macrophages and B lymphocytes) capture the antigen, digest it and re-expose fragments of it on their surface, in combination with molecules of the major histocompatibility complex (MHC) of class I or II.
When the T
4
lymphocytes “see” the antigen fragments combined with the major histocompatibility complex of class II, they proliferate, pass into activated form (synthesize IL-2), and in doing this stimulate the proliferation of the antibody-producing B lymphocytes and that of the T
8
lymphocytes (cytotoxic lymphocytes or CTL).
The B lymphocytes produce antibodies which interact with the circulating antigens so as to neutralize them.
Finally, the T
8
lymphocytes destroy the infected cells when they recognize the antibody fragments combined with the major histocompatibility complex of class I.
The standard immune response to any microbial agent can be schematically summarized as followed: the intervention of the non-specific immunity is almost immediate, then, if appropriate, it is followed within 48 to 72 hours by the appearance of the specific immune response. However, there are notable exceptions, in particular when the microbial agent is a virus. In this case, the absence of or the difficult induction of a specific immune response is sometimes observed.
The absence of induction could be explained by a suppressor effect induced by the viral agent due to an over-production of cytokines such as IFN-&agr;. These could prevent or halt the establishment of the immune response.
What precedes explains the failure of certain vaccination attempts. In fact, strongly immunogenic elements, which are potential candidates as vaccines (inactivated or attenuated virus or bacterium; proteins of viral, bacterial or parasitic origin) sometimes prove insufficient during tests in vivo, such as in AIDS or herpes.
HIV infections (human immunodeficiency virus) represent a typical case of what has just been mentioned. Quite particularly, t
Bizzini Bernard
Zagury Daniel
Zagury Jean-François
Browdy and Neimark
Neovacs
Parkin Jeffrey S.
Scheiner Laurie
LandOfFree
Immunogenic compounds with in particular an anti-cytokine... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Immunogenic compounds with in particular an anti-cytokine..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Immunogenic compounds with in particular an anti-cytokine... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2819835