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Treatment and diagnosis of infertitlity using TGFbeta or activin

a technology of infertility and activin, which is applied in the field of diagnosis of infertility using tgfbeta or activin, can solve the problems of high attendant social cost, high personal distress, and the inability to diagnose the condition, and achieve the effects of increasing the uterine gm-csf output, increasing the molecular weight activity, and increasing the output of murine uterine gm-cs

Inactive Publication Date: 2006-08-10
NOVOZYMES BIOPHARMA DK AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The patent text describes a method for treating infertility in humans or mammals by exposing the mother to TGFβ or an effective derivative or analog thereof before attempted conception. This exposure helps to elicit a transient hyporesponsive immune reaction to the antigens of the male partner, which can alleviate symptoms of the infertility condition. The method can be performed by exposing the mucosal surface of the mother, such as the genital mucosal surface, to the antigen. The patent also discusses the significance of TGFβ in the seminal plasma and the potential for tolerance to male antigens."

Problems solved by technology

An inability or reduced ability to have children can cause great personal distress and has a high attendant social cost, particularly in terms of the cost of medical intervention.
Undertaking an IVF program often causes great anguish, especially when there is no resultant successful pregnancy.
It is presently believed that the poor success rate in IVF treatment is due to an extraordinarily high rate of early embryonic loss (58, 59), possibly related to the patient's impaired reproductive state or the IVF process itself.
Current methods of increasing pregnancy rates during IVF treatment include placing multiple embryos (2-5) into the uterine cavity, but this is not always effective since uterine receptivity is believed to be at fault at least as commonly as embryonic viability.
Furthermore, the ensuing high rates of multiple pregnancy are associated with an increased maternal risk of pre-eclampsia, haemorrhage and operative delivery, and fetal risks including pre-term delivery with the attendant possibility of physical and mental handicap.
Similarly, early pregnancy loss is a major constraint in breeding programs for livestock and rare or threatened species.
Embryonic mortality during the pre- and per-implantation period is viewed as the major reason for poor pregnancy outcome when assisted reproductive technologies such as artificial insemination are used.
Even following natural mating, variability in litter size and in the viability of offspring arc additional limitations with serious economic implications.
Normal embryos appear to be lost primarily because the environment provided by the maternal tract during pre-implantation development or at the time of implantation into the endometrium is insufficient to nurture their growth and development.
Embryos may lose viability or developmental potential if the maternal tract milieu comprises inappropriate or insufficient nutrients or peptide growth factors.
Additionally the nature of the tolerance was unclear.

Method used

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  • Treatment and diagnosis of infertitlity using TGFbeta or activin
  • Treatment and diagnosis of infertitlity using TGFbeta or activin
  • Treatment and diagnosis of infertitlity using TGFbeta or activin

Examples

Experimental program
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Effect test

example 1

Seminal TGFβ Initiates the Post Mating Inflammatory Response in Mice and Humans

[0077] The cytokine GM-CSF, produced by the uterine epithelium following contact with seminal vesicle secretions, is thought to be pivotal to the generation of maternal tolerance since it is largely responsible for initiating the leukocytic influx into the female reproductive tract after mating and for increasing the antigen presenting capacity of these cells.

[0078] Seminal vesicle fluid was fractionated by size exclusion chromatography in order to identify GM-CSF-stimulating activity. Two fractions were identified; a high molecular weight (650 kDA) proteinacous moiety and a intermediate molecular weight, more heterogenous moiety eluting between 150-440 kDa (10.62). The latter moiety was identified as TGFβ1, on the basis of findings that it's GM-CSF stimulating activity was enhanced by acid activation, that TGFβ1 immunoactivity and bioactivity co-eluted in the same fraction, and that anti-TGFβ1 neutral...

example 2

Seminal Vesicle Fluid Modulates Maternal Reproductive Performance and the Maternal Immune Responsive to Paternal Antigens.

[0083] Previously, exposure to semen at mating was found to cause an intense but transient inflammatory response, and factors in seminal plasma derived from the seminal vesicle were implicated in this response. In studies in mice, the inventors have identified seminal vesicle fluid as a pivotal determinant in optimal embryo development and implantation. Furthermore, exposure to semen at mating has been shown to have an important role in inducing maternal tolerance prior to implantation, and factors present in seminal plasma have been identified as necessary for induction of this state, suggesting that the beneficial effect of seminal plasma on pregnancy outcome may at least in part be due to the immune deviating effects of this fluid.

[0084] To test the importance of exposure to seminal reside fluid for pregnancy success. Balb / c F1 females were mated with CBA m...

example 3

Seminal TGFβ is an Immune Deviating Agent

[0088] To assess the effect of TGFβ on induction of Th1 and Th2 immune responses against CBA sperm antigens, Balb / c F1 female mice were immunised by intra-uterine infusion with CBA sperm, in the presence or absence of rTGFβ, on two occasions separated by 4 weeks. Development of Th1 anti-sperm immunity was assessed two weeks later by measuring the DTH response to a subcutaneous sperm antigen challenge, and by measuring serum content of anti-sperm reactive immunoglobulin of the IgG2b subclass. Whereas sperm administered alone or in the presence of Freunds Complete Adjuvant elicited a strong DTH response and a moderate IgG2b antibody response, immunisation in the presence of TGFβ substantially diminished both of these parameters, and was comparable to the response elicited by natural mating (FIG. 8). In contrast, synthesis of sperm-reactive immunoglobulin of the IgG1 isotype (indicating induction of a Th2 response) occurred to a similar extent...

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Abstract

A method of treating an infertility condition in humans or mammals, by exposure of a prospective mother to TGFβ or derivative or analog of TGFβ. The exposure is advantageously in conjunction with one or more antigens of a prospective father so that a hyporesponsive immune reaction is mounted to the one or more antigens of the prospective father.

Description

FIELD OF THE INVENTION [0001] This invention relates to a diagnostic method for an infertility condition giving rise to reduced ability to have offspring and to a method of treating such a condition. BACKGROUND OF THE INVENTION [0002] An inability or reduced ability to have children can cause great personal distress and has a high attendant social cost, particularly in terms of the cost of medical intervention. A large proportion of couples fall into this category. In the USA, for example, it is said that some 10-15% of couples of reproductive age are unable to have children, whereas in the United Kingdom this is 14%. In 1995 it was calculated that 5.1 million women had impaired fertility in the USA alone, with this figure projected to increase to 5.9 million by the year 2020 (56). In the US, the cost of a pregnancy conceived by IVF varies between US$66.000 for the first cycle to US$114.000 by the sixth cycle (60). [0003] In the context of this patent an infertility condition is to ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00A61K38/18A61K35/14A61K38/22A61K38/48G01N33/68G01N33/74
CPCA61K35/19A61K38/1841A61K38/484A61K39/001A61K2039/55522G01N33/689G01N33/74G01N2333/495G01N2800/367A61K2300/00A61K9/0034
Inventor ROBERTSON, SARAH ANNETREMELLEN, KELTON PAUL
Owner NOVOZYMES BIOPHARMA DK AS